Research progress on mechanism of biotrauma caused by ventilation-induced lung injury / 中华危重病急救医学

Mechanical ventilation is an advanced life support treatment for patients with acute respiratory failure. While stabilizing respiratory function, it also acts as an injury factor to exacerbate or lead to lung injury, that is, ventilation-induced lung injury (VILI). There may be a more subtle form of damage to VILI known as "biotrauma". However, the mechanism of biotrauma in VILI is still unclear. This article intends to review the mechanism of biotrauma of VILI from the aspects of inflammatory response, oxidative stress and complement activation, in order to provide a new strategy for clinical prevention and treatment of biotrauma caused by VILI.

Role of innate immunity in the pathogenesis of ventilation-induced lung injury / 中华危重病急救医学

For patients receiving mechanical ventilation, mechanical ventilation is also an injury factor at the same time of treatment, which can lead to or aggravate lung injury, that is, ventilator-induced lung injury (VILI). The typical feature of VILI is that the mechanical stress is transmitted to cells through the pathway, leading to uncontrollable inflammatory cascade reaction, which causes the activation of inflammatory cells in the lung and the release of a large number of cytokines and inflammatory mediators. Among them, innate immunity is also involved in the occurrence and development of VILI. A large number of studies have shown that damaged lung tissue in VILI can regulate inflammatory response by releasing a large number of damage associated molecular pattern (DAMP). Pattern recognition receptor (PRR) participates in the activation of immune response by combining with DAMP, and releases a large number of inflammatory mediators to promote the occurrence and development of VILI. Recent studies have shown that inhibition of DAMP/PRR signaling pathway can play a protective role in VILI. Therefore, this article will mainly discuss the potential role of blocking DAMP/PRR signal pathway in VILI, and provide new ideas for the treatment of VILI.

Research progress of spontaneous respiration in mechanical ventilation of acute respiratory distress syndrome / 中华危重病急救医学

Mechanical ventilation is an important supportive treatment for acute respiratory distress syndrome (ARDS). However, improper mechanical ventilation can cause a "second hit" to the lung, that is, ventilator-induced lung injury (VILI), characterized by translocation of pulmonary inflammatory mediators into the bloodstream, aggravating systemic inflammatory response syndrome, and multiple organ failure. Although the current protective mechanical ventilation strategy plays an important role in supporting treatment, the mortality of ARDS with mechanical ventilation is still very high. Therefore, to explore the strategy of pulmonary protective ventilation has always been the key orientation of ARDS and has important clinical significance. This article reviews the application, advantages and disadvantages of assisted and non-assisted spontaneous respiration in ARDS patients undergoing mechanical ventilation, in order to provide a reference for research and development of new strategies for ARDS protective ventilation.

Effects of lead exposure and chelation therapy in different developmental stages on mouse short-term and long-term cognitive functions / 环境与职业医学

Background Lead (Pb) exposure impairs cognitive functions of children. Whether Pb exposure in different developmental stages induces long-term cognitive impairment, and whether chelation therapy could mitigate the cognitive impairment is rarely reported. Objective This experiment is designed to investigate effects of Pb exposure and chelation therapy during different developmental stages (breastfeeding, weaning, and early puberty periods) on mouse short-term and long-term cognitive functions. Methods C57BL/6 male mice in breastfeeding period, weaning period, and early puberty period (postnatal day 2, 21, and 41; PND 2, PND 21, and PND 41, n=30, respectively) were randomly divided into control, Pb exposure, and Pb+dimercaptosuccinic acid (DMSA) treatment groups (n=10 in each group). The control groups received standard food and deionized water. The Pb exposure mice received standard food and free drinking water containing Pb acetate (0.1% for dams, and 0.05% for pups). After receiving Pb acetate for 19 d, the Pb+DMSA treatment groups were given 1 mmol·kg−1·d−1 DMSA for 6 d with gastric infusion. Whole blood Pb levels were measured after DMSA treatment on experimental day 25. The effects on short-term cognitive function were tested in the Morris Water Maze task by the analyses of escape latency on PND 75−79, as well as target quadrant time and times of platform-crossing on PND 80. Hippocampal long-term potentiation of field excitatory postsynaptic potential (fEPSP) of mice on PND 365 was induced to demonstrate the effects on long-term cognitive function. Results The blood Pb levels among the Pb, Pb+DMSA, and control groups were statistically different for each developmental stage (Fbreastfeeding period=43.47, Fweaning period=228.6, Fearly period of puberty=274.2, all P<0.001). Compared to the counterpart control groups, blood Pb levels of the pb exposure groups (386.4, 265.0, and 178.1 μg·L−1 in breastfeeding period, weaning period, and early puberty period, respectively) were significantly higher for all stages. After the chelation therapy, the blood Pb significantly decreased for all stages (28.68, 47.29, and 20.93 μg·L−1 in the three periods, respectively, all P<0.001) and the Pb levels of the mice exposed in the breastfeeding period decreased most (by 92.58%, 82.15%, and 88.25% in the three periods, respectively, P<0.01). In the water maze task, the mice exposed to Pb in the breastfeeding period had a gentler decrease in escape latency (from 54.20 s on day 1 to 30.54 s on day 5, by 43.65 % decrease) than the control group (from 32.44 s on day 1 to 15.20 s on day 5, by 53.14 % decrease) (P<0.01) and a significant decrease in target quadrant time (P<0.05). After the chelation therapy, the escape latency of the DMSA-treated mice in the breastfeeding period (from 40.94 s on day 1 to 20.87 s on day 5, by 48.99 % decrease) was steeper than that of the Pb-exposed mice (P<0.05). The differences in the escape latency, target quadrant time, and times of platform-crossing were not significant between the Pb-exposed mice and the control mice in the weaning period and early period of puberty (all P>0.05). After the chelation therapy, such differences were also not significant compared with before therapy. Due to the small sample size, data were merged for different developmental stages in the long-term potentiation test. The amplitudes of fEPSP induced in the control, Pb-exposed, and DMSA treatment groups were significantly different (Fgroups=212.2, Ftime=11.36. P<0.001). The average fEPSP amplitude induced in the last 10 min recorded in the hippocampal slices in the Pb exposure group was significantly lower than that in the control group (P<0.05). After the DMSA treatment, no significant differences were observed in the fEPSP amplitudes between the Pb exposure group and the DMSA treatment group (P>0.05). When observing the fEPSP data by developmental stages, the fEPSP amplitude in the breastfeeding Pb-exposure group was 27.2% lower than that of the breastfeeding control group, while such changes were not obvious in the weaning period or in the early period of puberty. The fEPSP amplitude in breastfeeding DMSA treatment group was 44.3% higher than that of the breastfeeding Pb exposure group, while such changes were not observed in the weaning period or in early period of puberty. Conclusion Pb exposure during different developmental stages, especially in breastfeeding period, could affect short-term and long-term cognitive functions of mice. The harmful effects may be partially reversed by DMSA chelation therapy, especially being treated in breastfeeding period.

Prediction of the onset time of acute stroke by deep learning based on DWI and FLAIR / 中华放射学杂志

Objective:To evaluate the effect of deep learning based on DWI and fluid attenuated inversion recovery (FLAIR) to construct a prediction model of the onset time in acute stroke.Methods:A total of 324 cases of acute stroke with clear onset time, from January 2017 to May 2020 in Nanjing First Hospital, were retrospectively enrolled and analyzed. The patients were divided into a training set of 226 patients and a test set of 98 patients according to the complete randomization method using a 7∶3 ratio, and the patients were divided into ≤ 4.5 h and >4.5 h according to symptom onset time in each group. The acute infarction areas on DWI and the corresponding high signal area on FLAIR were manually outlined by physician. Using the InceptionV3 model as the basic model for image features extraction, the deep learning prediction model based on single sequence (DWI, FLAIR) and multi sequences (DWI+FLAIR) were established and verified. Then the area under curve (AUC), accuracy of human readings, single sequence model and multi sequence model in predicting the acute stroke onset time from imaging were compared.Results:DWI-FLAIR mismatch was found in 94 cases (94/207) of patients with symptom onset time from imaging ≤ 4.5 h, while in 28 cases (28/117) of patients with symptom onset time from imaging >4.5 h. ROC analysis showed that the AUC of DWI-FLAIR mismatch in predicting acute stroke onset time from imaging was 0.607, and the accuracy was 60.2%. The prediction model of deep learning based on single sequence showed that the AUC of FLAIR was 0.761 and the accuracy was 71.4%; the AUC of DWI was 0.836 and the accuracy was 81.6%. The AUC of predicting stroke onset time based on the multi-sequence (DWI+FLAIR) deep learning model was 0.852, which was significantly better than that of manual identification ( Z = 0.617, P = 0.002), FLAIR sequence deep learning model ( Z = 2.133, P = 0.006) and DWI sequence deep learning model ( Z = 1.846, P = 0.012). Conclusion:The deep learning model based on DWI and FLAIR is superior to human readings in predicting acute stroke onset time from imaging, which could provide guidance for intravenous thrombolytic therapy for acute stroke patients with unknown onset time.

A review of studies on the pathogenesis and preclinical drug therapy of acute respiratory distress syndrome / 中华危重病急救医学

Acute respiratory distress syndrome (ARDS) is a serious disease with high mortality, which is characterized by non-cardiogenic pulmonary edema and hypoxemia. In recent years, the development of supportive therapy has reduced the mortality to some extent, however, the high cost of treatment, side effects and the high mortality of moderate and severe ARDS limit its efficacy. So it is necessary to strengthen the research on specific drugs. The core pathological changes of ARDS are the uncontrolled inflammatory response and the impairment of pulmonary vascular endothelium and alveolar epithelial barrier function. Therefore, regulating the intensity of inflammatory response and promoting the endothelial and epithelial barrier have become two key factors in the current drug treatment of ARDS. This article summarizes the pathogenesis of ARDS and the related preclinical drug therapy of ARDS in recent years from two aspects: the uncontrolled inflammatory response and the destruction of alveolar epithelial and pulmonary vascular endothelial barrier, in order to provide reference for the later treatment of ARDS.

Benign and malignant classification of renal occupancy lesions CT images using convolutional neural networks / 国际生物医学工程杂志

Objective To investigate the feasibility and application value of the benign and malignant classificational methods of renal occupying CT images based on convolutional neural networks (CNN). Methods An image omics method that can automatically learn the image features and classify CT images was used. Firstly, the CNN model obtained by large-scale natural image training was used to migrate the characteristics of the renal occupancy lesions CT images, and then the fine-tuning of the full connection layer was used to realize the benign and malignant classification of the images. Results The evaluation indexes of the VGG19 model were lower than ResNet50 and Inception V3, and the training result showed obvious overfitting. The accuracy, sensitivity and negative prediction values of the Inception V3 model was 93.8％, 99.5％ and 99.1％, respectively, which were higher than that of the ResNet50 model. Conclusions The benign and malignant classification of renal occupancy lesions CT images using CNN is a reasonable and feasible method, and the fine-tuned Inception V3 model has a better classification performance.

Relationship between the expression of the BRCA_1 protein and clinicopathological characteristics of breast cancer / 中国癌症杂志

Purpose:To study the relationship between the expression of the BRCA 1 protein and clinico pathological characteristics of breast cancer,and to clarify the correlation of the expression of the BRCA 1 protein with expression of p53 and c erbB 2 . Methods:The expressions of BRCA 1 , p53 and c erbB 2 of breast cancer tissues taken from 60 breast cancer patients as well as 10 benign breast disease patients were examined using immunohistochemical LDP method. All tissues were taken from formalin fixed and paraffin embedded breast tumor specimens. We analyzed the correlation of the results with other parameters which included age of onset, family history, histological grade, status of estrogen receptor and progesterone receptor, axillary nodal status and so on. Results:The expression of BRCA 1 was 61.66% (37/60) in breast cancer patients and 0 (0/10) in benign diseases patients. The protein expressed was mainly located in the cytoplasm. The correlation between age of onset and the expression of BRCA 1 was significant (r=-0.295, P

~(99m)Tc-tetrofosmin SPECT for the evaluation of suspicious palpable breast lesions / 中国癌症杂志

Purpose:To assess the value of 99m Tc tetrofosmin SPECT in discrimination of malignant from benign breast mass.Methods:The trial was prospective, blind and diagnostic. From 2000.6 to 2001.12, one hundred one consecutive patients with breast mass detected by clinical examination were included. After injection of 740 MBq 99m Tc tetrofosmin intravenously in the arm contralateral to the breast lesion, 99m Tc tetrofosmin SPECT was performed additional to the regular diagnostic procedure. All patients underwent operation within one week. Using histological assessment as a golden standard, we calculated sensitivity, specificity, positive and negative predictive value for 99m Tc tetrofosmin SPECT of the breast mass. Results:The sensitivity for palpable breast lesions was 86 3%, specificity 84.0%, positive and negative predictive value were 84.6% and 85.7% respectively. Conclusions:The results suggested that 99m Tc tetrofosmin SPECT is a valuable tool for the evaluation of palpable breast lesions.