Objective To study the antagonism of glutathione(GSH) and taurine on acute oxidative damage caused by mercury(Hg). Methods 32 Wistar rats were randomly divided into four groups. The rats of control group were given 0.9% saline by subcutaneous injections. The rats in mercuric chloride (HgCl2) group were subcutaneously injected with 2.5 mg/kg HgCl2. Rats of the other two groups were pretreated with 3 mmol/kg GSH and 4 mmol/kg taurine, respectively and two hours later injected subcutaneously with 2.5 mg/kg HgCl2. Urine creatine and mercury contents were determined; mercury level, contents of GSH, MDA and GSH-Px in liver and kidney were evaluated. Results Compared with the control, urine mercury level, level of mercury in liver and in the renal cortex, contents of GSH, MDA and GSH-Px in kidney in the group treated with 2.5 mg/kg HgCl2 were significantly increased. In the rats pretreated with GSH and taurine, contents of MDA in kidney were significantly decreased compared with those treated with mercury only. The levels of GSH-Px in kidney in the group pretreated with GSH and taurine were significantly higher than that not only in the mercury group but also in the control. Compared with the mercury group, levels of mercury in urine and liver in GSH pretreated group were distinctly reduced. Conclusion Pretreated with GSH and taurine have certain protection for the acute oxidative damage caused by mercury.

Objective To study the changes of ventilatory function of young soldiers coming from different regions during cold - tol-erance training. Methods The recruited young soldiers were divided into 2 groups:Group Ⅰ (50 coming from the northern region)and group Ⅱ (50 coming from the southern region) . According to the new training outline of cold -tolerance in winter,their ventilatory func-tions were tested before training and 60 days after training. Ventilatory functions were compared between smoking and non - smoking sub-jects. Results 25% forced expiratory flow (FEF25%) , 50% forced expiratory flow (FEF50%) and 75% forced expiratory flow (FEF75 %) were significant different between two groups before the course of training (P < 0.05). After 60 days, ventilatory functions of two groups were improved significantly as compared with that before training (P <0.01 ,P <0.05). There was no significant difference in ventilatory between two groups after 60 days of training (P > 0.05). There was significant difference in partial small airway function be-tween smoking and non - smoking subjects. Conclusion Cold air could decline the small airway function of soldiers coming from south-ern region before training. Cold -tolerance training has significant influence on soldiers' ventilatory function. Long- term and heavy smok-ing could decline the small airway function.

Objective To investigate the curative effect of noninvasive mechanical ventilation (NMV) and its influence on plasma brain natriuretic peptide (BNP) and endothelin-1 (ET-1) in senile patients with cot pulmonale complicated with respiratory failure. Methods Eighty senile patients with cot pulmonale complicated with respiratory failure were randomly divided into treatment group (40 cases) and control group (40 cases). The treatment group was treated by NMV combined with routine therapy, and the control group was treated by only routine therapy including respiratory stimulant,lowering pulmonary artery pressure, cardiotonic agents, diuretics and nasal catheter oxygen inhalation. Blood pressure, heart rate (HR), respiratory rate (RR), blood gas analysis (pH, PaO2, PaCO2 ,SaO2) and clinical symptoms and signs were observed before and 72 hours after treatment. The plasma levels of BNP and ET-1 were also measured before and after treatment. Results Compared with the control group, the clinical symptoms and signs were significantly improved, SaO2 and PaO2 were significantly elevated, and PaCO2, HR and RR were significantly reduced in NMV group (t=2.23 ～ 3.92, P< 0.05 or P< 0.01). The plasma levels of BNP and ET-1 were significantly decreased after treatment in both groups,especially in the treatment group (t=2. 93,3. 56, P<0.01). The plasma levels of BNP and ET-1 had significantly negative correlation with PaO2 (r=-0.69,-0.61 ,P<0. 01) ,and positive correlation with PaCO2 (r= 0.51,0.42, P<0. 05). Conclusions NMV can improve hypoxemia and CO2 retention in senile patients with cot pulmonale complicated with respiratory failure,and may have some influences on neuroendocrine functions.

Objective: To study the response of Escherichia coli (E. coli) HB101 (plasmid pUC19) and its carried antibiotic resistance genes to the process of cholorination under different environmental conditions. Methods: The E. coli strain was reacted with sodium hypochlorite at the concentration of 0.5, 0.75, 1.00, and 0.55 mg/L, then the residual chlorine and the colonies were detected at the 0.25, 1, 2, 5, 10, 20, and 30 min of the reaction, respectively. The first order disinfection kinetic model and EFH model were used to evaluate the inactivation effect of E. coli (plasmid pUC19) treated by sodium hypochlorite, while the plasmid pUC19 and antibiotic resistance gene amp^r were detected by PCR method. Besides, the logarithm of Ct (residual chlorine in t) under different concentration were calculated. Results: The temperature and pH value played important roles on the inactivation of E. coli and elimination of plasmid pUC19 and amp^r under the function of sodium hypochlorite. The Ct value needed for 5-log of E.coli HB101(pUC19) inactivation at 4, 20, 36 ℃ was 11.92, 10.28, 7.67, respectively, and when the pH was in 6.0, 7.0, 8.0, with chloride concentration were 0.75, 0.70, 0.55 mg/L, the Ct value needed for reached to 6.68, 10.28, 15.73 min·mg/L. At pH 7.2 condition, when the temperature was 4, 20, 36 ℃, and chloride concentration were 9, 5, 3 mg/L.The required Ct values to completely destroy the transformation function of free antibiotic resistant plasmids were 36.11, 34.17,16.09 min·mg/L. Sodium hypochlorite disinfection can release free ampr gene and even the transformed plasmid pUC19, and pollute the water body. Only when the Ct value reached 903.03 min·mg/L, the complete ampr gene can be destroyed which was far more exceed the bacterial lethal Ct value. Conclusion Even if all the antibiotic resistant bacteria were inactivated, the antibiotic resistant plasmids or genes might still maintain complete with the transformable function, which may result in new potential risks of waterborne diseases.

Objective:To develop an approach for the automatic diagnosis of bone metastasis and to design a parameter of quantitative evaluation for tumor burden on bone scans based on deep learning technology.Methods:A total of 621 cases (389 males, 232 females, age: 12-93 years) of bone scan images from the Department of Nuclear Medicine in Tenth People′s Hospital of Tongji University from March 2018 to July 2019 were retrospectively analyzed. Images were divided into bone metastasis group and non-bone metastasis group. Eighty percent of the cases were randomly extracted from both groups as the training set, and the rest of cases were used as the test set. A deep residual convolutional neural network ResNet34 was used to construct the classification model and the segmentation model. The sensitivity, specificity and accuracy were calculated and the performance differences of the classification model in different age groups (15 cases of <50 years, 75 cases of ≥50 and <70 years, 33 cases of ≥70 years) were analyzed. The regions of metastatic bone lesions were automatically segmented by the segmentation model. The Dice coefficient was used to evaluate the effect of the segmentation model and the manual labeled results. Finally, the bone scans tumor burden index (BSTBI) was calculated to assess the tumor burden of bone metastases.Results:There were 280 cases with bone metastases and 341 cases with non-bone metastases, including 498 in training set and 123 in test set. The classification model could accurately identify bone metastases, with the sensitivity, specificity and accuracy of 92.59%(50/54), 85.51%(59/69) and 88.62%(109/123), respectively, and it performed best in the <50 years group (sensitivity, 2/2; specificity, 12/13; accuracy, 14/15). The specificity in the ≥70 years group (8/12) was the lowest. The Dice coefficient of bone metastatic area and bladder area were 0.739 and 0.925 in the segmentation model, which performed similarly in the three age groups. Preliminary results showed that the value of BSTBI increased with the increase of the number of bone metastatic lesions and the degree of 99Tc m-MDP uptake. The machine learning model in this study took (0.48±0.07) s for the entire analysis process from input to the final BSTBI calculation. Conclusions:The deep learning based on automatic diagnosis framework for bone metastases can automatically and accurately identify segment bone metastases and calculate tumor burden. It provides a new way for the interpretation of bone scans. The proposed BSTBI may be used as a quantitative evaluation indicator in the future to assess the tumor burden of bone metastases based on bone scans.

The theories of pathophysiology come from experimental research,and experimental teaching is an important part of pathophysiology course.Experimental teaching can cultivate the abilities of independent thinking and comprehensive analysis in students,improve their practical skills,and enhance their understanding and application of theoretical knowledge.However,teaching reform should be carried out due to the drawbacks of current pathophysiological experimental teaching.With the teaching idea centered on learning,the quality of pathophysiological experimental teaching can be enhanced by rational arrangement of experimental courses,optimization of teaching contents,and comprehensive application of various teaching models,so as to effectively improve the level of theoretical knowledge and comprehensive practical ability among students.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Objective: To investigate the clinicopathological features and immunohistochemical phenotypes of gastric SMARCA4-deficient undifferentiated carcinoma, and to discuss the daily diagnostics of this entity and analyze its prognosis. Methods: The cases of gastric SMARCA4-deficient undifferentiated carcinoma diagnosed at the Department of Pathology, Peking University Cancer Hospital, China from January 2010 to August 2022 were collected. The histological sections were reviewed, the immunohistochemical results and clinicopathological features were analyzed, and relevant literature was reviewed. Results: Pure foci of undifferentiated carcinoma were seen in 7 cases, and 1 case was accompanied by a moderately differentiated tubular adenocarcinoma component. Undifferentiated carcinoma foci showed similar sheet-like or solid diffuse growth pattern, medium-sized tumor cells characterized by 1-2 nucleoli, and abundant cytoplasm and rhabdoid appearance. The average patient age was 65±8 years. Six patients were male and 2 were female. Immunohistochemical staining showed that undifferentiated carcinoma of all 8 tumors were negative for SMARCA4 (BRG1). Among 7 patients who underwent SMARCA2 (BRM) and SMARCB1 (INI1) staining, 4 cases showed loss of BRM expression, 2 cases showed weakly positive staining, and 1 case was diffusely positive, but all 7 cases were diffusely strong positive for INI1. The neuroendocrine marker, synaptophysin, was weakly positive in 5 cases, while CgA and CD56 were negative in 8 cases. Ki-67 index was more than 70%. Two cases were mismatch repair deficient and showed the loss of MLH1/PMS2 expression, while 1 case showed only MSH2 loss. PD-L1 staining showed that combined positive score (CPS)≥1 in 4 cases (CPS ranging from 1 to 55) and CPS<1 in the other 3 cases. Four patients had clinical stage Ⅳ disease. Two of them died within 3 months after diagnosis. Conclusions: Gastric SMARCA4-deficient undifferentiated carcinoma/rhabdoid carcinoma is a rare group of highly malignant tumors with a poor prognosis. Loss of the core subunit of SWI/SNF complex may be associated with the development of dedifferentiated histological pattern and aggressive tumor progression, which may be more frequently accompanied with mismatch repair deficiency.
Male ; Female ; Humans ; Carcinoma/pathology* ; Adenocarcinoma ; Colorectal Neoplasms ; Cell Differentiation ; Stomach Neoplasms ; Biomarkers, Tumor ; DNA Helicases ; Nuclear Proteins ; Transcription Factors