Objective To investigate the impact of myeloid cell-specific knockout of the granulocyte colony-stimulating factor receptor(G-CSFR)on the progression of acute radiation pneumonitis.Methods Myeloid cell-specific G-CSFR knockout(G-CSFR-/-,Lyz2-cre)mice were constructed.G-CSFR-/-,Lyz2-cre and C57BL/6N mice underwent a single whole-body irradiation with 6.5 Gy of 60Co γ-rays to establish a model of radiation injury.The lung function of mice was assessed using a mouse lung function test system at 3,7 and 14-days post γ-ray irradiation.Pathological changes in the lung tissue were analyzed via hematoxylin and eosin(HE)staining of paraffin sections.Tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)levels were measured via radioimmunoassay.IL-8 and its receptor CXCR2 were quantified using enzyme-linked immunosorbent assay(ELISA).The infiltration of neutrophils in lung tissue was evaluated by immunohistochemical detection of myeloperoxidase.Results At 3-,7-and 14-days post-irradiation with 6.5 Gy of 60Co γ-rays,there were no significant differences observed in lung function or interstitial inflammatory lesions between G-CSFR-/-,Lyz2-cre mice and C57BL/6N mice.However,the infiltration of neutrophils in lung tissue of G-CSFR-/-,Lyz2-cre mice was significantly reduced(P＜0.01),and the levels of IL-8,CXCR2 and TNF-α in lung tissues were markedly lower than in C57BL/6N mice(P＜0.05).Conclusion The myeloid cell-specific knockout of G-CSFR can effectively diminish neutrophil infiltration as well as inflammatory cytokine levels in lung tissues following radiation exposure.

Objective:To analyze the monitoring results of brucellosis nationwide, learn about the current epidemic situation of brucellosis, and provide a basis for formulating brucellosis prevention and control strategies and measures.Methods:A retrospective analysis was conducted on the data collected from the "Infectious Disease Report Information Management System" of the Chinese Center for Disease Control and Prevention and various brucellosis national monitoring sites from 2019 to 2022, including national brucellosis epidemic data and monitoring data for a descriptive analusis.Results:From 2019 to 2022, a total of 227 186 cases of brucellosis were reported nationwide, with 267 brucellosis public health emergencies, the cases mainly concentrated in northern regions such as Inner Mongolia Autonomous Region, Ningxia Hui Autonomous Region, and Xinjiang Uygur Autonomous Region. The incidence rate of brucellosis in each year from 2019 to 2022 was 3.15/100 000, 3.37/100 000, 4.95/100 000 and 4.69/100 000, respectively. The gender distribution was mainly male, with a male to female ratio of 2.51∶1.00 (162 373 ∶ 64 813). The age range was mainly concentrated between 30 and 70 years old, accounting for 85.72% (194 754/227 186). The main occupation was farmers and herdsmen, accounting for 85.19% (193 536/227 186). The onset time was mainly concentrated between March and August, accounting for 66.39% (150 827/227 186). From 2019 to 2022, a total of 234 719 key populations were monitored, with 14 717 positive and a positivity rate of 6.27%. In inter animal epidemic monitoring, the positive rate of sheep was 0.18% (5 425/3 087 451), and the serological test positive rate of cattle was 0.17% (1 143/686 958). In pathogen monitoring, a total of 2 185 samples were tested, and 553 strains of Brucella were detected as positive, with a positive rate of 25.31%, mainly for sheep type 3. Conclusions:From 2019 to 2022, the incidence rate of brucellosis in China is increased. The high incidence season is spring and summer. Male young adults and farmers and herdsmen are the key population. We should continue to strengthen the monitoring of brucellosis in humans and livestock, take effective prevention and control measures in a timely manner, and control the occurrence and spread of the epidemic.

Objective:To analyze the monitoring results of brucellosis nationwide, learn about the current epidemic situation of brucellosis, and provide a basis for formulating brucellosis prevention and control strategies and measures.Methods:A retrospective analysis was conducted on the data collected from the "Infectious Disease Report Information Management System" of the Chinese Center for Disease Control and Prevention and various brucellosis national monitoring sites from 2019 to 2022, including national brucellosis epidemic data and monitoring data for a descriptive analusis.Results:From 2019 to 2022, a total of 227 186 cases of brucellosis were reported nationwide, with 267 brucellosis public health emergencies, the cases mainly concentrated in northern regions such as Inner Mongolia Autonomous Region, Ningxia Hui Autonomous Region, and Xinjiang Uygur Autonomous Region. The incidence rate of brucellosis in each year from 2019 to 2022 was 3.15/100 000, 3.37/100 000, 4.95/100 000 and 4.69/100 000, respectively. The gender distribution was mainly male, with a male to female ratio of 2.51∶1.00 (162 373 ∶ 64 813). The age range was mainly concentrated between 30 and 70 years old, accounting for 85.72% (194 754/227 186). The main occupation was farmers and herdsmen, accounting for 85.19% (193 536/227 186). The onset time was mainly concentrated between March and August, accounting for 66.39% (150 827/227 186). From 2019 to 2022, a total of 234 719 key populations were monitored, with 14 717 positive and a positivity rate of 6.27%. In inter animal epidemic monitoring, the positive rate of sheep was 0.18% (5 425/3 087 451), and the serological test positive rate of cattle was 0.17% (1 143/686 958). In pathogen monitoring, a total of 2 185 samples were tested, and 553 strains of Brucella were detected as positive, with a positive rate of 25.31%, mainly for sheep type 3. Conclusions:From 2019 to 2022, the incidence rate of brucellosis in China is increased. The high incidence season is spring and summer. Male young adults and farmers and herdsmen are the key population. We should continue to strengthen the monitoring of brucellosis in humans and livestock, take effective prevention and control measures in a timely manner, and control the occurrence and spread of the epidemic.

Objective To observe the value of ultrasound soft markers at 11-14 weeks of gestation for predicting adverse pregnancy outcomes using meta-analysis.Methods Literature about ultrasound soft markers at 11-14 weeks of gestation,including nuchal translucency(NT)thickening,nasal bone dysplasia,reversed or absent venous duct,tricuspid regurgitation and single umbilical artery,for predicting adverse pregnancy outcomes were searched in CNKI,Wanfang Med Online,VIP databases,PubMed,Cochrane Library,Embase and Web of Science databases from January 1,2000 to April 1,2024 by 2 researchers independently.The data were extracted,and the risk of bias was assessed.Stata 17.0 software was used for meta-analysis.Results Totally 37 articles involving 9 673 gravidas were enrolled.Meta-analysis showed that the more positive ultrasound soft markers at 11-14 weeks of gestation,the higher risk of adverse pregnancy outcomes.Among single positive markers,single umbilical artery had the highest incidence of adverse pregnancy outcomes,and NT≥3.0 mm had the highest incidence of chromosome abnormalities in fetuses,while tricuspid regurgitation suggested the lowest possibility of adverse pregnancy outcomes and chromosome abnormalities in fetuses.Conclusion Positive ultrasound soft markers at 11-14 weeks of gestation had certain predictive value for adverse pregnancy outcomes,especially chromosomal abnormalities.

Objective To observe the value of ultrasound soft markers at 11-14 weeks of gestation for predicting adverse pregnancy outcomes using meta-analysis.Methods Literature about ultrasound soft markers at 11-14 weeks of gestation,including nuchal translucency(NT)thickening,nasal bone dysplasia,reversed or absent venous duct,tricuspid regurgitation and single umbilical artery,for predicting adverse pregnancy outcomes were searched in CNKI,Wanfang Med Online,VIP databases,PubMed,Cochrane Library,Embase and Web of Science databases from January 1,2000 to April 1,2024 by 2 researchers independently.The data were extracted,and the risk of bias was assessed.Stata 17.0 software was used for meta-analysis.Results Totally 37 articles involving 9 673 gravidas were enrolled.Meta-analysis showed that the more positive ultrasound soft markers at 11-14 weeks of gestation,the higher risk of adverse pregnancy outcomes.Among single positive markers,single umbilical artery had the highest incidence of adverse pregnancy outcomes,and NT≥3.0 mm had the highest incidence of chromosome abnormalities in fetuses,while tricuspid regurgitation suggested the lowest possibility of adverse pregnancy outcomes and chromosome abnormalities in fetuses.Conclusion Positive ultrasound soft markers at 11-14 weeks of gestation had certain predictive value for adverse pregnancy outcomes,especially chromosomal abnormalities.

Objective:To investigate the effect of long noncoding RNA (lncRNA) 5033413D16Rik (lncRNA 5033413D16Rik) on the activity of interphotoreceptor retinoid-binding protein 1-20 (IRBP) 1-20-specific T helper 17 (Th17) cells in experimental autoimmune uveitis (EAU). Methods:Twelve SPF grade C57BL/6 female mice aged 8 to 10 weeks were selected and divided into EAU group and normal control group using the random number table method, with 6 mice in each group.Mice in the normal control group received no treatment.Mice in the EAU group were immunized with IRBP 1-20 emulsified in complete Freund's adjuvant to induce EAU.On day 13 after immunization, fundus examination and inflammation scoring were performed, and retinal histopathological changes were observed with hematoxylin and eosin staining.T cells were isolated from the spleen and lymph nodes of EAU mice, and the relative expression of lncRNA 5033413D16Rik was detected by real-time fluorescence quantitative PCR (qRT-PCR).In addition, the isolated T cells were divided into short hairpin RNA (shRNA)-5033413D16Rik transfected group and shRNA-negative control (NC) transfected group, and transfected with corresponding shRNAs, respectively.The knockdown efficiency of shRNA-5033413D16Rik was verified by qRT-PCR.T cells in the two groups were co-cultured with bone marrow-derived dendritic cells (BMDCs) under Th17 polarizing conditions.The relative expression of retinoic acid-related orphan receptor (RORγt), interleukin 17 (IL-17), IL-23 receptor (IL-23R), and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA in co-cultured cells were analyzed by qRT-PCR.The IL-17 concentration in co-culture supernatants was assayed by ELISA and percentages of Th17 cells were determined by flow cytometry.The use and care of experimental animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals promulgated by the State Science and Technology Commission.The study protocol was reviewed and approved by the Experimental Animal Ethics Committee of Tianjin Medical University (No.TJYY2019110117). Results:EAU model was established successfully.qRT-PCR analysis showed that the expression of lncRNA 5033413D16Rik was significantly decreased in T cells from EAU mice compared with normal control mice ( t=-13.332, P<0.001).Compared with the shRNA-NC transfected group, the relative expression of lncRNA 5033413D16Rik in T cells of the shRNA-5033413D16Rik transfected group was significantly reduced ( t=-6.338, P<0.01).In co-cultured T cells, the expression levels of RORγt, IL-17, IL-23R, and GM-CSF mRNA in shRNA-5033413D16Rik transfected group were 1.61±0.13, 1.51±0.13, 1.85±0.33 and 1.45±0.11, which were significantly higher than 1.00±0.01, 1.00±0.01, 1.00±0.01 and 1.00±0.01 in shRNA-NC-transfected group ( t=-6.839, -8.221, -4.538, -4.189; all at P<0.05).ELISA analysis revealed that IL-17 concentraion in shRNA-5033413D16Rik transfected group was (2 350.39±367.02)pg/ml, which was significantly higher than (1 513.31±310.37)pg/ml ( t=-3.016, P=0.039).Flow cytometry showed that the percentage of Th17 cells in shRNA-5033413D16Rik transfected group was (17.20±0.44)%, which was higher than (14.10±0.84)% in normal control group ( t=-3.264, P=0.031). Conclusions:LncRNA 5033413D16Rik can inhibit the expression of pathogenicity related genes in antigen-specific Th17 cells and negatively regulates IRBP 1-20-specific Th17 cell responses.

Objective:Through the analysis of the evaluation index system of the major rankings of universities and hospitals, this paper aims to provide a reference for the discipline construction of affiliated hospitals in universities.Methods:This paper comprehensively analyzes and compares the evaluation objectives and indicators of the five major rankings of universities and the three major rankings of hospitals in China and abroad.Results:Each main rankings have its own characteristics that both positive and with possible limitations.Conclusions:Hospital management departments can refer certain indicators in order to identify possible gaps of the hospital discipline development. Also, tailored corresponding measurements for discipline development can be developed in combination with real-needs.

Objective:To investigate the effect of P2X4R silencing on 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) cell model and its mechanism. Methods:(1) According to the 6-OHDA concentrations, the SH-SY5Y cells were divided into 0 μmol/L 6-OHDA group, 50 μmol/L 6-OHDA group, 100 μmol/L 6-OHDA group, and 150 μmol/L 6-OHDA group. CCK-8 was used to detect the cell survival rate, Western blotting was used to detect the P2X4R protein expression, and real time quantitative RT-PCR was used to detect the P2X4R mRNA expression. The optimal concentration of 6-OHDA was selected to induce PD cell model. (2) SH-SY5Y cells at logarithmic phase were transfected with P2X4R siRNA lentiviral plasmids of different sequences (P2X4R-siRNA540, P2X4R-siRNA792, and P2X4R-siRNA1401) and nonsense sequence normal control plasmid (NC-siRNA), respectively (P2X4R-siRNA540 group, P2X4R-siRNA792 group, P2X4R-siRNA1401 group, and NC-siRNA group); the P2X4R mRNA and protein expressions were detected by real time quantitative RT-PCR and Western blotting, and the P2X4R siRNA sequence with the best silencing effect was screened to establish P2X4R silencing cell line. (3) The PD cells induced by the optimal concentration of 6-OHDA were transfected by P2X4R-siRNA enjoying the best silencing effect, NC-siRNA, and P2X4R antagonist CORM-2 (PD+P2X4R-siRNA group, PD+NC-siRNA group, and PD+CORM-2 group); CCK-8 and flow cytometry were used to detect the survival rate and apoptosis rate of cells in each group, and Western blotting was used to detect the protein expressions of connexin (PANX1), toll-like receptor (TLR)-2, Caspase-3 and cleaved Caspase-3. (4) The PANX1 or TLR-2 over-expression plasmids (pCMV3-PANX1 and pCMV3-TLR2), and negative control plasmid (pCMV3-NCV) were transfected into cells from the PD+P2X4R-siRNA group (PD+P2X4R-siRNA+pCMV3-PANX1 group, PD+P2X4R-siRNA+pCMV3-TLR2 group, and PD+P2X4R-siRNA+pCMV3-NCV group); CCK-8 and flow cytometry were used to detect the survival rate and apoptosis rate of cells in each group; Western blotting was used to detect the TLR-2, Caspase-3 and cleaved Caspase-3 protein expressions. Results:(1) As compared with that in the 0 μmol/L 6-OHDA group, the cell survival rate in 50, 100, and 150 μmol/L 6-OHDA groups was significantly decreased in a dose-dependent manner, and the P2X4R protein and mRNA expression levels were significantly increased in a dose-dependent manner ( P<0.05); among them, 100 mol/L 6-OHDA was the most suitable concentration to induce PD cell model. (2) As compared with those in the NC-siRNA group, the P2X4R mRNA and protein expressions in P2X4R-siRNA540 group, P2X4R-siRNA792 group, and P2X4R-siRNA1401 group were significantly decreased ( P<0.05); P2X4R mRNA and protein expressions were the lowest in the P2X4R-siRNA540 group. (3) As compared with PD+NC-siRNA group, the PD+P2X4R-siRNA group and PD+CORM-2 group had significantly increased survival rate, significantly decreased apoptosis rate, and statistically decreased Caspase-3, cleaved Caspase-3, PANX1 and TLR-2 protein expression levels ( P<0.05). (4) As compared with PD+P2X4R-siRNA+pCMV3-NCV group, the TLR2 protein expression in PD+P2X4R-siRNA+pCMV3-PANX1 group was significantly lower ( P<0.05); as compared with PD+P2X4R-siRNA+pCMV3-NCV group, PD+P2X4R-siRNA+pCMV3-TLR2 group had significantly increased cell survival rate, significantly decreased apoptosis rate, and significantly decreased Caspase-3 and cleaved Caspase-3 protein expressions ( P<0.05). Conclusion:P2X4R silencing can significantly improve the survival rate of PD cell model induced by 6-OHDA, reduce apoptosis and expressions of apoptosis related proteins (Caspase-3 and cleaved Caspase-3), and play a neuroprotective role, whose mechanism may be related to PANX1/TLR-2 signal pathway.

Objective:To investigate the status of depression and physiological, psychological and social factors among people with type 2 diabetes(T2DM), as well as the mediating effects of illness perception and diabetes distress on glycemic control and depression.Methods:A total of 511 patients with type 2 diabetes were recruited and investigated using general demographic questionnaire, self-rating depression scale(SDS), brief illness perception questionnaire(BIPQ) and diabetes distress scale(DDS). Body mass index (BMI) and hemoglobin a1c (HbA1c) were detected in laboratory.Results:The mean score of SDS was (57.48±9.94). The distribution of depression condition were 138(27.0%)without depression, 179(35%)with mild depression, 174(34.1%)with moderate depression and 20(3.9%)with severe depression.SDS score was significantly positively correlated with poor glycemic control ( r=0.157, P<0.01), illness perception( r=0.359, P<0.01) and four dimensions of diabetes distress( r=0.177-0.354, P<0.01). Partially mediating effect of illness perception( B=0.216, 95% CI=0.112-0.372) was found in glycemic control and depression, the proportion of effect was 25.9%.The chain mediating effect ( B=0.086, 95% CI=0.042-0.149) of illness perception and diabetes distress was also found between glycemic control and depression, whose indirect effect size was 10.3%. Conclusion:Glycemic control is significantly related with depression.Illness perception and diabetes distress are partly mediating the effect between glycemic control and depression.

Objective:To systematically evaluate cardiotoxicity of programmed cell death 1 receptor (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors.Methods:Clinical trials of PD-1/PD-L1 inhibitor alone or in combination with other treatments for tumors were collected by searching related databases at home and abroad (up to March 2, 2019). The methodological quality of studies was evaluated using the internationally accepted Cochrane collaboration′s risk of bias assessment tool. A meta-analysis was performed using RevMan 5.3 software to compare the incidences of cardiotoxicity between PD-1/PD-L1 inhibitors (trial group) and placebo or other antineoplastic agents(control group).Results:A total of 10 randomized controlled trials (RCTs) were enrolled, 9 of which were about PD-1 inhibitor alone or in combination with other antineoplastic agents, and 1 of which was about PD-L1 inhibitor monotherapy. There were a total of 5 291 patients, including 3 022 in the trial group and 2 269 in the control group. Evaluation of the methodological quality for studies showed that 4 RCTs were at high risk of bias and the other 6 were at low risk of bias. The meta-analysis showed that the incidence of cardiotoxicity in the trial group was significantly higher than that in the control group, and the difference was statistically significant[1.13% (34/3 022) vs. 0.22% (5/2 269), RR=2.38, 95 %CI: 1.19 -4.78, P=0.01]. Conclusion:PD-1/PD-L1 inhibitors have the risk of causing heart related adverse events, which should be paid attention to in clinical application.