5.Application of whole exome sequencing in patients with primary ciliary dyskinesia
Ke CHEN ; Jing SHI ; Lijuan HU ; Li ZHANG ; Minlu CAO ; Wei GUO ; Meiling JIN
Chinese Journal of Clinical Medicine 2024;31(6):1006-1010
		                        		
		                        			
		                        			A 29-year-old man visited Zhongshan Hospital, Fudan University in December 2021. The patient presented with recurrent coughing, sputum, and wheezing, high level of serum total IgE, positive aspergillus fumigatus-specific IgE and extremely severe mixed ventilatory dysfunction. These features and thoracic CT results scan showed bronchiectasis and allergic bronchopulmonary aspergillosis. In consideration of his clinical characteristics, including low levels of fractional exhaled nitric oxide (FeNO), and nasal nitric oxide (nNO), persistent cough after birth, consanguineous marriage of his parents, etc. we ratiocinated a possibility of hereditary diseases, especially primary ciliary dyskinesia (PCD). From this perspective, whole exome sequencing (WES) was performed and the diagnosis of PCD was ultimately confirmed.
		                        		
		                        		
		                        		
		                        	
6.Epidemiological investigation of iron deficiency among preschool children in 10 provinces, autonomous regions, or municipalities in China
Lei WANG ; Jie SHAO ; Wenhong DONG ; Shuangshuang ZHENG ; Bingquan ZHU ; Qiang SHU ; Wei CHEN ; Lichun FAN ; Jin SUN ; Yue GAO ; Youfang HU ; Nianrong WANG ; Zhaohui WANG ; Tingting NIU ; Yan LUO ; Ju GAO ; Meiling TONG ; Yan HU ; Wei XIANG ; Zhengyan ZHAO ; Meng MAO ; Fan JIANG
Chinese Journal of Pediatrics 2024;62(5):416-422
		                        		
		                        			
		                        			Objective:To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China.Methods:A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test.Results:A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) μg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region ( χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference ( χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) ( χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant ( χ2=0.51, P=0.476). Conclusions:There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.
		                        		
		                        		
		                        		
		                        	
7.Effect of bluetongue virusinfection on type Ⅰ interferon response in BHK-21 cells
Shimei LUO ; Yunyi CHEN ; Qisha LI ; Yanmei ZHOU ; Yifei WANG ; Xinyu LIAO ; Xuer-Ou HU ; Yuanjian WEI ; Mengqin LI ; Meng ZHU ; Xun ZHANG ; Beirui CHEN ; Xianping MA ; Jiarui XIE ; Meiling KOU ; Haisheng MIAO ; Fang LI ; Huashan YI
Chinese Journal of Veterinary Science 2024;44(8):1639-1644,1690
		                        		
		                        			
		                        			Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.
		                        		
		                        		
		                        		
		                        	
8.Effectiveness of a preeclampsia risk prediction model based on maternal risk factors in the first trimester of pregnancy
Yulian HU ; Meiling SUN ; Cuili CHEN ; Pingping MENG ; Wei WEI ; Jingjing LI ; Lili QIN ; Limei SUN
Chinese Journal of General Practitioners 2024;23(7):722-727
		                        		
		                        			
		                        			Objective:To investigate the effectiveness of preeclampsia risk prediction models based on maternal risk factors during the first trimester in a local population.Methods:This was a diagnostic study. Pregnant women who underwent prenatal examination in People′s Hospital of Rizhao from May 2019 to May 2022 and had risk factors for preeclampsia were enrolled at 11-13 +6 weeks gestation, and were divided into preterm preeclampsia group, term preeclampsia group and non-preeclampsia group according to the occurrence and the gestational week. Baseline clinical data were collected. The effectiveness of different models in predicting preeclampsia risk was evaluated using receiver operating characteristic (ROC) curves. Results:Among the 559 pregnant women enrolled, 78(14.0%) had preeclampsia, including 35(6.3%) with preterm preeclampsia (preterm preeclampsia group), 43 (7.7%) with term preeclampsia (term preeclampsia group), and 481 (86.0%) without preeclampsia (non-preeclampsia group).The most effective model for predicting preterm preeclampsia in the first trimester was maternal risk factor+mean arterial pressure (MAP)+serum placental growth factor (PLGF)+uterine artery pulse index (UTPI). The area under ROC curve was 0.805, and the sensitivity was 56.6% with a false-positive rate of 10%; the most effective model for predicting term preeclampsia and preeclampsia was maternal risk factor+MAP+UTPI. The area under ROC curve was 0.777, and the sensitivity was 52.6% and 53.5% with a false-positive rate of 10%.Conclusion:The combined predicting strategy for preterm preeclampsia based on maternal risk factors in the first trimester maybe effective among our population.
		                        		
		                        		
		                        		
		                        	
9.Galectin-1 Promotes Gastric Carcinoma Progression and Cisplatin Resistance Through the NRP-1/c-JUN/ Wee1 Pathway
Zhengyang PAN ; Guoxi XU ; Yan ZHANG ; Meiling WU ; Jiahui YU ; Xujun HE ; Wei ZHANG ; Junfeng HU
Journal of Gastric Cancer 2024;24(3):300-315
		                        		
		                        			 Purpose:
		                        			Gastric cancer (GC) is among the deadliest malignancies and the third leading cause of cancer-related deaths worldwide. Galectin-1 (Gal-1) is a primary protein secreted by cancer-associated fibroblasts (CAFs); however, its role and mechanisms of action of Gal-1 in GC remain unclear. In this study, we stimulated GC cells with exogenous human recombinant galectin-1 protein (rhGal-1) to investigate its effects on the proliferation, migration, and resistance to cisplatin. 
		                        		
		                        			Materials and Methods:
		                        			We used simulated rhGal-1 protein as a paracrine factor produced by CAFs to induce GC cells and investigated its promotional effects and mechanisms in GC progression and cisplatin resistance. Immunohistochemical (IHC) assay confirmed that Gal-1 expression was associated with clinicopathological parameters and correlated with the expression of neuropilin-1 (NRP-1), c-JUN, and Wee1. 
		                        		
		                        			Results:
		                        			Our study reveals Gal-1 expression was significantly associated with poor outcomes.Gal-1 boosts the proliferation and metastasis of GC cells by activating the NRP-1/C-JUN/ Wee1 pathway. Gal-1 notably increases GC cell resistance to cisplatin The NRP-1 inhibitor, EG00229, effectively counteracts these effects. 
		                        		
		                        			Conclusions
		                        			These findings revealed a potential mechanism by which Gal-1 promotes GC growth and contributes to chemoresistance, offering new therapeutic targets for the treatment of GC. 
		                        		
		                        		
		                        		
		                        	
10.A tactical nanomissile mobilizing antitumor immunity enables neoadjuvant chemo-immunotherapy to minimize postsurgical tumor metastasis and recurrence.
Tao HE ; Mingxing HU ; Shunyao ZHU ; Meiling SHEN ; Xiaorong KOU ; Xiuqi LIANG ; Lu LI ; Xinchao LI ; Miaomiao ZHANG ; Qinjie WU ; Changyang GONG
Acta Pharmaceutica Sinica B 2023;13(2):804-818
		                        		
		                        			
		                        			Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8+ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.
		                        		
		                        		
		                        		
		                        	
            
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