1.Diagnostic value of 3D-PDUS assessment of fetal kidney for fetal growth restriction
Qinxiao WANG ; Wen ZHANG ; Liyi YOU ; Sisi YANG ; Haiying CHEN ; Yan JIAO
China Modern Doctor 2024;62(28):30-33
		                        		
		                        			
		                        			Objective To investigate the diagnostic value of three-dimensional power Doppler ultrasound(3D-PDUS)in fetal growth restriction(FGR).Methods A total of 120 pregnant women in the third trimester who were given birth in Wenzhou People's Hospital from September 2021 to December 2023 were selected as study objects,50 pregnant women with FGR confirmed by clinical and ultrasound were included in case group,and 70 pregnant women with normal fetal development were included in control group.The renal volume and renal blood flow parameters of the fetuses in two groups were compared.The pregnancy outcomes and perinatal conditions of two groups were compared.Receiver operating characteristic(ROC)curve was plotted to calculate the area under the curve(AUC),and the diagnostic efficacy of various blood flow parameters for FGR was evaluated.Results The renal volume/gestational week,renal vascularization index,vascularization flow index and renal artery peak systolic velocity of the fetuses in case group were significantly lower than those in control group,while renal artery peak systolic velocity/end diastolic velocity,pulsation index and resistance index were significantly higher than those in control group(P<0.05).There was no significant difference in renal flow index between two groups(P>0.05).ROC curve results showed that the diagnostic efficacy of renal volume/gestational week and renal artery peak systolic velocity were higher,while the diagnostic efficacy of combined application was the highest,with an AUC of 0.89.The rate of low birth weight infants in case group was significantly higher than that in control group,and neonatal Apgar score was significantly lower than that in control group(P<0.01).Conclusion 3D-PDUS quantitative analysis parameters evaluated renal volume and blood perfusion could predict FGR,which is conducive to early diagnosis of FGR and guide clinical intervention,and effectively reduce adverse pregnancy outcomes.
		                        		
		                        		
		                        		
		                        	
2.Association of whole blood copper,zinc,calcium,magnesium,and iron with non-alcoholic fatty liver disease in overweight and obese children
Zhihang HUANG ; Miyang LUO ; Wen DAI ; Zhenzhen YAO ; Sisi OUYANG ; Ning'an XU ; Haixiang ZHOU ; Xiongwei LI ; Yan ZHONG ; Jiayou LUO
Journal of Central South University(Medical Sciences) 2024;49(3):426-434
		                        		
		                        			
		                        			Objective:Non-alcoholic fatty liver disease(NAFLD)is a common metabolic disorder in overweight and obese children,and its etiology and pathogenesis remain unclear,lacking effective preventive and therapeutic measures.This study aims to explore the association between whole blood copper,zinc,calcium,magnesium and iron levels and NAFLD in overweight and obese children aged 6 to 17 years,providing a scientific basis for the prevention and intervention of early NAFLD in overweight and obese children. Methods:A cross-sectional study design was used to collect relevant data from overweight and obese children who visited the Hunan Children's Hospital from January 2019 to December 2021 through questionnaire surveys.Fasting blood samples were collected from the subjects,and various indicators such as blood glucose,blood lipid,and mineral elements were detected.All children were divided into an overweight group(n=400)and a NAFLD group(n=202).The NAFLD group was divided into 2 subgroups according to the ALT level:A non-alcoholic fatty liver(NAFL)group and a non-alcoholic steatohepatitis(NASH)group.Logistic regression analysis was used to analyze the association between minerals(copper,zinc,calcium,magnesium,and iron)and NAFLD,NAFL and NASH. Results:A total of 602 subjects were included,of whom 73.6%were male,with a median age of 10(9,11)years,and a body mass index(BMI)of 24.9(22.7,27.4)kg/m2.The intergroup comparison results showed that compared with the overweight group,the NAFLD group had higher levels of age,BMI,diastolic blood pressure(DBP),systolic blood pressure(SBP),triglyceride(TG),low density lipoprotein(LDL),alanine transaminase(ALT)and aspartate aminotransferase(AST),and lower level of high density lipoprotein(HDL).The NAFL group had higher levels of age,BMI,DBP,SBP,ALT,and AST,and lower levels of HDL compared with the overweight group.The levels of age,BMI,DBP,SBP,TG,LDL,ALT,and AST of NASH were higher than those in the overweight group,while the level of HDL was lower than that in overweight group(all P<0.017).After adjusting for a variety of confounders,the OR of NAFLD for the highest quantile of iron was 1.79(95%CI 1.07 to 3.00)compared to the lowest quantile,and no significant association was observed between copper,zinc,calcium,and magnesium,and NAFLD.The subgroup analysis of NAFLD showed that the OR for the highest quantile of iron in children with NAFL was 2.21(95%CI 1.26 to 3.88),while no significant association was observed between iron level and NASH.In addition,no significant associations were observed between copper,zinc,calcium,and magnesium levels and NAFL or NASH. Conclusion:High iron level increases the risk of NAFLD(more likely NAFL)in overweight and obese children,while copper,zinc,calcium,magnesium,and other elements are not associated with the risk of NAFLD in overweight and obese children.
		                        		
		                        		
		                        		
		                        	
3.Research progress in the application of biological activity assay in the quality control of traditional Chinese medicine
Sisi YU ; Miao WEN ; Jian ZHAO ; Yanlin WU
China Pharmacist 2024;28(9):170-180
		                        		
		                        			
		                        			Biological activity assay can effectively guarantee the effectiveness and safety of traditional Chinese medicine,has a good application prospect in the quality detection of traditional Chinese medicine,and can be combined with other quality detection methods to establish a diversified quality control model of traditional Chinese medicine.However,there are also some shortcomings in the biological activity assay,which faces many challenges and needs further exploration and development.Based on the introduction of the basic contents of biological activity assay,the advantages and applications of biological activity assay compared with chemical analysis and traditional sensory evaluation methods in the quality detection of traditional Chinese medicine were discussed through searching and reading domestic and foreign papers in this article,in order to discuss the application and research progress of biological activity assay in the quality control of traditional Chinese medicine.
		                        		
		                        		
		                        		
		                        	
4.Method for constructing a mouse model of bile stasis caused by partial bile duct ligation
Haiye TU ; Fangqi BAO ; Lizong ZHANG ; Chen JIANG ; Sisi WEN ; Ziyu ZHAO ; Mingsun FANG ; Minli CHEN
Acta Laboratorium Animalis Scientia Sinica 2024;32(5):620-629
		                        		
		                        			
		                        			Objective To observe the effects of different ligation sites and fasting method on a C57BL/6J mouse model of partial bile duct ligation(pBDL)-induced cholestasis,to establish a pBDL modeling method with a high modeling rate,typical symptoms,and good stability.Methods C57BL/6J mice were subjected to selective ligation of the left hepatic bile duct(L-pBDL)and left-to-median bile duct junction ligation(ML-pBDL)for modeling,and the effects of different pBDL ligation method on serum alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase(ALP),total bilirubin,total bile acid,and liver histopathology were observed.The effects of different fasting method on symptoms and liver injury in the ML-pBDL model were also observed after fasting for 12 and 16 h before surgery,and for 4 h after surgery.Results(1)The incidence of jaundice in the ML-pBDL group was 52.94%and the survival rate within 3 weeks after surgery was 64.71%,while the incidence of jaundice in the L-pBDL group was 11.76%and the survival rate within 3 weeks after surgery was 82.35%.Compared with those in the sham surgery group,serum liver function indicators were significantly increased in the L-pBDL and ML-pBDL groups(P<0.01),and ALP activity was significantly higher in the ML-pBDL group than in the L-pBDL group(P<0.05).Compared with mice in the L-pBDL group,mice in the ML-pBDL group had more severe liver fibrosis at 3 weeks post-surgery(P<0.01).(2)In addition,the incidence of jaundice in the 16 h fasting group was 93.33%and the survival rate within 3 weeks after surgery was 73.77%,while the incidence of jaundice in the 12 h fasting group was 42.86%and the survival rate within 3 weeks after surgery was 71.42%.Compared with those in the normal group,ALP activity,alanine aminotransferase/aspartate aminotransferase ratio,total bile acid level,and proportion of collagen fiber area were all significantly increased in the 16 h and 12 h fasting groups(P<0.05).Although the observed indicators were higher in the 16 h fasting group compared with those in the 12 h fasting group,the difference was not significant(P>0.05).Mice in the 12 h and 16 h fasting groups both showed significant bile duct hyperplasia and liver fibrosis(P<0.01),with more severe liver fibrosis in the 16 h fasting group(P<0.01).Conclusions Both L-pBDL and ML-pBDL ligation method can be used to establish a mouse model of cholestasis;however,symptoms in the L-pBDL model only exhibit transient damage characteristics,while the liver lesions in the ML-pBDL model are typical and stable.Prolonging the preoperative fasting time can improve the modeling rate and stability of the ML-pBDL model and produce more-typical pathological symptoms.
		                        		
		                        		
		                        		
		                        	
5.Comparison of hospital delivery costs between cesarean section and natural delivery and analysis of influencing factors.
Sisi OUYANG ; Zhenzhen YAO ; Wen DAI ; Yixu LIU ; Puying LIU ; Jiayou LUO
Journal of Central South University(Medical Sciences) 2023;48(5):733-742
		                        		
		                        			OBJECTIVES:
		                        			The increasing costs of hospital delivery have increased the economic burden of pregnant women, and the mode of delivery is the main factor affecting the costs of hospital delivery. This study aims to explore the difference in costs between cesarean section and natural delivery, and to provide reference for controlling the increase of hospital delivery costs.
		                        		
		                        			METHODS:
		                        			The data of inpatient delivery in the Hunan Maternal and Child Health Care Hospital from January 2016 to December 2020 were selected to compare the total inpatient costs and average daily costs of cesarean section and natural delivery. The linear trend model was used to analyze the trend change of inpatient delivery costs and the generalized linear model was used to analyze the influential factors for inpatient delivery costs.
		                        		
		                        			RESULTS:
		                        			The average hospitalization costs of cesarean section (10 447.25 yuan) were higher than that of natural delivery (5 567.95 yuan), and the average daily costs of cesarean section (1 902.57 yuan) were higher than those of natural delivery (1 666.40 yuan). There was no significant increase or decrease in trend for cesarean section, while the average annual growth rate of the costs of natural delivery was 11.79%. The main factors affecting the hospitalization costs of cesarean section and natural delivery included age, occupation, medical insurance, route of admission, length of stay, premature delivery and complications (all P<0.05).
		                        		
		                        			CONCLUSIONS
		                        			The total hospitalization costs and average daily costs of cesarean section are higher than those of natural delivery, but the costs of natural delivery show a faster growth trend, and the hospitalization costs of cesarean section and natural delivery should be controlled by targeted measures.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Pregnancy
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Cesarean Section
		                        			;
		                        		
		                        			Hospitalization
		                        			;
		                        		
		                        			Hospitals
		                        			;
		                        		
		                        			Hospital Costs
		                        			;
		                        		
		                        			Inpatients
		                        			;
		                        		
		                        			Retrospective Studies
		                        			
		                        		
		                        	
6.Engineered Bacillus subtilis alleviates intestinal oxidative injury through Nrf2-Keap1 pathway in enterotoxigenic Escherichia coli (ETEC) K88-infected piglet.
Chaoyue WEN ; Hong ZHANG ; Qiuping GUO ; Yehui DUAN ; Sisi CHEN ; Mengmeng HAN ; Fengna LI ; Mingliang JIN ; Yizhen WANG
Journal of Zhejiang University. Science. B 2023;24(6):496-509
		                        		
		                        			
		                        			Engineered probiotics can serve as therapeutics based on their ability of produce recombinant immune-stimulating properties. In this study, we built the recombinant Bacillus subtilis WB800 expressing antimicrobial peptide KR32 (WB800-KR32) using genetic engineering methods and investigated its protective effects of nuclear factor-E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway activation in intestinal oxidative disturbance induced by enterotoxigenic Escherichia coli (ETEC) K88 in weaned piglets. Twenty-eight weaned piglets were randomly distributed into four treatment groups with seven replicates fed with a basal diet. The feed of the control group (CON) was infused with normal sterilized saline; meanwhile, the ETEC, ETEC+WB800, and ETEC+WB800-KR32 groups were orally administered normal sterilized saline, 5×1010 CFU (CFU: colony forming units) WB800, and 5×1010 CFU WB800-KR32, respectively, on Days 1‒14 and all infused with ETEC K88 1×1010 CFU on Days 15‒17. The results showed that pretreatment with WB800-KR32 attenuated ETEC-induced intestinal disturbance, improved the mucosal activity of antioxidant enzyme (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)) and decreased the content of malondialdehyde (MDA). More importantly, WB800-KR32 downregulated genes involved in antioxidant defense (GPx and SOD1). Interestingly, WB800-KR32 upregulated the protein expression of Nrf2 and downregulated the protein expression of Keap1 in the ileum. WB800-KR32 markedly changed the richness estimators (Ace and Chao) of gut microbiota and increased the abundance of Eubacterium_rectale_ATCC_33656 in the feces. The results suggested that WB800-KR32 may alleviate ETEC-induced intestinal oxidative injury through the Nrf2-Keap1 pathway, providing a new perspective for WB800-KR32 as potential therapeutics to regulate intestinal oxidative disturbance in ETEC K88 infection.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Swine
		                        			;
		                        		
		                        			Enterotoxigenic Escherichia coli
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		                        			Kelch-Like ECH-Associated Protein 1
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		                        			Bacillus subtilis
		                        			;
		                        		
		                        			NF-E2-Related Factor 2
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		                        			Antioxidants
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		                        			Oxidative Stress
		                        			
		                        		
		                        	
7.Risk Factors of lateral cervical lymph node metastases and survival analysis in patients with medullary thyroid carcinoma
Sisi HUANG ; Hongqing XI ; Chen LI ; Zheng WAN ; Wen TIAN
Chinese Journal of Endocrine Surgery 2022;16(1):12-17
		                        		
		                        			
		                        			Objective:To investigate the risk factors of cervical lymph node metastasis (LNM) and survival analysis in patients with medullary thyroid carcinoma (MTC) .Methods:93 patients with MTC admitted to the Department of General Surgery and Department of Otorhinolaryngology, First Medical Center of PLA General Hospital from Sep. 2008 to Aug. 2020 were analyzed retrospectively, including 45 males and 48 females, with an average age of 47 years old. SPSS 26.0 statistical software was used for data processing of the initial surgical year and procedures, tumor pathological stages, preoperative calcitonin (Ctn) level, preoperative carcinoembryonic antigen (CEA) level, LNM status, recurrence free survival (RFS) , etc. The risk factors of LNM and prognosis of MTC patients were analyzed by COX univariate and multivariate regression. Kaplan Meier method was used to estimate the survival rates of independent risk factors affecting prognosis and draw their survival curves.Results:The median follow-up time of 93 patients was 53 months, ranging from 2 to 192 months. The 1-year, 3-year, 5-year and 10-year survival rates were 97.8%, 96.6%, 94.6% and 88.9% respectively. Multivariate COX regression analysis showed that Initial surgical procedures ( P=0.018) and preoperative Ctn level ( P=0.012) were independent risk factors of central cervical LNM. Preoperative Ctn level ( P=0.028) and Capsule invasion ( P=0.024) were the independent risk factors of lateral cervical LNM. Preoperative Ctn level≥180.30 pg/ml and ≥234.15pg/ml indicated central and lateral cervical LNM respectively (all P<0.001) . Distant metastasis was an independent risk factor of RFS ( P=0.037) of MTC. Conclusions:Standardized surgical procedures are recommended for initial treatment of MTC, which can reduce the possibility of residual occult metastasis and the risk of reoperation. Distant metastasis affects prognosis of MTC.
		                        		
		                        		
		                        		
		                        	
8.Study on the diagnostic value of benign and malignant thyroid nodules based on artificial intelligence (AI) technology combined with thyroid ultrasound imaging and data system (TI-RADS) grading
Zheng WAN ; Bing WANG ; Qinglei HUI ; Jing YAO ; Fengxia GONG ; Chen LI ; Linlin ZHANG ; Xin MIAO ; Lin LIU ; Kai ZHANG ; Yanbing JIAN ; Sisi HUANG ; Shengwei LAI ; Wen TIAN
Chinese Journal of Endocrine Surgery 2022;16(2):185-189
		                        		
		                        			
		                        			Objective:To study the diagnostic value of the artificial intelligence (AI) diagnostic system, ACR TI-RADS classification and AI+ ACR TI-RADS combined diagnostic performance in benign and malignant thyroid nodules and its guiding significance for surgical treatment.Methods:From Nov. 1, 2021, to Feb. 26, 2022, 349 patients with 605 thyroid nodules who received surgical treatment in Department of Thyroid (Hernia) Surgery, Department of General Surgery, the First Medical Center of the PLA General Hospital, were selected. There were 95 males and 254 females, male: female=1:2.67, aged 16-78 years, and the nodule diameter was 0.2-5.6 cm. SPSS 26.0 and R studio software were used for data processing. AI diagnostic system, ACR TI-RADS grading and AI+ ACR TI-RADS combined diagnostic efficacy were statistically analyzed, respectively. ROC curve analysis was performed in parallel.Results:The AUC value of AI+ ACR TI-RADS combined diagnosis was 0.900, greater than 0.857 of AI diagnostic system and 0.788 of ACR TI-RADS, and the difference was statistically significant ( Z= 7.631, both P<0.001) . The sensitivity of the combined diagnosis was 95.32%, the specificity was 84.61%, the accuracy was 92.56%, the positive predictive value was 94.69%, the negative predictive value was 86.27%, the missed diagnosis rate was 4.68%, and the misdiagnosis rate was 15.38%, which were better than the other two diagnostic methods. With an excellent coincidence rate with postoperative pathological results ( Kappa=0.804, P<0.001) . The accuracy of combined diagnosis in identifying the maximum diameter of different tumors was 89.58% for d≤0.5 cm, 96.09% for 0.5
		                        		
		                        	
9.Lipopolysaccharide induced intestinal epithelial injury: a novel organoids-based model for sepsis in vitro.
Sisi HUANG ; Sheng ZHANG ; Limin CHEN ; Xiaojun PAN ; Zhenliang WEN ; Yizhu CHEN ; Lidi ZHANG ; Jiao LIU ; Dechang CHEN
Chinese Medical Journal 2022;135(18):2232-2239
		                        		
		                        			BACKGROUND:
		                        			Advances in organoid culture technology have provided a greater understanding of disease pathogenesis, which has been rarely studied in sepsis before. We aim to establish a suitable organoids-based intestinal injury model for sepsis.
		                        		
		                        			METHODS:
		                        			Stable passaged organoids were constructed and pre-treated with lipopolysaccharide (LPS) to mimic sepsis-induced intestinal injury. The LPS-induced sepsis model was used as a reference. We used quantitative real-time polymerase chain reaction to evaluate the RNA levels of inflammatory factors and antimicrobial peptides. Enzyme-linked immunosorbent assay was used to evaluate the protein levels, hematoxylin and eosin staining was used to evaluate the pathology of the small intestine of mice, and immunohistochemistry and immunofluorescence were used to evaluate the intestinal epithelial barrier function. Perkin Elmer Operetta™ was used to obtain high-resolution images of three-dimensional organoids.
		                        		
		                        			RESULTS:
		                        			An LPS concentration >150 μg/mL after 24 h was identified to cause organoid growth restriction. The fluorescence intensity of zonula occludens-1 and occludins at LPS concentrations >100 μg/mL decreased significantly after 24 h. After LPS stimulation for 8 h, the RNA expression levels of interleukin (IL)-1α, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, IL-6, and regenerating islet-derived protein 3 alpha, beta, and gamma increased. These results resembled those of intestinal epithelial layer alterations in a mouse sepsis model. For IL-10, the RNA expression level increased only when the LPS level >200 μg/mL for 24 h.
		                        		
		                        			CONCLUSIONS
		                        			This study provides the primary intestinal in vitro model to study the effects of LPS-induced intestinal injury resembling sepsis. This model provides a platform for immune associated mechanism exploration and effective drug screening.
		                        		
		                        		
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Lipopolysaccharides/toxicity*
		                        			;
		                        		
		                        			Sepsis
		                        			;
		                        		
		                        			Intestinal Diseases
		                        			;
		                        		
		                        			Tumor Necrosis Factor-alpha
		                        			;
		                        		
		                        			Disease Models, Animal
		                        			;
		                        		
		                        			Organoids
		                        			;
		                        		
		                        			RNA
		                        			
		                        		
		                        	
10.Activating transcription factor 4 protects mice against sepsis-induced intestinal injury by regulating gut-resident macrophages differentiation
Zhenliang WEN ; Xi XIONG ; Dechang CHEN ; Lujing SHAO ; Xiaomeng TANG ; Xuan SHEN ; Sheng ZHANG ; Sisi HUANG ; Lidi ZHANG ; Yizhu CHEN ; Yucai ZHANG ; Chunxia WANG ; Jiao LIU
Chinese Medical Journal 2022;135(21):2585-2595
		                        		
		                        			
		                        			Background::Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury.Methods::Sepsis was induced in C57BL/6 wild type (WT) mice and Atf4-knockdown ( Atf4+/-) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Results::CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6C hi monocytes), the precursor cells of gMacs. Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice, Atf4+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes ( TNF-α, IL-1β), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting from Atf4 knockdown was not caused by the enhanced inflammatory effect of Ly6C hi monocytes and gMacs. Conclusion::ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.
		                        		
		                        		
		                        		
		                        	
            
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