1.Clinical application value of a predictive model for the efficacy of third-generation cephalosporin in treatment of community-acquired spontaneous bacterial peritonitis
Longchuan ZHU ; Wei WU ; Dakai GAN ; Wei ZHANG ; Yizhen XU ; Molong XIONG
Journal of Clinical Hepatology 2024;40(2):306-311
		                        		
		                        			
		                        			ObjectiveTo investigate the clinical application value of a predictive model for the efficacy of third-generation cephalosporin in the treatment of community-acquired spontaneous bacterial peritonitis (CASBP). MethodsThis prospective study was conducted among 50 patients with liver cirrhosis and CASBP who were admitted to The Ninth Hospital of Nanchang from January 2021 to June 2022, and the patients were randomly divided into optimized treatment group and traditional treatment group, with 25 patients in each group. The patients in the optimized treatment group received ceftazidime or imipenem for initial treatment based on the above predictive model, and those in the traditional treatment group received ceftazidime for initial treatment, with the subsequent use of antibiotics adjusted based on the efficacy of initial treatment. The two groups were compared in terms of the response rate of initial treatment, cure rate on day 5, and 30-day mortality rate. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsAll patients completed the study. The optimized treatment group had a significantly higher response rate of initial treatment than the traditional treatment group (88.0% vs 60.0%, χ2=5.094, P=0.024), while there was no significant difference in the cure rate on day 5 between the two groups (80.0% vs 56.6%, χ2=3.309, P=0.069). As for the patients who received ceftazidime for initial treatment, the optimized treatment group had a significantly higher response rate of initial treatment than the traditional treatment group (88.9% vs 60.0%, χ2=4.341, P=0.037), while there was no significant difference in the cure rate on day 5 between the two groups (83.3% vs 56.0%, χ2=2.425, P=0.119). There was no significant difference in 30-day mortality rate between the two groups (8.0% vs 20.0%, χ2=0.664, P=0.415). For all patients, there was a significant association between response of initial treatment and cure on day 5 (odds ratio [OR]=9.643, 95% confidence interval [CI]: 2.292 — 40.564) and between cure on day 5 and 30-day mortality (OR=0.138, 95%CI: 0.023 — 0.813). ConclusionThis predictive model for efficacy helps clinicians to identify the patients who can benefit from third-generation cephalosporin treatment and improve the efficacy of third-generation cephalosporin in the initial empirical treatment of CASBP. 
		                        		
		                        		
		                        		
		                        	
2.Analysis on the spatial-temporal distribution characteristics of hepatitis B incidence in a county of western Liaoning province from Jan 2011 to Dec 2021
Yizhen WU ; Xiaoling XUE ; Xinzu SHI
Journal of Shenyang Medical College 2024;26(3):299-303
		                        		
		                        			
		                        			Objective:To understand the incidence and spatial-temporal distribution characteristics of hepatitis B among residents in a county of western Liaoning province from Jan 2011 to Dec 2021.Methods:Data on hepatitis B incidence were obtained from the Disease Prevention and Control Center of the county,and its crude incidence and standardized incidence were calculated.ArcGIS software was used to analyze the global spatial autocorrelation analysis and local spatial autocorrelation analysis of hepatitis B incidence in the county.A space-time scan analysis was performed using SaTScan software to identify the case distribution and spatiotemporal clustering patterns of hepatitis B incidence.Results:From Jan 2011 to Dec 2021,there were 2 978 cumulative cases of hepatitis B in the county,with a crude incidence of 69.25 per 100 000 and a standardized incidence of 70.13 per 100 000.Among different regions,Toutai Manchu Town had the highest crude incidence of hepatitis B,followed by Gaotaizi Town and Chengguan Street.The global autocorrelation showed an aggregated distribution in 2014,2016,2019,and 2021.The local autocorrelation hotspots were clustered in the central and western parts of the county,the H-H clustering areas included Toutai Manchu Town and Jiudaoling Town from 2014 to 2016,Toudaohe Manchu Town,Yizhou Street and Chengguan Street from 2017 to 2019,and Qianyang Town and Yizhou Street from 2020 to 2021.The L-L clustering areas were mostly concentrated in the southwest of the county,including Dizangsi Manchu Township,Dadingbao Manchu Township and Liulonggou Manchu Township.A total of 4 clustering areas were obtained by temporal-spatial scanning analysis,the first-level area was Zhangjiapu Township in 2017,the second-level area included Qianyang Town and Chengguan Street from 2011 to 2015,the third-level area was Gaotaizi Town from 2013 to 2016,and the fourth-level area was Toutai Manchu Town from 2014 to 2017.Conclusions:From Jan 2011 to Dec 2021,the incidence of hepatitis B among residents in a county in western Liaoning Province is mainly concentrated in the central and northwest regions.The hepatitis B cases are clustered in the central and western areas of the county,and has a trend of gradually spreading to the northern areas over time.It is necessary to pay attention to the townships with high incidence of hepatitis B and carry out effective prevention and surveillance.
		                        		
		                        		
		                        		
		                        	
3.Design and application of clinical probation log based on subjective-objective-assessment-plan
Zhifeng WU ; Li MING ; Zhangya YANG ; Min WANG ; Yizhen SUN ; Wang YANG ; Zhiqiang CHEN ; Zhangxue HU ; Yuping ZHANG
Chinese Journal of Medical Education Research 2024;23(7):906-909
		                        		
		                        			
		                        			Objective:To investigate the application value of a new clinical probation log designed based on the subjective-objective-assessment-plan (SOAP) structured medical record.Methods:Quantitative and qualitative studies were conducted among 97 students in the autumn semester to evaluate the effect of the new clinical probation log based on the SOAP structured medical record on their academic performance and clinical thinking. SPSS 26.0 was used to perform the t-test and ANOVA. Results:The students using the new version had a significantly better score (96.29±1.38) than those using the old version (93.53±1.60) ( P<0.001), while the multivariate analysis showed that the students who first used the old version and then switched to the new version had a significantly better improvement in the score compared with those who first used the new version and then switched to the old version ( P<0.001). The qualitative interview showed that it was necessary to use handwritten internship log, and compared with the old version, the new version could better promote the ordered clinical thinking of students. The teacher comments could give feedbacks, and all the students interviewed thought that the new version held promise for clinical application. Conclusions:The clinical probation log based on the SOAP structured medical record can help to improve the effectiveness of probation and cultivate clinical thinking ability, and thus it holds promise for application in clinical probation teaching.
		                        		
		                        		
		                        		
		                        	
4.Prenatal diagnosis of fetal microdeletion and microduplication syndromes among pregnant women with advanced maternal ages
Fang DUAN ; Qichang WU ; Yasong XU ; Shiyu SUN ; Yizhen JI ; Li SUN
Chinese Journal of Medical Genetics 2024;41(4):486-493
		                        		
		                        			
		                        			Objective:To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) and/or copy number variation sequencing (CNV-seq) for the prenatal diagnosis for women with advanced maternal ages, and to explore the challenges of prenatal genetic counseling brought by the types of fetal CNVs and uncertainty of related phenotypes.Methods:A retrospective analysis was carried out on 1 841 women with advanced maternal age who underwent interventional prenatal diagnosis at the Prenatal Diagnosis Center of Xiamen University Affiliated Women and Children′s Hospital from January 2017 to December 2020. Routine chromosomal karyotyping analysis and CMA/CNV-seq detection were carried out.Results:CMA/CNV-seq had detected pathogenic variants in 2 cases which had failed karyotyping analysis. Two hundred and twenty one fetal chromosomal abnormalities were detected by karyotyping analysis, among which 187 were detected by CMA/CNV-seq. CMA/CNV-seq analysis of 23 cases with balanced chromosome structural aberrations and 10 cases with low proportion mosaicisms (including a marker chromosome) had yielded a negative result. In addition, 26 cases (26/1 841, 1.4%) with pathogenic CNVs were discovered among those with a normal karyotype, of which 13 (50.0%) were recurrent CNVs associated with neurocognitive impairment, with 22q11.21 microdeletions and microduplications being the most common types (26.92%).Conclusion:The combination of karyotyping analysis and CMA/CNV-seq not only increased the rate of prenatal diagnosis, but also complemented with each other, which has facilitated genetic counseling and formulation of prenatal diagnosis strategy for the affected families.
		                        		
		                        		
		                        		
		                        	
5.Clinical features and genetic analysis of two fetuses with ring chromosome 21 mosaicism.
Yizhen JI ; Yasong XU ; Li SUN ; Yunsheng GE ; Meijiao CAI ; Qichang WU
Chinese Journal of Medical Genetics 2023;40(8):1032-1035
		                        		
		                        			OBJECTIVE:
		                        			To investigate the perinatal clinical phenotype and genetic characteristics of two fetuses with ring chromosome 21 mosaicisms.
		                        		
		                        			METHODS:
		                        			Two fetuses who were diagnosed at the Xiamen Maternal and Child Health Care Hospital in November 2021 were selected as the study subjects. Clinical data of the two fetuses were collected. Conventional G-banded karyotyping and chromosomal microarray analysis (CMA) were carried out for the fetuses and their parents.
		                        		
		                        			RESULTS:
		                        			Prenatal ultrasonography of fetus 1 has revealed absence of nasal bone, ventricular septal defect, persistent left superior vena cava, and mild tricuspid regurgitation. Chromosomal karyotyping was 46,X?,dic r(21;21)(p12q22;q22p12)[41]/45,X?,-21[9]. CMA has revealed a 30.00 Mb quadruplication at 21q11.2q22.3 and a 3.00 Mb deletion at 21q22.3. For fetus 2, ultrasonography has revealed pointed echo of the nasal bone. The fetus was found to have a karyotype of 46,X?,r(21)(p12q22)[83]/45,X?,-21[14]/46,X?,dic r(21;21)(p12q22;q22p12)[3]. CMA has revealed a 5.10 Mb quadruplication at 21q22.12q22.3 and a 2.30 Mb deletion at 21q22.3.
		                        		
		                        			CONCLUSION
		                        			The perinatal phenotype of the two fetuses with ring chromosome 21 mosaicisms is related to the duplication of chromosomal segments near the breakpoints of the chromosomal deletions. The combined chromosomal karyotyping and CMA has enabled prenatal diagnosis and genetic counseling for these families.
		                        		
		                        		
		                        		
		                        			Pregnancy
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Mosaicism
		                        			;
		                        		
		                        			Ring Chromosomes
		                        			;
		                        		
		                        			Vena Cava, Superior
		                        			;
		                        		
		                        			Chromosome Aberrations
		                        			;
		                        		
		                        			Prenatal Diagnosis
		                        			;
		                        		
		                        			Microarray Analysis
		                        			;
		                        		
		                        			Fetus/diagnostic imaging*
		                        			
		                        		
		                        	
6.Identification of metabolites in different parts of Juandan Baihe (Lilium lancifolium) by UPLC-Q-TOF-MS and their hypoglycemic activities
ZHANG Luoqin ; WU Yizhen ; WANG Hong ; XIANG Sheng ; WANG Binghui ; TAN Xiaowen ; LI Zhongzheng
Digital Chinese Medicine 2023;6(4):426-437
		                        		
		                        			Objective :
		                        			To identify the main components in the extracts of different parts of Juandan Baihe (Lilium lancifolium) by ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technology and investigate their hypoglycemic activities.
		                        		
		                        			Methods:
		                        			The MS fragmentation pathways of the main types of compounds in Juandan Baihe (Lilium lancifolium) were studied, and the main components in the extracts were systematically identified using MS fragmentation pathways combined with MS mining technology. Based on the hyperglycemia male mouse model [specific pathogen free (SPF)-grade Kunming mice] induced by streptozotocin (intragastric administration of 80 mg/kg for 3 d), the hypoglycemic effects of extracts of Juandan Baihe (Lilium lancifolium) roots, stems, corms, leaves, and flowers were evaluated by measuring the changes of blood glucose, daily water consumption, daily food intake, and body weight.
		                        		
		                        			Result:
		                        			The MS fragmentation pathways of regalosides, dioscins, phenylpropanoids, flavonoids, and chlorogenic acids in Juandan Baihe (Lilium lancifolium) were clarified, and a mining method for compounds in this plant was constructed. A total of 58 compounds, including 6 chlorogenic acids, 14 regalosides, 13 phenylpropanoids, 5 flavonoids, and 20 dioscins, were identified from the roots, stems, corms, leaves, and flowers of Juandan Baihe (Lilium lancifolium). Among them, 30 compounds were reported for the first time from this plant. The root and corm extracts demonstrated significant hypoglycemic activities by reducing blood glucose levels from 23.76 ± 1.21 and 24.29 ± 1.35 mmol/L to 17.21 ± 1.23 and 18.78 ± 1.49 mmol/L, respectively (P < 0.05). The roots and corms extracts could also attenuate the symptoms of polydipsia (P < 0.01), polyphagia (P < 0.05), and weight loss caused by diabetes.
		                        		
		                        			Conclusion
		                        			This study clarifies that the roots of Juandan Baihe (Lilium lancifolium) are rich in regalosides and dioscins for the first time, and have significant hypoglycemic activities, providing the foundation for the comprehensive utilization of this plant and the development of hypoglycemic drugs.
		                        		
		                        		
		                        		
		                        	
7.Improvement of xeroderma and water content of the stratum corneum in children with a moisturizer containing oat kernel oil
Suhua WU ; Kefei ZHOU ; Ming LI ; Jingxin JIANG ; Yizhen ZHANG ; Yan LI ; Linfeng LI
Chinese Journal of Medical Aesthetics and Cosmetology 2023;29(3):218-222
		                        		
		                        			
		                        			Objective:To evaluate the influence of a moisturizer containing oat kernel oil for xeroderma and water content of the stratum corneum in children.Methods:From September to December 2022, 30 children with xeroderma were treated in the Dermatology Department of Tongzhou Maternal and Child Health Hospital of Beijing; 13 were males and 17 were females, and the age was 7.33±2.63 years. This was a single-center self-controlled trial. All children applied the moisturizer on the dry skin of the bilateral limbs two time per day for 14 days, and were followed up at 7 days and 14 days. Efficacy was evaluated according to the water content of the stratum corneum, visual scale, xerosis severity scale (XSS), Specified Symptom Sum Score (SRRC), Visual Analog Scale (VAS) and so on. and side-reactions were recorded.Results:After application of the moisturizer, the median of water content in the stratum corneum was 49.00 (33.83, 87.25), 48.84 (32.58, 100.34) at 7 d and 14 d respectively, showing significant increases compared with that at baseline (median 26.51 (16.00, 47.75) ( Z=-3.075, Z=-2.911, P<0.01). The visual scale, XSS, SRRC and VAS showed that compared with the baseline at 7 d, 14 d, the skin dryness and pruritus scores improved significantly ( Z=-4.424, -4.150, -3.943, -4.400; Z=-4.744, -4.409, -4.260, -4.409, P<0.01). Conclusions:The application of this moisturizer containing oat kernel oil could effectively improve skin dryness and the water content of the stratum corneum without serious adverse reactions.
		                        		
		                        		
		                        		
		                        	
8.Mechanisms of imperatorin on regulating P-glycoprotein in blood-brain barrier based on network pharmacology and in vitro experi-ment
Yizhen SONG ; Wanxin YIN ; Yicong MA ; Yufan AN ; Jiaqi HUANG ; Zhongjie YAN ; Xiuwen WU ; Yuanyu WANG
Chinese Journal of Pharmacology and Toxicology 2023;37(z1):17-18
		                        		
		                        			
		                        			OBJECTIVE To explore mecha-nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net-work pharmacology combined with in vitro experi-ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data-bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100 μ mol·L-1)on P-gp activity were monitored in hCMEC/D3in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans-mission regulation,neurotransmitter receptor activity,proteinkinaseregulationactivity,G protein-coupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig-naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi-cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu-lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro-tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer-ence basis for further exploration of the mecha-nisms of imperatorin on regulating P-gp in BBB.
		                        		
		                        		
		                        		
		                        	
9.Comparison of 68Ga-FAPI and 18F-FDG PET/CT for the diagnosis of primary and metastatic gastric signet-ring cell carcinoma
Long ZHAO ; Yizhen PANG ; Weizhi XU ; Tinghua MENG ; Jiayu CAI ; Tianxing PENG ; Zuoming LUO ; Long SUN ; Hua WU ; Haojun CHEN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(6):325-330
		                        		
		                        			
		                        			Objective:To investigate the clinical utility of 68Ga-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in the detection of primary and metastatic gastric signet-ring cell carcinoma (GSRCC) and compared the results with those of 18F-FDG PET/CT. Methods:A total of 21 patients (10 males, 11 females, average age 52 years) with primary and metastatic GSRCC who underwent 68Ga-FAPI and 18F-FDG PET/CT at the First Affiliated Hospital of Xiamen University from June 2020 to May 2022 were retrospectively analyzed. Pathological results of surgery and (or) biopsy were used as the " gold standard" for final diagnosis. In cases whose surgery or tissue biopsies were not available, clinical and radiographic follow-up results were used as the reference standards. Wilcoxon signed-rank test was used to compare the SUV max of 18F-FDG and 68Ga-FAPI. McNemar χ2 test was used to compare the detection rate between 18F-FDG and 68Ga-FAPI PET/CT. Results:68Ga-FAPI PET/CT showed higher SUV max than 18F-FDG in primary tumors (5.3(2.4, 15.7) vs 2.4(1.8, 2.5); z=2.31, P=0.021), local recurrences (7.8(6.0, 8.9) vs 2.4(1.9, 3.4); z=2.20, P=0.028), lymph nodes metastases (7.7(4.5, 12.2) vs 2.4(1.9, 3.6); z=6.01, P<0.001) and bone/visceral metastases (6.7(5.3, 11.1) vs 2.4(2.0, 3.4); z=11.36, P<0.001). Regarding diagnostic accuracy, 68Ga-FAPI PET/CT showed higher sensitivities than 18F-FDG for primary tumors (7/9 vs 2/9; χ2=3.20, P=0.063) and local recurrences (7/7 vs 2/7; χ2=3.20, P=0.063). It also demonstrated higher lesion detection rates than 18F-FDG for suspicious lymph node metastases (86%(65/76) vs 32%(24/76); χ2=31.37, P<0.001) and bone/visceral metastases (99%(184/185) vs 39%(73/185); χ2=107.08, P<0.001). Conclusions:68Ga-FAPI PET/CT showed higher tumor uptake and lesion detection rate than 18F-FDG in the primary and metastatic GSRCC. 68Ga-FAPI PET/CT demonstrates good diagnostic performance for tumor detection, staging, and restaging of GSRCC, which is helpful to further guide clinical treatment strategy.
		                        		
		                        		
		                        		
		                        	
10.Development of radiolabeled tetramer that targeting fibroblast activation protein and theranostic research in tumor xenografts
Liang ZHAO ; Jianhao CHEN ; Yizhen PANG ; Jianyang FANG ; Zhide GUO ; Hua WU ; Long SUN ; Qin LIN ; Haojun CHEN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(6):343-348
		                        		
		                        			
		                        			Objective:To develop a tetramer probe targeting fibroblast activation protein (FAP), named 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-4P(FAP inhibitor (FAPI)) 4, evaluate its biodistribution and PET image in FAP-positive-tumor bearing nude mice, and explore its feasibility as a novel radio-regent for treatment of FAP-positive tumor. Methods:FAP tetramer probe was constructed on the FAPI-46 motif with four mini-polyethylene glycol (PEG)(PEG 3) spacers between the four FAPI motifs, denoted as 4P(FAPI) 4. DOTA was used as the chelator for radiolabeling with 68Ga and 177Lu. The FAP binding characteristics were test by in vitro cell competitive binding experiment. Small-animal PET, in vivo biodistribution, and radionuclide targeting therapy were performed in HT-1080-FAP tumor bearing nude mice ( n=39). Independent-sample t test was performed to analyze tumor uptake data, and two-factor repeated measures analysis of variance was utilized to compare tumor volume data in radioactive isotope therapy. Results:Cell experiment showed that FAPI-tetramer and FAPI-monomer had similar half maximal inhibitory concentration values (3.29 and 2.15 nmol/L). 68Ga/ 177Lu radiolabeled FAPI-tetramer had better tumor uptake and retention than FAPI-monomer in small-animal PET and in vivo biodistribution experiment, with the tumor uptake for 177Lu-DOTA-4P(FAPI) 4 and 177Lu-FAPI-46 at 48 h of (18.72±1.32) vs (2.72±1.20) percentage activity of injection dose per gram of tissue (%ID/g) ( t=15.55, P<0.001). 177Lu-DOTA-4P(FAPI) 4 group showed best anti-tumor efficacy compared with 177Lu-FAPI-46 and control group in radionuclide targeting therapy. On the 2nd day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the control group (mean difference 67.19 mm 3, P=0.049); on the 14th day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the monomer treatment group (mean difference 414.33 mm 3, P=0.005). Conclusion:FAPI-tetramer can improve tumor uptake and retention ability compared with FAPI-46, and 177Lu-DOTA-4P(FAPI) 4 can be a promising radio-agent for FAP-positive tumor therapy.
		                        		
		                        		
		                        		
		                        	
            
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