1.Research progress on biomarkers for proficient mismatch repair/microsatellite stable colorectal cancer in the immunotherapy era
Mingxu YAN ; Yaqi WANG ; Lijun SHEN ; Zhen ZHANG
Chinese Journal of Gastrointestinal Surgery 2025;28(7):796-803
Immunotherapy based on immune checkpoint inhibitor (ICI) has shown remarkable efficacy in the treatment of microsatellite instability (MSI)-high CRC. However, the monotherapy of ICI in microsatellite stable (MSS) CRC has not been satisfactory. Some patients with MSS CRC can benefit from various combination immunotherapy regimens. Identifying appropriate biomarkers to select MSS-type CRC patients who will benefit from ICI treatment prior to therapy initiation and dynamically monitoring treatment efficacy during the therapeutic course have become crucial components of precision medicine in clinical practice. This article reviews the current research status of traditional biomarkers such as tumor mutation burden (TMB) and PD-L1 expression. It also explores the latest research progress and clinical translation potential of emerging biomarkers, including POLE/POLD1 mutations, immune score, circulating tumor DNA, and gut microbiome. Furthermore, it addresses the challenges in the clinical application of biomarkers, such as the controversy over TMB cutoff values and the heterogeneity of PD-L1 expression. Finally, it outlines future research directions with the aim of providing a basis for clinical decision-making in immunotherapy and facilitating the realization of precision medicine.
2.Genetic Analysis of Prenatal Renal Abnormalities in 17q12 Microdeletion Syndrome
Yongmei SHEN ; Yaqi LI ; Xiaomin ZHAO ; Lei ZHANG ; Liying YAO ; Jiasong CAO ; Qimei LIN ; Hefei WANG ; Maolin NIE ; Rongxin WEI ; Ying CHANG
Maternal-Fetal Medicine 2025;07(3):151-156
Objective::To analyze fetal renal abnormality genetic features and the prenatal characteristics of the 17q12 microdeletion syndrome.Methods::This prospective cohort study examined prenatal ultrasound findings of renal abnormalities in pregnant women who underwent single nucleotide polymorphism (SNP) array or copy number variation sequencing (CNV-seq) testing on amniotic fluid or fetal tissue at Tianjin Central Obstetrics and Gynecology Hospital between January 2016 and August 2022. The study cohort comprised women with advanced maternal age, fetal ultrasound anomalies, high-risk non-invasive prenatal testing results, or suspected 17q12 microdeletion syndrome. Comprehensive clinical data, including maternal age, detailed ultrasound findings, and pregnancy outcomes, were systematically collected. SNP-array analysis was conducted using an Affymetrix CytoScan 750 K Array Chip to identify CNVs and loss of heterozygosity, while CNV-seq was performed on the Illumina HiSeq 2000 platform. Detected variants were classified according to the American College of Medical Genetics and Genomics guidelines. Statistical analyses were performed using SPSS version 27.0.Results::Abnormal renal development was identified in 141 patients, among whom 26 exhibited hyperechogenic kidneys (HCK). Of these, 12 cases were associated with 17q12 microdeletion syndrome, while the remaining 14 were linked to other chromosomal abnormalities. When excluding patients with HCK, those diagnosed with polycystic kidney disease demonstrated a higher prevalence of chromosomal abnormalities compared to those with multicystic dysplastic kidney and renal dysplasia. Although isolated conditions such as horseshoe kidney, hydronephrosis, ectopic kidney, and unilateral kidney typically presented with normal chromosomal findings, the incidence of chromosomal abnormalities increased when these conditions coexisted with other anomalies. A detailed analysis of the correlation between 17q12 microdeletion syndrome and HCK revealed that 12 out of the 14 patients diagnosed with 17q12 microdeletion syndrome exhibited HCK. Genetic testing confirmed the syndrome in seven patients, with five cases attributed to novel mutations and two cases resulting from inherited mutations.Conclusion::Fetal HCK was closely associated with the 17q12 microdeletion syndrome, and polycystic kidney disease showed a higher rate of chromosomal abnormalities. Chromosome test results were mostly normal in patients with other renal abnormalities, such as kidney dysplasia, horseshoe kidneys, hydronephrosis, kidney deficiency, and ectopic kidneys. Prenatal diagnosis is recommended, especially in cases of non-isolated fetal renal abnormalities. This study provides strong evidence supporting a link between fetal renal abnormalities and genetic syndromes.
3.Correlation analysis of incidence trends of severe fever with thrombocytopenia syndrome (SFTS) and meteorological factors in Weifang city, Shandong province, 2015-2024
Ziliang FAN ; Xiyuan HUO ; Yaqi SHEN ; Cuimei GU ; Zhu YANG ; Senmei YUAN ; Miaomiao SHAN ; Jian ZHOU ; Ye ZHANG ; Dongying LI
Chinese Journal of Experimental and Clinical Virology 2025;39(2):154-161
Objective:To investigate the potential causes of the rising epidemic of severe fever with thrombocytopenia syndrome (SFTS) in Weifang, Shandong province.Methods:The temporal trend of SFTS epidemic was segmented using Joinpoint regression analysis. Changes in epidemiological characteristics across different periods were compared, and correlation analysis was conducted to identify meteorological factors influencing the epidemic trend.Results:Joinpoint regression revealed two distinct periods for SFTS epidemic in Weifang: 2015-2021 and 2022-2024. No significant trend was observed during 2015-2021 ( P=0.634), while a sharp annual increase of 46.69% occurred from 2022 to 2024 ( P=0.006). Spatial autocorrelation analysis demonstrated a global Moran’s I of 0.42 ( Z=8.55, P<0.001) for 2015-2021, with 15 high-high clustering areas identified. For 2022-2024, the global Moran’s I decreased to 0.37 ( Z=7.31, P<0.001), with 13 high-high clusters, including newly emerging hotspots in Anqiu and Zhucheng in the southeastern region. High-risk populations remained individuals aged ≥50 in mountainous and hilly areas, with a marked rise in incidence in these groups. The male-to-female ratio of cases was higher in plain areas than in mountainous/hilly regions. Autumn (September-November) temperatures from the preceding year showed a positive correlation with annual case numbers ( P=0.004, r=0.82). The linear regression expression is y=40.61x-580.78 (y is the annual incidence, and x is the average daily temperature of last autumn). Conclusions:The SFTS epidemic in Weifang is showing a rising trend. There is a linear correlation between the temperature of the previous autumn and the scale of SFTS epidemic in the following year. This correlation allows for predicting the subsequent year′s epidemic, thereby enabling early warning of SFTS.
4.Genetic Analysis of Prenatal Renal Abnormalities in 17q12 Microdeletion Syndrome
Yongmei SHEN ; Yaqi LI ; Xiaomin ZHAO ; Lei ZHANG ; Liying YAO ; Jiasong CAO ; Qimei LIN ; Hefei WANG ; Maolin NIE ; Rongxin WEI ; Ying CHANG
Maternal-Fetal Medicine 2025;07(3):151-156
Objective::To analyze fetal renal abnormality genetic features and the prenatal characteristics of the 17q12 microdeletion syndrome.Methods::This prospective cohort study examined prenatal ultrasound findings of renal abnormalities in pregnant women who underwent single nucleotide polymorphism (SNP) array or copy number variation sequencing (CNV-seq) testing on amniotic fluid or fetal tissue at Tianjin Central Obstetrics and Gynecology Hospital between January 2016 and August 2022. The study cohort comprised women with advanced maternal age, fetal ultrasound anomalies, high-risk non-invasive prenatal testing results, or suspected 17q12 microdeletion syndrome. Comprehensive clinical data, including maternal age, detailed ultrasound findings, and pregnancy outcomes, were systematically collected. SNP-array analysis was conducted using an Affymetrix CytoScan 750 K Array Chip to identify CNVs and loss of heterozygosity, while CNV-seq was performed on the Illumina HiSeq 2000 platform. Detected variants were classified according to the American College of Medical Genetics and Genomics guidelines. Statistical analyses were performed using SPSS version 27.0.Results::Abnormal renal development was identified in 141 patients, among whom 26 exhibited hyperechogenic kidneys (HCK). Of these, 12 cases were associated with 17q12 microdeletion syndrome, while the remaining 14 were linked to other chromosomal abnormalities. When excluding patients with HCK, those diagnosed with polycystic kidney disease demonstrated a higher prevalence of chromosomal abnormalities compared to those with multicystic dysplastic kidney and renal dysplasia. Although isolated conditions such as horseshoe kidney, hydronephrosis, ectopic kidney, and unilateral kidney typically presented with normal chromosomal findings, the incidence of chromosomal abnormalities increased when these conditions coexisted with other anomalies. A detailed analysis of the correlation between 17q12 microdeletion syndrome and HCK revealed that 12 out of the 14 patients diagnosed with 17q12 microdeletion syndrome exhibited HCK. Genetic testing confirmed the syndrome in seven patients, with five cases attributed to novel mutations and two cases resulting from inherited mutations.Conclusion::Fetal HCK was closely associated with the 17q12 microdeletion syndrome, and polycystic kidney disease showed a higher rate of chromosomal abnormalities. Chromosome test results were mostly normal in patients with other renal abnormalities, such as kidney dysplasia, horseshoe kidneys, hydronephrosis, kidney deficiency, and ectopic kidneys. Prenatal diagnosis is recommended, especially in cases of non-isolated fetal renal abnormalities. This study provides strong evidence supporting a link between fetal renal abnormalities and genetic syndromes.
5.Research progress on biomarkers for proficient mismatch repair/microsatellite stable colorectal cancer in the immunotherapy era
Mingxu YAN ; Yaqi WANG ; Lijun SHEN ; Zhen ZHANG
Chinese Journal of Gastrointestinal Surgery 2025;28(7):796-803
Immunotherapy based on immune checkpoint inhibitor (ICI) has shown remarkable efficacy in the treatment of microsatellite instability (MSI)-high CRC. However, the monotherapy of ICI in microsatellite stable (MSS) CRC has not been satisfactory. Some patients with MSS CRC can benefit from various combination immunotherapy regimens. Identifying appropriate biomarkers to select MSS-type CRC patients who will benefit from ICI treatment prior to therapy initiation and dynamically monitoring treatment efficacy during the therapeutic course have become crucial components of precision medicine in clinical practice. This article reviews the current research status of traditional biomarkers such as tumor mutation burden (TMB) and PD-L1 expression. It also explores the latest research progress and clinical translation potential of emerging biomarkers, including POLE/POLD1 mutations, immune score, circulating tumor DNA, and gut microbiome. Furthermore, it addresses the challenges in the clinical application of biomarkers, such as the controversy over TMB cutoff values and the heterogeneity of PD-L1 expression. Finally, it outlines future research directions with the aim of providing a basis for clinical decision-making in immunotherapy and facilitating the realization of precision medicine.
6.Correlation analysis of incidence trends of severe fever with thrombocytopenia syndrome (SFTS) and meteorological factors in Weifang city, Shandong province, 2015-2024
Ziliang FAN ; Xiyuan HUO ; Yaqi SHEN ; Cuimei GU ; Zhu YANG ; Senmei YUAN ; Miaomiao SHAN ; Jian ZHOU ; Ye ZHANG ; Dongying LI
Chinese Journal of Experimental and Clinical Virology 2025;39(2):154-161
Objective:To investigate the potential causes of the rising epidemic of severe fever with thrombocytopenia syndrome (SFTS) in Weifang, Shandong province.Methods:The temporal trend of SFTS epidemic was segmented using Joinpoint regression analysis. Changes in epidemiological characteristics across different periods were compared, and correlation analysis was conducted to identify meteorological factors influencing the epidemic trend.Results:Joinpoint regression revealed two distinct periods for SFTS epidemic in Weifang: 2015-2021 and 2022-2024. No significant trend was observed during 2015-2021 ( P=0.634), while a sharp annual increase of 46.69% occurred from 2022 to 2024 ( P=0.006). Spatial autocorrelation analysis demonstrated a global Moran’s I of 0.42 ( Z=8.55, P<0.001) for 2015-2021, with 15 high-high clustering areas identified. For 2022-2024, the global Moran’s I decreased to 0.37 ( Z=7.31, P<0.001), with 13 high-high clusters, including newly emerging hotspots in Anqiu and Zhucheng in the southeastern region. High-risk populations remained individuals aged ≥50 in mountainous and hilly areas, with a marked rise in incidence in these groups. The male-to-female ratio of cases was higher in plain areas than in mountainous/hilly regions. Autumn (September-November) temperatures from the preceding year showed a positive correlation with annual case numbers ( P=0.004, r=0.82). The linear regression expression is y=40.61x-580.78 (y is the annual incidence, and x is the average daily temperature of last autumn). Conclusions:The SFTS epidemic in Weifang is showing a rising trend. There is a linear correlation between the temperature of the previous autumn and the scale of SFTS epidemic in the following year. This correlation allows for predicting the subsequent year′s epidemic, thereby enabling early warning of SFTS.
7.Terpene extract from the stem of Celastrus orbiculatus inhibits actin cytoskeleton remodelling in gastric cancer cells by regulating the protein interaction between PTBP1 and ACTN4
Chu ZEWEN ; Zhu MIAO ; Luo YUANYUAN ; Hu YAQI ; Feng XINYI ; Shen JIACHENG ; Wang HAIBO ; Sunagawa MASATAKA ; Liu YANQING
Journal of Pharmaceutical Analysis 2024;14(8):1158-1175
Adjuvant chemoradiotherapy,molecular targeted therapy,and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer(GC).However,most of these treatments have toxic side effects,drug resistance,and limited improvements in survival and quality of life.Therefore,it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity.In previous studies,the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity;however,the specific mechanism was unclear.Our research utilising co-immunoprecipitation-mass spectrometry(Co-IP-MS),polypyrimidine tract binding protein 1(ptbp1)clustered regularly interspaced short palindromic repeat-associated protein 9(Cas9)-knockout(KO)mouse model,tissue microarray,and functional experiments suggests that alpha actinin-4(ACTN4)could be a significant biomarker of GC.PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4.Celastrus orbiculatus stem extract(COE)may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4,thereby exerting anti-GC effects.
8.Construction of nursing quality evaluation index system for radionuclide wards
Yaqi LU ; Xia SHEN ; Qianqian LI ; Qingbo YANG ; Xuehui NAN ; Lili WEI
Chinese Journal of Modern Nursing 2024;30(21):2890-2896
Objective:To construct the nursing quality evaluation index system for radionuclide wards, so as to provide scientific basis for monitoring the quality of nursing work in radionuclide wards.Methods:With Donabedian's "structure-process-outcome" three-dimensional quality evaluation model as the theoretical framework, literature review, Delphi method and analytic hierarchy process were used to determine the contents and weights of the evaluation index system of nursing quality in radionuclide wards. The enthusiasm of experts was expressed by the effective recovery rate of the questionnaire, the authority coefficient of experts was expressed by the authority coefficient, and the coordination degree of expert opinions was expressed by the coefficient of variation and the Kendall's harmony coefficient.Results:The effective recovery rates of the two rounds of expert correspondence questionnaires were 100.00% (15/15), the expert authority coefficients were 0.880 and 0.900, the coefficient of variation were 0.10-0.26 and 0-0.16 and the Kendall's harmony coefficients were 0.131 and 0.187 ( P<0.01). The final constructed nursing quality evaluation index system for radionuclide wards included three primary indicators, 12 secondary indicators and 56 tertiary indicators. Conclusions:The constructed nursing quality evaluation index system for radionuclide wards is scientific, reliable, practical and specialized, which is close to clinical nursing work and can provide a good evaluation method for nursing quality evaluation in radionuclide wards.
9.Analysis on the application of magnetic resonance enterography in children in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2012 to 2023
Shaofang WANG ; Yanjie ZHAO ; Qiuxia WANG ; Baodi DENG ; Fangqin TAN ; Jie ZHANG ; Daoyu HU ; Yaqi SHEN
Chinese Journal of Radiology 2024;58(10):1056-1062
Objective:To review the application of pediatric magnetic resonance enterography (MRE) at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2012 to 2023, and to provide referenceable data for MRE use in complex pediatric clinical scenarios.Methods:This study was a cross-sectional study. The clinical and imaging data from children aged≤18 years who underwent MRE at Tongji Hospital between December 2012 and December 2023 were retrospectively analyzed. Out of 186 children who intended to receive the MRE examination, 12 failed, remainder 174 participants (mean age 14±4 years, range 1 month to 18 years) were included. Participants were categorized into an inflammatory bowel disease (IBD) group (118 cases) and a non-IBD group (56 cases), and further divided by age into infants (0-6 years, 8 cases), children (7-12 years, 37 cases), and adolescents (13-18 years, 129 cases). The overall image quality and the intestinal filling quality were scored using a 5-point scale. Statistical analyses included χ2 tests for age distribution, history of intestinal reconstruction surgery, and MRE success rates between IBD and non-IBD groups. Mann-Whitney U test was employed to compare subjective image quality scores between the abovementioned two groups. The Kruskal-Wallis test was used to detect the differences among the three age groups. Results:The success rate of MRE significantly increased with age: 66.7% (8/12) in infants, 88.1% (37/42) in children, and 97.7% (129/132) in adolescents ( χ2=15.39, P<0.001). A statistically significant difference in age distribution was observed between the IBD and non-IBD groups ( χ2=17.94, P<0.001). The proportion of infants in the non-IBD group was 14.3% (8/56), which was higher than that of the IBD group. The majority of the IBD group were adolescents, accounting for 78.8% (93/118). There was a statistically significant difference in the intestinal reconstruction surgery history ( χ2=2.83, P=0.005). The non-IBD group had a higher incidence of intestinal reconstructive surgery (21.4%, 12/56), compared to the IBD group (6.8%, 8/118). MRE intestinal filling quality or overall image quality scores between the IBD and non-IBD groups or among different age sub-groups were not statistically significant ( P>0.05). Conclusion:Juvenilization of non-IBD children and intestinal reconstructive surgery history could make the inspection more complex. High-quality imaging can still be achieved by adhering to technical specifications.
10.Oroxylin A regulates cholinergic anti-inflammatory pathway to inhibit Mycobacterium tuberculosis-induced macrophage pyroptosis
Hemin ZHANG ; Jingjing SHEN ; Fanglin LIU ; Jianchao WU ; Yaqi LIU ; Xin JIANG
Chinese Journal of Microbiology and Immunology 2024;44(5):423-430
Objective:To investigate the effect of oroxylin A (OrA) on macrophage pyroptosis induced by Mycobacterium tuberculosis ( Mtb) infection and the underlying molecular mechanism. Methods:An in vitro infection model was constructed by infecting J774A.1 cells with Mtb. The MTT method was used to detect the effect of OrA on the viability of J774A.1 cells. Lactate dehydrogenase (LDH) assay kit was used to detect the release of LDH by J774A.1 cells. Western blot was used to detect the protein levels of pyroptosis-related proteins such as NOD-like receptor thermal protein domain associated protein 3 (NLRP3), GSDMD-N, caspase1-p20, apoptosis-associated speck-like protein containing a CARD (ASC), and α7 nicotinic acetylcholine receptor (α7nAChR) as well as the phosphorylation of NF-κB p65. ELISA was used to detect the levels of IL-1β in each group. Immunofluorescence was performed to detect the expression and localization of α7nAChR. Results:MTT results showed that OrA had no cytotoxicity to J774A.1 cells at concentrations below 80 μmol/L. OrA reduced the release of IL-1β, down-regulated the expression of NLRP3, GSDMD-N and caspase1-p20 at protein level, inhibited ASC oligomerization, promoted the expression of α7nAChR at protein level, and inhibited the phosphorylation of NF-κB p65. In the presence of α7nAChR agonist PNU282987, the protein levels of GSDMD-N decreased and the phosphorylation of NF-κB p65 was inhibited.Conclusions:OrA may inhibits Mtb infection-induced macrophage pyroptosis through regulating cholinergic anti-inflammatory pathway.

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