1.Genome-wide association study of rubella virus vaccine strain BRD-Ⅱ
Yingmei XU ; Yongqiang ZHU ; Xin ZHOU ; Zhaoyang LIU ; Leijun MA ; Zhewen CHEN ; Yueye ZHAO ; Tiaoxia ZHU
Shanghai Journal of Preventive Medicine 2025;37(5):461-466
ObjectiveTo perform a genome-wide association study of rubella virus vaccine strain BRD-Ⅱ, so as to fully grasp the sequence characteristics of this genome. MethodsSecond-generation sequencing method was used to conduct the whole-genome sequencing on the vaccine strain BRD-Ⅱ, and the affinity tree of this genome with some vaccine strains and wild-type rubella virus strains was analyzed using the maximum likelihood method. The average genetic distance of nucleic acid sequence of each vaccine strain protein was determined. And homology comparison of structural proteins of each rubella vaccine strain, plus the comparison between this genome with the AY258323.1 genome sequence, were conducted to analyze the homology of E1 protein between the wild-type rubella virus reference strain and vaccine strain BRD-Ⅱ. ResultsThe sequencing results showed that the BRD-Ⅱ strain was a single-molecule single-stranded positive-strand ribonucleic acid (RNA), composed of 9 778 nucleotides, with a GC content of 69.35 %. The C protein was composed of 300 amino acids, the E2 glycoprotein was composed of 282 amino acids, and the E1 glycoprotein was composed of 481 amino acids. The results of preliminary analysis showed that the average genetic distances of nucleic acid sequences were 0.066 700 for the P150 protein, 0.061 933 for the P90 protein, 0.057 850 for the C protein, 0.068 167 for the E2 protein, and 0.068 833 for the E1 protein, respectively. The amino acid sequences in the E2 protein and E1 protein regions of the two BRD-Ⅱ strains did not change, confirming the conserved regions of the E1 protein by comparison. ConclusionThe sequence characteristics of the genome are clarified, which have laid a broad foundation for the subsequent detection of the genetic stability of the main antigen genes.
2.Mechanism of action of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma
Xue YU ; Tianhao SHEN ; Cheng ZHOU ; Yu LIU ; Wei LI ; Tinghui JIANG ; Yongqiang ZHU ; Yan LIU
Journal of Clinical Hepatology 2025;41(3):588-593
Intrahepatic cholangiocarcinoma is a malignant tumor with an extremely poor prognosis, and its pathogenesis is complex and remains unclear. In recent years, more and more studies have focused on the role of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma. Bile-gut axis refers to the complex interaction between bile and gut microbiota, including bile salt metabolism, dynamic changes of microbiota, inflammatory response, and immune system regulation. This article elaborates on the potential mechanisms of bile-gut axis in intrahepatic cholangiocarcinoma, especially gut microbiota dysbiosis, abnormal bile salt metabolism, chronic inflammatory response, and immune system interaction, this article aims to provide new perspectives and possible therapeutic targets for future research and promote the early diagnosis and effective treatment of intrahepatic cholangiocarcinoma.
3.Initial clinical experience with the perceval sutureless aortic valve: insights from a single center
Tong TAN ; Yongqiang LAI ; Jiangang WANG ; Xiubin YANG ; Ran DONG ; Hao CUI ; Enjun ZHU ; Hongchang GUO
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(10):624-629
Objective:To summarize the early clinical outcomes of aortic valve replacement(AVR) using the Perceval sutureless aortic valve.Methods:This retrospective study included 50 patients who underwent AVR with the Perceval sutureless prostheses at Beijing Anzhen Hospital between June 2023 and January 2025. Surgical parameters, early clinical outcomes, valve function, and hemodynamic performance were evaluated to summarize clinical effectiveness.Results:The mean age of patients was(63.5±9.1) years, predominantly female(36/50). Severe aortic stenosis was present in 43 cases(86.0%). A preoperative aortic annulus dimension of 20.0(19.0, 21.0) mm measured in both anteroposterior and transverse diameters. Preoperative peak transvalvular gradient was(92.7±31.0)mmHg(1 mmHg=0.133 kPa), with a mean gradient of (58.0±21.2) mmHg. All procedures were successfully completed using the Perceval sutureless prostheses. Isolated AVR was performed in 20 patients(40.0%), with cardiopulmonary bypass and aortic cross-clamp times of 75.0(50.5, 99.5) min and 50.5(29.5, 71.5) min, respectively. Postoperative transesophageal echocardiography revealed an immediate reduction in the peak transvalvular gradient to 11.0(8.0, 18.0) mmHg, significantly lower compared to preoperative measurements( P<0.001). Two cases of paravalvular leakage and one case requiring permanent pacemaker implantation were reported postoperatively. All patients completed the 3-month follow-up, with one death during the follow-up period; the remaining patients exhibited normal prosthetic valve function without major adverse cardiovascular events. Significant postoperative reductions were observed in left ventricular end-diastolic diameter(45.8 mm vs. 43.2 mm, P=0.003) and left atrial diameter(53.9 mm vs. 44.6 mm, P<0.001) compared with baseline. Conclusion:AVR using the Perceval sutureless prostheses demonstrated safe and effective early clinical outcomes with excellent hemodynamic performance and low incidence of postoperative paravalvular leakage and permanent pacemaker implantation. The sutureless technique represents a viable alternative strategy, particularly advantageous for patients with small aortic annuli or complex surgical conditions, warranting broader clinical adoption.
4.Sex Differences of White Matter Damage in Alzheimer's Disease and Its Association with Cognitive Impairment
Yun LU ; Xiaoshu LI ; Wanqiu ZHU ; Ziwen GAO ; Yuqing LI ; Wenrui WANG ; Wei YE ; Xiao CHEN ; Ju MA ; Yongqiang YU
Chinese Journal of Medical Imaging 2025;33(6):618-626
Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.
5.Research progress and prospects on the mechanisms of circulating tumor cells in the invasion and metastasis of cholangiocarcinoma
Xue YU ; Tianhao SHEN ; Cheng ZHOU ; Yu LIU ; Tinghui JIANG ; Wei LI ; Yongqiang ZHU ; Yan LIU
China Oncology 2025;35(10):952-958
Cholangiocarcinoma,as a malignant tumor with strong invasiveness and poor prognosis,has a complex metastasis mechanism,and urgently needs in-depth research.Circulating tumor cells(CTC),as the key cell type for tumor cells to shed from the primary site and enter the bloodstream,have significant research significance.In recent years,studies have found that the invasive pseudopodia of CTC play a significant role in the migration and invasion of tumor cells.Among them,in terms of signal transduction pathways,the Rho family GTPases(RhoA,Rac1,Cdc42)work in coordination to regulate the contractility of the pseudofoot,the branching polymerization and orientation of actin,and the phosphoinositide3-kinase/protein kinase B(PI3K/AKT)pathway promotes the assembly of actin and cross-communicates with the Rho family by activating AKT.At the molecular mechanism level,long non-coding RNAs regulate the expression of pseudopolypod-related genes by adsorbing miRNAs and other means.Matrix metalloproteinase(MMP)degrades the extracellular matrix(ECM)to form an invasion positive feedback.In terms of the microenvironment,cancer-associated fibroblast(CAF)and the cytokines such as transforming growth factor-β(TGF-β)secreted by macrophages,epidermal growth factor(EGF),and interleukin-6(IL-6)activate pseudopodia to form signal transduction pathways.ECM hardness and fiber arrangement affect the extension direction of pseudopodia through mechanical force conduction.This article conducted a comprehensive analysis of the biological characteristics of CTC,the formation mechanism of invasive pseudopodia in cholangiocarcinoma,the metastatic features of cholangiocarcinoma cells and their clinical significance,as well as the role of CTC in the metastatic process of cholangiocarcinoma,in order to summarize the existing research results,explore potential therapeutic targets and future research directions,and provide new ideas for the clinical treatment of cholangiocarcinoma.
6.Research progress and prospects on the mechanisms of circulating tumor cells in the invasion and metastasis of cholangiocarcinoma
Xue YU ; Tianhao SHEN ; Cheng ZHOU ; Yu LIU ; Tinghui JIANG ; Wei LI ; Yongqiang ZHU ; Yan LIU
China Oncology 2025;35(10):952-958
Cholangiocarcinoma,as a malignant tumor with strong invasiveness and poor prognosis,has a complex metastasis mechanism,and urgently needs in-depth research.Circulating tumor cells(CTC),as the key cell type for tumor cells to shed from the primary site and enter the bloodstream,have significant research significance.In recent years,studies have found that the invasive pseudopodia of CTC play a significant role in the migration and invasion of tumor cells.Among them,in terms of signal transduction pathways,the Rho family GTPases(RhoA,Rac1,Cdc42)work in coordination to regulate the contractility of the pseudofoot,the branching polymerization and orientation of actin,and the phosphoinositide3-kinase/protein kinase B(PI3K/AKT)pathway promotes the assembly of actin and cross-communicates with the Rho family by activating AKT.At the molecular mechanism level,long non-coding RNAs regulate the expression of pseudopolypod-related genes by adsorbing miRNAs and other means.Matrix metalloproteinase(MMP)degrades the extracellular matrix(ECM)to form an invasion positive feedback.In terms of the microenvironment,cancer-associated fibroblast(CAF)and the cytokines such as transforming growth factor-β(TGF-β)secreted by macrophages,epidermal growth factor(EGF),and interleukin-6(IL-6)activate pseudopodia to form signal transduction pathways.ECM hardness and fiber arrangement affect the extension direction of pseudopodia through mechanical force conduction.This article conducted a comprehensive analysis of the biological characteristics of CTC,the formation mechanism of invasive pseudopodia in cholangiocarcinoma,the metastatic features of cholangiocarcinoma cells and their clinical significance,as well as the role of CTC in the metastatic process of cholangiocarcinoma,in order to summarize the existing research results,explore potential therapeutic targets and future research directions,and provide new ideas for the clinical treatment of cholangiocarcinoma.
7.Sex Differences of White Matter Damage in Alzheimer's Disease and Its Association with Cognitive Impairment
Yun LU ; Xiaoshu LI ; Wanqiu ZHU ; Ziwen GAO ; Yuqing LI ; Wenrui WANG ; Wei YE ; Xiao CHEN ; Ju MA ; Yongqiang YU
Chinese Journal of Medical Imaging 2025;33(6):618-626
Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.
8.Initial clinical experience with the perceval sutureless aortic valve: insights from a single center
Tong TAN ; Yongqiang LAI ; Jiangang WANG ; Xiubin YANG ; Ran DONG ; Hao CUI ; Enjun ZHU ; Hongchang GUO
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(10):624-629
Objective:To summarize the early clinical outcomes of aortic valve replacement(AVR) using the Perceval sutureless aortic valve.Methods:This retrospective study included 50 patients who underwent AVR with the Perceval sutureless prostheses at Beijing Anzhen Hospital between June 2023 and January 2025. Surgical parameters, early clinical outcomes, valve function, and hemodynamic performance were evaluated to summarize clinical effectiveness.Results:The mean age of patients was(63.5±9.1) years, predominantly female(36/50). Severe aortic stenosis was present in 43 cases(86.0%). A preoperative aortic annulus dimension of 20.0(19.0, 21.0) mm measured in both anteroposterior and transverse diameters. Preoperative peak transvalvular gradient was(92.7±31.0)mmHg(1 mmHg=0.133 kPa), with a mean gradient of (58.0±21.2) mmHg. All procedures were successfully completed using the Perceval sutureless prostheses. Isolated AVR was performed in 20 patients(40.0%), with cardiopulmonary bypass and aortic cross-clamp times of 75.0(50.5, 99.5) min and 50.5(29.5, 71.5) min, respectively. Postoperative transesophageal echocardiography revealed an immediate reduction in the peak transvalvular gradient to 11.0(8.0, 18.0) mmHg, significantly lower compared to preoperative measurements( P<0.001). Two cases of paravalvular leakage and one case requiring permanent pacemaker implantation were reported postoperatively. All patients completed the 3-month follow-up, with one death during the follow-up period; the remaining patients exhibited normal prosthetic valve function without major adverse cardiovascular events. Significant postoperative reductions were observed in left ventricular end-diastolic diameter(45.8 mm vs. 43.2 mm, P=0.003) and left atrial diameter(53.9 mm vs. 44.6 mm, P<0.001) compared with baseline. Conclusion:AVR using the Perceval sutureless prostheses demonstrated safe and effective early clinical outcomes with excellent hemodynamic performance and low incidence of postoperative paravalvular leakage and permanent pacemaker implantation. The sutureless technique represents a viable alternative strategy, particularly advantageous for patients with small aortic annuli or complex surgical conditions, warranting broader clinical adoption.
9.International experience of assistive technology service for the elderly in primary care and its inspiration
Zhengwen FENG ; Yongqiang HU ; Chenli ZHU ; Haijin LI ; Hui LI ; Juan DU
Chinese Journal of General Practitioners 2024;23(7):752-757
With the population ageing, the number of elderly with noncommunicable diseases and functional disabilities is increasing. The assistive technology can improve the ability of older adults for daily living activities and reduce dependence on caregivers to facilitate home-based care for the elderly. However, the provision of assistive technology service in China is still in the early stage and lacks implementable model. This article introduces international experiences on the delivery of assistive technology service, and discusses the status quo and problems of assistive technology service in China, to provide insights for promoting assistive technology service in the primary health care.
10.Levels of miRNA-21 and miRNA-330 in serum exosomes of non-small cell lung cancer patients with brain metastases and their clinical significances
Yingchao ZHU ; Lei ZHANG ; Jizhen WANG ; Yongqiang ZHAO ; Xiangdong LU ; Jinzhong ZHANG
Cancer Research and Clinic 2024;36(6):401-408
Objective:To investigate the expression levels of miRNA-21 (miR-21) and miRNA-330 (miR-330) in serum exosomes of non-small cell lung cancer (NSCLC) patients with brain metastases, and the correlation of the two with the prognosis of patients.Methods:A prospective cohort study was conducted. A total of 125 NSCLC patients who were admitted to the Affiliated People's Hospital of Shandong First Medical University from March 2021 to September 2022 were prospectively selected, and the brain metastasis was determined by CT, contrast-enhanced magnetic resonance imaging of the head, or surgical pathology. The NSCLC patients were divided into the metastatic group (58 cases) and the non-metastatic group (67 cases) according to whether they had brain metastases, and 50 patients with benign lung diseases and 50 healthy subjects who underwent physical examination in the same period were selected as benign group and healthy control group respectively. Serum samples were collected from all subjects (including patients' pre-treatment samples), the exosomes were extracted, and real-time fluorescence quantitative polymerase chain reaction was used to determine the relative expression of miR-21 and miR-330 in exosomes at the transcriptional level, and electrochemiluminescence immunoassay was used to detect the levels of serum tumor markers [neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA)]. The levels of miR-21 and miR-330 in serum exosomes and serum tumor markers in the 4 groups were compared, and the correlation between miR-21 and miR-330 in serum exosomes of NSCLC patients with brain metastases before treatment and the correlation between miR-21, miR-330 and serum tumor markers were analyzed by Pearson method. Using brain metastases identified by CT, contrast-enhanced magnetic resonance imaging of the head or surgical pathology as the gold standard, the receiver operating characteristic (ROC) curves were drawn to determine the occurrence of brain metastases in NSCLC patients based on the levels of miR-21, miR-330 and their combination in the serum exosomes before treatment. NSCLC patients were divided into the poor prognosis group and the good prognosis group according to whether or not they died of tumor during the follow-up period, and the clinical characteristics and levels of miR-21 and miR-330 in serum exosomes before treatment were compared between the two groups. The independent influencing factors of death due to tumor in NSCLC patients were analyzed by multivariate logistic regression.Results:Among 125 NSCLC patients, 68 (54.4%) were male and 57 (45.6%) were female; the age was (63±5) years old, ranging from 49 to 82 years old; 89 patients (71.2%) were adenocarcinoma and 36 patients (28.8%) were squamous cell carcinoma. The transcriptional level relative expression of miR-21 in serum exosomes of healthy control group, benign group, non-metastatic group and metastatic group increased sequentially, the transcriptional level relative expression of miR-330 decreased sequentially, the protein concentrations of NSE, CEA and SCCA increased sequentially, and the differences between each two groups were statistically significant (all P<0.001). Pearson correlation analysis showed that in the serum exosomes of NSCLC patients with brain metastases before treatment, miR-21 was positively correlated with serum NSE, CEA and SCCA levels ( r values were 0.641, 0.785 and 0.612, respectively; P values were 0.015, 0.011 and 0.019, respectively), miR-330 in the serum exosomes before treatment was negatively correlated with serum NSE, CEA, and SCCA levels ( r values were -0.612, -0.689 and -0.587, respectively; P values were 0.016, 0.021 and 0.013, respectively), and miR-21 was positively correlated with miR-330 in the serum exosomes before treatment ( r = -0.529, P = 0.023). ROC curve analysis showed that the area under the curve of miR-21, miR-330 and their combination in serum exosomes before treatment for determining the occurrence of brain metastases in NSCLC patients were 0.861 (95% CI: 0.792-0.931), 0.894 (95% CI: 0.840-0.947) and 0.906 (95% CI: 0.849-0.963), and the differences were statistically significant (all P < 0.001). The optimal cut-off value of miR-21 relative expression was 1.625, and the corresponding sensitivity and specificity were 77.4% and 71.5%, respectively; the optimal cut-off value of miR-330 was 0.611, and the corresponding sensitivity and specificity were 81.1% and 74.9%, respectively; the sensitivity and specificity when the two were combined to reach the optimal cut-off value were 84.5% and 73.8%, respectively. NSCLC patients were followed up for a median time of 19 months (95% CI: 17-21 months), and 23 cases (18.4%) died due to the tumor during the follow-up period. The proportions of patients with age ≥60 years old, clinical stage Ⅲ-Ⅳ and brain metastases and the relative expression of miR-21 in serum exosomes before treatment in the poor prognosis group were higher than those in the good prognosis group, the relative expression of miR-330 in the serum exosomes before treatment was lower than that in the good prognosis group, and the differences were all statistically significant (all P < 0.05). Multivariate logistic regression analysis showed that the high age (≥60 years old vs. <60 years old, OR = 3.750, 95% CI: 1.191-11.806, P = 0.024), late clinical stage (stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ, OR = 4.667, 95% CI: 1.303-16.716, P = 0.018), brain metastasis (with metastasis vs. non-metastasis, OR = 2.573, 95% CI: 1.008-6.611, P = 0.049), and elevated relative expression of miR-21 in serum exosomes before treatment ( OR = 2.585, 95% CI: 1.198-6.152, P = 0.008) were the independent risk factors for death due to tumor in NSCLC patients, and elevated relative expression of miR-330 in serum exosomes before treatment was an independent protective factor for death due to tumor ( OR = 0.821, 95% CI: 0.715-0.954, P < 0.001). Conclusions:miR-21 level is high and miR-330 level is low in serum exosomes of NSCLC patients with brain metastases before treatment, and there is a negative correlation between them, and they are closely related to various serum tumor markers of NSCLC patients with brain metastases and NSCLC patients' prognosis; the combination of the two may predict the occurrence status of brain metastases in NSCLC.

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