1.Effects of donor gender on short-term survival of lung transplant recipients: a single-center retrospective cohort study
Xiaoshan LI ; Shiqiang XUE ; Min XIONG ; Rong GAO ; Ting QIAN ; Lin MAN ; Bo WU ; Jingyu CHEN
Organ Transplantation 2025;16(4):591-598
Objective To evaluate the effect of donor gender on short-term survival rate of lung transplant recipients. Methods A retrospective analysis was conducted on the data of 1 066 lung transplant recipients. The log-rank test was used to evaluate the differences in short-term fatality among different donor gender groups and donor-recipient gender combination groups. Multivariate Cox regression, propensity score (PS) regression, and propensity score matching (PSM) were employed to control for confounding factors and further assess the differences in fatality. Subgroup analyses were also performed based on donor gender. Results Multivariate Cox regression analysis showed no statistically significant differences in fatality at 30 days, 1 year, 2 years and 3 years postoperatively between male and female donor groups (all P>0.05). After PS regression and PSM, univariate Cox regression analysis indicated that recipients from female donors had a higher fatality at 2 years postoperatively compared to those from male donors, with hazard ratios (95% confidence intervals) of 1.29 (1.01-1.65) and 1.36 (1.03-1.80) respectively. Multivariate Cox regression analysis also revealed no statistically significant differences in fatality at various follow-up time points among different donor-recipient gender combination groups (all P>0.05). Subgroup analyses based on donor sex showed no statistically significant differences in fatality among recipients of different gender within either male or female donor groups (all P>0.05). Conclusions Female donors may reduce the short-term postoperative survival rate of lung transplant recipients, but this negative impact is not sustainable in the long term. At present, there is no evidence to support the inclusion of sex as a factor in lung allocation rules.
2.Mechanism of electroacupuncture-induced macrophage polarization in promoting acute skeletal muscle injury repair in rats.
Yuting HUANG ; Yuye LIN ; Guojun ZHANG ; Chufan ZENG ; Xia ZHANG ; Jingyu ZHANG ; Yu KAN ; Yanping FANG ; Xianghong JING ; Jun LIAO
Chinese Acupuncture & Moxibustion 2025;45(6):791-800
OBJECTIVE:
To investigate the potential mechanism by which electroacupuncture (EA) induces macrophage polarization to promote muscle satellite cell proliferation and differentiation, accelerating the repair of acute skeletal muscle injury.
METHODS:
Forty-two SPF-grade SD rats were randomly divided into three groups: a blank group (n=6), a model group (n=18), and an EA group (n=18). The model and EA groups established acute blunt contusion model of the right gastrocnemius muscle using a self-made striking device. From day 1 after modeling, rats in the EA group received EA at "Chengshan" (BL57) and "Yanglingquan" (GB34) on the right side, using disperse-dense wave with a frequency of 2 Hz/100 Hz and a current of approximately 2 mA. The EA treatment was administered once daily for 30 minutes for 3, 7, or 14 days based on the designated sampling time points. Gait analysis was performed using the Cat Walk XTTM system. Hematoxylin-eosin (HE) staining was used to observe the morphological changes in the gastrocnemius muscle. Masson staining was applied to evaluate collagen fiber content. Immunofluorescence was used to detect the expression of proliferating cell nuclear antigen (PCNA) in muscle satellite cells. Immunohistochemistry was used to assess the expression levels of CD68 and CD206, markers of macrophages. Serum levels of pro-inflammatory cytokines (TNF-α, IL-1β) and anti-inflammatory cytokines (IL-10, IL-13) were detected using ELISA.
RESULTS:
Compared with the blank group, the model group showed a significant reduction in average movement speed on days 3 and 7 after modeling (P<0.05), and a decrease in the right hind limb stride length on day 3 (P<0.05). Compared with the model group, the EA group showed increased average movement speed and right hind limb stride length on day 7 (P<0.05). In the blank group, the gastrocnemius muscle on the right side showed uniform and consistent inter-fiber spacing, with neatly and regularly arranged muscle cells. In contrast, the model group exhibited enlarged inter-fiber spacing, edema, and significant infiltration of red blood cells and inflammatory cells, with progressively increasing fibrosis over time. By day 14 after modeling, the EA group showed a return to baseline levels of inflammatory cell infiltration, and the degree of fibrosis was significantly lower than that observed in the model group. Compared with the blank group, the ratio of collagen fibers in the gastrocnemius muscle of the model group increased significantly on days 3, 7, and 14 after modeling (P<0.05). Compared with the model group, the EA group exhibited a lower collagen fiber ratio on days 3, 7, and 14 (P<0.05). Compared with the blank group, PCNA positive expression in the gastrocnemius muscle of the model group was significantly increased on days 3, 7, and 14 after modeling (P<0.05). Compared with the model group, the EA group exhibited significantly higher PCNA positive expression on days 3 and 7 (P<0.05). Compared with the blank group, the model group showed a significant increase in CD68-positive macrophage expression in the gastrocnemius muscle on day 3 after modeling (P<0.05), while CD206-positive macrophage expression increased on days 3, 7, and 14 (P<0.05). Compared with the model group, CD68 expression was significantly lower in the EA group on day 3 (P<0.05), whereas CD206 expression was significantly higher on days 3 and 7 (P<0.05), peaking on day 7 with CD206 expression. Compared with the blank group, serum TNF-α levels were significantly elevated in the model group on days 3 and 7 after modeling (P<0.05), while serum IL-1β levels were increased on days 3, 7, and 14 (P<0.05). Serum IL-10 and IL-13 levels were significantly higher on day 7 after modeling (P<0.05). Compared with the model group, the EA group exhibited lower serum TNF-α level on day 3 (P<0.05) and reduced serum IL-1β levels on days 3 and 7 (P<0.05), while serum IL-10 and IL-13 levels were significantly increased on day 7 (P<0.05).
CONCLUSION
EA could promote the repair of acute blunt contusion-induced gastrocnemius muscle injury by regulating the proliferation and differentiation of muscle satellite cells. This process is closely related to macrophage polarization.
Animals
;
Electroacupuncture
;
Rats, Sprague-Dawley
;
Rats
;
Macrophages/immunology*
;
Muscle, Skeletal/immunology*
;
Male
;
Humans
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Female
;
Tumor Necrosis Factor-alpha/immunology*
;
Cell Proliferation
3.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.
4.Application of metagenomic next-generation sequencing in prevention and control of infection in solid organ transplantation
Lin MAN ; Xiaoshan LI ; Wenjing WANG ; Ting QIAN ; Min XIONG ; Hang YANG ; Jingyu CHEN ; Bo WU
Organ Transplantation 2024;15(2):289-296
Organ transplantation has become an effective treatment for multiple end-stage diseases. However, the recipients of organ transplantation need to take immunosuppressive drugs for a long time after operation, which leads to low immune function and relatively high incidence of bacterial, viral and fungal infections. Traditional microbial detection methods, such as pathogen culture, immunological detection and polymerase chain reaction, have been widely applied in infection detection, whereas these methods may cause problems, such as long detection time and presumed pathogens. Metagenomic next-generation sequencing has been widely adopted in infection prevention and control in organ transplantation in recent years due to high detection rate and comprehensive detection of pathogen spectrum. In this article, the application of metagenomic next-generation sequencing in the prevention and control of infection in solid organ transplantation was reviewed, aiming to provide reference for the diagnosis and treatment of transplantation-related infection.
5.Clinical significance of FOXA3 expression in colorectal cancer
Yujing CHEN ; Jingyu WANG ; Lin ZHANG ; Zhen WANG
Chinese Journal of Clinical and Experimental Pathology 2024;40(2):179-183
Purpose To analyze the expression of FOXA3 in colorectal cancer(CRC)and its correlation with clinicopatho-logical features.Methods FOXA3 mRNA expression in 31 CRC cancer tissues and their matched normal tissues was detec-ted by real-time quantitative PCR(RT-qPCR).The protein ex-pression of FOXA3 in 120 CRC cancer tissues was detected by immunohistochemical EnVision two-step method,and the clini-copathologic features such as lymph node metastasis and immu-nohistochemical expression were analyzed.Results The mRNA expression level of FOXA3 in colorectal cancer tissues was sig-nificantly higher than that in paired paracancer tissues(t=2.952,P=0.006 1).FOXA3 protein expression level in color-ectal cancer tissues was not significantly correlated with gender,age,site and size of patients,but significantly correlated with the degree of tissue differentiation(P=0.006)and lymph node metastasis(P=0.002).The degree of differentiation was nega-tively correlated with FOXA3 expression,while lymph node me-tastasis was positively correlated with FOXA3 expression.Sur-vival analysis showed that higher FOXA3 expression was associ-ated with worse overall survival(P<0.000 1),and FOXA3 was an independent risk factor for prognosis in patients with colorectal cancer.Conclusion This study suggests that FOXA3 may play a promoting role in the occurrence and development of colorectal cancer,and FOXA3 may be a molecular marker for the diagnosis,metastasis and prognosis of colorectal cancer.
6.Short- to mid-term outcomes of aortic valve plasty versus Ross procedure in children with severe aortic valve disease: A retrospective cohort study
Lin XIE ; Zhuheng WU ; Jingyu LIU ; Ke DIAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(12):1794-1802
Objective To compare the short- to mid-term outcomes of aortic valve plasty (AVP) and Ross surgery in children with severe aortic valve disease. Methods The patients (aged<18 years) with severe aortic valve disease who underwent AVP (an AVP group) or Ross surgery (a Ross group) at the Department of Cardiovascular Surgery, West China Hospital from January 2019 to September 2023 were retrospectively included. We compared perioperative and follow-up data between the groups. Results A total of 48 pediatric patients were included, including 28 males and 20 females, with an average age of (9.3±4.5) years. There were 25 patients in the AVP group, and 23 in the Ross group. Leaflet thinning (15/25, 60.0%) and leaflet extension (10/25, 40.0%) were the most common strategies used in the AVP group, while root replacement technique (12/23, 52.2%) and subcoronary technique (10/23, 43.5%) were the most frequently used strategies in the Ross group. There was no in-hospital death. The median follow-up time was 16.0 (7.0, 30.0) months. Peak flow velocity of the aortic valve was higher in the AVP group [2.0 (1.4, 2.9) m/s vs. 1.2 (1.0, 1.5) m/s, P<0.001], while there was no statistical difference in the postoperative aortic valve regurgitation severity between the two groups (P=0.127). During follow-up, the overall reoperation rate and aortic valve reoperation rate were similar between the AVP group and the Ross group (8.0% vs. 13.0%, P=0.922; 8.0% vs. 0.0%, P=0.266). The rate of recurrent aortic valve disease was higher in the AVP group (52.0% vs. 4.3%, P<0.001), while further analysis failed to recognize any risk factors. Conclusion AVP and Ross procedure show similar perioperative safety, survival and reoperation rate. The rate of recurrent aortic valve disease is higher in the AVP group, but further investigations are needed to confirm the causes.
7.Current status and prevention strategies for respiratory virus infections after lung transplantation
Min XIONG ; Xiaoshan LI ; Ting QIAN ; Lin MAN ; Hang YANG ; Jingyu CHEN ; Bo WU
Organ Transplantation 2024;15(6):970-976
Lung transplantation is an effective means of treating various end-stage lung diseases.However,compared with other solid organ transplants,the survival rate after lung transplantation is relatively low.The main reason is the numerous complications after lung transplantation,among which infection is one of the most common complications.Respiratory viral infections are an important type of infection after lung transplantation,which severely affect the survival time and quality of life of lung transplant recipients.Early identification,early prevention,and active diagnosis and treatment are of great significance in reducing the incidence and fatality of respiratory viral infections after lung transplantation.This article reviews the epidemiology,risk factors,prevention and treatment principles,and specific prevention and treatment progress of common viruses in respiratory viral infections after lung transplantation at home and abroad,in order to provide a reference for the prevention and treatment of respiratory viral infections after lung transplantation in clinical practice.
8.Effects of 4-day cigarette smoke exposure combined with poly(I:C)stimulation on lung immune response and interferon expression in mice
Xiaofei DONG ; Ziyao LIANG ; Long FAN ; Jingyu QUAN ; Lin LIN ; Yingfang ZHOU ; Lei WU ; Xuhua YU
Chinese Journal of Immunology 2024;40(1):67-71
Objective:To investigate effects of short-term cigarette smoke exposure combined with poly(I:C)stimulation on lung immune response and interferon expression in mice.Methods:BALB/c mice were randomly divided into 4 groups:control group,smoke group,poly(I:C)group and smoke combined poly(I:C)group.Total cell number and cell classification count of bronchoalveo-lar lavage fluid(BALF)were detected,and cell morphology was observed under ordinary light.Cytokines,chemokines,interferon and interferon stimulating genes expressions in lung tissues were detected by fluorescence quantitative PCR.Results:Compared with control group,total cell count,macrophage count and neutrophil count in smoke combined poly(I:C)group were significantly increased(P<0.05),and macrophage count was higher than that in poly(I:C)group.Macrophages of airway lavage fluid of mice in smoke combined with poly(I:C)group were larger in size,round or irregular in shape,and had more vacuoles in cytoplasm.Com-pared with control group,mRNA expressions of neutrophil chemokine CXCL1(P<0.05),CXCL2(P<0.01)and lymphocyte chemo-kine CCL2(P<0.01)in lung tissues of mice in smoke combined with poly(I:C)group were increased.IL-1β,IL-6,TNF-α mRNA expressions were significantly increased(P<0.01),IFN-β(P<0.01),IFN-γ(P<0.05),MX2(P<0.01)and IP-10(P<0.01)expre-ssions in lung tissues were significantly increased,and compared with poly(I:C)group,mRNA expressions of CXCL2(P<0.05),TNF-α(P<0.01)and IFN-β(P<0.05)in lung tissues of mice in smoke combined with poly(I:C)group were significantly increased.Conclusion:Cigarette smoke combined with poly(I:C)induces lung inflammation and expressions of interferon and interferon stimu-lating genes in mice.Cigarette exposure also increases poly(I:C)-induced acute lung inflammation and type Ⅰ interferon expression in mice.
9.Differences of gene expression profiles of different subpopulations of exhausted T cells in patients with active pulmonary tuberculosis
Weifang LIN ; Jingyu ZHOU ; Huaxin CHEN ; Siran LIN ; Zhe ZHOU ; Zhangyufan HE ; Yixuan YANG ; Xiaoqian HU ; Yiting TANG ; Yuanyuan LIU ; Lingyun SHAO
Chinese Journal of Infectious Diseases 2024;42(2):91-97
Objective:To explore the differences of gene expression profiles of precursors of exhausted T cells (Tpex) and terminal exhausted T cells (Tex) in the peripheral blood of patients with active pulmonary tuberculosis (ATB).Methods:Twenty-five cases of ATB, 13 cases of latent tuberculosis infection (LTBI) and 10 health controls were enrolled from January 2021 to October 2022 in the Fifth People′s Hospital of Wuxi. The proportions of Tpex and Tex in the peripheral blood mononuclear cells (PBMCs) of the three groups were detected by flowcytometry. PBMCs of ATB were separated into Tpex and Tex by fluorescence-activated cell sorting. RNA-sequencing was performed and up-regulated and down-regulated genes were screended. Differently expressed genes were analyzed by gene set enrichment analysis of gene ontology (GO) to find regulatory pathways affecting cell metabolism and function. Wilcoxon matched-pairs signed rank test, Kruskal-Wallis test and Dunn multiple comparsion test were used for statistical analysis.Results:The proportion of Tpex in ATB group was 2.86%(1.74%), which was lower than 7.93%(6.16%) of Tex, and the difference was statistically significant ( Z=-3.91, P<0.001). The proportions of Tpex and Tex in LTBI group were 9.47%(6.26%) and 7.43%(5.48%), respectively, and the difference was not statistically significant ( Z=-0.93, P=0.345). The proportions of Tpex and Tex in healthy control group were 8.42%(2.69%) and 6.49%(5.14%), respectively, with no statistical significance ( Z=-1.36, P=0.170). There was statistical difference of the proportion of Tpex among the three groups ( H=21.93, P<0.001), and the proportion of Tpex in ATB group was lower than those in LTBI and heathy control groups, and the differences were both statistically significant ( Z=4.16, P<0.001 and Z=3.34, P=0.003, respectively), while the proportions of Tex in these three groups were not statistically different ( H=2.17, P=0.338). Compared with Tex, the gene expressions of memory markers, such as B-cell lymphoma 2 of Tpex were up-regulated, and the gene expressions of exhausted markers, such as lymphocyte activation gene 3 were down-regulated. In terms of cellular metabolism, the gene expressions of mitochondrial protein complex, mitochondrial matrix and oxidative phosphorylation of Tpex were up-regulated, and the gene expressions of glycolysis were down-regulated. The gene expressions of pyruvate metabolism in Tex were up-regulated, and the gene expressions of CD4 + T lymphocyte activation and differentiation and glycolytic process in Tpex were down-regulated. Conclusions:Tpex in ATB express more characteristics of memory cells and less features of exhausted markers compared with Tex, and the function of mitochondria of Tpex preserves well.
10.The mediating role of self-hating between adverse childhood experience and self-injury behavior in adolescents
Ligang ZHANG ; Jingyu LIN ; Yanyan WEI ; Huiqun ZHU ; Yuhua JING ; Jingxu CHEN
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(11):1040-1045
Objective:To explore the impact of adverse childhood experience on self-injury behavior and the mediating role of self hating in adolescents.Methods:A cross-sectional survey was conducted in 6 high schools and 5 middle schools in Shandong Province from August 1 to December 31, 2022, using the adverse childhood experience questionnaire, self-hating scale and non-suicidal self-injury behavior rating questionnaire for adolescents. A total of 7 313 questionnaires were collected, of which 6 948 were valid. SPSS 22.0 software was used for Spearman correlation analysis, and biased-corrected non-parametric percentile Bootstrap method was used to test the significance of mediating effect.Results:(1) The scores of adverse childhood experience(4.0(2.0, 6.0)), self-hating (22.0 (13.0, 29.0)) and self-injury behavior (12.0 (7.0, 19.0)) in adolescents with self-injury behavior were higher than those without self-injury behavior(0(0, 2.0), 2.0(0, 9.0), 0(0, 1.0)), and the differences were statistically significant ( Z=-21.700, -22.654, -29.519, all P<0.001). (2) Adverse childhood experience was positively correlated with self-hating ( r=0.46, P<0.01) and self-injury behavior ( r=0.47, P<0.01). Self-hating was positively correlated with self-injury behavior ( r=0.51, P<0.01). (3) Adverse childhood experience directly predicted self-injury behavior with a direct effect of 0.163 (95% CI =0.127-0.200, P<0.01)and the effect size of 53.80%(0.163/0.303).Adverse childhood experiences indirectly predicted self-injury behavior through self-hating, with an indirect effect of 0.140 (95% CI=0.122-0.160, P<0.001) and the effect size of 46.20%(0.140/0.303).The total effect was 0.303 (95% CI=0.270-0.336, P<0.001). Conclusions:There is a close relationship between adverse childhood experiences, self-hating and self-injury behavior in adolescents. Adverse childhood experiences can directly predict self-injury behavior, and can also indirectly affect self-injury behavior through self-hating.

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