1.Dual immune checkpoint inhibitors combined with anlotinib in the treatment of alveolar soft part sarcoma: a case report
Xinghua FANG ; Wei LI ; Yuhong ZHOU
Chinese Journal of Clinical Medicine 2025;32(1):140-144
Clinical data of a patient with alveolar soft part sarcoma (ASPS) treated at Zhongshan Hospital, Fudan University were retrospectively analyzed. The patient was initially diagnosed with abdominal ASPS with multiple lung metastases. After 6 weeks of treatment with nivolumab and ipilimumab, the patient achieved stable disease (SD). In the 7th week, the treatment was changed to a combination of nivolumab (30 mg, d1, q3w), anlotinib (8 mg, d1-14, q3w) and ipilimumab (50 mg, d1, q6w). The patient remained SD at the 12th week. The patient then underwent iliac artery embolization and intensity-modulated radiation therapy for the lesion in the psoas major muscle, while continuing the combination treatment. By the 24th week, the evaluation showed partial remission (PR) of both primary tumor and lung metastases. The patient experienced mild adverse reactions during treatment.
2.Effect and mechanisms of highly active umbilical cord mesenchymal stem cells on aging spleen in elderly tree shrews
Li YE ; Chuan TIAN ; Xiaojuan ZHAO ; Mengdie CHEN ; Qianqian YE ; Qiang LI ; Zhuyin LIAO ; Ye LI ; Xiangqing ZHU ; Guangping RUAN ; Zhixu HE ; Liping SHU ; Xinghua PAN
Chinese Journal of Tissue Engineering Research 2025;29(19):4000-4010
BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.
3.Effect of childhood maltreatment on depression in college students: a moderated mediation model
Xinghua LAI ; Huitong ZHAO ; Ruofan XIAO ; Can CUI ; Ameng ZHAO ; Wei FU ; Jing JIANG ; Tinghuizi SHANG ; Honglong LI ; Zengyan YU
Sichuan Mental Health 2025;38(3):247-253
BackgroundCurrently, the problem of depressed mood in college students is becoming more prominent. The experience of childhood maltreatment is a significant contributor to depression among college students. Although the association between the two has been confirmed, the specific psychosocial mechanisms underlying how childhood maltreatment affects college students' mental health remain insufficiently evidenced. ObjectiveTo explore the mediating role of emotion regulation difficulties in the relationship between childhood maltreatment and depression among college students, and to investigate the moderated effects of psychological resilience and family socioeconomic status, aiming to provide references for improving depressive symptoms in college students. MethodsOn 14 March 2024, a cluster sampling method was employed to recruit 751 college students from a university in Heilongjiang Province. Participants were assessed with Childhood Trauma Questionnaire (CTQ), Difficulties in Emotion Regulation Scale (DERS), Patients' Health Questionnaire Depression Scale-9 item (PHQ-9), 10-item Connor-Davidson Resilience Scale (CD-RISC-10) and Family Socioeconomic Status Questionnaire. Pearson correlation analysis was adopted to examine the correlation between the scores of scales. Model 4 and model 7 in Process 4.2 were used to test the mediating effects of emotional regulation difficulties and the moderated effects of psychological resilience and family socioeconomic status. Results① A total of 712 (94.81%) valid questionnaires were collected. ② College students' CTQ score was positively correlated with DERS score and PHQ-9 score (r=0.296, 0.507, P<0.01), and negatively correlated with CD-RISC-10 score and Family Socioeconomic Status Questionnaire score (r=-0.148, -0.229, P<0.01). ③ The indirect effect value of difficulties in emotion regulation on the relationship between childhood maltreatment and depression was 0.091 (95% CI: 0.018~0.046), accounting for 17.95% of the total effect. ④ The first half of the mediation model "childhood maltreatment → difficulties in emotion regulation → depression" (childhood maltreatment → difficulties in emotion regulation) was moderated by psychological resilience (β=-0.030, t=-6.147, 95% CI: -0.040~-0.020) and family socioeconomic status (β=-0.051, t=-3.929, 95% CI: -0.077~-0.026). ConclusionChildhood maltreatment exerts both a direct effect on college students' depression and an indirect effect through emotion regulation difficulties. The childhood maltreatment → emotion regulation difficulties pathway in this mediation model is moderated by psychological resilience and family socioeconomic status. [Funded by Qiqihar Medical University Graduate Student Innovation Fund Project (number, QYYCX2023-48); Special Research Fund Project for Young Doctors of Qiqihar Academy of Medical Sciences (number, QMSI2021B-08)]
4.Construction of Knowledge Graph Based on Literature Data by Taking Treatment of Diabetic Peripheral Neuropathy with Traditional Chinese Medicine as An Example
Jiaqi CHAI ; Yumeng TAN ; Xinghua XIANG ; Miaomiao LI ; Tiancai WEN ; Hui ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):144-150
ObjectiveTo systematically sort out the knowledge framework and conceptual logic relationship of "disease-syndrome-treatment-prescription-medicine" in the existing literature on traditional Chinese medicine(TCM) treatment of diabetic peripheral neuropathy(DPN), to construct of the knowledge map of TCM treatment of DPN, and to promote the explicitation of the implicit knowledge in the literature on the treatment of DPN with TCM. MethodTaking the literature of China National Knowledge Infrastructure about TCM treatment of DPN as the main data source, TCM-related concepts and entities were constructed by manual citation, and the corresponding relationships between the entities were established. Structured data were formed by processing with Python 3.7, and the knowledge graph was constructed based on Neo4j 3.5.34 graph database. ResultThe resulting knowledge graph with TCM diagnosis and treatment logic, defined 12 node labels such as prescriptions, Chinese medicines and syndrome types at the schema layer, as well as 4 types of relationships, such as inclusion, correspondence, selection and composition. It could support the query and discovery of nodes(syndrome elements, syndrome types and treatment methods), as well as the relationship between each node. ConclusionBased on the literature data, this study constructed a knowledge map for TCM treatment of DPN, which brought together various methods of TCM treatment of DPN, including internal and external treatment. The whole chain knowledge structure of syndrome differentiation and classification for DPN treatment is formed from syndrome element analysis, syndrome type composition to treatment method selection, which can provide new ideas and methods for literature data to serve clinical and scientific research work, as well as reference for visualization of TCM literature knowledge, intellectualization of TCM knowledge services and the standardization of TCM diagnosis and treatment.
5.Research progress of alleviating depression among children and adolescents based on 24 h movement behaviors
GUO Liang, ZHANG Jing, ZENG Sai, LI Tiangeng, DENG Xinghua
Chinese Journal of School Health 2024;45(6):899-903
Abstract
Gurrently, healthy behaviors are the cornerstone of both physical and mental wellbeing,and more researches are focusing on improving behaviors to alleviate depression among children and adolescents. Based on the concept of 24 h movement behaviors proposed in recent years, the study examines the relationship among physical activity, sedentary behavior, sleep and depressive symptoms in children and adolescents. The research suggests that physical activity could effectively alleviate depression among children and adolescents, and its effectiveness is influenced by factors including type, intensity, duration and frequency of physical activity. Excessive sedentary behavior may increase depressive symptoms, and the impacts of different types, durations, and frequencies of sedentary behavior on depressive symptoms among children and adolescents vary. In addition to its direct impact on depression, sleep could also serve as a mediator among physical activity, sedentary behavior and depression, and there is also a crowdingout effect of time between physical activity and sedentary behavior. Future research should focus on the mechanisms and pathways underlying how 24 h movement behaviors affecting depression among children and adolescents, in order to provide more accurate solutions for the prevention and treatment of depression.
6.Role of Nrf2/HO-1 signaling pathway in human umbilical cord mesenchymal stem cells-derived exosomes-induced reduction of renal ischemia-reperfusion injury in mice
Huafeng WEI ; Lingyu LI ; Hao LUO ; Hao WANG ; Jiahui HE ; Yawei YAO ; Xinghua LYU
Chinese Journal of Anesthesiology 2024;44(1):97-103
Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxidase-1 (HO-1) in reduction of renal ischemia-reperfusion (I/R) injury by the human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes (hucMSCs-exo) in mice.Methods:The hucMSCs were cultured, and exosomes were extracted and identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. Thirty-six male SPF-grade C57BL/6 mice, weighing 20-25 g, were used. Thirty mice were selected and divided into 5 groups ( n=6 each) by a random number table method: sham operation group (Sham group), sham operation + Nrf2 inhibitor ML385 group (Sham + ML385 group), renal I/R group (I/R group), renal I/R + exosome group (I/R+ EXO group), and renal I/R + exosome + Nrf2 inhibitor ML385 group (I/R+ EXO+ ML385 group). A model of renal I/R injury was prepared by clamping the bilateral renal pedicles for 45 min followed by perfusion in anesthetized animals. ML385 30 mg/kg was intraperitoneally injected at 45 min before preparing the model in Sham+ ML385 group and I/R+ EXO+ ML385 group, and hucMSCs-exo 100 μg was injected via the tail vein at 15 min before reperfusion in I/R+ EXO group and I/R+ EXO+ ML385 group. Serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations were detected at 24 h of reperfusion. The renal tissues were obtained for examination of the pathological changes and for determination of contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA), superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels and expression of Nrf2 and HO-1 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction). The left 6 mice were allocated to sham operation group (Sham-IM group, n=3) and renal I/R group (I/R-IM group, n=3) by a random number table method for VISQUE in living imaging observation. Results:The exosomes showed a typical cup-shaped morphology with a transmission electron microscope, the nanoparticles tracked and analyzed the average diameter of the exosome, with an average diameter of 96.7 nm, and the positive expression of surface markers CD9, CD63 and TSG101 was detected using Western blot. The renal fluorescence intensity value was significantly increased in I/R-IM group as compared with Sham-IM group ( P<0.05). Compared with Sham group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R group, and no significant change was found in serum BUN and Cr concentrations in Sham+ ML385 group ( P>0.05). Compared with I/R group, the serum BUN and Cr concentrations were significantly decreased, the contents of IL-6, TNF-α and MDA and ROS levels were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 protein and mRNA was up-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in I/R+ EXO group. Compared with I/R+ EXO group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R+ EXO+ ML385 group. Conclusions:The mechanism by which hucMSCs-exo reduces renal I/R injury may be related to activation of the Nrf2/HO-1 signaling pathway in mice.
7.Prevalence of Anaplasma infections in sheep and goats in Anhui Province in 2020
Xinghua WU ; Jipu WANG ; Sichao GAO ; Xinyu LUO ; Qiaoqiao LI ; Dongqian CHEN ; Xinchao LIU ; Youfang GU ; Wenchao LI
Chinese Journal of Schistosomiasis Control 2024;36(6):620-625
Objective To investigate the prevalence and molecular characteristics of Anaplasma infections in sheep and goats in Anhui Province in 2020, so as to provide insights into ovine anaplasmosis prevention and control. Methods A total of 355 fresh blood samples were collected from 7 sheep and goat farms in Linquan County of Fuyang City, Lixin County of Bozhou City, Yu'an District of Lu'an City, Wangjiang County of Anqing City, Nanling County of Wuhu City, and Tianchang City and Fengyang County of Chuzhou City in Anhui Province from June to December 2020. A. bovis and A. phagocytophilum 16S ribosomal RNA (16S rRNA) gene, A. ovis major surface protein 4 (MSP4) gene and A. capra citric acid synthase (gltA) gene were amplified using PCR assay in all blood samples, and the prevalence of A. bovis, A. phagocytophilum, A. ovis and A. capra infections was calculated in sheep and goats. In addition, the positive amplification products were sequenced and subjected to genetic evolutionary analysis. Results The overall prevalence of Anaplasma infections was 17.5% (62/355) in sheep and goats in Anhui Province, and the prevalence of A. bovis, A. phagocytophilum, A. ovis and A. capra infections was 2.8% (10/355), 2.5% (9/355), 2.5% (9/355), and 7.0% (25/355), while the prevalence of A. bovis and A. phagocytophilum, A. phagocytophilum and A. ovis, A. phagocytophilum and A. capra and A. bovis, A. phagocytophilum and A. ovis co-infections was 0.8% (3/355), 1.1% (4/355), 0.3% (1/355) and 0.3% (1/355), respectively. No Anaplasma was detected in the sheep and goat farms in Fengyang County, while at least three Anaplasma species were detected in other sheep and goat farms, with co-infections of multiple Anaplasma species identified. The prevalence of Anaplasma infections was 14.7% (24/163) in goats and 19.8% (38/192) in sheep, and the prevalence of Anaplasma infections was 31.0% (31/100) in goats and sheep under 6 months of age, and 12.2% (31/255) in goats and sheep at ages of 6 months and older, respectively. A. bovis, A. phagocytophilum, A. ovis and A. capra were identified in sheep and goats of different breeds and ages. Conclusions Multiple Anaplasma species infections were commonly prevalent in goats and sheep in Anhui Province in 2020, notably A. phagocytophilum, A. ovis and A. capra, which have zoonotic risks. Improved surveillance and prevention and control of Anaplasma infections are required in sheep and goats in Anhui Province.
8.Discussion on Effects of Electroacupuncture on Intestinal Flora and Serum Inflammation Factors in Rheumatoid Arthritis Rabbits Based on"Gut-joint"Axis
Cui LIU ; Xiaozheng DU ; Weiyao JING ; Chenghong SU ; Limei LIU ; Bo YUAN ; Xinghua ZHANG ; Fengfan ZHANG ; Ping CHEN ; Xiangjun LI ; Haidong WANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(4):124-131
Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.
9.Research progress in chemical compositions and pharmacological effects of Dachengqi Decoction and predictive analysis on its quality marker
Xiao ZHANG ; Keyuan XIAO ; Chunxia HOU ; Junzhi WANG ; Yuqiang LIU ; Hong CHANG ; Xinghua LI
International Journal of Traditional Chinese Medicine 2024;46(4):541-544
Dachengqi Decoction is a classic prescription attacked by Yangming excessive syndromes in clinic, which has the effects of relieving heat, softening and dispersing knots, etc., and is often used in the treatment of gastrointestinal dysfunction caused by various diseases. This article reviewed the recent studies on the chemical compositions and pharmacological effects of Dachengqi Decoction in recent years. On this basis, combined with the "five principles" of TCM quality markers, the quality markers of Dachengqi Decoction were predicted and analyzed. It is suggested that emodin, Rhein, chrysophanol, aloe-emodin, synephrine, hesperidin, naringin, magnolol and magnolol can be used as quality markers of Dachengqi Decoction.
10.Characteristics of Emergency Health Systems Guidance Based on AGREE-HS
Danping ZHENG ; Wei YANG ; Nannan SHI ; Dongfeng WEI ; An LI ; Gezhi ZHANG ; Xue CHEN ; Fangqi LIU ; Zhaoshuai YAN ; Weixuan BAI ; Xinghua XIANG ; Yaxin TIAN ; Mengyu LIU ; Huamin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):137-148
This study used the Appraisal of Guidelines Research & Evaluation-Health Systems (AGREE-HS) to demonstratively compare 34 global coronavirus disease-2019 (COVID-19) health systems guidance documents (HSGs) and 6 World Health Organization (WHO) standard HSGs. The comparison involved topic, participants, methods, recommendations, and implementability, with the aim of exploring the characteristics of emergency HSGs. The results showed that the emergency HSGs had an overall average score of 49%, with topic having the highest score, recommendations having the second highest score, and participants having the lowest score. The standard HSGs had an overall average score of 79%, with high scores in all items. The emergency HSGs had lower scores in participants, methods, recommendations, and implementability than the standard HSGs (P<0.001), while the COVID-19 emergency HSGs developed by the WHO had higher score in topic than the standard HSGs (P<0.05). Compared with those released by countries, the COVID-19 emergency HSG developed by the WHO showed superiority in all items and overall scores (P=0.000 2). This indicates that emergency HSGs, represented by the COVID-19 emergency HSG, place equal emphasis on topic and recommendations as standard HSGs but have low requirements in terms of expert participation, evidence support, and comprehensive consideration in the time- and resource-limited context. They have the characteristics of prominent topics, clear purposes, orientation to demand, keeping up with the latest evidence, flexible adjustment, and timeliness, emphasizing immediate implementation effects, weakening long-term effects, and focusing on comprehensive benefits. Additionally, developers, types, and report completeness are important influencing factors.


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