1.Metabolic reprogramming nanomedicine potentiates colon cancer sonodynamic immunotherapy by inhibiting the CD39/CD73/ADO pathway.
Yuanyuan ZHANG ; Weiwei JIN ; Zhichao DENG ; Bowen GAO ; Yuanyuan ZHU ; Junlong FU ; Chenxi XU ; Wenlong WANG ; Ting BAI ; Lianying JIAO ; Hao WU ; Mingxin ZHANG ; Mingzhen ZHANG
Acta Pharmaceutica Sinica B 2025;15(5):2655-2672
Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.
2.Exploration into the relationship between dietary patterns and asthma based on Bayesian Poisson regression
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):859-865
Objective To explore the relationship between dietary patterns and the prevalence of asthma among residents in Gansu Province.Methods Based on the dietary and asthma prevalence data of permanent residents aged 35 to 74 years old collected in the baseline survey of the Urban and Rural Natural Population Cohort Establishment and Tumor Follow-up Study in Gansu Province,dietary patterns were established using factor analysis,and then the Bayesian Poisson regression model was built to analyze the relationship between dietary patterns and the prevalence of asthma.Results Of the 17 556 respondents,the prevalence rate of asthma was 0.66%.Five dietary patterns were extracted through factor analysis.After adjusting age,the type of medical insurance,physical exercise,gender,and body mass index(BMI),the sugar-fat pattern and the oil-fat pattern were found to be positively associated with the prevalence of asthma,with their RR values(95%CI)being 1.192(1.016-1.393)and 1.254(1.035-1.503),respectively.Conclusion The sugar-fat pattern and oil-fat pattern can increase the risk of asthma,and the onset and progression of asthma should be prevented through a reasonable diet.
3.Efficacy and safety of hybrid surgery for the recanalization of carotid artery occlusion after stenting
Zhengyu WANG ; Guangdong LU ; Tao WANG ; Wenlong XU ; Xia LU ; Fei CHEN ; Bin YANG ; Peng GAO ; Yabing WANG ; Yanfei CHEN ; Yan MA ; Liqun JIAO
Chinese Journal of Cerebrovascular Diseases 2024;21(8):505-513
Objective To investigate the efficacy and safety of hybrid surgery for the recanalization of carotid artery occlusion after stenting.Methods Clinical data and results of 17 patients with occlusion after carotid artery stenting and treated with hybrid surgery from June 2016 to April 2023 at the Department of Neurosurgery Cerebral Blood Flow Reconstruction Center of Xuanwu Hospital,Capital Medical University were retrospectively analyzed.According to whether the recanalization was successful,17 patients were divided into the the successful recanalization group and the failed recanalization group.Successful recanalization was defined as achieving modified thrombolysis in cerebral infarction(mTICI)grade ≥2b and residual stenosis<50%.Baseline data(age,sex,body mass index,smoking history,alcohol consumption history,hypertension history,diabetes history,hyperlipidemia history,coronary heart disease history),clinical data(National Institutes of Health Stroke Scale[NIHSS]score at admission,fasting blood glucose,low density lipoprotein,high density lipoprotein,total cholesterol,triglyceride,occlusion side and segment,combination with severe stenosis or occlusion of the contralateral carotid artery,opening of the anterior communicating artery,opening of the posterior communicating artery,compensation of the external and internal carotid artery,compensation of the pia artery,stump morphology,and time from imaging diagnosis of occlusion to recanalization)were documented and compared between groups.The recanalization of occlusive vessels and perioperative complications were recorded.Imaging and clinical follow-up were performed 3,6 months and≥1 year after surgery.Results Among the 17 patients,the ratio of successful recanalization was 13/17.One patient had re-occlusion after operation,which was re-opened after thrombolysis,but neck hematoma with dyspnea occurred,and recovered after emergency operation.There was no postoperative stroke or death.The incidence of perioperative complications was 1/17.Compared with the successful recanalization group,the levels of high density lipoprotein and total cholesterol in the failed recanalization group were higher,and the differences between the groups were statistically significant(high density lipoprotein[1.3±0.3]mmol/L vs.[0.9±0.3]mmol/L,t=-2.139;total cholesterol:[4.2±0.8]mmol/L vs.[3.1±0.7]mmol/L,t=-2.649;both P<0.05);There were no significant differences in other baseline data and clinical data(all P>0.05).Imaging follow-up was completed in 9 of the 13 patients in the successful recanalization group,and the follow-up time was 3.8-36.9 months,with a median follow-up time of 22.8(12.8,34.7)months.Among them,1 patient(1/9)developed restenosis of recanalization vessels at 33.0 months after surgery and underwent stent implantation again.Conclusions The preliminary analysis showed that the occlusion after carotid artery stenting had better recanalization success and lower perioperative complications.In patients with chronic occlusion after carotid stenting,the application of a hybrid surgery for opening may be attempted under multimodal imaging assessment.
4.Research progress in the prevention of hypothermia in patients undergoing neurointerventional surgery
Fang WANG ; Wenlong PAN ; Hongwei GAO
Journal of Interventional Radiology 2024;33(11):1255-1259
With the development of interventional technology and the innovation of interventional instruments,neurointerventional surgery has become one of the treatments for cerebrovascular diseases.Neurointervention has the advantages of less trauma,quick recovery and fewer complications.However,due to the complexity of cerebrovascular diseases and the vascular bending and variation,neurointerventional procedures often take a long time and require general anesthesia,which makes patients prone to hypothermia during surgery.At present,clinical studies on intraoperative hypothermia mainly focus on the surgical general anesthesia,and there are few studies related to hypothermia occurring in neurointerventional procedures,to which the clinical attention has not been highly paid.This paper aims to make a comprehensive review about the hypothermia during surgery,focusing on the effect of hypothermia on the body,the characteristics of neurointerventional therapy,the causes of hypothermia,and the prevention and treatment measures of intraoperative hypothermia,so as to provide reference for the medical staff working in the neurointerventional therapy department.
5.Spatial-temporal Distribution and Influencing Factors of Late Diagnosis of HIV/AIDS Based on Bayes Spatial-temporal Model
Li SHAO ; Jijun CHEN ; Yuqi ZHANG ; Jing XU ; Guo LI ; Wenlong GAO
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(2):243-252
ObjectivesTo analyze the spatial and temporal clustering characteristics and related influencing factors of late diagnosis of HIV/AIDS in Lanzhou, to identify its high-risk areas and time trends in Lanzhou, and to provide a theoretical basis for developing targeted HIV/AIDS prevention and control strategies in Lanzhou. MethodsThe subjects of this study were adult HIV/AIDS cases reported in Lanzhou City between 2011 and 2018. Data used in the study were sourced from the Lanzhou Center for Disease Control and Prevention and the Lanzhou Statistical Yearbook. To analyze the spatial distribution characteristics and influencing factors of the relative risk (RR) of late HIV/AIDS diagnosis, Bayes spatial-temporal model was used. ResultsA total of 1984 new HIV/AIDS cases were reported in Lanzhou from 2011 to 2018, with an mean age of 37.51 years and predominantly male (91.8%). The number of late diagnosis cases was 982, with an mean age of 39.67 years and a predominance of males (91.8%). Late diagnosis was more common in older individuals and women with HIV/AIDS. Chengguan District (51.1%), Anning District (50.3%) and Yuzhong County (51.9%) had an above-average proportion of late diagnosis of HIV/AIDS. The proportion of late diagnosis cases in Lanzhou showed a fluctuating upward trend from 2011 to 2018. The results of Bayes spatial-temporal model showed that the risk of late HIV/AIDS diagnosis in Lanzhou had fluctuated from 2011 to 2015, and then increased rapidly after 2015 [RR (95% credibility interval, 95%CI) increased from 1.01 (0.84, 1.23) to 1.11 (0.77, 1.97)]; the trends of risk of late diagnosis in Honggu district and three counties were similar to the overall trend in Lanzhou city, while the risk of late diagnosis in Chengguan District and Qilihe District showed a decreasing trend. The regions with the RR for late diagnosis greater than 1 included Yongdeng County (RR=1.07, 95% CI: 0.55, 1.96), Xigu District (RR=1.04, 95% CI: 0.67, 1.49), Chengguan District (RR=2.41, 95% CI: 0.85, 6.16), and Qilihe District (RR=2.03, 95% CI: 1.10, 3.27). Besides, the heatmap analysis showed that Chengguan District and Qilihe District were the hot spots. The influencing factors analysis showed that the higher GDP per capita (RR=0.65, 95% CI: 0.35, 0.90) and the larger proportion of males with HIV/AIDS cases (RR=0.53, 95% CI: 0.19, 0.92) could lead to the lower the relative risk of late HIV/AIDS diagnosis. However, the higher the population density (RR=1.35, 95% CI: 1.01, 1.81) caused the higher the risk of late diagnosis. ConclusionOur study shows the risk of late diagnosis of HIV/AIDS in Lanzhou was on the rise, and there are significant regional differences. GDP per capita, the proportion of males in HIV/AIDS cases and population density are influencing factors in the late diagnosis of HIV/AIDS. Therefore, for regions with a high risk of late diagnosis or related risk factors, targeted HIV screening and prevention services should be given priority in order to reduce the proportion and risk of late diagnosis of HIV/AIDS.
6.Sleep status and influencing factors among higher vocational college students
Yong LI ; Xiaomei XIONG ; Fang HUANG ; Xia HUANG ; Xiu XU ; Zhaoxia HE ; Wenlong ZHANG ; Jiang ZHAO ; Xueli LIU ; Ru GAO
Sichuan Mental Health 2023;36(4):366-371
BackgroundSleep disorder can adversely affect human physical and mental health, with important implications for socioeconomic development. And higher vocational college students are subject to various pressures and stimuli exerted by academic studies, job seeking and family socioeconomic status, which may contribute to the onset insomnia symptom or sleep disorder. ObjectiveTo discuss the sleep status and influencing factors among higher vocational college students, and to provide references for improving their sleep status. MethodsIn January and February, 2022, a stratified random sampling method was utilized to enroll 3 300 students from five higher vocational colleges in Wenjiang district of Chengdu city. All the participants were assessed using Insomnia Severity Index (ISI), Patient Health Questionnaire Depression Scale-9 item (PHQ-9) and Generalized Anxiety Disorder Scale-7 (GAD-7). Pearson correlation analysis was conducted to test the correlation of ISI with PHQ-9 and GAD-7 scores, and the Logistic regression analysis was performed to identify the influencing factors of insomnia symptom in higher vocational college students. ResultInsomnia symptom was detected in 81.90% (2 497 / 3 300) of higher vocational college students. The detection rate of insomnia symptom among vocational college students yielded statistical difference in terms of gender, family socioeconomic status, being an only child or having siblings, degree of psychological pressure exerted by academic studies or job seeking, amount of hours spent on Internet per day, frequency of physical exercise, and the presence or absence of anxiety symptom and depression symptom (χ2=21.032, 22.172, 8.983, 75.939, 36.781, 32.350, 54.512, 86.561, P<0.01 or 0.05). Among higher vocational college students, ISI score was positively correlated with GAD-7 and PHQ-9 scores (r=0.620, 0.714, P<0.01), and GAD-7 score was positively correlated with PHQ-9 score (r=0.824, P<0.01). Gender, family socioeconomic status, degree of psychological pressure exerted by academic studies or job seeking, amount of hours spent on Internet per day, frequency of physical exercise, and the presence or absence of anxiety symptom and depression symptom were effective factors in predicting the insomnia symptom in higher vocational college students (P<0.01 or 0.05). ConclusionFemale gender, average and below average family socioeconomic status, moderate-to-severe degree of psychological pressure exerted by academic studies or job seeking, spending 2~5 h, 5~7 h or >7 h on Internet per day, inadequate physical exercise and presence of depressive symptom are the risk factors for insomnia symptom in higher vocational college students.[Funded by Sichuan Provincial Primary Health Development Research Center in 2022, North Sichuan Medical College (number, SWFZ22-C-89)]
7.Research progress of measurement tools for health-related quality of life in patients with spinal metastases
Mengchen YIN ; Wenlong YU ; Lin LI ; Xin GAO ; Luosheng ZHANG ; Dingbang CHEN ; Quan HUANG ; Xinghai YANG ; Junming MA ; Jianru XIAO ; Wen MO
Chinese Journal of Orthopaedics 2023;43(16):1115-1122
The Health-Related Quality of Life (HRQoL) pertains to patients' subjective contentment concerning their physical, psychological, and social well-being throughout disease treatments. Predominantly employed HRQoL metrics in spinal metastases comprise the 36-item Short-Form Health Survey (SF-36), EuroQoL Five Dimensions Questionnaire (EQ-5D), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and the Functional Assessment of Cancer Therapy-General (FACT-G). In clinical applications, due to their broad application and diverse disease types, combined with the lack of specificity in the scale content and the prolixity of their questionnaires, these tools often fail to capture the nuanced experiences of patients, thereby compromising the reliability and validity of the results. The Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ), developed by the Spine Oncology Study Group, offers a tailored metric for spinal metastases, encapsulating both specificity and inclusivity. Its proven robust reliability and validity make it invaluable for decision-making and therapeutic efficacy appraisals. The Patient-Reported Outcome Measurement Information System (PROMIS), a novel metric suitable across many medical disciplines, facilitates cross-sector data acquisition, substantially augmenting the precision, sensitivity, and credibilityof assessments, and is pivotal in clinical investigations and interventions. As it continually evolves, PROMIS consistently outperforms traditional metrics in evaluative capacities, exhibiting impressive and consistent proficiency in prognostications, preoperative assessments, and therapeutic outcome evaluations within the spinal metastasis domain. Presently, Chinese research on the HRQoL of spinal metastasis patients remains scant, and choosing an apt, precise, and dependable metric holds significant clinical relevance. Drawing upon extant scholarly publications, this review concluded the current global HRQoL tools for spinal metastases, aiming to furnish insights for the clinical management and research pertaining to spinal metastases.
8.Prenatal diagnosis and genetic analysis of a fetus with partial deletion of Yq and mosaicism of 45,X.
Lijuan WANG ; Hui GUO ; Qi LIN ; Zhiyang HU ; Huiyan HE ; Mei YE ; Zhuojian LIANG ; Wenlong HU ; Hui GAO ; Di MA ; Yaqin SONG
Chinese Journal of Medical Genetics 2023;40(6):744-749
OBJECTIVE:
To carry out prenatal diagnosis and genetic analysis for a fetus with disorders of sex development (DSDs).
METHODS:
A fetus with DSDs who was identified at the Shenzhen People's Hospital in September 2021 was selected as the study subject. Combined molecular genetic techniques including quantitative fluorescence PCR (QF-PCR), multiplex ligation-dependent probe amplification (MLPA), chromosomal microarray analysis (CMA), quantitative real-time PCR (qPCR), as well as cytogenetic techniques such as karyotyping analysis and fluorescence in situ hybridization (FISH) were applied. Ultrasonography was used to observe the phenotype of sex development.
RESULTS:
Molecular genetic testing suggested that the fetus had mosaicism of Yq11.222qter deletion and X monosomy. Combined with the result of cytogenetic testing, its karyotype was determined as mos 45,X[34]/46,X,del(Y)(q11.222)[61]/47,X,del(Y)(q11.222),del(Y)(q11.222)[5]. Ultrasound examination suggested hypospadia, which was confirmed after elective abortion. Combined the results of genetic testing and phenotypic analysis, the fetus was ultimately diagnosed with DSDs.
CONCLUSION
This study has applied a variety of genetic techniques and ultrasonography to diagnose a fetus with DSDs with a complex karyotype.
Prenatal Diagnosis
;
Mosaicism
;
Chromosomes, Human, X
;
Chromosomes, Human, Y
;
Humans
;
Male
9.Manipulation of IME4 expression, a global regulation strategy for metabolic engineering in Saccharomyces cerevisiae.
Jianxun ZHU ; Tianyue AN ; Wenlong ZHA ; Ke GAO ; Ting LI ; Jiachen ZI
Acta Pharmaceutica Sinica B 2023;13(6):2795-2806
Metabolic engineering has been widely used for production of natural medicinal molecules. However, engineering high-yield platforms is hindered in large part by limited knowledge of complex regulatory machinery of metabolic network. N6-Methyladenosine (m6A) modification of RNA plays critical roles in regulation of gene expression. Herein, we identify 1470 putatively m6A peaks within 1151 genes from the haploid Saccharomyces cerevisiae strain. Among them, the transcript levels of 94 genes falling into the pathways which are frequently optimized for chemical production, are remarkably altered upon overexpression of IME4 (the yeast m6A methyltransferase). In particular, IME4 overexpression elevates the mRNA levels of the methylated genes in the glycolysis, acetyl-CoA synthesis and shikimate/aromatic amino acid synthesis modules. Furthermore, ACS1 and ADH2, two key genes responsible for acetyl-CoA synthesis, are induced by IME4 overexpression in a transcription factor-mediated manner. Finally, we show IME4 overexpression can significantly increase the titers of isoprenoids and aromatic compounds. Manipulation of m6A therefore adds a new layer of metabolic regulatory machinery and may be broadly used in bioproduction of various medicinal molecules of terpenoid and phenol classes.
10.The research progress on atypical teratoid/rhabdoid tumor of the central nervous system in children
Wenlong GAO ; Pan GOU ; Ping LIANG
Chinese Journal of Nervous and Mental Diseases 2023;49(11):682-688
Atypical teratoid/rhabdoid tumor(AT/RT)is a rare and highly malignant embryonal tumor of the central nervous system in children,characterized by diverse histological morphology,high malignancy,rapid clinical progression,and poor prognosis for affected children.The pathogenesis of AT/RT involves mutations in chromosomes and genes,particularly the loss of function of the SMARCB1 gene.The diagnosis of AT/RT primarily relies on histological and immunohistochemical analysis.Currently,there is no standardized treatment protocol for AT/RT.The main treatment modalities include surgery,chemotherapy,radiotherapy,as well as emerging targeted therapy and immunotherapy.Despite progress in research and clinical trials on AT/RT in recent years,the prognosis for affected children remains poor,necessitating further research to develop more effective treatment strategies to improve patient outcomes.

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