1.Dihuang Yinzi Improves Cognitive Function of Mouse Model of Learning and Memory Impairments by Regulating Synaptic Plasticity via SIRT2
Wenting WANG ; Yangjing HAO ; Wenna SU ; Qinqing LI ; Shifeng CHU ; Junlong ZHANG ; Wenbin HE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):9-17
ObjectiveTo investigate the effects of Dihuang Yinzi on the cognitive function in the mouse model of learning and memory impairments induced by scopolamine (SCOP) and explore the treatment mechanism. MethodsA mouse model of learning and memory impairment was induced by intraperitoneal injection of SCOP. Sixty male C57BL/6J mice were randomized into six groups: control (0.9% NaCl, n=10), model (SCOP 1 mg·kg-1·d-1, n=10), low-, medium-, and high-dose Dihuang Yinzi (SCOP 1 mg·kg-1·d-1 + Dihuang Yinzi 5.5, 11.0, and 22.0 g·kg-1·d-1, n=10), and donepezil (SCOP 1 mg·kg-1·d-1 + donepezil 0.84 mg·kg-1·d-1, n=10). Mice were administrated with corresponding drugs for 6 weeks. Modeling started in the 4th week, and mice in other groups except the control group were injected with SCOP intraperitoneally 40 min after daily gavage. Behavioral testing began in the 5th week, 30 min after modeling each day. The Morris water maze and novel object recognition tests were carried out to evaluate the spatial learning and memory function of mice. Nissl staining was employed to observe the survival of neurons and Nissl bodies in the hippocampal CA1 region. Western blot was employed to determine the protein levels of silent information regulator 2 (SIRT2), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor 1 (GluA1), protein kinase A (PKA), cAMP response element-binding protein (CREB), phosphorylated-CREB (p-CREB), postsynaptic density protein 95 (PSD95), growth-associated protein-43 (GAP-43), and synaptophysin (SYN) in the hippocampus. Immunofluorescence was used to detect the expression of doublecortin (DCX) in the hippocampal dentate gyrus (DG) region. ResultsCompared with the control group, the model group showed impaired learning and memory (P<0.01), obvious neuronal damage in the hippocampal CA1 region, a reduction in neuron survival (P<0.01), a decrease in DCX expression in the hippocampal DG region (P<0.01), down-regulated proteins levels of GluA1, PKA, p-CREB/CREB, PSD95, SYN, and GAP-43 in the hippocampal tissue (P<0.05, P<0.01), and an up-regulated protein level of SIRT2 (P<0.01). Compared with the model group, the medium- and high-dose Dihuang Yinzi groups and the donepezil group showed improvements in learning and memory (P<0.05, P<0.01), while the low-, medium-, and high-dose Dihuang Yinzi groups and the donepezil group had increased neuron survival (P<0.05, P<0.01). The medium-dose Dihuang Yinzi group and the donepezil group showed increased DCX expression (P<0.05, P<0.01). The medium- and high-dose Dihuang Yinzi groups and the donepezil group showed up-regulation in the protein levels of GluA1, PKA, p-CREB/CREB, PSD95, SYN, and GAP-43 (P<0.05, P<0.01) and down-regulation in the protein level of SIRT2 (P<0.01). ConclusionDihuang Yinzi can improve the cognitive function in the mouse model of learning and memory impairments induced by SCOP by inhibiting the upregulation of SIRT2, activating the PKA/CREB signaling pathway, improving synaptic plasticity, and reducing hippocampal neuronal damage.
2.Prognostic analysis of genes related to pyroptosis in prostate cancer cells and the regulatory role of NLRP1
Xiaolu MA ; Jiaqin CHEN ; Junlong FENG ; Qi ZHAO ; Bin WANG
Journal of Modern Urology 2025;30(1):73-81
[Objective] To analyze the prognostic value of prostate cancer (PCa) pyroptosis-related genes (PRGs) using gene expression databases and to explore the regulatory mechanism of nucleotidebinding oligomerization domain-like receptor containing pyrin domain 1 (NLRP1) in the pyroptosis of PCa cells. [Methods] Fragments per kilobase of exon model per million reads mapped (FPKM) data and clinical information from PCa and adjacent tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were obtained. Differentially expressed PRGs between PCa and adjacent tissues, classified subtypes and plotted survival curves were analyzed. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to screen prognosis-related PRGs, risk scores were calculated, and a prognostic risk model was constructed and validated. Patients were divided into high and low risk groups based on the median risk scores from the training and validation sets, and gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis were conducted on differentially expressed PRGs. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of NLRP1 in PCa cell lines, and pyroptosis was induced in DU145 and LNCaP cells while morphological changes were observed. Western blot (WB) was performed to detect the expression of pyroptosis-related molecules. [Results] A total of 6 prognostic-related PRGs were obtained, including CHMP4C, CYCS, GPX4, GSDMB, NLRP1, and PLCG1. The risk score was positively correlated with the risk of recurrence but negatively correlated with the progression-free survival (P<0.001). The area under the receiver operating characteristic curves (AUCs) for the training set at 1, 3, and 5 years were 0.769 (95%CI: 0.652-0.878), 0.804 (95%CI: 0.736-0.882), and 0.772 (95%CI: 0.631-0.905), respectively, while those for the validation set were 0.731 (95%CI: 0.647-0.826), 0.753 (95%CI: 0.674-0.818), and 0.763 (95%CI: 0.626-0.849), respectively. Differences in expression levels of the 6 PRGs were observed between the high and low risk groups in both the training and validation sets (P<0.05). Cox regression analysis showed that T stage, prostate specific antigen (PSA), Gleason grade, and risk score were independent predictors of PCa prognosis (P<0.05). Differences in risk scores were observed among patients of different ages, T stages, and Gleason grades (P<0.05). NLRP1 was found to be lowly expressed in PCa cell lines and was involved in the regulation of pyroptosis in DU145 and LNCaP cells. [Conclusion] The prognostic risk model constructed based on PRGs has a certain predictability for the prognosis of PCa patients, and NLRP1 may be involved in the regulation of pyroptosis in PCa cells.
3.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.
4.Clinical transfusion consultation investigation and typical case analysis
Junlong YANG ; Yanli BAI ; Xuli DU ; Bin ZHANG ; Bo WANG
Chinese Journal of Blood Transfusion 2024;37(5):561-566,574
Objective To analyze the characteristics of blood transfusion consultation cases and establish the consulta-tion route,so as to provide reference for blood transfusion doctors to participate in blood transfusion consultation practice.Methods The cases involved in clinical transfusion consultation in the blood transfusion department of our hospital from 2020 to 2023 were collected from the hospital information system(HIS),and then classified by department and consultation type to summarize the main points of transfusion consultation,formulate transfusion consultation routes,and conduct typical cases analysis.Results There were 315 clinical transfusion consultations from 2020 to 2023,with an increasing trend year by year(26 in 2020,67 in 2021,81 in 2022,141 in 2023).The consultations involved 24 departments,including cardio-vascular medicine 14.0%(44/315),orthopedics 12.7%(40/315),intensive care medicine 8.9%(28/315),general medi-cine 8.3%(28/315),cardiopulmonary disease 6.0%(19/315),etc.There were 8 categories of consultations,including 35.6%(112/315)autologous ozonized blood transfusion,23.8%(75/315)plasma exchange,14.9%(47/315)perioperative mass blood preparation(transfusion),11.4%(36/315)platelet-rich plasma therapy and 6.3%(20/315)autologous blood collection,etc.The clinical blood transfusion consultation route was formulated according to the consultation points.Six pa-tients with various diseases were treated by blood transfusion department.With effective treatment measures taken,all of them improved and were discharged.Conclusion The summary of key points of clinical blood transfusion consultation and formulation of the blood transfusion consultation route by department of blood transfusion are conducive to the implementation of blood transfusion consultation and guarantee the safety of patients.
5.Meta-analysis of comparison of efficacies between low-dose and standard-dose radiotherapy in human papillomavirus-associated oropharyngeal cancer
Jiewen HAO ; Shuxin WEN ; Li ZHANG ; Chen WANG ; Shuntu CHE ; Junlong LI ; Meifang LUO
Chinese Journal of Radiation Oncology 2024;33(7):599-605
Objective:To compare the efficacy and safety of low-dose and standard-dose radiotherapy (LD-RT vs. SD-RT) in the treatment of oropharyngeal cancer patients with positive human papillomavirus (HPV). Methods:All comparative studies of low-dose versus standard-dose radiotherapy in the treatment of HPV-positive oropharyngeal cancer were searched from PubMed, Web of Science, Cochrane Library, EMbase, Chinese Biomedical Literature Database (CBM), CNKI, Chongqing VIP, and Wanfang databases from January 1, 2000 to February 9, 2023. According to the inclusion and exclusion criteria, the data were strictly screened, and the RevMan 5.4 software was used for meta-analysis.Results:A total of 8 studies were included. The pooled results showed that the overall survival (OS) and progression-free survival (PFS) of patients in the LD-RT group were similar to those in the SD-RT group ( HR=0.83, 95% CI=0.59-1.18, P=0.31; HR=0.97, 95% CI=0.53-1.78, P=0.92), but the rate of percutaneous endoscopic gastrostomy (PEG) insertion was significantly reduced ( RR=0.45, 95% CI=0.28-0.72, P=0.001). Conclusion:LD-RT yields similar efficacy and lower rate of PEG insertion compared with SD-RT in HPV-positive oropharyngeal neoplasm patients.
6.The early prediction of umbilical cord blood S100β protein and lactate combined with amplitude integrated electroencephalogram in small for gestational age preterm infants with brain injury
Junlong CHEN ; Xiaoli WANG ; Xiaoling YANG ; Xuewen SU ; Fuhua JIA ; Shuli WU
International Journal of Pediatrics 2024;51(1):64-68
Objective:To explore the early predictive value of umbilical cord blood S100β protein and lactate combined with amplitude integrated electroencephalogram(aEEG)in small for gestational age(SGA)preterm infants with brain injury.Methods:One hundred and six cases of SGA preterm infants were enrolled in this study in Neonatology Department of Inner Mongolia People's Hospital from January 2019 to December 2021. Umbilical cord blood serum S100β protein and lactate at birth of All SGA preterm infants were tested,and aEEG was monitored at 6h and 72 h after birth,corrected gestational age of 32 weeks and 37 weeks. According to the diagnostic criteria of brain injury in preterm infants,SGA preterm infants were divided into brain injury group(45 cases)and non-brain injury group(61 cases),and compared the differences of S100β protein,lactate and the designated time aEEG between the two groups.SGA preterm infants with brain injury were further divided into symmetrical group(28 cases)and non-symmetrical group(15 cases). The differences of umbilical cord blood S100β protein and lactate level between the two groups were compared,and the diagnostic value in different types of SGA preterm infants with brain injury was also compared.Results:SGA preterm infants in the brain injury group had significantly higher levels of umbilical cord blood S100β protein[(0.826±0.218)μg/L vs(0.397±0.196)μg/L, t=8.316, P<0.05]and lactate[(8.5±1.3)mmol/L vs(3.8±0.9)mmol/L, t=3.281, P<0.05]than those in non-brain injury group.Symmetric SGA group had higher level of S100β protein than the asymmetric SGA group[(0.924±0.205)μg/L vs(0.438±0.196)μg/L, t=5.734, P<0.05].But there was no statistically significant difference in lactate levels[(5.6±1.4)mmol/L vs(3.9±1.2)mmol/L, t=0.932, P>0.05]between symmetric SGA group and asymmetric SGA group. The abnormal rates of aEEG in brain injury group and non-brain injury group were respectively 100%(45/45)vs 22.95%(14/61)at 6 h after birth,95.56%(43/45)vs 16.39%(10/61)at 72 h after birth,62.22%(28/45)vs 6.56%(4/61)at 32 weeks of corrected gestational age,22.22%(10/45)vs 3.28%(2/61)at 37 weeks of corrected gestational age. The abnormal rate of brain injury group was higher than the non-brain injury group in the same nodal time,and the differences were statistically significant( χ 2 value respectively 62.292,64.913,38.074,9.257,all P<0.05). Conclusion:There were significant value in umbilical cord blood S100β protein,lactate level and aEEG monitoring in the early diagnosis in preterm infants SGA with brain injury. The combination of the three might be more helpful for the early diagnosis and timely treatment of brain injury in SGA preterm infants.
7.Safety and Efficacy of Concomitant Mitral Valvuloplasty and Implantation of Domestic Third-generation Magnetically Levitated Left Ventricular Assist Device
Zhihua WANG ; Xiaoxia DUAN ; Zeyuan ZHAO ; Junlong HU ; Zhigao CHEN ; Jianchao LI ; Baocai WANG ; Zhaoyun CHENG
Chinese Circulation Journal 2024;39(3):242-248
Objectives:To investigate the safety and efficacy of concomitant mitral valvuloplasty(MVP)and implantation of domestic third-generation magnetically levitated Corheart 6 left ventricular assist device(LVAD). Methods:Clinical data of 13 end-stage heart failure patients who underwent Corheart 6 LVAD implantation and MVP at Central China Fuwai Hospital of Zhengzhou University from October 2021 to March 2023 were retrospectively analyzed.Mortality and complication events during hospitalization and at follow-up were collected,and changes in myocardial injury biomarkers,renal function,hemodynamics,and echocardiographic indices were observed. Results:There were no perioperative deaths and no MVP-related complications in these patients.During a mean follow-up of(14.2±5.6)months,2 patients died due to COVID-19 pneumonia and cardiac arrest respectively,11 cases(84.6%)survived.There were no recurrences of moderate-to-severe mitral regurgitation in the survived patients.Compared with preoperative value,higher cardiac output,lower central venous pressure,pulmonary artery systolic pressure(PASP),and mean pulmonary artery pressure(PAMP)were evidenced at 24 h and 72 h postoperatively,estimated glomerular filtration rate was also reduced at 1 week post operation(all P<0.010).High-sensitive troponin T level was significantly increased at 1 week post operation and then reduced at 1 month post operation,but still not returned to pre-operative level([125.5±281.9]pg/ml at baseline,[1 295.6±654.6]pg/ml at 1 week post operation and[278.0±300.5]pg/ml at 1 month post operation).Echocardiography showed that compared with preoperative period,the left ventricular ejection fraction tended to be higher at 1 and 6 months postoperatively(both P>0.017),whereas left ventricular end-diastolic dimension,PASP,and PAMP were significantly reduced(all P<0.010). Conclusions:Domestic third-generation magnetically levitated Corheart 6 LVAD implantation with concomitant MVP is safe and feasible,there is no recurrence of moderate-to-severe mitral regurgitation,a significant reduction in pulmonary artery pressure,and significant hemodynamic improvement in early to mid-term postoperatively are observed in survived patients.
8.Effect of Dihuang Yinzi Decoction (地黄饮子)on Retinal Insulin Content and Insulin Signaling Pathway Related Protein Expression in Alzheimer's Disease Model Mice
Dongyan WU ; Wanwei GUI ; Xiaodan WANG ; Qinqing LI ; Jinmiao CHAI ; Junlong ZHANG
Journal of Traditional Chinese Medicine 2024;65(15):1593-1601
ObjectiveTo observe the possible mechanism of Dihuang Yinzi Decoction (地黄饮子) for improving cognitive dysfunction in Alzheimer's disease (AD) from the perspective of retina. MethodsForty-five APP/PS1 mice (AD model mice) were randomly divided into model group, Dihuang Yinzi Decoction group, and memantine group, with 15 mice in each group, while 15 wild-type C57BL/6J mice from the same litter were used as blank group. Mice in Dihuang Yinzi Decoction group were given Dihuang Yinzi Decoction 30.03 g/(kg·d) by gavage, mice in the memantine group were given memantine hydrochloride 6.1 mg/(kg·d) by gavage, and mice in the blank group and the model group were given normal saline 2 ml/(kg·d) by gavage for 4 consecutive weeks. Fasting blood glucose was measured weekly. After 4 weeks of intervention, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed; Morris water maze was used to detect the changes in spatial memory ability of mice; glucose oxidase method was used to detect retinal glucose content of mice; enzyme-linked immunosorbent assay (ELISA) was used to detect serum and retinal insulin content of mice, and Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated. Hematoxylin-eosin (HE) staining was performed to observe the histopathological changes in the retina, and the retinal thickness and ganglion cell number were counted; protein immunoblotting was performed to detect the retinal pathway-associated proteins [insulin receptor substrate 1 (IRS1), phosphorylated insulin receptor substrate 1 (pIRS1), phosphatidylinositol-3-hydroxykinase (PI3K), protein kinase B (Akt1), phosphorylated protein kinase B (pAkt1)] expression; retinal glucose transporter protein 4 (GLUT4) expression was detected by immunohistochemistry. ResultsCompared with the blank group, fasting blood glucose of mice in the model group at weeks 1, 2, 3, and 4, blood glucose and area under the curve (AUC) at different time point of OGTT and ITT test, fasting serum insulin, and HOMA-IR increased (P<0.05, P<0.01); in the Morris water maze experiment, the escape latency increased from day 3 to day 5, and the number of crossing platforms, the percentage of target quadrant distance, and the percentage of target quadrant time decreased (P<0.05, P<0.01); the outer nuclear layer of the retina became sparse, thinner, and the number of ganglion cells decreases (P<0.01); the expression level of retinal glucose increased, while the expression levels of insulin, pIRS1/IRS1, PI3K/β-Actin, pAkt1/Akt1, and GLUT4 proteins decreased (P<0.01). Compared with the model group, fasting blood glucose at week 4, blood glucose at each time point of the OGTT and ITT tests AUC decreased (P<0.05, P<0.01), and fasting serum insulin and HOMA-IR decreased (P<0.05) in Dihuang Yinzi Decoction group; In the Morris water maze test, the escape latency shortened on day 4 and day 5, number of platform crossings, target quadrant distance as a proportion of total distance, and target quadrant movement time as a proportion of total time decreased (P<0.05, P<0.01); retinal pathological changes alleviated, and retinal thickness and ganglion cell number increased (P<0.01); retinal glucose content decreased, and retinal pIRS1/IRS1, PI3K/β-Actin, and GLUT4 protein expression elevated (P<0.05 or P<0.01). ConclusionsDihuang Yinzi Decoction can improve cognitive dysfunction of Alzheimer's disease, which may be related to regulating retinal insulin content and insulin signaling pathway.
9.Exploring the Cultural Origins and Developmental Patterns of Academic Schools in Traditional Chinese Medicine from a Constructivist Perspective
Xin LIN ; Zhaojuan WANG ; Jie LI ; Junlong SHEN
Journal of Traditional Chinese Medicine 2024;65(8):769-774
Using constructivism theory, this study explored the relationship between the "origin" and "flow" of academic schools in traditional Chinese medicine (TCM), clarified the developmental patterns of schools, and provided insights for the modernization, inheritance, and innovation of current schools. Academic schools originate from different cultural sources, and their differentiation and development are similar to the replication, spread and variation of biological "genes". The theoretical characteristics of constructivism align well with the principles of formation and differentiation of academic schools. The construction of academic thoughts and core diagnostic and therapeutic concepts within each school can be seen as a multilevel unity of self-construction, mutual construction among individuals, and social construction. Firstly, individual medical practitioners choose and inherit from the origins of TCM, integrating personalized understanding, which then differentiates into various schools in the history of academia. Secondly, during the process of cultural inheritance, medical practitioners from different times and regions gradually form academic schools and local medical schools through the method of "tailoring strategies to three categories of etiological factors" and mutual construction among individuals. Finally, in the context of the scientific, standardized, and intelligent development of modern medicine, the further evolution of academic schools needs to follow the evolutionary laws of traditional medicine, combine with the health needs of the new era, adopt a social construction approach, facilitate multi-party participation in the inheritance and innovation of academic thoughts and clinical experiences, and utilize the internet and intelligent technology means to empower modern development.
10.Early outcomes of domestic left ventricular assist device implantation with or without concomitant mitral valvuloplasty
Zhihua WANG ; Zeyuan ZHAO ; Junlong HU ; Junjie SUN ; Kun LIU ; Xiaoxia DUAN ; Sheng WANG ; Zhaoyun CHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(11):1599-1605
Objective To compare the early outcomes of domestic third-generation magnetically levitated left ventricular assist device (LVAD) with or without concomitant mitral valvuloplasty (MVP). Methods The clinical data of 17 end-stage heart failure patients who underwent LVAD implantation combined with preoperative moderate to severe mitral regurgitation in Fuwai Central China Cardiovascular Hospital from May 2018 to March 2023 were retrospectively analyzed. The patients were divided into a LVAD group and a LVAD+MVP group based on whether MVP was performed simultaneously, and early outcomes were compared between the two groups. Results There were 4 patients in the LVAD group, all males, aged (43.5±5.9) years, and 13 patients in the LVAD+MVP group, including 10 males and 3 females, aged (46.8±16.7) years. All the patients were successful in concomitant MVP without mitral reguragitation occurrence. Compared with the LVAD group, the LVAD+MVP group had a lower pulmonary artery systolic pressure and pulmonary artery mean pressure 72 h after operation, but the difference was not statistically different (P>0.05). Pulmonary artery systolic pressure was significantly lower 1 week after operation, as well as pulmonary artery systolic blood pressure and pulmonary artery mean pressure at 1 month after operation (P<0.01). There was no statistically significant difference in blood loss, operation time, cardiopulmonary bypass time, aortic cross-clamping time, mechanical ventilation time, or ICU stay time between the two groups (P>0.05). The differences in 1-month postoperative mortality, acute kidney injury, reoperation, gastrointestinal bleeding, and thrombosis and other complications between the two groups were not statistically significant (P>0.05). Conclusion Concomitant MVP with implantation of domestic third-generation magnetically levitated LVAD is safe and feasible, and concomitant MVP may improve postoperative hemodynamics without significantly increasing perioperative mortality and complication rates.

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