1.Mechanism of Huanglian Jiedutang in Improving Pyroptosis, Neuroinflammation, and Learning and Cognitive Functions in APP/PS1 Mice Based on NLRP3/Caspase-1/GSDMD Pathway
Wei CHENG ; Shuo YANG ; Zhangxin HE ; Wei CHEN ; Aihua TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):11-19
ObjectiveTo investigate the mechanism by which Huanglian Jiedutang (HLJDT) inhibits pyroptosis and neuroinflammation in Alzheimer's disease (AD) mice via the NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific protease-1 (Caspase)-1/gasdermin D (GSDMD) pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group (model group), the positive control group (Donepezil group, 0.65 mg·kg-1), and the HLJDT treatment group (HLJDT group, 5.2 g·kg-1). Ten C57BL/6 mice were assigned to the blank control group (control group). The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology, quantity, and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 (PSD95), amyloid precursor protein (APP), inflammatory factors including nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), as well as pyroptosis pathway-related proteins including NLRP3, Caspase-1, GSDMD, and GSDMD-N. ResultsCompared with the control group, the model group exhibited significantly decreased learning and memory abilities (P<0.01), reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly increased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.01). Protein levels of PSD95 were markedly decreased, while the expression levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly elevated (P<0.01). Compared with the model group, both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities (P<0.05, P<0.01), increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly decreased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.05, P<0.01). Protein levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly downregulated, while PSD95 expression was significantly upregulated (P<0.05, P<0.01). There was no statistically significant difference in GSDMD-N levels in the Donepezil group, while GSDMD-N expression was significantly decreased in the HLJDT group (P<0.05). ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice, and attenuate neuronal loss and synaptic damage, possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.
2.Mechanism of Kidney-tonifying and Liver-regulating Cyclical Therapy and Formula in Improving Endometrial Receptivity during "Implantation Window" in Rats with Polycystic Ovary Syndrome via miR-140-5p/VEGF Pathway
Quan LIU ; Yiqing HE ; Ying ZHANG ; Xi WANG ; Shuo YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):100-109
ObjectiveTo investigate the mechanism of kidney-tonifying and liver-regulating cyclical therapy and its formula in regulating endometrial receptivity during the "implantation window" in rats with polycystic ovary syndrome (PCOS). MethodsSix rats were randomly selected from 36 SPF SD female rats as the normal group, and the remaining rats were administered letrozole to induce a PCOS model. By using a random number method, the rats were divided into the following groups: normal group, model group, Xiaoyaosan group (11.97 g·kg-1), Sanzi Yangmo decoction group (28.35 g·kg-1), cyclical therapy group (11.97/28.35 g·kg-1), and aspirin group (8 × 10-3 mg·kg-1). After 12 days of continuous administration by gavage (equivalent to three estrous cycles), female and male rats were co-housed. On the fifth day of pregnancy, the number of blastocyst implantation in each group was counted. Hematoxylin-eosin (HE) staining was used to observe the pathological morphology of rat endometrial tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of estradiol (E2) and progesterone (P) in rat serum. Western blot was used to detect the protein expression of vascular endothelial growth factor (VEGF), progesterone receptor (PR), estrogen receptor (ER), androgen receptor (AR), and integrin(ITG) αvβ3 in rat endometrial blood vessels. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-140-5 P, VEGF, vascular endothelial growth factor receptor 2 (VEGFR2), PR, ER, AR, and ITGαvβ3 in rat endometrium. ResultsCompared with normal group, the estrous cycle of the rats in model group continued to be in the estrus interval and the estrous cycle lost regular changes. The endometrium was significantly thinner, the number of uterine glands and blood vessels were significantly reduced (P<0.01), and the pregnancy rate was significantly reduced. Compared with the model group, each drug group restored the regular estrous cycle to varying degrees, and the endometrial thickness and the number of blood vessels were significantly improved (P<0.01). The pregnancy rate of each drug group increased, and the effect of the cycle therapy group could reach the normal level. The results of molecular biology experiments showed that compared with the normal group, the levels of serum E2 and P in the model group were significantly decreased (P<0.01), the expression of VEGF, ER, PR and ITGαvβ3 protein was significantly decreased (P<0.05,P<0.01), the expression of AR protein was significantly increased (P<0.01), the expression of miR-140-5P and AR mRNA was significantly increased (P<0.01), and the expression of VEGF, VEGFR2, ER, PR and ITGαvβ3 mRNA was significantly decreased (P<0.01). Compared with model group, the serum E2 level in the Xiaoyaosan group was significantly increased (P<0.01).The levels of E2 and P in serum of rats in Sanzi Yangmo decoction group, cycle therapy group and aspirin group were significantly increased (P<0.01). The expression of AR protein in each drug group was significantly decreased (P<0.01). The expression of VEGF and ITGαvβ3 protein in Xiaoyaosan group was significantly increased (P<0.01). The expression of VEGF, ER and PR protein in Sanzi Yangmo decoction group was increased to varying degrees (P<0.05,P<0.01). The expression of VEGF, PR, ER and ITGαvβ3 protein in the cycle therapy group and the aspirin group increased to varying degrees (P<0.05,P<0.01). The expression of miR-140-5P and AR mRNA in each drug group was significantly decreased (P<0.01). The expression of VEGF, VEGFR2, ER, PR and ITGαvβ3 mRNA in each drug group increased to varying degrees (P<0.05,P<0.01). Compared with Xiaoyaosan group and Sanzi Yangmo decoction group, the expression of miR-140-5P, VEGFR2, ER, PR, AR and ITGαvβ3 mRNA in the cycle therapy group were significantly different (P<0.05,P<0.01). ConclusionThe kidney-tonifying and liver-regulating cyclical therapy may reduce the activity of miR-140-5P, target the upregulation of VEGF expression, mediate angiogenesis, and promote endometrial angiogenesis, thereby playing a synergistic role in improving endometrial receptivity in PCOS-induced infertility. Its efficacy in increasing pregnancy rates surpasses that of Xiaoyaosan or Sanzi Yangmo decoction used alone.
3.Mechanism of Huanglian Jiedutang in Improving Pyroptosis, Neuroinflammation, and Learning and Cognitive Functions in APP/PS1 Mice Based on NLRP3/Caspase-1/GSDMD Pathway
Wei CHENG ; Shuo YANG ; Zhangxin HE ; Wei CHEN ; Aihua TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):11-19
ObjectiveTo investigate the mechanism by which Huanglian Jiedutang (HLJDT) inhibits pyroptosis and neuroinflammation in Alzheimer's disease (AD) mice via the NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific protease-1 (Caspase)-1/gasdermin D (GSDMD) pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group (model group), the positive control group (Donepezil group, 0.65 mg·kg-1), and the HLJDT treatment group (HLJDT group, 5.2 g·kg-1). Ten C57BL/6 mice were assigned to the blank control group (control group). The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology, quantity, and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 (PSD95), amyloid precursor protein (APP), inflammatory factors including nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), as well as pyroptosis pathway-related proteins including NLRP3, Caspase-1, GSDMD, and GSDMD-N. ResultsCompared with the control group, the model group exhibited significantly decreased learning and memory abilities (P<0.01), reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly increased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.01). Protein levels of PSD95 were markedly decreased, while the expression levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly elevated (P<0.01). Compared with the model group, both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities (P<0.05, P<0.01), increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly decreased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.05, P<0.01). Protein levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly downregulated, while PSD95 expression was significantly upregulated (P<0.05, P<0.01). There was no statistically significant difference in GSDMD-N levels in the Donepezil group, while GSDMD-N expression was significantly decreased in the HLJDT group (P<0.05). ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice, and attenuate neuronal loss and synaptic damage, possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.
4.Mechanism of Kidney-tonifying and Liver-regulating Cyclical Therapy and Formula in Improving Endometrial Receptivity during "Implantation Window" in Rats with Polycystic Ovary Syndrome via miR-140-5p/VEGF Pathway
Quan LIU ; Yiqing HE ; Ying ZHANG ; Xi WANG ; Shuo YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):100-109
ObjectiveTo investigate the mechanism of kidney-tonifying and liver-regulating cyclical therapy and its formula in regulating endometrial receptivity during the "implantation window" in rats with polycystic ovary syndrome (PCOS). MethodsSix rats were randomly selected from 36 SPF SD female rats as the normal group, and the remaining rats were administered letrozole to induce a PCOS model. By using a random number method, the rats were divided into the following groups: normal group, model group, Xiaoyaosan group (11.97 g·kg-1), Sanzi Yangmo decoction group (28.35 g·kg-1), cyclical therapy group (11.97/28.35 g·kg-1), and aspirin group (8 × 10-3 mg·kg-1). After 12 days of continuous administration by gavage (equivalent to three estrous cycles), female and male rats were co-housed. On the fifth day of pregnancy, the number of blastocyst implantation in each group was counted. Hematoxylin-eosin (HE) staining was used to observe the pathological morphology of rat endometrial tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of estradiol (E2) and progesterone (P) in rat serum. Western blot was used to detect the protein expression of vascular endothelial growth factor (VEGF), progesterone receptor (PR), estrogen receptor (ER), androgen receptor (AR), and integrin(ITG) αvβ3 in rat endometrial blood vessels. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-140-5 P, VEGF, vascular endothelial growth factor receptor 2 (VEGFR2), PR, ER, AR, and ITGαvβ3 in rat endometrium. ResultsCompared with normal group, the estrous cycle of the rats in model group continued to be in the estrus interval and the estrous cycle lost regular changes. The endometrium was significantly thinner, the number of uterine glands and blood vessels were significantly reduced (P<0.01), and the pregnancy rate was significantly reduced. Compared with the model group, each drug group restored the regular estrous cycle to varying degrees, and the endometrial thickness and the number of blood vessels were significantly improved (P<0.01). The pregnancy rate of each drug group increased, and the effect of the cycle therapy group could reach the normal level. The results of molecular biology experiments showed that compared with the normal group, the levels of serum E2 and P in the model group were significantly decreased (P<0.01), the expression of VEGF, ER, PR and ITGαvβ3 protein was significantly decreased (P<0.05,P<0.01), the expression of AR protein was significantly increased (P<0.01), the expression of miR-140-5P and AR mRNA was significantly increased (P<0.01), and the expression of VEGF, VEGFR2, ER, PR and ITGαvβ3 mRNA was significantly decreased (P<0.01). Compared with model group, the serum E2 level in the Xiaoyaosan group was significantly increased (P<0.01).The levels of E2 and P in serum of rats in Sanzi Yangmo decoction group, cycle therapy group and aspirin group were significantly increased (P<0.01). The expression of AR protein in each drug group was significantly decreased (P<0.01). The expression of VEGF and ITGαvβ3 protein in Xiaoyaosan group was significantly increased (P<0.01). The expression of VEGF, ER and PR protein in Sanzi Yangmo decoction group was increased to varying degrees (P<0.05,P<0.01). The expression of VEGF, PR, ER and ITGαvβ3 protein in the cycle therapy group and the aspirin group increased to varying degrees (P<0.05,P<0.01). The expression of miR-140-5P and AR mRNA in each drug group was significantly decreased (P<0.01). The expression of VEGF, VEGFR2, ER, PR and ITGαvβ3 mRNA in each drug group increased to varying degrees (P<0.05,P<0.01). Compared with Xiaoyaosan group and Sanzi Yangmo decoction group, the expression of miR-140-5P, VEGFR2, ER, PR, AR and ITGαvβ3 mRNA in the cycle therapy group were significantly different (P<0.05,P<0.01). ConclusionThe kidney-tonifying and liver-regulating cyclical therapy may reduce the activity of miR-140-5P, target the upregulation of VEGF expression, mediate angiogenesis, and promote endometrial angiogenesis, thereby playing a synergistic role in improving endometrial receptivity in PCOS-induced infertility. Its efficacy in increasing pregnancy rates surpasses that of Xiaoyaosan or Sanzi Yangmo decoction used alone.
5.Exploration and practice of internal quality assurance system of graduate students in a military medical university based on training process management
Haiwei YU ; Tao HE ; Shuo ZENG ; Xin LI ; Yongtao HE
Chinese Journal of Medical Education Research 2024;23(4):470-473
This paper mainly discusses the practical significance of the internal quality assurance system of graduate students in a military medical university based on training process management. The integrated internal quality assurance system follows the direction of three core steps—course learning, scientific research practice training, and dissertation writing, and highlights nine key points—learning foundation in admission education and training, knowledge acquisition in course learning, application ability in teaching and scientific research practice, innovation ability in academic activities and innovation competitions, topic selection quality in thesis proposal, training quality in mid-term assessment, paper quality in dissertation writing, output quality in thesis defense, and comprehensive quality in diploma awarding. Our exploration and practical experience is shared in this article.
6.Study on anti-myocardial ischemia active components and mechanism of Xinkeshu tablets based on network pharmacology and zebrafish model
Lin-Hua HOU ; Hua-Zheng ZHANG ; Shuo GAO ; Yun ZHANG ; Qiu-Xia HE ; Ke-Chun LIU ; Chen SUN ; Jian-Heng LI ; Qing XIA
Chinese Pharmacological Bulletin 2024;40(5):964-974
Aim To study the active ingredients and mechanism of action of Xinkeshu tablets against myo-cardial ischemia by network pharmacology and ze-brafish model.Methods The anti-myocardial ische-mia activity of Xinkeshu tablets was evaluated by iso-prenaline hydrochloride(ISO)-induced zebrafish myo-cardial ischemia model and H2O2-induced H9c2 dam-age model.The active ingredients of Xinkeshu tablets were retrieved using databases such as TCMSP.The potential targets were predicted by PharmaMapper data-base.Myocardial ischemic disease targets were searched by OMIM database.The potential therapeutic targets of Xinkeshu tablets against myocardial ischemia were analyzed.GO and KEGG enrichment analysis were conducted on core targets.The active ingredients were verified by zebrafish and cell model.qRT-PCR was used to detect the expression of key targets.Re-sults Xinkeshu tablets could significantly alleviate ISO-induced pericardial edema and bradycardia.It al-so could increase sinus venous-bulb aortic(SV-BA)distance and improve the cell viability.The 30 poten-tial active ingredients of Xinkeshu tables mainly acted on 30 core targets,including ALB,AKT1 and MAPK1,to regulate 627 GO items,including protein phosphorylation,negative regulation of apoptosis and positive regulation of PI3K signal transduction.KEGG results showed that 117 signaling pathways,including PI3K/Akt,FOXO and Ras,exerted anti-myocardial ischemia effect.Salvianolic acid A,lithospermic acid,rosmarinic acid,salvianolic acid D,salvianolic acid B,ginsenoside Rg2,hyperoside,3'-methoxypuerarin,3'-hydroxypuerarin and ginsenoside Rg1 could alleviate ISO-induced zebrafish myocardial ischemia and im-prove the cell viability.Xinkeshu tablets could upregu-late the expression of genes such as ras and akt1,and downregulate the expression of genes such as mapk1 and mapk8.Conclusion The active ingredients,in-cluding salvianolic acid A in Xinkeshu tablets,exert anti-myocardial ischemia effects by targeting targets,such as AKT1,MAPK1,and regulating signaling path-ways,such as PI3K/Akt,MAPK and Ras.
7.ZBH2012001,a novel serotonin and norepinephrine reuptake inhibitor,exerts antidepressant effect via dual mechanism of monoamine enhancement and inflammation suppression
Jingwen ZHANG ; Qiongyin FAN ; Susu ZHANG ; Yang ZHANG ; Ya LUO ; Xinming SHEN ; Luyao LUO ; Beilei DONG ; Jincao LI ; Shuo LI ; Huajin DONG ; Xingzhou LI ; Yupeng HE ; Rui XUE ; Youzhi ZHANG
Chinese Journal of Pharmacology and Toxicology 2024;38(5):321-334
OBJECTIVE To evaluate the mechanisms underlying the antidepressant effect of ZBH2012001,a novel serotonin and norepinephrine reuptake inhibitor(SNRI),in general and its ability to enhance monoaminergic transmission and suppress neuroinflammation in particular.METHODS① Male ICR mice were divided into vehicle(distilled water),duloxetine(DLX,10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following ig administration,the antidepressant effect of ZBH2012001 was evaluated using the tail suspension test(TST)and forced swimming test(FST).② Radioligand binding assay was conducted to evaluate the affinity of ZBH2012001 for human serotonin transporters(hSERTs)and human norepinephrine transporters(hNETs).③ Mice were divided into vehicle(distilled water),DLX(10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following drug administration,the 5-hydroxytryptophan(5-HTP)-induced head-twitch test or yohimbine-induced lethality test were performed to evaluate the effect of ZBH2012001 on the function of the 5-hydroxytryptamine(5-HT)and norepinephrine(NE)systems.④ Mice were divided into vehicle(distilled water+0.1%acetic acid),reserpine model(distilled water+reserpine 5 mg·kg-1),DLX(DLX 20 mg·kg-1+reserpine 5 mg·kg-1)and ZBH2012001(ZBH2012001 5,10 and 20 mg·kg-1+reserpine 5 mg·kg-1)groups.One hour following drug administration,reserpine was injected intraperitoneally to establish a monoamine-depletion model.The ptosis,akinesia,and hypothermia assays were performed to evaluate the effect of ZBH2012001 on the down-regulation of the reserpine-induced monoamine system.The TST in mice was used to evaluate the effect of ZBH2012001 on reserpine-induced depressive-like behavior while high-performance liquid chromatography with electrochemical detection(HPLC-ECD)was used to measure the levels of monoamines and their metabolites in the hippocampal tissue of reserpine-induced monoamine-depletion mice.ELISA was employed to detect the contents of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.Western blotting was used to assess the expressions of ionized calcium-binding adapter molecule-1(Iba-1)and nuclear factor-kappa B(NF-κB)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.RESULTS ① Compared with the vehicle group,ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the immobility time both in the TST in mice(P<0.01,respectively),and ZBH2012001(20 mg·kg-1)and in the FST in mice(P<0.05).② ZBH2012001 competitively inhibited the binding of[3H]-imipramine to hSERTs and[3H]-nisoxetine to hNETs,with the half maximal inhibitory concentration(IC50)values of 84.95 and 712.90 nmol·L-1,respectively.③Com-pared with the vehicle group,ZBH2012001(10 and 20 mg·kg-1)significantly increased the head twitches induced by 5-HTP in mice(P<0.01,respectively)and increased the mortality rate in mice induced by yohimbine(P<0.05,P<0.01).④ In the reserpine-induced monoamine-depletion model in mice,compared with the vehicle group,mice in the reserpine model group exhibited ptosis,akinesia and hypothermia feature(P<0.01,respectively),significantly prolonged immobility time in the TST(P<0.01),significantly decreased the levels of NE,5-HT and dopamine(DA)(P<0.05,P<0.01),significantly increased the metabolic conversion rate of 5-HT and DA(P<0.01,respectively),significantly elevated levels of TNF-α and IL-6(P<0.05,respectively),and significantly increased expressions of Iba-1 and NF-κB(P<0.05,respectively)in the hippocampus.Compared with the model group,ZBH2012001(5,10 and 20 mg·kg-1)significantly antagonized ptosis and hypothermia behaviors induced by reserpine(P<0.01,respectively),ZBH2012001(10 and 20 mg·kg-1)significantly shortened the immobility time in reserpine-treated mice(P<0.05,P<0.01),ZBH2012001(20 mg·kg-1)significantly increased the levels of NE and 5-HT in the hippocampus of reserpine-treated mice(P<0.05,respectively),decreased the metabolic conversion rate of 5-HT(P<0.05),significantly reduced the contents of TNF-α and IL-6 in the hippocampus of reserpine-treated mice(P<0.05,respectively),ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the expression of Iba-1 protein in the hippocampus of reserpine-treated mice(P<0.01,respec-tively),and ZBH2012001(20 mg·kg-1)significantly reduced the expression of NF-κB protein in the hippocampus of reserpine-treated mice(P<0.05).CONCLUSION ZBH2012001 exerts its antidepres-sant effect through a dual mechanism involving monoamine enhancement and inflammation suppres-sion.
8.Risk factors and development of a risk assessment model for postoperative venous thromboembolism in Cushing′s disease
Wenjuan LIU ; Dan LIU ; Min HE ; Qing MIAO ; Lijin JI ; Lili CHEN ; Yifei YU ; Zengyi MA ; Xuefei SHOU ; Shuo ZHANG ; Yutao WANG ; Zhiyuan WU ; Chaoyun ZHANG ; Yao ZHAO ; Yiming LI ; Yongfei WANG ; Hongying YE
Chinese Journal of Endocrinology and Metabolism 2024;40(6):487-493
Objective:To investigate the incidence and prothrombotic risk factors of postoperative venous thromboembolism(VTE) in Cushing′s disease and to further develop an assessment model to identify those at high risk of postoperative VTE events.Methods:A retrospective study was performed in 82 patients who were admitted to Huashan Hospital, Fudan University during January 2019 and January 2020 and diagnosed with Cushing′s disease. These patients underwent the evaluation about their clinical, hormonal, and coagulation parameters, as well as ultrasonography and pulmonary angio-CT when necessary. The least absolute shrinkage and selection operator(LASSO) regression analysis was used to screen independent risk factors, and a nomogram model for postsurgical VTE risk assessment in Cushing′s disease was initially established, and Bootstrap method was used for internal verification. Finally, the predictive model was evaluated for calibration and clinical applicability in the study cohort.Results:Nineteen patients(23.17%) developed VTE events, with 14 cases occurring after endoscopic transsphenoidal surgery. Compared to patients without VTE, those in the VTE group were older( P<0.001), had longer postoperative bed rest, higher rates of current infection, higher HbA 1C levels, and more severe glucose tolerance impairment(all P<0.05). Through LASSO regression analysis, two independent risk factors for postoperative VTE were identified: Age and current infection. Then a VTE risk assessment nomogram model was established to predict the patients at high risk of VTE. In the nomogram model for VTE risk assessment, the area under the receiver operating characteristic curve was 0.868(95% CI 0.787-0.949), with the calibration curve closely aligning with the ideal diagonal line and the clinical decision curve exceeding the two extreme curves. Conclusions:Advanced perioperative assessment needs to be taken to screen those with high VTE risks in patients diagnosed with Cushing′s disease. Additionally, during the perioperative period, patients with Cushing′s disease should undergo mandatory physical activity or prophylactic anticoagulant therapy.
9.Modeling of medical equipment requirements for helicopter evacuation and rescue team based on AnyLogic
Shuo TANG ; Mi LI ; Li HE ; Bang-Fu ZHOU ; Liang ZHOU ; Nan XIAO ; Zhi-Gang ZHANG
Chinese Medical Equipment Journal 2024;45(5):28-33
Objective To provide references for reasonable equipping of airborne medical equipment oriented to different tasks by constructing a medical equipment requirement model for the helicopter evacuation and rescue team.Methods Relevant basic data were collected and organized on time for routine and emergency medical treatment and elementary medical equipment requirements for types of medical treatment.AnyLogic multi-agent modeling was used to established a medical equipment requirement model for the helicopter evacuation and rescue team,with the casualty,equipment and medical personnel as the agent modules and the logical relationship-based access rules between the agents.An example was taken with a Z-8 helicopter transformed into an ambulance platform to transport the rescue team and casualties,in which a variety of evacuation tasks with multi combinations of light and serious casualties were simulated and the model developed was used to record and analyze the data on waiting time for medical treatment,completion rate,personnel utilization rate and equipment requirement during 100 times of simulation flight.Results The model developed could provide generalized medical equipment allocation programs for the helicopter evacuation and rescue team to complete a variety of evacuation tasks in terms of electronic device,treatment equipment,auxiliary instrument and medical consumables.Conclusion The model developed facilitates rational allocation of medical equipment for the helicopter evacuation and rescue team.[Chinese Medical Equipment Journal,2024,45(5):28-33]
10.In vitro study of 5-FU combined with rhCYGB in treating hypoxia-induced chemotherapy resistance of hepatocellular carcinoma
Yi WANG ; Shuo HE ; Siyun YANG ; Jun ZHANG
The Journal of Practical Medicine 2024;40(22):3146-3154
Objective This study explores the efficacy and underlying mechanisms of combining rhCYGB with 5-FU to target hypoxia-induced treatment resistance in liver cancer.The aim is to develop a novel combinato-rial therapy strategy for improving outcomes in patients with refractory liver cancer.Methods The half-maximal inhibitory concentration(IC50)of drugs on liver cancer cells under normoxia and hypoxia was determined,and dose-response curves were generated to assess sensitivity to 5-FU.The combined effects of rhCYGB and 5-FU were analyzed withCompuSyn and SynergyFinder 3.0.Tumor stem cell sphere formation assays and flow cytometry for CD133-positive cells were conducted to evaluate the impact on cancer stemness.Wound healing assays assessed the effects on migration.Results The IC50 values under hypoxia exhibited a significant fold change compared to normoxia(P<0.05),specifically a 15.27-fold,4.25-fold,and 2.34-fold increase for Hep3B,Huh7,and HepG2 cells respectively.Assessment of drug combination effects demonstrated a synergistic interaction between 5-FU and rhCYGB.Compared to the 5-FU monotherapy group,the combination of 5-FU and rhCYGB exerted an inhibitory effect on the formation of liver cancer stem cell spheres(P<0.05)and significantly downregulated the proportion of CD133-positive subpopulations in Hep3B cells(P<0.05).Wound healing assay results revealed a synergistic inhibitory effect on the migration of Hep3B cells after 48 hours of treatment with rhCYGB combined with 5-FU undernormoxia(P<0.05).Conclusions The combination of rhCYGB and 5-FU demonstrates syner-gistic effects in liver cancer.The underlying mechanism may involve the modulation of stemness and cell migration capacity.

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