1.Effect of demethylase FTO knockout on 5-HT-induced abnormalities of coronary smooth muscle contractile function in mice with diabetes mellitus
Zi-fan WANG ; Liu-xiang JIANG ; Mei-ying LIANG ; Meng-yun LIU ; Mei-jiang CHEN ; Hui YANG ; Fang RAO ; Chun-yu DENG
Chinese Pharmacological Bulletin 2025;41(2):315-322
Aim To explore the influence of demethy-lase fat mass and obesity-related genes(FTO)on the abnormal contractile function of diabetic coronary smooth muscle.Methods Smooth muscle specific FTO knockout mice(FTOSMKO)were prepared by Cre-loxP recombinant technology.They were divided into four groups:control(WT)group,diabetes model group(DM),FTO knockout group(FTOSMKO),and FTOSMKO diabetic group(FTOSMKO-DM),with 15 mice in each group.Diabetic mice were prepared by intraperitoneal injection of streptozotocin(STZ);the remaining mice were injected with an equal amount of citric acid-sodi-um citrate buffer.The effects of 5-HTon the contractile response of coronary artery smooth muscle in the four groups of mice were observed by the technique of small-vessel ring tensiometry.Western blot and Dot blot were used to detect the changes of FTO protein and N6-methyladenine(m6A)methylation modification levels in mouse vascular tissues.Results Compared with the WT group,the DM group had significantly higher blood glucose(P<0.01)and lower body weight(P<0.05);the level of FTO protein in aorta of DM group increased(P<0.01),and the level of m6A methylation modification decreased(P<0.01).The 5-HT-induced contractile response significantly de-creased in the DM group compared with the WT group(P<0.01),whereas the contractile response signifi-cantly increased in the FTOSMKO-DM group compared with the DM group(P<0.01);the non-L-type calci-um channel-mediated vascular smooth muscle contrac-tile response was enhanced in the FTOSMKO-DM group,among which,the contractions induced by 1,4,5-triphosphate inositol receptor(IP3R)and caffeine-ac-tivated ranine receptor(RyR)mediated by sarcoplas-mic reticulum calcium release both significantly in-creased(P<0.05).Conclusions Specific knock-down of smooth muscle FTO improves coronary artery responsiveness to the vasoconstrictor 5-HT in diabetic mice,which may be related to abnormalities in the FTO-mediated 5-HT receptor signaling pathway.
2.CT manifestations of Fitz-Hugh-Curtis syndrome
Zhaohong YANG ; Fan ZHANG ; Shulin MA ; Weijian YUN ; Jian LING ; Rongjing WANG ; Jian GUAN
Chinese Journal of Medical Imaging Technology 2025;41(3):434-438
Objective To observe CT manifestations of Fitz-Hugh-Curtis syndrome(FHCS).Methods Data of 23 patients with FHCS were retrospectively analyzed,and non-enhanced and enhanced abdominal and pelvic CT manifestations were observed.Results All 23 cases were found with pelvic inflammation,peritonitis,perihepatic inflammation,as well as abdominal and pelvic adhesion.The main manifestations of pelvic inflammation included pelvic effusion(23/23,100%),inflammatory changes of uterus and accessories(17/23,73.91%),and the latter presented as tubal thickening(8/17,47.06%)or tubal cystic dilatation and effusion(9/17,52.94%),with ovarian enlargement(8/9,88.89%)or nodules on uterine surface(1/9,11.11%).The main CT manifestations of peritonitis were peritoneal thickening(23/23,100%)and peritoneal nodules(15/23,65.22%),of perihepatic inflammation were mainly liver capsule enhancement(23/23,100%),subcapsular transient perfusion abnormality(16/23,69.57%),perihepatic effusion(20/23,86.96%)and perihepatic"violin-string sign"(16/23,69.57%).No inflammation in the bare area of liver was noticed.Among 23 cases,3 cases(3/23,13.04%)complicated with mechanical ileus,19 cases(19/23,82.61%)were accompanied by mesenteric or retroperitoneal lymph nodes enlargement with uniform or circular enhancement.Conclusion The main CT manifestations of FHCS included pelvic inflammation,peritonitis,perihepatic inflammation,as well as abdominal and pelvic adhesion,having certain characteristics.
3.Effects of Jiedu Yizhi Formula on neuroinflammation in a mouse model of Alzheimer's disease via PI3K/Akt/mTOR signaling pathway
Jie WANG ; Jian LIU ; Xiao-ting ZHU ; Yun-qiang LI ; Xin-yue ZHANG ; Fan LI ; Jia-li WU ; Wei LI ; Ming-quan LI
Chinese Traditional Patent Medicine 2025;47(6):1843-1852
AIM To investigate the mechanism of Jiedu Yizhi Formula on cognitive function and neuroinflammation in a mouse model of Alzheimer's disease(AD).METHODS 50 APP/PS1 double transgenic mice were randomly divided into the model group,the donepezil group,and the low-dose,moderate-dose,and high-dose Jiedu Yizhi Formula group(1.78,3.56 and 7.12 g/kg),with 10 mice in each group,in contrast to the 10 WT mice of the blank group.Following anesthesia administration and 8-week oral gavage regimen with respective drugs,all mice underwent final tissue sample collection.The mice had their learning and memory ability assessed by Morris water maze and nesting behavior scores;their pathology of brain tissue and Aβ expression observed using HE,Nissl and IHC staining;their polarization of microglia and the expression of inflammatory factors in hippocampal tissue detected by IF and ELISA;their hippocampal expression of PI3K/Akt/mTOR signaling pathway detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group had lower scores in total swimming distance,frequency in crossing the platform,residence time in the target quadrant,and nesting behavior scores(P<0.05,P<0.01);prolonged evasion latency(P<0.01);more disorganized arrangement of pyramidal cells,solidification and deep staining,unclear demarcation,irregular cell shapes,reduction of Nyctinidia,and increased Aβ deposition in the brain tissue(P<0.01);elevated expression of hippocampal microglia M1-type markers CD16/32 and lba-1(P<0.01);decreased levels of M2-type marker CD206(P<0.05);elevated levels of TNF-α and IL-1β(P<0.01);decreased expressions of IL-13 and IL-4(P<0.01);and decreased levels of PI3K,Akt and mTOR mRNA,and reduced p-PI3K,p-Akt and p-mTOR protein expressions(P<0.01).Compared to the model group,the donepezil group and the Jiedu Yizhi Formula groups showed statistically significant improvements in the aforementioned indexes(P<0.05,P<0.01),with the magnitude of improvement being higher in the high-dose Jiedu Yizhi Formula group.CONCLUSION Jiedu Yizhi Formula suppresses microglia Ml-type polarization while enhancing M2-type polarization via activation the PI3K/Akt/mTOR signaling pathway,which subsequently reduces inflammatory cytokine secretion.This mechanism attenuates Aβ deposition in brain tissues and ameliorates cognitive dysfunction in AD mouse models.
4.Molecular epidemiological investigation of Babesia infection in small mammals in the Jinsha River Basin,Yunnan Province
Fan WANG ; Yun ZHANG ; Zongti SHAO ; Yuqiong LI ; Ennian PU ; Zhihai HE ; Mingguo YAO ; Shuangshuang BIE ; Jiafu JIANG ; Chunhong DU
Chinese Journal of Zoonoses 2025;41(7):767-774
This study was aimed at understanding the Babesia species makeup and distribution in small mammals in Jinsha River Basin of Yunnan Province,and the Babesia carriage status in small mammals in this area,to provide a scientific basis for the preven-tion and control of Babesia disease.A total of 1 493 small mammals belonging to 5 orders,10 families,25 genera,and 54 species were captured from 10 counties(cities)in the Jinsha River Basin of Yunnan Province in various agricultural and forest environments.DNA was extracted from liver and tick tissues,and 150 bp fragments of Babesia 18S rRNA were detected through molecular biological methods.The positive samples showed amplification of a 1 600 bp target fragment of 18S rRNA.Species characteristics were assessed through sequence comparison and phylogenetic analysis.A total of 14 small mammals infected with Babesia were detected in six coun-ties(cities)of Jinsha River Basin,Yunnan Province,with a positivity rate of 0.93%(14/1 493).The Otsu and Kobe types of Babesia voles were analyzed,and their sequences were compared with the sequences from human Babesia cases with high similarity and close evolutionary relationships.The positivity rates were 2.34%(3/128)in Qiaojia County,2.06%(2/97)in Yongshan County,1.88%(4/213)in Yuanmou County,1.03%(3/291)in Deqin County,0.95%(1/105)in Shangri-La City,and 0.78%(1/128)in Shuifu County.The positive small mammals belonged to one order,two families,six genera,and the following eight species:P.leucurus 5.56%(1/18),R.brunneusculus 3.36%(4/119),M.minutus 3.33%(1/30),E.custos 2.94%(1/34),N.confucianus 2.65%(3/113),N.fulvescens 2.35%(2/85),A.latronum 1.16%(1/86),and A.draco 0.98%(1/102).The detection of Babesia in M.minutus was re-poorted first time.Small animals infected with Babesia were detected in all three habitats and altitudes,and higher infection rates were observed in forest regions between 1 500 and 2 500 meters and high-altitude residential areas.Babesia infection was found in many small mammals in several counties(cities)along Jinsha River in Yunnan Province,and the epidemic status of Babesia in these areas warrants attention.
5.Feasibility study on road-rail medical vehicles
Jian-kang WANG ; Pei TIAN ; Fan WU ; Yun-ming LI ; Xia ZHANG ; Mu YUAN ; Xiao-li XU
Chinese Medical Equipment Journal 2025;46(10):84-90
The feasibility for the development of road-rail medical vehicles was discussed.The gap between China's ground medical evacuation system and medical evacuation requirements was analyzed,and the limitations of the existing mobile medical units in China were introduced.The key points for developing road-rail medical vehicles were discussed.The road-rail medical vehicle would be an ideal tool for casualty treatment and rapid evacuation at war time and peace time,which could be a future development direction of the road-rail vehicle and medical train.[Chinese Medical Equipment Journal,2025,46(10):84-90]
6.Fucoidan Provokes Ferroptosis via Inhibition of the PI3K/Akt Signaling Pathway in Human Osteosarcoma 143B Cells
Qiao LIN ; Qi-Qi WANG ; Xin-Yi BAO ; Yu-Ting WANG ; Lu-Bing ZHANG ; Yi-Ning FAN ; Jian FANG ; Yun ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(9):1298-1309
Fucoidan(FUC)is a natural seaweed-derived drug.Previously,our experiments have shown that FUC can significantly inhibit the cell viability of human osteosarcoma 143B cells and induce cell death,but the mechanism remains unclear.Ferroptosis,a novel form of cell death,has emerged as an important target for tumor therapy.This study aims to investigate whether FUC induces ferroptosis of 143B cells and elucidate its underlying molecular mechanisms.CCK-8 and LDH assays result showed that FUC(10,100,400 μg/mL)significantly reduced cell viability of 143B cells and induced cell death.Calce-in-AM staining,FeRhoNox-1 staining,and C11 BODIPY 581/591 staining indicated that FUC obviously increased the levels of labile iron pool(LIP),Fe2+,and lipid reactive oxygen species(Lip ROS)in 143B cells.Chemical colorimetric analysis revealed that FUC markedly decreased intracellular Glutathi-one(GSH)contents.Real-time quantitative PCR showed that FUC dramatically reduced the mRNA lev-els of ferroptosis-related factors solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while increasing the mRNA levels of prostaglandin endoperoxide synthase 2(PTGS2)and acyl-CoA synthetase long-chain family member 4(ACSL4).Western blotting analysis demonstrated that FUC significantly reduced the protein levels of SLC7A11 and GPX4,and the ratios of p-PI3K/PI3K,p-AktSer473/Akt,and p-AktThr308/Akt,but increased the protein level of ACSL4.Immunofluorescence staining showed that FUC obviously inhibited the nuclear translocation of p-AktSer473.The ferroptosis in-hibitor ferrostatin-1(Fer-1)and iron chelator deferoxamine(DFO)remarkably suppressed cell death in-duced by FUC in 143B cells.Additionally,the PI3K/Akt pathway activator 740Y-P significantly inhibi-ted FUC-induced iron overload and lipid peroxidation in 143B cells,and restored the protein levels of SLC7A11 and GPX4.In conclusion,FUC can induce ferroptosis of 143B cells by inhibiting the PI3K/Akt signaling pathway,which may be a potential target for the prevention and treatment of osteosarcoma.
7.STAT3-mediated polarization of A2 phenotype astrocytes alleviates painful diabetic peripheral neuropathy in type 1 diabetic rats
Tingting FAN ; Huili LI ; Ruijuan GUO ; Danxu MA ; Yun WANG
Basic & Clinical Medicine 2025;45(7):889-896
Objective To study the effect of STAT3 over-expression-mediated A2 astrocyte polarization on type 1 diabetic mellitus(T1DM)peripheral neuropathy.Methods STAT3 over-expression virus was intrathecally injected into type 1 diabetic rats with painful diabetic neuropathy(PDN).The rats were divided into four groups:control group,T1DM group,T1DM+vector group,and T1DM+STAT3 OE group.Paw withdrawal threshold and paw withdrawal latency were measured.Flow cytometry and RT-qPCR were used to sort astrocytes and determine the phenotype of reactive astrocytes.Immune-fluorescence staining microscopy was performed to observe the changes of A2 phenotype astrocytes in the spinal dorsal horn of each group.Results Compared to the control group,the me-chanical(P<0.001)and heat thresholds(P<0.05)were significantly reduced in the T1DM group.The mechanical threshold was significantly increased in the T1DM+STAT3 OE group as compared to that in the T1DM group(P<0.001).Histolgical analysis showed degenerative pathological changes of spinal dorsal horn astrocytes in the T1DM group.Astrocytes in the T1DM+STAT3 OE group were activated and polarized toward the A2 phenotype.Conclusions The STAT3 pathway in the spinal dorsal horn astrocytes of rats with type 1 diabetic neuropathy is im-paired.Restoring STAT3 expression promotes activation of astrocyte proliferation,activation,and polarization toward the A2 phenotype,thereby alleviating diabetic neuropathic pain.
8.Feasibility study on road-rail medical vehicles
Jian-kang WANG ; Pei TIAN ; Fan WU ; Yun-ming LI ; Xia ZHANG ; Mu YUAN ; Xiao-li XU
Chinese Medical Equipment Journal 2025;46(10):84-90
The feasibility for the development of road-rail medical vehicles was discussed.The gap between China's ground medical evacuation system and medical evacuation requirements was analyzed,and the limitations of the existing mobile medical units in China were introduced.The key points for developing road-rail medical vehicles were discussed.The road-rail medical vehicle would be an ideal tool for casualty treatment and rapid evacuation at war time and peace time,which could be a future development direction of the road-rail vehicle and medical train.[Chinese Medical Equipment Journal,2025,46(10):84-90]
9.Relationship between Serum CCL23,STC1 Level Expression and Prognosis in Patients with Severe Hypertensive Intracerebral Hemorrhage
Bo CHEN ; Yabin YUN ; Weizhi WANG ; Junfeng DU ; Hongyan FAN
Journal of Modern Laboratory Medicine 2025;40(1):143-147,157
Objective To investigate the relationship between serum C-C motif ligand 23 (CCL23),Stanniocalcin-1 (STC1) levels and prognosis in patients with severe hypertensive intracerebral hemorrhage (HICH). Methods A total of 122 severe HICH patients who visited the Department of Neurosurgery,Hohhot First Hospital from March 2021 to March 2023 were regarded as the study subjects (HICH group),122 patients with mild HICH during the same period (mild group) and 122 healthy individuals who underwent physical examinations were considered healthy. HICH patients were separated into survival group(n=94) and death group(n=28)based on prognosis. ELISA was applied to detect serum levels of CCL23 and STC1. Spearson on method was used to analyze correlations and multivariate COX regression was used to investigate the influencing factors of prognosis in HICH patients,and ROC curve was applied to analyze the predictive value of serum CCL23 and STC1 levels for the prognosis. Kaplan-Meier was applied to analyze the relationship between serum CCL23,STC1 levels and clinical outcomes. Results Serum CCL23(53.32±10.85pg/ml,78.49±11.21pg/ml,112.47±11.53pg/ml)and STC1 (15.12±2.63ng/ml,19.07±2.58ng/ml,22.15±2.75ng/ml)levels in the healthy group,mild disease group and HICH group were increased successively,and the differences was statistically significant (F=856.967,215.043,all P<0.05). The serum levels of CCL23 (108.02±13.51pg/ml) and STC1 (21.06±3.28ng/ml) in the survival group were lower than those in the death group(127.41±13.55 pg/ml,25.83±3.23 ng/ml),the Glasgow coma (GCS) score (8.95±0.92 ) of the survival group was higher than that of the death group(7.61±0.77),and the differences were statistically significant (t=6.663,6.810,7.005,all P<0.001). The serum levels of CCL23 and STC1 were negatively correlated with GCS score (r=-0.481,-0.426,all P<0.001). CCL23[OR(95%CI):1.240(1.091~1.409)],STC[OR(95%CI):1.754(1.215~2.533)]and GCS[OR(95%CI):0.087(0.020~0.382)]score were the influencing factors for poor prognosis in HICH patients . The AUC(95%CI) of CCL23 combined STC1 in the prediction of the prognosis of HICH patients was 0.939 (0.880~0.974) which was higher than that of single diagnosis (Z=1.974,2.040,P=0.048,0.041),the sensitivity and specificity of combined diagnosis were 85.71% and 94.68%,respectively. The 6-month follow-up survival rate of patients with high expression of CCL23 and STC1 (51.06% vs 93.33%,56.86% vs 91.55%) was lower than that of patients with low expression of CCL23 and STC1,and the differences were statistically signrficant (Log rank x2=34.777,23.781,all P<0.05). Conclusion The serum levels of CCL23 and STC1 are high in severe HICH patients,which are closely related to their prognosis. High expression of CCL23 and STC1 may indicate poor clinical outcomes in patients.
10.I-125 seed implantation improves the prognosis of pancreatic cancer patients treated with anti-PD-1 combined chemotherapy
Ke MIN ; Jia-ping JIANG ; Wei-min WANG ; Yun-fan WANG ; Yue-hua TANG ; Hong CHEN ; Qiang YAO ; Jun JIN
Fudan University Journal of Medical Sciences 2025;52(1):107-113
Objective To evaluate the prognosis and safety of patients with advanced pancreatic ductal adenocarcinoma(PDAC)who received I-125 seed implantation in treatment with anti-PD-1 monoclonal antibody+chemotherapy.Methods A retrospective analysis was conducted on patients with stage Ⅳ metastatic PDAC who received anti-PD-1 combined chemotherapy treatment at Yixing Hospital,Jiangsu University from Jan 2021 to Jun 2023.Patients were divided into two groups based on whether they received I-125 seed implantation:the I-125 seed implantation+anti-PD-1 monoclonal antibody+Chemotherapy group(IPC group)and the anti-PD-1 monoclonal antibody+chemotherapy group(PC group).The follow-up period ranged from 2 to 24 months,with a median follow-up time of 9 months.The prognosis of patients was analysed in combination with peripheral blood biomarkers.The peripheral lymphocyte subsets of patients in different treatment groups were preliminarily analysed by flow cytometry.Results A total of 13 patients were included,with 5 in the IPC group and 8 in the PC group.Progression-free survival(PFS)and overall survival(OS)in the IPC group were significantly longer than those in the PC group.The treatment in the IPC group was relatively safe,adverse reactions were controllable.The neutrophil-lymphocyte ratio(NLR)and CD4/CD8 ratio indicated that the prognosis of the IPC patients was better.The levels of regulatory T cells(Treg)and active regulatory T cells(aTreg)cells in the IPC patients were reduced after treatment compared with those of the PC patients.Conclusion The addition of I-125 seed implantation can improve the prognosis of patients with advanced PDAC who receive anti-PD-1 monoclonal antibody+chemotherapy,the post-treatment levels of patients'circulating aTreg cells are reduced,and the combination therapy has good safety.

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