1.Mechanism of Huayu Jiedu Prescription in Preventing and Treating Cerebral Ischemia Injury by Regulating NETosis After Acute Cerebral Infarction with Blood Stasis and Toxin Syndrome
Wuchaonan LIU ; Dingxiang LI ; Le YANG ; Jing LIU ; Shengping LUO ; Fang LEI ; Hanlin LEI ; Yihui DENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):50-59
ObjectiveTo investigate the material basis of the pathogenesis of cerebral ischemic injury with blood stasis and toxin syndrome and to explore the protective effects of Huayu Jiedu prescription (HYJDP) on neutrophil extracellular trap-related cell death (NETosis) in cerebral ischemic injury following acute cerebral infarction. MethodsSeventy-two Sprague-Dawley (SD) rats were randomly divided into six groups (n=12 per group): sham operation (Sham) group, blood stasis and toxin model (Model) group, low-, medium-, and high-dose HYJDP groups (HYJDP-L, HYJDP-M, and HYJDP-H; 9, 18, and 36 g·kg-1, respectively), and butylphthalide (NBP) group (0.06 g·kg-1). Except for the Sham group, rats in all other groups were subjected to carrageenan/dry yeast combined with a modified intraluminal filament method to establish a focal cerebral ischemia model of the middle cerebral artery with blood stasis and toxin syndrome. Neurological function was evaluated at 24 h after modeling using the Zea-Longa neurological deficit score. Cerebral infarction rate was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Pathological morphology of brain tissue was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of interleukin-8 (IL-8), myeloperoxidase-DNA complexes (MPO-DNA), and citrullinated histone H3 (CitH3). Protein expression of phosphorylated phosphatidylinositol 3-kinase (p-PI3K), protein kinase B (p-Akt), mammalian target of rapamycin (p-mTOR), sequestosome 1 (p62), and CitH3 in brain tissue was detected by Western blot. Immunofluorescence (IF) was used to detect the expression of neutrophil-specific marker Ly6G, CitH3, and neuron-specific nuclear protein (NeuN) in brain tissue. ResultsCompared with the Sham group, neurological deficit scores and cerebral infarction rates in the model group were significantly increased (P<0.01 for both). HE staining showed varying degrees of neuronal degeneration and necrosis, characterized by blurred neuronal structures, nuclear pyknosis and fragmentation, cytoplasmic dissolution into a vacuolated reticular pattern, and mild glial cell proliferation. ELISA results showed that serum levels of IL-8, MPO-DNA, and CitH3 were significantly increased (P<0.01). Western blot analysis demonstrated decreased expression of p-PI3K, p-Akt, p-mTOR, and p62, while CitH3 expression was significantly increased (P<0.01). IF results showed an increased number of NETs+ cells and a significant decrease in NeuN+ cells (P<0.01). Compared with the Model group, neurological deficit scores in the HYJDP-H group were significantly decreased (P<0.05), and cerebral infarction rates in the HYJDP-H and NBP groups were significantly reduced (P<0.01). HE staining showed that brain tissue damage was markedly alleviated in the HYJDP-H group. ELISA results showed that levels of IL-8, MPO-DNA, and CitH3 were significantly decreased in the HYJDP-M, HYJDP-H, and NBP groups (P<0.01). Western blot analysis showed that expression of p-PI3K, p-Akt, p-mTOR, and p62 was significantly increased in the HYJDP-H and NBP groups, while CitH3 expression was significantly reduced in all drug intervention groups (P<0.01). IF results showed that the number of NETs+ cells was significantly decreased and the number of NeuN⁺ cells was significantly increased in all drug intervention groups (P<0.01). ConclusionNETs may be the material basis of the pathogenesis of cerebral ischemic injury characterized by blood stasis and toxin. HYJDP can regulate the PI3K/Akt/mTOR signaling pathway, reduce the release of pro-inflammatory mediators and NETosis-related products, alleviate cerebral ischemic injury caused by autophagy-dependent NETosis, and thereby exert a neuroprotective effect.
2.Advances in the assessment of diabetic retinopathy severity in periarterial capillary-free zone by optical coherence tomography angiography
International Eye Science 2026;26(3):441-446
Diabetic retinopathy(DR), the most common microvascular complication of diabetes, has become a leading cause of visual impairment and blindness across all age groups. The early diagnosis and severity assessment of DR rely on the precise evaluation of retinal microvascular alterations. The periarterial capillary-free zone(paCFZ), a physiological avascular region surrounding retinal arteries, has recently been recognized as an important biomarker reflecting the status of retinal microcirculation. Advances in optical coherence tomography angiography(OCTA)have enabled noninvasive, high-resolution quantification of the paCFZ, offering a novel approach for the early detection and stratification of DR. This review systematically summarizes the definition and developmental mechanism of the paCFZ, as well as its morphological characteristics across different stages of DR, with a particular focus on the advantages of OCTA in visualizing and quantifying the paCFZ. We further discuss the differential manifestations of the paCFZ in nonproliferative DR and proliferative DR, and its associations with retinal ischemia and oxygenation status. In addition, the potential clinical value of paCFZ in evaluating responses to anti-vascular endothelial growth factor(VEGF)therapy and predicting disease progression is summarized. Finally, the challenges in clinical translation and future research directions are addressed, aiming to provide theoretical support and new perspectives for early screening, risk stratification, and personalized management of DR.
3.Experimental Study on Reverse Mechano-Electric Characteristics of Layered Structure of Articular Cartilage
Le ZHAO ; Zhengbiao YANG ; Meng ZHANG ; Jing CHEN ; Pengcui LI ; Yanqin WANG ; Yanru XUE ; Xiaogang WU ; Xiaochun WEI ; Weiyi CHEN
Journal of Medical Biomechanics 2025;40(5):1114-1121,1135
Objective To analyze the reverse mechano-electric effect of the layered structure of articular cartilage and its influencing factors.Methods The cartilage samples were classified according to their physiological thickness(approximately 0.4 mm for the upper layer,1 mm for the middle layer,and 0.6 mm for the lower layer).Through a non-contact external electric field testing method,how different influencing factors affected the reverse mechano-electric effect of articular cartilage was analyzed.Results When the electric field spacing decreased,water content increased,and in vitro time decreased,the displacement of normal layered cartilage in a non-contact electric field increased by 18,10,15 μm,respectively.In the case of simulated arthritis defects,as the defect depth and radius increased,the overall deviation deflection of articular cartilage gradually decreased by about 7 μm.Conclusions The three-layer cartilage differed in their reverse mechano-electricity effects,showing the greatest deflection in the middle layer at 90%water content,under 7 mm electric field spacing,and after 12 hours ex vivo.
4.Role of GLUT1-dependent glycolysis in attenuation of oxygen-glucose deprivation-reoxygenation injury by dexmedetomidine in HK-2 cells
Wei DING ; Wen-hui TAO ; Yu-le WU ; Jian-xiao WU ; Jing-yi GUO ; Li-fang XIE ; Bing-qian FAN ; Xue-song GU ; Yang LI ; Xian-wen HU
Chinese Pharmacological Bulletin 2025;41(3):444-450
Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P<0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P<0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P<0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P<0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.
5.MRI diagnosis of ovarian granulosa cell tumor and fibrothecoma and relative clinical analysis
Yi ZHANG ; Jing ZHANG ; Le LIU
Journal of Practical Radiology 2025;41(8):1338-1342
Objective To explore the value of MRI in the differential diagnosis of ovarian granulosa cell tumor(OGCT)with fibrothecoma,and to analyze the clinical characteristics of the two diseases to improve the accuracy of preoperative diagnosis.Methods The clinical features and MRI findings of 20 cases of OGCT and 26 cases of fibrothecoma confirmed by surgery and pathology were analyzed retrospectively.Results 95%(19/20)of patients with OGCT had symptoms,and 54%(14/26)of patients with fibrothecoma had symptoms.There was a statistical difference between OGCT and fibrothecoma in the number of patients of symptoms and hormone-related symptoms.95%(19/20)of OGCT were unilateral lesions,and 5%(1/20)were bilateral lesions(21 lesions in total),which 67%(14/21)had regular edges and 33%(7/21)had irregular edges.The length of lesions ranged from 3.2 cm to 14.7 cm,with an average of(8.1±3.3)cm.Among them,38%(8/21)lesions were solid,33%(7/21)lesions were cystic,and 29%(6/21)lesions were solid with cystic masses.96%(25/26)of fibrothecoma were unilateral lesions and 4%(1/26)were bilateral lesions(27 lesions in total),which 59%(16/27)had regular edges and 41%(11/27)had irregular edges.The length of lesions ranged from 2.2 cm to 19.0 cm,with an average of(7.69±4.12)cm,which 89%(24/27)lesions were solid,7%(2/27)lesions were cystic,and 4%(1/27)lesions were solid with cystic masses.On T1 WI images,86%(18/21)of OGCT showed high signal,and 81%(17/21)lesions showed bleeding signal.100%(27/27)of fibrothecoma showed isointensity.On T2WI images,71%(15/21)of OGCT showed hyperintensity and 90%(19/21)lesions had multiple varies cysts.On T2WI images,63%(17/27)lesions of fibrothecoma showed hypointensity and 4%(1/27)lesion had honeycomb sign.There were no statistical differences in the location,shape and size of the lesions between the two groups.There were statistical differences in cystic-solid type,T,WI and T2WI signals,honeycomb signs and bleeding signals(P<0.05).The mean apparent diffusion coefficient(ADC)value of OGCT was about(0.830±0.210)×10-3 mm2/s,and the mean ADC value of fibrothecoma was about(1.550±0.320)× 10-3 mm2/s,which had statistical difference.The critical value was 1.085 × 10-3 mm2/s of ADC value,which the sensitivity was 100%and the specificity was 90%.Conclusion The combination of clinical features,MRI signal characteristics and ADC value is helpful for the differential diagnosis of OGCT and fibrothecoma.
6.Metabolomic alterations in preterm infants with bronchopulmonary dysplasia
Yan-Yan WU ; Qi-Qi BU ; Xin WANG ; Tao LI ; Hong-Yan WU ; Le KANG ; Ying-Yuan WANG ; Da-Peng LIU ; Jing GUO ; Cai-Jun WANG ; Wen-Qing KANG
Chinese Journal of Contemporary Pediatrics 2025;27(12):1475-1481
Objective To analyze the serum metabolomic changes of preterm infants with bronchopulmonary dysplasia(BPD)at postmenstrual age(PMA)36 weeks,screen potential biomarkers and associated metabolic pathways,and assess their relationship with short-term respiratory outcomes.Methods A retrospective case-control study was conducted.Infants with gestational age 28-32 weeks admitted to the Children's Hospital Affiliated to Zhengzhou University from January to December 2024 were included.Twenty infants with BPD and 20 gestational age-,birth weight-,and sex-matched non-BPD preterm infants were included.Serum collected at PMA 36 weeks was subjected to untargeted metabolomics analysis,and associations with short-term respiratory outcomes were analyzed.Results Thirteen potential biomarkers distinguishing BPD were identified(area under the curve>0.75,P<0.05).Eight biomarkers—including terephthalic acid,phosphatidylinositol,fumarate,and lysophosphatidic acid—were significantly upregulated(FC≥1.5),while five biomarkers,such as 7α-hydroxy-3-oxo-4-cholestenoate ester and phosphatidylcholine,were significantly downregulated(FC≤1/1.5).Pathway analysis indicated five pathways associated with BPD,including glycerophospholipid metabolism and phenylalanine metabolism.Dysregulation of glycerophospholipid and bile acid metabolism may affect adverse short-term respiratory outcomes in infants with BPD.Conclusions The 13 significantly different metabolites may serve as biomarkers for the diagnosis of BPD.Glycerophospholipid metabolism is associated with the occurrence of BPD and with adverse short-term respiratory outcomes.
7.Experimental Study on Reverse Mechano-Electric Characteristics of Layered Structure of Articular Cartilage
Le ZHAO ; Zhengbiao YANG ; Meng ZHANG ; Jing CHEN ; Pengcui LI ; Yanqin WANG ; Yanru XUE ; Xiaogang WU ; Xiaochun WEI ; Weiyi CHEN
Journal of Medical Biomechanics 2025;40(5):1114-1121,1135
Objective To analyze the reverse mechano-electric effect of the layered structure of articular cartilage and its influencing factors.Methods The cartilage samples were classified according to their physiological thickness(approximately 0.4 mm for the upper layer,1 mm for the middle layer,and 0.6 mm for the lower layer).Through a non-contact external electric field testing method,how different influencing factors affected the reverse mechano-electric effect of articular cartilage was analyzed.Results When the electric field spacing decreased,water content increased,and in vitro time decreased,the displacement of normal layered cartilage in a non-contact electric field increased by 18,10,15 μm,respectively.In the case of simulated arthritis defects,as the defect depth and radius increased,the overall deviation deflection of articular cartilage gradually decreased by about 7 μm.Conclusions The three-layer cartilage differed in their reverse mechano-electricity effects,showing the greatest deflection in the middle layer at 90%water content,under 7 mm electric field spacing,and after 12 hours ex vivo.
8.Metabolomic alterations in preterm infants with bronchopulmonary dysplasia
Yan-Yan WU ; Qi-Qi BU ; Xin WANG ; Tao LI ; Hong-Yan WU ; Le KANG ; Ying-Yuan WANG ; Da-Peng LIU ; Jing GUO ; Cai-Jun WANG ; Wen-Qing KANG
Chinese Journal of Contemporary Pediatrics 2025;27(12):1475-1481
Objective To analyze the serum metabolomic changes of preterm infants with bronchopulmonary dysplasia(BPD)at postmenstrual age(PMA)36 weeks,screen potential biomarkers and associated metabolic pathways,and assess their relationship with short-term respiratory outcomes.Methods A retrospective case-control study was conducted.Infants with gestational age 28-32 weeks admitted to the Children's Hospital Affiliated to Zhengzhou University from January to December 2024 were included.Twenty infants with BPD and 20 gestational age-,birth weight-,and sex-matched non-BPD preterm infants were included.Serum collected at PMA 36 weeks was subjected to untargeted metabolomics analysis,and associations with short-term respiratory outcomes were analyzed.Results Thirteen potential biomarkers distinguishing BPD were identified(area under the curve>0.75,P<0.05).Eight biomarkers—including terephthalic acid,phosphatidylinositol,fumarate,and lysophosphatidic acid—were significantly upregulated(FC≥1.5),while five biomarkers,such as 7α-hydroxy-3-oxo-4-cholestenoate ester and phosphatidylcholine,were significantly downregulated(FC≤1/1.5).Pathway analysis indicated five pathways associated with BPD,including glycerophospholipid metabolism and phenylalanine metabolism.Dysregulation of glycerophospholipid and bile acid metabolism may affect adverse short-term respiratory outcomes in infants with BPD.Conclusions The 13 significantly different metabolites may serve as biomarkers for the diagnosis of BPD.Glycerophospholipid metabolism is associated with the occurrence of BPD and with adverse short-term respiratory outcomes.
9.Effect of preoperative oral carbohydrate on overweight or obese patients undergoing laparoscopic hysterectomy in Trendelenburg position
Guang-le WEI ; Rong-xiang LU ; Jing-hui QIU ; Chang CHEN ; Ti-jun DAI
Journal of Regional Anatomy and Operative Surgery 2025;34(11):1004-1007
Objective To clarify the effect of preoperative oral carbohydrate on overweight or obese patients undergoing laparoscopic hysterectomy in Trendelenburg position.Methods A total of 72 overweight or obese patients who underwent laparoscopic hysterectomy in Trendelenburg position at Yancheng Third People's Hospital from September 2022 to August 2024 were selected,and randomly divided into the control group and the observation group,with 36 cases in each group.The control group received routine restriction of fasting and fluid starting from 22:00 on the day before surgery,while the observation group was given an additional 300 mL of carbohydrate orally 2 hours before anesthesia on the basis of the control group.The preoperative ultrasound results of gastric antrum,Perlas classification,full stomach status,visual analogue scale(VAS)scores for thirst and hunger,awakening time,tracheal extubation time,intraoperative hypothermia,gastro-intestinal function recovery time,and adverse reactions were compared between the two groups.Results Before anesthesia,there was no statistically significant difference in the cross-sectional area of the gastric antrum(CSA)in the right lateral position,gastric volume(GV),or the ratio of gastric volume to body weight(GV/W)between the two groups(P>0.05).There was also no statistically significant difference in the Perlas classification of gastric antrum ultrasound or the incidence of full stomach between the two groups(P>0.05).Immediately before anesthesia,the VAS scores for thirst and hunger in the observation group were significantly lower than those in the control group(P<0.05).The awakening time,tracheal extubation time,and incidence of intraoperative hypothermia in the observation group were significantly shorter/lower than those in the control group(P<0.05).The observation group had significantly shorter time of first exhaust and defecation after surgery,as well as lower incidence of postoperative bloating,compared with the control group(P<0.05).Conclusion For overweight or obese patients undergoing laparoscopic hysterectomy in the Trendelenburg position,oral intake of 300 mL carbohydrate 2 hours before anesthesia does not increase the risk of regurgitation or aspiration,with safety and reliability.It not only can improve comfort of patients and promote post-anesthesia awakening,but also can reduce the incidences of intraoperative hypothermia and gastrointestinal adverse reactions,which is conducive to accelerating postoperative recovery.
10.Electroacupuncture Affects Microglial Activation and Subsequently Improves Postherpetic Neuralgia via HMGB1/TLR4/NF-κB Signaling Pathway
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2025;54(2):159-165
Objective To explore the mechanism by which electroacupuncture(EA)improves postherpetic neuralgia(PHN)by affecting the activation of microglia through the high mobility group box 1(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor kappa-B(NF-κB)signaling pathway.Methods Fifty SPF-grade SD rats were divided into the following groups:control(Vehicle)group,model(RTX)group,sham electroacupuncture(Sham-EA)group,electroacupuncture(EA)group,and electroacu-puncture+pathway inhibitor(EA+Gly)group.Behavioral tests in rats were conducted using mechanical withdrawal threshold testing,hot foot reflex latency testing,and tilt board testing.Hematoxylin-eosin(HE)staining was used to detect pathological morphological changes in the spinal dorsal horn tissue.TUNEL assay was used to detect cell apoptosis in the spinal dorsal horn tissue.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of pain-sensitive substances:prostaglandin E2(PGE2),substance P(SP),neurokinin 1(NK-1),and inflammatory factors:interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor α(TNF-α).Immunofluorescence was used to detect the expression of Iba1.Western blot was used to detect the expression of proteins involved in the HMGB1/TLR4/NF-κB pathway.Results Compared with Vehicle group,RTX group showed decreased mechanical withdrawal threshold,shortened hot foot reflex latency,reduced angle of balance on the tilt board,structural damage,disordered arrangement of nerve fibers,inflammatory cell infiltration,increased cell apoptosis rate,increased activation of microglia,and increased levels of PGE2,SP,NK-1,IL-6,IL-1β,TNF-α in the spinal dorsal horn tissue,with upregu-lated expression of HMGB1,TLR4,NF-κB p65 proteins(all P<0.01).Compared with RTX group,no significant difference was observed in Sham-EA group(P>0.05),while EA group showed increased mechanical withdrawal threshold,prolonged hot foot reflex latency,increased angle of balance on the tilt board,relieved morphological damage of nerve cells,more orderly arrangement,reduced in-flammatory cell infiltration,reduced cell apoptosis rate,reduced activation of microglia,and decreased levels of PGE2,SP,NK-1,IL-6,IL-1β,TNF-α in the spinal dorsal horn tissue,with downregulated expression of HMGB1,TLR4,NF-κB p65 proteins(all P<0.01).Com-pared with EA group,EA+Gly group showed increased mechanical withdrawal threshold,prolonged hot foot reflex latency,increased angle of balance on the tilt board,reduced degree of morphological damage and disorder of nerve cells,reduced cell apoptosis rate,re-duced activation of microglia,and decreased levels of PGE2,SP,NK-1,IL-6,IL-1β,TNF-α in the spinal dorsal horn tissue,with down-regulated expression of HMGB1,TLR4,NF-κB p65 proteins(all P<0.05).Conclusion EA exerts its therapeutic effect on PHN by in-hibition of HMGB1/TLR4/NF-κB signaling pathway and activation of microglia.

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