1.Experimental study on promotion of skin radiation damage repair by icarin via HIF-2α/VEGF/Notch pathway to enhance the paracrine function of adipose-derived stem cells.
Yuer ZUO ; Shuangyi LI ; Siyu TAN ; Xiaohao HU ; Zhou LI ; Haoxi LI
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(7):881-890
OBJECTIVE:
To investigate the effectiveness and preliminary mechanisms of icariin (ICA) in enhancing the reparative effects of adipose-derived stem cells (ADSCs) on skin radiation damagies in rats.
METHODS:
Twelve SPF-grade Sprague Dawley rats [body weight (220±10) g] were subjected to a single dose of 10 Gy X-ray irradiation on a 1.5 cm×1.5 cm area of their dorsal skin, with a dose rate of 200 cGy/min to make skin radiation damage model. After successful modelling, the rats were randomly divided into 4 groups ( n=3), and on day 2, the corresponding cells were injected subcutaneously into the irradiated wounds: group A received 0.1 mL of rat ADSCs (1×10 7cells/mL), group B received 0.1 mL of rat ADSCs (1×10 7cells/mL)+1 μmol/L ICA (0.1 mL), group C received 0.1 mL of rat ADSCs (1×10 7cells/mL) pretreated with a hypoxia-inducible factor 2α (HIF-2α) inhibitor+1 μmol/L ICA (0.1 mL), and group D received 0.1 mL of rat ADSCs (1×10 7cells/mL) pretreated with a Notch1 inhibitor+1 μmol/L ICA (0.1 mL). All treatments were administered as single doses. The skin injury in the irradiated areas of the rats was observed continuously from day 1 to day 7 after modelling. On day 28, the rats were sacrificed, and skin tissues from the irradiated areas were harvested for histological examination (HE staining and Masson staining) to assess the repair status and for quantitative collagen content detection. Immunohistochemical staining was performed to detect CD31 expression, while Western blot and real-time fluorescence quantitative PCR (qRT-PCR) were used to measure the protein and mRNA relative expression levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), fibroblast growth factor 2 (FGF-2), interleukin 10 (IL-10), transforming growth factor β (TGF-β), HIF-2α, and Notch1, 2, and 3.
RESULTS:
All groups exhibited skin ulcers and redness after irradiation. On day 3, exudation of tissue fluid was observed in all groups. On day 7, group B showed significantly smaller skin injury areas compared to the other 3 groups. On day 28, histological examination revealed that the epidermis was thickened and the dermal fibers were slightly disordered with occasional inflammatory cell aggregation in group A. In group B, the epidermis appeared more normal, the dermal fibers were more orderly, and there was an increase in new blood vessels without significant inflammatory cell aggregation. In contrast, groups C and D showed significantly increased epidermal thickness, disordered and disrupted dermal fibers. Group B had higher collagen fiber content than the other 3 groups, and group D had lower content than group A, with significant differences ( P<0.05). Immunohistochemical staining showed that group B had significantly higher CD31 expression than the other 3 groups, while groups C and D had lower expression than group A, with significant differences ( P<0.05). Western blot and qRT-PCR results indicated that group B had significantly higher relative expression levels of VEGF, PDGF-BB, FGF-2, IL-10, TGF-β, HIF-2α, and Notch1, 2, and 3 proteins and mRNAs compared to the other 3 groups ( P<0.05).
CONCLUSION
ICA may enhance the reparative effects of ADSCs on rat skin radiation damage by promoting angiogenesis and reducing inflammatory responses through the HIF-2α-VEGF-Notch signaling pathway.
Animals
;
Rats, Sprague-Dawley
;
Skin/pathology*
;
Rats
;
Vascular Endothelial Growth Factor A/genetics*
;
Basic Helix-Loop-Helix Transcription Factors/genetics*
;
Signal Transduction
;
Flavonoids/pharmacology*
;
Adipose Tissue/cytology*
;
Stem Cells/cytology*
;
Receptors, Notch/metabolism*
;
Radiation Injuries, Experimental/metabolism*
;
Wound Healing/drug effects*
;
Male
2.Construction of predictive model for early allograft dysfunction after liver transplantation
Xin LI ; Xinglin YI ; Yan CHEN ; Xin DENG ; Xiangfeng LIU ; Xianzhe LIU ; Ying JIANG ; Guanlei LIU ; Chunmei CHEN ; Fang QIU ; Jianteng GU
Journal of Army Medical University 2024;46(7):746-752
Objective To analyze the factors related to early allograft dysfunction(EAD)after liver transplantation and to construct a predictive model.Methods A total of 375 patients who underwent liver transplantation in our hospital from December 2008 to December 2021 were collected,including 90 patients with EAD and 266 patients without EAD.Thirty items of baseline data for the 2 groups were compared and analyzed.Aftergrouping in a ratio of 7∶3,univariate and multivariate logistic regression analyses were used in the training set to evaluate the factors related to EAD and construct a nomogram.Receiver operating characteristic(ROC)curve,decision curve analysis(DCA),sensitivity,specificity,positive predictive value,negative predictive value,Kappa value and other indicators were used to evaluate the model performance.Results The incidence of EAD after liver transplantation was 24%.Multivariate logistic regression analysis showed that preoperative tumor recurrence history(OR=3.15,95%CI:1.28~7.77,P=0.013)and operation time(OR=1.22,95%CI:1.04~1.42,P=0.015)were related to the occurrence of EAD after surgery.After predicting the outcome according to the cut-off point of 0.519 identified by the Youden index,the model performance in the both training set and validation set was acceptable.DCA suggested the model has good clinical applicability.Conclusion The risk factors for EAD after liver transplantation are preoperative tumor recurrence history and operation time,and the established model has predictive effect on prognosis.
3.A study of suctioning flexible ureteroscopy with intelligent pressure-control in treating patients with urogenic sepsis after drainage at different times
Wei MENG ; Feng LYU ; Huajun ZHANG ; Bo CHEN ; Shuaijiang LU ; Ningning LI ; Bo CAI ; Limin MA ; Yangbo GUAN
Journal of Modern Urology 2024;29(2):126-129
【Objective】 To investigate the safety and effectiveness of suctioning flexible ureteroscopy with intelligent pressure-control at different times after drainage for patients with urogenic sepsis complicated with upper urinary tract stones. 【Methods】 Clinical data of 59 patients treated in the Department of Urology, Affiliated Hospital of Nantong University during May 2022 and May 2023 were collected.The patients were divided into early lithotripsy (≤1 week) group (n=27) and late lithotripsy (>1 week) group (n=32).Baseline data, imaging data and postoperative data of the two groups were compared. 【Results】 There were no significant differences between the two groups in the stone-free rate, total incidence of complications, incidence of high-grade complications, length of stay after lithotripsy, hospitalization costs after lithotripsy and total hospitalization costs (P>0.05). 【Conclusion】 Both early lithotripsy (<1 week) and late lithotripsy (>1 week) are safe and effective in the treatment of urogenic sepsis after drainage.
4.Gastrodin inhibits microglia-mediated inflammatory response in isch-emic hypoxic neonatal mice via CCR5/JAK1/STAT1 signaling pathway
Jinsha SHI ; Haolong SHI ; Hanjun ZUO ; Tao GUO ; Xinglin ZHANG ; Ha-Onan ZHANG ; Jinghui LI ; Juanjuan LI
Chinese Journal of Pathophysiology 2024;40(2):309-316
AIM:To investigate the effect of gastrodin(GAS)on microglia-mediated inflammatory response after hypoxic-ischemic brain damage(HIBD)neonatal mice by regulating the expression of JAK1/STAT1 pathway through C-C chemokine recepeor 5(CCR5).METHODS:Forty-eight C57BL/6J mice at about 10 days after birth were randomly divided into sham group,HIBD model group and HIBD+GAS group.BV-2 microglia were divided into control(Con)group,oxygen glucose deprivation(OGD)group,oxygen glucose deprivation with gastrodin intervention(OGD+GAS)group,GAS group,Maraviroc(MVC)group,OGD+MVC group,and OGD+MVC+GAS group.The mRNA expression of CCL4 and CCR5 were detected by RT-qPCR.The protein expression of CCR5,p-JAK1,p-STAT1,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were detected by Western blot.The expression of CCR5,p-JAK1 and p-STAT1 in cells were observed by immunofluorescence staining.RESULTS:(1)Compared with sham group,the expression levels of CCL4 and CCR5 mRNA,and CCR5,p-JAK1 and p-STAT1 proteins were significantly higher in the ischemic side of the corpus callosum in HIBD group(P<0.05).(2)Compared with Con group,the protein levels of CCR5,p-JAK1 and p-STAT1 significantly increased in BV-2 cells of OGD group(P<0.05).The protein levels of CCR5,p-JAK1 and p-STAT1 in BV-2 cells of OGD+GAS group were significantly lower than those of OGD group(P<0.05).(3)Maraviroc did not cause significant BV-2 cell death in the 0~80 μmol/L range.The p-JAK1 and p-STAT1 protein levels in MVC+OGD group were significantly lowered compared with OGD group(P<0.05),but no significant difference was found between MVC+ OGD and OGD+MVC+GAS groups.CONCLUSION:Gastrodin can exert neuroprotective effects via CCR5/JAK1/STAT1 signaling pathway.
5.Gastrodin inhibits the lipopolysaccharide-induced microglia activation through the SOX2/β-catenin signaling pathway
Xinglin ZHANG ; Jinsha SHI ; Hongming FU ; Yurui HUANG ; Haolong SHI ; Hanjun ZUO ; Tao GUO ; Juanjuan LI
Chinese Journal of Neuroanatomy 2024;40(3):365-372
Objective:To investigate the effect of gastrodin(GAS)on the sex-determining region Y-box2(SOX2)/β-catenin pathway in microglia induced by lipopolysaccharide(LPS).Methods:BV2 microglia was cultured in vitro and divided into the following groups:Control group(Control),LPS group(LPS),LPS+0.17 mmol/L gastrodin treatment group(LPS+GAS-L),LPS+0.34 mmol/L gastrodin treatment group(LPS+GAS-H),SOX2 inhibitor pronethalolgroup(PR),LPS+PR group(LPS+PR),and LPS+PR+GAS group(LPS+PR+GAS).Effect of PR on BV2 microglia viability was detected by CCK-8.The expression of SOX2,β-catenin,mannose receptor(CD206)and tumor necrosis factor-α(TNF-α)was assessed using Western Blot and immunofluorescence double staining.Results:PR did not induce significant BV2 cell death in the 0~40 μmol/L range.After LPS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly increased in the LPS group,while CD206 decreased(P<0.05).Following GAS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly decreased,while CD206 increased(P<0.05).Compared to the LPS group,the expression levels of β-catenin and TNF-α significantly de-creased in the PR group(P<0.05),but no significant difference was observed between the LPS+GAS and LPS+PR+GAS group.Conclusion:GAS significantly inhibits LPS-induced microglia activation potentially through the inhibi-tion of the SOX2/β-catenin signaling pathway,and exerts anti-inflammatory effects.
6.Gastrodin alleviates microglia-mediated inflammatory responses in neonatal mice with hypoxic-ischemic brain damage by regulating CCR5/AKT signaling
Jinsha SHI ; Haonan ZHANG ; Xinglin ZHANG ; Haolong SHI ; Hanjun ZUO ; Tao GUO ; Zhao WANG ; Hang YU ; Juanjuan LI
Journal of Southern Medical University 2024;44(10):1850-1857
Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.
7.Gastrodin alleviates microglia-mediated inflammatory responses in neonatal mice with hypoxic-ischemic brain damage by regulating CCR5/AKT signaling
Jinsha SHI ; Haonan ZHANG ; Xinglin ZHANG ; Haolong SHI ; Hanjun ZUO ; Tao GUO ; Zhao WANG ; Hang YU ; Juanjuan LI
Journal of Southern Medical University 2024;44(10):1850-1857
Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.
8.Sarcopenia associated with chronic obstructive pulmonary disease
Shifang YANG ; Xinglin GAO ; Jing LI ; Lupeng JI
The Journal of Practical Medicine 2024;40(9):1181-1185
Sarcopenia is a progressive and systemic skeletal muscle disease and an important extrapulmo-nary complication of chronic obstructive pulmonary disease(COPD).Multiple studies have confirmed that COPD patients with sarcopenia have more severe airflow obstruction and emphysema,higher dyspnea index scores,reduced quality of life and exercise capacity,frequent acute exacerbations,and increased mortality.Although sarcopenia has been mentioned as a complication of COPD for many years,current clinical practice has received insufficient attention and insufficient intervention.The main reason is that its pathogenesis is unknown and drug treatment regi-mens are ineffective.As more and more research has been done on COPD combined with sarcopenia in recent years,this article reviews the current research progress to pay attention to further research and early intervention,including new mechanisms,diagnostic criteria,and drug treatment progress.
9.Clinical application value of single pass scanning using multi-slice spiral CT for polytrauma patients
Gang WANG ; Ying ZHANG ; Teng TANG ; Hongyang DAI ; Nan WANG ; Mimi QIU ; Hongwei XU ; Fangfang XIA ; Xinglin XIANG ; Jian LI
Chinese Journal of Radiological Medicine and Protection 2024;44(8):693-698
Objective:To explore the clinical application value of single pass scanning using muti-slice spiral CT for polytrauma patients.Methods:Totally 60 polytrauma patients treated from January to November in 2023 were randomly enrolled in this study. They were categorized into an experimental group and a control group using a random number table, with 30 patients in each group. The patients in the experimental group underwent single pass scaning for the head, neck, chest, and abdomen, whereas those in the control group receiving separate scanning for various parts. Then, the noise, signal-to-noise ratio (SNR), and contrast-to-noise (CNR) of the CT images of both groups were recorded. Furthermore, the objective and subjective evaluation, volume CT dose index (CTDI vol), effective dose ( E), scanning time, and scan ranges of the images were compared between both groups. Results:Compared to the control group, the test group exhibited lower SNR of the head ( t = -5.47, P < 0.05) and higher SNR and CNR of the chest scans ( t = -5.95, -6.15, P < 0.05). Furthermore, the test group demonstrated decreased ED, CTDIvol, scanning time, and scan range, which dropped from 18.53 mSv to 13.81 mSv ( t = 3.29, P < 0.001), from 15.77 mGy to 10.59 mGy ( t = 4.48, P< 0.001), from 31.68 s to 10.97 s ( t = 6.95, P < 0.001), and from 64.92 cm to 45.21 cm ( t = 9.05, P < 0.001), respectively compared to the control group. Conclusions:Single pass CT scanning can reduce E, scanning time, and scan range in the treatment of polytrauma patients while ensuring the high quality of CT images, thus warranting wide clinical applications.
10.Prevalence and risk factors of sleep apnea in patients with Alzheimer's disease
Zhanghui PENG ; Jun LIU ; Wanping LIU ; Jing KUANG ; Xinglin HE ; Li LIU
Journal of Public Health and Preventive Medicine 2023;34(3):157-160
Objective To analyze the prevalence and risk factors of sleep apnea syndrome (SAS) in patients with Alzheimer's disease (AD), and to provide theoretical basis for the prevention of SAS in AD patients. Methods A total of 130 AD patients admitted to the Department of Neurology of Guang'an People's Hospital of Sichuan Province from January 2019 to September 2022 were selected and divided into control group (without SAS) and observation group (with SAS) according to whether the patients were complicated with SAS{AHI ≥5 times/h}. Snoring, waking at night, dry mouth in the morning, AHI and SaO2 values were compared between the two groups. Clinical data of AD patients, including age, gender, body mass index (BMI), AD course, tobacco and alcohol history, and neurodegenerative diseases, were collected by self-made questionnaire and consulting the patient's electronic medical record bed. Univariate analysis and logistic regression were used to analyze the independent risk factors for SAS in AD patients. Results Among 130 AD patients, 43 cases (33.08%) of SAS occurred. The proportion of snoring, awakening at night, dry mouth in the morning and AHI value in the observation group were significantly lower than those in the control group (P<0.05). SaO2 value in observation group was significantly lower than that in control group (P<0.05). There were significant differences in age, duration of AD, BMI, smoking history, combined hypertension, neurodegenerative disease, PSQI score and PSQI score between the two groups (P<0.05). Multivariate logistic regression analysis showed that BMI≥28 kg/m2, PSQI score >16 points and CDR score ≥2 points were independent risk factors for SAS in AD patients (P<0.05). Conclusion The incidence of SAS associated with AD is higher, and the main risk factors are BMI≥28 kg/m2, PSQI score >16 and CDR score. Polysomnosis monitoring should be performed regularly to prevent SAS.


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