1.Celastrol attenuates sodium oxalate-induced acute kidney injury and crystal deposition by inhibiting NF-κB
Yiheng LIU ; Quanyou ZHENG ; Wanyuan ZHANG ; Chenhao YANG ; Siyu CHEN ; Wenbiao LIN ; Siyu ZHAO ; Guilian XU ; Keqin ZHANG
Journal of Army Medical University 2025;47(7):691-700
Objective To investigate the role and possible mechanism of celastrol(Cel)in sodium oxalate(NaOx)-induced acute kidney injury(AKI)and crystal deposition in the kidney tissues in mice.Methods Male C57BL/6 mice(aged 8~12 weeks,weighing 22~24 g)were randomly divided into 3 groups.Saline group(control group,intraperitoneal injection with normal saline and drinking water freely),NaOx group(injured group,intraperitoneal injection of 75 mg/kg NaOx,and drinking water containing 50 μmol/L NaOx),and NaOx+Cel group(treatment group,intraperitoneal injection of 1 mg/kg Cel firstly and then 75 mg/kg NaOx in 24 h later,drinking water containing 50 μmol/L NaOx).All specimens were collected in 24 h after NaOx injection.HK-2 cells were randomly divided into 4 groups:Medium group(no treatment),NaOx group(500 μmol/L NaOx),NaOx+Cel group(400 nmol/L Cel pre-treatment for 2 h followed by 500 μmol/L NaOx treatment),and NaOx+Cel+BA group[8 μmol/L betulinic acid(BA,NF-κB agonist)after the interventions as the NaOx+Cel group].Cells of each group were collected in 24 h after corresponding treatments.Von Koosa and cell adhesion assays were used to observe crystal deposition.HE staining was employed to observe renal histopathology and score the damage.CCK-8 assay was utilized to detect cell viability to obtain the optimal concentrations of NaOx and Cel.Serum urea and creatinine levels were detected.Immunohisotochemical assay was conducted to detect the expression of OPN,CD44,KIM-1,NGAL,p65,IL-1β,BAX,and Caspase-3,and Western blotting was performed for protein levels of OPN,CD44,KIM-1,p65,P-p65 and IL-1β.Results The mice in the NaOx+Cel group showed reduced crystal deposition(P<0.0001),attenuated renal tubular damage(P<0.01),decreased serum urea and creatinine levels(P<0.05),and declined expression levels of the renal adhesion molecules OPN and CD44,the kidney injury molecules KIM-1 and NGAL,the inflammation-associated molecules p65 and IL-1β,and the apoptosis related molecules BAX and Caspase-3 when compared with the NaOx group(P<0.05).In in vitro study,the NaOx+Cel group showed reduced crystal adhesion(P<0.0001),decreased expression of the adhesion molecules OPN and CD44(P<0.05),down-regulation of the inflammatory molecule IL-1β and P-p65/p65 ratio(P<0.05),and down-regulation of the renal injury molecule KIM-1(P<0.05)when compared with the NaOx group.In the NaOx+Cel+BA group,crystal adhesion was significantly increased(P<0.0001),the inflammatory molecule IL-1β and the ratio of P-p65/p65 were increased(P<0.05),and the kidney injury molecule KIM-1 was increased when compared with the NaOx+Cel group(P<0.05).Conclusion Cel may reduce NaOx-induced crystal deposition and AKI by inhibiting NF-κB activation.
2.Effects of long-term 2.65 GHz radiofrequency radiation on inflammatory response and intestinal microbiota in mice
Keqin LI ; Yanhui HAO ; Ying LIU ; Jun WANG ; Hongyan ZUO ; Hong YANG ; Yang LI ; Hua DENG
Journal of Army Medical University 2025;47(15):1815-1824
Objective To investigate the effects of long-term radiofrequency(RF)radiation at 2.65 GHz on behavior,inflammatory response,and intestinal microecology in mice in order to provide a basis for the safety assessment of long-term RF exposure.Methods One hundred and eight male C57BL/6N mice(17~21 g,6~8 weeks old)were randomly assigned to a control group(Con)and a RF exposure group.The mice of the RF exposure group were subjected to whole-body uniform exposure to 2.65 GHz RF radiation in an electromagnetic reverberation chamber for 3 h/day for 28 consecutive days.RF field distribution and changes in core body temperature were monitored using an electromagnetic radiation analyzer and a fiber-optic temperature probe,respectively.Cognitive function was assessed using the Y-maze and novel object recognition(NOR)test.Anxiety-like behaviors were evaluated through open field test(OFT)and elevated plus maze(EPM),while depressive-like behaviors were examined with sucrose preference test(SPT)and tail suspension test(TST).HE staining was used to observe the histopathological changes in mouse tissues.Radioimmunoassay(RIA)was employed to detect the expression of pro-inflammatory cytokines,TNF-α and IL-1 β,as well as anti-inflammatory cytokines,IL-4 and IL-10 in the serum,brain,jejunum,and spleen samples.Additionally,metagenomic sequencing was performed to assess alterations in the gut microbiota composition.Results Long-term RF radiation led to a maximal increase of 0.59℃in the core body temperature,but had no significant effects on cognitive function,anxiety-like behaviors,or depressive-like behaviors,or apparent damage of the hippocampal or jejunal tissues in the exposed mice.However,RF exposure significantly up-regulated the expression of the pro-inflammatory cytokine TNF-α in serum(P<0.05),and did not significantly alter the concentrations of other cytokines(IL-1β,IL-4,IL-10),caused significant decrease in α-diversity of the intestinal microbiota(P<0.01),with reduced relative abundances of Ligilactobacillus murinus and Acetatifactor muris(P<0.05),while elevated abundances of Lachnospiraceae bacterium(P<0.01).Conclusion Long-term exposure to 2.65 GHz RF radiation induces systemic inflammatory responses and disrupts gut microbiota homeostasis in mice.
3.The prediction value of the early efficacy of hepatic arterial infusion chemotherapy in patients with stageⅡ-Ⅲ hepatocellular carcinoma
Wenjuan YANG ; Meier WU ; Keqin ZHANG ; Haibin YU ; Jinming LIU ; Bing OUYANG ; Wenying WANG ; Ling WEI ; Shu XIONG
Journal of Interventional Radiology 2025;34(5):493-495
Objective To discuss the prediction value of the early efficacy of hepatic arterial infusion chemotherapy(HAIC)in treating stage Ⅱ-Ⅲ hepatocellular carcinoma(HCC).Methods The clinical data of 81 patients with stage Ⅱ-Ⅲ HCC,who received at least 3 times of HAIC at the Nanchang Municipal Central Hospital of China from November 2021 to March 2024,were retrospectively analyzed.CT or MRI was used to compare patient's local tumor response after each treatment cycle.Based on modified Response Evaluation Criteria in Solid Tumors(mRECIST),the curative effects of patients after receiving the first,the second,and the last HAIC treatment were compared between each other.The prediction value of the early efficacy of HAIC in treating patients with stage Ⅱ-Ⅲ HCC was analyzed.Results In the 67 patients,the efficacy of the last time HAIC was equal or similar to that of the first time HAIC,and in the remaining 14 patients the efficacy of the last time HAIC was different from that of the first time HAIC,with an efficacy prediction rate of 82.72%.The efficacy of the last time HAIC was equal or similar to that of the second time HAIC in 71 patients,and in the remaining 10 patients the efficacy of the last time HAIC was different from that of the second time HAIC,with an efficacy prediction rate of 87.65%.Conclusion In treating stage Ⅱ-Ⅲ HCC with HAIC,the early efficacy can be used to predict the final efficacy after completion of the total treatment course.
4.Roles of oligodendrocytes in cognitive impairment induced by microwave radiation in mice
Jun WANG ; Yujie LIU ; Xuefeng YANG ; Keqin LI ; Ying LIU ; Zhe YANG ; Yumeng YE ; Zehang LIU ; Hongyan ZUO ; Yanhui HAO ; Yang LI
Military Medical Sciences 2025;49(10):738-746
Objective To investigate the functional changes of oligodendrocytes in a mouse model of cognitive impairment induced by microwave radiation and the mechanism.Methods C57BL/6N male mice were exposed to S-band microwave at 2.856 GHz and 8 mW/cm2 for 15 min.The rectal temperature of mice was monitored by an optical fiber thermometer during microwave radiation.The changes of autonomous exploration behavior and learning and memory ability of mice on the 1st and 7th days after microwave radiation were detected via the open field test and novel object recognition test.Immunofluorescence was used to detect the expression and distribution of neuroglia-2 proteoglycan(NG2)and myelin basic protein(MBP)in the hippocampus of mice on the 1st and 7th days after radiation.Clemastine fumarate,a drug that promoted the maturation of oligodendrocyte precursor cells was administered by gavage,and the expression levels of brain-derived neurotrophic factor(BDNF)and fibroblast growth factor 2(FGF2)in hippocampal tissues were detected by radioimmunoassay at 1 and 7 days after radiation.The changes of myelin sheath structure an 1 and 7 days after radiation were observed by transmission electron microscopy.The effects of clemastine fumarate on learning and memory impairment induced by microwave exposure in mice were assessed via open field and new object recognition experiments.Results Under the experimental conditions,the rectal temperature in mice caused by microwave radiation increased by less than 1 ℃,which was within the thermal safety range of the body.The open field test showed that compared with the control group,the microwave radiation group didn't change significant in terms of movement speedon the 1st and 7th days,but the time spent exploring in the central area was significantly reducedon the 1st day after radiation(P<0.05).In the novel object recognition test,the indexes of the mice on the 1st day were significantly reduced(P<0.05),indicating that the anxiety like behavior and cognitive function of the mice were impaired after microwave radiation.Compared with the control group,the proportion of NG2+area in the hippocampus was significantly decreased(P<0.05)in the microwave radiation group,while that of MBP+area hardly changed on the 1st day after microwave radiation(P>0.05).The expression level of oligodendrocyte related BDNF in the hippocampus was significantly decreased(P<0.05).The myelin of the corpus callosum was broken,and the myelin g ratio was significantly increased(P<0.05),suggesting that micro wave radiation could reduce the number of oligodendrocyte precursors and damage the secretion and myelin function of oligodendrocyte.Compared with the radiation group,the expression levels of BNDF and FGF2 in the radiation combined with clemastine fumarate group were up-regulated,the myelin g ratio was significantly decreased on the 1st day after radiation(P<0.05),and the novel object recognition index was significantly increased(P<0.05).Conclusion Pulsed microwave radiation below the body's fever threshold can cause cognitive dysfunction and other brain damage in mice.The impaired secretion and myelin function of oligodendrocytes and the decreased self-repair ability are the important mechanisms of cognitive dysfunction induced by microwave radiation.
5.Analysis of the application value of ultrasound measuring gastric sinus cross-sectional area to guide the implementation of early individualized enteral nutrition in patients with sepsis
Tan LI ; Xiaoyue ZHANG ; Keqin LIU ; Hao ZENG ; Zhendong TANG ; Longgang SHAO
Chinese Journal of Emergency Medicine 2024;33(2):193-200
Objective:To explore the value of ultrasound measuring gastric sinus cross-sectional area (CSA) to guide early individualized enteral nutrition implementation strategies in sepsis patients.Methods:Thirty septic patients admitted to the EICU and comprehensive ICU of The Second Affiliated Hospital of Nanjing University of Chinese Medicine between January 2021 and December 2022 each were included. EICU patients used bedside ultrasound for gastric sinus CSA to guide the implementation of early enteral nutrition in septic patients, and a routine nutritional support strategy was adopted in the integrated ICU. The correlation of CSA and feeding intolerance in patients with septic gastrointestinal dysfunction, the ROC curve and other relevant indicators of gastrointestinal dysfunction gastrointestinal dysfunction score, SOFA score, APACHEⅡ score, intra-abdominal pressure (IAP), serum protein (PA), [albumin (Alb)]. By comparing the indicators related to inflammation, nutritional status and days of ICU stay after different strategies of the two groups, the advantages of different strategies were analyzed.Results:The baseline data of the two groups were balanced and comparable; the incidence of feeding intolerance was significantly higher (36.67%) than the conventional group (10.00%), with aggressive and early individualized treatment, the incidence rate on the third day was only 10.00%, significantly lower than that in the conventional treatment group (40.00%). Treatment up to the 5th day, the related function scores (gastrointestinal dysfunction score, APACHEⅡ score, SOFA score, IAP), nutritional status indicators (5 d hot card reaching the standard rate, PA, Alb) and inflammation indicators (WBC, PCT, hs-CRP) were significantly improved compared with admission, and is better than the conventional treatment group. In addition, the ICU hospital days and the incidence of aspiration were lower in the ultrasound treatment group ( P <0.05). CSA showed favorable correlation with gastrointestinal dysfunction score, APACHEⅡ score, SOFA score, IAP, PA and Alb, correlation coefficients were 0.79、0.60、0.66、0.71、-0.6 and -0.64( P <0.05). The ROC curve for predicting feeding intolerance by CSA showed the AUC was 0.828, 95% CI was 0.737-0.919, its optimal cutoff value for predicted feeding intolerance was 7.835 cm 2, the sensitivity and specificity were 88.20% and 71.80%. Conclusions:Ultrasound measuring CSA can early and effectively found the feeding intolerance in the patients with sepsis , via giving individualized enteral nutrition implementation strategy, significantly improve the organ function score, nutritional status and inflammation index, reduce the ICU hospital days and aspiration, and correlate with the conventional evaluation index, and sensitivity and specificity are high, worthy of the clinical further promotion.
6.Clinical and electrocardiographic characteristics of carriers with SCN5A mutations and non-SCN5A mutations in fever-induced Brugada syndrome
Keqin SHEN ; Zhonghe ZHANG ; Ganxiao CHEN ; Xiaoxiong LIU ; Guohua FAN ; Jinqiu LIU ; Hao XIA ; Hong JIANG ; Dan HU
Chinese Journal of Cardiology 2024;52(12):1377-1382
Objective:To investigate the differences in clinical and electrocardiographic characteristics between carriers of SCN5A mutations and non-SCN5A mutations in fever-induced Brugada syndrome.Methods:This study is a retrospective cohort study. A total of 263 patients with fever-induced Brugada syndrome who were admitted to Renmin Hospital of Wuhan University from January 2000 to December 2023 were selected. Their clinical manifestations, electrocardiographic characteristics, and major adverse cardiovascular events (MACE) at the time of diagnosis and during the follow-up period were collected. Among them, 200 patients underwent next-generation sequencing. Based on the genetic variation results, after excluding other mutations, they were divided into SCN5A mutation group, non-SCN5A sodium-related mutation group, potassium/calcium mutation group, and no mutation group. Comparisons were made among these groups in terms of their clinical and electrocardiographic characteristics.Results:Among the 263 patients with fever-induced Brugada syndrome, the mean age was (41.9±17.6) years, with 80.6% (212/263) being male. The median follow-up duration was 53.0 months, and 13.7% (36/263) of the patients experienced MACE. The rate of SCN5A mutation was 34.5% (69/200), while the rates of non-SCN5A sodium-related mutations and potassium/calcium-related mutations were 4.5% (9/200) and 3.5% (7/200), respectively. The SCN5A mutation group was younger than the non-SCN5A sodium-related mutation group and the no mutation group (ages were (33.8±14.7), (49.8±11.6), (44.6±15.7) years, respectively, P<0.001). The SCN5A mutation group also had a longer PR interval than the no mutation group ((176.8±32.3) ms vs. (163.9±28.6) ms, P=0.034). The incidence of MACE was higher in the non-SCN5A sodium-related mutation group than that in the no mutation group (55.6% (5/9) vs. 9.1% (9/99), P=0.002). Conclusions:Fever-induced Brugada syndrome patients carrying non-SCN5A mutations exhibit distinct clinical and electrocardiographic characteristics compared to those with SCN5A mutations. These differences warrant attention in clinical practice.
7.Intraoperative frozen section pathology of vaginal margin in radical hysterectomy on the prognosis and quality of life for patients with IB2–IIA2cervical cancer: study protocol for a multicenter randomized controlled trial
Yu LIU ; Weijuan XIN ; Ping WANG ; Mei JI ; Xiaoqing GUO ; Yunyan OUYANG ; Dong ZHAO ; Keqin HUA
Journal of Gynecologic Oncology 2024;35(3):e81-
Background:
Several risk factors have been identified that compromise the treatment outcome in patients with early-to-mid-stage cervical cancer (CC) who are primarily treated with radical surgery. However, there is no report on the impact of intraoperative frozen pathology examination of vaginal margins on the prognosis of patients with CC. This study aimed to conduct a randomized controlled trial (RCT) to determine whether selective vaginal resection can reduce the incidence of operative complications and the risk of postoperative radiotherapy. The impact of the length of the vagina removed in radical hysterectomy (RH) on prognosis and quality of life (QoL) for IB2–IIA2 CC patients will be investigated.
Methods
A multicenter, non-inferiority, RCT at 7 institutions in China is designed to investigate the effect of intraoperative frozen pathology exam of vaginal margin in RH on the survival outcomes for patients with IB2–IIA2 CC. Eligible patients aged 18–70 years will be randomly assigned online by one-to-one random allocation to receive intraoperative frozen pathology exam of vaginal margin or not. If frozen pathology indicates positive margin, continue resection of 1 centimeter of vaginal tissue until negative margin is achieved. The primary end point is 2-year disease-free survival (DFS). Adverse events (AEs) caused by further vagina resection, 5-year DFS, 2-year overall survival (OS), 5-year OS and AEs caused by radiotherapy and QoL are secondary end points. A total of 310 patients will be enrolled from 7 tertiary hospitals in China within 3-year period and followed up for 5 years.Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000035668
8.Intraoperative frozen section pathology of vaginal margin in radical hysterectomy on the prognosis and quality of life for patients with IB2–IIA2cervical cancer: study protocol for a multicenter randomized controlled trial
Yu LIU ; Weijuan XIN ; Ping WANG ; Mei JI ; Xiaoqing GUO ; Yunyan OUYANG ; Dong ZHAO ; Keqin HUA
Journal of Gynecologic Oncology 2024;35(3):e81-
Background:
Several risk factors have been identified that compromise the treatment outcome in patients with early-to-mid-stage cervical cancer (CC) who are primarily treated with radical surgery. However, there is no report on the impact of intraoperative frozen pathology examination of vaginal margins on the prognosis of patients with CC. This study aimed to conduct a randomized controlled trial (RCT) to determine whether selective vaginal resection can reduce the incidence of operative complications and the risk of postoperative radiotherapy. The impact of the length of the vagina removed in radical hysterectomy (RH) on prognosis and quality of life (QoL) for IB2–IIA2 CC patients will be investigated.
Methods
A multicenter, non-inferiority, RCT at 7 institutions in China is designed to investigate the effect of intraoperative frozen pathology exam of vaginal margin in RH on the survival outcomes for patients with IB2–IIA2 CC. Eligible patients aged 18–70 years will be randomly assigned online by one-to-one random allocation to receive intraoperative frozen pathology exam of vaginal margin or not. If frozen pathology indicates positive margin, continue resection of 1 centimeter of vaginal tissue until negative margin is achieved. The primary end point is 2-year disease-free survival (DFS). Adverse events (AEs) caused by further vagina resection, 5-year DFS, 2-year overall survival (OS), 5-year OS and AEs caused by radiotherapy and QoL are secondary end points. A total of 310 patients will be enrolled from 7 tertiary hospitals in China within 3-year period and followed up for 5 years.Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000035668
9.The value of preoperative MRI texture analysis in guiding postoperative prognosis of glioma
Huixi CHEN ; Yunchang LIU ; Keqin LIU ; Wenbo WANG ; Zhizhu PENG
Journal of Practical Radiology 2024;40(5):817-820,840
Objective To investigate the correlation between different grade glioma and MRI image texture parameters and the guiding value of texture analysis for postoperative prognosis.Methods A total of 107 glioma patients were selected,and the texture parameters of MRI images were recorded.The correlation between the grade of glioma and the texture parameters of MRI images was analyzed.The risk factors affecting postoperative adverse effects of glioma patients were analyzed,and the diagnostic efficacy of each texture parameter in predicting glioma grade and postoperative good condition was evaluated.Results Comparison of MRI image tex-ture parameters between patients with low-grade glioma and patients with high-grade glioma showed no significant differences in kur-tosis,skewness,standard deviation,contrast and uniformity,but significant differences in correlation,entropy,consistency and gap distance.Correlation,entropy,consistency and gap distance were significantly correlated with glioma grade.The diagostic efficiency of entropy in predicting glioma grade was significantly higher than that of correlation,consistency and gap distance.The combination of the four predicted glioma patients with good postoperative diagnostic efficacy was the highest.Conclusion The correlation,entropy,consistency and gap distance of MRI image texture parameters can effectively diagnose the grade of glioma,and the combination of the four parameters is more beneficial to the postoperative evaluation of glioma patients.
10.Effects of 2 650 MHz radiofrequency radiation on the behavior and hippocampal neurotransmitter release of mice
Yujie LIU ; Jun WANG ; Keqin LI ; Chenxu CHANG ; Ying LIU ; Hongyan ZUO ; Yang LI ; Hong YANG ; Yanhui HAO ; Hua DENG
Chinese Journal of Radiological Medicine and Protection 2024;44(5):354-360
Objective:To investigate the effects of 2 650 MHz radiofrequency (RF) exposure on the behavior and neurotransmitter release of mice.Methods:Adult male C57BL/6N mice were divided into a normal control (CON) group and a radiofrequency radiation (RFR) group using the random number table method. The mice in the RFR group were subjected to single-dose whole-body exposure to a uniform 2 650 MHz RF electromagnetic field for 3 h. During the RF exposure, the field strength in the effective working area of the RF radiation platform was measured using an electromagnetic radiation analyzer, and the changes in the anal temperature of the mice were monitored using an optical fiber thermometer. Moreover, the changes in the cognition, social interaction, and emotion of the mice were determined through the new object recognition test, social preference test, and open field test. Finally, the changes in the hippocampal neurotransmitter release levels of the mice were detected using microdialysis sampling and mass spectrometry, and the changes in the hippocampal tissue structure and ultrastructure were observed via microscopy.Results:Under the test conditions, RF radiation improved the anal temperature of the mice, with a maximum increasing amplitude of 0.61℃, falling within the range of thermal safety. The mice in the RFR group experienced a significant decrease in the frequency and time for exploring new objects ( t=4.50, 2.53, P < 0.05) in the new object recognition test, a significant decrease in the frequency ( t=0.08, P<0.01) and time ( t=0.03, P<0.05) for exploring other mice in the social preference test, and no significant change in the frequency and time for exploring the central area ( P > 0.05) in the open field test. Compared to the CON group, the RFR group showed an increase in the release of 5-hydroxytryptamine (5-HT) ( t=-2.56, P < 0.05) and a decrease in the release of acetylcholine (ACh) ( t=2.21, P < 0.05), no significant difference in the release of glutamate (Glu) and γ-aminobutyric acid (GABA) ( P > 0.05), and no evident damage to the hippocampal tissue and structure and synaptic ultrastructure. Conclusions:2 650 MHz RF radiation may induce cognitive impairment and abnormal social preference in mice, which is attributed to neuronal dysfunctions and neurotransmitter release disorders under RF exposure.

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