1.Dosimetric study of isolated neuronal networks under 2.6 GHz radiofrequency exposure
Yuqing WANG ; Xuelong ZHAO ; Qi LIU ; Guofu DONG ; Yu WEI ; Ni CHEN ; Xiaoman LIU ; Changzhen WANG ; Hongmei ZHOU
Military Medical Sciences 2024;48(2):95-100
Objective To evaluate the characteristics of dose distribution of neuronal networks in vitro on microelectrode arrays(MEAs)under 2.6 GHz radiofrequency(RF)exposure.Methods The MEAs were coupled with a real-time RF exposure setup,and electromagnetic simulation software was used to calculate the RF dose absorbed in cultured neuronal networks.A fiber-optic temperature probe was used for experimental validation and monitoring of the cell temperature during RF exposure.The MEAs were used to record the electrical activity of neurons.Results For an input power of 1 W,a specific absorption rate(SAR)level of(15.51±2.48)W/kg was calculated,and the variability of the SAR distribution was 16%.In our experimental system,the temperature elevation of neurons was up to 0.15℃for an SAR of 4 W/kg RF exposure.Conclusion The exposure device can provide high SAR efficiency and uniformity in the 2.6 GHz band,which is suitable for studying the real-time effects of RF fields on the electrical activity of neuronal networks in the 5G network band.
2.Research progress on the role of ferroptosis in infectious diseases
Linzhi YUE ; Tao MA ; Yumei DAI ; Wenya DU ; Guofu WANG ; Lixian WU
Chinese Journal of Comparative Medicine 2024;34(7):175-180
Ferroptosis is a newly discovered mode of programmed cell death characterized by the accumulation of intracellular iron-dependent lipid peroxidation.Current research has mainly focused on the role of ferroptosis in the field of cancer,but increasing evidence shows that ferroptosis is also related to the occurrence of infectious diseases.Ferroptosis has accordingly been detected in cases of COVID-19,tuberculosis,and cryptococcal meningitis,as well as other diseases.This article reviews the role of ferroptosis in infectious diseases,to provide new ideas for the prevention and treatment of ferroptosis-related infectious diseases.
3.Roles of Keap1-Nrf2 and NF-κB signaling pathways in lipopolysaccharide-induced brain injury
Yichen LIU ; Dongfei YAN ; Zhixin LI ; Yingchun MAO ; Zhihui LI ; Guofu DONG ; Changzhen WANG
Military Medical Sciences 2024;48(7):481-486
Objective To investigate the role of Kelch-like-epichlorohydrin-associated protein 1/nuclear factor erythroid-derived factor-2-related factor 2(Keap1-Nrf2)and nuclear factor-κB(NF-κB)signaling pathways in sepsis-associated encephalopathy(SAE).Methods Male C57BL/6J mice of SPF were randomly divided into four groups(n=10):the control group and LPS 6 h,24 h and 48 h groups.The behavioral changes of the mice were assessed based on their general conditions and open field test(OFT).ELISA was used to measure the levels of pro-inflammatory cytokines in mouse serum,and the antioxidant capacity assay kit to examine antioxidant activity in brain tissues of mice.Real-time quantitative PCR(qPCR)was adopted to detect the mRNA levels of toll-like receptor4(Tlr4),NF-κB,Keap1 and Nrf2 in the hippocampus,and to determine protein expressions of NF-κB a Nrf2、Keap1 and Tlr4 with Western blotting.Results Compared to the control group,the serum concentrations of interleukin 6(IL-6)in lipopolysaccharide(LPS)groups increased at 6 h,and reached the peak at 24 h and 48 h(P<0.01).The levels of serum interleukin 18(IL-18)in the LPS groups increased significantly at 6 h and 24 h(P<0.01)but there was no statistically significant difference compared with the 48h group.The results indicated the activity of superoxide dismutase(SOD)and glutathione(GSH)in brain tissues in LPS groups increased(P<0.01).OFT results showed the time spent in the center of the open field,the distance covered around the center,and total distance covered by mice in LPS groups were significantly reduced(P<0.01),except for the time spent in the center of the open field in the LPS 24 h group.The mRNA expressions of Tlr4 and(LPS 6 h,48 h)NF-κB in the hippocampus tissue of mice in LPS groups were elevated(P<0.05),so were the mRNA expressions of Keap1 and Nrf2 in LPS 6 h group.Additionally,the protein expressions of NF-κB,Keap1 and Tlr4 increased in LPS groups,so did the protein expression of Nrf2 in LPS 24 h and 48 h groups(P<0.05).Conclusion Keap1-Nrf2 and NF-κB signaling pathways may play a certain role in SAE.
4.Effects of pulsed electron beams with ultra-high dose rate and conventional dose rate on Caenorhabditis elegans
Shuang WU ; Zhihui LI ; Wenxi YANG ; Guofu DONG ; Changzhen WANG
Chinese Journal of Radiological Medicine and Protection 2024;44(11):903-908
Objective:To explore the effects of ultra-high dose rate pulsed electron beams on Caenorhabditis elegans ( C. elegans). Methods:The adult wild-type strain (N2) of C. elegans was synchronized and cultured to L4 stage, and then randomly divided into control group (SHAM group), conventional radiotherapy dose rate group (CONV group) and ultra-high dose rate radiation group (UHDR group). The CONV and UHDR groups were exposed to 3 Gy of the pulsed electron beam at dose rates of 0.3 and 200 Gy/s, respectively. After irradiation, the egg-laying capacity of each group was assessed, and the developmental progress, motility, and survival rates each were evaluated at day 3, 6, and 10. Results:On the 3 rd day post-irradiation, both the CONV and UHDR groups showed shorter body lengths compared to the SHAM group ( t=4.81, 4.83, P<0.05), with no significant differences in body width ( P>0.05). On the 6 th and 10 th days, the CONV group showed a significant reduction in both body length and width compared to the SHAM group ( t=3.18-3.63, P<0.05), whereas the UHDR group displayed a significant increase in body length ( t=-9.85, -2.87, P<0.05) with no significant change in body width. When comparing the UHDR group to the CONV group on day 6 and 10, a significant increase in body width was observed ( t=-4.43, -3.37, P<0.05). Motor activity, including head swinging and body bending, significantly decreased in the CONV and UHDR groups compared to the SHAM group on day 6 ( t=2.91, 3.52, 3.97, 2.71, P<0.05), with no significant differences among the three groups by day 10 ( P>0.05). Egg-laying capacity significantly reduced in both irradiated groups compared to the SHAM group ( t=1.72, 5.54, P<0.05), while the UHDR group exhibited higher fecundity than the CONV group ( t=-5.99, P<0.05). Lifespan was significantly shortened in the CONV group compared to the SHAM group ( χ2=8.49, P<0.05), whereas the survival time of the UHDR group was not significantly differ from that of the SHAM group ( P>0.05). Conclusions:Exposure to a conventional electron beam result in developmental delays, reduced mobility, decreased fecundity, and a shortened lifespan in C. elegans. However, only slight side effects were observed when C. elegans were exposed to an ultra-high dose rate pulsed electron beam at the same dosage.
5.Functional connectivity and regional spontaneous brain activity in a minimally-conscious state
Guofu MIAO ; Yu GONG ; Sirui WANG ; Hui CHEN ; Weijing LIAO
Chinese Journal of Physical Medicine and Rehabilitation 2023;45(4):297-301
Objective:To explore the characteristics of functional connectivity (FC) and regional spontaneous brain activity in patients in a minimally-conscious state (MCS).Methods:Resting-state functional near-infrared spectroscopy (rs-fNIRS) was used. Ten minimally-conscious patients were studied along with 12 healthy counterparts as healthy controls (HC). Five minutes of rs-fNIRS data were recorded from each subject and FC and the fractional amplitude of low-frequency fluctuations (fALFFs) of 53 channels were computed using the NIRS-KIT toolbox. The results were compared between the two groups.Results:Compared with the HC group, a significant decrease was observed in the average FC strength of seventeen channel pairs after false discovery rate (FDR) correction. Most were in the right and left frontal pole, as well as the dorsolateral prefrontal lobe. Compared with the HC group, the average fALFF values of Broca′s area (channel 2), the premotor cortex and the supplementary motor cortex (channels 4, 10, and 40), the dorsolateral prefrontal lobe (channels 6, 11, 25, 39), the eye motor area of the frontal lobe (channel 12) and the frontal pole (channels 23, 27, 36) were significantly greater in the MCS group. The fluctuations of the frontal pole (channel 19) were significantly less (after FDR correction).Conclusion:In an MCS spontaneous neural activity is over-active in the prefrontal lobe and some speech- and motor-related brain regions, and coordination of the internal prefrontal functional network is disordered.
6.The topology of resting-state functional networks in the brain after an ischemic stroke
Biru WANG ; Sirui WANG ; Guofu MIAO ; Zhuo CHEN ; Weijing LIAO
Chinese Journal of Physical Medicine and Rehabilitation 2022;44(11):982-988
Objective:To explore any changes in the topology of the brain′s resting-state functional networks after an ischemic stroke causing cognitive impairment (iPSCI) and their relationship with the impairment.Methods:Twenty-one patients with impaired cognition after a stroke were recruited into an iPSCI group, and 21 healthy counterparts matched in gender, age and the education level formed the control (HC) group. Three-dimensional T1-weighted anatomical images and resting state functional magnetic resonance images of all of the subjects were collected and any differences in brain network topology were analyzed using graph theory. The degree of centrality (DC), between centrality (BC) and the global topological properties of each brain region were compared using independent-sample t-tests. Spearman correlation coefficients were computed to analyze the significance of any correlation between topology differences and Montreal Cognitive Assessment Scale (MoCA) or Mini-Mental Status Examination (MMSE) scores.Results:Compared with the HC group, a significant DC increase was observed in the orbital part of the right of middle frontal gyrus (ORBmid.R), the right hippocampus (HIP.R), and the right thalamus (THA.R). There was a significant decrease in the left Rolandic operculum (ROL.L), the left postcentral gyrus (PoCG.L), the left supramarginal gyrus (SMG.L), the left angular gyrus (ANG.L), the left and right caudate nucleus (CAU.L and CAU.R), the putamen of the left lenticular nucleus (PUT.L), the left Heschl gyrus (HES.L), the left superior temporal gyrus (STG.L), and the temporal pole of the left superior temporal gyrus (TPOsup.L). Compared with the HC group, the brain regions of the iPSCI group in which the BC had increased significantly were the orbital part of the left middle frontal gyrus (ORBmid.L), the left cuneus (CUN.L), and the right precuneus (PCUN.R). DC was significantly decreased in the left caudate nucleus (CAU.L), the left temporal pole of the superior temporal gyrus (TPOsup.L), and the left of inferior temporal gyrus (ITG.L). Compared with the HC group, the area under the receiver operating curve (AUC) of the shortest path length (Lp) and the normalized Lp (λ) of the iPSCI group increased significantly, and the AUC of the normalized clustering coefficient (γ) and small-worldness (σ) decreased significantly. The DCs of the ROL.L, PoCG.L, CAU.L, HES.L, STG.L and TPOsup.L regions showed moderate positive correlation with the MoCA and MMSE scores ( r>0.4), as did the BC of the CAU.L and TPOsup.L regions ( r>0.4). Conclusions:Cognitive impairment is mainly associated with decreased nodal properties in the brain regions related to language and in the caudate nucleus. The topology of the frontal lobe, hippocampus, thalamus, striatum and default networks may self-repair after an iPSCI. The brain′s functional network after an iPSCI still has small-world properties, but with low efficiency and high cost.
7.Effects of 60Co γ-rays on brain injury and polarization of microglia/macrophages in mice
Xueli WANG ; Qiuli DU ; Zhihui LI ; Sen ZHOU ; Guofu DONG ; Changzhen WANG
Chinese Journal of Microbiology and Immunology 2022;42(7):501-509
Objective:To analyze the damage in hippocampal tissues of mice after whole-body irradiation with high- or low-dose ionizing radiation and to investigate the roles of microglia/macrophages polarization in the injury.Methods:C57BL/6 mice were randomly divided into three groups: sham irradiation group, low-dose group (0.05 Gy) and high-dose group (7 Gy). Low- and high-dose groups were respectively treated by whole-body irradiation with single dose of 60Co γ-rays. Hippocampal tissues of the mice were collected at 6 h, 1 d, 3 d and 7 d after irradiation. The morphology, structure and apoptosis of neurons were detected by HE staining, Nissl staining and Tunnel staining, respectively. RT-PCR and immunofluorescence assay were performed to detect the expression of M1 and M2 microglial markers at mRNA and protein levels in hippocampus tissues. The cognitive and emotional behaviors of mice were evaluated one month after the irradiation by Morris water maze, open field test, elevated plus maze and tail suspension test. Results:There were morphological and structural changes in the nerve cells in the hippocampus region of mice after irradiation, accompanied by apoptosis. Acute injuries occurred at 6 h after radiation, alleviated at 1 d and 3 d, and persisted at 7 d in a dose-dependent manner. The results of immunofluorescence staining and confocal imaging analysis showed that compared with the sham irradiation group, the high-dose group showed increased number of microglia, down-regulated expression of M1 microglial markers and up-regulated expression of M2 microglial markers in the hippocampus at 6 h and 1 d after radiation, while M2 microglial markers decreased at 3 d and 7 d after irradiation. PCR results showed that the expression of M1 and M2 microglial markers at mRNA level in the irradiation groups increased at 6 h after irradiation, but there was no statistical significance. The expression of related proinflammatory/anti-inflammatory factors was significantly up-regulated. The results of behavioral experiments showed that compared with the sham irradiation group, there was no statistical difference in cognitive or emotional behaviors at one month after irradiation.Conclusions:60Co γ-rays could damage mouse hippocampal tissues and result in the overexpression and different polarization patterns of microglia/macrophages in mice.
8.Quantitative evaluation of apparent diffusion coefficient and renal volume on fetal renal development and renal disease
Chang'an CHEN ; Yingfang WANG ; Shulei CAI ; Lei LING ; He ZHANG ; Ming ZHU ; Guofu ZHANG
Chinese Journal of Perinatal Medicine 2022;25(4):256-262
Objective:To explore the value of apparent diffusion coefficient (ADC) and renal volume in assessing fetal kidney development and disease.Methods:From January 2016 to October 2020, 84 fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) were identified with MRI (CAKUT group), and 97 fetuses with no significant abnormalities on MRI or postnatal follow-up (control group) from the Obstetrics and Gynecology Hospital of Fudan University were enrolled and analyzed retrospectively. ADC value and renal volume were measured to compare the two groups, and the relationship was analyzed between these two parameters in the control group with gestational age, location (left or right kidney), and fetal gender. Two independent or paired sample t-tests, and linear correlation analyses, were adopted for the statistical analysis. Results:(1) There were 84 pregnant women in the CAKUT group, including a twin pregnancy, with an average age of (29±4) years old, ranging from 21 to 39 years old. The gestational age at MRI was (26±4) weeks with a range of 21-34 weeks. Of the 85 fetuses, 52 were male (61.2%), and 33 were female (38.8%). The polycystic dysplastic kidney was found in 32 cases (37.6%), hydronephrosis in 29 cases (34.1%), and an isolated kidney in 24 cases (28.2%). There were 97 singleton pregnancies in the control group, including 45 (46.4%) male and 52 (53.6%) female fetuses. The average maternal age was (30±5) years old, with a range of 19-41 years old, and the gestational week at MRI was (27±4) weeks, with a range of 21-34 weeks. (2) In the control group, the mean ADC value and renal volume were (1.255±0.112)×10 -3 mm2/s and (4 747±2 479) mm 3, which were negatively ( R 2=0.30, P<0.01) and positively correlated ( R 2=0.80, P<0.01) with the gestational age, respectively. There was no significant difference between ADC value and renal volume between different fetal gender in the control group. (3) The ADC value and the renal volume of fetuses with polycystic dysplastic kidney [(1.720±0.200) ×10 -3 mm2/s and (8 154±8 337) mm 3] were higher than those in the control group ( t=-13.11 and-3.08, P<0.001 and P=0.004). Compared with the control group, ADC of fetuses with hydronephrosis [(1.333±0.171) ×10 -3 mm2/s] was higher ( t=-3.90, P<0.001); and the renal volume [(7 201±4 460) mm 3] was larger but without statistical significance. The fetuses with an isolated kidney had an increasing trend in renal volume [(5 239±4 244) mm 3] and a decreasing trend in the ADC value [(1.239±0.125) ×10 -3 mm2/s] when compared with the normal fetuses, but neither difference was significant. Conclusions:In normal fetuses, the ADC value decreases, and the renal volume increases with the gestational age. Fetuses with CAKUT may have a larger kidney than normal.
9.Pregnancy outcome of fetal tethered cord diagnosed by MRI: analysis of 38 cases
Jue WANG ; Shulei CAI ; Zhongpeng FU ; Chengqiu LU ; Xirong XIAO ; Shouxin GU ; Guofu ZHANG ; He ZHANG
Chinese Journal of Perinatal Medicine 2021;24(3):214-219
Objective:To evaluate the pregnancy outcomes of fetal tethered cord (TC) prenatally diagnosed by MRI.Methods:Clinical data of 38 fetuses diagnosed as having TC by MRI, including 36 singletons and two fetuses who were both one of dichorionic diamniotic twins, were retrospectively collected and analyzed in the Obstetrics and Gynecology Hospital of Fudan University from January 2015 to August 2019. According to whether conus medullaris was located above the bladder or reached the lower edge of the bladder, all cases were divided into high or low groups. Pregnancy outcomes were compared between the two groups using Fisher's exact test and Student's t-test. Results:(1) The gestational age at MRI was (25.5±4.7) weeks. Among the 38 cases, 14 (36.8%) were isolated TC, 24 (63.2%) were complicated by other anomalies. The meningocele was responsible for the most (39.5%, n=15). The results of the ultrasound were consistent with those of MRI in 24 cases (63.2%). While in the other 14 cases (36.8%), the ultrasound only showed vertebral body's abnormal morphology, after which further MRI examination revealed a tethered cord. (2) Twenty-nine women (76.3%) chose to terminate the pregnancy. One patient (2.6%) underwent fetal reduction at 23 gestational weeks (one normal twin was delivered prematurely), and one (2.6%) was lost to follow-up. Seven (18.4%) cases continued the pregnancies to delivery. The postnatal follow-up period was 8.1 months (4.0 to 54.9 months). Two infants without comorbidities showed normal growth and development. Another three cases underwent surgeries after birth, and two cases died in the neonatal period. (3) The average width of the medullary cone was (2.5±0.8) cm. There was no significant difference in the spinal cord width between the high [(2.5±0.8) cm, n=34] and low group [(2.7±1.1) cm, n=4]. Six pregnancies (17.6%) in the high group was continued to delivery, and one of the neonates died of severe hydrocephalus. One patient in the low group (1/4) was delivered, while the baby died of neonatal asphyxia. Conclusions:Fetuses with isolated TC are prone to have a good prognosis. Further study should focus on the relation between the high or low position of the conus medullaris and pregnancy outcomes.
10.Experimental study on measurement of short pulsed and high-dose-rate X-ray by therapeutic grade ionization chamber
Dawei LI ; Yunlong JI ; Yong YUAN ; Hongmei ZHOU ; Guofu DONG ; Qi WANG ; Jing NING
Chinese Journal of Radiological Medicine and Protection 2021;41(8):626-630
Objective:To investigate the application of therapeutic grade ionization chamber to rapid measurement of short pulsed and high-dose-rate X-ray.Methods:The half-value layer of pulsed X-ray caused by an electron accelerator was measured by interpolation method and its equivalent energy was estimated. The cumulative doses from a certain amount of pulsed radiation at different distances in the same direction around the equipment were compared using the therapeutic grade ionization chamber and thermoluminescence measurement method . The relationship between the measurement result by using ionization chamber dosimeter and the distances away from source was analyzed. The cumulative doses from a certain amount of pulsed radiation at the same location at different frequencies were compared.Results:In working condition, 100 pulses of radiation were received accumulatively at 1 to 12 meters away from the outer wall of the equipment. The range of air Kerma was 0.08-9.65 mGy measured by using thermoluminescence dometers and 0.08 - 9.85 mGy using the ionization chamber dosimeters, respectively. The difference between both is within 10%. At different frequencies (1-10 Hz), there was no significant difference in X-ray air Kerma from 100 pulses measured by ionization chamber dosimeter at 2 m away from the front of the equipment ( P>0.05). Conclusions:The therapeutic grade ionization chamber dosimeter can be used for the rapid measurement of short pulsed X-ray radiation dose in the range of dose rates and pulse frequencies involved in the experimental accelerator device.

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