Objective:To explore differences in the radiation-induced intestinal injury in mice exposed to ultra-high dose rate (FLASH) and conventional-dose-rate (CONV) pulsed X-ray irradiation in order to provide evidence for the application of ultra-high dose rate pulsed X-rays in gastrointestinal radiotherapy.Methods:Using the random number table method, 32 C57BL/6J mice were randomly divided into four groups: a sham irradiation group (SHAM), two conventional dose rate groups (CONV0.067 and CONV0.1), and an ultra-high dose rate group (F215), with each group containing eight mice. All groups, except SHAM, received a single 12 Gy abdominal X-ray irradiation at dose rates of 0.067, 0.1, and 215 Gy/s, respectively. At 3 d post-irradiation, histopathological (hematoxylin-eosin staining, HE staining), immunohistochemical, and Western blot analysis were performed to assess the histopathological markers and oxidative stress indicators of intestinal tissues, as well as relevant proteins involved in signaling pathways.Results:At 3 d post-irradiation, mice in all irradiation groups suffered from varying degrees of intestinal tissue degeneration and necrosis, epithelial cell shedding, villus shortening, and crypt loss ( t = 5.75, 8.79, 5.71, P < 0.05). Regarding oxidative stress, at 3 d post-irradiation, mice in the CONV0.067 and CONV0.1 groups showed significantly lower levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), glutathione (GSH), and total antioxidant capacity (T-AOC) compared to those in the F215 group ( t = 7.06-10.64, P < 0.01). In contrast, their malondialdehyde (MDA) levels were significantly elevated ( t = 11.06, 8.31, P < 0.01), with no statistical significance observed between them and mice in the F215 group ( P > 0.05). Immunohistochemical and Western blot analyses indicated that at 3 d post-irradiation, mice in the three irradiation groups exhibited an upward trend in the Nrf2 and HO-1 protein levels and a downward trend in the Keap1 protein level compared to those in the SHAM group. Notably, statistical significance was observed between the F215 group and the two conventional dose rate groups ( t = 4.89-20.95, P < 0.05). These result were consistent with the prior changes in antioxidant markers. Conclusions:Ultra-high-dose-rate X-ray irradiation reduces acute RIII by alleviating oxidative stress and modulating the expression of the Keap1-Nrf2-HO-1 signaling pathway.

Objective:To evaluate the mediating effect of electrocardiographic (ECG) indicators in the association between short-term exposure to fine particulate matter (PM 2.5) and blood pressure and to explore the key PM 2.5 element constituents that produce the mediating effect. Methods:Based on a cross-sectional survey across 10 cities in the Beijing-Tianjin-Hebei region and surrounding areas, PM 2.5 and its element constituents were collected from the nearest air monitoring superstation. Blood pressure and ECG indicators of participants were obtained through physical examinations. A multivariate linear regression was used to evaluate the effect of short-term exposures to PM 2.5 on blood pressure. A mediation analysis was used to identify the mediating effect of ECG indicators in the association between exposure to PM 2.5 and its element constituents and blood pressure. Results:The age of the 1 793 participants was (65.1±13.3) years, and 885 (49.4%) were males. During the study period, the daily mean concentration of PM 2.5 was (70±45) μg/m 3, and the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) were (139±20), (82±11), (101±13), and (57±17) mmHg (1 mmHg=0.133 kPa), respectively. The results of the multivariate linear regression showed that for every 10 μg/m 3 increase in PM 2.5 on the same day (lag 0), DBP increased by 0.15 (95% CI: 0.02-0.28) mmHg, and PP decreased 0.18 (95% CI: 0.36-0.01) mmHg. The exposure to 14 elemental constituents, such as Ga, Co and Se, was associated with an increase in DBP, while the exposure to 17 elemental constituents, such as Cs, Se and Ag, was associated with a decrease in PP. At lag 0, the PM 2.5-induced increase in DBP was mediated by the QRS interval (mediation percentage of 18.98%), and the PM 2.5-induced decrease in PP was mediated by the QT interval (mediation percentage of -6.31%). The exposure to K, Br, Pb, Zn, Ca, Co, Pd, Cu, and As constituents was associated with increases in DBP mediated by prolonged QRS interval. The exposure to Pb, Zn, K, and As constituents was associated with decreases in PP mediated by prolonged QRS interval. Conclusion:ECG indicators such as QRS interval may mediate the association between short-term exposure to PM 2.5 and its element constituents and blood pressure.

Objective To explore the protective effect of miR-374c-5p on hydrogen peroxide(H2O2)-induced apoptosis of human umbilical vein endothelial cells(HUVECs).Methods HUVECs were cultured in vitro and the harvested cells were divided into four groups:control group,H2O2 group,H2O2+miR-374c-5p mimics trans-fection group,and H2O2+miR-374c-5p inhibitor transfection group.Cell activity was assessed by CCK-8 prolifer-ation rate assay,apoptosis was detected by TUNEL staining microscopy.Expression of miR-374c-5p and Fas mRNA by RT-qPCR,and Fas protein in HUVECs by was detected by Western blot.Results Proliferation of HUVECs was significantly inhibited(P＜0.001);H2O2 was significantly increased as compared with the H2O2 in-tervention group(P＜0.001);Proliferation in H2O2+miR-374c-5p inhibitor transfection group was significantly increased as compared to H2O2 intervention group(P＜0.001).Conclusions miR-374c-5p protectes the HUVECs against apoptosis induced by H2O2.

BACKGROUND:One-hole split endoscope as a new type of endoscopic technique is suitable for the treatment of far lateral lumbar disc disease.However,there are few research data on L5/S1,which has a very low incidence of far lateral lumbar disc herniation at home and abroad,and there is no detailed image anatomical data describing the one-hole split endoscope treatment of L5/S1 far lateral lumbar disc herniation. OBJECTIVE:Through the three-dimensional image reconstruction,the bony landmarks were determined to accurately locate the positional relationship between the L5 outlet nerve root,the L5/S1 intervertebral space and other structures.One-hole split endoscope via posterolateral approach was used to accurately,safely and effectively decompress the L5 outlet nerve root and treat the L5/S1 far lateral lumbar disc herniation. METHODS:Twenty-nine patients with L5/S1 unilateral far lateral lumbar disc herniation who met the inclusion and exclusion criteria were selected,including 12 males and 17 females at the age of 48-74 years.The lumbar CT data of the patients were imported into Mimics 21.0 software to reconstruct the three-dimensional lumbar model.Measurement of L5/S1 related parameters:(1)Measurement on the sagittal plane at the intersection(H)of the lower edge of the transverse process and the lateral edge of the isthmus:The vertical distance between H and the upper and lower edges of L5 outlet nerve root(a1,a2);the vertical distance between H and the lower endplate of L5 and the upper endplate of S1(b1,b2);vertical distance from the lower edge of the pedicle from H to L5(c).(2)Horizontal distance between the left and right sides of the sagittal surface where the medial wall of the pedicle was located from H to L5(d).(3)The horizontal distance from H to the left and right side of the sagittal plane where the lateral margin of the dura was located(e).(4)Horizontal distance(f)between the left and right sides of the sagittal plane at the outermost edge of the lower endplate from H to L5.(5)Measurements were made on the sagittal plane where the outermost edge of the lower endplate of L5:The vertical distance between the cross section of H and the upper and lower edges of L5 outlet nerve root(g1,g2);vertical distance(h1,h2)between the transverse section of H and the lower endplate of L5 and the upper endplate of S1,respectively;(6)anteroposterior horizontal distance from H to L5 in the coronal plane where the last edge of the nerve root exits(i);(7)anteroposterior horizontal distance from the highest point of the posterior margin of the sacral wing to the last margin of the inferior endplate of L5 in the coronal plane(j). RESULTS AND CONCLUSION:(1)There was no significant difference in the relevant measurement parameters between men and women(P>0.05).(2)a1,a2,b1,b2,c,d,e,f,h1,h2,g1,g2,i,and j on the affected side were not significantly different from the healthy side(P>0.05).(3)There was no significant difference between a1 and c(P>0.05),indicating that the lower edge of the pedicle was the upper edge of the L5 outlet nerve root;the L5 outlet nerve root was close to the lower edge of the pedicle and ran anterolateral behind the L5 vertebral body,and H was located above the L5 outlet nerve root.(4)With H as the bony marker point,it was not necessary to probe upward or to remove the isthmus,but only to grind part of the bone downward and laterally to reveal the L5 outlet nerve root and vertebral space,and to have enough safe distance to avoid damage to the dural membrane to complete exploration and decompression of the lateral recess and foraminal region.(5)The surgeon could operate in the sagittal plane where the most lateral edge of the L5 inferior endplate was located,and in the"rectangular area"formed by the L5 transverse process and the sacral wing.The closer to the medial and inferior area(Kambin triangle),the safer the operation was.(6)It is suggested that using H as the bony landmark point to locate the L5 outlet nerve root and intervertebral space through one-hole split endoscope via posterolateral approach can achieve accurate,safe and effective decompression of L5/S1 far lateral lumbar disc herniation.

Objective:To explore differences in the radiation-induced intestinal injury in mice exposed to ultra-high dose rate (FLASH) and conventional-dose-rate (CONV) pulsed X-ray irradiation in order to provide evidence for the application of ultra-high dose rate pulsed X-rays in gastrointestinal radiotherapy.Methods:Using the random number table method, 32 C57BL/6J mice were randomly divided into four groups: a sham irradiation group (SHAM), two conventional dose rate groups (CONV0.067 and CONV0.1), and an ultra-high dose rate group (F215), with each group containing eight mice. All groups, except SHAM, received a single 12 Gy abdominal X-ray irradiation at dose rates of 0.067, 0.1, and 215 Gy/s, respectively. At 3 d post-irradiation, histopathological (hematoxylin-eosin staining, HE staining), immunohistochemical, and Western blot analysis were performed to assess the histopathological markers and oxidative stress indicators of intestinal tissues, as well as relevant proteins involved in signaling pathways.Results:At 3 d post-irradiation, mice in all irradiation groups suffered from varying degrees of intestinal tissue degeneration and necrosis, epithelial cell shedding, villus shortening, and crypt loss ( t = 5.75, 8.79, 5.71, P < 0.05). Regarding oxidative stress, at 3 d post-irradiation, mice in the CONV0.067 and CONV0.1 groups showed significantly lower levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), glutathione (GSH), and total antioxidant capacity (T-AOC) compared to those in the F215 group ( t = 7.06-10.64, P < 0.01). In contrast, their malondialdehyde (MDA) levels were significantly elevated ( t = 11.06, 8.31, P < 0.01), with no statistical significance observed between them and mice in the F215 group ( P > 0.05). Immunohistochemical and Western blot analyses indicated that at 3 d post-irradiation, mice in the three irradiation groups exhibited an upward trend in the Nrf2 and HO-1 protein levels and a downward trend in the Keap1 protein level compared to those in the SHAM group. Notably, statistical significance was observed between the F215 group and the two conventional dose rate groups ( t = 4.89-20.95, P < 0.05). These result were consistent with the prior changes in antioxidant markers. Conclusions:Ultra-high-dose-rate X-ray irradiation reduces acute RIII by alleviating oxidative stress and modulating the expression of the Keap1-Nrf2-HO-1 signaling pathway.

Objective:To evaluate the mediating effect of electrocardiographic (ECG) indicators in the association between short-term exposure to fine particulate matter (PM 2.5) and blood pressure and to explore the key PM 2.5 element constituents that produce the mediating effect. Methods:Based on a cross-sectional survey across 10 cities in the Beijing-Tianjin-Hebei region and surrounding areas, PM 2.5 and its element constituents were collected from the nearest air monitoring superstation. Blood pressure and ECG indicators of participants were obtained through physical examinations. A multivariate linear regression was used to evaluate the effect of short-term exposures to PM 2.5 on blood pressure. A mediation analysis was used to identify the mediating effect of ECG indicators in the association between exposure to PM 2.5 and its element constituents and blood pressure. Results:The age of the 1 793 participants was (65.1±13.3) years, and 885 (49.4%) were males. During the study period, the daily mean concentration of PM 2.5 was (70±45) μg/m 3, and the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) were (139±20), (82±11), (101±13), and (57±17) mmHg (1 mmHg=0.133 kPa), respectively. The results of the multivariate linear regression showed that for every 10 μg/m 3 increase in PM 2.5 on the same day (lag 0), DBP increased by 0.15 (95% CI: 0.02-0.28) mmHg, and PP decreased 0.18 (95% CI: 0.36-0.01) mmHg. The exposure to 14 elemental constituents, such as Ga, Co and Se, was associated with an increase in DBP, while the exposure to 17 elemental constituents, such as Cs, Se and Ag, was associated with a decrease in PP. At lag 0, the PM 2.5-induced increase in DBP was mediated by the QRS interval (mediation percentage of 18.98%), and the PM 2.5-induced decrease in PP was mediated by the QT interval (mediation percentage of -6.31%). The exposure to K, Br, Pb, Zn, Ca, Co, Pd, Cu, and As constituents was associated with increases in DBP mediated by prolonged QRS interval. The exposure to Pb, Zn, K, and As constituents was associated with decreases in PP mediated by prolonged QRS interval. Conclusion:ECG indicators such as QRS interval may mediate the association between short-term exposure to PM 2.5 and its element constituents and blood pressure.

ObjectiveTo investigate the possible mechanism of Hewei Anshen Formula （和胃安神方） in the treatment of insomnia. MethodsSixty male SD rats were randomly divided into the normal group， the model group， the eszopiclone group and the low-， medium- and high-dose Hewei Anshen Formula groups. The insomnia model was constructed by intraperitoneal injection of p-chlorophenylalanine （PCPA） for 2 days in all groups except the normal group. After successful modelling， the eszopiclone group was given 0.33 mg/（kg·d） eszopiclone aqueous solution by gavage， the low-， medium- and high-dose Hewei Anshen Formula groups were given 10 ml/kg of Hewei Anshen Formula with a concentration of 1， 2 and 4 g/ml， respectively， and the rats in the normal group and the model group were given 10 ml/kg of saline by gavage， once a day for 7 consecutive days. The general condition of the rats was observed during the experiment， and the body mass of the rats was measured every day after medication administration. The following day after the last medication administration， pentobarbital sodium co-test was used to observe the sleep condition， and the sleep latency and sleep duration were recorded； immunohistochemistry and Western blot were used to detect the expression of hypothalamic clock rhythm regulating protein （CLOCK） and brain and muscle aromatic hydrocarbon receptor nuclear transporter-like protein 1 （BMAL1） in the rats. ResultsThe body mass of rats in the model group was lower than that of rats in the normal group at all time points （P＜0.01）； compared with the same time in the eszopiclone group， the body mass of rats in the low-dose Hewei Anshen Formula group was elevated on the 5th， 6th and 7th days of medication administration （P＜0.05）. Compared with the normal group， the sleep duration of rats in the model group was shortened （P＜0.01）； compared with the model group， the sleep duration of rats in each dosage group increased （P＜0.01）， and the difference between the high-dose Hewei Anshen Formula group and the eszopiclone group showed no statistically significant （P＞0.05）， while the sleep duration of the low- and medium-dose Hewei Anshen Formula groups were shorterned than the eszopiclone group （P＜0.01）. The difference in sleep latency showed no statistically significant among each group （P＞0.05）. The results of both immunohistochemistry and Western blotting showed that the expression of CLOCK and BMAL1 in the hypothalamus of rats in the model group was significantly reduced compared with that in the normal group （P＜0.01）； the expression of CLOCK and BMAL1 in the hypothalamus of rats in the low- and high-dose Hewei Anshen Formula groups increased than that in the model group （P＜0.05 or P＜0.01）. ConclusionHewei Anshen Formula can improve insomnia in model rats， and its mechanism of action may be related to the up-regulation of the expression of the hypothalamic biological clock genes CLOCK and BMAL1 protein.

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.

BACKGROUND:One-hole split endoscope technique has been widely used in the treatment of lumbar degenerative diseases,but there is no relevant literature on the safety analysis of this technique in the treatment of upper lumbar disc herniation. OBJECTIVE:To observe the position relationship of nerve roots,intervertebral space and bone landmarks in the upper lumbar spine by three-dimensional lumbar CT reconstruction technology,and to provide a basis for the clinical operation of one-hole split endoscope surgery. METHODS:Twenty-six patients with upper lumbar disc herniation underwent a lumbar CT scan.Mimics 17.0 software was imported to measure the related imaging parameters of L1/2 to L3/4 segments:(1)Measurement of vertical distance:In coronal view,the distance(a)from the intersection point of the medial facet of the superior articular process and the superior endplate(N)to the apex of the articular process(S);in the coronal view,the distance(b)from the sagittal intersection(M)of N and the inferior endplate to the apex of the inferior articular process(X).(2)Measured horizontal distance:the distance(c)between the cross-section of N and the lower edge of the outlet nerve root(N2);distance(d)between the cross-section of N and the intersection point of neural tissue(N1);N1 to N2 distance(e);distance(f)between the cross-section of M and the lateral edge of the nerve tissue(M1);M to M cross-section and exit nerve root intersection(M2)distance(g);distance(h)from M1 to M2;distance(i)from M2 to N1;distance(j)from the posterior edge of the articular surface(R)to M2 in sagittal view of the superior articular process. RESULTS AND CONCLUSION:(1)With the decrease of the segment,the distances a and b gradually increased,and the distance j gradually decreased.There was no significant difference between L1/2 and L2/3 segments(P>0.05).(2)With the decrease of the segment,distance d first decreased and then increased;distance f gradually decreased;distances c,e,g,h and i gradually increased;and there was no significant difference between L2/3 and L3/4 segments(P>0.05).(3)Distance i was the shortest distance without pulling nerve roots in the natural state,and the area of the safety zone was between four points M1,M2,N1,and N2.The bone was removed to the upper and lower endplates by biting the bone downward and upward through S and X,respectively,to expose the intervertebral space,and the window of distance g to M2 could be opened outward to avoid injury of the outlet nerve roots.(4)In conclusion,the upper lumbar vertebrae have unique anatomical characteristics.Based on the relevant measurements of nerve roots,spinal dura and intervertebral space,the parameters of the one-hole split endoscope technique are more accurate and safe during operation.

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.