Objective:To conduct a comparative analysis of the radiation damage to zebrafish embryos and the associated biological mechanism after ultra-high dose rate (FLASH) and conventional dose rate irradiation.Methods:Zebrafish embryos at 4 h post-fertilization were exposed to conventional and FLASH irradiation (9 MeV electron beam). The mortality and hatchability of zebrafish after radiation exposure were recorded. Larvae at 96 h post-irradiation underwent morphological scoring, testing of reactive oxygen species (ROS) levels, and analysis of changes in oxidative stress indicators.Results:Electron beam irradiation at doses of 2-12 Gy exerted subtle effects on the mortality and hatchability of zebrafish embryos. However, single high-dose irradiation (&ge; 6 Gy) could lead to developmental malformation of larvae, with conventional irradiation showing the most significant effects ( t = 0.87-9.75, P < 0.05). In contrast, after FLASH irradiation (&ge; 6 Gy), the ROS levels in zebrafish and its oxidative stress indicators including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were significantly reduced ( t = 0.42-15.19, P < 0.05). There was no statistically significant difference in ROS levels in incubating solutions after conventional and FLASH irradiation ( P > 0.05). Conclusions:Compared to conventional irradiation, FLASH irradiation can reduce radiation damage to zebrafish embryos, and this is in a dose-dependent manner. The two irradiation modes lead to different oxidative stress levels in zebrafish, which might be a significant factor in the reduction of radiation damage with FLASH irradiation.

OBJECTIVE To analyze the medication rules of Professor Shen Hong's TCM treatment of Crohn's disease(CD)and form the core prescription using data mining technology,and to retrospectively analyze the clinical efficacy of the core prescription com-bined with ustekinumab in the treatment of CD with dampness-stasis interjunction syndrome.METHODS CD patient outpatient re-cords treated by Professor Shen Hong were collected,and the property,taste and meridian tropism,drug frequency,association rules and complex network analysis of drugs were summarized,in order to sort out the core prescription.62 cases of active ileocolic CD with TCM syndrome of dampness-stasis interjunction were retrospectively included,with 32 patients in the control group and 30 patients in the observation group.The control group was only given ustekinumab,and the observation group was given the core prescription oral treatment on the basis of the treatment in the control group.The observation course was 8 weeks.The improvement of clinical symptoms and changes of inflammatory indicators[erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),fecal calprotectin(FC)]before and after treatment were analyzed.RESULTS The core prescription was obtained by combining drug frequency,association rules and cluster analysis,which included scutellaria baicalensis,radix sophorae flavescentis,smilax glabr,angelicae sinensis,angeli-ca dahurica,atractylodes,tangerine peel,paeoniae alba,saposhnikovia,coicis semen,yam,nidus vespae,cynanchum paniculatum,radix aucklandiae,massa medicata fermentata,glycyrrhiza uralensis,and was named Qingchang Tongluo Formula by Professor Shen Hong.Retrospective clinical research showed that after treatment,the TCM syndrome scores of the 2 groups of patients were significant-ly reduced(P<0.05,P<0.01),the total TCM syndrome score of the observation group was better than that of the control group(P<0.01),and the TCM clinical significant recovery rate of the observation group was better than the control group(P<0.05);the ESR,CRP,and FC levels of patients in both groups were significantly reduced(P<0.01),and the improvement in the observation group was better than that in the control group(P<0.05).No obvious drug-related adverse reactions were found in the 2 groups of patients during treatment.CONCLUSION Professor Shen Hong distinguishes the treatment of CD by clearing heat and removing blood stasis,strengthening spleen and healing lesions.The core prescription Qingchang Tongluo prescription,combined with ustekinumab can im-prove clinical symptoms and inflammation levels.It can be used clinically as an effective treatment for ileocolonic Crohn's disease with dampness-stasis interjunction syndrome.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective To obtain the metabolomics characteristics of patients in the active stage of ulcerative colitis(UC)with syndrome of dampness-heat in large intestine through non-target metabolomics technology,and to provide a basis for promoting the theoretical system of traditional Chinese medicine(TCM)syndrome differentiation of disease syndrome combination and micro-macro combinations.Methods Non-target metabolomics technology was used to detect the serum samples from 159 patients in the active stage of UC(81 cases with syndrome of dampness-heat in large intestine and 78 cases with syndrome of non-dampness-heat in large intestine)and 30 healthy volunteers.The orthogonal partial sample least squares discriminant analysis model was constructed to screen metabolites with significant changes among groups.The variable importance in projection&ge;1,P<0.05,and fold change(FC)>1.20 or FC<0.83 were used as the criteria for the screening of differential metabolites.The Kyoto Encyclopedia of Genes and Genomes(KEGG)was used to annotate differential metabolites,and MetaboAnalyst software was used for pathway analysis.Results Between patients in active stage of UC with syndrome of dampness-heat in large intestine and syndrome of non-dampness-heat in large intestine,a total of 99 differential metabolites were screened in the positive ion mode,of which 48 were upregulated and 51 were downregulated.In the negative ion mode,a total of 38 differential metabolites were screened,of which 19 were upregulated and 19 were downregulated.The KEGG enrichment analysis showed that there were 21 metabolic pathways,and the pathway analysis showed that there were mainly four metabolic pathways involved in tryptophan metabolism,sphingolipid metabolism,glycerophospholipid metabolism,and pyrimidine metabolism.Conclusion Patients in the active stage of UC with syndrome of dampness-heat in large intestine have abnormal metabolic pathways,which can provide a basis for TCM syndrome differentiation and treatment for UC with syndrome of dampness-heat in large intestine.

FLASH radiotherapy (FLASH-RT) has garnered considerable attention globally in recent years. Compared to conventional radiotherapy, FLASH-RT can deliver the total radiation dose to the target volume in an extremely short time, reducing the radiation-induced damage to normal tissue while maintaining similar anti-tumor effects. FLASH-RT has been in the clinical trial stage, with several clinical research result being reported. Based on the collected global clinical research result of FLASH-RT in recent years, this study systematically reviewed FLASH-RT′s safety, radiation-related side effects, treatment efficacy, opportunities, and challenges in clinical trials.

Objective:To investigate the accuracy of magnetic resonance imaging (MRI) cine sequences in determining the range of tumor motion in radiotherapy, providing a basis for the precise delineation of the target volume in motion for radiation therapy.Methods:A modified chest motion phantom was placed in a MRI scanner, and a water-filled sphere was used to simulate a tumor. True fast imaging with steady precession (TrueFISP) MRI cine sequences from Siemens were used to capture the two-dimensional motion images of the simulated tumor. The phantom experiments were divided into three modes: head-foot motion mode, rotation motion mode, and actual respiratory waveform mode. In the head-foot motion mode, respiratory motion period (3, 4, 5, 6, 7 and 8 s), amplitude (5, 10 and 15 mm), and respiratory waveform of the simulated tumor (sin and cos4) were set, resulting in a total of 36 motion combinations. In the rotation motion mode, a cos4 waveform was used for respiration, with respiratory periods of 3, 4, 5, 6, 7 and 8 s, head-foot motion set amplitudes of 5, 10 and 15 mm, and anterior-posterior (AP) and left-right (LR) motion set amplitudes in three combinations ([2.5, 2.5] mm, [2.5, 5.0] mm, [5.0, 5.0] mm), resulting in a total of 54 motion combinations. In the actual respiratory waveform mode, respiratory waveforms of 5 randomly selected patients from Affiliated Cancer Hospital of Zhengzhou University were obtained. Under each motion combination, TrueFISP cine images (30 frames, with an acquisition time of 11 s per frame) were obtained. The code was used to automatically identify the two-dimensional coordinates of the center of the simulated tumor in each image, and sin and cos4 functions were separately employed to fit the tumor position in the motion direction, thereby obtaining the fitted motion period and amplitude. The difference between the maximum and minimum values of the tumor's center coordinates in the head-to-foot direction is taken as the range of movement, referred to as the calculated amplitude. For the actual respiratory waveform, the distance between the measured maximum and minimum positions is used to calculate the amplitude.Results:In the head-foot motion mode, the fitted amplitudes of both sin and cos4 waveforms deviated from the set amplitudes by 0-0.51 mm, with relative deviations of 0%-4.2%. The deviation range between the calculated amplitudes and the set amplitudes of the two waveforms were 0.08-0.94 mm, with relative deviations of 1.1%-6.3%. In the rotation motion mode, the fitted amplitudes deviated from the set amplitudes by 0-0.61 mm, with relative deviations of 0%-6.2%. And the deviation range between the calculated amplitudes and the set amplitudes were 0.16-0.94 mm, with relative deviations of 0%-6.3%. In the actual respiratory waveform motion mode, the deviation range between the calculated amplitudes and the set amplitudes were 0.10-0.48 mm, with relative deviations of 2.2%-8.6%.Conclusion:TrueFISP cine sequences show minimal deviations in determining the range of tumor head-foot motion and effectively captures the tumor's movement state, thereby providing important support for the precise definition of the tumor movement target area during radiotherapy .

Objective To compare the image quality of three high-resolution dynamic MRI methods for evaluating the motion of temporomandibular joint disc and condyle. Methods Twenty-five patients with suspected temporomandibular joint disorders were examined by single-shot fast spin-echo (SSFSE),fast imaging employing steady-state acquisition (FIESTA),and spoiled gradient echo (SPGR) on the oblique sagittal position.Two radiologists performed subjective and objective evaluation on the images with double-blind method.The subjective evaluation included the signal intensity of mandibular condyle,articular disc,soft tissue around articular disc,and lateral pterygoid muscle,the contrast between articular disc and condyle,the contrast between articular disc and surrounding soft tissue,condylar motion,and disc movement.The objective evaluation indexes included image signal intensity,signal-to-noise ratio (SNR),and contrast-to-noise ratio (CNR).The subjective and objective indexes of the image quality were compared between the three sequences. Results The SSFSE sequence had lower signal intensity of articular disc and higher signal intensity of condyle and surrounding soft tissue than FIESTA and SPGR sequences (all P<0.001).The SPGR sequence showed higher signal intensity of lateral pterygoid muscle than the SSFSE and FIESTA sequences (P=0.017,P<0.001).Among the three sequences,SSFSE sequence showed the clearest articular disc structure (χ²=41.952,P<0.001),the strongest contrast between articular disc and condyle (χ²=35.379,P<0.001),the strongest contrast between articular disc and surrounding soft tissue (χ²=27.324,P<0.001),and the clearest movement of articular disc (χ²=44.655,P<0.001).SSFSE and FIESTA sequences showed higher proportion of disc displacement and reduction than SPGR sequence (all P<0.001).The CNR (χ²=21.400,P<0.001),SNR (χ²=34.880,P<0.001),and condyle signal intensity (F=337.151,P<0.001) demonstrated differences among SSFSE,FIESTA,and SPGR sequences.The CNR of SSFSE sequence was higher than that of FIESTA sequence (P<0.001),while it had no significant difference between SSFSE and SPGR sequences (P=0.472).In addition,the SSFSE sequence had higher SNR and signal intensity than FIESTA and SPGR sequences (all P<0.001). Conclusion The best image quality can be observed from SSFSE sequence where both the structure and movement of temporomandibular joint are well displayed.Therefore,SSFSE is preferred for the examination of temporomandibular joint movement.
Humans ; Temporomandibular Joint/diagnostic imaging* ; Motion ; Plastic Surgery Procedures

Objective To investigate the neuroprotective effect and mechanism of cerebrotein hydrolysate- (CH-) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinson's disease (PD) mice. Methods Totally 36 healthy male C57BL/6 mice were randomly divided into control group(Ctrl), model group(MPTP) and CH- group. MPTP was used to induce PD model in mice, and CH- was injected intraperitoneally for intervention. The behavioral function of mice was detected by pole test, the expression of tyrosine hydroxylase (TH) was detected by immunohistochemistry, and the composition and diversity of intestinal microflora were detected by gene sequencing and bioinformatics analysis. Results Compared with the control group, MPTP induced behavioral deficits in PD mice after modeling (P<0.05), after CH- treatment, the behavioral defects of PD mice were improved compared with MPTP group (P<0.05). Immunohistochemical result showed that MPTP decreased the expression of the rate-limiting enzyme TH in dopamine synthesis, and increased the expression of TH after CH- treatment. The result of microbial diversity showed that the intestinal microflora diversity of mice decreased after MPTP treatment (P<0.05). At the “phylum” level, the number of Epsilonbacteraeota and Deferribacteres decreased sharply, while the number of Verrucomicrobia increased significantly. At the level of “family”, the number of Desulfovibrionaceae, Lachnospiraceae, Helicobacteraceae and Rikenellaceae decreased, while the number of Akkermansiaceae and Erysipelotrichaceae increased, suggesting that the original homeostasis of intestinal microflora was destroyed. After CH- treatment, the number of intestinal microflora tended to be normal, which reduced the abundance of pathogenic microbiota and increased the relative abundance of beneficial bacteria. Conclusion CH- can improve the composition of intestinal microflora and the behavioral function of PD mice by decreasing the abundance of pathogenic microbiota and increasing the relative abundance of beneficial bacteria.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Objective:To compare the effects on DNA strand break induced by ultra-high dose rate (FLASH) electron beam and conventional irradiation, and investigate whether FLASH effect was correlated with a reduction of radiation response.Methods:Aqueous pBR322 plasmid was treated with FLASH (125 Gy/s) and conventional irradiation (0.05 Gy/s) under physioxia (4% O 2) and normoxia (21% O 2). Open circle DNA and linear DNA were detected by agarose gel electrophoresis, and the plasmid DNA damage was quantified with an established mathematical model to calculate the relative biological effect (RBE) of DNA damage. In some experiments, Samwirin A (SW) was applied to scavenge free radicals generated by ionizing radiation. Results:Under physioxia, the yields of DNA strand breakage induced by both FLASH and conventional irradiation had a dose-dependent manner. FLASH irradiation could significantly decrease radiation-induced linear DNA compared with conventional irradiation ( t=5.28, 5.79, 7.01, 7.66, P<0.05). However, when the aqueous plasmid was pretreated with SW, there was no difference of DNA strand breakage between FLASH and conventional irradiation ( P>0.05). Both of the yields of open circle DNA and linear DNA had no difference caused by FLASH and conventional radiotherapy at normoxia, but were significantly higher than those under physioxia. In addition, the yields of linear DNA and open circle DNA induced by FLASH irradiation per Gy were (2.78±0.03) and (1.85±0.17) times higher than those of conventional irradiation, respectively. Conclusions:FLASH irradiation attenuated radiation-induced DNA damage since a low production yield of free radical in comparison with conventional irradiation, and hence the FLASH effect was correlated with oxygen content.