Objective:To investigate the differential effects of proton FLASH irradiation and conventional dose rate (CONV) irradiation on human normal liver cells WRL68 and human hepatocellular carcinoma cells HepG2.Methods:Using a 100 MeV high-current proton cyclotron accelerator, WRL68 and HepG2 cells were subjected to CONV (0.8 Gy/min) and FLASH (40 Gy/s) irradiation with 4 Gy protons. After irradiation, changes in cell proliferation, apoptosis, and cell cycle arrest were detected at different time points. Additionally, transcriptome sequencing was employed to analyze alterations in the gene expression profiles of the two cell lines.Results:For WRL68 cells, compared with CONV irradiation, proton FLASH irradiation enhanced cell proliferative activity ( t=10.18-16.67, P<0.05), reduced the apoptotic rate ( t=3.21-8.30, P<0.05), and decreased the proportion of cells arrested in the G 2 phase at the same time points ( t=34.08-65.16, P<0.05). In contrast, for HepG2 cells, proton FLASH irradiation significantly inhibited cell proliferation ( t=2.57-9.39, P<0.05), increased the apoptotic rate ( t=3.25-66.70, P<0.05), and similarly induced cell cycle arrest predominantly in the G 2 phase ( t=10.87-27.47, P<0.05). Transcriptome sequencing identified 906 differentially expressed genes (DEGs) between the FLASH group and the CONV group in WRL68 cells, and 1 243 DEGs were detected in HepG2 cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these DEGs suggested that cellular adhesion and oxygen effect may serve as crucial microscopic mechanisms underlying FLASH radiotherapy. Conclusions:Under proton FLASH irradiation, the radiation-induced damage to human normal liver cells was significantly alleviated, whereas the damage to hepatocellular carcinoma cells was aggravated. The identified DEGs are involved in multiple radiobiological functional pathways.

Objective To carry out a joint simulation exercise of tabletop deduction for the staff performing overseas medical services on hospital ships,so as to improve the infection prevention and control.Methods Sixty mission members were selected by convenience sampling to carry out joint simulation drills for tabletop deduction.The effects of the drills were assessed by the survey on the satisfaction and participation of mission members,before-and-after control study,and mission execution.Results Overseas medical service tasks were successfully completed through the desktop-propelled joint simulation drills.The total score of response for infectious emergencies,prevention score,preparedness score,and rescue score after training were higher than those before training(P<0.05).There were high degrees of participation and satisfaction in the drills(≥4.5 points).Conclusion The tabletop deduction and simulation exercise achieve good results in the infection prevention and control of hospital ships.The scheme of tabletop deduction combined with simulation drills will be optimized to continuously improve the infection prevention and control of hospital ships.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

AIM:This study explores whether curcumin(Cur)promotes mitophagy to attenuate nonalcoholic steatohepatitis(NASH)in mice,as well as the possible molecular mechanisms involved.METHODS:A high-fat and high-cholesterol diet was used to replicate the NASH mouse model.Thirty-two male C57BL/6J mice were randomly divided into normal control(NC)group,high-fat and high-cholesterol model(M)group,M+low-dose Cur(Cur-L)group,and M+high-dose Cur(Cur-H)group,with 8 mice in each group.The weight of 8 mice in each group was recorded weekly.After feeding for 18 weeks,the serum and liver of mice were collected.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL-C),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and tumor necrosis factors-α(TNF-α)were measured.Liver index was calculated,and steatosis,inflammation,and fibrosis of the liver were observed by HE and Masson staining.Western blot analysis was performed to detect the protein expression of mi-tophagy-related protein,TNF-α and α-SMA in the liver.(2)HepG2 cells were treated with oleic acid and cholesterol to replicate the hepatocyte injury model,which was divided into NC group,Cur group,M group,and M+Cur group.Small interfering RNA for PTEN-induced kinase 1(PINK1)knockdown was used to explore the relationship between PINK1-me-diated mitophagy and NASH.Compound C(CC)was used to inhibit AMP-activated protein kinase(AMPK)to explore the effect of the AMPK/silent information regulator 1(Sirt1)pathway on mitophagy.The lipid droplets of HepG2 cells were ob-served by oil red O staining,and the levels of TC,TG,LDL-C,ALT,and AST in cell suspension were detected.RE-SULTS:(1)Compared with M group,treatment with Cur significantly reduced the body weight,liver coefficient,and se-rum levels of TC,TG,LDL-C,ALT,AST,and TNF-α in NASH mice,while the steatosis and fibrosis in the liver were improved(P<0.05).(2)Different concentrations of Cur could increase or decrease the expression of mitophagy-related proteins in HepG2 cells in a concentration gradient.Compared with the M group,Cur reduced lipid droplets and de-creased TC,TG,LDL-C,ALT,and AST levels(P<0.05).(3)Compared with the NC group,the expression levels of mi-tophagy-related proteins in the liver of mice in the M group decreased,and the expression levels of TNF-α and α-SMA pro-teins increased.Different concentrations of Cur intervention promoted the increase of mitophagy-related proteins and the decrease of TNF-α and α-SMA proteins(P<0.05).(4)After Cur intervention,the expression levels of mitophagy-related proteins increased and the expression levels of in TNF-α and α-SMA levels decreased in HepG2 cells induced by oleic acid and cholesterol(P<0.05).(5)Compared with M group,oleic-acidand cholesterol-induced mitophagy function in HepG2 cells was decreased after PINK1 knockdown(P<0.05).After CC inhibited AMPK,Cur increased the expression of p-AMPK(P<0.01),Sirt1(P<0.01),peroxisome proliferator-activated receptor γ coactivator-1α(P>0.05),PINK1(P<0.01)and parkin(P<0.01)proteins to some extent.CONCLUSION:Treatment with Cur attenuates liver injury in NASH mice and reduces lipid accumulation in HepG2 cells induced by oleic acid and cholesterol,and the mechanism may be related to promotion of mitophagy,which may involve the AMPK/Sirt1 signaling pathway.

Objective:To investigate the differential effects of proton FLASH irradiation and conventional dose rate (CONV) irradiation on human normal liver cells WRL68 and human hepatocellular carcinoma cells HepG2.Methods:Using a 100 MeV high-current proton cyclotron accelerator, WRL68 and HepG2 cells were subjected to CONV (0.8 Gy/min) and FLASH (40 Gy/s) irradiation with 4 Gy protons. After irradiation, changes in cell proliferation, apoptosis, and cell cycle arrest were detected at different time points. Additionally, transcriptome sequencing was employed to analyze alterations in the gene expression profiles of the two cell lines.Results:For WRL68 cells, compared with CONV irradiation, proton FLASH irradiation enhanced cell proliferative activity ( t=10.18-16.67, P<0.05), reduced the apoptotic rate ( t=3.21-8.30, P<0.05), and decreased the proportion of cells arrested in the G 2 phase at the same time points ( t=34.08-65.16, P<0.05). In contrast, for HepG2 cells, proton FLASH irradiation significantly inhibited cell proliferation ( t=2.57-9.39, P<0.05), increased the apoptotic rate ( t=3.25-66.70, P<0.05), and similarly induced cell cycle arrest predominantly in the G 2 phase ( t=10.87-27.47, P<0.05). Transcriptome sequencing identified 906 differentially expressed genes (DEGs) between the FLASH group and the CONV group in WRL68 cells, and 1 243 DEGs were detected in HepG2 cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these DEGs suggested that cellular adhesion and oxygen effect may serve as crucial microscopic mechanisms underlying FLASH radiotherapy. Conclusions:Under proton FLASH irradiation, the radiation-induced damage to human normal liver cells was significantly alleviated, whereas the damage to hepatocellular carcinoma cells was aggravated. The identified DEGs are involved in multiple radiobiological functional pathways.

AIM:This study explores whether curcumin(Cur)promotes mitophagy to attenuate nonalcoholic steatohepatitis(NASH)in mice,as well as the possible molecular mechanisms involved.METHODS:A high-fat and high-cholesterol diet was used to replicate the NASH mouse model.Thirty-two male C57BL/6J mice were randomly divided into normal control(NC)group,high-fat and high-cholesterol model(M)group,M+low-dose Cur(Cur-L)group,and M+high-dose Cur(Cur-H)group,with 8 mice in each group.The weight of 8 mice in each group was recorded weekly.After feeding for 18 weeks,the serum and liver of mice were collected.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL-C),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and tumor necrosis factors-α(TNF-α)were measured.Liver index was calculated,and steatosis,inflammation,and fibrosis of the liver were observed by HE and Masson staining.Western blot analysis was performed to detect the protein expression of mi-tophagy-related protein,TNF-α and α-SMA in the liver.(2)HepG2 cells were treated with oleic acid and cholesterol to replicate the hepatocyte injury model,which was divided into NC group,Cur group,M group,and M+Cur group.Small interfering RNA for PTEN-induced kinase 1(PINK1)knockdown was used to explore the relationship between PINK1-me-diated mitophagy and NASH.Compound C(CC)was used to inhibit AMP-activated protein kinase(AMPK)to explore the effect of the AMPK/silent information regulator 1(Sirt1)pathway on mitophagy.The lipid droplets of HepG2 cells were ob-served by oil red O staining,and the levels of TC,TG,LDL-C,ALT,and AST in cell suspension were detected.RE-SULTS:(1)Compared with M group,treatment with Cur significantly reduced the body weight,liver coefficient,and se-rum levels of TC,TG,LDL-C,ALT,AST,and TNF-α in NASH mice,while the steatosis and fibrosis in the liver were improved(P<0.05).(2)Different concentrations of Cur could increase or decrease the expression of mitophagy-related proteins in HepG2 cells in a concentration gradient.Compared with the M group,Cur reduced lipid droplets and de-creased TC,TG,LDL-C,ALT,and AST levels(P<0.05).(3)Compared with the NC group,the expression levels of mi-tophagy-related proteins in the liver of mice in the M group decreased,and the expression levels of TNF-α and α-SMA pro-teins increased.Different concentrations of Cur intervention promoted the increase of mitophagy-related proteins and the decrease of TNF-α and α-SMA proteins(P<0.05).(4)After Cur intervention,the expression levels of mitophagy-related proteins increased and the expression levels of in TNF-α and α-SMA levels decreased in HepG2 cells induced by oleic acid and cholesterol(P<0.05).(5)Compared with M group,oleic-acidand cholesterol-induced mitophagy function in HepG2 cells was decreased after PINK1 knockdown(P<0.05).After CC inhibited AMPK,Cur increased the expression of p-AMPK(P<0.01),Sirt1(P<0.01),peroxisome proliferator-activated receptor γ coactivator-1α(P>0.05),PINK1(P<0.01)and parkin(P<0.01)proteins to some extent.CONCLUSION:Treatment with Cur attenuates liver injury in NASH mice and reduces lipid accumulation in HepG2 cells induced by oleic acid and cholesterol,and the mechanism may be related to promotion of mitophagy,which may involve the AMPK/Sirt1 signaling pathway.

Objective:To compare image quality and diagnostic parameters of whole-brain CT perfusion scans under different scanning conditions and assess the utility of deep learning image reconstruction algorithm (DLIR) in reducing tube current during low-dose scans.Methods:Method A total of 105 patients with suspected acute ischemic stroke (AIS) were prospectively enrolled in the First Affiliated Hospital of Zhengzhou University from March, 2022 to March, 203 and their baseline information was recorded. All patients underwent head non-contrast CT and CT perfusion (CTP) examinations. CTP scanning was performed at 80 kV in two groups with the tube current of 150 mA (regular dose) and 100 mA (low dose), respectively. The CTP images of 150 mA group were reconstructed using filtered back-projection algorithm as well as adaptive statistical iterative reconstruction-V (ASIR-V) at 40% and 80% strength levels, which were denoted as groups A-C. The CTP images of 100 mA group were reconstructed using ASIR-V80%, DLIR-M, and DLIR-H, which were denoted as groups D-F. Clinical baseline characteristics and radiation doses were compared between the two groups under different scanning conditions. Furthermore, we assessed the subjective and objective image quality, conventional perfusion parameters, and abnormal perfusion parameters of AIS patients across the six groups of reconstructed CTP images.Results:Under the scanning conditions of 150 mA and 100 mA, 47 and 48 patients were diagnosed with AIS, respectively. There were no significant differences in the baseline characteristics between the two groups. However, there was a significant difference in the mean effective radiation dose (5.71 mSv vs. 3.80 mSv, t = 2 768.30, P < 0.001). The standard deviation (SD) of noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of gray matter (GM) and white matter (WM) were significantly different among the six groups of reconstructed images ( F = 40.58-212.13, P < 0.001). In GM, the SD values in groups C, D, and F were lower than those in other groups ( P < 0.05), and the SNR values in groups C and F were higher than those in other groups ( P < 0.05). In WM, the SD and SNR values in groups C and F were significantly different from those in other groups ( P < 0.05). Additionally, CNR values in groups C and F were higher than those in other groups ( P < 0.05). There was no significant difference in subjective scores among groups B, C, and F ( P > 0.05). Regarding perfusion parameters in the brain GM, groups D and E had lower cerebral blood volume (CBV) values compared to groups A to C ( P < 0.05), and group F had lower CBV values than group B ( P < 0.05). In the brain WM, group D had consistently lower mean transit time (MTT) values compared to the other groups ( P < 0.05). Notably, there were no significant differences in AIS lesion detection rates and relevant diagnostic parameters across the six image groups. Conclusions:Low-tube current CTP scan combined with the DLIR-H algorithm can enhance image quality without affecting perfusion parameters such as CBV and MTT, while reducing radiation dose by 30%. This algorithm can be routinely applied in brain CTP examinations.

Objective With the complex evolution of the social system,patients experience varying degrees of delay in obtaining medical and health services under the combined drive of internal and external environment.In order to alleviate the dilemma of seeking medical treatment in crisis situations,it analyzes the causes of the public's use behavior of Internet medical and health services after delayed medical treatment and the ways to improve it.Methods It employs the method of QCA analysis to explore the crisis management strategies adopted by 183 public.Based on Anderson medical treatment model as the theoretical guidance,conditional variables were constructed.Through deductive logic,it analyzes the complex linkage effect of seven variables,including accessibility level,traumatic life events,panic mood and satisfaction with Internet medical use,on the use of Internet medical services.Results it found that panic has a decisive role in promoting the public's use of Internet medical services.Five behavioural models of Internet medical use are proposed to reveal the potential driving mechanism of the public's adoption of Internet medical strategies.Conclusion By analyzing the synergistic effects between variables,it proposes comprehensive strategies,providing a new perspective for public health emergency management,and offering empirical evidence for policymakers to optimize smart medical services.

Objective With the complex evolution of the social system,patients experience varying degrees of delay in obtaining medical and health services under the combined drive of internal and external environment.In order to alleviate the dilemma of seeking medical treatment in crisis situations,it analyzes the causes of the public's use behavior of Internet medical and health services after delayed medical treatment and the ways to improve it.Methods It employs the method of QCA analysis to explore the crisis management strategies adopted by 183 public.Based on Anderson medical treatment model as the theoretical guidance,conditional variables were constructed.Through deductive logic,it analyzes the complex linkage effect of seven variables,including accessibility level,traumatic life events,panic mood and satisfaction with Internet medical use,on the use of Internet medical services.Results it found that panic has a decisive role in promoting the public's use of Internet medical services.Five behavioural models of Internet medical use are proposed to reveal the potential driving mechanism of the public's adoption of Internet medical strategies.Conclusion By analyzing the synergistic effects between variables,it proposes comprehensive strategies,providing a new perspective for public health emergency management,and offering empirical evidence for policymakers to optimize smart medical services.