In proton therapy,prompt gamma-ray imaging is considered as one of the most promising methods for assessing proton beam range.Prompt gamma-ray imaging detector evaluates the proton beam range based on the prompt gamma-ray distribution obtained by the prompt gamma-ray imaging system,which enables high-precision measurement of the proton beam range.Herein a proton beam range verification algorithm is designed for the newly developed prototype of the range verification detector(pixelated prompt gamma-ray imaging detector),which verifies the range estimation accuracy of the prototype for different phantoms and different energies of homogeneous media through Monte Carlo simulation.The results show that the accuracy of the proton beam range verification algorithm is within 0.5 mm of the safety margin error of the Bragg peak,and the measurement accuracy is significantly improved with the increase of the number of protons,indicating that the prototype algorithm is feasible for proton beam range verification.

AIM:This study aims to investigate whether vitamin E succinate(VES)induces autophagy in hu-man gastric cancer cells through the promotion of mitochondria-associated endoplasmic reticulum membranes(MAMs).METHODS:Human gastric cancer cell lines MKN28 and MKN45 were cultured in vitro.Cell viability was assessed us-ing the CCK8 assay,and two cell growth curves were plotted to determine the treatment concentration of VES.Control groups,VES dose groups(MKN28:5,10,20,and 40 mg/L;MKN45:10,20,40,and 80 mg/L),an autophagy-posi-tive control group(rapamycin,RAPA,100 nmol/L),and a MAMs-positive control group(oligomycin A,10 mg/L)were set up.Cells were harvested after 24 h of treatment for subsequent experiments.The formation of autophagosomes and MAMs was observed using transmission electron microscopy.The expression levels of autophagy-related proteins,includ-ing beclin-1,LC3-II/LC3-I,and p62,were detected by Western blot.MAMs labeled with split green fluorescent protein(GFP)were visualized by fluorescence microscopy.The expression of mitofusin 2(MFN2),a key molecule of MAMs,was also detected by Western blot.To inhibit MFN2 specifically,the cells were treated with mitochondrial fusion inhibitor 8(MFI8)and simultaneously transfected with an MFN2 plasmid to achieve MFN2 overexpression(OE-MFN2).The cells were divided into control group,MFI8(20 μmol/L)group,VES groups(20 mg/L for MKN28 cells and 40 mg/L for MKN45 cells),VES+MFI8 group,OE-MFN2+MFI8 group and OE-MFN2+VES+MFI8 group.The MAMs were visualized by fluorescence microscopy,and the expression changes of MFN2,beclin-1 and LC3-II/I were detected by Western blot.RESULTS:The results of the CCK8 assay showed that VES significantly inhibited the viability of both human gastric can-cer cell lines(P<0.05).After VES treatment,the formation of typical autophagosomes and MAMs was observed in both cell lines by transmission electron microscopy.Fluorescence microscopy showed a significant increase in GFP signals of MAMs.Western blot analysis showed that with increasing doses of VES,the expression levels of MFN2,beclin-1,and LC3-II/I were significantly up-regulated,while that of p62 was significantly down-regulated(P<0.05).Compared with VES group,the cells pretreated with MFI8 followed by VES exposure showed markedly reduced GFP signals of MAMs and much lower protein levels of MFN2,beclin-1 and LC3-II/LC3-I(P<0.05).Transfection with an MFN2 overexpression plasmid rescued MFN2 expression.Compared with VES+MFI8 group,the cells in OE-MFN2+VES+MFI8 group had much higher protein expression levels of MFN2,beclin-1 and LC3-II/LC3-I(P<0.05).CONCLUSION:The VES may partici-pates in the regulation of autophagy in human gastric cancer cells by promoting the formation of MAMs.

Objective:To evaluate the imaging stability of a portable boom-type ophthalmic ultra-high-resolution optical coherence tomography (OCT) device in multiple application scenarios.Methods:The boom-type mode and handheld mode of the portable boom-type OCT and the desktop OCT were used to perform three-dimensional imaging tests on three healthy adults undergoing physical examinations at the Zhongshan Ophthalmic Center, Sun Yat-sen University as well as on OEMI-7 model eyes in a sitting position.The same two modes of the portable boom-type OCT were used to perform three-dimensional imaging on four awake non-sedated infants, two sedated infants and four healthy adults in the supine position.The obtained 3D imaging data were processed using a correlation analysis method between adjacent B-scans, and the offset of B-scan in the axial (z-axis) and the fast axis transverse (x-axis) were calculated.The procedures for in vivo human eye experiments followed the Declaration of Helsinki and were approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2020 KYPJ154).All subjects and infant guardians signed the informed consent form. Results:Compared with the handheld imaging mode, the axial and fast axis lateral motion offsets of the model eye were significantly reduced in the boom-type imaging mode from (124.00±12.49)μm to (48.00±15.87)μm and from (24.00±1.00)μm to (2.67±0.57)μm, respectively ( t=2.932, 4.337; both P<0.001).In both human and model eyes, the axial and fast axis lateral motion offsets of the boom-type mode were significantly lower than in the traditional handheld operation mode (both P<0.001).The axial and lateral motion offsets between the boom-type mode and desk-top OCT imaging were comparable, without significant differences (both P>0.05).In both sedated and awake, non-sedated infants in the supine position, the axial offset of the portable boom-type OCT system was similar to that of the healthy adults, without significant difference in the overall comparison ( P=0.385), and the lateral offsets were higher than those of healthy adults, with statistically significant differences (both P=0.013).There was no significant difference in axial deviation between sedated and non-sedated infants ( P>0.05).The lateral deviation of non-sedated infants was higher than that of sedated infants, though the difference was not statistically significant ( P=0.247). Conclusions:The portable boom-type OCT system can maintain high-speed, high-resolution imaging performance while achieving imaging stability comparable to traditional desktop OCT systems.It is more suitable for bedside imaging of supine subjects, especially uncooperative infants, and has good clinical application prospects.

Objective:To investigate the relationship between nerve growth factor (NGF) concentration in follicular fluid and abnormal menstrual cycle in infertile patients with polycystic ovary syndrome (PCOS).Methods:A retrospective cohort study was conducted on 100 infertile patients with PCOS who underwent in vitro fertilization and embryo transfer (IVF-ET) at Department of Obstetrics and Gynecology, Peking University Third Hospital from March 2017 to June 2019. For comparison, the 100 patients with PCOS were divided into low NGF group ( n=50) and high NGF group ( n=50) based on the median NGF concentration (1 644.03 ng/L) in follicular fluid. Baseline characteristics, menstrual status and clinical outcomes of assisted reproductive technology were compared. We performed multiple linear regression analysis to examine the effect of NGF in follicular fluid on menstrual cycle length for multivariate analysis. Results:1) PCOS patients in the low NGF group had significantly higher body mass index [(27.24±5.17) kg/m 2] and white blood cell count [7.31(5.99, 8.43)×10 9/L ] than those in the high NGF group [(25.03±4.46) kg/m 2, P=0.024; 5.95(5.08,7.01)×10 9/L, P=0.001], while high-density lipoprotein cholesterol [1.15 (0.98, 1.36) mmol/L] and basic follicle-stimulating hormone level [6.51 (5.10,7.95) U/L] in the low NGF group were significantly lower than those in the high NGF group [1.36 (1.09,1.52) mmol/L, P=0.039;6.51 (5.10,7.95)U/L, P=0.040]. 2) PCOS patients in the low NGF group had significantly higher menstrual cycle length [60.00 (35.00, 180.00) d] than the high NGF group [32.50 (27.00,67.50) d, P=0.001]. 3) Multiple linear regression analysis revealed that after adjustment for body mass index, age, infertility duration, infertility type, and glucose and lipid metabolic parameters, the NGF concentration in the follicular fluid independently and negatively correlated with menstrual cycle length ( P<0.05). 4) The NGF concentration in follicular fluid was not correlated with assisted reproductive outcomes. Conclusion:NGF concentration in follicular fluid is closely related to the degree of menstrual cycle abnormalities in patients with PCOS.

Objective:To investigate the relationship between nerve growth factor (NGF) concentration in follicular fluid and abnormal menstrual cycle in infertile patients with polycystic ovary syndrome (PCOS).Methods:A retrospective cohort study was conducted on 100 infertile patients with PCOS who underwent in vitro fertilization and embryo transfer (IVF-ET) at Department of Obstetrics and Gynecology, Peking University Third Hospital from March 2017 to June 2019. For comparison, the 100 patients with PCOS were divided into low NGF group ( n=50) and high NGF group ( n=50) based on the median NGF concentration (1 644.03 ng/L) in follicular fluid. Baseline characteristics, menstrual status and clinical outcomes of assisted reproductive technology were compared. We performed multiple linear regression analysis to examine the effect of NGF in follicular fluid on menstrual cycle length for multivariate analysis. Results:1) PCOS patients in the low NGF group had significantly higher body mass index [(27.24±5.17) kg/m 2] and white blood cell count [7.31(5.99, 8.43)×10 9/L ] than those in the high NGF group [(25.03±4.46) kg/m 2, P=0.024; 5.95(5.08,7.01)×10 9/L, P=0.001], while high-density lipoprotein cholesterol [1.15 (0.98, 1.36) mmol/L] and basic follicle-stimulating hormone level [6.51 (5.10,7.95) U/L] in the low NGF group were significantly lower than those in the high NGF group [1.36 (1.09,1.52) mmol/L, P=0.039;6.51 (5.10,7.95)U/L, P=0.040]. 2) PCOS patients in the low NGF group had significantly higher menstrual cycle length [60.00 (35.00, 180.00) d] than the high NGF group [32.50 (27.00,67.50) d, P=0.001]. 3) Multiple linear regression analysis revealed that after adjustment for body mass index, age, infertility duration, infertility type, and glucose and lipid metabolic parameters, the NGF concentration in the follicular fluid independently and negatively correlated with menstrual cycle length ( P<0.05). 4) The NGF concentration in follicular fluid was not correlated with assisted reproductive outcomes. Conclusion:NGF concentration in follicular fluid is closely related to the degree of menstrual cycle abnormalities in patients with PCOS.

Objective:To evaluate the imaging stability of a portable boom-type ophthalmic ultra-high-resolution optical coherence tomography (OCT) device in multiple application scenarios.Methods:The boom-type mode and handheld mode of the portable boom-type OCT and the desktop OCT were used to perform three-dimensional imaging tests on three healthy adults undergoing physical examinations at the Zhongshan Ophthalmic Center, Sun Yat-sen University as well as on OEMI-7 model eyes in a sitting position.The same two modes of the portable boom-type OCT were used to perform three-dimensional imaging on four awake non-sedated infants, two sedated infants and four healthy adults in the supine position.The obtained 3D imaging data were processed using a correlation analysis method between adjacent B-scans, and the offset of B-scan in the axial (z-axis) and the fast axis transverse (x-axis) were calculated.The procedures for in vivo human eye experiments followed the Declaration of Helsinki and were approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2020 KYPJ154).All subjects and infant guardians signed the informed consent form. Results:Compared with the handheld imaging mode, the axial and fast axis lateral motion offsets of the model eye were significantly reduced in the boom-type imaging mode from (124.00±12.49)μm to (48.00±15.87)μm and from (24.00±1.00)μm to (2.67±0.57)μm, respectively ( t=2.932, 4.337; both P<0.001).In both human and model eyes, the axial and fast axis lateral motion offsets of the boom-type mode were significantly lower than in the traditional handheld operation mode (both P<0.001).The axial and lateral motion offsets between the boom-type mode and desk-top OCT imaging were comparable, without significant differences (both P>0.05).In both sedated and awake, non-sedated infants in the supine position, the axial offset of the portable boom-type OCT system was similar to that of the healthy adults, without significant difference in the overall comparison ( P=0.385), and the lateral offsets were higher than those of healthy adults, with statistically significant differences (both P=0.013).There was no significant difference in axial deviation between sedated and non-sedated infants ( P>0.05).The lateral deviation of non-sedated infants was higher than that of sedated infants, though the difference was not statistically significant ( P=0.247). Conclusions:The portable boom-type OCT system can maintain high-speed, high-resolution imaging performance while achieving imaging stability comparable to traditional desktop OCT systems.It is more suitable for bedside imaging of supine subjects, especially uncooperative infants, and has good clinical application prospects.

AIM:This study aims to investigate whether vitamin E succinate(VES)induces autophagy in hu-man gastric cancer cells through the promotion of mitochondria-associated endoplasmic reticulum membranes(MAMs).METHODS:Human gastric cancer cell lines MKN28 and MKN45 were cultured in vitro.Cell viability was assessed us-ing the CCK8 assay,and two cell growth curves were plotted to determine the treatment concentration of VES.Control groups,VES dose groups(MKN28:5,10,20,and 40 mg/L;MKN45:10,20,40,and 80 mg/L),an autophagy-posi-tive control group(rapamycin,RAPA,100 nmol/L),and a MAMs-positive control group(oligomycin A,10 mg/L)were set up.Cells were harvested after 24 h of treatment for subsequent experiments.The formation of autophagosomes and MAMs was observed using transmission electron microscopy.The expression levels of autophagy-related proteins,includ-ing beclin-1,LC3-II/LC3-I,and p62,were detected by Western blot.MAMs labeled with split green fluorescent protein(GFP)were visualized by fluorescence microscopy.The expression of mitofusin 2(MFN2),a key molecule of MAMs,was also detected by Western blot.To inhibit MFN2 specifically,the cells were treated with mitochondrial fusion inhibitor 8(MFI8)and simultaneously transfected with an MFN2 plasmid to achieve MFN2 overexpression(OE-MFN2).The cells were divided into control group,MFI8(20 μmol/L)group,VES groups(20 mg/L for MKN28 cells and 40 mg/L for MKN45 cells),VES+MFI8 group,OE-MFN2+MFI8 group and OE-MFN2+VES+MFI8 group.The MAMs were visualized by fluorescence microscopy,and the expression changes of MFN2,beclin-1 and LC3-II/I were detected by Western blot.RESULTS:The results of the CCK8 assay showed that VES significantly inhibited the viability of both human gastric can-cer cell lines(P<0.05).After VES treatment,the formation of typical autophagosomes and MAMs was observed in both cell lines by transmission electron microscopy.Fluorescence microscopy showed a significant increase in GFP signals of MAMs.Western blot analysis showed that with increasing doses of VES,the expression levels of MFN2,beclin-1,and LC3-II/I were significantly up-regulated,while that of p62 was significantly down-regulated(P<0.05).Compared with VES group,the cells pretreated with MFI8 followed by VES exposure showed markedly reduced GFP signals of MAMs and much lower protein levels of MFN2,beclin-1 and LC3-II/LC3-I(P<0.05).Transfection with an MFN2 overexpression plasmid rescued MFN2 expression.Compared with VES+MFI8 group,the cells in OE-MFN2+VES+MFI8 group had much higher protein expression levels of MFN2,beclin-1 and LC3-II/LC3-I(P<0.05).CONCLUSION:The VES may partici-pates in the regulation of autophagy in human gastric cancer cells by promoting the formation of MAMs.

In proton therapy,prompt gamma-ray imaging is considered as one of the most promising methods for assessing proton beam range.Prompt gamma-ray imaging detector evaluates the proton beam range based on the prompt gamma-ray distribution obtained by the prompt gamma-ray imaging system,which enables high-precision measurement of the proton beam range.Herein a proton beam range verification algorithm is designed for the newly developed prototype of the range verification detector(pixelated prompt gamma-ray imaging detector),which verifies the range estimation accuracy of the prototype for different phantoms and different energies of homogeneous media through Monte Carlo simulation.The results show that the accuracy of the proton beam range verification algorithm is within 0.5 mm of the safety margin error of the Bragg peak,and the measurement accuracy is significantly improved with the increase of the number of protons,indicating that the prototype algorithm is feasible for proton beam range verification.

Objective:To establish an accurate retinal vascular network segmentation method for multiple fundus diseases, and to investigate the changing patterns of retinal vascular morphological parameters in these diseases.Methods:A retrospective study was conducted.Color fundus photography data of 829 patients with fundus diseases and 146 healthy adults were collected at Zhongshan Ophthalmic Center, Sun Yat-sen University from January 2020 to December 2023.The multi-path segmentation network was fine-tuned, and the color fundus photography data of diabetic retinopathy (DR), glaucoma and age-related macular degeneration (AMD) patients and healthy adults in the fundus image vessel segmentation public dataset were input for training until the loss value of the model stopped decreasing, and finally the trained multi-disease retinal vascular segmentation model was obtained.The retinal blood vessel morphological characteristics analysis method previously developed by our research group was used to analyze the subjects' color fundus images centered on the macula, the retinal blood vessel fractal dimension (D f), vascular area ratio (VAR), mean diameter (D m), tortuosity (τ) and other morphological characteristics parameters were extracted and compared among various disease groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2023KYPJ344).Written informed consent was obtained from each subject. Results:The accuracy of the multi-disease color fundus photography vessel segmentation model on the test set was 0.987, and the area under the receiver operating characteristic curve was 0.995.After adjustment for age and sex, there were statistically significant differences in adjusted D f, adjusted VAR, adjusted D m and τ among different groups ( F=27.87, 47.60, 26.48, 4.63; all at P<0.001).Adjusted D f in AMD group, DR group, diabetic macular edema (DME) group, retinitis pigmentosa (RP) group, branch retinal vein occlusion (BRVO) group and central retinal vein occlusion (CRVO) group was significantly decreased than in normal control group, and the differences were statistically significant (all at P<0.05).Adjusted VAR in all disease groups except optic neuritis group and central serous chorioretinopathy group was significantly decreased compared with normal control group, and the differences were statistically significant (all at P<0.05).The adjusted D m in DME, glaucoma, RP, BRVO and CRVO groups was significantly decreased than that in normal control group, and the differences were statistically significant (all at P<0.05).τ was not affected by age or sex and did not require adjustment.τ in DR group and DME group was significantly increased compared with normal control group, and the differences were statistically significant (both at P<0.05). Conclusions:An accurate retinal blood vessel segmentation method for various fundus diseases was successfully constructed.This method shows high accuracy in retinal blood vessel segmentation in color fundus photographs of various retinal diseases.There are significant differences in the morphological characteristics of retinal blood vessels among different retinal diseases.

Contrast-induced acute kidney injury(CI-AKI)is an iatrogenic acute kidney injury(AKI)observed after diagnostic or therapeutic angiographic interventions with the intravascular application of contrast media(CM).CM leads to impaired renal function through tubular toxicity,intrarenal vasocon-striction,and excessive reactive oxygen species(ROS)production.Dexmedetomidine(DEX)is a selective α2 adrenergic receptor agonist that has been shown to have good antioxidant and anti-inflammatory effects,and its organ protective effect in the perioperative period is increasingly prominent.Several studies have found that DEX has an excellent protective effect on postoperative renal function.This article aims to explore the protective effect,possible mechanism,and clinical application of DEX in CI-AKI.