Objective:To study and design one kind of flash radiotherapy(Flash-RT)equipment with ultra-high dose rate,which can be used in the mechanism research of Flash-RT with ultra-high dose rate.Methods:Based on the technique roadmap of high-power petal accelerator,the Flash-RT equipment can realize the requirement of Flash-RT for ultra-high dose rate and multiple irradiation angles.The corresponding design and research work were carried out on the basis of the overall design of the equipment,the main components and characteristics,the dynamics design of beam,the construction of movable and preliminary experimental platform,etc.Result:The dose rate of the designed equipment can reach to 100 Gy/s at a distance of 0.8 meters from the target point,which is easy to realize the radiotherapy method with multi angles.Conclusion:The designed X-ray equipment based on the technique roadmap of high-power petal accelerator can realize the research for the mechanism of medical Flash-RT equipment with ultra-high dose rate.

The protection effect of flash-radiotherapy(Flash-RT)with super-high dose on normal tissue has obtained wide attention in therapeutic radiology since it was found in 2014 year.The increasing research demand of Flash-RT with super-high dose-rate proposed new challenge for the existing radiotherapy equipment.Based on the demands of FLASH-RT research and clinical application,this review analyzed the proposed new requirement of Flash-RT for equipment,and introduce current scientific facilities with the experimental ability of X-ray FLASH-RT,as well as the situation of the specialized FLASH-RT equipment which were developing.The research of Flash-RT mechanism need the existing equipment with high-energy X-ray source develop toward high power,while the clinical application of Flash-RT demand these transient high-power devices should possess a series of radiotherapy techniques such as multi angle irradiation,conformal radiotherapy and others.Currently,China's X-ray FLASH-RT research is at the forefront of the world,which is expected to achieve the first breakthrough of high-end medical equipment in the X-ray Flash RT field.

BACKGROUND:Steroid-induced osteonecrosis of the femoral head is a refractory disease in the field of orthopedics.There is no definitive idea to fully explain its pathogenesis.With the increased research on the active ingredients of Panax notoginseng interfering with the signaling pathways related to various diseases,the active ingredients of Panax notoginseng that treat steroid-induced necrosis of the femoral head via the regulation of relevant signaling pathways have gradually become a hot research topic. OBJECTIVE:To systematically summarize the literature on the pathological mechanism of steroid-induced osteonecrosis of the femoral head and the regulation of signaling pathways by the active ingredients of Panax notoginseng in recent years,thereby providing a reference for the follow-up study on the active ingredients of Panax notoginseng in the treatment of this disease. METHODS:CNKI,WanFang,and PubMed were searched for relevant literature with the key words of"glucocorticoid,steroid-induced osteonecrosis of the femoral head,pathological mechanism,signaling pathway,Panax notoginseng,active ingredient"in Chinese and English.Documents related to the pathological mechanism of steroid-induced osteonecrosis of the femoral head as well as related to the intervention of active ingredients of Panax notoginseng on the signaling pathway of steroid-induced osteonecrosis of the femoral head were retrieved.A total of 63 documents were finally included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The main ingredients of Panax notoginseng include Panax notoginseng saponins,ginsenoside,Panax notoginseng saponins,quercetin,kaempferol,etc.Panax notoginseng saponins,ginsenoside Rb1 and quercetin can promote bone repair and angiogenesis by acting on the transforming growth factor-β/bone morphogenetic protein pathway.Panax notoginseng saponins,ginsenoside CK and kaempferol can promote osteogenic differentiation and lipid metabolism by acting on the Wnt/β-catenin pathway.Panax notoginseng saponins and Panax notoginseng saponins R1/R2 act on the MAPK pathway to inhibit osteoclastogenesis and promote bone repair.Panax notoginseng saponins,ginsenoside Rb2 and quercetin can inhibit osteoclast proliferation and promote osteoblastic differentiation by acting on the RANKL/RANK/OPG pathway.Panax notoginseng saponins,quercetin and kaempferol can repair vascular injury and promote osteogenesis by acting on the hypoxia-inducible factor-1α pathway.Panax notoginseng saponins R1,quercetin combined with hydroxyapatite nanoparticles,Panax notoginseng saponins combined with polyethylene-L-lactic acid and other biomaterials have good research prospects in the treatment of steroid-induced osteonecrosis of the femoral head.The active ingredients of Panax notoginseng can regulate the signaling pathways related to steroid-induced osteonecrosis of the femoral head through various mechanisms,and play an active intervention role in the disease.However,the depth and breadth of relevant research are insufficient at present,and the future research should be based on the existing mechanism to explore the specific mechanism of Panax notoginseng regulating different pathways and the interaction between pathways,which will be beneficial to the multi-development of the active ingredients of Panax notoginseng in the treatment of steroid-induced osteonecrosis of the femoral head.

Objective:To investigate the clinical characteristics of 130 children with severe SARS-CoV-2 infection in Yunnan province after the relaxation of non-pharmaceutical interventions, and analyze the risk factors for mortality.Methods:This study is a retrospective case summary that analyzed the demographic data, underlying diseases, clinical diagnoses, disease outcomes, and laboratory results of 130 children with severe COVID-19 infections admitted to nine top-tier hospitals in Yunnan Province from December 2022 to March 2023. According to the prognosis, the patients were divided into survival group and death group. The clinical and laboratory data between the two groups were compared, and the risk factors of death were evaluated. The χ2 test and Mann-Whitney U test were employed to compare between groups, while Spearman correlation test and multiple Logistic regression were used to analyze the risk factors for death. The predictive value of independent risk factors was evaluated by receiver operating characteristic curve. Results:The 130 severe patients included 80 males and 50 females with an onset age of 28.0 (4.5, 79.5) months. There were 97 cases in the survival group and 33 cases in the death group with no significant differences in gender and age between the two groups ( P>0.05). Twenty-five cases (19.2%) out of the 130 patients had underlying diseases, and the number with underlying diseases was significantly higher in death group than in survival group (36.4% (12/33) vs. 13.4%(13/97), χ2=8.36, P=0.004). The vaccination rate in the survival group was significantly higher than that in the death group (86.1% (31/36) vs. 7/17, χ2=9.38, P=0.002). A total of 42 cases (32.3%) of the 130 patients were detected to be infected with other pathogens, but there was no significant difference in the incidence of co-infection between the death group and the survival group (39.3%(13/33) vs. 29.9% (29/97), χ2=1.02, P>0.05). Among the 130 cases, severe respiratory cases were the most common 66 cases (50.8%), followed by neurological severe illnesses 34 cases (26.2%) and circulatory severe 13 cases (10%). Compared to the survival group, patients in the death group had a significantly higher levels of neutrophil, ferritin, procalcitonin, alanine aminotransferase, lactate dehydrogenase, creatine kinase isoenzyme, B-type natriuretic peptide, interleukin-6 and 10 (6.7 (4.0, 14.0) vs. 3.0 (1.6, 7.0)×10 9/L, 479 (298, 594) vs. 268 (124, 424) μg/L, 4.8 (1.7, 10.6) vs. 2.0 (1.1, 3.1) μg/L, 66 (20, 258) vs. 23 (15, 49) U/L, 464 (311, 815) vs. 304 (252, 388) g/L, 71(52, 110) vs. 24(15, 48) U/L, 484 (160, 804) vs. 154 (26, 440) ng/L, 43 (23, 102) vs. 19 (13, 27) ng/L, 216 (114, 318) vs. 86 (45, 128) ng/L, Z=-4.21, -3.67, -3.76, -3.31, -3.75, -5.74, -3.55, -4.65, -5.86, all P<0.05). The correlated indexes were performed by multivariate Logistic regression and the results showed that vaccination was a protective factor from death in severe cases ( OR=0.01, 95% CI 0-0.97, P=0.049) while pediatric sequential organ failure assessment (PSOFA) ( OR=3.31, 95% CI 1.47-7.47, P=0.004), neutrophil-to-lymphocyte ratio (NLR) ( OR=1.56, 95% CI 1.05-2.32, P=0.029) and D dimer ( OR=1.49, 95% CI 1.00-1.02, P=0.033) were independent risk factors for death (all P<0.05). The area under the curve of the three independent risk factors for predicting death were 0.86 (95% CI 0.79-0.94), 0.89 (95% CI 0.84-0.95) and 0.87 (95% CI 0.80-0.94), all P<0.001, and the cut-off values were 4.50, 3.66 and 4.69 mg/L, respectively. Conclusions:Severe SARS-CoV-2 infection can occur in children of all ages, primarily affecting the respiratory system, but can also infect the nervous system, circulatory system or other systems. Children who died had more severe inflammation, tissue damage and coagulation disorders. The elevations of PSOFA, NLR and D dimer were independent risk factors for death in severe children.

Objective To investigate the prevalence of hepatitis D virus (HDV) infection among patients with chronic hepatitis B virus (HBV) infection in some regions of China. Methods Serum samples were collected from 3 131 patients with chronic HBV infection in 10 provinces, cities, and autonomous regions of China from March 2021 to June 2022, and anti-HDV IgG ELISA was used for the detection of all serum samples. Nested reverse transcription-polymerase chain reaction (nRT-PCR) was used to detect HDV RNA in anti-HDV IgG-positive samples, and the nRT-PCR amplification products of HDV RNA-positive samples were sequenced and analyzed to determine HDV genotype. The clinical features of anti-HDV IgG-positive patients were analyzed. The Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results The positive rate of anti-HDV IgG in the 3 131 patients with chronic HBV infection was 0.70% (22/3 131), and that in the patients with chronic HBV infection in Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region, Beijing, and Hunan Province was 1.81% (16/886), 0.88% (2/226), 0.28% (2/708), and 1.00% (2/200), respectively; the patients with chronic HBV infection in Inner Mongolia Autonomous Region had a significantly higher positive rate of anti-HDV IgG than those in Beijing ( P =0.004), and there was no significant difference between the other regions ( P > 0.05). Clinical features of the patients with chronic HBV infection in Inner Mongolia Autonomous Region showed that compared with the anti-HDV IgG-negative group, the anti-HDV IgG-positive group had a significantly higher proportion of patients with Mongol nationality ( P =0.001), abnormal alanine aminotransferase ( P =0.007), or antiviral treatment ( P =0.029), as well as a significantly lower median HBV DNA level ( P =0.030). A total of 19 HDV RNA-positive samples were identified, all of which had HDV genotype 1. Conclusion The prevalence rate of HDV varies greatly across different regions of China, with a higher prevalence rate of HDV in patients with chronic HBV infection from Inner Mongolia Autonomous Region. HDV genotype 1 is the predominant genotype in some provinces and cities of northern China.

Objective:To study the association of non-alcoholic fatty liver disease(NAFLD) and advanced liver fibrosis with osteoporosis in patients with type 2 diabetes mellitus(T2DM).Methods:Data was collected from 391 in-patients with type 2 diabetes mellitus(T2DM) from September 2019 to September 2020 at the Department of Endocrinology and Geriatric Medicine, Affiliated Huai′an First Hospital of Nanjing Medical University in this cross-sectional study. Participants were divided into T2DM with coexistent NAFLD(TCN) and with no NAFLD(TON) group via liver B-mode ultrasound.Also, the patients were divided into low and middle-high risk group via fibrosis index based on 4 factors index(FIB-4). Participant characteristics, laboratory results, and dual energy x-ray absorptiometry were obtained and analyzed. Multivariable logistic regression models were used to evaluate the association of NAFLD and advanced liver fibrosis with osteoporosis in T2DM. Interaction and stratified analyses were conducted according to age, sex, body mass index(BMI) and duration of diabetes(DD).Results:There was no significant difference in risk of osteoporosis and bone mineral density(BMD) loss between TCN and TON group(all P>0.05). After adjusting for age, sex, BMI, and DD, total hip BMD( β=-0.044, 95% CI -0.087--0.001, P=0.046) and lumbar L 1-L 4BMD( β=-0.044, 95% CI -0.087--0.002, P=0.044) were significantly reduced, and the risk of osteoporosis was significantly increased( OR=2.428, 95% CI 1.124-5.244, P=0.024) in FIB-4 middle-high risk group compared with low risk group. The subgroup analysis showed that overweight patients with T2DM had a significantly increased risk of osteoporosis( OR=4.240, 95% CI 1.637-10.987, interaction P=0.018) in FIB-4 middle-high risk group compared with low risk group. Conclusion:There was no significant difference in risk of osteoporosis and BMD loss between TCN and TON group. However, among T2DM patients who were overweight, NAFLD-related progressive liver fibrosis emerged as an independent risk factor for both BMD decline and the development of osteoporosis.

Objective:To investigate the risk factors of restenosis after dilation of anastomotic stenosis in patients with esophageal cancer surgery.Methods:Clinical data of 997 patients who underwent endoscopic dilation due to anastomotic stenosis after esophageal cancer radical surgery in the Affiliated Huai′an First Hospital of Nanjing Medical University from June 2015 to July 2021, were retrospectively analyzed. There were 486 cases receiving single dilation (single dilation group) and 511 cases receiving more than two dilations (multiple dilation group). The risk factors of restenosis were explored using univariate and multivariate logistic regression analysis.Results:There were 682 males and 315 females with a median age of 65 years, the median distance between the stenosis and incisor was 20 (20, 22) cm, the median stenosis diameter was 4 (3, 5) mm, and the median stenosis diameter after dilation was 11 (11, 13) mm. Univariate analysis showed that there were significant differences in the distance of the stenosis and incisor ( Z=-2.303, P<0.05), stenosis diameter ( Z=-4.637, P<0.05) and stenosis diameter after dilation ( Z=-5.773, P<0.05) between single and multiple dilation groups. Stratified multivariate logistic regression showed that for male patients, risk of multiple dilations dropped by approximately 3% for every 1-mm increase in the distance between the stenosis and incisor ( OR=0.97, 95% CI:0.93-1.00, P=0.047); the risk of multiple dilations decreased by about 15%, for every 1-mm increase in stenosis diameter ( OR=0.85, 95% CI:0.76-0.94, P=0.004); the risk of multiple dilations decreased by about 13% for every 1-mm increase in stenosis diameter after dilation ( OR=0.87, 95% CI:0.78-0.96, P=0.007). For females patients under 60 years old, the risk of multiple dilations decreased by about 31%, for every 1-mm increase in stenosis diameter after dilation ( OR=0.69, 95% CI:0.47-0.98, P=0.049); for female patients≥60 years old, the risk decreased by about 5%, for every 1-year increase in age ( OR=0.95, 95% CI:0.91-1.00, P=0.037), risk of multiple dilations dropped by 17%( OR=0.83, 95% CI:0.70-0.99, P=0.039) for every 1 mm increase in stenosis diameter after dilation. Stratified smooth curve fitting indicated that the distance between the stenosis and incisor≤23 mm, stenosis diameter≤4.5 mm, stenosis diameter after dilation≤12 mm were risk factors for multiple dilations. Conclusions:The study indicates that patients with the distance between the stenosis and incisor≤23 mm, stenosis diameter≤4.5 mm, stenosis diameter after dilation≤12 mm may need multiple dilations; and the first dilation should expand the stenosis diameter to 12 mm or above as far as possible to reduce the risk of restenosis in patients receiving esophageal cancer radical surgery.

Objective:To investigate the radiotherapy discipline construction and existing problems in non-public hospitals in Zhejiang province and put forward suggestions for improvement.Methods:In 2022, on-site inspection and investigation were carried out in 14 non-public hospitals in Zhejiang province, including equipment configuration and source, discipline setting, personnel qualification and professional experience, academic leaders and admission of patients, etc. Results:For 14 non-public hospitals in Zhejiang province, 19 treatment equipment, 15 positioning equipment and 77 quality control equipment were equipped, and a total of 249 radiotherapy practitioners were employed. A total of 4 224 patients were admitted throught 2022.Conclusion:Multiple problems exist in non-public radiotherapy hospitals in Zhejiang province, such as unscientific discipline setting, fewer professionals, lack of personnel training, unclear management mode, unqualified qualification of partial radiotherapy doctors, and insufficient refinement of clinical quality management, which need to be further improved.

Objective:Socioeconomic status(SES)is associated with childhood obesity,but the underlying factors remain unknown.This study aimed to identify mediators that may explain SES disparities in childhood obesity in China.Methods:Nationally representative longitudinal data from the China Education Panel Survey of 11 019 chil-dren(13.03±0.79)collected from 2013-2014 to 2016-2017 academic years.Overweight/obesity was de-fined using Chinese national body mass index cut-points.Principal component analysis was used to con-vert the four SES indicators(maternal and paternal education,and occupation)into one comprehensive vari-able.Mediation analysis for SES disparities in childhood obesity was conducted using structure equation models.Results:The prevalence of overweight/obesity was 12.8％,and was higher in boys than in girls(17.8％vs.7.6％,P＜0.001)at baseline.Among boys,relative risk(RR)of obesity was 1.23(95％CI:1.09 to 1.40,P＜0.001)for per unit change in SES.There was no significant association between obesity and SES among girls.Mediation analyses showed that among boys,birth weight,being the only child in the family and children's self-perceived weight status mediated 70.0％of the effects of SES on obesity.No mediation effect was detected in girls.Conclusions:Chinese boys are more likely to be overweight or obese than girls.SES may impact childhood obesity through birth weight,being the only child in the family and children's self-perceived body weight status in boys,but not in girls.More attention should be made to address childhood obesity in high SES families among boys.Interventions targeting at these mediators are needed.

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
Amyloidogenic Proteins/metabolism* ; Amyotrophic Lateral Sclerosis/genetics* ; Animals ; COVID-19 ; Cytoplasmic Granules/metabolism* ; Mammals ; SARS-CoV-2 ; Stress Granules