Geminiviruses cause substantial crop yield losses worldwide. The replication initiator protein (Rep) encoded by geminiviruses is indispensable for geminiviral replication. The Rep protein encoded by beet severe curly top virus (BSCTV, genus Curtovirus, family Geminiviridae) induces VARIANT IN METHYLATION 5 (VIM5) expression in Arabidopsis leaves upon BSCTV infection. VIM5 functions as a ubiquitination-related E3 ligase to promote the proteasomal degradation of methyltransferases, resulting in reduction of methylation levels in the BSCTV C2-3 promoter. However, the specific domains of Rep responsible for VIM5 induction remain poorly characterized. Although Rep proteins from several geminiviruses act as viral suppressors of RNA silencing (VSRs), whether BSCTV Rep also possesses VSR activity remains to be illustrated. In this study, we employed a transient expression system in the 16c-GFP transgenic and the wild-type Nicotiana benthamiana plants to analyze the VSR and the VIM5-inducing activities of different truncated Rep proteins haboring distinct domains. We found that the N-terminal domain (amino acids 1-180) of Rep suppressed GFP silencing in 16c-GFP transgenic N. benthamiana leaves. The minimal N-terminal fragment (amino acids 1-104) induced VIM5 expression upon co-infiltration, while C-terminal truncations lacked VIM5-inducing activity. Our results indicate that the N-terminal domain of Rep encoded by BSCTV mediates the suppression of RNA silencing and induces VIM5 expression. Thus, our findings contribute to a better understanding of interactions between geminiviral Rep and plant hosts.
Geminiviridae/genetics* ; Nicotiana/metabolism* ; Arabidopsis/metabolism* ; RNA Interference ; Viral Proteins/metabolism* ; Arabidopsis Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Protein Domains ; Plant Diseases/virology* ; Methyltransferases/metabolism* ; Ubiquitin-Protein Ligases/metabolism* ; DNA Helicases/genetics*

OBJECTIVE To investigate the anti-inflammatory mechanisms of demethylzeylasteral(Dem)in ulcerative colitis(UC)and collagen-induced arthritis(CIA),focusing on its regulation of Th17 cell differentiation and associated signaling pathways.METHODS UC was induced in C57BL/6 mice using dextran sulfate sodium(DSS),and Dem was administered by gavage at low(1 mg·kg-1)or high(2 mg·kg-1)doses.Disease severity was assessed by body weight loss,colon length,and stool consisten-cy.Serum cytokines(TNF-α,IL-1β,IL-6)were quantified by ELISA,and Th17 cell ratio in mesenteric lymph nodes was deter-mined by flow cytometry.The anti-inflammatory efficacy of Dem was further validated using a CIA mouse model.The efficacy of Dem was further verified in the CIA model,and the expression of JAK2 and STAT3 was intervened by siRNA to investigate its mechanism of action in Th17 differentiation.RESULTS Dem-treated mice showed reduced weight loss and colon shortening,and decreases in ser-um TNF-α,IL-1β,and IL-6 levels(P<0.01)and Th17 cell proportion(P<0.01).Western blot and siRNA assays showed that Dem significantly inhibited the differentiation and activation of Th17 cells by suppressing the phosphorylation of the JAK2-STAT3 path-way.Dem also significantly alleviated arthritis symptoms and related markers in the CIA model,confirming its anti-inflammatory effects.CONCLUSION Dem improves UC and rheumatoid arthritis by downregulating the JAK2-STAT3 signaling pathway,inhibi-ting Th17 cell differentiation and pro-inflammatory cytokine expression,suggesting its potential therapeutic value in immune-related diseases.

Objective:To investigate the current status of application of stereotactic body radiation therapy (SBRT) in China, aiming to provide reference for promoting the development of this technology.Methods:From January to March 2024, a questionnaire was designed and distributed online, targeting member units of the Professional Committee of Stereotactic Radiosurgery Treatment, which covers 175 radiotherapy units in 30 provinces and regions nationwide. The survey focused on the current application of SBRT technology and its utilization in the treatment of early-stage non-small cell lung cancer (NSCLC). A statistical description of the survey results was presented.Results:Of 175 questionnaires distributed, a total of 130 valid responses were collected, with an effective response rate of 74.3%. A total of 81.5% (106/130) of the units had implemented SBRT technology, and 99.1% of the respondents believed it was necessary to further promote SBRT technology, yet the actual training rate was only 67.0%. SBRT equipment configuration: there were a total of 267 SBRT equipment, featuring a diverse range of types, with traditional linear accelerators as the mainstays, accounting for 76.0% ( n=203), followed by 12.0% ( n=32) for TOMO, 6.4% ( n=17) for Cyber knife, 3.7% ( n=10) for Gamma knife, and proton/heavy ion equipment at 1.5% ( n=4), respectively. The percentage of units with multi-leaf collimator leaf widths ≤0.5 cm was 93.4% (99/106). The application of SBRT: the first radiotherapy unit commenced SBRT in 2000, and this technology entered a period of rapid growth after 2015, sustaining a steady increase over the past decade; SBRT technology was mainly applied in the brain, lung, liver, bone, adrenal gland, and kidney, with application rates of 97.2%, 94.3%, 86.8%, 71.7%, 56.6%, and 27.4%, respectively, while the application rates for the pancreas, metastatic lymph nodes, and other parts were less than 5%. Current status of SBRT technology application in early-stage NSCLC: 90.6% (96/106) of units had implemented SBRT; pre-treatment multi-disciplinary diagnosis and treatment accounted for 77% (74/96); the proportion of application units for peripheral and central type lung cancer lesions both exceeded 57.3%, whereas the application rate for ultra-central type and lesions > 5 cm lung cancer was less than 30%; there was significant variability in the selection of reference guidelines, dose fractionation patterns, and the concept of central type among units. Conclusions:The development of SBRT technology in China is in a period of steady growth, but several issues such as low training rate and lack of standardization still exist. The survey results provide important reference for clinical training and promotion of SBRT technology in China.

Objective:To reveal the differences in the transcriptome maps of brain tissues in mice subjected to Flash irradiation and conventional dose rate irradiation with electron beams and to explain the biological effect and mechanisms of Flash irradiation from multiple perspectives.Methods:Following the principle of grouping based on approximate body weights, 36 female C57BL/6J mice were divided into three groups, i. e., the control, conventional dose rate irradiation (CONV), and Flash irradiation (Flash) groups, with 12 mice in each group. Both the CONV and Flash groups received a single 15 Gy whole-brain irradiation with 9 MeV electron beams. At 3 d post-irradiation, the whole-brain tissue specimens were collected for hematoxylin-eosin (HE) staining to observe pathological changes. At 1, 3, and 10 weeks post-irradiation, the motion function, cognitive ability, depression level, and spatial memory capacity of the mice were assessed using ethology. At 1 and 10 weeks after behavioral experiments, brain tissue samples were collected and snap-frozen in liquid nitrogen for reference-based transcriptome sequencing. Accordingly, the differences in the transcriptome maps of radiation-induced brain injury between CONV and Flash groups were analyzed.Results:The HE staining-based pathological result revealed that compared to the CONV group, the Flash group exhibited reduced glial cell hyperplasia and inflammatory cell infiltration in brain tissues. Ethological research result at 1 week post-irradiation showed that the CONV group manifested a significantly decreased total traveled distance compared to the control and Flash groups ( t = 5.51, 2.38, P < 0.05) and a significantly increased immobility time compared to the control group ( t = 3.60, P < 0.05). Ethological research result at 3 weeks post-irradiation indicated that compared to the CONV group, the Flash group displayed significantly alleviated cognitive impairment ( t = 3.35, P < 0.05) and reduced depression levels ( t = 2.39, P < 0.05). Ethological research result at 10 weeks post-irradiation demonstrated that the CONV group showed the worst cognitive performance, significantly differing from the control group ( t = 4.53, P < 0.05). Transcriptome sequencing result revealed that besides immune-related pathways, the Flash group also exhibited multiple upregulated metabolic pathways and fibroblast growth factor (FGF)-related pathways compared to the CONV group. Conclusions:Compared to conventional dose rate irradiation, Flash irradiation can effectively alleviate radiation-induced brain injury in mice. This effect is associated with various metabolic pathways (including amino acid metabolism) and FGF-related pathways besides immune pathways.

Objective:To investigate the current status of breast reconstruction after breast cancer surgery in hospitals in China.Methods:This study was a cross-sectional study using convenience sampling. A self-designed survey questionnaire was used to investigate nurses of department of breast diseases in China from May to August 2023. The content of the questionnaire included four aspects: identification information, basic hospital information, the implementation situation of breast reconstruction after breast cancer surgery, and the situation of medical and nursing human resources for breast reconstruction, with a total of 39 items. Statistical analysis was performed using SPSS 26.0 software. The non-normally distributed measurement data were expressed as M( Q1, Q3), and the Mann-Whitney U test was used for comparison between groups. Numeric data were expressed as frequency and percentage, and comparisons between groups were made using the χ2-test or Fisher’s exact probability method. P<0.05 indicated that the difference was statistically significant. Results:A total of 212 public hospitals from 31 provinces, autonomous regions and municipalities participated in the survey. Two hundred and three hospitals (95.8%) returned valid data, including 155 Grade Ⅲ Level A hospitals, 19 Grade Ⅲ Level B and C hospitals, and 29 Grade Ⅱ hospitals. There were 157 general hospitals, 32 specialized cancer hospitals, and 14 other hospitals. Thirty-nine hospitals did not perform breast reconstruction surgery. A total of 164 hospitals (80.8%) had already carried out breast reconstruction surgery, among which the proportion of breast reconstruction in Grade Ⅲ Level A hospitals [90.3% (140/155)] was significantly higher than that in Grade Ⅲ Level B and C hospitals [52.6% (10/19)] and Grade Ⅱ hospitals [48.3% (14/29)] ( P<0.01). The proportion of breast reconstruction in specialized cancer hospitals [96.9% (31/32)] was significantly higher than that in general hospitals [79.0% (124/157)] and other types of hospitals [64.3% (9/14)] ( P<0.05). Among the 164 hospitals, 310 (150, 637.5) patients underwent breast cancer surgery and 30 (10, 100) patients underwent breast reconstruction in 2022. The proportion of patients undergoing breast reconstruction surgery among breast cancer surgery patients was 13.3% (4.0%, 20.0%). The number of patients receiving immediate breast reconstruction was 11 (2.5, 46.5) cases, and the number of those receiving delayed breast reconstruction was 5 (0, 18.5) cases. Among 203 hospitals, the median proportions of breast oncoplastic surgeons and specialized nurses among healthcare providers in breast surgery departments were 28.6% (2/7) and 75.0% (12/16), respectively. In comparison of the 164 hospitals offering breast reconstruction surgery and 39 hospitals not, the median numbers of breast oncoplastic surgeons were 3 (1, 8) versus 1 (0, 3), and qualified breast reconstruction nurses were 12 (6, 16) versus 1 (0, 8), respectively. All differences were statistically significant (all P<0.01). Conclusion:About 80% of hospitals in China have offered breast reconstruction procedures after breast cancer surgery, and the proportion of Grade Ⅲ Level A hospitals and specialized cancer hospitals is higher than that of other types of hospitals. The proportion of patients undergoing breast reconstruction after breast cancer surgery is relatively low, and there is a considerable potential of improvements. Breast oncoplastic surgeons and nurses are insufficient, so it is necessary to strengthen the training of specialized medical staff and improve surgical techniques and the level of nursing services simultaneously, so as to improve the quality of life of breast cancer patients.

Objective To review the damage outcomes of patients in medical damage events and to analyze the influencing factors of medical causality determination in medical damage events in Tianjin city,with a view to reducing the occurrence of medical damage events by avoiding risk factors and standardizing the diagnostic and therapeutic activities of medical personnel.Methods 316 cases of medical damage events handled by the Medical Damage Identification Office of Tianjin Medical Association from 2017 to 2023 were selected as the research object,and descriptive analysis was used to summarize the basic situation of medical damage events,and the medical fault factors affecting the magnitude of the cause force of the medical side of medical damage events were explored through single-factor analysis and the construction of multiomal logistic regression models.Results Medical malpractice(OR=3.140)and incomplete preoperative assessment(OR=6.008)are factors that influence the determination of the liability of the medical institution in medical malpractice events(P＜0.05),and all three regression coefficients were greater than 0,all three were positively correlated with the probability that the medical cause power was judged to be greater than or equal to the equivalent cause.Conclusion The number of medical damage incidents in Tianjin shows a fluctuating downward trend.In Tianjin,the number of medical injury incidents showed a fluctuating downward trend,and the number of medical injury incidents in tertiary public general hospitals was the largest.Therefore,medical institutions should establish and improve multidisciplinary diagnosis and treatment mode to improve the level of diagnosis and treatment.Strengthen preoperative evaluation to avoid surgical risk.

Hashimoto thyroiditis(HT)is one of the most common autoimmune diseases."Wood depression and earth stagnation"is its important pathogenesis.Liver depression and qi stagnation,wood depression multiplies the earth,spleen deficiency and earth stagnation,phlegm and blood stasis intermingle,resulting in wood depression and earth stagnation.Or middle-earth stagnation insults wood in turn,liver yang deficiency,wood depression,and failure to disperse and discharge,resulting in earth stagnation and wood depression.It may be related to the intestinal immune mechanism in modern medical study.Based on the theory of"wood depression and earth stagnation",this article discussed the pathogenesis of HT from the perspective of wood depression and imbalance of microbe-gut-brain axis,earth stagnation and dysbiosis of intestinal flora,damage to the intestinal barrier,and proposed the treatment principles,i.e.,"disperse stagnated liver qi for relieving qi stagnation,ascend yang and regulate qi""eliminate stagnation and remove turbidity,invigorate spleen and restore normal movement",which could provide the ideas for mechanism research and clinical treatment of HT.

OBJECTIVE To investigate the anti-inflammatory mechanisms of demethylzeylasteral(Dem)in ulcerative colitis(UC)and collagen-induced arthritis(CIA),focusing on its regulation of Th17 cell differentiation and associated signaling pathways.METHODS UC was induced in C57BL/6 mice using dextran sulfate sodium(DSS),and Dem was administered by gavage at low(1 mg·kg-1)or high(2 mg·kg-1)doses.Disease severity was assessed by body weight loss,colon length,and stool consisten-cy.Serum cytokines(TNF-α,IL-1β,IL-6)were quantified by ELISA,and Th17 cell ratio in mesenteric lymph nodes was deter-mined by flow cytometry.The anti-inflammatory efficacy of Dem was further validated using a CIA mouse model.The efficacy of Dem was further verified in the CIA model,and the expression of JAK2 and STAT3 was intervened by siRNA to investigate its mechanism of action in Th17 differentiation.RESULTS Dem-treated mice showed reduced weight loss and colon shortening,and decreases in ser-um TNF-α,IL-1β,and IL-6 levels(P<0.01)and Th17 cell proportion(P<0.01).Western blot and siRNA assays showed that Dem significantly inhibited the differentiation and activation of Th17 cells by suppressing the phosphorylation of the JAK2-STAT3 path-way.Dem also significantly alleviated arthritis symptoms and related markers in the CIA model,confirming its anti-inflammatory effects.CONCLUSION Dem improves UC and rheumatoid arthritis by downregulating the JAK2-STAT3 signaling pathway,inhibi-ting Th17 cell differentiation and pro-inflammatory cytokine expression,suggesting its potential therapeutic value in immune-related diseases.

Objective This study focuses on the analysis of disaster vulnerability among multiple hospital districts to ex-plore the core of integrated emergency management among these districts.Methods Taking the First Affiliated Hospital of Guan-gzhou Medical University as an example,the Kaiser model analysis tool was used to identify risk events in the three hospital dis-tricts.A 42-item questionnaire was developed based on four dimensions,and surveys were conducted among administrative de-partment heads and some frontline staff in the three districts.After selecting valid data,the arithmetic mean of single-item scores from multidimensional scorers was calculated as the final single-item score for risk evaluation.Results The analysis revealed significant differences in the ranking of the top 10 risk events among the three hospital districts.The top risk event in the riverside district was typhoon,with a risk coefficient of 60.2％,which was higher than the top risk events in the Tan Sha district(55.2％)and Hai Yin district(52.8％).This indicates that the overall risk coefficient in the riverside district is higher,with a higher probability of different types of risk events occurring.Conclusion The study found differences in risk events among multiple hospital districts and identified conflicts in the implementation of integrated collaborative emergency management.To ad-dress these differences and conflicts,it is necessary to establish a unified command system,enhance information sharing,in-tegrate resources,strengthen risk assessment,and optimize management culture,thereby achieving efficient operation of compre-hensive emergency management in multiple hospital districts.