Objective:To explore differences in the radiation-induced intestinal injury in mice exposed to ultra-high dose rate (FLASH) and conventional-dose-rate (CONV) pulsed X-ray irradiation in order to provide evidence for the application of ultra-high dose rate pulsed X-rays in gastrointestinal radiotherapy.Methods:Using the random number table method, 32 C57BL/6J mice were randomly divided into four groups: a sham irradiation group (SHAM), two conventional dose rate groups (CONV0.067 and CONV0.1), and an ultra-high dose rate group (F215), with each group containing eight mice. All groups, except SHAM, received a single 12 Gy abdominal X-ray irradiation at dose rates of 0.067, 0.1, and 215 Gy/s, respectively. At 3 d post-irradiation, histopathological (hematoxylin-eosin staining, HE staining), immunohistochemical, and Western blot analysis were performed to assess the histopathological markers and oxidative stress indicators of intestinal tissues, as well as relevant proteins involved in signaling pathways.Results:At 3 d post-irradiation, mice in all irradiation groups suffered from varying degrees of intestinal tissue degeneration and necrosis, epithelial cell shedding, villus shortening, and crypt loss ( t = 5.75, 8.79, 5.71, P < 0.05). Regarding oxidative stress, at 3 d post-irradiation, mice in the CONV0.067 and CONV0.1 groups showed significantly lower levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), glutathione (GSH), and total antioxidant capacity (T-AOC) compared to those in the F215 group ( t = 7.06-10.64, P < 0.01). In contrast, their malondialdehyde (MDA) levels were significantly elevated ( t = 11.06, 8.31, P < 0.01), with no statistical significance observed between them and mice in the F215 group ( P > 0.05). Immunohistochemical and Western blot analyses indicated that at 3 d post-irradiation, mice in the three irradiation groups exhibited an upward trend in the Nrf2 and HO-1 protein levels and a downward trend in the Keap1 protein level compared to those in the SHAM group. Notably, statistical significance was observed between the F215 group and the two conventional dose rate groups ( t = 4.89-20.95, P < 0.05). These result were consistent with the prior changes in antioxidant markers. Conclusions:Ultra-high-dose-rate X-ray irradiation reduces acute RIII by alleviating oxidative stress and modulating the expression of the Keap1-Nrf2-HO-1 signaling pathway.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of ileocecal valve lipoma.Methods:A retrospective cohort study was performed on data of ileocecal lipoma patients who underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2013 to June 2023. According to the lesion location, the patients were divided into ileocecal valve group and cecum group. The operation time, operation speed, en bloc resection rate, complications, and follow-up outcomes between the two groups were compared.Results:A total of 59 patients with ileocecal lipoma were enrolled, including 31 patients in the ileocecal valve group and 28 patients in the cecum group.There were no significant differences in gender, age, specimen size, or lesion size between the two groups ( P>0.05). Lipomas in both the ileocecal valve group and the cecum group were successfully resected by ESD. The en bloc resection rates were 100.0% (31/31) and 92.9% (26/28) respectively, and the difference was not statistically significant ( χ2=0.033, P=0.133). Median operative duration significantly differed between the two groups ( ileocecal valve group 26 min VS cecum group 20 min, Z=-0.136, P=0.027), as did resection speed (ileocecal valve group 0.14 cm2/min VS cecum group 0.24 cm2/min, Z=-0.223, P=0.022). Adverse events included one postoperative fever in the ileocecal valve group and one delayed bleeding in the cecum group. During the median follow-up of 38 months (7-106 months), there was no case of residual tumor or recurrence. Conclusion:Despite technical challenges in ESD of ileocecal valve lipoma, it is still a safe, feasible and effective treatment method.

Objective:To explore differences in the radiation-induced intestinal injury in mice exposed to ultra-high dose rate (FLASH) and conventional-dose-rate (CONV) pulsed X-ray irradiation in order to provide evidence for the application of ultra-high dose rate pulsed X-rays in gastrointestinal radiotherapy.Methods:Using the random number table method, 32 C57BL/6J mice were randomly divided into four groups: a sham irradiation group (SHAM), two conventional dose rate groups (CONV0.067 and CONV0.1), and an ultra-high dose rate group (F215), with each group containing eight mice. All groups, except SHAM, received a single 12 Gy abdominal X-ray irradiation at dose rates of 0.067, 0.1, and 215 Gy/s, respectively. At 3 d post-irradiation, histopathological (hematoxylin-eosin staining, HE staining), immunohistochemical, and Western blot analysis were performed to assess the histopathological markers and oxidative stress indicators of intestinal tissues, as well as relevant proteins involved in signaling pathways.Results:At 3 d post-irradiation, mice in all irradiation groups suffered from varying degrees of intestinal tissue degeneration and necrosis, epithelial cell shedding, villus shortening, and crypt loss ( t = 5.75, 8.79, 5.71, P < 0.05). Regarding oxidative stress, at 3 d post-irradiation, mice in the CONV0.067 and CONV0.1 groups showed significantly lower levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), glutathione (GSH), and total antioxidant capacity (T-AOC) compared to those in the F215 group ( t = 7.06-10.64, P < 0.01). In contrast, their malondialdehyde (MDA) levels were significantly elevated ( t = 11.06, 8.31, P < 0.01), with no statistical significance observed between them and mice in the F215 group ( P > 0.05). Immunohistochemical and Western blot analyses indicated that at 3 d post-irradiation, mice in the three irradiation groups exhibited an upward trend in the Nrf2 and HO-1 protein levels and a downward trend in the Keap1 protein level compared to those in the SHAM group. Notably, statistical significance was observed between the F215 group and the two conventional dose rate groups ( t = 4.89-20.95, P < 0.05). These result were consistent with the prior changes in antioxidant markers. Conclusions:Ultra-high-dose-rate X-ray irradiation reduces acute RIII by alleviating oxidative stress and modulating the expression of the Keap1-Nrf2-HO-1 signaling pathway.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of ileocecal valve lipoma.Methods:A retrospective cohort study was performed on data of ileocecal lipoma patients who underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2013 to June 2023. According to the lesion location, the patients were divided into ileocecal valve group and cecum group. The operation time, operation speed, en bloc resection rate, complications, and follow-up outcomes between the two groups were compared.Results:A total of 59 patients with ileocecal lipoma were enrolled, including 31 patients in the ileocecal valve group and 28 patients in the cecum group.There were no significant differences in gender, age, specimen size, or lesion size between the two groups ( P>0.05). Lipomas in both the ileocecal valve group and the cecum group were successfully resected by ESD. The en bloc resection rates were 100.0% (31/31) and 92.9% (26/28) respectively, and the difference was not statistically significant ( χ2=0.033, P=0.133). Median operative duration significantly differed between the two groups ( ileocecal valve group 26 min VS cecum group 20 min, Z=-0.136, P=0.027), as did resection speed (ileocecal valve group 0.14 cm2/min VS cecum group 0.24 cm2/min, Z=-0.223, P=0.022). Adverse events included one postoperative fever in the ileocecal valve group and one delayed bleeding in the cecum group. During the median follow-up of 38 months (7-106 months), there was no case of residual tumor or recurrence. Conclusion:Despite technical challenges in ESD of ileocecal valve lipoma, it is still a safe, feasible and effective treatment method.

Objective To compare and analyze the differences between customized models and commercial universal models in the segmentation of organs-at-risk in cervical cancer,and to investigate the feasibility of customized models.Methods A retrospective analysis was conducted on 270 cervical cancer patients.Senior clinicians manually delineated organs-at-risk,including the bladder,rectum,small intestine,pelvic bone marrow,femoral heads,and kidneys.The cases were randomly selected to develop customized models,with 202 cases allocated to the training set,38 cases to the test set,and 30 cases to the validation set.The universal and customized models were used for segmentation on the test set,and the automatic segmentation results obtained by the two models were compared with manual segmentation results to assess the performance of the customized model.Results Both customized model and universal model had comparable DSC values to manual segmentation,demonstrating satisfactory delineation outcomes(DSC values ranging from 0.7 to 0.9).However,in terms of deviation of centroid and 95％Hausdorff distance,the customized model surpassed the universal model.Conclusion Compared with the universal model,the customized model offers superior accuracy in delineating the structures of organs-at-risk in cervical cancer.As the customized model is optimized based on specific datasets,it provides precise support for clinical decision-making and holds promising applications in the treatment of cervical cancer.

Objective:To investigate the correlation between the clinical features and endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) in patients with cirrhosis.Methods:A total of 148 patients with cirrhosis and portal hypertension who underwent EUS-PPG measurement at the Third Xiangya Hospital of Central South University from March 15, 2022 to June 20, 2023 were selected. The clinical data of patients collected before EUS-PPG measurement were analyzed. Variations in the EUS-PPG across different clinical data subgroups were analyzed. Multivariate linear regression analysis was used to explore the independent factors influencing EUS-PPG.Results:The EUS-PPG was significantly elevated in patients exhibiting red signs (16.62±5.33 mmHg VS 13.44±5.34 mmHg, t=3.616, P<0.001), gastroesophageal varices (15.78±5.30 mmHg VS 9.70±4.77 mmHg, t=4.247, P<0.001), hepatic encephalopathy (20.83±7.52 mmHg VS 14.92±5.35 mmHg, t=2.606, P=0.010), thrombocytopenia (15.66±5.39 mmHg VS 13.29±5.83 mmHg, t=2.136, P=0.034), hypoproteinemia (16.13±5.86 mmHg VS 14.12±5.03 mmHg, t=2.230, P=0.027), and an increased international normalized ratio (16.25±6.00 mmHg VS 14.40±5.11 mmHg, t=2.022, P=0.045). Conversely, the EUS-PPG was significantly reduced in patients with a history of splenectomy and devascularization (13.17±5.88 mmHg VS 15.73±5.34 mmHg, t=-2.379, P=0.019). The EUS-PPG in patients with varying degrees of ascites (no VS slight VS moderate or severe: 13.40±5.48 mmHg VS 15.90±5.49 mmHg VS 16.69±5.17 mmHg, F=5.188, P=0.007) and different Child-Pugh classifications (A VS B VS C: 14.07±5.05 mmHg VS 15.69±5.74 mmHg VS 17.64±5.99 mmHg, F=3.066, P=0.049) increased gradually. Multivariable linear regression analysis showed that red signs ( β=2.44, t=2.732, P=0.007), gastroesophageal varices ( β=4.45, t=2.990, P=0.003), ascites ( β=1.75, t=2.368, P=0.019), and hepatic encephalopathy ( β=5.82, t=2.644, P=0.009) were independent factors for the elevated EUS-PPG. Conclusion:There is a significant correlation between EUS-PPG and the clinical features related to the severity of cirrhotic portal hypertension, which indicates the feasibility of EUS-PPG in evaluating cirrhotic portal hypertension.

Objective To explore basement membrane markers and potential drugs for treatment in idiopathic pulmona-ry fibrosis(IPF).Methods IPF-related datasets were downloaded from the Gene Expression Omnibus(GEO)database,processed to construct basement membrane gene expression matrices associated with IPF,and screened for differential basement membrane genes(DEBMs);DEBMs were enriched for function and pathways,and machine learning algorithms were used to ob-tain candidate signature genes,receiver operating characteristic(ROC)curves were used to identify signature genes and con-struct a nomogram.We performed ssGSEA analysis to explore the correlation between signature genes and immune cells and their functions and predicted the corresponding miRNAs and therapeutic drugs by signature genes.Results A total of 56 DEBMs were extracted;enrichment analysis showed that DEBMs were mainly enriched in"extracellular matrix tissue","extracellular structural tissue",etc.,and were closely related to"ECM-receptor interaction"and"local adhesion spot"pathways.The ma-chine learning has identified six candidate signature genes(TIMP3,P3H2,ITGA7,ITGA4,ADAMTS2,COL8A2),all of which meet the requirements of the signature genes by the ROC curve test,and the nomogram diagnostic value was outstanding(AUC=0.991 523);B cells and Macrophages in IPF were significantly different from the normal group.Finally,miRNAs were predicted to be dominated by miR-4305,miR-3684,progesterone,and tert-butyl hydroperoxide as therapeutic agents with strong relevance to IPF.Conclusion Signature genes and predictive miRNAs may serve as novel markers for IPF diagnosis,and pre-dictive drugs may be a potential source of drugs for treating IPF.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

[Objective]To present a case of complete androgen insensitivity syndrome (CAIS) coexisting with Müllerian duct remnants (MDR) and to review previous reports in the literature to enhance the understanding of the clinical manifestations and pathophysiology of CAIS.[Methods]The study aimed to diagnose complete androgen insensitivity syndrome (CAIS) by conducting physical examinations,chromosomal analysis,whole exome sequencing,laboratory tests including follicle-stimulating hormone (FSH),luteinizing hormone (LH),total testosterone,estradiol,anti-Müllerian hormone (AMH),inhibin B,dehydroepiandrosterone sulfate (DHEAS),androstenedione,17-hydroxyprogesterone,and imaging studies such as pelvic ultrasound and pelvic magnetic resonance imaging (MRI). Laparoscopy revealed the presence of Müllerian duct structures. Additionally,the study reviewed similar cases of CAIS combined with Müllerian duct remnants reported in the literature.[Results]The child presented with female phenotype,elevated levels of FSH,LH,and testosterone. Pelvic MRI showed bilateral cryptorchidism without visible uterus or fallopian tubes. The chromosomal karyotype was 46,XY,and whole exome sequencing identified a pathogenic variant in the androgen receptor (AR) gene,c.2359C>T (p.Arg787*). No abnormalities were found in the AMH and AMHR2 gene tests. Laparoscopic exploration revealed underdeveloped testes and an underdeveloped uterus. Pathology showed the presence of fallopian tube-like structures next to the testicles. A total of 11 cases with genetically confirmed diagnosis of CAIS coexisting with MDR were retrieved from the database. The findings suggest that the initial clinical presentation,biochemical data,and gonadal pathology of CAIS with MDR are similar to those without MDR.[Conclusion]The study reports a patient with CAIS coexisting with MDR,which broadens the clinical spectrum of CAIS and provides a perspective for basic research on Müllerian duct regression that is independent of the AMH-AMHR2 signaling pathway.

Treponema pallidum(Tp),a common sexually transmitted pathogen,can infect the fetus via pla-cental vertical transmission,leading to congenital syphilis(CS).This infection results in adverse pregnancy outcomes,such as stillbirth,miscarriage,preterm birth,and fetal growth restriction.However,the exact pathogenesis remains un-clear.Studies indicate that patients with early syphilis primarily exhibit pro-inflammatory immune responses.The Tp has been proven to induce dysfunction in various immune cells and abnormal expression of cytokines,potentially disrupting im-mune tolerance homeostasis and leading to adverse pregnancy outcomes.Grounded in the current understanding of CS and maternal-fetal immunology by scholars both domestically and internationally,this paper provides a comprehensive review of the potential mechanisms of Tp interacting with the cells of the maternal-fetal interface,ultimately leading to adverse pregnancy outcomes.It summarizes the pathogenesis characteristics,clinical manifestations,and maternal-fetal immune responses of CS.