Objective:To investigate whether ultra-high dose rate (FLASH) irradiation can reduce radiation-induced intestinal injuries of mice compared to conventional dose rate (CONV) irradiation.Methods:Both FLASH and CONV irradiation were delivered with electron beam, with dose rates of 750 Gy/s and 0.5G y/s, respectively. A total of 105 mice were randomly divided into groups using a simple randomization method. Twenty-one mice were selected for weight observation, 7 mice in each group. After 9 Gy FLASH and CONV irradiation on the abdomen, the weight changes of mice were measured every other day, and compared among three groups. Twenty-four mice were selected for pathological examination including 5 mice in the control group. Three-and-a-half-day days after 12 Gy FLASH ( n=10) and CONV irradiation ( n=9) on the abdomen, the intestines of the mice were taken. Pathological sections were stained with hematoxylin-eosin (HE) to compare the number and percentage of regenerated crypts of the small intestine between two groups. After 12 Gy FLASH ( n=10) and CONV irradiation ( n=10) on the abdomen, the survival of 20 mice was observed. After FLASH using 4.5 Gy×2 times ( n=10) and CONV irradiation at 9 Gy×1 time ( n=10) on the abdomen, the weight changes were observed. After FLASH using 6 Gy×2 times ( n=10) and CONV irradiation at 12 Gy×1 time ( n=10) on the abdomen, the survival of mice was observed. The time interval between two irradiation was 1 min. EBT3 film was employed to monitor the actual exposure dose of the mice. The variables conforming to normal distribution were expressed by Mean±SD. Inter group comparison was performed by independent t-test. The survival of mice among different groups was compared by log-rank test. Results:After 9 Gy of abdominal irradiation, the mean weight of mice in the FLASH group was significantly higher than that in the CONV group. The weight of mice in the FLASH and CONV groups was (19.8±0.8) g and (18.0±1.8)g ( P=0.036) at 7 days after irradiation, (22.0±1.0)g and (21.2±0.5)g ( P=0.075) at 15 days after irradiation, and (24.2±1.4)g and (22.0±1.2)g ( P=0.012) at 25 days after irradiation, respectively. After 12 Gy irradiation, the mean survival of mice in FLASH and CONV groups was 4 days and 4.7 days ( P=0.029). After 12 Gy total abdominal irradiation, the mean number of intestinal regenerative crypts in the FLASH and CONV groups was 2.9/mm and 1.2/mm ( P=0.041), and the percentage of intestinal regenerative crypts was 34.1% and 14.1%, respectively. The survival of mice irradiated by FLASH using 6 Gy×2 times was longer compared with that of mice after CONV irradiation at 12 Gy×1 time. The weight of mice after 4.5 Gy×2 times irradiation was higher than that of mice after CONV irradiation at 9 Gy×1 time. Conclusion:Weight, survival and the number of intestinal regenerative crypts in the FLASH group are higher than those in the CONV group after irradiation, indicating that radiation-induced intestinal injury caused by FLASH irradiation is slighter than that of CONV irradiation.

Objective To investigate the expression and role of neutrophil extracellular traps(NETs)in oral squamous cell carcinoma(OSCC).Methods Immunofluorescence and immunohistochemistry were used to detect the expression of NETs in OSCC.The clinico-pathological characteristics and prognosis of patients with different NETs expression levels were analyzed.Density gradient centrifugation was used to isolate neutrophils from human peripheral blood.NETs were induced by phorbol 12-myristate 13-acetate(PMA)and co-cultured with OSCC cells.CCK-8 assay was used to detect changes in OSCC cell proliferation ability.OSCC cell migration ability was detected by Transwell cell migration assay and cell scratch assay.Western blotting(WB)assay was used to detect the effect of NETs on the index of epithelial-mesenchymal transition(EMT).Results NETs'expression in OSCC was higher than that in normal tissues(P＜0.001).The prognosis of patients with high NETs expression was worse than that of patients with low NETs expression(P＜0.05).The expression level of NETs was correlated with the clinical grade,invasion and recurrence degree of OSCC patients(P＜0.05).NETs pro-moted the proliferation and migration of Cal27 and HN6 cells(P＜0.05),and inhibited the protein expression level of epithelial marker and promoted the protein expression level of mesenchymal markers(P＜0.05),which could be reversed by the NETs inhibitor DNaseⅠ.Conclusion NETs are expressed at high levels in OSCC.NETs can promote the proliferation and migration of OSCC cells by regulating epithelial-mesenchymal transition and can affect the prognosis of OSCC patients.

With the advancement in surgical techniques, an increasing number of women with complex congenital heart diseases (such as tetralogy of Fallot, transposition of the great arteries, and single ventricle) survive to childbearing age and conceive, significantly raising the mortality risks for both mother and infant. Early diagnosis, surgical intervention, comprehensive pre-pregnancy assessment, and multidisciplinary collaboration during pregnancy and delivery are crucial to reducing maternal and infant complications and mortality rates in patients with pregnancy complicated by complex congenital heart disease. Therefore, this article provides a review of the current advances in the diagnosis and treatment of pregnancy complicated by complex congenital heart disease.

ObjectiveTo observe the pharmacodynamic effects of Cinnamomi Cortex on the incretin effect in the rat model of diabetes mellites （DM） induced by streptozotocin （STZ） and explore the underlying mechanism from glucagon-like peptide-1 （GLP-1） and dipeptidyl peptidase-4 （DPP-4）. MethodForty SD rats were randomly assigned into blank， model， sitagliptin （0.1 g·kg^-1）， and low- and high-dose Cinnamomi Cortex （0.45 and 0.9 g·kg^-1， respectively） groups. The DM rat model was established by a high-fat diet combined with intraperitoneal injection of 40 mg·kg^-1 STZ in other groups except the blank group. The intervention lasted for 8 weeks. The status， body weight， water intake， food intake， and fasting blood glucose （FBG） of the rats were observed and determined. Hematoxylin-eosin staining was employed to reveal the pathological changes of the pancreas， and immunohistochemistry to detect the expression of glucagon in the pancreas. Biochemical assay was employed to measure the serum levels of lipid metabolism indexes such as total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL）. Enzyme-linked immunosorbent assay was employed to determine the levels of glycosylated hemoglobin， insulin， glucagon， GLP-1， and glucose-dependent insulinotropic polypeptide （GIP） in rat serum， and Western blot to determine the protein levels of GLP-1 and DPP-4 in the pancreas. ResultAfter 8 weeks of intervention， the model group showed higher body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and lower HDL， GLP-1， and GIP than the blank group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed lower body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and higher HDL， GLP-1， and GIP than the model group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed recovered morphology of islet cells and no nucleus aggregation. Compared with the model group， the Cinnamomi Cortex groups showed declined levels of glucagon in the center of islet cells. Compared with the blank group， the model group showed up-regulated protein level of DPP-4 and down-regulated protein level of GLP-1 （P<0.01）. Compared with the model group， the high-dose Cinnamomi Cortex groups showed down-regulated protein level of DPP-4 and up-regulated protein level of GLP-1 （P<0.05）. ConclusionCinnamomi Cortex may reduce blood glucose and improve incretin effect to lower the blood glucose level by regulating DPP-4 and GLP-1 in DM rats.

OBJECTIVE: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. METHODS: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. RESULTS: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. CONCLUSION Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
Humans ; Loeys-Dietz Syndrome/genetics* ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Receptor, Transforming Growth Factor-beta Type II/genetics* ; Transforming Growth Factor beta3 ; Face

Objective:To study the logistic regression model and Chi-square automatic interaction detection decision tree model in the prediction of the recurrence of acute pancreatitis (AP).Methods:Clinical data of 364 patients with AP admitted to the Affiliated Hospital of Jiangnan University from June 2021 to June 2022 were retrospectively analyzed, including 219 males and 145 females, aged 53 (19-91) years. The patients were divided into the recurrence group ( n=63), those who experienced a second or more episodes of AP, and the initial group ( n=301), those who were diagnosed of AP for the first time. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with recurrence of AP, and the decision tree model was used to analyze those factors. Receiver operating characteristic (ROC) curve were plotted to analyze the predictive performance of the two models. Results:Multivariate logistic regression analysis showed that age ( OR=0.969, 95% CI: 0.949-0.990, P=0.004), body mass index ( OR=1.142, 95% CI: 1.059-1.232, P=0.001), and hyperlipidemia ( OR=3.034, 95% CI: 1.543-5.964, P=0.001) were independent factors influencing the recurrence of AP. The accuracy of the model in predicting recurrence was 83.2% (303/364). The decision tree model showed that hyperlipidemia and body mass index were factors influencing the recurrence of AP, with an accuracy of 82.7% (301/364) in predicting recurrence. The area under the ROC curve was larger in the logistic regression model compared to that in the decision tree model (0.776 vs 0.730, Z=2.02, P=0.043). Conclusion:The logistic regression model and the Chi-square automatic interaction detection decision tree model can help predict the recurrence of AP. It is recommended to combine the two models to better guide clinical practice.

Objective:To evaluate the relationship between preoperative widespread pain and chronic post-surgical pain (CPSP) following total knee arthroplasty (TKA) in the patients with knee osteoarthritis.Methods:Two hundred American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients with knee osteoarthritis, aged 40-70 yr, undergoing elective the first unilateral primary TKA under general anesthesia, were enrolled.The widespread pain index, visual analogue scale score, Hospital Anxiety and Depression Scale and Central Sensitization Inventory scores were recorded at 1 day before surgery.The patients were divided into CPSP-positive group and CPSP-negative group according to visual analogue scale score at 6 months after surgery.Risk factors for CPSP were analyzed by logistic regression.Results:The results of logistic regression analysis showed that increased preoperative widespread pain index score, Central Sensitization Inventory score and Hospital Anxiety and Depression Scale score and female were risk factors for CPSP after TKA.Conclusions:Preoperative widespread pain is a risk factor for CPSP following TKA in the patients with knee osteoarthritis.

Objective:To study the differences of intestinal flora between neonatal rats with intrauterine hypoxia and healthy neonatal rats using high-throughput sequencing technology to determine the effects of intrauterine hypoxia on neonatal intestinal flora.Methods:Intrauterine hypoxia model were established in neonatal rats. On d1 and d7 after birth, intestinal samples were collected from intrauterine hypoxic group and normal control group and assigned into INH1 group (intrauterine hypoxia d1), INH7 group (intrauterine hypoxia d7), NOR1 group (normal control d1) and NOR7 group (normal control d7). 16S rRNA sequencing were conducted using these samples and the differences in the diversity, richness and composition of the flora among the groups were compared.Results:(1) The Alpha diversity of the intestinal flora in the INH1 group was higher than the NOR1 group. Specifically, both sobs and chao indices, representing the richness of the flora, in INH1 group were significantly higher than the NOR1 group (sobs index: 114.5±35.6 vs. 50.5±21.3, chao index: 135.6±38.5 vs. 73.9±28.8)( P<0.05). Compared with the NOR7 group, the mean values of sobs, ace, chao, simpson and shannon indices in the INH7 group showed no significant differences ( P>0.05). (2) At the phylum and genus level, the dominant bacterial groups in the intrauterine hypoxia group on d1 were firmicutes and streptococcus and proteus and escherichia for the normal control group. The difference of intestinal flora between intrauterine hypoxia group and the normal control group on d7 was smaller than the difference between the two groups on d1. Compared with INH1 group, the INH7 group had increased escherichia composition and decreased streptococcus composition. Conclusions:Intrauterine hypoxia changes the initial colonization and later affects the abundance and structural composition of the intestinal flora in newborn rats.

Objective:To review clinical outcomes of extended V-Y latissimus dorsi myocutaneous flap in reconstruction of chest wall defects.Methods:Patients receiving chest wall defect reconstruction with extended V-Y latissimus dorsi myocutaneous flap at Fudan University Zhongshan Hospital from January 2016 to December 2018 were enrolled. Patients were followed up for more than 6 months to detect complications such as blood supply disorder of the flap, wound dehiscence, seroma or tumor recurrence.Results:A total of 16 patients, aged 28-78 years, with an average age of 54.8 years, were included. The chest wall defect size ranged from 10 cm×15 cm to 19 cm×26 cm. Among these cases, 1 case had venous congestion in the distal triangle area of the flap, 1 case had partial wound dehiscence of the flap, 2 cases developed seroma on the back and 2 cases under the flap. All cases healed after changing dressing and drain placement. All the other cases had complete flap survival and primary wound healing. All cases were followed up from 7 to 29 months, with good flap appearance and function and patient satisfaction with results.Conclusions:Chest wall defect reconstruction with V-Y latissimus dorsi myocutaneous flap is safe and reliable. It can repair a large chest wall wound and allow primary closure of the donor site simultaneously, which is worthy of being popularized in chest wall reconstruction.

Objective:To present a melanoma research platform, a big data and artificial intelligence tool, to realize the structured storage and accurate management of medical data, and improve the efficiency of clinical research.Methods:The multi-system data of the period from October 2007 to September 2020 was extracted from Zhongshan Hospital, Fudan University. The data was standardized, structured, and fully integrated. The big data technology was used to extract and integrate the data from various subsystems in the hospital, and a melanoma big database was established. Through artificial intelligence algorithm the disease characteristics were deeply mined, and the survival analysis was carried out using in-database algorithms.Results:The big data and artificial intelligence research platform for melanoma provides data screening and export, statistical analysis, original record tracing, and automatic selection of analysis algorithm. The melanoma platform achieved the aims of data visualization, trials preview, second response, and artificial intelligence automatic data extraction and storage. It can build a closed-loop research procedure efficiently. After screening, 152 patients with complete information were collected. There were 78 males and 74 females; the median age was 61 years (range, 30-97 years). Foot (133 patients) was the most common site of tumor, while groin (2 patients) and back (2 patients) were the least common site of tumor. The maximum diameter of the tumor ranged from 1 to 80 mm, with an average of 23.55 mm and a median of 20 mm. The most common Clark’s level was Ⅳ (62 patients). Ulceration was found in 17 patients. 10 patients had lymph node metastasis. Lung (5 patients) was the most common distant metastasis organ. More than 80% of patients’ Breslow thickness was less than 1 mm. Survival analysis showed that age ≥ 70 years, Clark’s level ≥ Ⅳ and Breslow thickness ≥ 4 mm were risk factors for poor prognosis ( P<0.05). Conclusions:The big data and artificial intelligence research platform for melanoma realizes the structured storage and accurate management of clinical data regarding melanoma, which provides a promising solution for the efficient use of clinical data.