Objective:To investigate the value of CT imaging radiomics in predicting the therapeutic effect of extracorporeal shock wave lithotripsy (ESWL) for pancreatic duct stones.Methods:The clinical data of 167 patients with pancreatic duct stones treated with ESWL in the Department of Gastroenterology, the First People's Hospital of Hangzhou, Westlake University from July 2016 to January 2023 were retrospectively analyzed. Patients were divided into complete lithotripsy group (stone diameter ≤3 mm, n=94) and incomplete lithotripsy group (stone diameter>3 mm, n=73), according to the size of the largest residual stone after the first ESWL treatment. ITK SNAP software was used to delineate the images of pancreatic duct stones, and the artificial intelligence tool kit developed by United Shadow Company was used to extract the image radiomics characteristics. The pancreatic duct stone data set was randomly assigned into the training set ( n=118) and the test set ( n=29) in the ratio of 8∶2, and the absolute maximum normalization treatment was used, followed by peacekeeping selection through the minimum absolute contraction and selection operator (Lasso) to calculate the CT image radiomics score, and the logistic regression classifier was used to construct the ESWL treatment effect prediction model of pancreatic duct stones. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) and sensitivity, specificity, and accuracy were calculated to assess the performance of the prediction model. Decision curve analysis was used to evaluate the clinical value of CT radiomics score in the diagnosis of ESWL for pancreatic duct stones. Results:A total of 2 287 imaging radiomics characteristics were extracted, and 11 optimal imaging radiomics characteristics were finally screened by Lasso regression dimensionality reduction to establish a prediction model for ESWL treatment effect of pancreatic duct stones. The AUC values of the training set and the test set were 0.89 and 0.87, respectively, and the sensitivity, specificity, and accuracy were 82% and 79%, 82% and 82%, 82% and 80%, respectively. The AUC value in the independent validation set was 0.90, and the sensitivity, specificity, and accuracy were 78%, 90%, and 85%, respectively. The results of decision curve analysis showed that when the probability of ESWL efficacy in the diagnosis of pancreatic duct stones with CT image radiomics score was >0.05, the use of CT image radiomics score in the diagnosis of ESWL efficacy in pancreatic duct stones was more beneficial to patients in clinical practice than not.Conclusions:The treatment effect of ESWL for pancreatic duct stones can be predicted by CT imaging radiomics model.

Objective To observe the value of feature pyramid network(FPN)for automatic segmentation and semantic feature classification of spontaneous intracerebral hemorrhage(sICH)hematoma showed on non-contrast CT.Methods Non-contrast CT images of 408 sICH patients in hospital A(training set)and 103 sICH patients in hospital B(validation set)were retrospectively analyzed.Deep learning(DL)segmentation model was constructed based on FPN to segment the hematoma region,and its efficacy was assessed using intersection over union(IoU),Dice similarity coefficient(DSC)and accuracy.Then DL classification model was established to identify the semantic features of sICH hematoma.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of DL classification model for recognizing semantic features of sICH hematoma.Results The IoU,DSC and accuracy of DL segmentation model for 95％sICH hematoma in training set was 0.84±0.07,0.91±0.04 and(88.78±8.04)％,respectively,which was 0.83±0.07,0.91±0.05 and(88.59±7.76)％in validation set,respectively.The AUC of DL classification model for recognizing irregular shape,uneven density,satellite sign,mixed sign and vortex sign of sICH hematoma were 0.946-0.993 and 0.714-0.833 in training set and validation set,respectively.Conclusions FPN could accurately,effectively and automatically segment hematoma of sICH,hence having high efficacy for identifying semantic features of sICH hematoma.

[摘 要] 目的：评价口服携带HPV16 E7 shRNA和IL-12基因的重组短双歧杆菌在小鼠体内抗宫颈癌移植瘤的效果。方法：将pMG36e-E7 shRNA、pMG36e-mIL-12D质粒分别转化短双歧杆菌，经筛选鉴定并扩增获得携带HPV16 E7 shRNA和IL-12 基因的重组短双歧杆菌。通过小鼠皮下宫颈癌细胞移植建立荷瘤小鼠模型。口服重组短双歧杆菌1、7 d后，检测小鼠主要器官（心、肝、脾、肺、肾）和肿瘤组织匀浆液或血清在PYG培养基中形成的菌落数量，评价短双歧杆菌的肿瘤靶向性，以小鼠体内肿瘤生长曲线评估重组短双歧杆菌的抗肿瘤效果，通过主要器官切片H-E染色和检测荷瘤小鼠血清相关细胞因子水平评价口服重组短双歧杆菌的安全性。结果：成功制备重组短双歧杆菌和宫颈癌TC-1细胞移植瘤小鼠。7 d后，移植瘤组织匀浆液和血清的菌落数量证实短双歧杆菌具有靶向体内瘤组织的定殖能力，口服重组短双歧杆菌明显抑制荷瘤小鼠的肿瘤生长（P<0.05或P<0.01），但联合使用携带HPV16 E7 shRNA和IL-12基因的重组双歧杆菌的肿瘤抑制率与单独使用的并无显著差异，治疗后未见对荷瘤小鼠主要器官的损伤和血清中IL-12及IFN-γ的水平明显变化。结论：短双歧杆菌可用作靶向肿瘤的治疗性基因分子递送载体，其对宫颈癌移植瘤的疗效明显且安全可控。

Objective:To explore the effect of Notch1 signaling on regulatory T cells and its roles in vascular damage in patients with Kawasaki disease (KD).Methods:A total of 42 children with KD were enrolled in the present study from March 2019 to June 2020, as 32 age-matched healthy children were recruited as control. The proportions of CD4 +CD25 hiFoxp 3+ regulatory T cells (Treg) and expressions of transcription factor forkhead box protein 3 (Foxp3), cytotoxic T lymphocyte associated antigen-4 (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), and Notch1 protein were evaluated by flow cytometry. Chromatin immunoprecipitation was conducted to detect acetylation level of histone H4 (H4Ac) associated with the promoter of Foxp3 gene and its binding abilities of Notch1 intracellular domain 1 (NICD1), recombination signal binding protein for immunoglobulin kappa J region (RBP-J) and p300 in CD4 + T cells. Transcription levels of Foxp3, presenilin 1 (PSEN1), mastermind like transcriptional coactivator 1 (MAML1), and RBP-J in CD4 + T cells were determined by real-time polymerase chain reaction (PCR). Concentrations of interleukin (IL)-10 and transforming growth factor-β (TGF-β) in plasma and culture supernatant stimulated with Jagged1 were measured by enzyme linked immunosorbent assay. Independent-sample t-test, Pearson correlation analysis was used as the statistical method in this study. Results:① The frequencies of Treg in acute KD patients decreased significantly [(4.3±1.5)% vs (7.9±2.9)%; t=6.41, P<0.001], as protein levels of Foxp3, CTLA4 and GITR and concentrations of IL-10 and TGF-β in plasma reduced remarkably in acute KD patients ( t=6.87, P<0.001; t=4.26, P<0.001; t=7.88, P<0.001; t=8.42, P<0.001; t=13.01, P<0.001). All parameters afore-mentioned in patients combined with coronary artery lesions (CAL) were lower than those of patients without coronary artery lesions (NCAL) ( t=5.83, P<0.001; t=3.83, P<0.001; t=3.28, P=0.002; t=5.05, P<0.001; t=5.96, P<0.001; t=5.17, P<0.001), and increased after therapy ( t=7.13, P<0.001; t=6.10, P<0.001; t=4.31, P<0.001; t=6.55, P<0.001; t=7.40, P<0.001; t=7.84, P<0.001). ② H4Ac associated with promoter of Foxp3 gene and the binding abilities of NICD1 and p300 in acute KD patients were lower than those of the controls ( t=10.25, P<0.001; t=6.93, P<0.001; t=6.75, P<0.001), and increased remarkably after therapy ( t=7.72, P<0.001; t=4.16, P<0.001; t=5.76, P<0.001). Meanwhile, the three items in CAL group were found to be less than those of NCAL group ( t=6.08, P<0.001; t=2.66, P=0.011; t=6.02, P<0.001). Pearson correlation analysis showed a positive correlation between H4Ac associated with Foxp3 promoter and its mRNA level in acute KD patients ( r=0.47, P<0.001). No statistical significant difference about the binding ability of RBP-J with Foxp3 promoter were found among the groups ( t=0.57, P>0.05; t=0.61, P>0.05; t=1.20, P>0.05). ③ Protein level of Notch1 and the expressions of PSEN1, MAML1 and RBP-J mRNA in CD4 + T cells from acute KD patients were down-regulated remarkably ( t=5.28, P<0.001; t=6.31, P<0.001; t=11.78, P<0.001; t=8.06, P<0.001), and restored after therapy ( t=4.77, P<0.001; t=6.43, P<0.001; t=11.95, P<0.001; t=7.79, P<0.001). In parallel, the four indexes aforementioned of CAL group were lower than those of NCAL group ( t=3.16, P=0.003; t=4.13, P<0.001; t=5.42, P<0.001; t=4.05, P<0.001). Upon rhJagged1 stimulation for 48 hours, H4Ac level of Foxp3 promoter and its binding abilities with NICD1 and p300 in CD4 + T cells in KD patients and control group was significantly higher than those of untreated group [(KD: t=15.36, P<0.001; t=7.25, P<0.001; t=14.29, P<0.001), (Ctrl: t=7.87, P<0.001; t=5.71, P<0.001; t=8.74, P<0.001)], as the binding ability of RBP-J with Foxp3 promoter increased slightly without statistically significant difference (KD: t=1.11, P>0.05; Ctrl: t=1.37, P>0.05). Simultaneously, H4Ac level of Foxp3 promoter and its binding abilities with NICD1 and p300 in KD group were still lower than those of the control group after stimulation ( t=3.86, P<0.001; t=3.42, P=0.001; t=2.85, P=0.006). ④ After incubation of PBMC from heathy children with KD serum, the proportion of Treg cells, protein level of Foxp3 and expressions of Notch1 and RBP-J in CD4 + T cells in the group treated with IVIG increased significantly compared with the untreated group ( t=7.10, P<0.001; t=10.16, P<0.001; t=8.06, P<0.001; t=9.77, P<0.001), as well as H4Ac level of Foxp3 promoter and its binding abilities with NICD1 in the group treat with IVIG were also higher than the latter ( t=7.24, P<0.001; t=8.24, P<0.001). Conclusion:Insufficiency and impaired function of Treg caused by aberrant Notch1 signaling may be the important factor contributing to immune dysfunction and vascular damage in KD.

Objective:To investigate the efficacy and safety of low dose S-ketamine in analgesia of elderly patients with non-traumatic acute abdomen (NTAA) in emergency department.Methods:This was a randomized controlled trail. From January to August 2021, elderly patients with NTAA in the Emergency Department of the No. 904 Hospital of the Joint Logistic Support Force were selected. Analgesia was administered intravenously with 0.3 mg/kg S-ketamine or 0.1 mg/kg morphine injection for 15 min. Visual analogue score (VAS), respiratory rate, heart rate, non-invasive blood pressure and pulse oxygen saturation were recorded at 15 min, 30 min, 60 min and 90 min. The mini-mental state examination (MMSE) scores were recorded at 90 min after injection. The incidence of salvage analgesia, incidence of adverse reactions and diagnostic accuracy after analgesia were recorded in the two groups. VAS scores and vital signs were compared between the two groups by two-way repeated measures analysis of variance, and multiple comparisons between and within groups were performed.Results:A total of 137 elderly patients with NTAA were selected and randomly divided into two groups: S-ketamine group (SK group, 68 cases) and morphine group (M group, 69 cases). After the exclusion of patients with abscission, 39 cases were included in the SK group and 45 cases in the M group. VAS score of the SK group was significantly lower than that of the M group in 15 min after administration [(3.1±1.8) vs. (4.8±2.2)], and the difference was statistically significant ( P=0.013). There were no significant differences in vital signs and MMSE score between the two groups or within the group at each time point after medication (all P>0.05). However, the incidence of dizziness in the SK group was significantly higher than that in the M group (61.54% vs. 31.11%, P=0.005). Conclusions:Intravenous administration of low dose S-ketamine is not considered to be more effective than morphine in alleviating acute abdominal pain in elderly patients with NTAA. S-ketamine provides not only satisfactory analgesia but also short recovery time and high controllability. S-ketamine is one of the recommended analgesic alternatives of NTAA for elderly patients in emergency.

Objective:To compare the clinical effects of hip arthroplasty through direct anterior approach (DAA) in lateral decubitus in the treatment of hip osteoarthritis caused by Kaschin-Beck disease and congenital acetabular dysplasia.Methods:The prospective study method was used to select the patients who needed hip arthroplasty in the Fourth Department of Orthopedics, the Second Affiliated Hospital of Harbin Medical University from January 2015 to December 2019. All of them were operated with lateral decubitus DAA. According to the inclusion criteria, they were divided into Kacshin-Beck disease hip osteoarthritis group (group A) and congenital acetabular dysplasia hip osteoarthritis group (group B). Hip Harris score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, visual analogue scale (VAS) score were conducted, and hip abduction angle and flexion angle were measured before surgery, 3, 14 days and 1, 3, and 12 months after surgery.Results:Nineteen and twenty-two patients were included in group A and group B, respectively. All patients successfully completed the surgery. There was no significant difference in Harris score between the two groups before surgery, 3, 14 days, and 1, 12 months after surgery ( P > 0.05). There were no significant differences in WOMAC score, VAS score, hip abduction angle and hip flexion angle between the two groups before surgery and each time point after surgery ( P > 0.05). In the same group, there were significant differences in Harris score, WOMAC score, VAS score, hip abduction angle and hip flexion angle at different time points ( P < 0.001). All postoperative indicators were significantly improved compared with those before surgery. Conclusions:There is no significant difference in the clinical effects of hip arthroplasty through lateral decubitus DAA in the treatment of hip osteoarthritis caused by Kaschin-Beck disease and congenital acetabular dysplasia. This surgical method has good therapeutic effect on both types of hip osteoarthritis.

Objective:To investigate the changes and significance of granulocyte-like myeloid-derived suppressor cells (G-MDSC) in the acute phage of Kawasaki disease (KD).Methods:Forty-two children with acute KD were enrolled in the present study and 32 age-matched healthy children were selected as control group. The proportion of HLA-DR -CD11b + CD33 + CD14 -CD15 + G-MDSC, the concentration of reactive oxygen species (ROS) and the expression of arginase-1 (Arg-1), programmed death-ligand 1 (PD-L1), cytotoxic T lymphocyte associated protein 4 (CTLA4), glycoprotein 130 (gp130) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) at protein level were detected by flow cytometry. Quantitative real-time PCR was used to measure the expression of inducible nitric oxide synthase (iNOS), interferon regulatory factor 8 (IRF-8), IL-6 receptor α subunit (IL-6Rα), granulocyte colony-stimulating factor receptor (G-CSFR), CCAAT/enhancer binding protein β (C/EBPβ), suppressor of cytokine signaling 1 (SOCS1) and SOCS3 at mRNA level in G-MDSC. Chromatin immunoprecipitation was performed to detect the acetylation of histone H3 at the promoters of SOCS1 and SOCS3 genes. Plasma concentrations of IL-6 and granulocyte colony-stimulating factor (G-CSF) and protein levels of IL-10, transforming growth factor-β (TGF-β) and nitric oxide (NO) in the culture supernatant of G-MDSC stimulated with LPS were measured by ELISA. Results:(1) Compared with the control group, the proportion of HLA-DR -CD11b + CD33 + CD14 -CD15 + G-MDSC as well as the concentration of ROS and the expression of inhibitory molecules (Arg-1, PD-L1 and CTLA4) in G-MDSC increased significantly in patients with acute KD ( P<0.05). Moreover, the concentrations of IL-10 and TGF-β in culture supernatant of G-MDSC were also higher than those of the control group after stimulation with lipopolysaccharide for 48 h ( P<0.05). All of the seven afore-mentioned indexes in KD patients with coronary artery lesion (CAL group ) were lower than those in patients without coronary artery lesion (NCAL group) ( P<0.05), and restored to some extent after IVIG therapy ( P<0.05). There were no statistical differences in iNOS expression or NO concentration in culture supernatant of G-MDSC among different groups ( P<0.05). (2) Plasma concentrations of IL-6 and G-CSF, and the expression of IL-6Rα, gp130, G-CSFR, pSTAT3 and C/EBPβ increased remarkably during acute phase of KD ( P<0.05). The expression of IRF-8 at transcription level in patients with acute KD was found to be lower than that of healthy controls ( P<0.05), and restored significantly after IVIG therapy ( P<0.05). Moreover, the plasma concentrations of IL-6 and G-CSF and the expression of IL-6Rα, gp130, G-CSFR and IRF-8 in the CAL group were higher than those in the NCAL group ( P<0.05), while the expression of pSTAT3 and C/EBPβ was lower in the CAL group ( P<0.05), which were restored by IVIG therapy ( P<0.05). (3) In patients with acute KD, the expression of SOCS1 and SOCS3 at mRNA level and histone acetylation at the promoters of SOCS1 and SOCS3 genes were reduced significantly in comparison with those in healthy controls ( P<0.05) , but were increased remarkably after IVIG treatment( P<0.05). The four indexes were higher in the CAL group than in the NCAL group ( P<0.05). Pearson correlation analysis showed the expression of SOCS1 and SOCS3 was negatively correlated with the protein level of pSTAT3 in G-MDSC of patients with acute KD ( r=-0.46 and -0.32, P<0.05). Conclusions:Changes in the number and function of G-MDSC caused by aberrant histone acetylation at SOCS1 and SOCS3 genes might contribute to the immune dysfunction and vascular damage in patients with KD.

Objective:To investigate the changes of monocytic myeloid-derived suppressor cells (M-MDSC) in children with acute Kawasaki disease (KD) and its roles in the immunological pathogenesis of KD.Methods:A total of 38 children with acute KD were enrolled in the present study and 32 age-matched healthy children were selected as control group. The proportions of HLA-DR -CD11b + CD33 + CD15 -CD14 + M-MDSC and CD4 + CD25 + CD127 - regulatory T cells (Treg) in peripheral blood, concentrations of reactive oxygen species (ROS) and expression of arginase-1 (Arg-1), CD39, CD73, CD40, CD40L and CCR5 at protein levels were detected by flow cytometry. Quantitative real-time PCR was used to evaluate the transcription levels of inducible nitric oxide synthase (iNOS) in M-MDSC and the transcription levels of cytotoxic T-lymphocyte associated antigen 4 (CTLA4) and lymphocyte-activation gene 3 (LAG3) in Treg. Concentrations of NO, CCL3, CCL4, CCL5, IL-10 and TGF-β in the supernatants of cell culture were measured by ELISA. Results:(1) The proportion of HLA-DR -CD11b + CD33 + CD15 -CD14 + M-MDSC, the concentration of intracellular ROS and the expression of iNOS, CD39 and CD73 in M-MDSC decreased significantly in patients with acute KD as compared with those in the control group ( P<0.05), and the concentrations of NO, IL-10 and TGF-β in culture supernatant of M-MDSC were lower than those in the control group upon lipopolysaccharide (LPS) stimulation for 48 h ( P<0.05). All of the aforementioned indexes restored to some extent after intravenous immunoglobulin (IVIG) therapy ( P<0.05). No statistical differences were found in Arg-1 expression between healthy controls and patients with KD before or after IVIG therapy ( P<0.05). (2) CD40 expression on M-MDSC was significantly lower in the acute KD group than in the control group ( P<0.05). The concentrations of CCL3, CCL4 and CCL5 in the culture supernatants of M-MDSC were lower in the acute KD group than in the control group after LPS stimulation ( P<0.05). With IVIG treatment, all of the indexes were up-regulated significantly ( P<0.05), although CD40 expression was still lower in the acute KD group than in the control group ( P<0.05). (3) The proportion of CD4 + CD25 + CD127 -Treg and the expression of CTLA4, LAG3, CD40L and CCR5 reduced significantly in patients with acute KD as compared those in healthy controls ( P<0.05), and all increased remarkably after IVIG therapy ( P<0.05). Pearson correlation analysis showed a positive correlation between the proportions of M-MDSC and Treg in patients with acute KD ( r=0.58, P<0.05). Conclusions:Insufficiency and impaired function of M-MDSC might be a major cause of immune dysfunction in patients with acute KD.

Objective:To analyse the effect of preoperative renal function classification on early outcomes for patients with acute type A aortic dissection(AAAD) and to estimate the risk factors of postoperative major adverse events.Methods:From January 2012 to December 2019, 226 patients with AAAD who underwent total arch replacement at our institution were retrospectively analysed, including 146 males and 80 females, aged(54.4±12.5) years old. Stages of preoperative renal function were defined as follows: Normal[estimated glomerular ltration rate(eGFR)≥90 ml·min -1·1.73 m -2, 68 cases], Mild(eGFR 60-89 ml·min -1·1.73 m -2, 73 cases); Moderate(eGFR 30-59 ml·min -1·1.73 m -2, 57 cases), Severe(eGFR<30 ml·min -1·1.73 m -2, 28 cases). The independent risk factors for postoperative death were analyzed by logistic regression analysis. The area under the receiver operating characteristic curve was used to assess the efficiency of eGFR for predicting the postoperative hemodialysis. Results:In-hospital death occurred in 24(10.6%) cases. Major complications included postoperative hemodialysis in 49(21.7%) cases, stroke in 19(8.4%) cases and tracheotomy in 15(6.6%) cases. The best cut-off value of the eGFR for predicting postoperative hemodialysis was 36.5 ml·min -1·1.73 m -2(area under the receiver operating characteristic curve was 0.793). The following variables were found to be risk factors of in-hospital mortality in multivariate logistic regression analysis: serum creatinine, eGFR<30 ml·min -1·1.73 m -2, neural malperfusion, bowel malperfusion, postoperative stroke and hemodialysis. Conclusion:Total arch replacement can be safely performed in patients with AAAD and mild renal dysfunction. Preoperative renal dysfunction is a risk factor for postoperative hemodialysis, and eGFR is useful for predicting the requirement for hemodialysis after total arch replacement. The severity of preoperative renal dysfunction could greatly influence the outcomes after total arch replacement for AAAD. More importance should be attached to the assessment of preoperative renal function during clinical risk assessment.

Osteosarcoma is a kind of primary malignant tumor of bone originated from mesenchymal tissue, which mainly occurs in children and adolescents, and presents the characteristics of high malignancy, rapid growth, early metastasis and poor prognosis. Currently, most of the studies at home and abroad mainly focused on therapeutic procedures. However, reliable prediction indices or evaluation systems are also pivotal for monitoring disease change, guiding treatment and evaluating prognosis. Multiple clinical predictors have been reported to be related to the prognosis of osteosarcoma, which can be roughly divided into 9 categories according to their characteristics. Each kind of predictor owns its inherent advantage and disadvantage, and full understanding of them and their characteristics can be helpful to improve the prognosis of osteosarcoma.