Objective:To identify the risk factors for simple congenital ptosis.Methods:A case-control study was performed.A total of 106 children diagnosed with simple congenital ptosis at the Second Affiliated Hospital of Zhejiang University School of Medicine from October 2018 to January 2021 were recruited as a case group, and 106 sex-matched children without congenital abnormalities were enrolled as a control group at the same period.Ophthalmic examinations, including interpalpebral fissure height and margin reex distance 1, were performed on all participants.A questionnaire survey was administered to their mothers.The questionnaire included demographic information, prenatal maternal diseases, medical treatments and environmental exposures during pregnancy.Univariate analysis was used to compare the differences in variables between the case and control groups.Variables with P<0.20 were retained for multivariate logistic regression analysis to identify the risk factors for simple congenital ptosis.The goodness of fit of the model was evaluated by the Hosmer-Lemeshow test, and collinearity was assessed by the variance inflation factor (VIF). This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (No.2019-136). The method and purpose of the study were fully explained to the children's guardians and written informed consent was obtained. Results:Comparisons of gestational age <37 weeks, birth order ≥2, maternal age, antibiotic use in the first trimester, paternal smoking ≥half a pack per day, and prenatal maternal passive smoking between the two groups were all with P<0.20.Multivariate logistic regression analysis showed that gestational age <37 weeks (odds ratio [ OR]=4.58; 95% confidence interval [ CI]: 1.24-16.85), paternal smoking ≥half a pack per day ( OR=2.28; 95% CI: 1.22-4.28) and prenatal maternal passive smoking ( OR=3.13; 95% CI: 1.16-8.41) were risk factors for simple congenital ptosis.No significant collinearity was found among these identified factors (all VIF<5). Conclusions:Preterm birth, paternal smoking, and prenatal maternal passive smoking are risk factors for simple congenital ptosis.

Objective To investigate the expressions of IL-18, IL-18 binding protein isoform a (IL-18BPa) and IL-18 receptor α (IL-18Rα) in blood CD4⁺ Th2 cells of patients with allergic rhinitis (AR) and the effects of allergens on their expressions. Methods Blood samples of AR patients and healthy control subjects (HCs) were collected. Peripheral blood mononuclear cells (PBMCs) and CD4⁺ T cells sorted by immunomagnetic beads were stimulated by crude extract of Artemisia sieversiana wild allergen (ASWE), Platanus pollen (PPE) and house dust mite extract (HDME). Flow cytometry was used to detect the expression of IL-18, IL-18BPa and IL-18Rα in CD4⁺ Th2 cells, and BioPlex was used to detect the level of plasma IL-4 and analyze its correlation with the proportion of IL-18⁺ Th2 cells. Results Compared with HCs, the proportion of IL-18⁺ cells was increased in Th2 cells of AR patients; MFI of IL-18 was increased, while that of IL-18Rα was decreased. Moreover, allergens induced IL-18 and IL-18Rα expression in sorted CD4⁺ Th2 cells of HCs and induced IL-18Rα in that of AR patients. Additionally, elevated plasma IL-4 level was found in AR patients, which was moderately correlated with the percentage of IL-18⁺ Th2 cells. Conclusion Allergens may be involved in the pathogenesis of AR by inducing expression of IL-18 in peripheral blood CD4⁺ Th2 cells.
Humans ; Th2 Cells ; Interleukin-18/metabolism* ; Up-Regulation ; Leukocytes, Mononuclear/metabolism* ; Interleukin-4/metabolism* ; Rhinitis, Allergic/metabolism* ; Allergens ; Cytokines/metabolism*

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. Dysmorphic neurons are the major histopathological feature of type II FCD, but their role in seizure genesis in FCD is unclear. Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients. Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in type II FCD, including an enlarged soma, aberrant dendritic arbors, increased current injection for rheobase action potential firing, and reduced action potential firing frequency. Intriguingly, the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na⁺-K⁺-Cl^- cotransporter. In addition, we found a depolarizing shift of the GABA reversal potential in the CamKII-cre::PTEN^flox/flox mouse model of drug-resistant epilepsy, suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons. Thus, imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in type II FCD.
Animals ; Drug Resistant Epilepsy/surgery* ; Epilepsy/pathology* ; Malformations of Cortical Development/pathology* ; Malformations of Cortical Development, Group I ; Mice ; Neurons/pathology* ; Seizures/pathology*

ObjectiveTo investigate the effects of 4 weeks of aerobic exercise combined with traditional Chinese medicine （TCM） on the regulation of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/glycogen synthase kinase-3β （GSK-3β） signaling pathway and related apoptotic proteins in AD rats， and to explore its mechanism of action in improving cognitive function of AD rats. MethodFifty male SD rats were randomly divided into Sham group， exercise （EX） group， Alzheimer's disease （AD） group （model）， TCM group （Dabuyuan Jian）， and EX+TCM group， 10 in each group. Aβ_25-35 oligomer solution was injected into the hippocampal region to establish the AD rat model， and the EX group underwent 6 days/week of running table training. The TCM group was given Dabuyuan Jian （5.36 g∙kg^-1） by gavage， and the EX+TCM group received running table training combined with intragastric administration of Dabuyuan Jian. An equal volume of purified water was given to the Sham， AD， and EX groups by gavage. The rats' learning memory was evaluated by Morris water maze. The morphological changes and ultrastructural changes of hippocampal neurons were observed by hematoxylin-eosin （HE） staining and transmission electron microscopy， respectively. Western blot was performed to detect the protein expression levels of Akt， p-Akt， GSK-3β， p-GSK-3β， β-catenin， Bcl-2， Bax， and cleaved Caspase-3 in the hippocampus of rats. ResultCompared with the Sham group， the AD group showed an increase in escape latency and total swimming distance， and a decrease in the residence time in the target quadrant （P<0.01）， with loose and disorganized arrangement of hippocampal pyramidal cells， a decrease in density， myelin-like changes in hippocampal ultrastructure， and a blurring of mitochondrial swelling. In addition， the expression of Bcl-2， p-Akt， p-GSK-3β and β-catenin was down-regulated （P<0.05， P<0.01） while the expression of cleaved Caspase-3 was up-regulated （P<0.05）. Compared with the conditions in the AD group， the escape latency and swimming distance were reduced in the EX， TCM， and EX+TCM groups， while the residence time in the target quadrant was increased （P<0.05，P<0.01）， with regularly arranged pyramidal cells， elevated number of cells， and reduced myelin-like changes and improved mitochondrial swelling as seen by transmission electron microscopy. Moreover， the expression of Bcl-2， p-Akt and p-GSK-3β was up-regulated， while the expression of cleaved Caspase-3 was down-regulated（P<0.05，P<0.01）. The EX+TCM group had increased level of β-catenin while the EX and TCM groups were not statistically significant compared with the AD group. Compared with the EX+TCM group， the EX and TCM groups had increased escape latency and swimming distance and decreased residence time in the target quadrant（P<0.05，P<0.01）， with loosely arranged pyramidal cells and reduced synaptic integrity under transmission electron microscopy（P<0.01）. Furthermore， the levels of Bcl-2， p-Akt， p-GSK-3β and β-catenin were lowered （P<0.05，P<0.01）while the level of cleaved Caspase-3 was elevated（P<0.05）. ConclusionAerobic exercise combined with Dabuyuan Jian could improve the cognitive dysfunction of AD rats， and the mechanism might be related to the elevated expression of key proteins in the PI3K/Akt/GSK-3β signaling pathway. The combined use was better than the use of exercise or drugs alone.

Objective: To investigate the prognostic factors of hyperamylasemia following pancreaticoduodenectomy (PD) . Methods: Clinical data of 359 patients were collected prospectively who underwent PD by the same group at Changhai Hospital of Navy Medical University from January 2017 to June 2018.There were 212 males and 147 females.The median age was 63 years old (range: 23 to 82 years old) .According to whether the patient′s serum amylase was greater than 120 U/L at 0 or 1 day after surgery,the patients were divided into hyperamylasemia group and non-hyperamylasemia group. Univariate analysis and multivariate analysis were used to find out the prognostic factors of hyperamylasemia after PD. Results: Of the 359 patients, 238 cases (66.3%) developed hyperamylasemia.The incidence rate of clinically related pancreatic fistula (15.1% vs.2.5%, P<0.01) , grade B/C post pancreatectomy hemorrhage (8.8% vs. 2.5%, P<0.01) , and surgical site infection (9.2% vs. 3.3%, P=0.04) was significantly higher in the hyperamylasemia group.The severity of complications (CD grade≥Ⅲ: 11.3% vs.4.1%, P=0.023) and postoperative hospital stay (11 days vs. 9 days, P=0.001) were higher in the hyperamylasemia group.In the multivariate analysis, the main pancreatic duct diameter (MPD) ≤3 mm (OR=4.469, 95% CI: 2.563-7.793, P<0.01) , pathological type of disease (pancreatic cancer or pancreatitis) (OR=0.230, 95% CI: 0.122-0.436, P<0.01) and soft texture of pancreas (OR=3.297, 95%CI: 1.930-5.635, P<0.01) were independent prognostic factors for hyperamylasemia. Conclusions Post-PD hyperamylasemia increased the incidence and severity of postoperative complications after PD.MPD≤3 mm, soft texture of pancreas and pathological type of disease were independent prognostic factors of hyperamylasemia.

Objective To investigate the clinical efficacy of pancreaticoduodenectomy using artery first approach and prior portal vein (PV)-superior mesenteric vein (SMV) shunting for complicated pancreatic head tumors.Methods The retrospective cohort study was conducted.The clinicopathological data of 91 patients with pancreatic head cancer who were admitted to the Changhai Hospital of Navy Medical University from February 2011 to December 2016 were collected.Among 91 patients undergoing pancreaticoduodenectomy combined with vascular resection and reconstruction,27 using artery first approach and PV-SMV shunting and reconstruction were allocated into the PD-PVR group,23 using conventional approach were allocated into the PD-CVR group,and 41 receiving pancreaticoduodenectomy with vascular resection were allocated into the PD-SVR group.Observation indicators:(1) comparison of intra-and post-operative situations among groups;(2) comparison of postoperative pathological results among groups;(3) comparison of postoperative survival among groups.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 2017.Comparisons among groups of count data were done by the chi-square test or Fisher exact probability.Measurement data with normal distribution were represented as x±s,comparisons among groups were analyzed using the ANOVA,and pairwise comparison was done using the LSD method.Measurement data with skewed distribution were described as M(Q),comparison among groups was analyzed using the Kurskal-Wallis rank sum test,and pairwise comparison was done using the paired comparison with adjusted P value.Ordinal data were compared using the nonparametric test.The survival rate and curve were respectively calculated and drawn by the Kaplan-Meier method,and Log-rank test was used for survival analysis.Results (1) Comparison of intra-and post-operative situations among groups:operation time,time of hepatic inflow occlusion,volume of intraoperative blood loss,cases with intraoperative blood transfusion,length of PV or SMV removal,cases with vascular grafts,grading 1,2,3,4 and 5 of Clavien-Dindo classification of postoperative complications and duration of hospital stay were respectively (274±36)minutes,(22±7)minutes,1 661 mL (110 mL,3 800 mL),20,(5.6±1.4)cm,6,11,1,1,1,1,(20±7)days in the PD-PVR group and (281±41)minutes,(27±5)minutes,1 888 mL (176 mL,4 162 mL),18,(5.4±1.5) cm,3,1,8,2,0,0,(21±7)days in the PD-CVR group and (201± 36)minutes,(16±6)minutes,1052 mL (74 mL,3 926 mL),17,(3.2±2.0) cm,5,15,2,3,1,1,(13± 6)days in the PD-SVR group,with statistically significant differences among groups (F=37.060,34.530,x2=13.771,14.015,F=32.260,x2 =39.309,F =19.880,P＜0.05).Patients with postoperative complications were improved by symptomatic and supporting treatment.(2) Comparison of postoperative pathological results among groups:mnaximum tumour dimension was respectively (3.6± 1.3) cm,(4.0± 1.3) cm and (2.6± 1.3) cm in the PD-PVR,PD-CVR and PD-SVR groups,with a statistically significant difference among groups (F =7.845,P＜0.05).Cases with high-differentiated,moderate-differentiated and low-differentiated tumors of tumor differentiation,staging Ⅱ A and Ⅱ B of tumor staging,nerve invasion,positive lymph node,positive resection margins in neck of pancreas,bile duct and SMV were respectively 0,13,14,17,10,17,21,0,0,0 in the PD-PVR group and 1,12,10,10,13,15,19,1,0,0 in the PD-CVR group and 1,29,11,17,24,30,29,2,1,1 in the PD-SVR group,with no statistically significant difference among groups (x2 =4.122,3.306,0.902,1.214,P＞0.05).(3) Comparisons of postoperative survival among groups:of 91 patients,52 were followed up for 3.0-69.3 months,with a median time of 18.0 months and follow-up rate of 57.1％ (52/91),including 16 in the PD-PVR group and 14 in the PD-CVR group and 22 in the PD-SVR group.The median survival time,1-,2-and 3-year overall survival rates in 52 patients were respectively 16.6 months,63.5％,35.7％ and 26.8％.The survival time in the PD-PVR,PD-CVR and PD-SVR groups were respectively 12.3 months (3.9-69.3 months),15.0 months (3.0-63.3 months) and 20.0 months (6.0-65.2 months),with a statistically significant difference in survival among groups (x2=6.201,P＜0.05),and between PD-PVR and PD-SVR groups (x2 =4.412,P＜0.05).There was no statistically significant difference in survival between PD-PVR and PD-CVR groups (x2 =0.001,P＞0.05).Conclusion Pancreaticoduodenectomy using artery first approach and PV-SMV shunting and reconstruction for complicated pancreatic head tumors can reduce the time of hepatic inflow occlusion,it also contributes to the risk control of surgery for complicated pancreatic tumors,increases surgical safety and improves patients' prognosis.

Objectives To investigate the role of lymphangiogenesis in the perineural micrometastasis of pancreatic adenocarcinoma. Methods The clinical data of 30 pancreatic adenocarcinoma patients who were admitted from Sep. 2005 to Oct. 2006 for extended radical surgery were collected. The samples including pancreatic cancer, adjacent tissue, lower bile duct, pancreatic tail, the structure surrounding the SMA (peripancreatic nerve plexus) and lymph nodes were collected during operation. They were subjected to conventional pathological examination. The lymphatic capillaries weredetected by double immunohistochemical staining and the lymphatic vessel density ( LVD) was measured. Results Intra-pancreatic and/or peripancreatic neural invasion was observed in 25 patients (83. 3% ) , of which 20 were found to have both the peri-pancreatic and intra-pancreatic neural invasion. The other 5 only had the intrapancreatic neural fiber invasion and there was no single patient with peri-pancreatic neural fiber invasion only. Peri-neural invasion was not significantly associated with patients' age, gender, lymph node metastasis, tumor size and the location (P > 0.05) , but was obviously associated with JPS clinical staging ( P < 0. 05 ). The mean intratumoral LVD was (4.2 ±3.4) per field, which was significantly lower than (11.3 ±6.9) per field of adjacent tissue and (10.8 ±4.4)per field of normal pancreatic tissue(P<0.01). The mean intratumoral LVD between adjacent tissue and normal pancreatic tissue was not statistically different. Lymphatic vessel invasion was observed in non-malignant tissues in 18 patients, and there was a distribution correlation between lymphatic vessel invasion and extra-pancreatic neural plexus invasion (P<0.05). Conclusions The incidence of peri-neural invasion was high, peri-neural invasion was associated with JPS clinical staging and lymphatic vessel invasion, which suggested the possibility of the cancer spreading by peritumoral lymphangiogenesis route into the peri-SMA neural plexuses.

Objective To construct a human endostatin adenovirus vector and investigate its inhibitory effect on pancreatic carcinoma in nude mice.Methods Animal model of pancreatic carcinoma bearing nude mice was established by subcutaneous injection of SW1990 cells.All mice were randomized into Ad-hEnd group,Ad-LacZ group and control group with 8 mice in each group.The endostatin gene recombinant adenovirus were intratumorally injected every two days for 4 times.The rate of tumor growth was observed.lmmunohistochemical staining was employed to investigate the expression of vascular endothelial growth factor (VEGF) and micro-vessel density (MVD).TUNEL in situ was used to examine tumor cell apoptosis.Results The tumor formation rate was 100%.4 weeks later,the volumes of the tumors were (921.9±279.7 )mm3,(2804.4±553.5 )mm3 and ( 3040.6±487.6 ) mm3 in Ad-hEnd group,Ad-LacZ group and control group,respectively;the weights of the tumors were (1.19±0.18 ) g,( 2.38±0.42 ) g and ( 2.41±0.47 ) g,respectively;the VEGF positive rates were (36.3±7.1 )%,(81.2±6.6)% and (79.4±6.2)%,respectively;the levels of MVD were 12±4,27±5 and 25±6,respectively;the apoptotic rates were (31.2 ±5.4) %,( 9.4±4.9 ) % and ( 8.5±3.7 ) %,respectively.Compared with Ad-LacZ group and control group,the parameters in Ad-hEnd group were statistically different (P ＜0.01 ).The difference betweon Ad-LacZ group and control group was not statistically different.Conclusions Human endostatin gene mediated by recombinant adenovirus could inhibit tumor growth,angiogenesis and promote cell apoptosis of pancreatic carcinoma and could be used as geue therapy for pancreatic carcinoma.

Objective To improve the prognosis and radical resection of the extended pancreaticoduodenectomy for patients with pancreatic cancer in the ucinate process involving mesentery mot. Methods From Jan. 2004 to Dec. 2007, a total of 23 ( 14 male and 9 female, aged between 30 and 72 years old) patients with pancreatic cancer in the ucinate process involving mesentery root were treated in our department. Curative resection was performed for all patients by the extended pancreaticoduodenectomy with superior mesenteric artery (SMA) isolation and mesentery root resection. The surgical procedure, the safety and prognosis were analyzed retrospectively. Results 12 patients underwent the procedure, among them 11 also underwent combined SMV partial resection and reconstruction. The operation time was (4.2 ± 1.1 ) hours, and the blood loss was ( 1 635 ± 1 362) ml with the blood transfusion of ( 1 609 ± 1 462 ) ml. There was no operation related death in this case series, and mild to severe diarrhea occurred in 6 cases. The post-operative stay ranged 9 to 30 days. The pathological examination showed that the tumor size was (5.3 ± 1.4) cm. 13 patients (57%) had one or more lymph nodes metastasis. 20 patients (87%) had nerve involvement. Among 11 patients with SMV partial resection and reconstruction, 10 patients had endangium involvement. 22 patients had negative surgical margins for all specimens. Rapid intra-operative frozen pathological examination showed negative surgical margins in one patient, however, post-operative paraffin section pathological examination revealed nerve involvement between SMA and celiac trunk. After a follow-up of 5 to 42 months, liver metastasis occurred in 4 patients, and local recurrence occurred in 3 patients. The 1-year and 2-year accumulated survival rates were 77.2% and 42.5%, respectively. Conclusions Isolation SMA and the mesentery resection in extended pancreaticodudenectomy were safe and useful. Using this modified technique, Radical operation resection could be achieved in the treatment of pancreatic cancer in uncinate process.

The efficiency of Siemens E.CAM is evaluated by analyzing and practicing the technology of Siemens U-fly.Basic testing procedure is run.Standard source 99mTc and 57Co is used respectively and the operation is performed according to the instruction.The detecting head's uniformity can be corrected in this way with satisfactory results.It is suggested uniformity should be tested every day before study because it is the most important factor for the quality of clinical images.