Objective To investigate the occurrence law of autophagy in trophoblast cells from preeclampsia and its underlying mechanisms.Methods Twenty cases of placenta tissues were collected from women suffered from preeclampsia and normal pregnant women respectively.Autophagosome of trophoblast cells were observed by transmission electron microscope.The expressions of LC3-Ⅱ/Ⅰ and Atg4B in placenta tissues were detected by western blot and real-time PCR.Results Compared with the control group,typical autophagosomes of trophoblast cells were observed by transmission electron microscope.The ratio of LC3-Ⅱ / Ⅰ in placenta of PE patients was increased (1.43 ± 0.23) compared with control group (0.59 ±0.12),and the expression of Atg4B was up-regulated in both mRNA [(1.73 ±0.16) folds] and protein levels (0.71 ± 0.13) compared with control group (P ＜ 0.05).Conclusions Autophagy was significantly up-regulated in trophoblast cells from patients suffered from preeclampsia.Thus,all the data suggest that autophagy might be involved in the generation of preeclampsia.

Objective To evaluate the safety of Ad-Mathl administration to inner ear and provide the base data for vestibular dysfunction gene therapy.Methods Ten mature Wistar rats were divided into normal control group(srats) and adenovirus(E1,E3-Deleted and carried mathl and enhanced green fluorescent protein report gene,Ad-Mathl-EGFP)scala vestibuli transfer group(5 rats).Right ears of the Ad-Mathl-EGFP transfering group rats were deliveried 5ul Ad-Mathl-EGFP(physieal tite 2.1 10~(11)v.P./ml)into cochleas through the way of drilling scala vestibuli of cochlear basal turn.As a control,the normal group received nothing to inner ear.In order to estimate functional condition of vestibule and cochlea,the click-evoked potentials on the surface of the cervical dura mater(CDM-CEP),auditory brain stem response(ABR)and swimming time were recorded in all rats at 7 days after treatment,and then histologic and morphologic observation were carried out after animals were sacrificed.Results All animals' morphologic observation showed that inner ear hair cells were normal after transfer.Seven days after transfer,the swimming time was 4.0±0.71 s in normal control group and 5.0±0.71 s in scala vestibuli delivery group.The threshold of CDM-CEP and ABR were 85±3.54 dB SPL and 37±4.47 dB SPL in normal control group,and 89±6.52 dB SPL and 40±3.54 dB SPL in Ad-Mathl-EGFP scala vestibuli delivery group,respectively.There was no significant difference existed between control group and Ad-Mathl-EGFP scala vestibuli delivery group.Conclusion The Ad(E1,E3-Deleted)is safe for vestibular and cochlea hair cells and can be used as an ideal vector of gene transfer.

Objective To assess the feasibility of adenoviral vectors mediate cochlear gene transfer by postau-ricular microinjection through the round window membrane in mouse. Methods Twelve 5-week old C57BL/6J mice were selected for the study: 8 were implanted with Ad-EGFP by postauricular microinjection through the round window membrane, and 4 with artificial perilymphatic fluid. On postoperative days 5 and 14, the animals were sac-rificed and the surface preparation of cochleae was observed. Results Two animals died after operation. Bright green fluorescence in the cochleae was observed in Ad- EGFP groups. Gene expression on day 14 after operation was higher than that on day 5. However, the control group was free of fluorescence. Oonclusion The postauricular route of the cochlear gene transfer in mice is simple to operate with little side-effect. The technique of transgenic delivery into the inner ear through RWM by mieroinjection is feasible and effective.

Objective To investigate the quality of life of post-operative patients with cholecystolithiasis and analyze the influencing factors. Methods About 206 patients with cholecystolithiasis were enrolled in the investigation by gastrointestinal quality of life index (GIQLI). Multivariate linear regression analysis was used to explore the influencing factors of their quality of life. Results The GIQLI score of 206 patients was (115.81 ±9.22) and the index value was 80.42%. Three independent variables such as breakfast habit, exercise, three hyperlipidemia, were the factors that affected the quality of life (P<0.05). Conclusions The quality of life of patients after cholelithiasis is lower than that of normal people. Patients should develop good eating habits and exercise habits, strengthen the interventions with high blood lipids, high blood pressure and hyperglycemia to improve the quality of life of post-operative patients with cholecystolithiasis.

Objective:To investigate the risk factors for hemorrhagic transformation (HT) in patients with acute posterior circulation ischemic stroke (PCIS) and its impact on outcomes.Methods:From July 2016 to October 2019, patients admitted to the Department of Neurology, the People's Hospital of Zhengzhou and diagnosed as PCIS were enrolled retrospectively. Their demography, clinical data, laboratory and imaging findings were collected. HT was defined as no intracranial hemorrhage detected by the first head CT/MRI after onset, and intracranial hemorrhage was found during head CT/MRI reexamination within 10 d after onset. Symptomatic HT was defined as intracranial hemorrhage indicated by imaging reexamination and the National Institutes of Health Stroke Scale (NIHSS) score was higher than the baseline. The outcome was evaluated by the modified Rankin Scale at 3 months after onset, and >2 were defined as poor outcome. Multivariate logistic regression analysis was used to identify the independent risk factors for HT, symptomatic HT, and poor outcomes. Results:A total of 242 patients with PCIS were enrolled. Their age was 68.02±12.0 years, and 111 were females (45.9%). The baseline median NIHSS score was 5.9 (interquartile range: 3.1-8.8). HT occurred in 19 patients (7.9%), and 14 of them (73.7%) were symptomatic HT. Follow-up at 3 months showed that 74 patients (30.58%) had poor outcomes, of which 12 died. Multivariate logistic regression analysis showed that higher baseline systolic blood pressure (odds ratio [ OR] 1.076, 95% confidence interval [ CI] 1.021-1.135, P=0.006; OR 1.161, 95% CI 1.087-1.240, P<0.001) and larger infarct volume ( OR 31.293, 95% CI 4.542-215.592, P<0.001; OR 2.084, 95% CI 1.414-3.073, P<0.001) were the independent risk factors for HT and symptomatic HT. The higher NIHSS score ( OR 1.511, 95% CI 1.307-1.746; P<0.001), diabetes mellitus ( OR 2.041, 95% CI 1.054-3.952; P=0.034) and symptomatic HT ( OR 4.514, 95% CI 1.458-13.979; P=0.009) were the independent risk factors for poor outcomes. Conclusions:HT is rare in patients with PCIS. Higher baseline systolic blood pressure and larger infarct volume are the independent risk factors for HT in patients with PCIS. Higher baseline NIHSS scores, diabetes mellitus, and symptomatic HT are the independent risk factors for poor outcomes in patients with PCIS.

Objective:To study the toxicity of dioctyl phthalate (DOP) on adrenal pheochromocytoma (PC12) cells and its effect on processing of amyloid precursor protein (APP) -enzymolysis.Methods:In vitro experiments, PC12 cells were divided into blank control (CT) , low DOP (DOP1) , medium DOP (DOP2) , high DOP (DOP3) , low DOP+Aβ 25-35 (DOP1+Aβ) , medium DOP+Aβ 25-35 (DOP2+Aβ) , high DOP+Aβ 25-35 (DOP3+Aβ) , Aβ 25-35 (Aβ) , a total of 8 groups, each with 4 samples. The cell viability was measured by MTT assay, the contents of lactate dehydrogenase (LDH) , malondialdehyde (MDA) and nitric oxide (NO) were measured, and cysteine protease 3 (Caspase-3) was determined by Western blot. In the transfection experiment, the hamster ovary (CHO) cells were transfected with APP695 and treated with different concentrations of DOP. They were divided into V-Flag control (V-Flag) , APP695-Flag (APP695) , low DOP (DOP1+APP695) , medium DOP (DOP2+APP695) , high DOP (DOP3+APP695) , a total of 5 groups, each with 4 samples. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of Aβ 1-40 and the activity of γ-secretase. In vivo experiment, 50 male Kunming mice of SPF grade, weighing (20±2) g, were selected and randomly divided into control, lead (Pb) , low DOP (DOP1＇) , medium DOP (DOP2＇) , high DOP (DOP3＇) consisted of 5 groups, each with 10 mice, continuously gavage for 6 weeks. Morris water maze method was used to detect the effect of different concentrations of DOP on learning and memory in mice, and ELISA method was used to detect β-secretase, γ-secretase activity and Aβ 1-40 content in brain tissue. Results:Compared with the CT group, the cell viabilities of the DOP2 and DOP3 groups were decreased, and the contents of LDH, MDA, and NO were increased, and the differences were statistically significant ( P<0.05) . Compared with the CT group, the cell viabilities of DOP1+Aβ, DOP2+Aβ and DOP3+Aβ groups were decreased, the contents of LDH, MDA, NO were increased, the differences were statistically significant ( P<0.05) . Compared with the Aβ group, the cell viability of DOP3+Aβ group was decreased, the contents of LDH, MDA, NO were increased, the differences were statistically significant ( P<0.05) . Compared with the Aβ group, the contents of LDH and NO in the DOP2+Aβ group were increased, and the differences were statistically significant ( P<0.05) . Compared with the CT group, the expression levels of Caspase-3 in the DOP2 and DOP3 groups were increased, and the differences were statistically significant ( P<0.05) . Compared with the Aβ group, the expression levels of Caspase-3 in the DOP2+Aβ and DOP3+Aβ groups were increased, and the differences were statistically significant ( P<0.05) . Compared with the APP695 group, the contents of Aβ 1-40 and the activities of γ-secretase of the DOP2+APP695 and DOP3+APP695 groups were increased ( P<0.05) . Compared with the control group, the activities of β-secretase, γ-secretase and the content of Aβ 1-40 in the brain tissue of DOP3＇group were increased, and the differences were statistically significant ( P<0.05) . Compared with the Pb group, the activities of β-secretase, γ-secretase and the content of Aβ 1-40 of the DOP3＇group were increased, and the differences were statistically significant ( P<0.05) . Compared with the control group, the target quadrant stay time and the number of crossings in the DOP2＇and DOP3＇groups were reduced, and the differences were statistically significant ( P<0.05) . Conclusion:DOP has a certain toxic effect on PC12 cells, causing learning and memory impairment in mice, and may promote the pathological progression of Alzheimer＇s disease.

Objective:To study the toxicity of dioctyl phthalate (DOP) on adrenal pheochromocytoma (PC12) cells and its effect on processing of amyloid precursor protein (APP) -enzymolysis.Methods:In vitro experiments, PC12 cells were divided into blank control (CT) , low DOP (DOP1) , medium DOP (DOP2) , high DOP (DOP3) , low DOP+Aβ 25-35 (DOP1+Aβ) , medium DOP+Aβ 25-35 (DOP2+Aβ) , high DOP+Aβ 25-35 (DOP3+Aβ) , Aβ 25-35 (Aβ) , a total of 8 groups, each with 4 samples. The cell viability was measured by MTT assay, the contents of lactate dehydrogenase (LDH) , malondialdehyde (MDA) and nitric oxide (NO) were measured, and cysteine protease 3 (Caspase-3) was determined by Western blot. In the transfection experiment, the hamster ovary (CHO) cells were transfected with APP695 and treated with different concentrations of DOP. They were divided into V-Flag control (V-Flag) , APP695-Flag (APP695) , low DOP (DOP1+APP695) , medium DOP (DOP2+APP695) , high DOP (DOP3+APP695) , a total of 5 groups, each with 4 samples. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of Aβ 1-40 and the activity of γ-secretase. In vivo experiment, 50 male Kunming mice of SPF grade, weighing (20±2) g, were selected and randomly divided into control, lead (Pb) , low DOP (DOP1＇) , medium DOP (DOP2＇) , high DOP (DOP3＇) consisted of 5 groups, each with 10 mice, continuously gavage for 6 weeks. Morris water maze method was used to detect the effect of different concentrations of DOP on learning and memory in mice, and ELISA method was used to detect β-secretase, γ-secretase activity and Aβ 1-40 content in brain tissue. Results:Compared with the CT group, the cell viabilities of the DOP2 and DOP3 groups were decreased, and the contents of LDH, MDA, and NO were increased, and the differences were statistically significant ( P<0.05) . Compared with the CT group, the cell viabilities of DOP1+Aβ, DOP2+Aβ and DOP3+Aβ groups were decreased, the contents of LDH, MDA, NO were increased, the differences were statistically significant ( P<0.05) . Compared with the Aβ group, the cell viability of DOP3+Aβ group was decreased, the contents of LDH, MDA, NO were increased, the differences were statistically significant ( P<0.05) . Compared with the Aβ group, the contents of LDH and NO in the DOP2+Aβ group were increased, and the differences were statistically significant ( P<0.05) . Compared with the CT group, the expression levels of Caspase-3 in the DOP2 and DOP3 groups were increased, and the differences were statistically significant ( P<0.05) . Compared with the Aβ group, the expression levels of Caspase-3 in the DOP2+Aβ and DOP3+Aβ groups were increased, and the differences were statistically significant ( P<0.05) . Compared with the APP695 group, the contents of Aβ 1-40 and the activities of γ-secretase of the DOP2+APP695 and DOP3+APP695 groups were increased ( P<0.05) . Compared with the control group, the activities of β-secretase, γ-secretase and the content of Aβ 1-40 in the brain tissue of DOP3＇group were increased, and the differences were statistically significant ( P<0.05) . Compared with the Pb group, the activities of β-secretase, γ-secretase and the content of Aβ 1-40 of the DOP3＇group were increased, and the differences were statistically significant ( P<0.05) . Compared with the control group, the target quadrant stay time and the number of crossings in the DOP2＇and DOP3＇groups were reduced, and the differences were statistically significant ( P<0.05) . Conclusion:DOP has a certain toxic effect on PC12 cells, causing learning and memory impairment in mice, and may promote the pathological progression of Alzheimer＇s disease.

Objectives: . Despite the efficacy of surgical treatments, the high rate of recurrence in juvenile nasopharyngeal angiofibroma (JNA) after surgery remains an unresolved problem. The present study comprehensively analyzed the risk factors and characteristics of JNA recurrence, providing clinical guidance for reducing recurrence. Methods: . A total of 123 patients who underwent surgery for JNA between 1997 and 2019 at a single hospital were analyzed retrospectively. Univariate and multivariate analyses were used to assess the clinical risk factors for the recurrence of JNA. The relapse-free survival and annual cumulative recurrence rates were analyzed for subgroups defined according to clinical parameters. Results: . After screening, 78 of the 123 patients were included in the present study. The main risk factors associated with JNA recurrence included the year of diagnosis, tumor size, sphenoid bone invasion, Radkowski stage, surgical approach, and intraoperative bleeding. Importantly, the surgical approach and sphenoid bone invasion were independent prognostic factors affecting recurrence. Patients who underwent endoscopic surgery without sphenoid bone invasion exhibited longer relapse-free survival. In the present study, the overall cumulative recurrence rate of JNA was 38.7%, and recurrence occurred mainly in the first year after the initial surgery. Conclusion . Endoscopic surgery achieved better relapse-free survival in JNA patients, and patients with sphenoid bone invasion should be carefully explored to avoid residual JNA. The recurrence rate of JNA differed among subgroups defined based on clinical parameters and was highest in the first year after surgery. Computed tomography or magnetic resonance imaging, along with close follow-up, should be performed strictly within 1 year after the primary operation.

Objective:To investigate the risk factors and prognoses of cerebral venous sinus thrombosis (CVST) caused by pegasparaginase (PEG-Asp).Methods:A total of 252 children with acute lymphoblastic leukemia (ALL) were treated with PEG-Asp chemotherapy in our hospital from December 2016 to July 2021, including 8 children with CVST. The clinical manifestations, laboratory and imaging features, treatments and prognoses of these children with CVST caused by PEG-Asp were analyzed retrospectively.Results:(1) CVST occurred during induction chemotherapy in 4 children, during re-induction chemotherapy in 3 children, and during consolidation stage in one child. CVST occurred in two children who received PEG-ASP chemotherapy once, in one child who received PEG-Asp chemotherapy twice, and 5 children who received PEG-Asp chemotherapy more than twice. The median time between CVST occurrence and last treatment of PEG-Asp was 20.5 d. (2) The clinical manifestations included paroxysmal headache ( n=4), nausea or vomiting ( n=3), convulsions ( n=2) and persistent blurred vision ( n=1). (3) CVST appeared at the sigmoid sinus ( n=6), transverse sinus ( n=4) and superior sagittal sinus ( n=4), of which one child was complicated with hemorrhage in left frontal parietal and right parietal cortex, and one with reversible posterior encephalopathy syndrome; 8 children were not complicated with thrombus in other parts. (4) Some of the children were complicated with abnormal blood coagulation. When CVST occurred, fibrinogen level decreased in 3 children, anti-thrombin III level decreased in 2 children, and D-dimer level increased in 3 children. (5) Six children were treated with low molecular weight heparin (LMWH), of which, 4 were treated with rivasaban and one with warfarin sequentially. The total course of anticoagulation was 56 d. (6) The symptoms of 6 children disappeared after anticoagulation; Magnetic resonance venography (MRV) showed disappeared thrombus in 4 children and reduced thrombus range in 2 children. One child with intracranial hemorrhage did not use PEG-Asp anymore; 7 accepted PEG-Asp further during follow-up chemotherapy, of which one had CVST recurrence and the range of thrombus was reduced after anticoagulant therapy. Conclusions:When children with ALL develop unexplained neurological symptoms during PEG-Asp chemotherapy, CVST should be highly vigilant. Enhanced MRI and MRV should be performed for early diagnosis. Some children are complicated with abnormal blood coagulation, and LMWH, warfarin and rivasaban are effective. The prognosis is good and there are no sequelae. Most children accepted PEG-Asp again will not have CVST again.

Objective:To analyze the value of 68Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in the detection of myocardial injury in patients treated with anti-tumor therapy. Methods:A retrospective study was conducted on 164 patients who underwent 68Ga-FAPI-04 PET/CT to evaluate the efficacy of anti-tumor therapy in Renji Hospital, School of Medicine, Shanghai Jiao Tong University between August 2021 and March 2024. The patients were divided into 68Ga-FAPI-04-positive group ( n=63, 36 males, 27 females, age (66.7±9.6) years) and 68Ga-FAPI-04-negative group ( n=101, 42 males, 59 females, age (55.2±14.1) years) based on the uptake of left ventricular myocardium (LVM). Moreover, FAPI-04 uptake was analyzed based on different types and locations, and the corresponding SUV max differences were analyzed by Kruskal-Wallis rank sum test. The differences of SUV max between 68Ga-FAPI-04-positive group and 68Ga-FAPI-04-negative group were analyzed by Mann-Whitney U test. The clinical factors such as gender, age, body mass index (BMI), previous history of coronary heart disease, left ventricular ejection fraction (LVEF), smoking history, hypertension, diabetes, cancer types and immune checkpoint inhibitors (ICIs) treatment were collected, and their predictive values for LVM 68Ga-FAPI-04 uptake were investigated by the binary logistic regression analysis. Results:Fifty patients of the 68Ga-FAPI-04-positive group (79.4%, 50/63) showed focal uptake of LVM, 7 patients (11.1%, 7/63) showed multifocal myocardial uptake, and 6 patients (9.5%, 6/63) showed diffuse myocardial uptake. A total of 127 uptake lesions were found, and most of them were located in the septum (37.8%, 48/127). The SUV max of LVM in 68Ga-FAPI-04-positive group and 68Ga-FAPI-04-negative group were 4.00(3.10, 5.40) and 1.31(1.20, 1.40) respectively ( z=-10.82, P<0.001). Differences of the SUV max among focal uptake group, multifocal myocardial uptake group, and diffuse myocardial uptake group were not significantly different (4.00(3.00, 5.10) vs 7.60(3.60, 9.30) vs 3.95(3.05, 5.05); H=3.81, P=0.149). There is no statistically significant difference either in FAPI uptake among different sites of LVM ( H=1.51, P=0.825). Age, previous history of coronary heart disease, BMI, LVEF and ICIs treatment were independent predictive factors for positive 68Ga-FAPI-04 uptake in the LVM (odds ratio ( OR) values: 0.87-10.43, all P<0.05). Conclusion:68Ga-FAPI-04 PET/CT is a potential new imaging method for the visualization of myocardial injury in patients with anti-tumor therapy.