Objective To evaluate the diagnostic value of the metabolic parameters for differentiating focal autoimmune pancreatitis (F-AIP) and pancreatic cancer (PC) by dual time 18F-FDG PET/CT scan.Methods Ten F-AIP patients and 20 PC patients in Changhai Hospital from May 2011 to November 2014 were enrolled in this study.All the AIP patients were histological confirmed or diagnosed by clinical follow up.The PC patients were histological confirmed and gender-and age-matched with F-AIP patients.50％ SUVmax was set as the threshold to fine-tune the boundary of interest.The extracted parameters included SUV SUV metabolic tumor volume (MTV),total lesion glycolysis (TLG),target-to-background ratio (TBR) and the retention indexes(RI) of all the parameters above.The PET/CT imaging features were also observed.Results The high metabolic lesions were observed in both F-AIP patients and PC patients.There were 6 F-AIP patients whose lesion was located in pancreas head,4 F-AIP patients whose lesion was located in pancreas body and tail.There were 12 PC patients whose lesion was located in pancreas head,8 PC patients whose lesion was located in pancreas body and tail.In F-AIP patients,2 cases had dilated pancreatic duct,6 had dilated biliary duct,8 had increased metabolism in mediastinal lymph node and 2 had abdominal lymphadenopathy,which were 8,5,5 and 14 cases in PC patients.The positive rate of mdeiastinal lymphadenopathy in F-AIP patients was statistically higher than that in PC patients,while the positivity rate of abdominal lymphadenopathy in AIP patients was lower than that in PC patients.The difference was statistically significant (both P ＜ 0.05).There were no statistical differences on the positivity rate of the dilated pancreatic duct,intra-and extra-hepatic bile duct between two groups.SUVmax,SUVmean and MTV in F-AIP were 5.37 ± 0.88,3.48 ± 0.66,21.79 ±15.60 in early stage and 6.45 ±1.51,4.23 ± 1.10,19.36 ± 14.63 in delayed stage,and those in PC were 8.31 ±3.08,5.41±1.95,9.26±8.35 in early stage,and 9.75±3.86,6.36±2.56,9.09±10.71 in delayed stage.SUVmax and SUVmean in F-AIP were lower than those in PC,whereas MTV were larger in F-AIP than that in PC.ROC curves for SUVmax,SUVmean and MTV were made.The AUC of SUV was the highest at 0.85,the cut-off value was 4.45,the corresponding sensitivity was 65％ and the specificity was 90％.TLG,TBR and RI of all the parameters were not statistically different in F-AIP and PC.Conclusions The 18F-FDG PET/CT metabolic parameters,such as SUVmax,SUVmean,MTV,could be of special diagnostic significance in discriminating F-AIP from PC.

Objective To investigate the expression and function of retinoic acid-inducible gene Ⅰ(RIG-Ⅰ) in monocyte-derived dendritic cells (MoDC) at different stages of hepatitis B virus(HBV)infection and to explore the role of RIG-Ⅰ in the disease progression after HBV infection. Methods Peripheral blood samples were collected from 28 hepatitis B virus-infected persons, including 21 cases of chronic hepatitis B (CHB) and 7 of acute hepatitis B (AHB). Eighteen healthy subjects were recruited as controls. Purified CD14~+ monocytes were isolated by CD14 microbeads. MoDCs were induced from CD14~+ monocytes with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 for 7 days, and then were infected with vesicular stomatitis virus (VSV) to stimulate RIG-Ⅰ expression. The mRNA expression levels of RIG-Ⅰ, interferon (IFN )-promoter stimulating factor-1 (IPS-1) and IFN-β at 16 hours and 24 hours after infection with VSV were measured by real-time quantitative polymerase chain reaction (PCR). Data with normal distribution were tested by analysis of variance. Continuous variables between groups were compared using Mann-Whitney U test. Comparison among multiple groups was done by Kruskal-Wallis test. Results The expression levels of RIG-Ⅰ in MoDCs from CHB patients were significantly lower than those in AHB patients and healthy controls at 16 hours (2.44±2.03, 19. 54±3. 15, 21. 48±8. 39, respectively; F=7.451,P=0.002) and 24 hours (2. 68±2. 93, 10. 31 ±3. 88, 14. 01 ±5. 04, respectively, F = 7. 908, P = 0. 001)following VSV stimulation. The IPS-1 levels in both CHB patients and AHB patients were higher than those in healthy controls at 16 hours (2. 05±l. 08, 1. 99±1. 56, 0. 60±0. 31, respectively) F=7.246,P =0.003) and 24 hours (2. 27±2. 16, 3.24 ± 1.21, 1. 08±0. 73, respectively; F= 13. 598, P = 0. 001).Furthermore, the IFN-β expression levels were significantly lower in CHB patients compared to AHB patients and healthy controls at 16 hours and 24 hours after VSV stimulation. Conclusions The expressions of RIG-Ⅰ and IPS-1 in MoDC are abnormal in HBV infected persons, which indicates that RIG-Ⅰ signaling pathway might be blocked by HBV. The impaired function of MoDC may play a role in HBV infection and chronicity.

Objective:To investigate the effect of luteolin(Lut)on the proliferation and ferroptosis of human adriamycin(ADR)resistant chronic myeloid leukemia(CML)K562/ADR cells and the underlying molecular mechanism. Methods:K562 and K562/ADR cells were treated with different concentrations of ADR.The sensitivity of K562 and K562/ADR cells to ADR was evaluated by CCK-8 assay;the effect of different concentrations of Lut on the proliferation of K562/ADR cells was assessed by CCK-8 assay,and the half inhibitory concentration(IC50)was calculated for subsequent experiments;the morphological changes of the cells were observed by an inverted microscope;CCK-8 assay was used to examine the sensitizing effect of Lut on ADR;FCM assay was used to study the effect of Lut on the apoptosis of K562/ADR cells;fluorescence probe DCFH-DA,Fe2+colorimetric assay and glutathione(GSH)kit were used to detect the content of reactive oxygen species(ROS),Fe2+and GSH in K562/ADR cells,respectively;Western blotting was used to examine the expression levels of glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in K562/ADR cells;the effects of Lut on the proliferation of K562/ADR cells,ROS content,GSH content,Fe2+content and GPX4 expression were studied after treatment with ferroptosis inhibitor Ferrostatin-1(Fer-1). Results:Compared with control group(cells treated with 0 μmol/L Lut),Lut significantly inhibited the proliferation of K562/ADR cells(P＜0.001),improved the chemosensitivity of K562/ADR cells to ADR(P＜0.05),increased apoptosis rate(P＜0.001)and ROS level(P＜0.05)of K562/ADR cells,reduced the GSH level(P＜0.001),and increase Fe2+content(P＜0.01).Compared with control group(cells treated with 0 μmol/L Lut),the protein expressions of GPX4,Nrf2 and HO-1 decreased with the increase of Lut concentration(P＜0.05).Compared with the Lut treatment alone,the inhibitory effect on the proliferation of K562/ADR cells induced by Lut was partially restored by Fer-1 intervention(P＜0.05),and intracellular ROS level was decreased(P＜0.001),GSH level was increased(P＜0.001),Fe2+content was decreased(P＜0.001)and the expression of GPX4 was increased(P＜0.01)in K562/ADR cells. Conclusion:Lut can inhibit the proliferation of K562/ADR cells through ferroptosis pathway,improve the chemosensitivity to ADR,and the potential mechanism may be related to the Nrf2/HO-1 signaling pathway,which provides experimental basis for the treatment of leukemia by ferroptosis.

Objective:To investigate the effects of targeted silencing of muscle blind-like protein 1 (MBNL1) gene on the proliferation, apoptosis and migration abilities of leukemia cell line K562 and their possible mechanisms.Methods:Single gene analysis was used to search for differences in MBNL1 gene expression between leukemia samples (173 cases) and healthy control samples (70 cases) in The Cancer Genome Atlas (TCGA) database. The data were updated in 2018. The logarithmic growth phase leukemia cell line K562 was taken and divided into sh-MBNL1 group (transfected with shRNA sequence with targeted silencing of MBNL1 gene), sh-NC group (transfected with corresponding negative control shRNA sequence) and blank control group (not transfected with shRNA sequence). Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of MBNL1, transforming growth factor β 1 (TGF-β 1) and Smad7 mRNA in each group of cells; Western blotting was used to detect the relative expression levels of cell migration-related proteins, apoptosis-related proteins, TGF-β 1, and Smad7 proteins; CCK-8 method was used to detect cell proliferation ability; Transwell method was used to detect cell migration ability. Results:In TCGA database, the relative expression level of MBNL1 gene in leukemia samples was higher than that in healthy control samples ( P < 0.05). The relative expression levels of MBNL1 protein in the sh-MBNL1 group, sh-NC group and blank control group were 0.71±0.11, 1.00±0.11 and 1.03±0.10, respectively, and the difference was statistically significant ( F = 7.78, P < 0.05); the relative expression level of MBNL1 protein in the sh-MBNL1 group was lower than that in the sh-NC group and blank control group (both P < 0.05). The results of CCK-8 assay showed that the cell proliferation ability of sh-MBNL1 group at 72 and 96 hours after transfection was higher than that of sh-NC group and blank control group (both P < 0.05). The Transwell method detection results showed that the number of cell membrane penetration in the sh-MBNL1 group, sh-NC group and blank control group were 666±135, 1 072±157 and 1 006±51, respectively, and the difference was statistically significant ( F = 9.40, P = 0.014); the number of cell membrane penetration in the sh-MBNL1 group was less than that in the sh-NC group and blank control group (both P < 0.05). The relative expression level of E-cadherin protein in the sh-MBNL1 group was higher than that in the sh-NC group and blank control group (both P < 0.01); the relative expression levels of Vimentin, Bax, caspase-3, TGF-β 1, and Smad7 proteins in the sh-MBNL1 group were lower than those in the sh-NC group and blank control group (all P < 0.01). The qRT-PCR detection results showed that the relative expression levels of TGF-β 1 mRNA and Smad7 mRNA in the sh-MBNL1 group were lower than those in the sh-NC group and blank control group (both P < 0.05). Conclusions:Silencing of MBNL1 gene can promote the proliferation of leukemia cell line K562, weaken its migration ability, and affect cell apoptosis. The mechanism may be related to the regulatory effect of TGF-β-Smad signaling pathway.

Objective To evaluate it' s prognosis according to the follow-up statistics of coronary reimplantation of anomalous left coronary artery originating from the pulmonary artery (ALCAPA).Methods Analyze the preoperative,peri-operative and postoperative data of 20 ALCAPA patients having undergone coronary artery reimplantation.Results After coronary reimplantation,patient' s cardiothoracic ratio was obviously decreased,the degree of myocardial ischemia was improved according to electrocardiogram,the left ventricular ejection fraction and fractional shortening showed a trend of rise,mostof the patients recover in 6 months to 1 year after coronary artery reimplantation.Left ventricular end-diastolic volume index over time gradually returned to normal,mitral regurgitation gradually.improved.Conclusion ALCAPA is rare and fatal,therefore it should be diagnosed and treated as early as possible.It is also significant to avoid missed diagnosis and misdiagnosis.After coronary reimplantation,cardiac function can be gradually restored with low mortality and good prognosis result.The left ventricularejection fraction of most patients recovers to the normal standard in six months to one year' s time.

Objective:To investigate the pathological features of gastric tumor originated from the fundic gland, including oxyntic gland adenoma (OGA) and gastric adenocarcinoma of the fundic gland (GA-FG).Methods:A retrospective analysis of 2 cases of OGA and 2 cases of GA-FG admitted to our hospital from February 2019 to September 2019 was performed. The histological features were analyzed by immunohistochemical staining combined with endoscopic observation.Results:The four cases arose from the deep layer of the lamina propria mucosae and well differentiated. Two cases of OGA confined to the mucosa, including 1 case of irregular tubules showing low-degree dysplasia and another case of irregular branching and anastomosing tubules showing high-degree dysplasia. Two cases of GA-FG combined with submucosal invasion, showed irregular branching and anastomosing tubules and formed a so-called "endless glands" pattern. Atypia, helicobacter pylori (HP) infection, chronic gastritis, intestinal metaplasia, or gastric atrophy were not observed in the superficial epithelium covering the tumor extent. Two cases of OGA and 2 cases of GA-FG showed the same result of immunohistochemical staining: pepsinogen-1 was diffusely positive in the tumor tissues and indicated chief cell differentiation, while positive ATPase and PDGFRA-α indicated parietal cells differentiation. The expression of Syn were positive in all cases, while CD10, MUC2 and CD-X2 were negative. The upregulation of p53 protein or nuclear positivity of β-catenin was not observed. The Ki-67 labeling index in the hot area was approximately 1-5%.Conclusions:GA-FG is a well-differentiated, low-grade malignant novel subtype of gastric cancer. The immunohistochemical markers and narrowband imaging combined with magnifying endoscopy (NBI-ME) enhance the diagnostic sensitivity. Whether Syn positive expression can be one of the diagnostic item needs to be further investigate. The process of tumorigenesis of GA-FG might be the transition from low-grade dysplasia to high-grade dysplasia of OGA and further to submucosal infiltration. However, the mechanism of GAFG was still unclear. Disregulation of the Shh and Wnt/β-catenin signaling pathway might be associated with tumorigenesis of GA-FG. Endoscopic submucosal dissection (ESD) is often the preferred and curative treatment.

Objective:To investigate the pathological features of gastric tumor originated from the fundic gland, including oxyntic gland adenoma (OGA) and gastric adenocarcinoma of the fundic gland (GA-FG).Methods:A retrospective analysis of 2 cases of OGA and 2 cases of GA-FG admitted to our hospital from February 2019 to September 2019 was performed. The histological features were analyzed by immunohistochemical staining combined with endoscopic observation.Results:The four cases arose from the deep layer of the lamina propria mucosae and well differentiated. Two cases of OGA confined to the mucosa, including 1 case of irregular tubules showing low-degree dysplasia and another case of irregular branching and anastomosing tubules showing high-degree dysplasia. Two cases of GA-FG combined with submucosal invasion, showed irregular branching and anastomosing tubules and formed a so-called "endless glands" pattern. Atypia, helicobacter pylori (HP) infection, chronic gastritis, intestinal metaplasia, or gastric atrophy were not observed in the superficial epithelium covering the tumor extent. Two cases of OGA and 2 cases of GA-FG showed the same result of immunohistochemical staining: pepsinogen-1 was diffusely positive in the tumor tissues and indicated chief cell differentiation, while positive ATPase and PDGFRA-α indicated parietal cells differentiation. The expression of Syn were positive in all cases, while CD10, MUC2 and CD-X2 were negative. The upregulation of p53 protein or nuclear positivity of β-catenin was not observed. The Ki-67 labeling index in the hot area was approximately 1-5%.Conclusions:GA-FG is a well-differentiated, low-grade malignant novel subtype of gastric cancer. The immunohistochemical markers and narrowband imaging combined with magnifying endoscopy (NBI-ME) enhance the diagnostic sensitivity. Whether Syn positive expression can be one of the diagnostic item needs to be further investigate. The process of tumorigenesis of GA-FG might be the transition from low-grade dysplasia to high-grade dysplasia of OGA and further to submucosal infiltration. However, the mechanism of GAFG was still unclear. Disregulation of the Shh and Wnt/β-catenin signaling pathway might be associated with tumorigenesis of GA-FG. Endoscopic submucosal dissection (ESD) is often the preferred and curative treatment.

Objective:To investigate the relationship between plasma atherogenic index (AIP) trajectory and the risk of hypertension in health examination population.Methods:In this retrospective cohort study, a total of 15 389 subjects who had undergone health examinations at the Health Management Center of the Second Affiliated Hospital of Dalian Medical University three or more times from January 2012 to December 2022 were consecutively selected. The general data, anthropometric parameters and laboratory parameters were collected. The study population without hypertension at baseline inclusion was screened, and AIP trajectory groups of different genders were determined by group-based trajectory modeling. The baseline characteristics and the incidence of hypertension at the end of follow-up were observed in each AIP trajectory group of men and women. Cox proportional hazards regression models were used to analyze the association of AIP trajectories with the risk of hypertension.Results:Four AIP trajectory groups (low level group, low gain group, medium gain group and high gain group) were identified in both male and female subjects, with the highest incidence of hypertension in the low gain group (38.18% in females and 40.92% in males). After adjusting for all confounders, the risk of hypertension was positively associated with increased AIP trajectories in the low ( HR=1.29, 95% CI: 1.02-1.63), medium ( HR=1.66, 95% CI: 1.23-2.23), and high ( HR=1.89, 95% CI: 1.26-2.85) gain groups in women; the risk of hypertension was positively associated with increased AIP trajectories in only the high gain group in men ( HR=1.33, 95% CI: 1.01-1.74). Conclusion:Elevated AIP trajectory is positively correlated with the risk of hypertension in health examination population.

Objective To explore the changes of whole brain white matter ( WM) structural net-work topological property in patients with schizophrenia (SP) and the associations between WM networks to-pological efficiency and clinical variables in patients. Methods Deterministic tractography was used to con-struct the WM networks of 59 patients with SP ( patients group) and 41 age-, handedness-, and gender-matched healthy controls (HCs),and graph theoretical methods were applied to investigate abnormalities in the global and nodal properties of the WM network in these patients. Partial correlation analysis was used to analyze the relationship between global and nodal properties of the WM network and clinical variables in pa-tients with SP. Results Both the patients with SP and HCs showed small-world organization of the WM net-works. However,compared with HCs,the patients with SP exhibited significant abnormal global topology,in-cluding increased shortest path length ( t=7. 95, P=0. 0001) and decreased global efficiency ( 30. 83 ± 16. 08,8. 25±6. 13,t=-9. 81,P=0. 002),clustering coefficiency (0. 03±0. 01,0. 02±0. 01,t=-4. 48,P=0. 0003),the average clustering coefficiency (t=-8. 28,P=0. 002),the small-worldness (3. 92±0. 79,2. 79 ±0. 56,t=-7. 82,P=0. 001) of their WM structural networks(all P<0. 005,FDR corrected). Further,the patients with SP showed a reduction in nodal efficiency predominately in the cingulate gyrus ( t=-4. 11, P=0. 000),superior occipital gyrus ( t=-6. 05, P=0. 002), superior temporal gyrus ( t=-10. 46, P=0. 001),middle temporal gyrus (t=-10. 38,P=0. 000),thalamus (t=-6. 10,P=0. 000) and putamen ( t=-8. 38,P=0. 000) (P<0. 005,FDR corrected). Partial correlation results showed that there was no signifi-cant correlation between global topological properties,node efficiency and clinical symptoms in patients group (Eglob:r=-0. 14,P=0. 279;Eloc:r=-0. 06,P=0. 628;Lp:r=0. 28,P=0. 031;Cp:r=0. 27,P=0. 043;λ:r=-0. 18,P=0. 166;γ:r=-0. 29,P=0. 026;σ:r=0. 26,P=0. 048;nEglob:r=0. 36,P=0. 005;nEloc:r=0. 02,P=0. 901). Conclusions The patients with SP exhibit the abnormal of whole brain WM structural network topological property and the node efficiencies of cortico-striato-thalamo circuitry are significantly re-duced.

Objective:To observe the local reactions and efficacy of CD19 CAR-T therapy in recurrence/refractory B-cell non-Hodgkin's lymphoma (R/R NHL) patients with >7.5 cm lesions.Methods:32 R/R NHL patients with >7.5 cm lesions were enrolled and injected with CD19 CAR-T cells. Flow cytometry was used to detect and observe the amplification of CD19 CAR-T cells in vivo. Enzyme-linked immunosorbent assay (ELISA) was used to detect cytokines in peripheral blood of patients. The side effects of CD19 CAR-T cell therapy included systemic side effects and local reactions of tumor. The local side effects were observed by Ultrasound, Computed tomography and Magnetic resonance imaging. Treatment options included glucocorticoid, interleukin-6 antibody and drainage of exudate. Overall response rate (ORR) and overall survival rate (OS) were observed.Results:①Among the 32 patients, CR (40.63%) , PR (31.25%) and ORR (71.88%) were 13, 10 and 23, respectively. ②In all 23 patients received ORR, 13 patients had grade 1-2 CRS, while 10 patients had grade 3-4 CRS. All the 9 patients in the SD+PD group had grade 1-2 CRS ( P=0.030) . ③A total of 15 patients with tumor local reactions, included 9 patients with CR, 5 patients with PR and 1 patient with SD. The local reactions of the tumor included that the diameter of the superficial lesions increased with redness, swelling and heat pain. The deep lesions presented abdominal pain, abdominal distension, suffocation and local pain, and burning of the tumor. The deep lesions were enlarged or accompanied by local edema. The local exudative lesions were found in the abdominal cavity and pleural cavity. ④ Peak proportion of CD19 CAR-T cells in ORR group was higher than that of in SD+PD group[16.8% (5.3%-48.2%) vs 2.9% (1.5%-5.7%) , z=-4.297, P<0.001]. The peak proportion of CD19 CAR-T cells in ORR group with local reactions was higher than that of in patients without local reactions [22.2% (10.5%-48.2%) vs 12.6% (5.3%-21.6%) , z=-3.213, P=0.001]. The peak proportion of CD19 CAR-T cells in multiple lesion group was higher than that of in single lesion group [35.8% (1.5%-48.2%) vs 16.8% (10.5%-18.5%) , z=-2.023, P=0.040]. ⑤Occurrence of local reactions and tumor shrinkage time were both delayed compared with systemic side effects. ⑥In the ORR group, the OS of patients with tumor local reactions was longer than that of patients without tumor local reactions, but there was no difference in the two groups (75% vs 34.6%, P=0.169) . Conclusions:CD19 CAR-T cell therapy in R/R NHL patients with >7.5 cm lesions might cause tumor local reactions later than systemic side effects.Clinicaltrial::ChiCTR1800018059