Intraductal papillary mucinous neoplasm (IPMN) is a kind of epithelial neoplasms of mucin-producing cells arising in the main duct and/or branch ducts of the pancreas,and it is one of the precancerous lesions of the pancreatic cancer.With the development of pathology and radiology,the diagnostic rate of IPMN has been gradually increased and given a new understanding on the pathological characteristics,clinical diagnosis and treatment of IPMN.This review overviewed the classification,diagnosis,management and prognosis of IPMN,aiming to deepen the understanding of IPMN and improve the level of diagnosis and treatment.

Aim To investigate the effect of indirubin derivative PHⅡ-7 and TRAIL on proliferation in breast cancer cell MCF-7 and its MDR counterpart MCF-7/ADR and the mechanism.Methods Growth inhibition rate was examined respectively by MTT assay under treatment with TRAIL or PHⅡ-7 or in combination. Cell apoptosis and ROS production were examined by flow cytometry.The change of TRAIL receptors(DR4/DR5 )in mRNA was analysed by realtime PCR.Re-sults IC50 of PHⅡ-7 on MCF-7 and MCF-7/ADR was (4.49 ±1.55 ),(3.44 ±0.90 )μmol · L-1 respec-tively;MDA-MB-231 was TRAIL sensitive cell line, and apparently TRAIL induced apoptosis in MDA-MB-23 1 .Low concentration of PHⅡ-7 in combination with TRAIL could augment TRAIL-induced cytotoxic effect including apoptosis while TRAIL or PHⅡ-7 treatment alone had limited cytotoxity to those cells.Besides, PHⅡ-7 at this concentration had little toxicity to hu-man peripheral blood mononuclear cells even if in com-bination with TRAIL.PHⅡ-7 generated ROS produc-tion inside MCF-7 and MCF-7/ADR cells and up-regu-lated DR4/DR5 expression concentration dependently. Once upon ROS scavenger NAC involved,the effect of TRAIL receptors up-regualtion by expression was abro-gated.Conclusions PHⅡ-7 at low concentration could improve the sensitivities of breast cancer cell MCF-7 and MCF-7/ADR to TRAIL,the mechanism of which may be the ability of ROS production by PHⅡ-7 help up-regulated TRAIL receptor DR4,DR5 .Our re-search set a solid foundation for PHⅡ-7 in combination with TRAIL in future clinical application.

Objective:To investigate the expressions of leptin receptor (OBR) and phosphorylated protein kinase B (p-AKT) in patients with diffuse large B-cell lymphoma (DLBCL) and its significance.Methods:Immunohistochemistry was applied to detect the expressions of OBR and p-AKT in tissues from 90 patients with DLBCL and 20 patients with reactive lymphoid hyperplasia (RLH) between 2010 and 2015 in Shandong Provincial Hospital Affiliated to Shandong First Medical University. Cell proliferation assay was used to detect the effect of leptin on the proliferation of SUDHL4 and SUDHL5 in DLBCL cell lines, and the expression of p-AKT in SUDHL4 and SUDHL5 after the cultured leptin was detected by using Western blot.Results:The high expression rate of OBR and p-AKT of DLBCL was 47.7% (43/90) and 27.7% (25/90), respectively, and low expression was found in 20 cases of RLH. There were statistically differences in the expressions of OBR and p-AKT in DLBCL and RLH ( P < 0.01, P = 0.027). The expressions of OBR and p-AKT were not correlated with age, gender, extranodal infiltrations, clinical staging, lactic dehydrogenase (LDH) level, B-symptom and international prognostic index (IPI) score (all P > 0.05). The expression of OBR was positively related with that of p-AKT in DLBCL patients ( r = 0.532, P < 0.05). Leptin could increase the proliferation of SUDHL4 and SUDHL5 cells and promote the expression of p-AKT. Conclusion:Leptin and OBR can promote the proliferation of DLBCL cells and may be involved in the occurrence and development of DLBCL by activating PI3K-AKT pathway.

Objective Nicotinamide phosphoribosyltransferase (Nampt) is a new therapeutic target for ischemic stroke. The aim of this study was to investigate protective effect of liver-derived Nampt on ischemic stroke. Methods Liver-specific Nampt knockout mice were generated using the Cre/loxP system. Nampt^loxP/loxP mice were crossed with liver-specific Cre recombinase expression mice (Alb-Cre), and the progeny genotypes were identified by polymerase chain reaction. Body weight of knockout mice and control mice were measured. Nampt in liver and brain was determined by Western blot assay. Middle cerebral artery occlusion (MCAO), a classical ischemic stroke model, was generated in liver-specific Nampt knockout mice and control mice by electrocoagulation. After 24 h of modeling, neurological deficit scores of each group were evaluated and TTC staining was performed to determine the cerebral infarction volume. The level of plasma Nampt in each group was determined by ELISA. Results Liver-specific Nampt knockout mice with the genotype of Nampt^loxP/loxPAlb-Cre were successfully constructed. The hepatic Nampt expression in knockout mice was significantly decreased by 74.2% compared to control mice, while there was no significant difference in the expression of brain Nampt protein between the knockout group and the control group. Specific knockout of liver Nampt gene expression had no effect on the body weight of mice. Under normal physiological conditions, there was no significant difference in plasma Nampt levels between liver-specific Nampt knockout mice and control mice of the same gender. 24 h after MCAO modeling, there were no significant differences in neurological deficit scores, cerebral infarct volume and plasma Nampt concentration between liver-specific Nampt knockout group and control group. Conclusion Liver-specific Nampt knockout mice are successfully constructed. Liver-derived Nampt has no significant protective effects on ischemic stroke.

Objective:To compare the efficacy of lateral elbow dislocation approach with non-dislocation approach for open reduction and internal fixation of distal humeral coronal fracture.Methods:A retrospective cohort study was used to analyze the clinical data of 26 patients with distal humeral coronal fracture admitted to Qilu Hospital (Qingdao) of Shandong University from January 2018 to October 2021, including 10 males and 16 females, aged 15-80 years [(51.6±4.9)years]. According to Dubberley classification, there were 10 patients with type 2A, 5 with type 2B, 6 with type 3A and 5 with type 3B. Overall, 12 patients were operated via lateral elbow dislocation approach (dislocation approach group) and 14 via lateral elbow non-dislocation approach (non-dislocation approach group). The operation time, intraoperative bleeding volume, incision healing, three-dimensional CT assessment of the reduction within one week after surgery (separation or step>2 mm as poor), Mayo elbow performance score (MEPS) at 3 months after surgery and fracture healing at the last follow-up were recorded in both groups. Complications were also compared between the two groups.Results:All patients were followed up for 3-18 months [(10.5±3.3)months]. The operation time was (146.9±15.5)minutes in dislocation approach and (122.7±11.1)minutes in non-dislocation approach group ( P>0.05). The intraoperative bleeding volume was (113.3±9.7)ml in dislocation approach and (112.9±10.1)ml in non-dislocation approach group ( P>0.05). All incisions healed uneventfully in stage I. All patients had good reduction in dislocation group, while only 7 patients had good reduction and the other 7 patients presented a separation or step>2 mm in non-dislocation group ( P<0.05). The MEPS was (90.0±1.4)points in dislocation approach group at 3 months after surgery, including 9 patients being rated as excellent and 3 good, with the excellent and good rate of 100%. In constrast, the MEPS was (78.9±2.9)points in non-dislocation approach group at 3 months after surgery, including 5 patients being rated as excellent, 4 good, 4 fair and 1 poor, with the excellent and good rate of 64.3% ( P<0.05). All fractures were healed at the last follow-up. In non-dislocation approach group, osteoarthritis occurred in 7 patients, including 3 with screw protrusion, 2 with heterotopic ossification and 2 of advanced age with osteophyte formation around the joint. In dislocation approach group, osteoarthritis occurred only in 2 patients of advanced age, showing osteophyte formation around the elbow joint, with no screw cutting or heterotopic ossification. Conclusion:For distal humeral coronal fracture, the lateral elbow dislocation approach is able to provide complete exposure of the articular surface, obtain anatomic reduction, restore elbow function and reduce complications when compared with the non-dislocation approach.

Objective:To compare reconstruction of acromioclavicular ligament versus internal fixation of acromioclavicular joint with clavicle hook plate in the treatment of Rockwood Ⅲ-Ⅴ acromioclavicular dislocation by reconstruction of coracoclavicular ligament with suture anchor.Methods:A retrospective analysis was conducted of the 56 patients who had been treated for Rockwood Ⅲ-Ⅴ acromioclavicular dislocation from January 2015 to June 2019 at Department of Orthopaedic Trauma, Qilu Hospital of Shandong University (Qingdao). Of them, 26 were treated by reconstruction of coracoclavicular ligament with suture anchor plus reconstruction of acromioclavicular ligament (reconstruction group) and 30 by reconstruction of coracoclavicular ligament with suture anchor plus internal fixation of acromioclavicular joint with clavicle hook plate (plate group). The 2 groups were compared in terms of operation time, intraoperative blood loss, Constant-Murley score and Subjective Shoulder Rating System (SSRS) score at the last follow-up, and complications.Results:The 2 groups were comparable because there were no significant differences between them in the baseline data before operation ( P>0.05). The reconstruction group was followed up for 6 to 15 months (average, 7.9 months) while the plate group for 7 to 18 months (average, 11.3 months). The average operation time was (79.9±12.6) min for the reconstruction group and (69.1±8.5) min for the plate group, showing a significant difference ( P<0.05). No significant difference was found between the 2 groups in the intraoperative blood loss [(68.5±19.1) mL versus (65.0±16.6) mL] ( P>0.05). The differences were statistically significant between the 2 groups in Constant-Murley score (87.9±3.4 for the reconstruction group versus 91.9±3.5 for the plate group) and in SSRS score (85.1±4.1 for the reconstruction group versus 88.6±3.0 for the plate group) ( P<0.05). All the wounds healed well in the reconstruction group except for one patient who reported numbness around the wound which disappeared spontaneously 3 months postoperation. In the plate group, incision infection occurred in 2 cases, the redness and swelling in one which responded to dressing change 3 weeks later and numbness around the incision in one which was recovered 5 months after operation. Conclusions:Both surgical procedures can achieve good to excellent clinical outcomes. Although reconstruction of both acromioclavicular and coracoclavicular ligaments takes more operation time, it may lead to better Constant-Murley and SSRS scores and fewer complications, and spare secondary operation.

Objective:To investigate the therapeutic effect of bidirectional-traction, Steinmann pin poking reduction,anatomic plate and raft technique in the treatment of hyperextension tibial plateau fractures.Methods:The data of 25 patients with hyperextension tibial plateau fractures admitted to Qilu Hospital of Shandong University (Qingdao) from July 2017 to June 2022 were retrospectively analyzed. According to the treatment methods, they were divided into bidirectional-traction group (treated with bidirectional-traction, Steinmann pin poking reduction, anatomic plate and raft technique) and open reduction group (treated with open reduction, bone grafting and two plates fixation). The bidirectional-traction group included 14 patients, with 8 males and 6 females; the age was 50.29±9.23 years (range, 38-61 years). The cause of the injury was a traffic accident in 4 patients, a fall from height in 7 patients and a fall from standing height in 3 patients. According to Schatzker classification, there were 5 Schatzker type V and 9 type VI fractures. The open reduction group included 11 patients (7 males and 4 females); with a mean age of 58.00±10.58 years (range, 48-69 years). 3 cases were injured by traffic accident, 6 cases by falling from height, and 2 cases by falling from standing height. According to Schatzker classification, there were 4 type V and 7 type VI. Preoperative waiting time, operative time, blood loss and percentage of blood loss, incision length, fracture healing time, tibial posterior inclination, medial proximal tibial angle, visual analogue scale (VAS) on the first day after surgery, Hospital for Special Surgery (HSS) score 6 months after surgery were compared between the two groups.Results:Patients in both groups were followed up for more than 6 months. The follow-up time was 7 to 48 months with an average of 22.76 months. There were significant differences in the preoperative waiting time [6 (4, 8) d vs. 8 (7, 11) d, W=114.00, P=0.043], the incision length [15.0 (12.5, 16.0) cm vs. 30.0 (28.0, 31.0) cm, W=154.00, P<0.001], postoperative VAS [4 (3, 4) points vs. 5 (5, 6) points, W=143.00, P<0.001], blood loss [147 (107, 206) ml vs. 267 (191, 362) ml, W=116.00, P=0.033], blood loss percentage [2.95% (2.58%, 5.20%) vs. 6.40% (4.05%, 7.00%), W=118.00, P=0.027] between the bidirectional-traction group and open reduction group. There were not significant differences in the operation time [120 (118, 120) min vs. 119 (101, 154) min, W=68.50, P=0.656], fracture healing time (8.18±1.03 weeks vs. 8.86±1.27 weeks, t=1.49, P=0.149), HSS score (8.43±3.72 vs. 85.18±7.73, t=1.28, P=0.221) and medial proximal tibial angle 6 months after surgery (87.66°±1.53° vs. 86.47°±2.24°, t=1.57, P=0.130) between the two groups. Postoperative tibial posterior inclination was improved in both groups. There was no significant difference in the tibial posterior inclination before surgery, immediately after surgery and 6 months after surgery (-14.96°±6.44°, 5.55°±1.02°, 5.61°±0.82°) in the bidirectional-traction group and -12.26°±2.93°, 7.07°±3.21° and 7.14°±3.17° in the open reduction group, P>0.05). There were no postoperative complications such as acute compartment syndrome or knee stiffness in both groups. Conclusion:The treatment of hyperextension tibial plateau fracture with bidirectional-traction, Steinmann pin poking reduction, anatomic plate and raft technique can shorten preoperative waiting time, reduce incision length, decrease blood loss and lower VAS. It is a minimally invasive, rapid and effective method, which has achieved good clinical results and is worth promoting.

OBJECTIVETo evaluate the clinicopathological features and prognostic factors of carcinoma in the remnant stomach (CRS).

METHODSClinicopathological data of 217 consecutive CRS patients from January 2000 to March 2017 at Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University were retrospectively analyzed. CRS was defined as the primary cancer arising from the remnant stomach following gastrectomy, regardless of the initial disease or operation, and at no special time interval. The clinicopathological features and treatment were compared between CRS after benign disease operation (CRS-B) group and CRS after gastric cancer operation (CRS-C) group, and factors influencing prognosis were analyzed using Cox regression model analysis.

RESULTSOf 217 patients, 189 were male and 28 were female with mean age of (60.9±11.2) years. The interval between the first and the second operations was (18.3±15.1) years. The CRS-B group comprised 108 patients and the CRS-C group comprised 109 patients. Compared to CRS-C group, CRS=B group had higher ratio of male [92.6% (100/108) vs. 81.7% (89/109), χ=5.779, P=0.016], longer interval [30(25-40) years vs. 4(1.5-8.0) years, Z=-1.685, P=0.000], longer tumor diameter [(5.9±3.2) cm vs. (3.9±2.4) cm, t=3.390, P=0.000] and later tumor stage [patients in stage I(, II(, III(, and IIII(: 6 (8.0%), 14 (18.7%), 41 (54.7%), and 14 (18.7%) vs. 16 (25.4%), 14 (22.2%), 21(33.3%), and 12(19.0%), respectively, Z=-2.018, P=0.044]. A total of 138 patients underwent surgery, including 118(85.5%) patients of curative resection and 20(14.5%) patients of palliative resection. The other 79 patients did not receive surgery due to extensive metastasis or miscellaneous reasons. Among 138 patients receiving surgery, 3 patients underwent endoscopic resection, 6 patients underwent minimally invasive surgery (laparoscopy or robot), and 129 patients underwent laparotomy. Forty-eight patients underwent surgery involving combined resection. The median postoperative hospital stay was 10(8-14) days. The incidence of postoperative complication was 23.2%(32/138). A total of 91 patients were followed up for 7-120 months, including 51 patients in CRS-B group and 40 in CRS-C group. The overall 1-, 3-, and 5-year survival rates of the 75 patients receiving curative resection were 80.7%, 55.1%, and 41.6%, respectively. The overall 1-, 3-, and 5-year survival rates were 73.5%, 48.3%, and 29.0% respectively in CRS-B group and 83.1%, 51.2%, and 32.5% respectively in CRS-C group. There was no significant difference between two groups (P=0.527). Multivariate analysis showed that age (RR=1.879, 95%CI: 1.015-3.479, P=0.045), radical procedure (RR=2.956, 95%CI: 1.421-6.150, P=0.004) and TNM stage (RR=1.570, 95%CI: 1.047-2.354, P=0.029) were independent prognostic factors for CRS.

CONCLUSIONSAs compared to the CRS-C group, the CRS-B group has higher percentage of male, longer interval, larger tumor diameter and later TNM stage. Radical resection indicates better prognosis.

Aged ; Female ; Gastrectomy ; Gastric Stump ; pathology ; surgery ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; pathology ; surgery ; Survival Rate

Objective:To investigate the therapeutic effect of rat bone marrow mesenchymal stem cells (BMSCs) transfected with recombinant rat platelet-derived growth factor BB (rrPDGF-BB) gene on the distraction osteogenesis.Methods:From October, 2019 to June, 2020, 48 batches of BMSCs were cultured from 48 young SD rats, 24 of which were transfected with rrPDGF-BB gene by lentivirus. Meanwhile, other 72 male adult SD rats were randomly selected to establish the right femoral distraction osteogenesis model. The rats were equally divided into 3 groups. PBS, BMSCs without intervention and BMSCs transfected with rrPDGF-BB gene were injected into the distraction space of each group of rats assigned as Blank group, Negative group and Experimental group, respectively. Results of the experiment were evaluated by means of imaging and immunohistochemistry. P<0.05 indicated a statistically significant difference. Results:The cultured BMSCs grew well. The expression of CD34(0.1%) and CD45(2.8%) in the third generation of BMSCs was low, and that of CD29 (95.1%) was high, which was consistent with the phenotype of BMSCs described in literatures. After transfection, the expression of green fluorescence gradually increased with the extension of transfection time, confirming the success of transfection. After 14 days, all rats reached the expected distance of distraction. The rats were observed at assigned time points in 2, 4 and 8 weeks. The photos of femur specimen showed that continuous callus could be seen in the experimental group, the hardness and colour were close to the normal bone tissue, and the activity of the distraction space was poor, which was lower than that of the blank group. X-ray examination showed that there were more new callus in the experimental group, and the bone marrow cavity was re-canalized earlier than that of the blank group; Micro-CT examination, in sagittal plane, showed that the distraction space of the experimental group healed well, the broken end was connected, and the recanalization of bone marrow cavity was earlier than that of the blank group; Micro-CT parameters of each group showed that trabecular thickness[(0.297±0.005) mm], trabecular number [(1.663±0.032) mm], bone volume fraction[(59.832±2.187)%] and bone mineral density[(0.586±0.014) g/cm 3] of the experimental group were the greatest, while trabecular separation[(0.399±0.051) mm] of the experimental group was the smallest. There was statistical difference between each group( P < 0.05); HE staining and VEGF immunohistochemistry showed that the vessels and chondrocytes formed earlier and were more in the experimental group than that in the blank group. In 8 weeks, the new callus joined into one piece under the microscope in the experimental group, and the bone marrow cavity was re-canalized with a large number of red blood cells. Conclusion:Studies have shown that BMSCs transfected with rrPDGF-BB gene can promote the formation of callus in the distraction area of rats, shorten the mineralisation time of new callus, and promote the maturation of new bone in the area of distraction osteogenesis.

BackgroundTo date， pharmacologic therapy is considered the standard first-line treatment for insomnia disorder， but there are still some concerns over the adverse reactions. Repetitive transcranial magnetic stimulation （rTMS） and cognitive behavioral therapy for insomnia （CBT-I） as an alternative to pharmacologic therapy have the advantages of fewer side effects and better patient tolerance in the treatment of chronic insomnia disorder. ObjectiveTo explore the clinical efficacy of rTMS and CBT-I on chronic insomnia disorder， so as to provide a novel therapeutic option for the treatment of chronic insomnia disorder. MethodsA total of 50 patients with chronic insomnia disorder attending the outpatient clinic of Inner Mongolia Autonomous Region Mental Health Center or community hospital from September 21， 2020 to December 16， 2021 and fulfilling the International Classification of Sleep Disorders， third edition （ICSD-3） diagnostic criteria were enrolled. Additionally， 16 age- and sex-matched healthy controls recruited from the community were set as control group. Patients were randomly divided into rTMS group and CBT-I group， 25 cases in each group， and received rTMS or CBT-I intervention for 6 weeks respectively. At enrollment and completion of intervention， patients were subjected to Polysomnography （PSG）， Pittsburgh Sleep Quality Index （PSQI）， Insomnia Severity Index （ISI） and Repeatable Battery for the Assessment of Neuropsychological Status （RBANS）. All participants underwent resting-state functional magnetic resonance imaging （rs-fMRI） scans， and amplitude of low-frequency fluctuation （ALFF） was calculated. The brain regions with statistically different ALFF values between patient group and control group were chosen as regions of interest （ROIs）， and whole-brain seed-based functional connectivity analyses were conducted. ResultsAfter a 6-week intervention in the two groups， the main effect of time was significant for PSQI （F=41.160， P<0.05）， ISI （F=69.615， P<0.05） and RBANS immediate memory （F=47.923， P<0.05）， language （F=12.090， P<0.05） and delayed memory indices （F=28.193， P<0.05）. A significant main effect of time for total sleep time （F=8.995， P<0.05）， a significant main effect of time for sleep efficiency （F=12.414， P<0.05）， a significant main effect of group for sleep efficiency （F=4.342， P<0.05） and a significant main effect of time for N1% （F=7.806， P<0.05） were observed. Sleep efficacy in CBT-I group improved significantly from pre- to post-test （t=-2.785， P<0.05）. Patients in rTMS group showed increased functional connectivity between the orbital superior frontal gyrus and other regions including left lentiform nucleus putamen （t=4.991， P<0.05）， right median cingulate and paracingulate gyri （t=4.471， P<0.05） and right postcentral gyrus （t=4.922， P<0.05）， and increased functional connectivity between the orbital superior frontal gyrus and left middle frontal gyrus was found in CBT-I group （t=6.586， P<0.05）. ConclusionrTMS and CBT-I may help alleviate insomnia and improve cognitive function of patients with chronic insomnia disorder. [Funded by Science and Technology Planning Projects in Inner Mongolia Autonomous Region （number， 201802142）］