Welcome to JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION)

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Supervisor: Ministry of Education of the People's Republic of China

Sponsor: Sichuan University

Host unit: Editorial Board of Journal of Sichuan University (Medical Science Edition)

Editor-in-Chief: Yuquan Wei

CN 51-1644/R

ISSN 1672-173X

Postal code: 62-72

Establishment Time: 1959

Address: 17,Section 3,Renmin Nanlu,Chengdu,Sichuan,610041,People's Republic of China

Tel: 028-85501320

Email: scuxbyxb@scu.edu.cn

 

Abstract:
A 5+-day-old male patient was hospitalized due to significant increase of urine protein for 5+ days. A 36+4 weeks preterm male infant was found with III° polluted amniotic fluid and excessive placenta, presented with proteinuria, hypoproteinemia, and progressive edema after birth. Two heterozygous mutations of NPHS1 gene, c.3325C>T (p.Arg1109*) and c.2479C>T (p.Arg827*), were found through the whole exon gene detection. The latter has not been reported domestically andthe diagnosis of congenitalnephrotic syndrome of the Finnish type (CNF) is definite. The report of c.2479C>T mutation gene will expand the mutation spectrum of CNF gene data in China. Early genetic testing is recommended for cryptogenic congenital nephrotic syndrome (CNS) and early genetic diagnosis of CNF is important for prognostic evaluation, genetic counseling and clinical management.
Abstract:
Objective To examine copper transporter 1 (CTR1) expression in pancreatic carcinoma cells, orthotopicxenograft pancreatic tumor model and clinical samples, and verify the effect of copper chelating agent ammonium tetrathiomolybdate (TM) regulate the expression of CTR1 in pancreatic carcinoma cells and the inhibition of pancreatic carcinoma. Methods The expression of copper transporter CTR1 and antioxidant protein 1 (ATOX1) in 22 clinical pancreatic ductal carcinoma and paracancer tissues 0.5-1 cm away from the tumor were measured by immunohistochemistry (IHC). PANC-1 cells were used to construct 5 orthotopic xenograft pancreatic tumor of nude mice models. Pancreatic cancer tissues and corresponding normal pancreatic tissues were collected, and the expression of CTR1 and ATOX1 were detected by IHC and compared with clinical tissues. The proliferation of pancreatic carcinoma cells PANC-1 treated with 10, 30, 50, 100 μmol/L TM for 24 h, 48 h, 72 h measured by CCK8 assay. The migration abilities of PANC-1 cells treated with 50 μmol/L TM for 24 h, 48 h were detected by scratch test. The expression of CTR1, vascular endothelial growth factor (VEGF) and CyclinD1 proteins in PANC-1 cells treated with 10, 30, 50, 100 μmol/L TM for 48 h measured by Western blot. Then the subcutaneous tumor-bearing model of nude mice were established with PANC-1 cells, and the growth of tumor was observed after oral administration of 0.3 mg/d and 1.0 mg/d of TM, respectively. Results The immunohistochemical results indicated that 19 of the 22 clinical pancreatic ductal cancer tissues of carcinoma patients had high expression of CTR1, and the same high expression of CTR1 was found in the orthotopic transplanted tumor tissues of PANC-1 nude mice. The proliferation inhibition of PANC-1 cells increased with the concentration of TM increased and the treatment time prolonged. The expression of intracellular CTR1, VEGF and CyclinD1 all decreased with the concentration of TM increased. The cell migration ability decreased after the PANC-1 cells treated with TM. The tumor growth of PANC-1 tumor-bearing nude mice was inhibited after different doses of TM were delivered. The reduction in tumor volume and weight was more pronounced in the high-dose TM group (P<0.05). Conclusion The expression of CTR1 is abnormally elevated in pancreatic carcinoma, and treatment with copper chelating agent for this target may help to inhibit pancreatic carcinoma.
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Abstract:
Compared with traditional surgery, minimally invasive surgery has the advantages of less complications and quick postoperative recovery. Therefore, modern surgery is developing towards the direction of minimally invasive. while minimally invasive pancreatic surgeries are rather challenging and develop slowly, due to the limits with different operation techniques, long operation time and different operation outcomes, which are only carried out in high-volume pancreatic surgery centers. This special coverage topic will elaborate our long-term experience and the key points to overcome the operational difficulties in laparoscopic and robotic pancreas surgery. In order to promote the development of minimally invasive pancreatic technology and benefit more patients (especially pancreatic cancer patients), some suggestions and prospects with the latest research results at home and abroad are put forward for the future development of this field.
Abstract:
Objective To optimize operative procedure on intraoperative exploration, resection and reconstruction in total laparoscopic pancreaticoduodenectomy (LPD). Methods The clinical data of patients who underwent total LPD in West China Hospital (and Shangjin Hospital) of Sichuan University from Dec. 2015 to Dec. 2017 were retrospectively analyzed. The diagnosis of the patients included ampullar cancer, distal common bile duct cancer, benign and maligant tumors of pancreatic head and chronic pancreatitis of pancreatic head. The patients were divided into experimental group and control group according to weather the optimization of operative procedure was used. The position and Trocar arrangement in both groups were same. Two Chief Surgeons Model was used in experimental group, the procedure was divided into three key steps: laparoscopic exploration, resection and reconstruction, each followed anticlockwise operative process, from left to right, from shallow to deep (see the Videos 1 to 3 in Supplemental Contents, http://ykxb.scu.edu.cn/article/doi/10.12182/202007606108). As to control group, the chief operation was finished by chief surgeon and no specific operative procedure was applied. All the patients were followed up to postoperative 90 d. Results A total of 146 patients were collected, including 76 patients undergoing LPD with optimization of operative procedure and 70 patients in the control group. There was no significant difference in preoperative data between the two groups regarding to ASA scoring, age, gender, body mass index and laboratory tests (P>0.05). Compared with the control group, the operative time in the experimental group was significantly shorter (341 min vs. 397 min, P<0.05), estimated blood loss was significantly reduced (110 mL vs. 180 mL, P<0.05). The conversive rate, transfusion rate, length of postoperative hospital stay, number of harvested lymph nodes, post pancreatectomy hemorrhage, bile leakage, pancreatic fistula (Grade B+C), reoperation, the occurrence of severe postoperative morbidity (Clavien-Dindo Ⅲ-Ⅳ), and postoperative 90 d mortality were no statistically difference. Conclusion With Two Chief Surgeons Model combined with anticlockwise operative process could optimize operative procedure in total LPD. It is safe and feasible, and could shorten the operation time and reduce intraoperative blood loss.
Abstract:
Objective To explore the feasibility and safety of teres hepatis ligament flap plasty around the gastroduodenal artery (GDA) stump to prevent postoperative hemorrhage after laparoscopic pancreatoduodenectomy (LPD). Methods A total of 108 patients with GDA stump wrapped by pedicled teres hepatis ligament after LPD in our center were included for analysis from March 2018 to March 2019. After completion of LPD, teres hepatis ligament was dissected from the ventral abdominal cephalad along the ventral attachment, and the teres hepatis ligament was separated from the falciform ligament by ultrasonic scalpel or Ligasure. At the junction to the liver, the teres hepatis ligament is freed from the ventral hepatic surface. The junction between liver and teres hepatis ligament should not be cut off to ensure blood supply. Division of the GDA was performed using a Prolene 4-0 suture stitch or two clamps as a standard (see the Video 1 in Supplemental Contents, http://ykxb.scu.edu.cn/article/doi/10.12182/20200760602). The pedicled teres hepatis ligament then was used to completely cover the skeletonized GDA stump, and part of the common hepatic artery and the proper hepatic artery. The mobilized ligament can be transposed without tension. Results A total of 108 patients completed the procedure of GDA stump wrapped with pedicled teres hepatis ligament during LPD. There were no complications caused by GDA stump after operation. The main steps to wrap the GDA stump took an average of 10 min. Clinically relevant postoperative pancreatic fistula (CR-POPF) occurred in 8 cases (7.4%) (including 6 cases of grade B pancreatic fistula and 2 cases of grade C pancreatic fistula), and intra-abdominal infection in 8 cases (7.4%), including 3 cases (2.8%) of intra-abdominal abscess, postoperative gastrointestinal ulcer bleeding occurred in 2 cases (1.9%), and no intra-abdominal hemorrhage occurred. Conclusion It is a safe and feasible procedure of wrapping GDA stump with pedicled teres hepatis ligament to prevent postoperative hemorrhage after LPD. The procedure is easy to perform without relevant additional surgical trauma or prolongation of the operation time.
Abstract:
Objective To explore the individualized surgical strategies and surgical methods which can greatly improve the efficacy and safety of laparoscopic pancreaticoduodenectomy in difficult and complicated situations, such as pancreatic head malignant tumors invade the major vascular and chronic pancreatitis with severe abdominal adhesions. Methods Case 1: A 65-year-old man with jaundice was diagnosed preoperatively with a pancreatic acinus process with superior mesenteric vein (SMV) invasion. In order to ensure R0 resection, the patient underwent laparoscopic pancreaticoduodenectomy combined with SMV resection and reconstruction, taking the way of the superior mesenteric artery (SMA)-first approach. The length of SMV removed was 2 cm (see the Video 1 in Supplemental Contents, http://ykxb.scu.edu.cn/article/doi/10.12182/20200760501). The portal vein (PV)-SMV occlusion time was 26 min, the reconstruction time was 17 min. The duration of the surgery was 340 min, with 200 mL of blood loss and no transfusion. Case 2: A 47-year-old man with abdominal pain was admitted with preoperative diagnosis of pancreatic head mass with obstructive jaundice. His past medical history included small bowel resection and bowel anastomosis for abdominal trauma, open Roux-en-Y choledochojejunostomy for acute pancreatitis and obstructive jaundice. In the operation, we used ultracision harmonic scalpel, hook electrode, laparoscopic scissors, and other means to separate the adhesion of different parts of the abdominal, adjusted traditional modular surgical procedure for laparoscopic pancreaticoduodenectomy with Easy First strategy to perform surgical resection (see the Video 2 in Supplemental Contents, http://ykxb.scu.edu.cn/article/doi/10.12182/20200760501). Emergencies such as mass bleeding, used Two Chief Surgeons Model to control bleeding and suture the bleeding site. The duration of the surgery was 400 min, with 500 mL of blood loss and no transfusion. Results Case 1: The patient’s postoperative course was uneventful, with a hospital stay of 9 d. Histology confirmed the diagnosis of a 3.6 cm×2.4 cm×1.8 cm pancreatic ductal adenocarcinoma tumor (R0 and lymph nodes 1/26, AJCC 8th T2N1M0, stage ⅡA). The removed SMV layer was invased and the cut edges were negative. The patient underwent 6 cycles of GS (gemcitabine+tegio) chemotherapy. The patient was asymptomatic 1 year later, with no tumor recurrence and no pancreatic insufficiency. Case 2: The patient’s postoperative course was uneventful, with a hospital stay of 11 d. Histology confirmed the diagnosis of a 6 cm pancreatic inflammatory mass. The patient was asymptomatic 20 months later, with no recurrence of acute pancreatitis again. Conclusion With different surgical methods and individualized surgical strategies, laparoscopic pancreaticoduodenectomy in difficult and complicated situations is safe and feasible in the experienced pancreas minimally invasive center.
Abstract:
Objective To explore the clinical efficacy of pancreaticoduodenectomy (PD) combined with vascular resection and reconstruction under robotic surgery system in the treatment of borderline resectable pancreatic cancer. Methods The clinical data of 17 patients with borderline resectable pancreatic cancer who underwent PD combined with vascular resection and reconstruction (see the Video 1 in Supplemental Contents, http://ykxb.scu.edu.cn/article/doi/10.12182/20200760202) under robotic surgery system between August 2011 and September 2018 was analyzed retrospectively. Results There were 4 cases required conversion because of serious tumor invasion and soft pancreas texture, the other 13 cases were successfully completed. 16 cases (94%) achieved margin-negative resection (R0 resection), 14 cases combined with vein resection, and 3 cases combined with arterial resection. The mean operation time was (401±170) min, the mean blood loss was (647±345) mL, the mean postoperative length of hospital stay was (20±8) d. There was no perioperative death. Postoperative pathology findings and follow-up outcomes were as follows: 1 patient was diagnosed as intraductal papillary mucinous neoplasm (IPMN) and 1 patient was diagnosed as pancreatic neuroendocrine tumors (PNET) (Grade 1), 8 patients with pancreatic ductal adenocarcinoma (PDAC). 1 patient with pancreatic neuroendocrine carcinoma (PNEC) died because of tumor recurrence and metastasis during the follow-up period, the median (Min-Max) survival time was 12 (8-26) months. 5 patients with PDAC and 1 patient with malignant IPMN were currently in the follow-up period. Conclusion It is safe and feasible to perform RPD with vascular resection and reconstruction. The patient's condition should be fully evaluated before surgery to select the most appropriate treatment.
Abstract:
Objective To investigate the clinical efficacy of robotic surgery for pancreatic serous cystadenoma. Methods There were 148 patients with pancreatic serous cystadenoma underwent robotic surgery from April 2015 to June 2019 in our department, the clinical data including intraoperative data, perioperative complications, and histopathological results were retrospectively analyzed. Results Among the 148 patients, there were 39 cases (26.4%) of the tumors located in pancreatic head, 15 cases (10.1%) in pancreatic neck and 94 cases (63.5%) in pancreatic body and tail. Pancreaticoduodenectomy, distal pancreatectomy, central pancreatectomy, and enucleation were performed in 26 cases (17.6%), 71 cases (48.0%), 24 cases (16.2%) and 27 (18.2%) cases, respectively. The incidence of serious postoperative complications were 7.7%, 2.8%, 0, 0, respectively, and grade B pancreatic fistula were 7.7%, 7.0%, 41.7%, 14.8%, respectively. 90-day mortality was 0. Compared with pancreaticoduodenectomy, enucleation of the pancreatic head tumor had shorter operation time (P<0.001), less intraoperative blood loss (P<0.001), and shorter length of hospital stay (P<0.001). Compared with central pancreatectomy+pancreaticojejunostomy, Rong central pancreatectomy had shorter operation time (P=0.007) and length of hospital stay (P=0.040). Conclusion Robotic surgery for pancreatic serous cystadenomaisis safe and feasible. Rong central pancreatectomy for serous cystadenoma in middle segmental pancreas could achieve feasible results.
Abstract:
Objective To screen the key odontogenic genes in mice and verify the odontogenic inducing effect on amniotic epithelial cells (WISH). Methods The spatially and temporally different expression of bone morphogenetic proteins 4 (BMP4), fibroblast growth factor 8 (FGF8), sonic hedgehog (SHH), lymphoid enhancer factor 1 (LEF1) proteins and their genes expression in the early odontogenesis stage (embryo day 10.5 (E10.5)、E11.5、E14.5) in fetal mice were detected by immunohistochemistry staining and quantitative real-time PCR (RT-qPCR). According to the results, we screened the probable key odontogenic genes. Then adding osteogenic inducing solution to induce non-odontogenic epithelium cells, WISH. After 3 weeks culture of non-odontogenic epithelial WISH for osteogenic induction, the epithelial-mesenchymal transformation cap ability was evaluated by using Alizarin (ALZ) red staining and RT-qPCR on the alkaline phosphatase (ALP) mRNA expression level. Using germ layer recombination experiment to observe and verify whether the screened genes can induce non-odontogenic epithelium cells acquire odontogenesis ability. The recombined tissue grafts containing key genes were transplanted beneath the renal capsule of mice. Results The results of immunohistochemistry staining and RT-qPCR showed that on E10.5 BMP4 protein and gene were differently expressed in the first and second branchial arch epithelium, which synchronized the odontogenic capability transferring from epithelium to mesenchyme from E10.5-E14.5. Though the expression of FGF8 protein and gene existed such difference in the first and second branchial arch epithelium, there was no synchronization in transfer. The expression of LEF1 and SHH proteins and genes had neither difference nor synchronization. So far, we considered the BMP4 was the probable key odontogenic gene. Through 3 weeks’ osteogenic induction, ALZ red stained positively and calcium nodules were observed in WISH, and the expression level of ALP mRNA increased. In the germ layer recombination experiment, exogenous BMP4 protein enabled the second branchial arch mesenchyme forming tooth-like structures after recombined with the second branchial arch epithelium or WISH. Conclusions The proteins and genes of BMP4, FGF8, SHH and LEF1 are spatially and temporally differently expressed in the early tooth development stage in mice. The protein and gene of BMP4 are differently expressed between the first and second branchial arch epithelium and enables the non-odontogenic epithelium acquiring odontogenic ability. BMP4 is the possible key odontogenic gene.
Abstract:
Objective To investigate the effects and the mechanism of geniposide on the neuroinflammation occured in the neurodegeneration course of a chronic cerebral hypoperfusion rat model. Methods Permanent bilateral common carotid arteries occlusions was performed to induce gradient cognitive deficit in rats. The sham group was used as control group. Then 18 rats that met the Screening Criteria were randomly selected 8 weeks post surgery, and were randomly divided into three groups, the 2-VO rats with saline solution group (2-VO+saline group), 2-VO rats with 50 mg/kg per day geniposide group (2-VO+G50) and 2-VO rats with 100 mg/kg per day geniposide group (2-VO+G100). All intervention groups were daily administered with geniposide or saline for 4 weeks. The sham-operated rats were administrated with saline. Then the rats were tested for Morris water maze to evaluate the memory and learning ability. Rats were sacrificed to obtain cortex and hippocampus tissues for HE staining and to detect expression level of glial fibrillary acidic protein (GFAP), inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB), and the level of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin (IL)-6. Results The 2-VO+saline group rats showed significant longer escape latency and less percent time in target quadrant, compared with sham-operation group (P<0.05). The escape latency of 2-VO+G50 and 2-VO+G100 groups were shorter than the 2-VO+saline group (P<0.05), but still longer than the sham group (P<0.05), the percent time in target quadrant of which were more than the 2-VO+saline group and less than the sham group. However, there was no significant difference between these two groups. HE staining of sham group showed that neurons in the cortex and hippocampus lined up in order, cellar nucleus were big and globular. HE staining results showed that there were obviously neuoral cells loss, severe cytomorphosis, structural disappearance and nuclear fragmentation in the 2-VO+saline group. The 2-VO+G50 and 2-VO+G100 groups showed less neurodamage than the 2-VO+saline group with less neuoral cells loss, cytomorphosis and ambiguous nucleus. GFAP, iNOS, NF-κB were all highly expressed in the process of cognitive dysfunction in rats after chronic cerebral ischemia, however geniposide intervention (50 and 100 mg/kg per day) significantly decreased the expression of the above proteins. In addition, much more TNF-α and IL-6 were released in brain induced by chronic cerebral ischemia, and the levels were decreased after chronic geniposide oral treatment. No significant differences were detected between 2-VO+G50 and 2-VO+G100 groups. Conclusion These findings demonstrated that geniposide significantly prevented cognition deterioration induced by chronic cerebral hypoperfusion in rats. Geniposide inhibited neuroinflammation occurred in the process of chronic cerebral ischemia probably via reducing iNOS and NF-κB expression and suppressing the release of inflammatory factor TNF-α and IL-6.
Abstract:
Objective To investigate the effect of phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKt) signaling pathway on the apoptosis of alveolar macrophages (AM) induced by nano-silica (NS) dust. Methods After exposure to different concentrations of NS suspension, CCK-8 assay was used to detect the AM viability; the cellular morphology of apoptotic AM was observed under fluorescence microscopy; the apoptosis rate and mitochondrial transmembrane potential of cells were detected by flow cytometry before and after pretreatment with phosphatidyl inositol 3-kinase (PI3K) inhibitor LY294002; Western blot was used to detect the expression of apoptosis-related proteins Bax, Bcl-2, p-PI3K and p-AKt. Resluts The survival rate of AM was decreased in a time-dose relationship after NS exposure. With LY294002 pretreatment, the mitochondrial transmembrane potential level and the expressions of p-PI3K, p-AKt and Bcl-2 were decreased, the expression of Bax and the apoptosis rate were increased. Conclusion Our data suggested that the activation of PI3K/AKt signaling pathway played an important role in NS-induced apoptosis in alveolar macrophages.

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