1.OAS1 promotes the proliferation of pancreatic cancer cells by enhancing mTOR signaling pathway
Yuheng ZHU ; Jianlei WEI ; Zonghao DUAN ; Xueshiyu MA ; Qinyuan JIA ; Yongwei SUN ; Li CHEN
Tumor 2024;44(3):215-228
Objective:To investigate the expression pattern,clinical significance,and the regulatory role of 2',5'-oligoadenylate synthetase 1(OAS1)in the proliferation of pancreatic ductal adenocarcinoma(PDAC)cells.Methods:Public databases such as Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)were used to analyze the expression of OAS1 in pancreatic cancer tissues.Immunohistochemical staining was applied to validate the expression level of OAS1 in PDAC tissue microarrays,and the association between OAS1 expression level and the prognosis of patients was analyzed.Real-time fluorescence quantitative PCR was performed to examine the expression level of OAS1 mRNA in different PDAC cell lines.CCK-8 assay and colony formation assay was used to assess the effect of OAS1 on the proliferation of PDAC cells after OAS1 silencing in Patu-8988 and PDC0034 cells by siRNA treatment.Further,Gene Set enrichment analysis(GSEA)was performed to screen for possible molecular mechanism of the regulatory role of OAS1 in PDAC.Cell viability and cholesterol level was analyzed after treatment with mTOR signaling activator MHY1485 in OAS1-silenced Patu-8988 and PDC0034 cells in order to verify the underlying mechanism of the regulatory role of OAS1 in PDAC cell proliferation.Results:Database analysis showed significant upregulation of OAS1 expression in pancreatic cancer tissues(P<0.05).Immunohistochemical staining results from PDAC tissue microarray showed that OAS1 expression was significantly upregulated in PDAC tissues compared with the paired paracancerous tissues,and high OAS1 expression was associated with poor prognosis(P<0.05).Real-time fluorescence quantitative PCR and Western blotting analysis show that OAS1 expression was higher in PDAC cells lines compared with normal ductal cells of the pancreas.The proliferative activity of PDAC cells decreased significantly after OAS1 silencing in Patu-8988 and PDC0034 cells(P<0.001).GSEA results indicated that OAS1 may affect PDAC cell proliferation through mTOR signaling pathway and cholesterol metabolism associated pathway.The mTOR signaling pathway may be inhibited and the total cellular cholesterol decreased after OAS1 silencing.Treatment with mammalian target of rapamycin(mTOR)activator MHY1485 partially reversed the inhibitory effect of OAS1 silencing on the proliferation and cholesterol metabolism of PDAC cells.Conclusion:OAS1 expression is upregulated in PDAC tumor tissues and cells and is associated with poor prognosis.OAS1 may promote the proliferation of pancreatic cancer cells by enhancing cholesterol metabolism through activation of the mTOR signaling pathway.
2.Practical research on the training of intensive care medicine talents in Xizang based on cloud teaching rounds
Wei DU ; Guoying LIN ; Xiying GUI ; Li CHENG ; Xin CAI ; Jianlei FU ; Xiwei LI ; Pubu ZHUOMA ; Yang CI ; Danzeng QUZHEN ; Lü JI ; Ciren SANGZHU ; Wa DA ; Juan GUO ; Cheng QIU
Chinese Journal of Medical Education Research 2024;23(8):1065-1068
In view of the problem of slow development of intensive care medicine in Xizang, the research team made full use of the national partner assistance to Xizang, gathered resources across all cities in Xizang, and formed a national academic platform for critical care medicine in plateau areas. Adhering to the academic orientation with hemodynamics as the main topic, critical care ultrasound as the bedside dynamic monitoring and evaluation method, and blood flow-oxygen flow resuscitation as the core connotation, we have achieved the goals of improving the critical care talent echelon throughout Xizang, driving the overall progress of intensive care medicine in Xizang, making a figure in China, and focusing on training of top-notch talents.
3.Clinical efficacy comparison of ankle arthroscopy combined with closed reduction guide and open reduction in the treatment of trimalleolar fracture
Jixin LI ; Lei WANG ; Yuhang ZHANG ; Zengbo WEI ; Jianlei YANG ; Youjun LIU ; Tongjun YU
Tianjin Medical Journal 2024;52(11):1197-1201
Objective To compare the clinical efficacy of ankle arthroscopy combined with closed reduction guide and conventional surgical incision in the treatment of trimalleolar fracture.Methods A total of 60 patients with ankle fracture were divided into two groups according to different surgical plans:the ankle arthroscopy combined with closed reduction guide surgery group(arthroscopy group)and the conventional incision surgery group(incision group),with 30 cases in each group.The operative time,intraoperative blood loss and complications of the two groups were observed and compared.Pain and functional recovery of patients were evaluated by the American Orthopaedic Foot&Ankle Society(AOFAS)ankle and hind foot scores and Foot and Ankle Disability Index(FADI)scores.Results All 60 patients were followed up.Compared with the arthroscopy group,patients in the incision group had a longer surgical time,a shorter incision length in the medial malleolus,a reduced number of cases of skin numbness and reduced bleeding(P<0.05).The AOFAS score and the FADI score at 12 months after surgery were higher in the arthroscopic group than those of the incision group(P<0.05).After 12 months of surgery,the AOFAS score in patients without cartilage injury of the arthroscopic group were higher than those of patients with cartilage injury(P<0.05),while there were no significant differences in pain and force line scores between patients with cartilage injury and patients without cartilage injury(P>0.05).Conclusion The application of ankle arthroscopy combined with closed reduction guide in the treatment of trimalleolar fracture can achieve better postoperative results,but it has no obvious advantages in operation time and incision infection compared with the incision surgery.
4.OAS1 promotes the proliferation of pancreatic cancer cells by enhancing mTOR signaling pathway
Yuheng ZHU ; Jianlei WEI ; Zonghao DUAN ; Xueshiyu MA ; Qinyuan JIA ; Yongwei SUN ; Li CHEN
Tumor 2024;44(3):215-228
Objective:To investigate the expression pattern,clinical significance,and the regulatory role of 2',5'-oligoadenylate synthetase 1(OAS1)in the proliferation of pancreatic ductal adenocarcinoma(PDAC)cells.Methods:Public databases such as Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)were used to analyze the expression of OAS1 in pancreatic cancer tissues.Immunohistochemical staining was applied to validate the expression level of OAS1 in PDAC tissue microarrays,and the association between OAS1 expression level and the prognosis of patients was analyzed.Real-time fluorescence quantitative PCR was performed to examine the expression level of OAS1 mRNA in different PDAC cell lines.CCK-8 assay and colony formation assay was used to assess the effect of OAS1 on the proliferation of PDAC cells after OAS1 silencing in Patu-8988 and PDC0034 cells by siRNA treatment.Further,Gene Set enrichment analysis(GSEA)was performed to screen for possible molecular mechanism of the regulatory role of OAS1 in PDAC.Cell viability and cholesterol level was analyzed after treatment with mTOR signaling activator MHY1485 in OAS1-silenced Patu-8988 and PDC0034 cells in order to verify the underlying mechanism of the regulatory role of OAS1 in PDAC cell proliferation.Results:Database analysis showed significant upregulation of OAS1 expression in pancreatic cancer tissues(P<0.05).Immunohistochemical staining results from PDAC tissue microarray showed that OAS1 expression was significantly upregulated in PDAC tissues compared with the paired paracancerous tissues,and high OAS1 expression was associated with poor prognosis(P<0.05).Real-time fluorescence quantitative PCR and Western blotting analysis show that OAS1 expression was higher in PDAC cells lines compared with normal ductal cells of the pancreas.The proliferative activity of PDAC cells decreased significantly after OAS1 silencing in Patu-8988 and PDC0034 cells(P<0.001).GSEA results indicated that OAS1 may affect PDAC cell proliferation through mTOR signaling pathway and cholesterol metabolism associated pathway.The mTOR signaling pathway may be inhibited and the total cellular cholesterol decreased after OAS1 silencing.Treatment with mammalian target of rapamycin(mTOR)activator MHY1485 partially reversed the inhibitory effect of OAS1 silencing on the proliferation and cholesterol metabolism of PDAC cells.Conclusion:OAS1 expression is upregulated in PDAC tumor tissues and cells and is associated with poor prognosis.OAS1 may promote the proliferation of pancreatic cancer cells by enhancing cholesterol metabolism through activation of the mTOR signaling pathway.
5.The Extra-Oral Measuring Technique of Initial Restoring Force Produced by Orthodontic Archwire Based on Dental Model
Jianlei WU ; Yunfeng LIU ; Jianxing ZHANG ; Wei PENG ; Chen CHEN
Journal of Medical Biomechanics 2020;35(3):E319-E324
Objective To realize the extra-oral measurement of initial recovery force produced by orthodontic wire using simulated dental model. Methods A clinical patient was selected as the study objective, and maxillary dental models, which were in accordance with the real dentition of patient, were fabricated by three-dimensional printing. An orthodontic force measuring system was constructed using Nano17 F/T mechanical sensors to measure the initial recovery forces on two maxillary central incisors, which were produced by a standard circle Ni-Ti wire with the diameter of 355.6 μm after the archwire was assembled on the dental model. Results Central incisor 21 suffered a lager initial orthodontic force compared with incisor 11, and the force systems on two incisors were both adverse to tooth ideal movement, therefore, an assistive device was necessary to improve force status of the teeth. When the orthodontic treatment plan was optimized, a satisfactory result was obtained after 18 months of treatment. Conclusions Force systems caused by orthodontic wire and exerted on the teeth could be accurately measured using the simulated dental model of patient, so as to predict the teeth moving type, and improve teeth treatment plan on this basis. The extra-oral measuring technique of orthodontic force provides an important reference for clinical orthodontic treatment, and creates a novel idea for the optimal design of orthodontic plan.
6.Clinical characteristics of carbapenem-resistant Enterobacteriaceae infection in pediatric liver transplantation recipients
Yan SUN ; Hong ZHENG ; Jianlei ZHANG ; Lixin YU ; Bing WANG ; Wei GAO ; Jinzhen CAI ; Yihe LIU
Chinese Journal of Pediatrics 2020;58(8):640-645
Objective:To explore the clinical features and treatment of carbapenem-resistant Enterobacteriaceae (CRE) infection in pediatric liver transplantation recipients and discuss the significance of CRE colonization by screening with rectal swabs. Methods:A total of 286 cases of pediatic liver transplantation recipients, who came from Tianjin First Central Hospital during August 1,2017 to August 1, 2018, were retrospectively investigated. The clinical characteristics, antibiotic susceptibity test, treatment outcomes and prognosis of CRE infection patients were analyzed. CRE colonization were screened by rectal swabs after liver transplantation. All cases were divided into CRE colonization group and non-CRE colonization group based on CRE colonization results. The high risk factors of CRE colonization and its relationship with CRE infection were investigated. χ 2 test was used for the comparison between groups.The single-factor analysis was used to screen risk factors. Results:The 286 cases included 132 male and 154 female cases. The age was (8±4) months.CRE infection rate after liver transplantation was 7.3% (21/286). The time of CRE infection was the 5 th (1 th-14 th) days after transplantation. Abdominal infection was the most common (95.2%, 20/21), followed by bloodstream infection (12 cases) and pulmonary infection (8 cases). Infection in two or more sites accounted for 71.4% (15/21); 27 CRE strains, in which 24 strains were carbapenem-resistant Klebsiella pneumonia (88.9%), 2 strains were carbapenem-resistant Escherichia coli (7.4%) and one strain was carbapenem-resistant Enterobacter aerogenes (3.7%). The drug resistance rate of CRE strains to carbapenems, penicillin antibiotics, second-and third-generation cephalosporin was 100.0%. Medication treatment included meropenem+fosfomycin (13 cases) and meropenem+tegacycline (8 cases). The treatment was effective in 16 cases and the time was 19 (1-27) d. The 1-year survival rate among CRE infection group and non-CRE infection group were 71.4% (15/21) and 98.1% (260/265), respectively (χ 2=37.460, P<0.01). CRE infection rate among CRE colonization group and non-CRE colonization group were 26.4% (19/72) and 0.9% (2/214), respectively (χ 2=51.300, P<0.01). Factors before transplantation, including third-generation cephalosporin or carbapenems exposure, prolonged hospital stay within 3 months, CRE infection, and factors after transplantation, including emergency surgery, mechanical ventilation more than 24 hours (χ 2=20.570, 6.411, 13.960, 14.600, 9.560, all P<0.01) were high risk factors for CRE colonization. Conclusions:The prognosis of CRE infection after pediatric liver transplantation is poor. Timely diagnosis and treatment are of great importance. Much attention should be paid on CRE rectal colonization and its risk factors. Screening of CRE colonization is important for early warning and control of CRE infection.
7.Applied anatomic study of narrow pedicle in thoracolumbar spine of adults
Wei HE ; Yu QIAN ; Wanlei YANG ; Weiqi HAN ; Xuanyuan LU ; Cong JIN ; Jianlei LI
Chinese Journal of Orthopaedics 2017;37(1):36-43
Objective To explore the demographic factors and the risk of the pedicle screw insertion of the narrow pedi?cles. Methods Thoracolumbar spine thin?section CT image data of 312 adults from September 2014 to September 2015 were ana?lyzed. The pedicle width,medial and lateral cortical thickness, spongy bone thickness, spongy bone thickness/cortical thickness, e angle and screw path length of each pedicle were measured. The incidence and the distribution characteristics of the narrow pedi?cle were analyzed. Anatomic parameters and age, gender and stature were compared between the narrow pedicle group and non?narrow pedicle. The risk of the pedicle screw insertion of the narrow pedicle was assessed. Results Among the 3 081 pedicles, 74 narrow pedicles were determined as their pedicles width were less than 5 mm, and the proportion of narrow pedicle was 2.40%. Among the 312 subjects, 26 subjects were found having narrow pedicles, and the proportion of individuals with narrow pedicles in the population was 8.33% (26/312). The incidences of narrow pedicle in thoracolumbar spine were T10 0.32%, T11 0.32%, T12 0.98%, L1 7.54%, L2 2.92%. The spongy bone thickness, spongy bone thickness/cortical thickness of narrow pedicle were lower than non?narrow pedicle. However, there were no significant differences of medial and lateral cortical thickness, e angle and screw path length between the narrow pedicle and non?narrow pedicle. Difference of the mean age between the two subjects groups had no statistical significance. The percentage of female in narrow pedicle subjects group was 84.6%(22/26), which was higher than that in non?narrow pedicle subjects group (49.7%, 142/286). The mean stature of the male and female of stenosis pedicle group subjects were 163.8±1.3 cm and 152.5±4.3 cm, which were shorter than those of non?narrow subjects pedicle group (169.5±5.6 cm, 160.1±6.6 cm). The percentage of the cortical bone breakthrough by the pedicle screws of narrow pedicle group was (84.6%, 27/32), which was higher than that of non?narrow pedicle group (14.7%, 33/224). Conclusion L1 is the most common segment of thoracolumbar spine that narrow pedicle exist, which is the result of reduction of the spongy bone thickness. Narrow pedicle mostly appears in short stature female. There is high risk of cortical bone breakthrough by insertion of the posterior pedicle screws in the narrow pedicle.
8.The comparison of cost and effectiveness between internal fixation and hemiarthroplasty in the treatment of displaced femoral neck fracture for the elderly
Jixin LI ; Yunhu JIANG ; Jianlei YANG ; Zengbo WEI ; Honghua WU
The Journal of Practical Medicine 2017;33(13):2164-2168
Objective To analyze the total cost and clinical effectiveness of internal fixation and hemiar-throplasty in the treatment of femoral neck fracture for the elderly. Methods From October 2013 to May 2015,85 patients above 60-year old who were diagnosed as displaced femoral neck fracture and received operation in our hospital. All the patients were divided into internal fixation(IF)group and hemiarthroplasty(HA)group respec-tively. There were 40 cases in the IF group and 45 cases in the HA group. The total cost associated with fracture in a year was collected by medical record ,telephone interview and standard methods. At the last follow-up ,we ap-plied Harris scores to evaluate the clinical outcome for each group. Results All the patients completed the operation successfully. During 1 year follow-up the total cost in the IF group was less than that in the HA group including higher primary hospitalization cost and less post-discharge cost. The total cost was 44,556.1 Yuan in the IF group and 72,198.0 Yuan in the HA group respectively. The data showed that the total cost of HA was 1.6 times higher than that of IF. At the last follow-up the mean Harris scores was 71.1 ± 12.1 in the IF group and 74.3 ± 10.3 in the HA group while the EQ-5D index was 0.74 ± 0.15 and 0.76 ± 0.13 respectively which showed no significant differ-ence(P > 0.05). Conclusions Both internal fixation and hemiarthroplasty have effective treatment for elderly pa-tients with femoral neck fracture. Compared to hemiarthroplasty IF can provide similar clinical effectiveness with less total cost. Therefore IF may contribute to decrease the economic burden for elderly patients in China.
9.Study on extended-spectrum β-lactamases and their genotypes of Shigella isolated from Tianjin
Xiaoni WANG ; Dianjun WEI ; Jianlei ZHANG ; Wanchen LI
Chinese Journal of Infectious Diseases 2012;30(2):71-75
Objective To study genotypes,antibiotic resistance and epidemiology of extendedspectrum β-lactamases (ESBL)-producing Shigella isolated in Tianjin,and to discuss the relationship between ESBL-producing Shigella and drug-resistance plasmid.Methods A total of 136 Shigella spp.were isolated from stool specimens of patients with diarrhea who presented mainly with bloody purulent stool from Tianjin Children's Hospital,Tianjin Medical University No.2 Hospital and Tianjin No.1 Central Hospital between May 2009 and September 2010.Suspicious ESBL-producing isolates were screened by K-B disc diffusion method. The conjugation experiment was performed in the confirmed ESBL-producing strains and antibiotic resistance was compared between clinical strains and transconjugants to confirm the plasmid-mediated resistance. The genotypes of these isolates were detected by polymerase chain reaction (PCR) using universal primers for TEM,SHV,CTX-M-1 group,CTX-M-2 group,CTX-M-9 group,respectively.Intergenic consensus PCR (ERIC-PCR) was employed to understand the molecular homology of the ESBL-producing isolates. The data were analyzed by x2 test.ResultsESBL were identified in 14.7% (20/136) of Shigella isolates,but no AmpC enzyme were detected.Among all the Shigella isolates,16 strains were genotype CTX-M-14,4 were genotype CTX-M-15.The strains with CTX-M ESBL were resistant to multiple antibiotics,while 100% sensitive to imipenem.The transconjugant test of 18 ESBL-producing isolates were positive,and these conjugations were only resistant to β-lactamases. Conclusions CTX-M type is the common genotype of ESBL-producing Shigella isolates in Tianjin. ESBL-producing is the main cause of multiple resistance to β-lactams.The transmission of CTX-M producing strains is mainly mediated by plasmids.
10.Peroxisome proliferator activated receptor β agonist, GW501516,ameliorates insulin resistance in glucose intolerant mouse model
Wei CHEN ; Lili WANG ; Hongying LIU ; Jianlei KANG ; Song LI
Chinese Journal of Pharmacology and Toxicology 2008;22(2):88-94
AIM The effects of GW501516, a peroxisome proliferator-activated receptor β (PPARβ) agonist, in long term diet induced obesity (DIO, high fat and maltose diet for 4 months) mice were evaluated, and the efficacy of GW501516 against insulin resistance and the involved mechanism was investigated. METHODSMice were divided into 3 groups: normal control, DIO model and DIO model+GW501516. GW501516 (10 mg·kg-1·d-1) was administered by ig once a day for 14 d. During the treatment, body weight and food intake were monitored every other day. The oral glucose tolerance test, and the serum biochemical parameters including the serum triglyceride, total cholesterol and high density lipoprotein cholesterol (HDL-C) levels were measured according to the specifications. To confirm the GW501516-mediated PPARβ activation, the mRNA levels of downstream genes related to glucose, lipid metabolism and energy expenditure was measured. RESULTS GW501516 treatment effectively improved the glucose intolerance, increased the area under the glucose curves[DIO model, (32.4±4.6) mmol·h·L-1 compared with DIO model+GW501516, (23.4±2.5) mmol·h·L-1, n=7-8, P<0.05], normalized the fasted blood glucose, and increased serum HDL-C level, besides, histological analysis revealed the decreased hepatic lipid accumulation and hypertrophy of hepatocyte in DIO mice. Moreover, RT-PCR results indicated that carnitine palmitoyltransferase 1b, uncoupling protein 2, uncoupling protein 3 and glucose transport protein 4 were all upregulated. CONCLUSIONGW501516 significantly ameliorates glucose intolerance, decreases fasted blood glucose and hepatic steatosis, which might be related to ① the enhancement of fatty acid oxidation and energy uncoupling in muscle, and ②the improvement of insulin-stimulated glucose transportation in skeletal muscle in the long term DIO mice.

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