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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


A 53-year-old woman was found "an occupant in the left ciliary body" two years ago and underwent the surgery of "left eye ball removal". Pathological results confirmed the diagnosis of malignant melanoma. The patient was admitted to our hospital again due to newly found heart murmur. With the combination of cardiac magnetic resonance (CMR) imaging characteristics, including high signals on T1-weighted and fat-suppressed T1-weighted images, the high signal on T2-weighted images, uneven first-pass perfusion and late gadolinium enhancement (LGE), as well as PET signal characteristics, the diagnosis of malignant melanoma cardiac metastasis was made. This case suggests that multimodality CMR, including T1-weighted, T2-weighted, first-pass perfusion, late gadolinium enhancement, and cine imaging, can be used to monitor and detect cardiac metastasis of melanoma in a relatively early stage. Therefore, we recommend a routine echocardiography screening for patients diagnosed with melanoma. In addition, CMR examinations and PET/CT may help early detection and timely intervention of melanoma cardiac metastasis, as for their good specificity in detecting, this disease in clinical practice.
Objective To present our institutional experience in laparoscopic spleen-preserving distal pancreatectomy (Lap-SPDP) using Kimura technique with or without early occlusion of the root of the splenic artery. In addition, to explore the safety and feasibility of this occlusion technique, especially its advantages in intraoperative hemorrhage control and spleen preservation. Methods From February 2011 to May 2019, 54 consecutive patients who were diagnosed as benign or low-grade malignant space-occupying lesions at the body and the tail of pancreas underwent Lap-SPDP using Kimura technique in our institution. Twenty-five patients before 2015 were allocated into non-occlusion group (n=25, non-occlusion group) and 29 patients after 2015 were allocated into occlusion group (n=29, occlusion group). The non-occlusion group underwent direct dissection of the distal pancreas with blood supply from the splenic artery as well as traditional traction of the splenic artery without occlusion. Whereas the occlusion group underwent temporary occlusion of the root of the splenic artery by Bulldog clip after transecting the neck of the pancreas and distal pancreas was excised under a relatively bloodless situation. Surgical techniques were described in detail. Data between groups were retrospectively collected and stratification analysis was performed based on the diameter of tumor (>3 cm or ≤3 cm). Results Before stratification, there was a statistical difference in age between the two groups (P=0.033), but no difference in body mass index (BMI) (P=0.069). The median lesion diameter of the two groups was 2.5 cm and 4 cm, respectively, with no statistical difference (P=0.065). The success rates of spleen preservation in the two groups were 93.1% and 92% respectively, showing no significant difference (P=1.000). The length of hospital stay was slightly longer in the non-occlusion group than that in the occlusion group (P=0.020). Comparing with the non-occlusion group, the occlusion group had significantly shorter operation time (median, 165 min vs. 235 min) and less estimated blood loss (median, 100 mL vs. 200 mL) (P<0.05). After stratification by the tumor diameter, there were 2 cases of failed spleen preservation both in occlusion and non-occlusion group with tumor diameter >3 cm (occlusion group: 2/8, 25% and non-occlusion group: 2/14,14.3%). However there was no statistical difference between the two groups (P=0.602). When the tumor diameter ≤3 cm, the spleen preservation rate of both groups reached 100%. When the tumor diameter was >3 cm, the operation time ofthe occlusion group was shorter than that of the non-occlusion group (P=0.005). In terms of intraoperative blood loss, regardless of tumor size, the occlusion group had less estimated blood loss than that of the non-occlusion group (P<0.05). In the occlusion group, no conversion or blood transfusion was needed intraoperatively and/or postoperatively. After stratification, there was no difference in the length of hospital stay between two groups (P>0.05). During the follow-up period (median (Min-Max), 13.5 (3-96) months), no perioperative death, disease recurrence, portal vein or splenic vein thrombosis, gastric varices or upper gastrointestinal bleeding was noted. Conclusion Lap-SPDP using Kimura technique with early occlusion of the root of splenic artery was safe and feasible and could be generally applied. By using this technique, we could reduce the operation time and blood loss, as well as sustain a high probability of spleen preservation.
Objective To construct a recombinant Listeria ivanovii (LI) strain that expressed Mycobacterium tuberculosis (MTB) specific antigen protein as a novel multistage tuberculosis (TB) vaccine candidate, and evaluate the biosafety and immunogenicity in mouse model. Methods T cell epitopes of four genes related to different stages of MTB infection were fused in series to form an antigen gene, i.e. the multistage antigen gene (named msv). Then msv was inserted into the targeting plasmid that contained LI homologous sequences. Recombinant LI strain was obtained by transfecting LI with targeting plasmid and screening the recombinant LI strain that carried msv in the genome after series of homologous gene recombination processes. The growth rate of the recombinant LI strain in vitro was observed and the expression of target protein was verified by Western blot. The 50% lethal dose (LD50) of the recombinant strain to C57BL/6 mice was measured. Mice were intravenously inoculated with vaccine candidate in dose of 0.1×LD50.The serum alanine aminotransferase (ALT) levels, bacterial load in organs, and organ pathological sections before and 1, 2, 3, 5, 7, 14 d after vaccination were used to evaluate the safety of vaccine candidate strain. To analyze the immunogenicity of vaccine candidate strain, mice were intravenously inoculated with LI-msv, LI, and NS respectively. Nine days post immunization, the spleens were isolated under sterile conditions and splenocytes were collected and stimulated. Lyphocytes which secret specific cytokines, interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-2 were analyzed by flow cytometry. Results A recombinant strain named LI-msv which was capable of expressing the multistage TB antigen protein was successfully constructed. The LD50 value of LI-msv for C57BL/6 mice (i.v.) was 3.3×108 CFU. After intravenously immunized the mice, this strain mainly multiplied in the liver and spleen, and was cleared at 7 d post innoculation. Such infection process caused transient pathological damages of the liver and spleen. Results of flow cytometry showed specific IFN-γ+ CD4+ and IFN-γ+ CD8+ T lymphocytes were successfully induced in LI-msv immunized mice spleen lymphocytes. The frequency of IFN-γ positive CD4+ and CD8+ T cells was significantly higher than those of vector control group and NS control group (P<0.005). Additionally, the frequency of specific TNF-α+ CD4+ T cell in LI-msv immunized group was significantly higher than that of vector control (P<0.01) and NS control group (P<0.005), and TNF-α+ CD8+ T cell frequency obviously increased than NS control group (P<0.005). Conclusions A novel multistage TB vaccine candidate expressing TB multistage antigen based on LI was successfully constructed. This vaccine candidate is safe and can induce specific cellular immune response to some extent. It is promising to be further studied as a candidate vaccine against tuberculosis.
Objective To study the effects of genistein (GEN) on reproductive system in prepubertal male rats. Methods Thirty SPF-rated male SD rats were randomly divided into control group (Con group), low-dose group (G1 group) and high-dose group (G2 group), with 10 rats in each group. Corn oil, 150 mg/kg and 300 mg/kg GEN dissolved in corn oil of equal volume were respectively administered every day and weighed the next day. After 6 weeks, the rats were sacrificed, and the testis, epididymis and prostate were dissected, and organ coefficients were calculated. Histopathological changes of testis was observed. The number of sperm was counted and the rate of sperm malformation was calculated. The concentrations of serum testosterone and estradiol were detected by radioimmunoassay. The protein phosphatase 2, regulatory subunit B, gamma (PPP2R2C) protein expression in testicular tissue was detected by immunofluorescence assay. The mRNA and protein expression levels of PPP2R2C and cyclin dependent protein kinases 2 (CDK2) in rat testis were detected by real-time quantitative fluorescence PCR (RT-qPCR) and Western blot, respectively. The protein phosphatase 2A (PP2A) activity in testicular tissue was detected by immunoprecipitation. Results There were no statistically significant differences in body mass, sperm number, serum estradiol and PP2A enzyme activity among the groups (P>0.05). The pathological structure of testicular in G2 group was disordered. Sperm abnormality rate in G1 and G2 groups was higher than that in Con group (P<0.05). Serum testosterone concentration in G2 group was lower than that in Con group (P<0.05). The expression of PPP2R2C and CDK2 in G2 group was higher than that in Con group (P<0.05), but the protein level was lower than that in Con group (P<0.05). PPP2R2C protein was expressed in testicular tissue in each group. Conclusion Long-term exposure to high dose (300 mg/kg) GEN during prepuberty may cause adverse effects on reproductive function in adult male rats. Further investigation is needed to determine whether PPP2R2C-PP2A-CDK2 phosphorylation pathway affects reproductive system in rats.
Objective To investigate the effects of Akkermansia muciniphila (A. muciniphila) on the proliferation, apoptosis and insulin secretion of rat pancreatic islet cell tumor cells (INS-1). Methods INS-1 cells were divided into three groups, normal, repair, and protect groups, and subsequently every group was subjected with A. muciniphila metabolites, live A. muciniphila orpasteurized A. muciniphila for 48 h. A group that did not treat with anything was set as blank control. After intervention, the cell viability was determined by MTT method, the insulin secretion level stimulated by glucose was determined by ELISA, the expressions of the genes involved in insulin secretion and apoptosis were tested by qRT-PCR, and the expression of apoptosis related protein Bax was evaluated by Western blot. Results There was no significant change in INS-1 cell morphology after co-incubation with 3 types of A. Muciniphila interventions for 48 h. The proliferative activity of INS-1 cells was decreased in the repair group that treated with live A. muciniphila than that of control (P<0.005). A. muciniphila intervention had no effect on insulin secretion in INS-1 cells in normal, repair or protection group (P>0.05). A. muciniphila secretions promoted the expression of glucose transporter 2 (Glut2) in 3 groups and the expression of glucokinase (GCK) in repair group (P<0.05). The expression of Bax of the INS-1 cell in the normal group was decreased after intervented with 3 kinds of A. muciniphila intervention materials (P<0.001).The expression of Bax gene of the INS-1 cell in the repair group that treated with dead A. muciniphila was decreased (P<0.05). The expression of Bax protein of INS-1 cells that treated with A. muciniphila interventions was decreased. Conclusion A. muciniphila can promote the expression of insulin secretion-related genes in INS-1 cells, inhibit the expression of apoptotic genes and apoptosis protein Bax.This research provides a new direction for applying A. muciniphila in improving type 2 diabetes.
Objective To study the expression and secretion of alternative complement pathway regulator complement factor H (CFH) in spontaneously produced or induced human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE). Methods RPE cells were acquired by spontaneous differentiation from hESC (sdRPE), a source of hESC-RPE, according to the method used in clinical trials. RPE cells were also acquired under the induction of growth factors and small molecules for 14 d (iRPE). Acquired cells were kept culturing for 3 month for maturation. All differentiated cells(P3)were cultivated for 4-5 weeks prior to characterization with qRT-PCR and immunofluorescence. Secretion levels of CFH were investigated by ELISA. ARPE-19 cell line was served as control. Results Both sdRPE and iRPE showed high similarity in cell morphology and the pattern of specific gene expression with human RPE. The relative CFH mRNA expression levels of both sdRPE and iRPE were significantly higher than that of ARPE-19 (P<0.05). The CFH secretion levels of sdRPE in the 24 h-, 48 h- and 72 h-culture medium were higher than those of iRPE (P=0.000 2); and this CFH secretion levels of both sdRPE and iRPE were higher than that of the ARPE-19 cell line (P<0.000 1). Conclusion Both sdRPE and iRPE derived by different differentiation methods expressed and secreted CFH, suggesting that hESC-RPE may have certain ability to regulate the alternative complement pathway.
Objective To investigate the effect of antisense oligodeoxynucleotides (ASODN) of Homeobox A1 gene (HOXA1) on proliferation, apoptosis, invasion and migration of esophageal carcinoma cells. Methods The expression of HOXA1 protein in normal esophageal epithelial cells Het-1A and esophageal cancer TE-1, EC9706 and Eca109 cells was detected by Western blot. Screening of highly expressed of HOXA1 protein esophageal squamous cell carcinoma cells for follow-up experiments. HOXA1 antisense oligonucleotide (ASODN) chains, sense oligodeoxynucleotides (SODN) chain, and nonsense oligodeoxy nucleotides (N-ODN) chain were designed. The screened esophageal squamous cell carcinoma cells with high expression were divided into HOXA1 ASODN group (5, 10, 15 μmol/L HOXA1 ASODN transfected Eca109 cells), control group (conventional culture medium, no cell transfection), SODN group (cells transfected with 15 μmol/L of SODN) and N-ODN group (cells transfected with 15 μmol/L N-ODN). Cell viability, apoptosis rate and invasion and migration ability were detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) method, flow cytometry, transwell chamber respectively; The expression of HOXA1, phosphorylation serine/threonine kinase (p-AKT), proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP-2) and B-cell lymphoma2 (Bcl-2) associated X protein (Bax) protein was detected by Western blot. Results Compared with normal esophageal epithelial cells Het-1A, the expression of HOXA1 protein in human esophageal squamous cell carcinoma cells TE-1, EC9706 and Eca109 was significantly higher (P<0.05). The expression of HOXA1 protein was the highest in Eca109 cells, therefore, Eca109 cells were selected for follow-up experiments. The expression of HOXA1 protein in Eca109 cells transfected with HOXA1 ASODN was significantly decreased (P<0.05). After transfection of Eca109 cells with HOXA1 ASODN, the viability of Eca109 cells decreased with the increase of concentration and time, the difference was significant compared with the control, SODN and N-ODN groups (P<0.05). 15 μmol/L HOXA1 ASODN significantly inhibited cell viability. After 15 μmol/L HOXA1 ASODN was transfected into Eca109 cells, the invasion and migration abilities of cells were significantly decreased, the apoptosis rate was increased, the expressions of p-AKT, PCNA and MMP-2 were significantly decreased, and the expression of Bax was significantly increased (P<0.05). Conclusion Antisense oligodeoxynucleotides of HOXA1 gene can inhibit the proliferation, invasion and migration of esophageal cancer cells, and induce apoptosis. The mechanism is related to the inhibition of PI3K/AKT signaling pathway.
Objective To explore the relationship between the imaging features of ultrasonography and thermal tomography and molecular subtypes of breast cancer. Methods 404 female breast cancer patients with complete imaging data and pathological findings from January 2014 to June 2017 were reviewed in the West China Hospital of Sichuan University. Breast cancer pathological molecules were classified into Luminal A like type, Luminal B like type, human epidermal growth receptor-2 (HER-2) overexpression type and Basal like type according to the expression of various immune markers. The correlation of ultrasonographic BI-RADS signs, thermal tomography characteristics and immunohistochemical results of breast cancer was analyzed. Results Breast cancer lesions with regular morphology, sharp margins, and enhanced posterior echo were more common in Basal like type; Microcalcification was more likely tend to appear in HER-2 expression breast cancer than other subtypes; The q-r curve of Luminal A like breast cancer was nearly 30°, and that was more common between 30°and 45° of HER-2 expression and Basal like breast cancer; The ratio of vertical and horizontal ≥1 of tumors and limited lymph node metastasis could not be used for distinguishing between different subtypes. Conclusion Different molecular subtypes of breast cancer may behave routine ultrasound and thermal tomography imaging features.
Objective We analyzed the brain structure of schizophrenia patients from multiple perspectives to explore the relationship between the duration of untreated psychosis (DUP) and clinical outcomes. Methods For 85 patients and 86 controls, clinical symptoms and cognitive function were evaluated, magnetic resonance imaging (MRI) and free surfer analysis were used to extract the cortical indicator, such as brain cortex thickness, surface area, volume, and so on. The patients were divided into four subgroups according to the boundary of March, June and two year due to the distribution and median of DUP. Finally multi-group comparison and correlation analysis for above indicators were analysed. Results DUP was associated with the surface area of the left insula, parsorbitalis, right hippocampus, superior frontal gyrus, frontal pole, and temporal pole; DUP mainly influenced the cortical thickness of left posterior cingulate gyrus, postcentral gyrus, right lateral occipital cortex, parsopercularis, medial orbitofrontal cortex, and the bilateral precentral gyrus. For cortical volume, DUP significantly affected left postcentral gyrus, right precuneus, lateral occipital cortex, parsopercularis, lingual gyrus, superior temporal gyrus, bilateral cuneus, pericalcarine cortex, precentral gyrus,superior parietal lobule, and insula.The first three months after onset is a critical period for the deterioration of cortical morphology and clinical function. Conclusion DUP in first-episode schizophrenia is associated with cortical morphological changes of temporal lobe, precentral, orbitofrontal cortex and the majority of medial regions of occipital lobe, it is very important to conduct early intervention for patients.
Objective To explore the value of a radiomics approach based on MRI texture analysis (TA) in identifying intraductal carcinoma of the prostate gland (IDCP). Methods MRI images of 56 patients with pathological proven prostate cancer were analyzed retrospectively, including 31 patients with pure prostate adenocarcinoma and 25 patients with IDCP component in the prostate adenocarcinoma lesions. After imaging features of lesions were analyzed, then enhanced arterial and venous phase images were imported into Omni-Kinetics software for the extraction the TA features of region of interests’ lesion according to the T2-weighted imaging. In order to set up a regression prediction model which based on texture parameters and morphological features. Furthermore, the comparison of diagnostic accuracy of each TA regression models were assessed by operating characteristic curves (ROC). Results Among the imaging features of peripheral lesions, the incidence of surgical capsule invasion, prostatic capsule involvement, and seminal vesicle invasion in patients with IDCP was higher than that in patients with adenocarcinoma alone (P<0.05). Among the imaging features of transitional zone lesions, patients with adenocarcinoma containing IDCP had a higher incience of imaging features as benign prostatic hyperplasia, extracapsular invasion of the prostate, seminal vesicles invasion, and vascular nerve bundles than that in pure adenocarcinoma group (P<0.05). In order to differential diagnosis of simple adenocarcinoma and adenocarcinoma containing IDCP, 4 arterial phase texture features were used to build the regression model in the peripheral zone group, and the area under the curve (AUC) of the TA model and combined model with or without seminal vesicles invasion were 0.890 and 0.938, respectively. In the transitional zone group, 2 arterial phase texture features and 2 venous phase features were used in TA regression model, and the AUC of texture model and the combined model with or without vascular nerve bundles were 0.844 and 0.901, respectively. Conclusion The incidence of adenocarcinoma with IDCP is higher in high-grade invasive prostate cancer. It is wonderful that when compared with T2WI, enhanced sequential texture analysis is more valuable when using the radiomics approach based on MRI texture analysis in identifying IDCP in prostate cancer.
Objective To compare the effect of different first-trimester screening programmes for Down syndrome in Sichuan Province. Methods We retrospectively collected the data of singleton pregnancies that were screened by serum biochemistry markers combined with nuchal translucency screening tests in the first trimester in Prenatal Diagnosis Center of West China Second University Hospital of Sichuan University from January 2011 to December 2017. The fetal chromosome results were obtained by amniocentesis or by telephone follow-up. The screening effect of maternal age, nuchal translucency thickness, maternal serum biochemistry markers and combined screening in the first trimester were analyzed. Results Among the 21 723 singleton pregnancies, 33 cases were diagnosed as Down syndrome, and 19 cases were diagnosed as trisomy 18 sex chromosome abnormalities were found in 4 cases, and other chromosome abnormalities were found in 8 cases. For the combined screening, the detection rate of Down syndrome was 72.73%, and the false positive rate was 2.49%; the detection rate of trisomy 18 syndrome was 73.68% with the false positive rate of 0.39%. With a 5% false positive rate, maternal age, nuchal translucency thickness, serum biochemistry markers and combined screening would respectively detect 15.15%, 57.58%, 60.61% and 87.88% of Down syndrome fetuses. Conclusion Compared with the other three screening programmes, the combined screening can effectively screen fetuses with Down syndrome and other chromosomal abnormalities.
Objective To analyze the risk factors of dyslipidemia of adult residents in Shunqing District of Nanchong City. Methods A five-stage stratified cluster sampling method was used to select adult residents from 9 communities in the urban area of Shunqing District of Nanchong City from January 2013 to April 2018 for questionnaires survey,physical measurement and laboratory test. Univariate analysis and multivariate logistic regression analysis were used to study the influencing factors of dyslipidemia. Results A total of 105 956 people was investigated,and the prevalence rate of dyslipidemia was 34.2% (36 272 cases). Among them, the prevalence rate of male was 38.11%, and 31.91% for female (P<0.01). The proportion of dyslipidemia with hypertension, diabetes, and coronary heart disease was 13.46%, 5.74%, and 0.39%, respectively. The proportion of hypertension with diabetes was 2.79%. Multivariate logistic regression analysis showed that gender (odds ratio (OR)=1.276, P<0.001), body mass index (OR=1.052, P<0.001), education level (set ≤elementary school as reference, high school OR=1.094, P<0.001, ≥graduated OR=1.185, P<0.001), smoking history (OR=1.124, P<0.001), coronary heart disease (OR=1.189, P<0.001), hypertension (OR=1.148, P<0.001),sdiabetes (OR=1.967, P<0.001), and family history of dyslipidemia (OR=1.760, P<0.001) were the influencing factors of dyslipidemia in residents of this region. Conclusions The dyslipidemia of urban residents in Nanchong area is highly concerned with hypertension, diabetes, and coronary heart disease. Male, obesity, high education level, smoking, coronary heart disease, hypertension, diabetes, and family history of dyslipidemia are risk factors for dyslipidemia in urban residents of Nanchong area. It is necessary to actively target the above risk factors and high-risk groups.

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