Different adverse childhood experiences and adolescents' altruism: The mediating role of life history strategy.

INTRODUCTION: The present study sought to investigate whether the relationship between childhood trauma, childhood socioeconomic (SES), and adolescents' altruism were mediated by their life history strategies and different adverse childhood experiences may function diversely on altruism, with two waves of data collected 6 months apart in a longitudinal design among Chinese adolescents. METHODS: A total of 658 adolescents (Mage = 13.51, SD = 0.73 at T1) were recruited and completed the online survey; their life history strategies were measured by the Mini-K, the Delayed of Gratification Questionnaire (DOG), and the Chinese version of the Adolescent Risk-Taking Questionnaire (ARQ-RB) together, and their altruism was collected again after six months. RESULTS: After controlling for gender and their altruism at T1, the results showed that childhood trauma (i.e., emotional maltreatment, physical maltreatment), as well as low SES and fast life history strategy, were significantly negatively correlated with adolescents' altruism at T2. Importantly, life history strategy at T1 mediated the relationship between T1 emotional maltreatment, T1 low SES, and adolescents' altruism at T2. However, the effect of physical maltreatment on altruism was not mediated by life history strategy. CONCLUSIONS: This study indicated that emotional maltreatment and low SES can affect adolescents' altruism by influencing the formation of adolescents' life history strategies. The findings revealed the different influences of adverse childhood experiences on adolescents' altruism, which supplied new empirical evidence for the life history theory and provided certain reference values for cultivating adolescents' altruism.

Gabexate Mesylate-Poloxamer 407 Conjugate Alleviates Sodium Taurocholate-Induced Severe Acute Pancreatitis in an Optimized Rat Model.

BACKGROUND AND AIMS: We have previously shown that gabexate mesylate-poloxamer 407 conjugate (GMTI) alleviates traumatic pancreatitis in rats. In this study, we evaluated the therapeutic effect of GMTI on sodium taurocholate-induced severe acute pancreatitis (SAP) in an optimized rat model. METHODS: An SAP rat model was established via microinjection of 3.5% sodium taurocholate and retention in the bile duct for 1 min. SAP rats were administered GMTI via tail vein injection (i.v.) or tail vein injection + intraperitoneal injection (i.v. + i.p.). All rats were sacrificed at 12 h after treatment. Biochemical approach and enzyme-linked immunosorbent assay were performed to measure the serum levels of amylase (AMY), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Hematoxylin and eosin staining and TUNEL assay were conducted to examine histopathology and acinar cell apoptosis in the rat pancreas. RESULTS: SAP was successfully induced in all model rats, as evidenced by progressively aggravating SAP symptoms and signs, pancreatic histopathological abnormalities, as well as elevated serum levels of TNF-α, IL-6, and AMY. The mortality rates at 1 h, 6 h, and 12 h were 0%, 0%, and 25%, respectively. GMTI therapy via i.v. or i.v. + i.p. significantly reduced pancreatic wet weights, ascites amounts, pathological scores, and circulating levels of TNF-α and IL-6 while promoting acinar cell apoptosis in SAP rats. GMTI therapy via i.v. + i.p. outperformed i.v. in improving pancreatic histology and reducing TNF-α and IL-6 serum levels in SAP rats. CONCLUSIONS: Our optimized SAP rat model is reliable and reproducible. GMTI therapy is a promising approach against SAP.

FoXA2 promotes esophageal squamous cell carcinoma progression by ZEB2 activation.

BACKGROUND: It has been reported that Forkhead transcription family member (FOXA2) regulates esophageal squamous cell carcinoma (ESCC) progression. However, the specific mechanism, by which FOXA2 promotes ESCC malignant progression, remains unclear. MATERIALS AND METHODS: QRT-PCR and western blotting were applied to measure FOXA2 expression in ESCC tissues, while CCK-8 assay and Transwell assays were used to investigate the effect of FOXA2 on ESCC. Luciferase reporter assay, followed by fast chromatin immunoprecipitation (ChIP) assay, was used to study the relationship between FOXA2 and ZEB2. RESULTS: FOXA2 was significantly increased in ESCC tissues, when compared to normal tissues. Moreover, high expression of FOXA2 was also found in ESCC cells. Knockdown of FOXA2 inhibited ESCC cell proliferation, invasion, and migration. Mechanically, FOXA2 was verified to regulate ZEB2 expression at transcription level. Moreover, ZEB2 reversed the inhibitory effect of FOXA2 on ESCC proliferation, invasion, and migration. The relationship between ZEB2 and FOXA2 in ESCC tissues was negative. CONCLUSIONS: These results indicate that FOXA2 plays a critical role in ESCC progression and may become a potential candidate target for ESCC treatment.

Radiofrequency ablation versus total thyroidectomy in patients with papillary thyroid microcarcinoma located in the isthmus: a retrospective cohort study.

OBJECTIVE: This retrospective study aimed to examine the benefits and complications of radiofrequency ablation (RFA) in patients with papillary thyroid microcarcinoma (PTMC) in the isthmus. METHODS: This retrospective study included patients with PTMC in the isthmus and treated at the Chinese People's Liberation Army hospital from 05/2014 to 05/2018. The patients were divided into the RFA and total thyroidectomy (TT) groups. The outcomes were operation-related complications, rate of recurrence, metastasis rate, and thyroid carcinoma-specific questionnaire of quality of life (THYCA-QOL). RESULTS: Among 218 patients, 115 patients underwent RFA, and 103 underwent TT. The rates of disappearance of the ablation zone at 1, 3, 6, 12, and 18 months after RFA were 0.8% (1/115), 10.4% (12/115), 51.3% (59/115), 90.4% (104/115), and 100% (115/115), respectively. Surgical time, blood loss, hospital stays, and treatment costs were higher with TT than with RFA (all p < 0.001). The final THYCA-QOL score of the RFA group was significantly higher than in the TT group (p < 0.001). Minor pain at the operation site was seen in all patients in the RFA group. No distant metastasis was detected in all patients, but one patient in the RFA group had a recurrence after 6 months. The final THYCA-QOL score of the RFA group was significantly lower than in the TT group (p < 0.001). CONCLUSION: These results suggest that RFA for PTMC in the isthmus had similar outcomes than TT. It will have to be confirmed in future studies.

Tanshinone IIA attenuates AOM/DSS-induced colorectal tumorigenesis in mice via inhibition of intestinal inflammation.

CONTEXT: Tanshinone IIA is a natural extract derived from a Chinese medicinal herb with multiple bioactivities; however, whether and how tanshinone IIA protects against colorectal cancer (CRC) are uncertain. OBJECTIVE: We investigated the potential beneficial effects of tanshinone IIA in a colitis-associated colorectal tumorigenesis mouse model and its underlying mechanisms. MATERIALS AND METHODS: Male C57BL/6 mice were treated with azoxymethane (AOM) 10 mg/kg body weight and dextran sulphate sodium (2.5% DSS) to induce a colitis-associated cancer model. Tanshinone IIA (200 mg/kg body weight) was given to the mice intraperitoneally. After 12 weeks, all mice were sacrificed to measure tumour formation, intestinal permeability, neutrophil infiltration, and colonic inflammation. In addition, whether tanshinone IIA has inhibitory effects on neutrophil activation was determined through in vitro investigations. RESULTS: We observed that tanshinone IIA significantly decreased tumour formation in AOM/DSS-treated mice compared to AOM/DSS-treated alone mice (0.266 ± 0.057 vs. 0.78 ± 0.153, p = 0.013). Tanshinone IIA also decreased intestinal permeability compared to that in AOM/DSS-treated alone mice (3.12 ± 0.369 vs. 5.06 ± 0.597, p = 0.034) and consequently reduced neutrophil infiltration of the colonic mucosa (53.25 ± 8.85 vs. 107.6 ± 13.09, p = 0.014) as well as intestinal inflammation in mice. Mechanistically, tanshinone IIA downregulated the NF-κB signalling pathway in the colonic tumours of AOM/DSS-treated mice. In vitro assays further validated that tanshinone IIA suppressed LPS-induced neutrophil activation. CONCLUSION: These data suggest that tanshinone IIA alleviates colorectal tumorigenesis through inhibition of intestinal inflammation. Tanshinone IIA may have a therapeutic potential for CRC in clinical practice.

Evaluation of Ultrasound-Guided Radiofrequency Ablation as a Treatment Option for Papillary Thyroid Microcarcinoma in the Isthmus: A Retrospective Study.

Background: About 3-9.2% of papillary thyroid carcinomas (PTC) are found in the isthmus, which has unique anatomic properties, making treatment more challenging. The aim of this study was to evaluate the treatment and undesirable effects of ultrasound-guided radiofrequency ablation (RFA) for PTC in the isthmus. Methods: This retrospective case series study assessed 112 patients with single papillary thyroid microcarcinoma in the isthmus, pathologically diagnosed before RFA at the General Hospital of Chinese PLA in 2014-2018. Follow-up was performed by contrast-enhanced ultrasound (CEUS) and ultrasound examinations at 1, 3, and 6 months and every 6 months thereafter. The complete ablation (CAR), disappearance (DR), and volume reduction (VRR) rates of nodules, the incidence of complications, and the rate of lymph-node metastasis were recorded. Results: The CAR of the tumors was 100%. During follow-up, the volume of coagulation necrosis gradually decreased. DRs at 1, 3, 6, 12, and 18 months after RFA were 0.8% (1/112), 10.7% (12/112), 51.7% (58/112), 91.0% (102/112), and 100% (112/112), respectively. The VRR evaluated by ultrasound and CEUS gradually increased. One recurrent case (0.8%) was found at 7 months after RFA. No complications, lymph node metastasis confirmed by ultrasound, and abnormal thyroid function were observed. Conclusions: This retrospective study shows that RFA is beneficial for the treatment of PTMC in the isthmus.

Effects of positive acceleration (+Gz stress) on liver enzymes, energy metabolism, and liver histology in rats.

BACKGROUND: Exposure to high sustained +Gz (head-to-foot inertial load) is known to have harmful effects on pilots' body in flight. Although clinical data have shown that liver dysfunction occurs in pilots, the precise cause has not been well defined. AIM: To investigate rat liver function changes in response to repeated +Gz exposure. METHODS: Ninety male Wistar rats were randomly divided into a blank control group (BC group, n = 30), a +6 Gz/5 min stress group (6GS group, n = 30), and a +10 Gz/5min stress group (10GS group, n = 30). The 6GS and 10GS groups were exposed to +6 Gz and +10 Gz, respectively, in an animal centrifuge. The onset rate of +Gz was 0.5 G/s. The sustained time at peak +Gz was 5 min for each exposure (for 5 exposures, and 5-min intervals between exposures for a total exposure and non-exposure time of 50 min). We assessed liver injury by measuring the portal venous flow volume, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver tissue malondialdehyde (MDA), Na+-K+-ATPase, and changes in liver histology. These parameters were recorded at 0 h, 6 h, and 24 h after repeated +Gz exposures. RESULTS: After repeated +Gz exposures in the 6GS and the 10GS groups, the velocity and flow signal in the portal vein (PV) were significantly decreased as compared to the BC group at 0 h after exposure. Meanwhile, we found that the PV diameter did not change significantly. However, rats in the 6GS group had a much higher portal venous flow volume than the 10GS group at 0 h after exposure. The 6GS group had significantly lower ALT, AST, and MDA values than the 10GS group 0 h and 6 h post exposure. The Na+-K+-ATPase activity in the 6GS group was significantly higher than that in the 10GS group 0 h and 6 h post exposure. Hepatocyte injury, determined pathologically, was significantly lower in the 6GS group than in the 10GS group. CONCLUSION: Repeated +Gz exposures transiently cause hepatocyte injury and affect liver metabolism and morphological structure.

Establishment and evaluation of a Beagle model of grade III pancreatic trauma.

Pancreatic trauma (PT) is a severe abdominal injury that is often combined with multiple organ injury. It is a severe disease that is difficult to diagnose and has a high mortality rate, particularly for grade III PT. The pathogenesis, disease progress and complications have not been fully investigated due to the lack of a reliable animal model. To address this, a Beagle model of grade III PT was established in the present study using a procedure involving rupture of the main pancreatic duct. Peripancreatic effusions and the degree of pancreatic damage were examined by routine ultrasound and contrast-enhanced ultrasound (CEUS). Also, ascites were collected for the examination of amylase and lipase levels, and whole blood samples were collected for the analysis of amylase, lipase, C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels in the serum. Urine samples were also collected for the examination of trypsinogen activation peptide (TAP). In addition, the pancreas was sectioned and stained with hematoxylin and eosin. In comparison with routine ultrasound, CEUS showed a large area of focal trauma, with a depth greater than half of the anteroposterior diameter of the pancreas, with a clear boundary, clear capsular rupture and trauma induced by active bleeding. The volume of ascites peaked at 48 h post-trauma and decreased thereafter. Amylase and lipase levels in the ascites were elevated at 24 h post-trauma and significantly decreased at 48 and 72 h post-trauma (P<0.01). In addition, serum amylase and lipase levels increased to peak levels at 48 h post-trauma and then decreased (P<0.05), while serum CRP, IL-6 and TNF-α levels peaked at 24 h post-trauma and then decreased (P<0.05). Urinary TAP levels also peaked at 24 h post-trauma and subsequently decreased (P<0.05). At 72 h post-trauma, the pancreatic cells were loosely distributed, with damaged acini, hyperchromatic nuclei and severe inflammatory cell invasion. These results indicated that the Beagle model of grade III PT was satisfactorily established, and that CEUS is potentially useful as an auxiliary diagnosis method for PT. This animal model may be useful for studying the pathogenesis, disease progress and complications of PT.

Assessment of Tumor Stiffness With Shear Wave Elastography in a Human Prostate Cancer Xenograft Implantation Model.

OBJECTIVES: To investigate the stiffness of human prostate cancer in a xenograft implantation model using shear wave elastography and compare the pathologic features of tumors with varying elasticity. METHODS: Human prostate cancer DU-145 cells were injected into 24 nude male mice. The mice were divided into 3 groups according to the time of transplantation (6, 8, and 10 weeks). The volume, elasticity, and Young modulus of tumors were recorded by 2-dimensional sonography and shear wave elastography. The tumors were collected for pathologic analyses: hematoxylin-eosin staining, Ponceau S, and aniline staining were used to stain collagen and elastic fibers, and picric acid-sirius red staining was used to indicate type I and III collagen. The area ratios of collagen I/III were calculated. The correlation between the Young modulus of the tumor and area ratio of collagen I/III were evaluated. Immunohistochemistry of vimentin and α-smooth muscle actin was performed. RESULTS: Nineteen tumors in 3 groups were collected. The volume and mean Young modulus increased with the time of transplantation. There were more collagen fibers in the stiff tumors, and there were significant differences in the area ratios of collagen I/III between groups 1 (mean ± SD, 0.50 ± 0.17) and 3 (1.97 ± 0.56; P < .01). The Young modulus of the tumors showed a very significant correlation with the area ratios of collagen I/III (r = 0.968; P < .05). The expression level of α-smooth muscle actin protein was higher in group 3 than in the other groups, but differences in vimentin expression were barely seen. CONCLUSIONS: Shear wave elastography is a novel useful technology for showing the elasticity of human prostate cancer xenograft implantation tumors. Collagen fibers, especially collagen type I, play a crucial role in the elasticity in the human prostate cancer xenograft implantation model.

Protection Provided by a Gabexate Mesylate Thermo-Sensitive In Situ Gel for Rats with Grade III Pancreatic Trauma.

BACKGROUND/AIMS: This study investigated the protection provided by gabexate mesylate thermo-sensitive in-situ gel (GMTI) against grade III pancreatic trauma in rats. METHODS: A grade III pancreatic trauma model with main pancreatic duct dividing was established, and the pancreas anatomical diagram, ascites, and serum biochemical indices, including amylase, lipase, C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), were examined. The pancreas was sliced and stained with hematoxylin eosin and subjected to terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: Ascites, serum amylase, lipase, CRP, IL-6, and TNF-α levels were significantly increased in the pancreas trauma (PT) groups with prolonged trauma time and were significantly decreased after GMTI treatment. The morphological structure of the pancreas was loose, the acinus was significantly damaged, the nuclei were irregular and hyperchromatic, and there was inflammatory cell invasion in the PT group compared to the control. After GMTI treatment, the morphological structure of the pancreas was restored, and the damaged acinus and inflammatory cell invasion were decreased compared to the PT group. Moreover, the cell apoptosis index was significantly increased in the PT group and restored to the same levels as the control group after GMTI treatment. CONCLUSIONS: GMTI, a novel formulation and drug delivery method, exhibited specific effective protection against PT with acute pancreatitis therapy and has potential value as a minimally invasive adjuvant therapy for PT with acute pancreatitis.

A novel thermosensitive in-situ gel of gabexate mesilate for treatment of traumatic pancreatitis: An experimental study.

Gabexate mesilate (GM) is a trypsin inhibitor, and mainly used for treatment of various acute pancreatitis, including traumatic pancreatitis (TP), edematous pancreatitis, and acute necrotizing pancreatitis. However, due to the characteristics of pharmacokinetics, the clinical application of GM still needs frequently intravenous administration to keep the blood drug concentration, which is difficult to manage. Specially, when the blood supply of pancreas is directly damaged, intravenous administration is difficult to exert the optimum therapy effect. To address it, a novel thermosensitive in-situ gel of gabexate mesilate (GMTI) was developed, and the optimum formulation of GMTI containing 20.6% (w/w) P-407 and 5.79% (w/w) P188 with different concentrations of GM was used as a gelling solvent. The effective drug concentration on trypsin inhibition was examined after treatment with different concentrations of GMTI in vitro, and GM served as a positive control. The security of GMTI was evaluated by hematoxylin-eosin (HE) staining, and its curative effect on grade II pancreas injury was also evaluated by testing amylase (AMS), C-reactive protein (CRP) and trypsinogen activation peptide (TAP), and pathological analysis of the pancreas. The trypsin activity was slightly inhibited at 1.0 and 5.0 mg/mL in GM group and GMTI group, respectively (P<0.05 vs. P-407), and completely inhibited at 10.0 and 20.0 mg/mL (P<0.01 vs. P-407). After local injection of 10 mg/mL GMTI to rat leg muscular tissue, muscle fiber texture was normal, and there were no obvious red blood cells and infiltration of inflammatory cells. Furthermore, the expression of AMS, CRP and TAP was significantly increased in TP group as compared with control group (P<0.01), and significantly decreased in GM group as compared with TP group (P<0.01), and also slightly inhibited after 1.0 and 5.0 mg/mL GMTI treatment as compared with TP group (P<0.05), and significantly inhibited after 10.0 and 20.0 mg/mL GMTI treatment as compared with TP group (P<0.01). HE staining results demonstrated that pancreas cells were uniformly distributed in control group, and they were loosely arranged, partially dissolved, with deeply stained nuclei in TP group. Expectedly, after gradient GMTI treatment, pancreas cells were gradually restored to tight distribution, with slightly stained nuclei. This preliminary study indicated that GMTI could effectively inhibit pancreatic enzymes, and alleviate the severity of trauma-induced pancreatitis, and had a potential drug developing and clinic application value.

[Construction of a lentiviral vector of FoxM1 shRNA and its transfection into human prostate cancer cell lines in vitro].

OBJECTIVE: To construct a recombinant lentiviral vector that co-express green fluorescent protein (GFP) and FoxM1 shRNA and establish a prostate cancer cell line with stable FoxM1 down-regulation. METHODS: Three interfering sequences targeting FoxM1 were designed and inserted into the lentiviral vector pHBLV-U6-ZsGreen-Puro. After identification by DNA sequencing, the lentiviral vectors carrying Foxm1 shRNA were packaged in 293 cells. The lentiviral particles were collected to infect human prostate cancer DU-145 cells, and the transfection efficiency was observed under fluorescence microscope; the interference efficiency was assessed using real-time PCR. DU-145 cells with stable FoxM1 down-regulation were screened with puromycin, and the expression level of FoxM1 was detected by Western blotting and the cell growth was observed using MTT assay. The stably transfected cells were examined for cell apoptosis and cell clone formation capacity with flow cytometry and colony formation assay. RESULTS: DNA sequencing demonstrated successful construction of the 3 FoxM1 shRNA lentivirus vectors. Real-time PCR showed a high interference efficiency of FoxM1 shRNA1 vector, which resulted in obvious down-regulation of FoxM1 in DU-145 cells. Western blotting showed that the expression of FoxM1 protein was decreased in FoxM1 shRNA1 lentivirus-transfected cells, which displayed a suppressed cell proliferation, increased apoptosis rate, and attenuated clonogenic ability. CONCLUSION: We have successfully established a prostate cancer cell model with stable FoxM1 down-regulation, which shows lowered proliferative and clonogenic activities with increased cell apoptosis.

Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer.

Forkhead box M1 (FoxM1) transcription factor is related to the pathogenesis of various malignancies and recent evidence indicates that FoxM1 promotes epithelial-mesenchymal transition (EMT) in breast cancer. Metformin can inhibit the progression of cancer. However, whether FoxM1 plays a role in EMT in prostate cancer (PCa) and whether metformin can suppress EMT through FoxM1 in PCa remain unresolved issues. In this study, we investigated the expression levels of the FoxM1 protein in 62 PCa and 39 benign prostate hyperplasia (BPH) samples and found that the expression levels of FoxM1 were higher in the PCa tissues (66.1%) compared with the BPH tissues (28.2%) (p<0.05). We observed that FoxM1 was expressed in the PCa cell lines and that metformin suppressed cell proliferation and the expression of FoxM1. We induced EMT in the PCa cells by the addition of transforming growth factor (TGF)-ß1 and verified the process by examining EMT-related gene (E-cadherin, vimentin and Slug) expression. In addition, the knockdown of FoxM1 by shRNA in the PCa cells reversed EMT and markedly reduced cell migration. These results indicate that metformin suppresses EMT by inhibiting FoxM1. We demonstrate that the suppression of FoxM1 may be an effective therapeutic strategy for PCa and provide further evidence of the anticancer effects of metformin.

Left ventricle geometry remolding after heart transplantation: a two-dimensional ultrasound study.

The function of the transplanted heart will be affected by acute allograft rejection, chronic rejection, high blood pressure and so on, which may induce the reconstruction of the left ventricle and the increase of left ventricular mass (LVM), and eventually lead to left ventricular hypertrophy that will significantly affect the prognosis of heart transplantation (HT). The purpose of this study was to dynamically monitor the changes of left ventricular geometric patterns after HT using two-dimensional echocardiography and to understand the remodeling process and its possible influencing factors. The left ventricular internal diameter, interventricular septal wall thickness, posterior wall thickness at end diastole were measured and the relative wall thickness (RWT), left ventricular mass, left ventricular mass index were calculated respectively in 34 HT patients and 34 healthy volunteers by two-dimensional echocardiography. The type of left ventricular geometry was identified based on the echocardiographic determination of LVM index (LVMI) and RWT. The HT patients were divided into three groups according to the time length after surgery: A (3 months postoperatively), B (6 months postoperatively) and C (12 months postoperatively). We compared the parameters of left ventricle between HT group and normal control group, and explored the risk factors causing the increase of LVM. The results showed that 4 patients (16%) in group A had concentric remodeling. Nine patients (34.62%) in group B had reconstruction, including 5 cases of concentric remodeling, 2 cases of concentric hypertrophy and 2 cases of eccentric hypertrophy. The hypertrophy incidence rate was 15.4% in group B. 15 patients (62.5%) had reconstruction in group C, including 9 cases of concentric remodeling, 5 cases of concentric hypertrophy, and 1 case of eccentric hypertrophy. The prevalence of hypertrophy was 25%. Multivariate analysis showed that hypertension and acute rejection history were the risk factors that resulted in left ventricular hypertrophy. It is concluded that the left ventricular remodeling occurs following cardiac transplantation at an early stage and the incidence of left ventricular hypertrophy increases with survival time. In this study, the one-year prevalence of left ventricular hypertrophy was 25% after surgery. Hypertension and acute rejection history are risk factors that can predict the left ventricular hypertrophy.