Variability in surgical approaches to hernias in patients with ascites.

BACKGROUND: Hernias in patients with ascites are common, however we know very little about the surgical repair of hernias within this population. The study of these repairs has largely remained limited to single center and case studies, lacking a population-based study on the topic. STUDY DESIGN: The Michigan Surgical Quality Collaborative and its corresponding Core Optimization Hernia Registry (MSQC-COHR) which captures specific patient, hernia, and operative characteristics at a population level within the state was used to conduct a retrospective review of patients with ascites undergoing ventral or inguinal hernia repair between January 1, 2020 and May 3, 2022. The primary outcome observed was incidence and surgical approach for both ventral and inguinal hernia cohorts. Secondary outcomes included 30-day adverse clinical outcomes as listed here: (ED visits, readmission, reoperation and complications) and surgical priority (urgent/emergent vs elective). RESULTS: In a cohort of 176 patients with ascites, surgical repair of hernias in patients with ascites is a rare event (1.4% in ventral hernia cohort, 0.2% in inguinal hernia cohort). The post-operative 30-day adverse clinical outcomes in both cohorts were greatly increased compared to those without ascites (ventral: 32% inguinal: 30%). Readmission was the most common complication in both inguinal (n = 14, 15.9%) and ventral hernia (n = 17, 19.3%) groups. Although open repair was most common for both cohorts (ventral: 86%, open: 77%), minimally invasive (MIS) approaches were utilized. Ventral hernias presented most commonly urgently/emergently (60%), and in contrast many inguinal hernias presented electively (72%). CONCLUSION: A population-level, ventral and incisional hernia database capturing operative details for 176 patients with ascites. There was variation in the surgical approaches performed for this rare event and opportunities for optimization in patient selection and timing of repair.

CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple-negative breast cancer.

Elevated expression of Copine 1 (CPNE1) has been observed in multiple cancers; however, the underlying mechanisms by which it affects cancer cells are unclear. We aimed to study the effect of CPNE1 on the tumorigenesis and radioresistance of triple-negative breast cancer (TNBC). Quantitative real-time polymerase chain reaction was used to detect the expression of CPNE1 in TNBC tissues and cell lines. Western blot, immunohistochemistry, and immunofluorescence were used to investigate the levels of CPNE1, p-AKT, AKT, cleaved caspase-3, cleaved PARP1, and γ-H2AX. Cell viability and apoptosis were measured by CCK-8 and flow cytometry, respectively. CPNE1 was overexpressed in TNBC tissues and cell lines and was associated with tumor size, distant metastases, and survival rates of patients with TNBC. Moreover, function study shows that CPNE1 promoted cell viability and inhibited cell apoptosis in vitro and inhibited the radiosensitivity of TNBC. Importantly, inactivation of AKT signaling inhibited the tumorigenesis and radioresistance mediated by CPNE1 in TNBC cells. In vivo xenograft study also shows that CPNE1 knockdown inhibited tumor growth and promoted cell apoptosis. Overall, our findings suggest that CPNE1 promotes tumorigenesis and radioresistance in TNBC by regulating AKT activation and targeted CPNE1 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

[Diffusion weighted imaging and perfusion weighted imaging in the differential diagnosis of benign and malignant renal masses on 3.0 T MRI].

OBJECTIVE: To explore the value of diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) in identifying benign and malignant renal masses and differentiating the histological types of renal masses. METHODS: Fifteen healthy volunteers and 46 patients with renal masses proven by pathology, including clear cell carcinomas (n = 18), papillary carcinomas (n = 8), chromophobe carcinomas (n = 7) and angiomyolipomas (n = 13), were examined with DWI and PWI scan at 3.0 T MRI. ANOVA was employed to compare the values of transfer constant (K(trans)), rate constant of backflux (Kep) and extra-vascular extra-cellular space fractional volume (Ve) proceeded by PWI and the value of ADC resulted from DWI between normal kidney and different histological types of renal masses. Receiver operating characteristics (ROC) curve was used to analyze and compare the diagnostic value of the methods of PWI and DWI in differentiating benign and malignant renal masses. RESULTS: The ADC value of normal renal parenchyma was (2.10 ± 0.24) × 10⁻³ mm²/s, which was statistically higher than benign and malignant renal masses (P < 0.05). The ADC value of benign masses was statistically higher than that of all histological types of malignant masses (P < 0.05). Among three histological types of malignancies, clear cell carcinoma showed the statistically highest ADC value (P < 0.05). But the difference between papillary carcinoma and chromophobe carcinoma had no statistical significance (P > 0.05).Values of K(trans), Kep and Ve between normal renal parenchyma and different histological types of renal masses had statistical differences.Values of K(trans) and Ve in three histological types of malignant renal masses were statistically higher than those of benign renal masses.Kep value of clear cell carcinoma was significantly higher than that of benign renal masses (P < 0.05).However, other histological types of malignant masses had no significant difference with benign masses.For three malignant masses, K(trans) of clear cell carcinoma, papillary carcinoma and chromophobe carcinoma were (0.85 ± 0.27), (0.51 ± 0.04) and (0.39 ± 0.05)/min respectively. All values gradually reduced. And the differences were statistically significant (P < 0.05). The Ve value of renal clear cell carcinoma was statistically higher than that of papillary carcinoma (P < 0.05). ROC curve was used to analyze and compare the diagnostic value of PWI versus DWI in differentiating benign and malignant renal masses. The K(trans) of benign and malignant renal masses had the largest AUC (AUC = 0.937) at a threshold of 0.38/min. And there were a sensitivity of 87.9% and a specificity of 85.7%. The AUC of ADC was 0.823, sensitivity 72.7% and specificity 92.9%. The ADC threshold for differentiating benign from malignant masses was 1.40 × 10⁻³ mm²/s; AUC of Ve 0.803, sensitivity 78.8% and specificity 71.4%, a threshold of 0.29/min; Kep showed lower diagnostic value. CONCLUSION: 3.0 T MRI DWI and PWI can effectively differentiate benign and different histological types of malignant renal masses. And PWI is superior to DWI in differentiating benign and malignant renal masses.K(trans) with the largest AUC showed the highest diagnostic value. And ADC is also irreplaceable in providing the information of cellular structural features and the movement of water diffusion.

[In vivo labeling of rat neural progenitor cells in subventricular zone with superparamagnetic iron oxide for tracking of magnetic resonance imaging].

OBJECTIVE: To explore the feasibility of in vivo labeling of adult rat neural progenitor cells (NPCs) in subventricular zone (SVZ) with superparamagnetic iron oxide particles (SPIOs) for tracking of magnetic resonance imaging (MRI). METHODS: A total of 7 SD rats were stereotactically injected with 3 µl SPIOs (7 mg Fe/ml) into anterior horn of right lateral ventricle and then 5-bromo-2'-deoxyuridine (BrdU) was injected intraperitoneally once daily for 1 week. MRI was performed at 1, 3, 7 and 14 days post-injection. After the final MRI scan, all rats were transcardially perfused and their brains removed and fixed. The sections were processed for Prussian blue iron staining and Prussian blue plus BrdU immunohistochemical staining. RESULTS: In all experimental animals, SPIOs were predominantly located in the anterior horn of right lateral ventricle and partial SPIOs entered the ventricular system. A needle path and a distribution of SPIOs along rostral migratory stream (RMS) towards olfactory bulb (OB) were depicted at the sagittal view of T2(*)WI, moderate MR artifact was visible and SPIOs tracking NPCs were successful (success rate of 100%). The result of staining showed SPIOs labeling NPCs were effective. And the labeling rates were 75.5%, 42.3%, 23.6% in SVZ, RMS and OB respectively. CONCLUSION: Effective in vivo labeling of adult rat NPCs in SVZ with SPIOs is feasible. And dynamical migration of labeling NPCs along RMS towards OB may be visualized on MRI.

MicroRNA-145 regulates the proliferation of the human gastric cancer cells by targeting tuftelin 1 (TUFT1).

MicroRNA-145 (miR-145) has been shown to regulate the development of different human cancer. However, the role of miR-145 via modulation of tuftelin 1 (TUFT1) expression has not been studied in gastric cancer. TUFT1The results showed that gastric cancer tissues and cell lines exhibit significant (P<0.05) downregulation of miR-145. Overexpression of miR-145 significantly (P<0.05) inhibited the viability and colony formation of the MGC-803 gastric cancer cells. Annexin V/PI staining revealed that miR-145 exerts its tumor-suppressive effects via induction of apoptosis. The apoptotic cell percentage increased from 5.75% in negative control to 22.95% in miR-145 overexpressing MG-803 cells. This was also accompanied by upregulation of Bax and downregulation of Bcl-2 expression. TargetScan analysis and the dual luciferase assay revealed TUFT1 as the functional target of miR-145. The expression of TUFT1 was significantly (P<0.05) upregulated in gastric cancer tissues and cell lines. However, overexpression of miR-145 causes inhibition of the TUFT1 expression. Silencing of TUFT1 mimicked the tumor-suppressive effects of miR-145. However, tuftelin 1 overexpression attenuated the tumor-suppressive effect of miR-145 in MGC-803 gastric cancer cells. Taken together, the results of the present study indicate that miR-145 targets TUFT1 at translational level to exert its tumor suppressive effects in gastric cancer.

Duration of immunogenicity of high-dose and prolonged-schedule hepatitis B vaccine among patients with chronic kidney disease: A one year follow-up study in China.

BACKGROUND: Patients with chronic kidney disease (CKD) have immunological defects that result in reduced production and faster decay of anti-HBs after hepatitis B vaccination. We assessed the duration of the immunogenicity after four-standard-dose and four-triple-dose regimens among patients with CKD. METHODS: A randomized controlled trial was conducted between May 2019 and February 2020. Patients were randomly allocated to receive three or four doses of 20 µg    , or four doses of 60 µg   of hepatitis B vaccine. Immunogenicity was assessed for 18 months till February 2021. RESULTS: Between months 7 and 18, the seroconversion rate decreased from 81.7% (58/71) to 64.3% (36/56) in IM20 × 3 group, from 93.0% (66/71) to 77.4% (41/53) in IM20 × 4 group, and from 93.2% (68/73) to 90.7% (49/54) in IM60 × 4 group. Seroconversion was higher in IM60 × 4 group than in IM20 × 3 group at month 18 (P < 0.05). In multivariate analysis, CKD patients without immune suppression or hormone therapy or patients with IM60 × 4 were more likely to have durable immunogenicity at month 18. CONCLUSIONS: Patients receiving four-triple-dose regimen of hepatitis B vaccine showed improved duration of immunogenicity at the one-year follow-up. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03962881).

Immunogenicity and safety of a high-dose and prolonged-schedule hepatitis B vaccine among chronic kidney disease patients: a randomized, parallel-controlled trial.

Background: The immunogenicity against hepatitis B vaccine is unsatisfactory in the chronic kidney disease (CKD) patients, and studies evaluating augmented vaccine regimens to enhance immunogenicity have been inconclusive.Objectives: To evaluate the immunogenicity and safety of four-standard-dose and four-triple-dose regimens hepatitis B vaccine among CKD patients in China.Research design and methods: We conducted a multicenter, randomized, parallel-controlled trial including 273 patients with CKD who were randomly allocated to receive 3 or 4 doses of 20 or 60 µg of recombinant hepatitis B vaccine.Main outcome measures: Seroconversion rates, high-level response rates, and geometric mean concentrations (GMCs) of anti-HBs at months 3 and 7.Results: The seroconversion rates and high-level responses in the IM20 × 4 group and the IM60 × 4 group were higher than those in the IM20 × 3 group at months 3 and 7 (P < 0.05). The IM60 × 4 group had better immune responses than the IM20 × 4 group at month 3 (P < 0.05); however, no significant difference was noted at month 7 (P > 0.05).Conclusions: Both the four-standard-dose and four-triple-dose regimens improved immune response compared to the three-standard-dose regimen of hepatitis B vaccination in CKD patients, and the additional effect of higher dose was minimal.Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT03962881).

Immunogenicity and persistence of high-dose recombinant hepatitis B vaccine in adults infected with human immunodeficiency virus in China: A randomized, double-blind, parallel controlled trial.

OBJECTIVES: To explore the immunogenicity and persistence of the 60 µg hepatitis B vaccine in adults infected with human immunodeficiency virus (HIV). METHODS: We conducted a randomised controlled trial for adults infected with HIV. A total of 182 patients were randomly allocated to receive 20 µg (IM20 group) or 60 µg (IM60 group) of recombinant hepatitis B vaccine at months 0, 1, and 6 to assess the immunogenicity and were followed-up from month 7 to 42 to assess long-term immunogenicity. RESULTS: Our data showed that the response rate and geometric mean concentration (GMC) of antibodies to hepatitis B surface antigen (anti-HBs) in the IM60 group at month 7 were higher than those in the IM20 group (P > 0.05). The GMC of anti-HBs among the two groups decreased rapidly during the follow-up period (P > 0.05). Survival analysis showed that 25% of patients with anti-HBs ≥ 10 mIU/mL were 20 months in the IM60 group and 9.3 months in the IM20 group. CONCLUSION: The three-dose 60 µg hepatitis B vaccine showed partially better immunogenicity and persistence than the three-dose 20 µg vaccine. TRIAL REGISTRATION: The trial was registered on clinicaltrials.gov, NCT03316807.

Long-term persistent immunogenicity after successful standard and triple-dosed hepatitis B vaccine in hemodialysis patients: A 3-year follow-up study in China.

BACKGROUND: Although the efficacy of hepatitis B vaccines among hemodialysis patients has been documented, the long-term persistence of immunogenicity in this population remains largely unknown. We explored the long-term persistence of immunogenicity induced by different hepatitis B vaccine regimens in hemodialysis patients. METHODS: In initial study, we conducted a randomized, multicenter, double-blind, parallel-controlled trial among hemodialysis patients in 13 hospitals in Shanxi Province, China. A total of 352 hemodialysis patients were allocated to receive 3-dose 20 µg (IM20 group) and 3-dose 60 µg (IM60 group) recombinant hepatitis B vaccine at months 0, 1, and 6. Vaccine-induced immune responses were measured at month 7. In this study, the responders (anti-HBs ≥ 10 mIU/mL) were followed up at months 18, 24, 30, 36 and 42, respectively. We used the generalized log-rank test and generalized estimating equations (GEE) to analyze the long-term durability of responses and the kinetics of anti-HBs levels, respectively. RESULTS: A total of 284 patients were involved in the extended follow-up period. The duration of vaccine-induced response with 75% of patients maintained protective antibody were 12 months and 18 months in the IM20 group and IM60 group, respectively (P = 0.291). The long-term persistent immunogenicity induced by 3-dose 60 µg was more satisfactory than that by 3-dose 20 µg hepatitis B vaccine in patients with hemodialysis duration ≥ five years (P = 0.023). The peak anti-HBs levels in 100-1000 mIU/mL or ≥ 1000 mIU/mL were more likely to maintain long-term protective antibody compared to anti-HBs levels in 10-100 mIU/mL (P ＜ 0.05). The kinetic profile was similar between the two groups (P = 0.334). CONCLUSION: High-dose 60 µg hepatitis B vaccine could lead a satisfactory long-term durability of immunogenicity among patients with hemodialysis duration of five years or more. Peak anti-HBs level after vaccination was associated with the long-term persistence of immunogenicity.

Predicting related factors of immunological response to hepatitis B vaccine in hemodialysis patients based on integration of decision tree classification and logistic regression.

The non/hypo-response rate of the hepatitis B vaccine among hemodialysis (HD) patients is still high, it is of great significance to explore the influencing factors and their relationships. To study the related factors and their relationships using logistic regression model and Chi-squared Automatic Interaction Detection (CHAID) decision tree model. A randomized controlled trial was conducted between February 2014 and May 2015 in China. HD patients being serologically negative for HBsAg and anti-HBs were randomly assigned to receive three intramuscular injections of the standard dose (20 µg) or high dose (60 µg) of recombinant hepatitis B vaccine at months 0, 1, and 6. Those with anti-HBs concentrations <100 mIU/mL, and ≥100 mIU/mL at month 7 were considered as non/hypo-response and high-level response, respectively. The non/hypo-response was 31.34% (89/284). After adjustment for confounders, logistic analysis showed that males (OR = 2.203, 95%CI: 1.109-4.367) and those with higher dialysis frequency (>4 times per 2 weeks) (OR = 1.918, 95%CI: 1.015-3.626) had a significant risk of non/hypo-response. While the CHAID analysis showed that gender, dose, and dialysis frequency were influencing factors of non/hypo-response, and gender is most important. The interaction between gender and dialysis frequency had the greatest effect on immunization, and followed by the interaction between dialysis frequency and vaccine dose. Taken together, gender, dose and dialysis frequency were influencing factors of hepatitis B vaccine in HD patients.

[Study of bone mesenchymal stem cells tropism for hepatic tumors and effect on the form of tumor stromal].

OBJECTIVE: To investigate the tropism capacity of the rat bone mesenchymal stem cells (BMSC) for hepatic tumors microenvironment and the effect on the form of tumor stromal. METHODS: Rat BMSC were isolated, cultured and expanded, then incubated with superparamagnetic iron oxide (SPIO) nanoparticles. Prussian blue stain was performed for showing intracellular irons. Walker-256 cells were injected into the rat livers directly to establish hepatic tumor models. The experiment was divided into two experimental groups (the group venous injected with BMSC after tumors becoming mass: tail venous injected with BMSC after MR showed the presence of tumors at 6-8 days after operation and the group venous injected with BMSC before tumors becoming mass: tail venous injected with BMSC when MR showed no presence of tumors at 3 days after operation) and one control group. To the experimental groups animals, MRI was made before venous injection of BMSC and at 5, 10, 15 days after BMSC transplantation. The rats were killed at corresponding period. The pathologic examinations were analyzed, including HE, Prussian blue stain. The expression of vascular endothelial growth factor (VEGF), CD31, von Willebrand factor (vWF) in the specimens harvested at 10 days after BMSC transplantation were detected immunohistochemically. RESULTS: Prussian blue staining of SPIO labeled BMSC demonstrated cells could be effectively labeled and the labeling efficiency was almost 90%. After BMSC transplantation, two experimental groups were showed tuberculous signal intensity loss at the margin of tumors on T(2) weighted MR images at 5, 10 days after transplantation and the signal intensity loss was not visualized at 15 days after transplantation. The control group was not observed signal intensity decrease. Prussian blue staining of histological analysis showed blue-stained iron particles distributed at the margin of tumor at 5, 10, 15 days after transplantation. Immunohistochemical examination showed that the expression of VEGF, CD31, vWF in two experimental groups at 10 days after transplantation were higher than that in the control group (F = 34.03, P < 0.01; F = 84.24, P < 0.01; F = 7.08, P < 0.05). CONCLUSION: Rat BMSC have the ability to migrate towards hepatic tumors in vivo and promote to form vascular endothelium.

Long-term durability of immunogenicity induced by standard and triple-dose hepatitis B vaccine in patients receiving methadone maintenance treatment.

OBJECTIVES: We explored the long-term immunogenicity induced by 60 µg and 20 µg hepatitis B vaccines among patients receiving methadone maintenance treatment (MMT). METHODS: In initial study, a randomized controlled trial was conducted, in which patients receiving MMT were administered 20 µg (IM20 group) or 60 µg (IM60 group) hepatitis B vaccines at months 0, 1, and 6. In this study, the responders at month 7 were followed-up at months 18, 30, and 42 to estimate long-term immunogenicity. RESULTS: The response rate decreased from 78.0% (39/50) to 31.1% (14/45) in the IM20 group, and from 86.0% (43/50) to 50.0% (20/40) in the IM60 group from month 7 to 42. Vaccine-induced responses in 75% of patients were observed for 14.2 months in the IM20 group and for 20.0 months in the IM60 group, and differences between these two groups were non-significant (P > 0.05). CONCLUSION: The three-dose 20 µg and 60 µg hepatitis B vaccines showed similar rapid hepatitis B surface antibody decreases. Abbreviations: HBV, hepatitis B virus; MMT, methadone maintenance treatment; HCC, hepatocellular carcinoma; HBsAg, hepatitis B surface antigen; anti-HBs, hepatitis B surface antibody; HR, hazard ratio; CI, confidence interval; IQR, interquartile range; GEE, generalized estimated equation.

[Effects of mesenchymal stem cell transplantation on growth of liver cancer: experiment with rats].

OBJECTIVE: To evaluate the effects of mesenchymal stem cell (MSC) transplantation on the growth of liver cancer. METHODS: MSCs were isolated from the bone marrows of SD rats. Walker-256 cancer cells were isolated from the cancerous ascites of rat and cultured. Forty-five SD rats were randomly divided into 3 equal groups: mixed transplantation group undergoing laparotomy and transplantation of cancer cells mixed with MSCs into the liver, MSC IV transplantation group undergoing injection of MSCs into the caudal vein, and control group undergoing only MSC transplantation into the liver. MR imaging was performed s at days 3, 6, 9 and 12 after modeling to measure the maximum cross section area of the tumor. At day 12 the rats were killed after MR imaging with their livers taken out to undergo HE staining and pathological examination. Immunohistochemistry was used to detect the expression of vascular endothelial cell growth factors (VEGF), nm23 gene, a tumor metastasis inhibiting gene, and proliferating cell nuclear antigen (PCNA), a nuclear polypeptide necessary in the DNA synthesis. RESULTS: No significant evidence of tumor formation was detected by MRI at days 3 and 6 after modeling in all rats and tumor nodules were observed since day 9. The maximum cross section areas of tumor of the mixed transplantation group and MSC IV transplantation group were significantly larger than that of the control group at days 9 and 12 (F = 4.21, P < 0.05; F = 8.52, P < 0.01). Immunohistochemistry showed that VEGF expression levels of the two study groups were both significantly higher than that of the control group (F = 9.58, P < 0.01), while the nm23 gene expression levels of the 2 study groups were both significantly lower than that of the control group (F = 4.61, P < 0.05). The PCNA expression level of the mixed transplantation group was significantly higher than that of the control group (d'((1, 0.05)) = 0.34, d'((1, 0.01)) = 0.63, P < 0.05), however, there was no significant difference in the PCNA expression level between the MSCs IV transplantation group and the control group (d'((1, 0.05)) = 0.32, d'((1, 0.01)) = 0.48, P > 0.05). There was no significant difference in the tumor apoptotic index between the 2 study groups and the control group (F = 1.25, P > 0.05). CONCLUSION: MSC transplantation increases the expression of VEGF and PCNA, while decreases the expression of nm23 gene in cancer cells, thus favoring the tumor growth.

Effects of a Portable Peritoneal Lavage Device on Dogs with Seawater-Immersed Open Abdominal Injury.

BACKGROUND: Seawater-immersed open abdominal injury is a special injury during marine activities. Effective warmed peritoneal lavage in the field early after injury is the key to treatment. This pilot study aimed at exploring the treatment effects of a self-developed portable peritoneal lavage device compared with conventional treatment model. MATERIAL AND METHODS: Beagle dogs were used to develop models of seawater-immersed open abdominal injury. A conventional lavage method or a novel peritoneal lavage device was used for lavage and rewarming. The vital signs, electrolyte, serum inflammatory cytokine expression levels, histological changes of mucosa, and microstructure variety of different groups were observed and compared before and after immersion and 2 h, 1 d, 3 d, and 5 d after lavage. RESULTS: The levels of TNF-α, IL-1ß, IL-8, IFN-γ, VEGF, and TGF-ß in the blood and the damage of tissues and cells in three groups were increased after immersion and decreased at the later points of time after lavage. The concentration of Na+, K+, Cl-, lactate, and lactate dehydrogenase in the plasma was significantly higher than that before immersion (P < 0.05), and the concentration of Ca2+ and HCO3 - and plasma pH decreased slightly (P < 0.05). The degree of tissue inflammation and mucosal injury in the delayed control group and device group was lower than the control group. CONCLUSIONS: Timely lavage and rewarming using a portable peritoneal lavage device reduced the inflammatory response of seawater-immersed open abdominal injury dogs and reduced the damage of multiple organs. The dogs recovered better and faster than the conventional treatment group.

[Anxiety disease: decreased of functional connectivity in left superior temporal gyrus (GTs) and right GTs].

OBJECTIVE: Neuronal circuits involved in the pathophysiology of anxiety are not yet fully understood. We used functional connectivity MRI to explore the characteristic of functional connectivity in anxiety disorders patient and the neural mechanism of this disease. This work was selected as an oral presentation in 2006 ISMRM. METHODS: Twenty right-handed subjects were included in this study, and were divided into two groups. The anxiety (P) group (n = 10; 7 male, mean age 42 years) consisted of patients meeting DSM-IV criteria for a principal diagnosis of anxiety disorder. The control (C) group consisted of volunteers free of psychiatric symptoms, and was matched on age and gender (n = 10; 7 male) with the panic patients. The subjects underwent noninvasive functional magnetic resonance imaging while listening actively to (1): emotionally neutral word alternating with no word as the control condition (CN, PN), and (2): threat-related words alternating with emotionally neutral word as the experimental condition (CT, PT). Each word was presented in pseudorandom order in each 16 s block of 12 words of the same type. Eight alternating blocks of neutral words were presented for about 256 s. The subject was only asked to passively listen to each word. All MRI data were obtained on a 1.5-Tesla scanner Data analysis was performed with SPM99 to find significant activations in two tasks for two groups. Based on group t-test, we chose two anatomically defined regions: left superior temporal gyrus (GTs) and right GTs. Then, based on individual t-map, the voxel with the largest t-value within two regions was taken as the subject-specific peak voxel. We define clusters based on faces and edges, but not corners, so each voxel has 18 neighbors. Subject-specific averaged time series were extracted by averaging the time series of 19 voxels. Since healthy control subjects showed no significant activation (corrected, P < 0.05) during processing of anxiety word to neutral word, region of interest during processing of neutral word to no word was used as substitution. The connectivity degree eta(i j) between the node i and the node j is used to identify the change of the functional connectivity associated with differential tasks, which calculated by using the methods that have developed by ourselves. Moreover, we just consider coherence in low-frequency (0-0.15 Hz). RESULTS: The activation brain regions have been reported in our previous work. Patients were significant different from normal controls on two experiments. The connectivity degree of left Gts and right Gts in two tasks across all subjects was calculated. Comparing during processing neutral word to blank, a significant decrease (P < 0.001) in functional degree was observed during processing of threaten word to neutral word (eta = 0.5636 for CN, eta = 0.555 for CT, eta = 0.5616 for PN, eta = 0.4926 for PT). Especially, the greater decrease connectivity degree was identified for patient group compared with normal control during threat-related words alternating with emotionally neutral word condition. The connectivity degree identifies that functional interactions change with differential task. CONCLUSION: This result suggests decreased functional connectivity among left superior temporal gyrus and right GTs during processing of anxiety word to neutral word in anxiety patients. This dysfunction may mediate the neural mechanism of this sort of disease.

[CT and pathological manifestations of intraductal papillary mucinous neoplasm of pancreas: a comparative study].

OBJECTIVE: To evaluate the diagnostic value of CT in pancreas intraductal papillary mucinous neoplasm (IPMN) by analyzing its CT feature and pathological findings. METHODS: The clinical and CT data was analyzed among 39 patients with IPMN whose diagnosis was confirmed by pathology. The CT manifestations were classified into 3 types: simple main pancreatic duct enlargement; main pancreatic duct enlargement combined with pancreatic cystic lesion; and simple pancreatic cystic lesion. The correlation between the CT types and Takada pathological types (main duct type, branch type, and mixed type) was analyzed. All the cases were pathologically classified into benign and malignant/boundary groups. Statistical tests of the difference of CT features (mural nodule, septa, size, caliber of main pancreatic duct and common bile duct) between the 2 groups were performed. RESULTS: The CT type I matched the main duct type, the CT type II mainly matched the branch type and mixed type, and the CT type III matched the branch type (P < 0.001). The probability of benign lesion was 92% with no mural nodule in the lesion, while the probability of benign lesion was only 42% with mural nodule presented (P = 0.003). In terms of the septa, there was no significant difference between benign and malignant lesions (P = 0.793). The size of malignant/boundary lesions exceeded that of benign lesions (P = 0.016). There were no significant difference in calibers of main pancreatic duct and common bile duct between the benign and malignant/ boundary groups. Without considering pathological grouping the caliber of main pancreatic duct exceeded that of the common bile duct in all the cases (P = 0.02). CONCLUSION: CT typing of IPMN well matches the pathological typing which benefits the CT diagnosis of IPMN. The caliber of main pancreatic duct usually exceeds that of common bile duct in IPMN. This feature contributes to its diagnosis.

Polyethylene glycol-poly(ε-benzyloxycarbonyl-l-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma.

A polyethylene glycol-poly(ε-benzyloxycarbonyl-l-lysine) (PEG-SS-PLL) block copolymer based on a disulfide-linked, novel biodegradable catiomer bearing a PEG-sheddable shell was developed to avoid "PEG dilemma" in nanoparticle intracellular tracking of PEG-PLL where PEG was nondegradable. However, PEG-SS-PLL catiomers have not been used to deliver small interfering VEGF RNA (siVEGF) in antiangiogenesis gene therapy. In this study, we aimed to investigate whether this novel biodegradable catiomer can deliver siVEGF into cancer cells and at the same time have an antitumor effect in a xenograft mouse model. It was found that PEG-SS-PLL efficiently delivered siVEGF with negligible cytotoxicity, and significantly decreased the expression of VEGF at both the messenger-RNA and protein levels both in vitro and in vivo, and thus tumor growth was inhibited. Our findings demonstrated that PEG-SS-PLL/siVEGF could potentially be applied to antiangiogenesis gene therapy for hepatocellular carcinoma.

Three-locus and four-locus QTL interactions influence mouse insulin-like growth factor-I.

A previous analysis of serum insulin-like growth factor I (IGF-I) levels in a mouse population (n = 961) derived from a cross of (BALB/cJ x C57BL/6J) F1 females and (C3H/HeJ x DBA/2J) F1 males documented quantitative trait loci (QTL) on chromosomes 1, 10, and 17. We employed a newly developed, random walk-based method to search for three- and four-way allelic combinations that might influence IGF-I levels through nonadditive (conditional or epistatic) interactions among 185 genotyped biallelic loci and with significance defined by experiment-wide permutation (P < 0.05). We documented a three-locus combination in which an epistatic interaction between QTL on paternal-derived chromosomes 5 and 18 had an opposite effect on the phenotype based on the allele inherited at a third locus on maternal-derived chromosome 17. The search also revealed three four-locus combinations that influence IGF-I levels through nonadditive genetic interactions. In two cases, the four-allele combinations were associated with animals having high levels of IGF-I, and, in the third case, a four-allele combination was associated with animals having low IGF-I levels. The multiple-locus genome scan algorithm revealed new IGF-I QTL on chromosomes 2, 4, 5, 7, 8, and 12 that had not been detected in the single-locus genome search and showed that levels of this hormone can be regulated by complex, nonadditive interactions among multiple loci. The analysis method can detect multilocus interactions in a genome scan experiment and may provide new ways to explore the genetic architecture of complex physiological phenotypes.

An Intracranial Gliosis Mimicking Neoplasm: A Dilemma.

Intracranial gliosis has no typical clinical signals or imaging characteristics. Therefore, it can be easily misdiagnosed as neoplasm. Hereby, we report a unique case of gliosis that grew outward from the surface of the brain. MRI depicted its signal and enhancement pattern similar to the cerebral gray matter. The diagnosis was confirmed by pathology and immunohistochemistry. Although it was difficult to reach a diagnosis, correlating its origin, growing pattern and MR features and knowing that gliosis can present this way may help in differentiating it from other diseases.

Biodegradable gadolinium-chelated cationic poly(urethane amide) copolymers for gene transfection and magnetic resonance imaging.

Theranostic nano-polyplexes containing gene and imaging agents hold a great promise for tumor diagnosis and therapy. In this work, we develop a group of new gadolinium (Gd)-chelated cationic poly(urethane amide)s for gene delivery and T1-weighted magnetic resonance (MR) imaging. Cationic poly(urethane amide)s (denoted as CPUAs) having multiple disulfide bonds, urethane and amide linkages were synthesized by stepwise polycondensation reaction between 1,4-bis(3-aminopropyl)piperazine and a mixture of di(4-nitrophenyl)-2, 2'-dithiodiethanocarbonate (DTDE-PNC) and diethylenetriaminepentaacetic acid (DTPA) dianhydride at varied molar ratios. Then, Gd-chelated CPUAs (denoted as GdCPUAs) were produced by chelating Gd(III) ions with DTPA residues of CPUAs. These GdCPUAs could condense gene into nanosized and positively-charged polyplexes in a physiological condition and, however, liberated gene in an intracellular reductive environment. In vitro transfection experiments revealed that the GdCPUA at a DTDE-PNC/DTPA residue molar ratio of 85/15 induced the highest transfection efficiency in different cancer cells. This efficiency was higher than that yielded with 25kDa branched polyethylenimine as a positive control. GdCPUAs and their polyplexes exhibited low cytotoxicity when an optimal transfection activity was detected. Moreover, GdCPUAs may serve as contrast agents for T1-weighted magnetic resonance imaging. The results of this work indicate that biodegradable Gd-chelated cationic poly(urethane amide) copolymers have high potential for tumor theranostics.