The Therapeutic Effects of Noninvasive Brain Stimulation Combined with Cognitive Training in Elders with Alzheimer's Disease or Amnesic Mild Cognitive Impairment.

BACKGROUND: Recent studies have indicated that noninvasive brain stimulation combined with cognitive interval (NIBS-CI) improved cognitive function in people with Alzheimer's disease (AD) or Amnesic mild cognitive impairment (a-MCI). While previous interventions have demonstrated that a single targeted cognitive intervention can improve cognitive function, the outcomes of using both interventions simultaneously are less well-established. Therefore, this study aims to perform a meta-analysis to determine the effectiveness of NIBS-CI in treating cognitive impairment associated with AD and a-MCI, with the goal of obtaining novel insights into this combined intervention. METHODS: PubMed, Web of Science, ProQuest and Central Cochrane library databases were searched up to December 2022. The primary cognitive outcomes were extracted from the included article. A mean difference (MD) and standardized mean difference (SMD) with a 95% confidence interval were calculated by using random-effect models. RESULTS: Twelve studies with a total of 587 AD patients were included. The findings demonstrated that NIBS-CI significantly improved cognitive function of AD patients in cognitive outcomes (SMD = -0.52, 95%CI (-0. 93, -0.11)) and ADAS-COG (MD = -1.16, 95%CI (-1.69, -0.63)). The pooled results showed that NIBS-CI did not improve cognitive function of AD patients in short-time memory (SMD = 0.057, 95%CI (-0.13, 0.25), P = 0.56) and long-time memory (SMD = 0.001, 95%CI (-0.20, 0.20), P = 0.99). CONCLUSIONS: There is evidence for a positive effect of NIBS-CI on overall cognitive function of AD and a-MCI. Considering the limited sample size, it is important to interpret the findings related to memory with caution. To obtain more robust results, future studies should be conducted with larger sample sizes and incorporate objective neurophysiological and neuroimaging tools. These methodological enhancements will allow for a better understanding of the therapeutic targets and provide a more comprehensive assessment of the effects of NIBS-CI treatment.

[Epidemiological characteristics of pulmonary tuberculosis in Motuo County, Tibet Autonomous Region from 2012 to 2021].

To analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) in Motuo County from 2012 to 2021 and provide evidence for the prevention and control of PTB. A total of 223 cases of PTB were reported from 2012 to 2021 in Motuo County, with an average annual reported incidence rate of 171.39/100 000. Joinpoint regression model analysis showed that the average decline rate was 9.2% (P<0.001) from 2012 to 2021. Among the various types of PTB patients reported from 2012 to 2021, there were 69 cases of etiologic-positive cases which increased from 28.57% to 52.63%. Results from the circular distribution methods showed that there was no obvious peak time of PTB in Motuo County. There was no statistical difference in the average annual incidence of PTB between different genders (χ2=0.108, P=0.743). Among all age groups, the 20-29 years group had the highest proportion (26.91%, 60/223). The Monpa ethnic group (153 cases, 68.61%) had the largest number of cases, followed by the Lhoba people (44 cases, 19.73%) and the Tibetan (22 cases, 9.87%). Farmers (168 cases, 75.34%) had the highest occupational composition ratio, followed by students (40 cases, 17.94%). The main detection methods of PTB were clinical consultation and transferring consultation. Overall, the incidence rate of PTB decreased from 2012 to 2021. The majority of PTB patients were young adults with high transmission risk. It is necessary to pay more attention to the key populations and strengthen the comprehensive prevention and control for reducing the risk of PTB.

Comparative transcriptomic analysis reveals candidate genes for seasonal breeding in the male Lion-Head goose.

1. Due to seasonal breeding, geese breeds from Southern China have low egg yield. The genetic makeup underlying performance of local breeds is largely unknown, and few studies have investigated this problem. This study integrated 21 newly generated and 50 publicly existing RNA-seq libraries, representing the hypothalamus, pituitary and testis, to identify candidate genes and importantly related pathways associated with seasonal breeding in male Lion-Head geese.2. In total, 19, 119 and 302 differentially expressed genes (DEGs) were detected in the hypothalamus, pituitary and testis, respectively, of male Lion-Head geese between non-breeding and breeding periods. These genes were significantly involved in the neuropeptide signalling pathway, gland development, neuroactive ligand-receptor interaction, JAK-STAT signalling pathway, cAMP signalling pathway, PI3K-Akt signalling pathway and Foxo signalling pathway.3. By integrating another 50 RNA-seq samples 4, 18 and 40 promising DEGs were confirmed in hypothalamus, pituitary and testis, respectively.4. HOX genes were identified as having important roles in the development of testis between non-breeding and breeding periods of male Lion-Head geese.

[Effects of composite laser technique combined with multipoint microinjection of triamcinolone acetonide in the treatment of hypertrophic scars in burn children].

Objective: To explore the effects of pulsed dye laser (PDL) and ultra-pulsed fractional carbon dioxide laser (UFCL) combined with multipoint microinjection of triamcinolone acetonide in the treatment of red hypertrophic scar at early stage in burn children. Methods: A retrospective cohort before-after control study in the same patients was conducted. From February 2019 to December 2020, a total of 67 burn children who met the inclusion criteria (32 males and 35 females, aged 1 to 12 years) with red hyperplastic scar at early stage, were treated in Hunan Provincial People's Hospital (1st Affiliated Hospital of Hunan Normal University). All the children were treated with composite laser technique (PDL and UFCL) combined with triamcinolone acetonide (hereinafter referred to as combined treatment). After 2 months, they received the second combined treatment. Before the first combined treatment and 6 months after the last combined treatment, the scar of children was evaluated with the patient and observer scar assessment scale (POSAS) by physicians and family members. Six months after the last combined treatment, the satisfaction of the patients' family members with the efficacy was recorded and the overall satisfaction rate was calculated. Adverse reactions were recorded throughout the treatment process. Data were statistically analyzed with paired sample t test. Results: Six months after the last combined treatment, the POSAS scores of children on the thickness, blood vessels distribution, color, surface roughness, texture, scope, and overall evaluation of scar evaluated by the physicians, and the POSAS scores of children on the color, degree of pain, degree of itching, hardness, thickness, shape and size, and overall evaluation of scar evaluated by the family members were significantly lower than those before the first combined treatment (with t values of 17.32, 16.73, 15.00, 14.91, 19.62, 28.74, 29.83, 17.43, 20.52, 29.01, 28.82, 24.91, 20.30, and 42.13, respectively, P<0.01). Six months after the last combined treatment, 62 (93%), 3 (4%), and 2 (3%) children's family members were very satisfied, satisfied, and relatively satisfied with the treatment effect, respectively, and the overall satisfaction rate was 97% (65/67). Six months after the last combined treatment, no scar thickening or infection occurred in all the wounds of children. Conclusions: Composite laser technique combined with multipoint microinjection of triamcinolone acetonide in the treatment of red hypertrophic scar at early stage in burn children can improve the appearance and texture of scar, reduce scar pain and pruritus, with high satisfaction of children's family members to the treatment effect and less adverse reactions.

[Clinical application of bipolar tweezers-clamp for hepatic parenchymal transection].

Objective: To investigate the clinical value of the bipolar tweezers-clamp for the hepatic parenchymal transection in the resection of hepatocellular carcinoma. Methods: From January 2020 to January 2021,63 patients with the hepatocellular carcinoma for hepatectomy at Department of Hepatopancreatobiliary Surgery,Yuebei People's Hospital Affiliated to Shantou University Medical College were analyzed retrospectively.According to the different instruments used in the hepatic parenchymal transection,the patients were divided into bipolar tweezers-clamp group and ultrasonic scalpel group.There were 32 patients in bipolar tweezers-clamp group,with age of (55.5±10.5)years(range:37 to 78 years),including 22 males and 10 females,tumor size was (6.0±3.4)cm(range:2.4 to 13.4 cm). There were 6 patients with portal vein tumor thrombus and 5 patients with portal hypertension. There were 31 patients in ultrasonic scalpel group,with aged(57.8±10.1)years(range:37 to 79 years),including 27males and 4 females,tumor size was(7.9±5.1)cm(range: 2.4 to 21.3 cm),3 patients with portal vein tumor thrombus and 2 patients with portal hypertension. The preoperative baseline data,operation time,blood loss,postoperative liver function and the complications were compared between two groups using t test,χ2 test and Fisher exact probabilityrespectively. Results: The operation was successfully completed in both groups.Compared with the ultrasonic scalpel group,the operation time was significantly shorter((219.3±76.4)minutes vs.(294.0±100.8)minutes,t=-3.322,P=0.002),the blood loss was less((250(475)ml vs. 500(1 050)ml,t=-2.307,P=0.026),the concentrate red blood cells transfusion volume was less(0.92(0.88)U vs. 2.32(4.00)U,Z=-1.987,P=0.047) in the bipolar tweezers-clamp group.The postoperative serum ALB level was higher in the bipolar tweezers-clamp group than that in the ultrasonic scalpel group((33.5±6.1)g/L vs. (29.5±4.2)g/L,t=3.226,P=0.020) on postoperative day 1;((35.7±4.5)g/L vs.(30.1±3.2)g/L,t=5.575,P<0.01) on postoperative day 3;((33.2±3.7)g/L vs. (31.0±4.4)g/L,t=3.020,P=0.004) on postoperative day 7. There was no significant difference in serum ALT,TBIL and PT level between the two groups(all P>0.05).No postoperative bile leakage occurred in both groups.The postoperative complications occurred in 8 cases(25.0%)in the bipolar tweezers-clamp group,including liver failure in one,and in 11 cases(35.5%)in the ultrasonic scalpel group,including liver failure in two(P>0.05). Conclusion: The bipolar tweezers-clamp is a safe and reliable method for the hepatic parenchymal transaction,which is quick and less bleeding during the hepatic resection.

Pediatric allergic rhinitis with functional gastrointestinal disease: Associations with the intestinal microbiota and gastrointestinal peptides and therapeutic effects of interventions.

Children are susceptible to allergic rhinitis (caused by external allergens) accompanied by functional gastrointestinal disease, which seriously affects physical and mental health. Antihistamines and nasal spray hormones are commonly used in clinical treatment, but these drugs often have unsatisfactory efficacy and result in high recurrence rates. Therefore, understanding the pathogenesis of allergic rhinitis with functional gastrointestinal disease and seeking safer treatment and prevention methods is essential. Herein, molecular ecology and immunoassays were used to analyze correlations between pediatric allergic rhinitis with functional gastrointestinal disease and both the intestinal microbiota and gastrointestinal peptide levels. Fifty healthy children (healthy group) and 80 children with allergic rhinitis with functional gastrointestinal disease (case group: evenly divided into a control group (conventional drug therapy) and an intervention group (conventional drug therapy + glutamine+probiotics)), were enrolled. Bifidobacterium and Lactobacillus counts and the gastrin and motilin levels were lower in the case group than in the healthy group, whereas Enterobacter, yeast, and Enterococcus counts and the somatostatin, serotonin, and vasoactive intestinal peptide levels were higher. Post treatment, intestinal microbiota indices, gastrointestinal peptide levels, and intestinal barrier function were better in the intervention group than in the control group (p < 0.05). The intervention group had a significantly higher total therapeutic response rate (95.00%) than the control group (77.50%). The intestinal microbiota was closely associated with gastrointestinal peptide levels. Treatment with glutamine and probiotics regulated these levels, re-established balance in the intestinal microbiota, and restored intestinal barrier function.

Baduanjin Qigong Improves Balance, Leg Strength, and Mobility in Individuals With Chronic Stroke: A Randomized Controlled Study.

BACKGROUND: Effective and sustainable exercise training methods for improving balance poststroke are needed. OBJECTIVE: To evaluate the effect of Baduanjin Qigong for improving balance after stroke. METHODS: This was a single-blinded randomized controlled study in which only the assessor was blinded. Fifty-eight people with chronic stroke (mean age: 62.5 ± 11.8 years) were randomly assigned to the experimental (n = 29) or control group (n = 29). The experimental group underwent 8 weeks of supervised Baduanjin training (3 sessions per week). This was followed by home-based practice of the same exercises 3 days a week for another 8 weeks. The control group underwent 2 sessions of supervised conventional fitness training in the first week, followed by home-based exercise practice 3 days a week until the end of week 16. All outcomes were measured at baseline, week 8, and week 16. RESULTS: Significantly greater improvements in the Mini-Balance Evaluation Systems Test (Mini-BESTest), composite equilibrium score (Sensory Organization Test), 5 Times Sit to Stand, and Timed Up and Go test were detected at week 8 in the experimental group than in the control group (P < .017). Further improvement in the Mini-BESTest was observed from week 8 to 16 in the experimental group (P < .001). Other outcomes (Limit of Stability, Fall-Efficacy Scale, Modified Barthel Index, Stroke-Specific Quality of Life) showed no significant results. CONCLUSION: Baduanjin is effective in improving balance, leg strength, and mobility and is a safe and sustainable form of home-based exercise for people with chronic stroke.

[MRI associated biomarker analysis for diagnosis of lymph node metastasis in T1-2 stage rectal cancer].

Objective: To explore the diagnostic accuracy improved by magnetic resonance imaging (MRI) biomarkers for lymph node metastasis in T1-2 stage rectal cancer before treatment. Methods: Medical records of 327 patients with T1-2 rectal cancer who underwent pretreatment MRI and rectal tumor resection between January 2015 and November 2019 were retrospectively analyzed. Fifty-seven cases were divided into the lymph node metastasis group (N+ group) while other 270 cases in the non-lymph node metastasis group (N-group) according to the pathologic diagnosis. Two radiologist evaluated the tumor characteristics of MRI images. The relationship of the clinical and imaging characteristics of lymph node metastasis was assessed by using univariate analysis and multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic abilities for the differentiation of N- from N+ tumors. Results: Among the 327 patients, MR-N evaluation was positive in 67 cases, which was statistically different from the pathological diagnosis (P<0.001). The sensitivity, specificity and accuracy of MRI for lymph node metastasis were 45.6%, 84.8% and 78.0%, respectively. Multivariate regression analysis showed that tumor morphology (P=0.002), including mucus or not (P<0.001), and MR-N evaluation (P<0.001) were independent influencing factors for stage T1-2 rectal cancer with lymph node metastasis. The area under the ROC curve of rectal cancer with lymph node metastasis analyzed by the logistic regression model was 0.786 (95%CI: 0.720~0.852). Conclusions: Tumor morphology, including mucus or not, and MR-N evaluation can serve as independent biomarkers for differentiation of N- and N+ tumors. The model combined with these biomarkers facilitates to improve the diagnostic accuracy of lymph node metastasis in T1-2 rectal cancers by using MRI.

[Effect of pulsed dye laser in combination with ultra-pulsed fractional carbon dioxide laser in treating pediatric burn scars at early stage].

Objective: To explore the effect of combined application of pulsed dye laser (PDL) and ultra-pulsed fractional carbon dioxide laser (UFCL) in the treatment of pediatric large burn scars at early stage. Methods: One hundred and twenty pediatric patients with large burn scars at early stage conforming to the study criteria were admitted to the People's Hospital of Hunan Province from January 2016 to December 2019. Their data were retrospectively analyzed by the method of single case-control study. There were 78 males and 42 females with age of (4.2±0.8) years and scar area of (100.3±0.7) cm(2). PDL combined with UFCL was used for the first time. The treatment interval of PDL was a month and the treatment interval of UFCL was 3 months. The total treatment cycle was 6 months, with 2 PDL treatments alone and two combined treatments. Before the first combined treatment and 6 months after two combined treatments, the curative effect was assessed using Patient and Observer Scar Assessment Scale (POSAS) by doctors and family members of pediatric patients. Satisfaction degrees of the family members of pediatric patients were recorded, and the overall satisfaction rate was calculated 6 months after two combined treatments. The adverse effects during the whole treatment course were recorded. Data were statistically analyzed with paired t test. Results: (1) Six months after two combined treatments, the scores of pediatric patients' scar vascularity, pigment, thickness, relief, pliability, surface area, and overall valuation in POSAS by doctors and the scores of pain, itch, color, stiffness, thickness, irregularity, and overall valuation in POSAS by family members of pediatric patients were all significantly lower than those before the first combined treatment (t=16.6, 16.0, 16.9, 14.9, 20.8, 29.3, 30.7, 20.4, 29.3, 18.1, 27.9, 25.8, 20.8, 45.3, P<0.01). The overall evaluation scores by doctors were (8.1±0.8) and (2.7±0.6) points, and the overall evaluation scores by family members of pediatric patients were (8.2±0.8) and (2.4±0.5) points respectively before the first combined treatment and six months after two combined treatments. (2) Six months after two combined treatments, 110 (92%) family members of pediatric patients were very satisfied with the curative effect, 6 (5%) family members of pediatric patients were satisfied, and 4 (3%) family members of pediatric patients were relatively satisfied with no unsatisfied reported. The overall satisfaction rate was 97% (116/120). (3) During the treatment, pruritus and rash appeared in 5 pediatric patients 3 to 4 days after the first treatment; pigmentation appeared in 3 pediatric patients 3 weeks after the first treatment; pruritus and vesicle appeared in 1 patient 1 week after the third treatment. No adverse effects such as aggravated scar or infection were observed on the wounds. Conclusions: In treating pediatric large burn scars at early stage, PDL combined with UFCL has demonstrated significant effect with short treatment cycle, few adverse effects. The combined treatment can alleviate symptoms and improve the quality of pediatric patients' life, and is worthy to be popularized and applied in clinic.

The impact of stroke on bone properties and muscle-bone relationship: a systematic review and meta-analysis.

To systematically review available evidence related to the characteristics of bone changes post-stroke and the relationship between various aspects of muscle function (e.g., strength, spasticity) and bone properties after stroke onset. An extensive online database search was undertaken (last search in January 2019). Articles that examined the bone properties in stroke patients were included. The quality of the studies was evaluated with the National Institutes of Health (NIH) Study Quality Assessment Tools. Publication bias of meta-analyses was assessed using the Egger's regression asymmetry test. The selection and evaluation of the articles were conducted by two independent researchers. Fifty-nine studies were identified. In subacute and chronic stroke studies, the skeletal sites in the paretic limbs sustained a more pronounced decline in bone quality than did their counterparts in the non-paretic limbs. The rate of changes showed a decelerating trend as post-stroke duration increased, but the timing of achieving the steady rate differed across skeletal sites. The magnitude of bone changes in the paretic upper limb was more pronounced than the paretic lower limb. There was a strong relationship between muscle strength/mass and bone density/strength index. Muscle spasticity seemed to have a negative impact on bone integrity in the paretic upper limb, but its influence on bone properties in the paretic lower limb was uncertain. Substantial bone changes in the paretic limbs occurred particularly in the first few months after stroke onset. Early intervention, muscle strength training, and long-term management strategies may be important to enhance bone health post-stroke. This review has also revealed the knowledge gaps which should be addressed in future research.

Dual roles of misshapen/NIK-related kinase (MINK1) in osteoarthritis subtypes through the activation of TGFß signaling.

OBJECTIVE: To identify the role of misshapen/NIK-related kinase (MINK1) in age-related Osteoarthritis (OA) and injury-induced OA, and the effects of enhanced TGFß signaling in these progresses. DESIGN: The effect of MINK1 was analyzed with MINK1 knock out (Mink1-/-) mice and C57BL/6J mice. OA progress was studied in age-related OA and instability-associated OA (destabilization of the medial meniscus, DMM) models. The murine knee joint was evaluated through histological staining, Osteoarthritis Research Society International (OARSI) scores, immunohistochemistry, and µCT analysis. Primary chondrocytes were isolated from wild type and Mink1-/- mice and subjected to osteogenic induction and Western blot analysis. RESULTS: MINK1 is highly expressed during cartilage development and in normal cartilage. Mink1-/- mice displayed markedly lower OARSI scores, aggrecan degradation neoepitope positive cells and increased Safranin O and pSMAD2 staining in aging-related OA model. However, in injury-induced OA, loss of MINK1 accelerates extracellular matrix (ECM) destruction, osteophyte formation, and subchondral bone sclerosis. Accelerated subchondral bone remodeling in Mink1-/- mice was accompanied with increased numbers of nestin-positive mesenchymal stem cells (MSCs) and osterix-positive osteoprogenitors. pSMAD2 staining was increased in the subchondral bone marrow of Mink1-/- mice and overexpression of MINK1 inhibited SMAD2 phosphorylation in vitro. CONCLUSIONS: This study shows for the first time that activation of TGFß/SMAD2 by MINK1 deficiency plays opposite roles in aging-related and injury-induced OA. MINK1 deficiency protects cartilage from degeneration in aging joints through increased SMAD2 activation in chondrocytes, while accelerating OA progress in injury-induced model through enhanced osteogenesis of MSCs in the subchondral bone. These findings provide insights for developing precision OA therapeutics targeting TGFß/SMAD2 signaling.

Operation of RF-driven negative hydrogen ion source in China Spallation Neutron Source.

The China Spallation Neutron Source started delivering neutron beams to users in March 2018. To upgrade the beam power to 500 kW and improve the performance of the ion source, an RF-driven negative hydrogen (H-) ion source is under development. The source has a silicon nitride ceramic plasma chamber surrounded by a 4.5-turn antenna. The plasma is ignited by a pulsed DC spark gap and then driven by a 2 MHz solid-state amplifier with a repetition rate of 25 Hz. The commissioning of the source started in January 2019. When uncesiated, it produced about 20 mA beam at an RF power of 32 kW and pulse width of 450 µs. This paper describes the configuration of the ion source, several peculiar technologies used in it, and the first negative hydrogen (H-) ion beam extraction.

[Comparison of Imaging and Pathologic Findings of Retroperitoneal Dedifferentiated Liposarcoma].

Objective: To investigate the imaging appearance of CT and MRI in retroperitoneal dedifferentiated liposarcoma (DDL) based on pathological findings. Methods: Twelve patients with retroperitoneal DDL (13 lesions) who were surgically and pathologically confirmed were retrospectively collected in the Cancer Hospital of Chinese Academy of Medical Sciences. The correlation of CT and MRI features with histopathologic findings was analyzed. Results: The CT and MRI images of retroperitoneal DDLs were large, heterogeneous soft-tissue masses, mostly lobulated (30.8%, 4/13) or multinodular (46.2%, 6/13), invading adjacent anatomic structures (46.2%, 6/13). The lesions contained different proportions of fatty and non-fatty components, and usually with clear boundaries. The CT images of dedifferentiated components showed non-fatty masses of soft tissue density or mixed density, among which ground-glass nodules may be related to mucinous components. Occasionally calcification or ossification was seen (45.5%, 5/11). The contrast-enhanced CT and MRI images of non-fatty components commonly showed intense heterogeneous enhancement (84.6%, 11/13), central cystic changes and necrosis (61.5%, 8/13), pathologically corresponding to multiple types of soft tissue sarcomas without significant specificity. The well-differentiated components were fatty masses with irregular fibrous septa or soft tissue nodules, which is pathologically corresponding to well differentiated liposarcoma. Lymph node or distant metastasis was rare. Conclusions: The imaging manifestations of retroperitoneal DDLs are diverse and closely related to the proportion and distribution of different components. CT, MRI and contrast-enhanced imaging has a certain diagnostic value for retroperitoneal DDLs.

[Comparison of parameters for diffusion-weighted intravoxel incoherent motion imaging in lung cancer patients with different histopathological subtypes].

Objective: To explore the intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) model in lung cancer patients with different histopathological subtypes. Methods: A total of 105 patients were recruited, including 68 cases of adenocarcinoma, 22 cases of squamous carcinoma and 15 cases of small cell carcinoma. All patients underwent magnetic resonance examination consisting of axial IVIM-DWI sequence on a 3.0 T whole body scanner, then the standard ADC (sADC), diffusion coefficient (D), pseudo-diffusion coefficient(D(*)), perfusion fraction (f), distributed diffusion coefficient (DDC) and water diffusion heterogeneity index (α) were calculated for each lesion within the IVIM-DWI model. Results: Mean sADC values were (1.45±0.26) ×10(-3)mm(2)/s, (1.36±0.48) ×10(-3)mm(2)/s and (1.35±0.40) ×10(-3)mm(2)/s for adenocarcinoma, squamous carcinoma and small cell carcinoma, respectively. Mean f values were (59.75±16.37) %, (47.41±18.69) % and (48.96±19.88) % for adenocarcinoma, squamous carcinoma and small cell carcinoma, respectively. Mean α values were 0.72±0.13 for adenocarcinoma, 0.62±0.12 for squamous carcinoma, and 0.63±0.11 for small cell carcinoma, respectively. Statistical analyses indicated that the sADC, f and α values among different histopathological subtypes were significantly different (P<0.05), while there was no significant difference in D, D(*) and DDC values (P>0.05). Furthermore, the comparison showed that the sADC, f and α values of patients with adenocarcinoma were significantly higher than those with squamous carcinoma or small cell carcinoma (P<0.05), whereas there was no significant difference between squamous carcinoma group and small cell carcinoma group (P>0.05). Conclusions: The sADC, f and α values derived from the IVIM-DWI model can be used for comprehensive non-invasive evaluation of diffusion, perfusion and heterogeneity of microenvironment in lung cancer patients. And the IVIM-DWI model may be a promising tool for predicting histopathological subtypes of lung cancer.

VEGFR2 and VEGF-C Suppresses the Epithelial-Mesenchymal Transition Via YAP in Retinal Pigment Epithelial Cells.

BACKGROUND: Whereas retinal pigment epithelial (RPE) cells are known to secrete VEGF-A and VEGFR2, the functions of the autocrine VEGF signaling remain unclear. Meanwhile, anti-VEGF therapies have been applied routinely to treat ocular vascular diseases. OBJECTIVE: The aim of this study was to determine the functions of the VEGF signaling in RPE cells and evaluate the consequences of its interruption. METHODS: The genes involved in the VEGF and Hippo signal pathways were knocked down with siRNAs in both ARPE-19 cell line and human primary RPE cells via transient transfection whereas overexpression of VEGFR2 was mediated via adenovirus transduction. Expression of the epithelial-mesenchymal transition (EMT) markers and the downstream genes of YAP were determined by real-time PCR and Western Blot analysis. Immunofluorescence staining was utilized to determine gene expression in tissue and mouse samples. RESULTS: Knockdown of VEGFR2 results in epithelial-mesenchymal transition in vitro and in vivo. Overexpression of VEGFR2 suppresses TGF ß-mediated EMT in RPE cells. Loss of VEGF-C rather than VEGF-A induces EMT. Mechanistically, the VEGFR2 ablation-induced EMT in RPE cells is mediated by activation of YAP, an effector of the Hippo pathway. Finally, the immunohistochemical analysis of VEGFR2 and YAP in human proliferative vitreoretinopathy (PVR) membranes indicates a tendency of an inverse correlation between VEGFR2-positive and YAP-positive cells. CONCLUSIONS: Our results disclose unexpected novel roles of VEGFR2 and VEGF-C in the process of EMT of RPE cells and in the Hippo pathway. The data shown here demonstrated that VEGFR2 and VEGF-C are important to maintain the normal physiological state of RPE cells.

[Combined T2-weighted and diffusion-weighted MR imaging for staging of rectal cancers].

Objective: To compare the diagnostic value of T2 weighted imaging (T2WI), diffusion-weighted imaging (DWI), and T2WI+ DWI magnetic resonance imaging (MRI) for staging of rectal cancers for improving the accuracy of tumor staging. Methods: From January 2011 to December 2013, 120 cases of rectal cancers proved by colonoscopy without receiving any anti-tumor treatment were enrolled retrospectively. The MRI data for these patients were divided into three groups, ie., T2WI, DWI and T2WI+ DWI, for evaluating the tumor stages. The results were compared with histopathologic findings. The sensitivity and specificity were calculated and compared with chi-square test. The nodal staging was predicted by using T2WI+ DWI. Results: The accuracy for prediction of tumor staging was 83.3%, 65.0% and 92.5% for T2WI, DWI, and T2WI+ DWI respectively. The specificity for evaluating T1 and T2 stage, and the sensitivity for evaluating T3 by DWI was significantly lower than those using T2WI and T2WI+ DWI in rectal cancers. The sensitivity for evaluation of T2 by DWI was lower than that using T2WI+ DWI (63.0% vs. 88.9%). The sensitivity for evaluation T2 and specificity for T3 by T2WI+ DWI was higher than thouse using T2WI only (88.9% vs. 51.9%, 94.0% vs. 72.0%). The accuracy for prediction of nodal staging by using T2WI+ DWI was 62.1% (72/116). Conclusions: T2WI is the key sequence for staging of rectal cancers. Although the diagnostic accuracy was not good by using DWI alone, the combination of T2WI and DWI can improve the accuracy significantly for tumor staging in rectal cancers, whereas the nodal staging was still a hard task for radiologists.

Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study.

Background: The phase III RAISE trial (NCT01183780) demonstrated that the vascular endothelial growth factor (VEGF) receptor (VEGFR)-2 binding monoclonal antibody ramucirumab plus 5-fluororuracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo + FOLFIRI as second-line metastatic colorectal cancer (mCRC) treatment. To identify patients who benefit the most from VEGFR-2 blockade, the RAISE trial design included a prospective and comprehensive biomarker program that assessed the association of biomarkers with ramucirumab efficacy outcomes. Patients and methods: Plasma and tumor tissue collection was mandatory. Overall, 1072 patients were randomized 1 : 1 to the addition of ramucirumab or placebo to FOLFIRI chemotherapy. Patients were then randomized 1 : 2, for the biomarker program, to marker exploratory (ME) and marker confirmatory (MC) groups. Analyses were carried out using exploratory assays to assess the correlations of baseline marker levels [VEGF-C, VEGF-D, sVEGFR-1, sVEGFR-2, sVEGFR-3 (plasma), and VEGFR-2 (tumor tissue)] with clinical outcomes. Cox regression analyses were carried out for each candidate biomarker with stratification factor adjustment. Results: Biomarker results were available from >80% (n = 894) of patients. Analysis of the ME subset determined a VEGF-D level of 115 pg/ml was appropriate for high/low subgroup analyses. Evaluation of the combined ME + MC populations found that the median OS in the ramucirumab + FOLFIRI arm compared with placebo + FOLFIRI showed an improvement of 2.4 months in the high VEGF-D subgroup [13.9 months (95% CI 12.5-15.6) versus 11.5 months (95% CI 10.1-12.4), respectively], and a decrease of 0.5 month in the low VEGF-D subgroup [12.6 months (95% CI 10.7-14.0) versus 13.1 months (95% CI 11.8-17.0), respectively]. PFS results were consistent with OS. No trends were evident with the other antiangiogenic candidate biomarkers. Conclusions: The RAISE biomarker program identified VEGF-D as a potential predictive biomarker for ramucirumab efficacy in second-line mCRC. Development of an assay appropriate for testing in clinical practice is currently ongoing. Clinical trials registration: NCT01183780.

Contributors to the substantial variation in on-treatment testosterone levels in men receiving transdermal testosterone gels in randomized trials.

There is substantial inter-individual variability in serum testosterone levels in hypogonadal men treated with testosterone gels. We aimed to elucidate participant-level factors that contribute to inter-individual variability in testosterone levels during testosterone therapy. An exploratory aim was to determine whether polymorphisms in genes encoding testosterone-metabolizing enzymes could explain the variation in on-treatment testosterone concentrations in men who were randomized to testosterone arm in TOM Trial. We used data from three randomized trials that used 1% transdermal testosterone gels and had testosterone levels measured 2-4 weeks after randomization for dose adjustment: Testosterone in Older Men with Mobility Limitation (TOM), Effects of Testosterone on Pain Perception (TAP), and Effects of Testosterone on Atherosclerosis Progression (TEAAM). Forty-seven percent, 38%, and 9% of participants in TAP, TEAAM, and TOM trials, respectively, failed to raise testosterone levels >400 ng/dL; 6, 8, and 30% of participants had on-treatment testosterone levels >1000 ng/dL. Even after dose adjustment, there was substantial variation in on-treatment levels at subsequent study visits. Baseline characteristics (age, height, weight, baseline testosterone, SHBG, hematocrit, and creatinine) accounted for only a small fraction of the variance (<8%). Polymorphisms in SHBG and AKR1C3 genes were suggestively associated with on-treatment testosterone levels. To conclude, baseline participant characteristics account for only a small fraction of the variance in on-treatment testosterone levels investigated. Multiple dose titrations are needed to maintain on-treatment testosterone levels in the target range. The role of SHBG and AKR3C1 polymorphisms as contributors to variations in on-treatment testosterone levels should be investigated.

[Measurement reproducibility of parameters derived from introvoxel incoherent motion diffusion-weighted MRI imaging of rectal cancer].

Objective: To study the measurement reproducibility of parameters derived from introvoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI)-MRI of rectal cancer between- and within- radiologists. Methods: Clinical data of 34 patients with rectal cancer were prospective analyzed. Conventional MRI sequences, IVIM DWI-MRI with sixteen b values and dynamic contrast enhancement (DCE)-MRI sequences of rectum were acquired by GE 3.0-T MRI imager. The IVIM sequence images with b value=1000 sec/mm(2) were selected to measure the maximum axial section of tumor by a radiologist with 15 year-experiences in gastrointestinal cancer imaging.Two radiologists (radiologist 1 and radiologist 2 with 2 and 10 years of experience in gastrointestinal cancer imaging, respectively) independently draw a freehand region of interest (ROI) that contained the largest available tumor area on the selected section. Monoexponential apparent diffusion coefficient (ADC) and biexponential IVIM metrics maps and IVIM parameters were generated automatically by the software. The repeated measurement was performed at an interval of one week. The average values of each measurement were used for statistical analysis. ADC values and IVIM parameters obtained between- and within- radiologists were analyzed by Wilcoxon signed-rank test. Intraclass correlation coefficients (ICC) and Bland-Altaman plots were used to analyze the parameter reproducibility of two measurements between- and within- radiologists. Results: The first and second measured ADC (×10(-3)mm(2)/s), true diffusivity (D, ×10(-3)mm(2)/s), false diffusivity (D(*,) mm(2)/s) and perfusion fraction (f, %) by radiologist 1 were 0.997, 0.692, 0.043, 34.6 and 0.993, 0.691, 0.038, 32.8, respectively. The first and second measured ADC (×10(-3)mm(2)/s), D (×10(-3)mm(2)/s), D(*) (mm(2)/s), f (%) by radiologist 2 were 0.987, 0.651, 0.046, 32.8 and 0.996, 0.689、0.041, 32.7, respectively. No statistically significant differences were observed in ADC and IVIM parameters obtained between- and within- radiologists (P>0.05). The ADC values and the f values of two times were significantly correlated between- and within- radiologists. The D values were significantly correlated within a radiologist, and the correlation of D(*) values within a radiologist was significantly higher than that between radiologists. The 95% limits of agreement (LoA) of ADC values and f values were smaller than those of D values and D(*) values between- and within- radiologists. The 95% LoA of ADC values was the least, while that of D(*) values varied most.The 95% LoA of f values and D values kept steady within a radiologist, and 95% LoA of f values was slightly smaller than that of D values. The 95% LoA of IVIM parameters (ADC, D, f, D(*) values) within radiologists 2 were better than those within radiologist 1. Conclusions: The reproducibilities of ADC and f values are the best, while the reproducibility of D(*) values is relatively poorer in rectal cancer. Measurement reproducibility of parameters derived from IVIM may be improved by increasing radiologists' experiences in drawing ROI.