Growth Hormone Replacement Therapy in Adult Growth Hormone Deficiency and Risk of Cancer: A Meta-Analysis

The growth hormone (GH) replacement therapy in adult growth hormone deficiency (AGHD) is now well developed, nevertheless, the safety of GH replacement, especially the incidence of cancer in these patients remains to be further clarified. To summarize the evidence on the safety of using GH in AGHD, we conduct this meta-analysis to assess the relationship between the risk of cancer and GH replacement therapy. Randomized controlled trials and cohort studies involved in GH therapy for AGHD were selected. Meta-analysis was performed and risk ratio (RR) was pooled with 95% confidence interval (CI) to investigate the relationship between GH replacement and the risk of cancer. The result indicated that there was no evidence to draw a conclusion that GH replacement therapy will increase the risk of cancer (P = 0.001, RR = 0.77, 95% CI [0.65, 0.90]). Meanwhile, according to the calculated analysis, the replacement therapy might even reduce the risk of cancer. Furthermore, subgroup analysis demonstrated that there was no correlation between replacement therapy of GH and the risk of cancer both in prospective and retrospective cohort design research, and in prospective group, the risk of cancer even decreased (P = 0.0002, RR = 0.71, 95%CI [0.59, 0.85]). In conclusion, our study corroborates evidence from previous studies showing that GH replacement therapy in AGHD patients would not increase the risk of cancer;instead, it might be even decrease cancer risk. The results suggested that GH replacement therapy in AGHD patients was safe.

Incidence and Risk Factors of Cognitive Impairment 3 Months after First-ever Stroke: A Cross-sectional Study of 5 Geographic Areas of China

This study examined the incidence, neuropsychological characteristics and risk factors of cognitive impairment 3 months after stroke in China. Five regions that differed in geography and economy in China were selected. Patients from the hospitals located in the five regions were prescreened at admission, and the demographic data, vascular risk factors and clinical characteristics of stroke were obtained. A battery of cognitive-specific domain tests was performed in the patients who failed to pass cognitive screening 3 months post stroke. Patients were diagnosed as having post-stroke cognitive impairment (PSCI) or no cognitive impairment (NCI) based on the results of the neuropsy-chological tests. Univariate analysis was performed for suspect risk factors, and significant variables were entered in multivariable logistic regression analysis. Our results showed that a total of 633 patients were recruited 3 months after stroke; complete cognitive tests were performed in 577 of the stroke pa-tients. The incidence of PSCI in these Chinese patients was 30.7%. There were 129 (22.4%) patients with visuospatial impairment, 67 (11.6%) with executive impairment, 60 (10.4%) with memory impairment and 18 (3.1%) with attention impairment. The risk factors associated with PSCI were older age (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.20–2.58), low education level (OR 2.45, 95% CI 1.65–3.64), depressive symptom (OR 1.69, 95% CI 1.09–2.61), obesity (OR 2.57, 95% CI 1.41–4.71), stroke severity 3 months post stroke (OR 1.62, 95%CI 1.10–2.37) and cortex lesion (OR 1.55, 95% CI 1.04–2.31). It was concluded that PSCI occurs commonly 3 months after first-ever stroke in Chinese patients. Visuospatial ability may be the most frequently impaired cognitive domain for the patients with stroke. The critical risk factors of PSCI are older age, low education level, depressive symptom, obesity, stroke severity 3 months post stroke and cortex lesion.

Semaphorin 7a participants in pterygium by regulating vascular endothelial growth factor

AIM: To investigate the relationship between semaphorin 7a expression and cell proliferation and migration in pterygium fibroblasts. METHODS: Twenty-six patients with surgically diagnosed pterygium were enrolled, including 15 cases of primary pterygium and 11 cases of recurrent pterygium. In addition, 12 cases of normal conjunctival tissue were collected. The expression of semaphorin 7a in normal conjunctival tissue, primary pterygium and recurrent pterygium was detected by real-time polymerase chain reaction. Recurrent pterygium fibroblasts were isolated and cultured, and the expression of semaphorin 7a was silenced by small interfering RNA(siRNA) interference technique. Furthermore, the effects of si-semaphorin 7a interference on the mRNA and protein levels of β1-integrin, vascular endothelial growth factor A(VEGFA) and vascular endothelial growth factor receptor(VEGFR), and on fibroblast proliferation were analyzed. Transwell assay was used to detect the effect of semaphorin 7a interference on fibroblast migration. RESULTS: Semaphorin 7a was highly expressed in the primary pterygium and recurrent pterygium samples than that of the normal conjunctival tissue. Compared with the primary pterygium, the expression of semaphoring 7a in the recurrent pterygium samples was significantly increased(P<0.05). The mRNA and protein expression levels of β1-integrin, VEGFA and VEGFR were decreased after si-semaphorin 7a transfection, and as well as the cell proliferation and migration. CONCLUSION: Semaphorin 7a might play important roles in the pathogenesis of pterygium by affecting the expression of β1-integrin, VEGFA and VEGFR.

Correlation of Forkhead Box c2 with Subtypes and Invasive Ability of Invasive Breast Cancer

Forkhead Box c2 （FOXC2） is a member of forkhead/winged-helix family of transcription factors. The relationship between FOXC2 and invasive breast cancers, including basal-like breast cancer （BLBC, a subtype of breast cancer）, remains to be elucidated. In this study, immunohistochemistry was used to detect the expression of FOXC2 in samples from 103 cases of invasive breast cancers and 15 cases of normal mammary glands. The relationship between FOXC2 and clinical parameters of invasive breast cancers such as patient＇s age, tumor size, lymph node metastasis, tumor grade, the expression of ER, PR, HER-2 and p53, and Ki-67 labeling index （LI） was evaluated. The expression of FOXC2 was detected in parent MCF7 ceils, MCF cells transfected with FOXC2 expression vectors and MDA-MB- 435 cells by immunohistochemistry and Western blotting. Transwell assay was used to determine the invasive ability of these cells. The results showed that FOXC2 was strongly expressed in basal epithelial cells in normal mammary glands and weakly expressed or even not expressed in glandular epithelial cells. The majority of invasive breast cancers （71.8%, 74/103） had negative or weak expression of FOXC2. However, FOXC2 was strongly expressed in 60.7% of BLBCs. Moreover, FOXC2 was related with tumor grade, p53 expression, ki-67 LI and lymph nodes metastasis. It was expressed in FOXC2- transfected MCF cells and MDA-MB-435 cells but not in parent MCF cells. Transwell assay revealed that MCF cells transfected with FOXC2 expression vectors were more aggressive than the parent MCF ceils, suggesting a positive correlation between FOXC2 and the invasion of breast cancer. It was con- cluded that there is a significant association between FOXC2 and the metastasis of invasive breast can- cer. FOXC2 may be used as a new marker for the diagnosis and prognosis prediction of different sub- tvpes of invasive breast cancers.

Self-Assembly of Dimer Motors under Confined Conditions

Chemically synthetic nanomotors can consume fuel in the environment and utilize the self-generated concentration gradient to self-propel themselves in the system.We study the collective dynamics of an ensemble of sphere dimers built from linked catalytic and noncatalytic monomers.Because of the confinement from the fuel Held and the interactions among motors,the ensemble of dimer motors can self-organize into varlous nanostructures,such as a radial pattern in the spherical fuel field and a staggered radial pattern in a cylindrical fuel Held.The influence of the dimer volume fraction on the self-assembly is also investigated and the formed nanostructures are analyzed in detail.The results presented here may give insight into the application of the self-assembly of active materials.

Functional Connectivity Difference Detected in Bilateral Occipital Lobes Between the Abacus Experts and Control Groups: Using Nonlinear Processing Method

Objective:This paper is to investigate functional connectivity differences between the abacus experts and control groups by using nonlinear processing method spatiotemporal Lyapunov exponent.Methods:11 right-handed healthy control children and 12 abacus children were undergone functional magnetic resonance imaging(fMRI).After preprocessing fMRI data with SPM,linear and nonlinear methods for connectivity analysis were both employed.Results:Connectivity differences between the two groups were statistically P<0.05 by the correlation method,while the P value by the nonlinear method were P<0.01.Conclusion:There are significant differences between the two groups in functional connectivity of bilateral occipital lobes.The nonlinear method proposed here seems to be more specific compared with the common linear correlation method.

SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer

AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients. METHODS: One hundred and fifty-six CRC patientswere followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was performed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics analysis involving a Support Vector Machine (SVM) was used to determine the best prognostic model from combinations of these markers. RESULTS: Seven markers (SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK) were significantly related to the prognosis and clinical pathological features of the CRC patients (P < 0.05). Prognostic models were established through SVM from combinations of these 7 markers and proved able to differentiate patients with dissimilar survival, especially in stage Ⅱ/Ⅲ patients. According to the best prognostic model, the p53/SPARCL1 model, patients having high p53 and low SPARCL1 expression had about 50% lower 3-year survival than others (P < 0.001). CONCLUSION: SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are potential prognostic markers in CRC. A p53/SPARCL1 bioinformatics model may be used as a supplement to tumor-nodes-metastasis staging.

MicroRNA regulation network in colorectal cancer metastasis

Colorectal cancer is the third most common cancer worldwide. Metastasis is a major cause of colorectal cancer-related death. Mechanisms of metastasis remain largely obscure. MicroRNA is one of the most important epigenetic regulators by targeting mRNAs posttranscriptionally. Accumulated evidence has supported its significant role in the metastasis of colorectal cancer, including epithelial-mesenchymal transition and angiogenesis. Dissecting microRNAome potentially identifies specific microRNAs as biomarkers of colorectal cancer metastasis. Better understanding of the complex network of microRNAs in colorectal cancer metastasis provide new insights in the biological process of metastasis and in the potential targets for colorectal cancer therapies and for diagnosis of recurrent and metastatic colorectal cancer.

Protective effects of edaravone on ischaemia-reperfusion injury in rabbits with haemorrhagic shock

目的观察兔失血性休克再灌注过程中血浆丙二醛（MDA）、一氧化氮（NO）与超氧化物岐化酶（SOD）水平的动态变化，以及肺脏、肾脏病理改变；并探讨依达拉奉的保护作用。方法29只家兔全身肝素化后随机分为三组：假手术组（C组，n=7）、失血性休克再灌注组（I／R组，n=10）和依达拉奉保护组（I／R—edaravone组，n=12）。后两组制作失血性休克再灌注模型，在10min内通过左股动脉放血，维持平均动脉压（MAP）40 mmHg达到60 min。I／R-edaravone组静脉应用依达拉奉。然后开始复苏，要求在60 min内回输全部失血和等量生理盐水，使MAP维持在失血前70％以上。休克后10 h I／R—edamvone组静脉再次应用依达拉奉。在复苏后20h处死所有家兔，同时取所有兔的右肺部分组织和右肾部分组织作病理检查。分别测休克前、休克1 h、再灌注后1 h、5 h及20 h血浆MDA、SOD、NO含量。结果休克前三组动物血浆MDA、NO及SOD含量均无显著统计学差异。休克后I／R组家兔血浆MDA（5．35±0．29）μmol／L及NO（27．75±2．88）μmol／L水平均较C组的[（4．44±0．59）μmol／L，（25．01±4．95）μmol／L]要高，而I／R组的SOD水平（194．58±14．42）U／ml较C组（210．86±24．54）U／ml要低（P均〈0．01）。复苏后20h这些变化更加明显，I／R组MDA和NO水平持续增加l（5．69±0．24）μmol／L，（28．01±3．10）μmol／L，P〈0．05]，而SOD水平继续下降[（151．83±9．36）U／ml，P〈0．05]。与I／R组比较，I／R-edaravone组的MDA水平显著降低[（3．48±0．23）μmol／L，P〈0．01]，SOD水平明显升高[（19．5．10±11．87）U／ml，P〈0．01]。病理检查提示依达拉奉可以减轻肺脏和肾脏病理损害。结论依达拉奉通过清除自由基，有效减轻失血性休克再灌注过程中重要脏器的损害。

Rationale,design,and baseline characteristics of Chinese registry in early detection and risk stratification of coronary plaques(C-STRAT)study

To the Editor:Coronary computed tomographic angiography(CCTA)has been considered as one of the most important noninvasive imaging modalities in diagnosing coronary artery disease(CAD).[1]Modern scanner of CCTA can provide precise coronary atherosclerotic plaque information,showing improved diagnostic accuracy and sensitivity for identifying obstructive CAD with a preferable temporal and spatial resolution.Several studies have demonstrated the prognosis value of CCTA for the prediction of future adverse CAD events.

Curcumin-incorporated 3D bioprinting gelatin methacryloyl hydrogel reduces reactive oxygen species-induced adipose-derived stem cell apoptosis and improves implanting survival in diabetic wounds

Background:Gelatin methacryloyl(GelMA)hydrogels loaded with stem cells have proved to be an effective clinical treatment for wound healing.Advanced glycation end product(AGE),interacting with its particular receptor(AGER),gives rise to reactive oxygen species(ROS)and apoptosis.Curcumin(Cur)has excellent antioxidant activity and regulates intracellular ROS production and apoptosis.In this study,we developed a Cur-incorporated 3D-printed GelMA to insert into adiposederived stem cells(ADSCs)and applied it to diabetic wounds.Methods:GelMA hydrogels with Cur were fabricated and their in vitro effects on ADSCs were investigated.We used structural characterization,western blot,ROS and apoptosis assay to evaluate the antioxidant and anti-apoptotic activity,and assessed the wound healing effects to investigate the mechanism underlying regulation of apoptosis by Cur via the AGE/AGER/nuclear factor-κB(NF-κB)p65 pathway.Results:A 10%GelMA scaffold exhibited appropriate mechanical properties and biocompatibility for ADSCs.The circular mesh structure demonstrated printability of 10%GelMA and Cur-GelMA bioinks.The incorporation of Cur into the 10%GelMA hydrogel showed an inhibitory effect on AGEs/AGER/NF-κB p65-induced ROS generation and ADSC apoptosis.Furthermore,Cur-GelMA scaffold promoted cell survival and expedited in vivo diabetic wound healing.Conclusions:The incorporation of Cur improved the antioxidant activity of 3D-printed GelMA hydrogel and mitigated AGE/AGER/p65 axis-induced ROS and apoptosis in ADSCs.The effects of scaffolds on wound healing suggested that Cur/GelMA-ADSC hydrogel could be an effective biological material for accelerating wound healing.