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Radiation-induced sarcomas (RIS) are iatrogenic malignancies that arise following high-dose radiotherapy, posing a significant clinical challenge due to their poor prognosis and resistance to conventional treatments. The incidence of RIS is increasing with advancements in radiotherapy techniques. This report presents a case of a 71-year-old male diagnosed with stage III rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and curative surgery. Three years postoperatively, he developed a low-grade radiation-induced leiomyosarcoma in the perianal region. Histopathological examination confirmed a spindle cell neoplasm with notable immunohistochemical markers. RIS often presents as aggressive high-grade tumors resistant to radiotherapy and chemotherapy, necessitating surgical resection as the primary treatment. This case underscores the importance of long-term surveillance post-radiotherapy and highlights the need for innovative therapeutic strategies, including immunotherapy. Despite being rare, RIS poses a significant risk following cancer treatment, making early detection through vigilant monitoring and advancements in therapeutic approaches crucial for improving patient outcomes.

A well-designed flow field is a key factor to improve the surface quality of products by removing spatter, which is often generated during the selective laser melting (SLM) process. In the present study, three typical schemes are developed for the gas flow system of large-scale SLM equipment. In this regard, the flow deviation and velocity increase indices are implemented to characterize the flow uniformity in the chamber and gas flow velocity in the clearing area. The obtained results show that the inlet size significantly improves the flow uniformity and the segmented inlet increases the flow velocity above the machining surface. More specifically, when the velocity deviation index decreases from 0.3335 to 0.1538, the corresponding velocity index increases from 10.16% to 29.83%. To improve the flow uniformity on the machining surface, the effect of the inlet flow rate on the airflow over the machining surface is investigated. The obtained results show that when the inlet flow rate reduces to 0.2 m/s, the removal spatter improves while the airflow remains uniform. The results of this study can provide a reference for the design of SLM gas flow systems.

Abstract Studies have indicated dietary restriction of methionine/cystine provided a therapeutic benefit in diseases such as cancer. However, the molecular and cellular mechanisms that underlie the interaction between methionine/cystine restriction (MCR) and effects on esophageal squamous cell carcinoma (ESCC) have remained elusive. Here, we discovered the dietary restriction of methionine/cystine has a large effect on cellular methionine metabolism as assayed in a ECA109 derived xenograft model. RNA-seq and enrichment analysis suggested the blocked tumor progression was affected by ferroptosis, together with the NFκB signaling pathway activation in ESCC. Consistently, GSH content and GPX4 expression were downregulated by MCR both in vivo and in vitro. The contents of Fe2+ and MDA were negatively correlated with supplementary methionine in a dose-dependent way. Mechanistically, MCR and silent of SLC43A2, a methionine transporter, diminished phosphorylation of IKKα/β and p65. Blocked NFκB signaling pathway further decreased the expression of SLC43A2 and GPX4 in both mRNA and protein level, which in turn downregulated the methionine intake and stimulated ferroptosis, respectively. ESCC progression was inhibited by enhanced ferroptosis and apoptosis and impaired cell proliferation. In this study, we proposed a novel feedback regulation mechanism underlie the correlation between dietary restriction of methionine/cystine and ESCC progression. MCR blocked cancer progression via stimulating ferroptosis through the positive feedback loop between SLC43A2 and NFκB signaling pathways. Our results provided the theoretical basis and new targets for ferroptosis-based clinical antitumor treatments for ESCC patients.

Objective: In this study, alterations in oxidative stress-related indicators were evaluated in drug-naïve, first-episode schizophrenia (SCZ) patients, and the effectiveness of blood serum glucose, superoxide dismutase (SOD), bilirubin in the objective assistive diagnosis of schizophrenia was explored.Materials and methods: We recruited 148 drug-naïve, first-episode SCZ patients and 97 healthy controls (HCs). Blood biochemical indexes including blood glucose, SOD, bilirubin and homocysteine (HCY) in participants were measured, the indexes were compared between patients with SCZ and HCs. The assistive diagnostic model for SCZ was established on the basis of the differential indexes.Results: In SCZ patients, the blood serum levels of glucose, total (TBIL), indirect bilirubin (IBIL) and homocysteine (HCY) were significantly higher than those in HCs (p < 0.05), and the serum levels of SOD were significantly lower than those in HCs (p < 0.05). There was a negative correlation between SOD with the general symptom scores and total scores of PANSS. After risperidone treatment, the levels of uric acid (UA) and SOD tended to increase in patients with SCZ (p = 0.02, 0.19), and the serum levels of TBIL and HCY tended to decrease in patients with SCZ (p = 0.78, 0.16). The diagnostic model based on blood glucose, IBIL and SOD was internally cross-validated, and the accuracy was 77%, with an area under the curve (AUC) of 0.83.Conclusion: Our study demonstrated an oxidative state imbalance in drug-naïve, first-episode SCZ patients, which might be associated with the pathogenesis of the disease. Our study proved that glucose, IBIL and SOD may be potential biological markers of schizophrenia, and the model based on these markers can assist the early objective and accurate diagnosis of schizophrenia.

Background. Calcific aortic valve disease (CAVD) is the most common native valve disease. Valvular interstitial cell (VIC) osteogenic differentiation and valvular endothelial cell (VEC) dysfunction are key steps in CAVD progression. Circular RNA (circRNAs) is involved in regulating osteogenic differentiation with mesenchymal cells and is associated with multiple disease progression, but the function of circRNAs in CAVD remains unknown. Here, we aimed to investigate the effect and potential significance of circRNA-miRNA-mRNA networks in CAVD. Methods. Two mRNA datasets, one miRNA dataset, and one circRNA dataset of CAVD downloaded from GEO were used to identify DE-circRNAs, DE-miRNAs, and DE-mRNAs. Based on the online website prediction function, the common mRNAs (FmRNAs) for constructing circRNA-miRNA-mRNA networks were identified. GO and KEGG enrichment analyses were performed on FmRNAs. In addition, hub genes were identified by PPI networks. Based on the expression of each data set, the circRNA-miRNA-hub gene network was constructed by Cytoscape (version 3.6.1). Results. 32 DE-circRNAs, 206 DE-miRNAs, and 2170 DE-mRNAs were identified. Fifty-nine FmRNAs were obtained by intersection. The KEGG pathway analysis of FmRNAs was enriched in pathways in cancer, JAK-STAT signaling pathway, cell cycle, and MAPK signaling pathway. Meanwhile, transcription, nucleolus, and protein homodimerization activity were significantly enriched in GO analysis. Eight hub genes were identified based on the PPI network. Three possible regulatory networks in CAVD disease were obtained based on the biological functions of circRNAs including: hsa_circ_0026817-hsa-miR-211-5p-CACNA1C, hsa_circ_0007215-hsa-miR-1252-5p-MECP2, and hsa_circ_0007215-hsa-miR-1343-3p- RBL1. Conclusion. The present bionformatics analysis suggests the functional effect for the circRNA-miRNA-mRNA network in CAVD pathogenesis and provides new targets for therapeutics.

Abstract Background The differential diagnosis of endometrial stromal tumor (EST) and uterine cellular leiomyoma (CL) remains a challenge in clinical practice, especially low grade endometrial stromal sarcoma (ESS) and CL, suggesting the need for novel immunomarkers panels for differential diagnosis. Interferon-induced transmembrane protein 1 (IFITM1) is a novel immunomarker for endometrial stromal cells, h-caldesmon is an immunomarker for smooth muscle cells and has a higher specificity than smooth muscle actin (SMA). So this study aimed to evaluate whether IFITM1, cluster of differentiation 10(CD10), SMA, and h-caldesmon are useful biomarker combinations for the differential diagnosis of EST and CL. Methods Tissue microarrays were used to detect IFITM1, CD10, SMA, and h-caldesmon immunohistochemical staining in 30 EST and 33 CL cases. Results The expressions of IFITM1 and CD10 were high in EST (86.7 and 63.3%, respectively) but low in CL (18.2 and 21.2%), whereas those of h-caldesmon and SMA were high in CL (87.9 and 100%) and low in EST (6.9 and 40%). In diagnosing EST, IFITM1 shows better sensitivity and specificity (86.7 and 81.8%, respectively) than CD10 (63.3 and 78.8%). The specificity of h-caldesmon in diagnosing CL was significantly higher (93.1%) than that of SMA (60%). When all four antibodies were combined for the differential diagnosis, the area-under-the-curve (AUC) predictive value was 0.995. The best combination for diagnosing EST was IFITM1 (+) or CD10 (+) and h-caldesmon (−) (sensitivity 86.7%, specificity 93.9%). Conclusion The best combination for diagnosing CL were h-caldesmon (+) and SMA (+) (sensitivity 87.9%, specificity 100%). IFITM1, CD10, SMA, and h-caldesmon are a good combination for the differential diagnosis of EST and CL.

Abstract Preclinical studies have shown that the gut microbiota can play a role in schizophrenia (SCH) pathogenesis via the gut-brain axis. However, its role in the antipsychotic treatment response is unclear. Here, we present a 24-week follow-up study to identify gut microbial biomarkers for SCH diagnosis and treatment response, using a sample of 107 first-episode, drug-naïve SCH patients, and 107 healthy controls (HCs). We collected biological samples at baseline (all participants) and follow-up time points after risperidone treatment (SCH patients). Treatment response was assessed using the Positive and Negative Symptoms Scale total (PANSS-T) score. False discovery rate was used to correct for multiple testing. We found that SCH patients showed lower α-diversity (the Shannon and Simpson’s indices) compared to HCs at baseline (p = 1.21 × 10−9, 1.23 × 10−8, respectively). We also found a significant difference in β-diversity between SCH patients and HCs (p = 0.001). At baseline, using microbes that showed different abundance between patients and controls as predictors, a prediction model can distinguish patients from HCs with an area under the curve (AUC) of 0.867. In SCH patients, after 24 weeks of risperidone treatment, we observed an increase of α-diversity toward the basal level of HCs. At the genus level, we observed decreased abundance of Lachnoclostridium (p = 0.019) and increased abundance Romboutsia (p = 0.067). Moreover, the treatment response in SCH patients was significantly associated with the basal levels of Lachnoclostridium and Romboutsia (p = 0.005 and 0.006, respectively). Our results suggest that SCH patients may present characteristic microbiota, and certain microbiota biomarkers may predict treatment response in this patient population.

Background: Butyric acid, a major short-chain fatty acid (SCFA), has an important role in the microbiota–gut–brain axis and brain function. This study investigated the role of butyric acid in treatment response in drug-naïve first episode schizophrenia.Methods: The study recruited 56 Chinese Han schizophrenia inpatients with normal body weight and 35 healthy controls. Serum levels of butyric acid were measured using Gas Chromatography-Mass Spectrometer (GC-MS) analysis at baseline (for all participants) and 24 weeks after risperidone treatment (for patients). Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) for patients at both time points.Results: At baseline, there was no significant difference in serum levels of butyric acid between patients and healthy controls (p = 0.206). However, there was a significant increase in serum levels of butyric acid in schizophrenia patients after 24-week risperidone treatment (p = 0.030). The PANSS total and subscale scores were decreased significantly after 24-week risperidone treatment (p's < 0.001). There were positive associations between baseline serum levels of butyric acid and the reduction ratio of the PANSS total and subscale scores after controlling for age, sex, education, and duration of illness (p's < 0.05). Further, there was a positive association between the increase in serum levels of butyric acid and the reduction of the PANSS positive symptoms subscale scores (r = 0.38, p = 0.019) after controlling for potential confounding factors.Conclusions: Increased serum levels of butyric acid might be associated with a favorable treatment response in drug-naïve, first episode schizophrenia. The clinical implications of our findings were discussed.

Abstract Whether SOX2 and ACTL6A/TP63 interact with the Hippo‐YAP1 pathway in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we reveal that SOX2, ACTL6A, and TP63 are co‐amplified and upregulated in ESCC samples. Multiple SOX2 binding peaks in the locus of WWC1, a Hippo‐YAP1 regulator, and an inverse correlation between the expression of SOX2 and WWC1 are identified, suggesting direct repression of WWC1 by SOX2. Expression scores of SOX2 are higher in tumors than normal tissues and positively correlated with nuclear YAP1 staining in primary ESCC. Moreover, SOX2 gain‐of‐function significantly promotes nuclear YAP1 expression in ESCC cells while silencing of SOX2 expression inhibits YAP1 activation. SOX2 overexpression leads to a significant enhancement of cell migration and invasion as well as chemoresistance to cisplatin, whereas knockdown of SOX2 or ectopic expression of WWC1 suppresses the SOX2‐induced migration ability and invasive potential. Disruption of this SOX2‐WWC1‐YAP1 axis could be a therapeutic strategy for SOX2‐dependent tumors.

This paper focuses on obtaining the optimum process parameters and improving the mechanical properties of ultrahigh strength steel BR1500S. Many experimental data are obtained, and then response surface methodology (RSM) is used to obtain the optimum parameters. Combining the experimental data with RSM, some conclusions are summarized. When the cooling rate reaches 30°C/s, martensite content in microstructure reaches up to 95%. The optimum regions of quenching hardness, tensile strength, and elongation are obtained when the temperature is about 900°C, and the holding time is about 0∼4 min. Results of multiobjective optimizations show that global optimal value is gained at 906.5°C, and the holding time is 0 min. Predicted optimum values of quenching hardness, tensile strength, and elongation are not less than 51.03 HRC, 1,671 MPa, and 8.75%, respectively. The application of RSM is notably successful in predicting the process parameters of hot forming.

Abstract Background Novel therapies tailored to the molecular composition of esophageal squamous cell carcinoma (ESCC) are needed to improve patient survival. We investigated the regulatory network of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) and sex-determining region Y-box 9 (SOX9), and their therapeutic relevance in ESCC. Methods Linc-ROR and SOX9 expression were examined in ESCC specimens, cell lines, and cultured tumorspheres. We investigated the effects of linc-ROR on SOX9 expression and malignant phenotypes by CCK8, colony formation, Transwell, and sphere-forming assay. The linc-ROR/SOX9 interaction mediated by multiple microRNAs (miRNAs) was confirmed by bioinformatic analysis, luciferase assay, and RNA-binding protein immunoprecipitation, transient overexpression or antagonizing endogenous candidate miRNAs. The effect of linc-ROR depletion on tumor growth was assessed by xenograft assay. Results A positive correlation between linc-ROR and SOX9 expression was found in clinical ESCC specimens (r = 0.562, P = 0.036), cell lines, and tumorspheres. Silencing of linc-ROR significantly inhibited cell proliferation, motility, chemoresistance, and self-renewal capacity. Mechanistically, linc-ROR modulating the derepression of SOX9 by directly sponging multiple miRNAs including miR-15b, miR-33a, miR-129, miR-145, and miR-206. Antagonizing these miRNAs counteracted with linc-ROR silencing, whereas the repression of SOX9 abrogated malignant phenotypes induced by the cocktail of miRNA inhibitors. Moreover, linc-ROR disruption was sufficient to attenuate tumor growth and cancer stem cell marker expression in vivo. Conclusions Our results demonstrate that the linc-ROR–miRNA–SOX9 regulatory network may represent a novel therapeutic target for ESCC.

Ultrahigh-strength steel BR1500HS was chosen as the research object. The parameters of insert hot stamping die’s cooling system in the synchronous quenching process were calculated, and the cooling system was designed based on the temperature distribution of formed part. Then, by combining FEM simulation and thermal-mechanical coupling theory of synchronous quenching process of hot stamping, the cooling system was optimized. After that, the punch and die were optimally designed based on the simulation of temperature field of formed part as well as dies, and their temperature decreased by 15°C and 12°C, respectively. Next, the microstructural evolution in austenization and synchronous quenching processes was analyzed. By adopting a synchronous cooling system in hot stamping, by optimizing the parameters and control strategies, and by controlling the water velocity in various inserts, the homogeneity of martensitic phase transitions was improved. The results of the application test show that martensitic phase transitions of major parts are uniform under given working conditions, and hardness difference of each part was small.

Vascular endothelial growth factor (VEGF) and Matrix metalloproteinases (MMPs) are believed to participate in infiltration of tumors. High mortality of esophageal squamous cell carcinoma (ESCC) related to its primary infiltration; however, it is not clear whether the expression of VEGF and MMPs is involved in this process. Screening of The Cancer Genome Atlas (TCGA) database showed that among the VEGF family and MMP9, VEGF-A, VEGF-C, and MMP-9 mRNA were overexpression in ESCC. This result was verified using the Oncomine database and in Kazakh patients with ESCC. Overexpression of VEGF-C and MMP-9 and positive association with advanced esophageal cancer and invading ESCC cells (Gene Expression Omnibus (GEO): GSE21293). Immunohistochemical staining revealed that VEGF-C and MMP-9 were overexpressed in Kazakh ESCCs. VEGF-C expression was related to invasive depth, tumor-node-metastasis (TNM) staging, lymphatic, and lymph node metastasis of ESCC. The linear association between them was further confirmed in TCGA database and the specimens from Kazakh patients with ESCC. Patients with both proteins expression had tumors with greater aggressiveness, suffered from poor prognosis compared with patients who did not express either protein or expressed protein alone. Both proteins expression predicted high invasiveness of ESCC, which is related to worse prognosis of Kazakh ESCCs.

Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinflammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic–polyribocytidilicacid (Poly I:C) during pregnancy using 11C-PK11195 positron emission tomography (PET) and immunohistochemistry.Objective The study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I:C exposed rats.Methods Offspring of Poly I:C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition (PPI) and latent inhibition (LI) test (including active avoidance conditioning task and passive avoidance conditioning task). Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats. 11C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation.Results The treatment group showed hyperlocomotion and deficits in PPI and LI compared with the control group. The treatment group also showed an increased 11C-PK11195 uptake ratio in the prefrontal cortex (t=−3.990, p=0.003) and hippocampus (t=−4.462, p=0.001). The number of activated microglia cells was significantly higher in the treatment group than in the control group (hippocampus: t=8.204, p

The epithelial-to-mesenchymal transition (EMT) and the reverse process (the mesenchymal-to-epithelial transition [MET]) have been shown to be associated with tumor cell invasion and metastasis in different carcinomas. The EMT and MET have recently been shown to play a key role in the pathogenic processes of sarcomas, which are completely different from those of carcinomas. However, the definitive roles of the EMT in the tumorigenesis of synovial sarcomas remain unknown. Here, we explored whether transforming growth factor (TGF)-β signaling, an important oncogenic event in synovial sarcoma, modulates tumor cell characteristics related to the EMT, such as cell adhesion, migration, invasion, and proliferation. Interestingly, we found that TGF-β1 induced tumor cell activation, resulting in a tendency to aggregate and biphasic-like features. TGF-β1 also caused downregulation of E-cadherin and subsequent upregulation of N-cadherin, Snail, and Slug, which are responsible for EMT-like phenomena and increased cell motility and invasion. To further investigate the roles of TGF-β1 in the EMT, we established a SW982 cell line with stable TGF-β1 inhibition viaSB431542.These cells exhibited significantly decreased motility, migration, and proliferation (P = 0.001). Taken together, our data demonstrated that alterations in the TGF-β1/Smad signaling pathway could regulate the expression of EMT-related factors and the EMT process, resulting in changes in tumor cell invasion, migration, and proliferation in synovial sarcoma cells. These results may provide a important insights into therapeutic interventions and contribute to the present understanding of tumor progression in patients.

The Kazakh population in Xinjiang Province in northwestern China exhibits a high incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of esophageal carcinoma (EC) has not been elucidated, there are reports of the involvement of an immunologic mechanism. In the current study, 268 Kazakh ESCC patients and 500 age- and sex-matched control subjects were recruited. DNA was extracted from paraffin-embedded tumor specimens from the patients and peripheral blood lymphocytes from the controls and used for LMP2/LMP7 genotyping. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect LMP2/LMP7 gene single-nucleotide polymorphisms (SNPs). We found a clear increased risk of ESCC in the Kazakh population for the heterozygous LMP2 R/C genotype and the homozygous C/C genotype (OR = 1.470, 95%CI = 1.076-2.008, p = 0.015 forLMP2R/C; OR = 2.048, 95% CI = 1.168-3.591, p = 0.011 for LMP2 C/C). Conversely, the heterozygous LMP7 Q/K polymorphism was found to decrease the risk of ESCC in this population (OR = 0.421, 95% CI = 0.286-0.621, p = 8.83×10-6). Moreover, LMP2 R/C+C/C genotype was associated with increased tumor invasion depth (p = 0.041). Haplotype analysis showed that haplotype A, which includes wild-type homozygous LMP2/TAP1 and mutant LMP7, decreases susceptibility to ESCC in the Kazakh population; in contrast, haplotype E, which includes wild-type homozygous LMP2/LMP7/TAP1, acts as a risk factor for increased susceptibility to ESCC. This is the first study to report that the heterozygous LMP2 R/C and homozygous C/C genotypes increase susceptibility to ESCC in the Kazakh population and that the heterozygous LMP7 Q/K genotype decreases susceptibility to ESCC in this population. Nevertheless, neither LMP2 nor LMP7 was associated with human papillomavirus (HPV) infection. Understanding LMP2/LMP7 genetic variability will provide a new therapeutic perspective for Kazakh patients with ESCC.

BACKGROUNDThis study was to examine the insular cortical functional connectivity in drug naïve patients with first episode schizophrenia and to explore the relationship between the connectivity and the severity of clinical symptoms.METHODSThirty-seven drug naïve patients with schizophrenia and 25 healthy controls were enrolled in this study. A seed-based approach was used to analyze the resting-state functional imaging data. Insular cortical connectivity maps were bilaterally extracted for group comparison and validated by voxel-based morphometry (VBM) analysis. Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS).RESULTSThere were significant reductions in the right insular cortical connectivity with the Heschl's gyrus, anterior cingulate cortex (ACC), and caudate (p'sCONCLUSIONReduced insula-Heschl's functional connectivity is present in drug naïve patients with first episode schizophrenia, which might be related to the manifestation of clinical symptoms.

A meta-analysis was conducted to assess the efficacy of mesenchymal stem cell (MSC) transplantation in small animal coronary vessels after balloon injury, to provide data for the design of future pre-clinical experiments and human clinical trials.The search strategy included the PubMed, EMBASE, Chinese Biomedical Literature (CBM), and China National Knowledge Infrastructure (CKNI) databases. The endpoint was the ratio of vascular neointima/media (I/M). Moreover, neointimal area, re-endothelialization, and proliferating cell nuclear antigen (PCNA) expression were analyzed. Pooled analyses were conducted using random effects models. Heterogeneity and publication bias were also explored. All data were analyzed using RevMan 5.2 and Stata 12.0.Fifteen studies were reviewed from 238 retrieved animal studies. Compared with controls, MSC transplantation resulted in greater I/M reduction (pooled difference, 0.39; 95% CI, 0.57-0.21; P < 0.0001), greater neointimal area reduction (pooled difference, 0.16; 95% CI, 0.22-0.10; P < 0.0001), decreased PCNA expression (pooled difference, 17.69; 95% CI, 28.94-6.44; P = 0.002), and enhanced re-endothelialization (pooled difference, 3.37; 95% CI, 1.78-4.95; P < 0.0001). The multivariable meta-regression analysis showed that a higher number of transplanted cells (>106; P = 0.017) and later time point of I/M measurement (P = 0.022) were significantly associated with I/M reduction. Subgroup analysis demonstrated a trend for a greater reduction in the ratio of I/M with late MSC transplantation (>1 day), MSCs transplanted through intravenous injection, and atherosclerotic vessels.The meta-analysis results demonstrate that MSC transplantation might improve injured vascular remodeling. In addition to greater efficacy with a greater number of transplanted MSCs (>106), the long-term effect of MSC transplantation appears to be more significant. The findings of this meta-analysis may help to design future, effective MSC trials.

ObjectiveThe present study aimed to evaluate the efficacy and safety of adjunctive aripiprazole treatment in schizophrenia patients with risperidone-induced hyperprolactinemia.MethodsOne hundred and thirteen patients who were receiving a stable dose of risperidone were randomly assigned to either adjunctive aripiprazole treatment (10 mg/day) (aripiprazole group) or no additional treatment (control group) at a 1:1 ratio for 8 weeks. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Rating scales and safety assessments (RSESE, BARS, UKU) were performed at baseline and at weeks 4 and 8. Serum levels of prolactin were determined at baseline and at weeks 2, 4, 6 and 8. Metabolic parameters were determined at baseline and again at weeks 4 and 8.ResultsOne hundred and thirteen patients were enrolled in this study, and 107 patients completed the study (54 in the aripiprazole group, and 53 in the control group). PANSS-total scores in the aripiprazole group decreased significantly at week 4 (P = 0.003) and week 8 (P = 0.007) compared with the control group. PANSS-negative scores in the aripiprazole group also decreased significantly at week 4 (P = 0.005) and week 8 (P< 0.001) compared with the control group. Serum levels of prolactin in the aripiprazole group decreased significantly at week 2 (P< 0.001), week 4 (P< 0.001), week 6 (P< 0.001) and week 8 (P< 0.001) compared with the control group. There were no significant differences in changes of Fasting Plasma Glucose, Total cholesterol, Triglycerides and High Density Lipoprotein within each group at week 4 and 8 execpt low density lipoproteins. There was no significant difference in the incidence of adverse reactions between the two groups.ConclusionsAdjunctive aripiprazole treatment may be beneficial in reducing serum levels of prolactin and improving negative symptoms in schizophrenia patients with risperidone-induced hyperprolactinemia.Trial registrationchictr.org ChiCTR-IOR-15006278.

Invasion and metastasis are the major causes of death in patients with esophageal squamous cell carcinoma (ESCC). Epithelial-mesenchymal transition (EMT) is a critical step in tumor progression and transforming growth factor-β1 (TGF-β1) signaling has been shown to play an important role in EMT. In this study, we investigated how TGF-β1 signaling pathways contributed to EMT in three ESCC cell lines as well as 100 patients of nomadic ethnic Kazakhs residing in northwest Xinjiang Province of China. In vitro analyses included Western blotting to detect the expression of TGF-β1/Smad and EMT-associated proteins in Eca109, EC9706 and KYSE150 cell lines following stimulation with recombinant TGF-β1 and SB431542, a potent inhibitor of ALK5 that also inhibits TGF-β type II receptor. TGF-β-activated Smad2/3 signaling in EMT was significantly upregulated as indicated by mesenchymal markers of N-cadherin and Vimentin, and in the meantime, epithelial marker, E-cadherin, was markedly downregulated. In contrast, SB431542 addition downregulated the expression of N-cadherin and Vimentin, but upregulated the expression of E-cadherin. Moreover, the TGF-β1-induced EMT promoted invasion capability of Eca109 cells. Tumor cells undergoing EMT acquire fibroblastoid-like phenotype. Expressed levels of TGF-β1/Smad signaling molecules and EMT-associated proteins were examined using immunohistochemical analyses in 100 ESCC tissues of Kazakh patients and 58 matched noncancerous adjacent tissues. The results showed that ESCC tissues exhibited upregulated expression of TGF-β1/Smad. We also analyzed the relationship between the above proteins and the patients' clinicopathological characteristics. The TGF-β1/Smad signaling pathway in human Eca109 ESCC cells may carry similar features as in Kazakh ESCC patients, suggesting that TGF-β1/Smad signaling pathway may be involved in the regulation of EMT in ethnic Kazakh patients with ESCC from Xinjiang, China.

Objectives. We performed this meta-analysis to summarize all the results from available studies, aiming delineating the prognostic role of miRNA in esophageal cancer. Design and Methods. We searched the electronic databases PubMed, EMBASE, and ISI Web of Science without time restrictions for the correlative literature to aggregate the survival results. Relevant data were extracted from studies investigating the relationship between miRNAs expression and survival in esophageal cancer patients. Pooled hazard ratios of miR-21and miR-375 for OS in ESCC were calculated. Results. A total of 25 studies involving 2,258 subjects analyzed the relationship between miRNA and prognosis of EC. In all, thirty-nine miRNAs associated with prognosis were reported in these studies. The pooled HR of higher miR-21 expression compared with lower miR-21 expression in ESCC was 1.84 (95% CI: 1.41–2.40, P

Background: Prostate cancer (PCa) is challenging to treat. It is necessary to screen for related biological markers to accurately predict the prognosis and recurrence of prostate cancer. Methods: Three data sets, GSE28204, GSE30521, and GSE69223, from the Gene Expression Omnibus (GEO) database were integrated into this study. After the identification of differentially expressed genes (DEGs) between PCa and normal prostate tissues, network analyses including protein-protein interaction (PPI) network, and weighted gene co-expression network analysis (WGCNA) were used to select hub genes. Gene Ontology (GO) term analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to annotate the functions of DEGs and hub modules of the networks. Survival analysis was performed to validate the correlation between the key genes and PCa relapse. Results: In total, 867 DEGs were identified, including 201 upregulated and 666 downregulated genes. Three hub modules of the PPI network and one hub module of the weighted gene co-expression network were determined. Moreover, four key genes (CNN1, MYL9, TAGLN, and SORBS1) were significantly associated with PCa relapse (p < 0.05). Conclusions: CNN1, MYL9, TAGLN, and SORBS1 may be potential biomarkers for PCa development. [ABSTRACT FROM AUTHOR]