Pan-cancer analysis reveals CCL5/CSF2 as potential predictive biomarkers for immune checkpoint inhibitors.

BACKGROUND: Currently, there are no optimal biomarkers available for distinguishing patients who will respond to immune checkpoint inhibitors (ICIs) therapies. Consequently, the exploration of novel biomarkers that can predict responsiveness to ICIs is crucial in the field of immunotherapy. METHODS: We estimated the proportions of 22 immune cell components in 10 cancer types (6,128 tumors) using the CIBERSORT algorithm, and further classified patients based on their tumor immune cell proportions in a pan-cancer setting using k-means clustering. Differentially expressed immune genes between the patient subgroups were identified, and potential predictive biomarkers for ICIs were explored. Finally, the predictive value of the identified biomarkers was verified in patients with urothelial carcinoma (UC) and esophageal squamous cell carcinoma (ESCC) who received ICIs. RESULTS: Our study identified two subgroups of patients with distinct immune infiltrating phenotypes and differing clinical outcomes. The patient subgroup with improved outcomes displayed tumors enriched with genes related to immune response regulation and pathway activation. Furthermore, CCL5 and CSF2 were identified as immune-related hub-genes and were found to be prognostic in a pan-cancer setting. Importantly, UC and ESCC patients with high expression of CCL5 and low expression of CSF2 responded better to ICIs. CONCLUSION: We demonstrated CCL5 and CSF2 as potential novel biomarkers for predicting the response to ICIs in patients with UC and ESCC. The predictive value of these biomarkers in other cancer types warrants further evaluation in future studies.

Asian Screening Array and Next-Generation Sequencing Based Panels Applied to Preimplantation Genetic Testing for Monogenic Disorders Preclinical Workup in 294 Families: A Retrospective Analysis.

OBJECTIVE: Currently, the most commonly used methods for linkage analysis of pre-implantation genetic testing for monogenic disorders (PGT-M) are next generation sequencing (NGS) and SNP array. We aim to investigate whether the application efficacy of Asian screening array (ASA) in PGT-M preclinical workup for the Chinese population is superior to NGS based single nucleotide polymorphism (SNP) panels. METHODS: We conducted a retrospective analysis by reviewing 294 couples from a single center over the past 4 years and compared the detection results between NGS-based SNP panels and ASA. Using the numbers of informative SNPs upstream and downstream flanking of variants, we assessed the detection efficiency of both methods in monogenic diseases, chromosomal microdeletion syndrome and males with de novo variants, among other scenarios. RESULTS: Results indicate that ASA offers a greater number of informative SNPs compared with NGS-based SNP panels. Additionally, data analysis for ASA is generally more straightforward and may require less computational resources. While ASA can address most PGT-M challenges, we have also identified certain genes in previous tests that are not suitable for PGT-M using ASA. CONCLUSION: The application of ASA in PGT-M preclinical workup for Chinese populations has good practical value as it can perform linkage analysis for most genetic variants. However, for certain variants, NGS or other testing methods, such as mutated allele revealed by sequencing with aneuploidy and linkage analysis (MARSALA), may still be necessary for completion.

Aflatoxin B1-exposed hepatocyte-derived extracellular vesicles: Initiating hepatic stellate cell-mediated liver fibrosis through a p53-Parkin-dependent mitophagy pathway.

Environmental aflatoxin B1 (AFB1) exposure has been proposed to contribute to hepatocellular carcinoma by promoting liver fibrosis, but the potential mechanisms remain to be further elucidated. Extracellular vesicles (EVs) were recognized as crucial traffickers for hepatic intercellular communication and play a vital role in the pathological process of liver fibrosis. The AFB1-exposed hepatocyte-derived EVs (AFB1-EVs) were extracted, and the functional effects of AFB1-EVs on the activation of hepatic stellate cells (HSCs) were explored to investigate the molecular mechanism of AFB1 exposure-induced liver fibrogenesis. Our results revealed that an environment-level AFB1 exposure induced liver fibrosis via HSCs activation in mice, while the AFB1-EVs mediated hepatotoxicity and liver fibrogenesis in vitro and in vivo. AFB1 exposure in vitro increased PINK1/Parkin-dependent mitophagy in hepatocytes, where upregulated transcription of the PARK2 gene via p53 nuclear translocation and mitochondrial recruitment of Parkin, and promoted AFB1-EVs-mediated mitochondria-trafficking communication between hepatocytes and HSCs. The knockdown of Parkin in HepaRG cells reversed HSCs activation by blocking the mitophagy-related AFB1-EVs trafficking. This study further revealed that the hepatic fibrogenesis of AFB1 exposure was rescued by genetic intervention with siPARK2 or p53's Pifithrin-α (PFTα) inhibitors. Furthermore, AFB1-EVs-induced HSCs activation was relieved by GW4869 pharmaceutic inhibition of EVs secretion. These results revealed a novel mechanism that AFB1 exposure-induced p53-Parkin signal axis regulated mitophagy-dependent hepatocyte-derived EVs to mediate the mitochondria-trafficking intercellular communication between hepatocytes and HSCs in the local hepatotoxic microenvironment to promote the activated HSCs-associated liver fibrogenesis. Our study provided insight into p53-Parkin-dependent pathway regulation and promised an advanced strategy targeting intervention to EVs-mediated mitochondria trafficking for preventing xenobiotics-induced liver fibrosis.

[Effects of different exercise modes on neuromuscular junction and metabolism of skeletal muscle-related proteins in aging rats].

The present study aimed to explore the effects of different exercise modes on neuromuscular junction (NMJ) and metabolism of skeletal muscle-related proteins in aging rats. Ten from 38 male Sprague-Dawley (SD) rats (3-month-old) were randomly selected into young (Y) group, while the rest were raised to 21 months old and randomly divided into elderly control (O), endurance exercise (EN) and resistance exercise (R) groups. After 8 weeks of corresponding exercises training, the gastrocnemius muscles of rats were collected, and the expression of S100B in Schwann cells was detected by immunofluorescence staining. Western blot was used to detect the protein expression levels of agglutinate protein (Agrin), low-density lipoprotein receptor-related protein 4 (Lrp4), muscle- specific kinase protein (MuSK), downstream tyrosine kinase 7 (Dok7), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target rapamycin (p-mTOR), and phosphorylated forkhead box O1 (p-FoxO1) in rat gastrocnemius muscles. The results showed that, endurance and resistance exercises increased the wet weight ratio of gastrocnemius muscle in the aging rats. The protein expression of S100B in the R group was significantly higher than those in the O and EN groups. Proteins related to NMJ function, including Agrin, Lrp4, MuSK, and Dok7 were significantly decreased in the O group compared with those in the Y group. Resistance exercise up-regulated these four proteins in the aging rats, whereas endurance exercise could not reverse the protein expression levels of Lrp4, MuSK and Dok7. Regarding skeletal muscle-related proteins, the O group showed down-regulated p-Akt, and p-mTOR protein expression levels and up-regulated p-FoxO1 protein expression level, compared to the Y group. Resistance and endurance exercises reversed the changes in p-mTOR and p-FoxO1 protein expression in the aging rats. These findings demonstrate that both exercise modes can enhance NMJ function, increase protein synthesis and reduce the catabolism of skeletal muscle-related proteins in aging rats, with resistance exercise showing a more pronounced effect.

A novel nano material for anti-cerebral ischaemia: preparation and application of borneol angelica polysaccharide liposomes.

OBJECTIVE: To investigate the preparation of novel nanoliposomes (Borneol Angelica Polysaccharide Liposomes, BAPL) for anti-cerebral ischaemia and verify its curative effects and mechanism. METHODS: By applying a uniform experiment design to investigate the fitting combination of BAPL. Encapsulation Efficiency Evaluation of BAPL Preparation; Particle Size and Surface Potential Evaluation of BAPL Biological activity; Cerebral ischaemia models of rats Evaluation of BAPL curative effects and mechanism. RESULTS: (1) The fitting combination of lecithin, Cholesterol, AP mass and the borneol mass was 60 mg, 60 mg, 45 mg and 5 mg. the highest encapsulation efficiency was 80.4%, the particle size was 179.1 nm, and the surface zeta potential was -17.2 mV. It conforms to the nano-material standards. (2) The results of animal experiments show that: In the BAPL group, the infarct volume of TTC staining was significantly decreased, and the expression levels of NF-κBp65, TLR-4, IL-8, IL-6, IL-1ß in brain tissue were significantly decreased, while the expression levels of ZO-1, ZO-2, IL-10 were significantly increased after cerebral ischaemia-reperfusion. CONCLUSION: BAPL is a novel nano and effective material for anti-cerebral ischaemia.

Rhythm disturbance in osteoarthritis.

Osteoarthritis (OA) is one of the main causes of disabilities among older people. To date, multiple disease-related molecular networks in OA have been identified, including abnormal mechanical loadings and local inflammation. These pathways have not, however, properly elucidated the mechanism of OA progression. Recently, sufficient evidence has suggested that rhythmic disturbances in the central nervous system (CNS) and local joint tissues affect the homeostasis of joint and can escalate pathological changes of OA. This is accompanied with an exacerbation of joint symptoms that interfere with the rhythm of CNS in reverse. Eventually, these processes aggravate OA progression. At present, the crosstalk between joint tissues and biological rhythm remains poorly understood. As such, the mechanisms of rhythm changes in joint tissues are worth study; in particular, research on the effect of rhythmic genes on metabolism and inflammation would facilitate the understanding of the natural rhythms of joint tissues and the OA pathology resulting from rhythm disturbance. Video Abstract.

Down-regulation of kappa opioid receptor promotes ESCC proliferation, invasion and metastasis via the PDK1-AKT signaling pathway.

BACKGROUND: As a class of the opioid receptors, the kappa opioid receptor (KOR) has been verified to be a potential biomarker and therapeutic target for human malignant tumors. However, a thorough understanding of whether KOR affects progression of esophageal squamous cell carcinoma (ESCC) is still lacking. This study focused on exploring the effect of knocking down KOR in ESCC and its underlying mechanism. METHODS: Bioinformatics analysis was used to compare the different expression level of OPRK1 (KOR gene) in tumor and adjacent normal tissues, and predict the relationship between KOR expression and overall survival. RNA-sequence analysis was performed to detect the altered functions and mechanisms after down regulating KOR. The in vitro and in vivo assays were used to detect the effects of down-regulated KOR on cell proliferation, migration and invasion. Substrate gel zymography and 3D cell culture assays were used to find the effect of KOR knockdown on the degradation of extracellular matrix (ECM), and immunefluorescence was performed to detect the altered cytoskeleton. Western blotting and immunohistochemistry were used to explore the underlying mechanism pathway. RESULTS: Bioinformatics analysis revealed that the expression of OPRK1 was lower in tumor tissue than that in adjacent normal tissues, and lowered expression of KOR was associated with poorer overall survival. The in vitro assays demonstrated that down-regulation of KOR enhanced ESCC proliferation, metastasis and invasion. Western blotting revealed that down-regulation of KOR could activate PDK1-AKT signaling pathway, which actively regulated the cancer progression. Down-regulation of KOR enhanced the formation of invadopodia, secretion of matrix metalloproteinase-2 (MMP2) and rearrangement of cytoskeleton, which were positively related with the invasion of ESCC. KOR knockdown enhanced the tumor invasion and elevated the AKT phosphorylation in nude mice. The AKT kinase inhibition could reverse the effect of down-regulation of KOR. CONCLUSION: KOR might act as a tumor suppressor in ESCC and down-regulation of KOR could enhance the ESCC tumor phenotype. Video Abstract.

Efficient Visible-Light-Driven Hydrogen Production over Cu-Modified Polyoxotungstate Hybrids.

Hydrogen energy is a renewable and clean source, which makes a great difference in future sustainable energy systems. Visible-light-driven photocatalysis reaction involves harnessing the abundance of sunlight for hydrogen production among many catalytic technologies. However, the fabrication of photocatalysts that have distinctive performance in visible light is still the primary challenge. Herein, two new Cu-modified polyoxotungstate hybrids, {[Cu2(bim)4(H2O)2](HBW12O40)2·(H2bim)2·8H2O} (1) (bim = [1,1'-methylenebis(1H-imidazole)]) and {[Cu2(bim)4(H2O)2](H3PW10Ti2O40)2·(H2bim)2·8H2O} (2), have been successfully isolated by bridging two saturated Keggin polyoxotungstates and copper-azole complexes. Not surprisingly, 2 holds higher reduction activity due to the more negative charge and stronger basicity on the terminal oxygen of Ti═O and bridge oxygen of Ti-O-W. The H2 yield was 17075 µmol g-1 h-1 for 2 in the tunable light-driven H2 production system, which is promising in the field of photocatalysis.

[Preliminary Study on the Effect of Whole-Process Case Management Based on Service Process Design on the Function and Satisfaction of Patients Undergoing Total Knee Arthroplasty].

Objective: To investigate the effect of whole-process case management based on service process design on patients undergoing total knee arthroplasty (TKA) in areas including pain, function, satisfaction, and complications. Methods: A total of 204 patients who underwent unilateral TKA between April 2021 and March 2022 at the Department of Orthopedics, West China Hospital, Sichuan University were enrolled. By using a random number table, the patients were randomly assigned to two groups, 102 in the general case management group (group G) and 102 in the whole-process case management group (group W). Patients in group G received traditional perioperative case management, while those in the whole-process case management group received integrated case management optimized on the basis of the service process design. The two groups of patients were studied through comparison of their general data, Visual Analogue Scale (VAS) pain score, knee flexion and range of motion, Hospital for Special Surgery (HSS) knee score, the 18-item Patient Satisfaction Questionnaire Short Form (PSQ-18), ability to climb stairs, and complications at 3 days and 3, 8, and 12 weeks after TKA. Results: There was no significant difference between the two groups in patient general information or baseline data collected at the time of enrollment ( P>0.05). There was no significant difference in HSS score, joint range of motion, and VAS pain score between the two groups before the surgery and 3 days after the surgery ( P>0.05). However, the HSS score, joint range of motion, and VAS pain scores of group W were significantly superior to those of group G at 3, 8 and 12 weeks after the surgery (all P<0.05). In addition, group W demonstrated significantly better ability to climb up and down stairs than that of group G at 12 weeks after the surgery ( P< 0.001). In terms of satisfaction, patients in group W were significantly more satisfied than those in group G at 3 days, and 3, 8, and 12 weeks after the surgery ( P<0.001). Conclusion: Whole-process case management based on service process design has a positive effect of relieving pain, increasing range of motion, improving function, increasing satisfaction, and reducing complications in patients undergoing TKA.

An Unprecedented Bird Nest Molybdenum(V) Cobalto-Phosphate Nanosized Wheel Constructed from the [H55 (Mo24 O48 )(Co4 O)2 Co16 (PO4 )42 (py)6 (EtOH)2 (H2 O)11 ]3- Anion.

An unprecedented bird-nest high-nuclear molybdenum(V) cobalto-phosphate nanosized wheel modified by imidazole (im) and pyridine (py), {[H55 (Mo24 O48 )(Co4 O)2 Co16 (PO4 )42 (py)6 (EtOH)2 (H2 O)11 ]- @[(Him)2 (Hpy)]}(N-Et-py)(H2 PO4 )(py)7 (EtOH)⋅12 H2 O (1), has been successfully synthesized by self-assembly. The anionic huge wheel consists of two rare {Co4 O} squares, four {Co4 } tetramers, four {Mo4 } tetramers and four {Mo2 } dimers, linked by bridging oxygen atoms and [PO4 ] groups and encloses two imidazolium cations and a protonated pyridium for charge balance. Surprisingly, 1 represents the first twisted wheel-shaped cluster with a record high-nuclear molybdenum(V) cobalto-phosphate. The delocalized electron effects of the cluster are enhanced with the help of coordinated py ligands, which endows 1 with an excellent third-order nonlinear optical (NLO) response. Additionally, 1 also shows a better photocatalytic water oxidation activity than Co(NO3 )2 with the O2 production of 205 µmol during 6 h in the absence of the [Ru(bpy)3 ]2+ photosensitizer.

Two 2D Layered P4Mo6 Clusters with Potential Bifunctional Properties: Proton Conduction and CO2 Photoreduction.

Two hourglass-type molybdophosphate hybrids with the formulas [Cd(H2O)2DABT]4[Cd(H7P4Mo6O31)2]·19H2O (1) and (C2H5OH)(C3H5N2)6[Co3(H6P4Mo6O31)2]·H2O (2) (DABT= 3,3'-diamino-5,5'-bis(1H-1,2,4-triazole)) have been successfully designed and synthesized via a hydrothermal method. Structure analysis revealed that the inorganic moieties in compounds 1 and 2 are made up of hourglass-type {M[P4Mo6]2} (M = Cd/Co) structure, which were constructed by two (P4Mo6) units with single transition metal (TM) (Cd/Co) atom as the central metal. The {M[P4Mo6]2} (M = Cd/Co) structures were then further connected by TM to constitute a 2D layered structure. Surprisingly, under the condition of 60 °C and 98% RH, compounds 1 and 2 exhibited excellent proton conductivity of 1.35 × 10-3 and 3.78 × 10-3 S cm-1, respectively. Furthermore, compound 2 can act as heterogeneous catalyst for CO2 photoreduction, which indicates that it may be a bifunctional POM-based material with great promise.

Development and validation of a nomogram for predicting overall survival of gastric cancer patients after D2R0 resection.

OBJECTIVE: The aim of the study was to find factors associated with overall survival (OS) and establish a nomogram predicting OS of patients with gastric cancer (GC) after D2R0 resection. METHODS: Demographic and clinicopathologic factors of patients with GC underwent D2R0 surgical resection were retrospectively collected from medical records, telephone interview or outpatient follow-up. To find factors significantly associated with OS, univariate and multivariate analyses were conducted. The concordance index (C-index) was used to measure the accuracy of the nomogram. Discrimination and calibration of the nomogram were tested using the patients in the validation set. RESULTS: Overall, patients with 890 GC underwent D2R0 surgical resection were included. Based on the results of univariate analysis and multivariate analysis, T stage, number of metastatic local lymph nodes, lymph node positive rate, adjuvant chemotherapy and diameter of tumour were used to construct a nomogram predicting OS of patients with GC after surgical resection. In the validation cohort, the C-index was 0.73 and the nomogram performed well in predicting OS. CONCLUSION: The nomogram was able to accurately predict OS of patients with GC underwent curative surgery and performed well in internal validation, which would also be useful for the decision-making of doctors.

[Effects of shRNA on Cisplatin-resistant Non-small Cell Lung Cancer Cell A549 via Silencing CCAT2].

OBJECTIVE: To investigate the effects of short hairpin RNA (shRNA) on the proliferation, invasion, apoptosis and tumor formation of non-small cell lung cancer cisplatin-resistant cell line (A549/DDP) via silencing of colon cancer associated transcript 2 ( CCAT2). METHODS: TA549/DDP cells were transfected with shRNA- CCAT2 (sh- CCAT2) or shRNA-negative control (shRNA-NC), and untransfected A549/DDP cells were used as the control group. CCAT2 mRNA expression in three groups of A549/DDP cells was detected by quantitative real-time PCR (qRT-PCR). The proliferation of three groups of A549/DDP cells treated with different mass concentrations of DDP (0-8 mg/L) was detected by MTT. According to the proliferation experiment results, 2 mg/L was selected as DDP concentration for subsequent experiments. The effects of 2 mg/L DDP treatment on the proliferation, apoptosis, and invasion ability of each group of cells (with untreated A549/DDP cells as the control group) were tested by clone formation experiments, flow cytometry analysis and Transwell experiments. The expression levels of cell proliferation marker proteins (Ki67, PCNA), apoptosis marker proteins (Caspase-3, Caspase-9) and invasion marker proteins (VEGF, MMP-14) were detected by Western blot. Nude mice were injected subcutaneously with A549/DDP cells, A549/DDP cells transfected with shRNA-NC or A549/DDP cells transfected with sh- CCAT2. DDP was intraperitoneally injected at the concentration of 2 mg per kilogram of mice body weight totally for 7 times with an interval of 3 d. A control group was injected subcutaneously with A549/DDP cells, and an equal volume of normal saline instead of DDP was injected intraperitoneally. The tumor volume was detected every 5 d for a total of 30 d. Mice were sacrificed and tumor tissues were taken out 30 d later. CCAT2 mRNA expression level in tumor tissues was detected by RT-PCR, and tumor cell apoptosis was detected by TUNEL staining. RESULTS: Compared with the control group and the shRNA-NC transfection group, the expression level of CCAT2 mRNA was decreased in sh- CCAT2 transfected A549/DDP cells ( P<0.01). The decrease degree of cell proliferation was more pronounced after treating with 2 to 8 mg/L of DDP ( P<0.01). Compared with the control group, in the three groups that treated with DDP, the formation of clones and the expression of proliferation marker proteins Ki67 and PCNA were reduce ( P<0.01), while the rate of apoptosis and the expression of apoptosis marker proteins Caspase-3 and Caspase-9 were increased ( P<0.01). Also, the number of invasion cell and the expression of invasion marker proteins VEGF and MMP-14 were reduced in the three groups that treated with DDP ( P<0.01). Among the three groups of DDP-treated cells, the changes in sh- CCAT2 transfected cells was the most obvious ( P<0.01). Compared with the control group, the tumor volume of the three DDP treatment groups was smaller and the differences were statistically significant at 30 d ( P<0.01). The expression of CCAT2 mRNA was decreased in tumor tissues ( P<0.01), while apoptosis increased ( P<0.01). Among the three DDP treatment groups, the A549/DDP cell group transfected with sh- CCAT2 showed the most notable changes ( P<0.01). CONCLUSION: sh- CCAT2 can inhibit the proliferation of A549/DDP cells, induce apoptosis and reduce the cell invasion ability, thereby inhibiting the growth of A549/DDP cells.

[Clinical Application Assessment of KaryoLite BoBs Combined with QF-PCR in the Detection of Products of Conception].

OBJECTIVE: To assess the accuracy and discuss the feasibility of KaryoLite bacterial artificial chromosome on beads (KL-BoBs) and quantitative fluorescent polymerase chain reaction (QF-PCR) in genetic testing of products of conception (POC) by comparing with the chromosomal microarray analysis (CMA) test results. METHODS: Eighty-one cases of abortion samples were collected in the prenatal diagnosis center of West China Second University Hospital in Sichuan University from May to August 2016,including 61 cases of placenta tissues,19 cases of fetal muscle tissues and 1 case of fetal liver tissue. KL-BoBs and QF-PCR were used to detect the samples. The results were compared with those of CMA test to evaluate the accuracy of KL-BoBs and QF-PCR. RESULTS: Of the 81 POC samples,the results of 70 samples tested by KL-BoBs was consistent with that of CMA. Among them,36 cases were normal karyotype and 34 cases were abnormal karyotypes (aneuploidy). Triploid could not been detected by KL-BoBs (the results were shown 2 cases were normal karyotype and 5 cases were aneuploidy),whereas CMA and QF-PCR could be detected. Copy number variation of small segments could not been detected by KL-Bobs. Four cases of copy number variationwere detected by CMA.Compared with CMA,the positive coincident rate of KL-BoBs combined with QF-PCR was 91.1% (41/45),the negative coincidence rate was 100% (36/36). The accuracy rate of KL-BoBs was 86.4% (70/81),the false positive was 0% and the false negative was 13.3% (6/45). Whereas both KL-BoBs and QF-PCR were simultaneously detected,the accuracy rate would be improved to 95.1% (77/81). CONCLUSION: The accuracy rate of KL-BoBs combined with QF-PCR was high for testing early pregnancy abortion tissue. It can be used as a first-tier test.

Fascin phosphorylation sites combine to regulate esophageal squamous cancer cell behavior.

Filopodia are dynamic membrane extensions generated by F-actin bundling and are involved in cancer cell migration, invasion and metastasis. Fascin is the crucial actin-bundling protein in filopodia, with phosphorylation at fascin serine 39 being well characterized to regulate fascin-mediated actin bundling in filopodia. However, increasing evidence indicates that fascin is phosphorylated at a number of sites. Whether phosphorylation at other sites also regulates fascin function is unknown. In this study, we show that four potential phosphorylation sites in fascin, specifically tyrosine 23, serine 38, serine 39 and serine 274, regulate cell behavior and filopodia formation in esophageal squamous cancer cells. Expression of non-phosphorylatable mutations at each of the four sites promoted anchorage-independent growth, cell motility and filopodia formation, whereas phosphomimetic mutations at each of these sites inhibited these cell behaviors, implying that fascin function in esophageal squamous cancer is regulated by fascin phosphorylation at multiple sites. Furthermore, phosphorylation at S38 and S39 cooperatively regulated cell behavior and filopodia formation, with dual dephosphorylation at both S38 and S39 residues maximally enhancing cell proliferation, migration and filopodia formation, and phosphorylation at any of the two phosphorylatable sites resulting in reduced enhancement. Taken together, our results reveal that phosphorylation at fascin amino acids Y23, S38, S39 and S274, in combination, downregulates the extent of anchorage-independent growth, cell migration and filopodia formation in esophageal squamous cancer cells.

[Application of chromosomal microarray analysis for the diagnosis of children with intellectual disability/developmental delay and a normal karytype].

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the diagnosis of children with intellectual disability/developmental delay (ID/DD) but a normal karytype. METHODS: Peripheral blood samples from 92 ID/DD patients were analyzed with CMA using Affymetrix CytoScan 750K arrays. The results were analyzed by ChAS v3.0 software. RESULTS: Eighteen cases (19.57%) were detected with abnormalities by CMA, among which 10 cases were diagnosed with microdeletion/microduplication syndromes. These included 2 Williams-Beuren syndromes, 2 Angelman syndromes, 2 Russell-Silver syndromes, 1 Smith-Magenis syndromes, 1 Wolf-Hirschhorn syndromes, 1 15q26 overgrowth syndrome and 1 Xq28 (MECP2) duplication syndrome. In addition, 8 cases were diagnosed with pathogenic copy number variations (pCNV). CONCLUSION: CMA can significantly improve the diagnostic rate for patients with ID/DD, which is of great value for the treatment of such children and guidance of reproduction for their parents. Therefore, CMA should become the first-line diagnostic test for patients with ID/DD.

[Application of chromosomal microarray analysis in prenatal diagnosis for fetal abnormalities detected by ultrasonography].

OBJECTIVE: To analyze the outcome of chromosomal microarray analysis (CMA) in prenatal diagnosis for fetal abnormalities detected by ultrasonography. METHODS: Amniotic fluid samples from 477 pregnancies with abnormal ultrasound findings but without common aneuploidies were detected by CMA with Affymetrix CytoScan 750K arrays. The results were analyzed with ChAS v3.0 software. RESULTS: Among the 477 samples, 24 (5.03%) were detected with pathogenic copy number variations (pCNVs) by CMA. Six (9.68%) among 62 cases with structural fetal abnormalities in multiple organ systems were detected with pCNVs, 11 (7.48%) among 147 cases with a single structural anomaly were detected with pCNVs, and 7 (2.61%) among 268 cases with a soft marker were detected with pCNVs. CONCLUSION: CMA has offered a clear advantage over conventional karyotyping for the detection of fetal chromosomal abnormalities, and can provide an effective diagnostic tool for those with one or more structural abnormalities detected by ultrasound.

[Application of Chromosomal Microarray Analysis for Chromosomal Abnormalities of Spontaneously Aborted Fetuses].

OBJECTIVE: To evaluate the clinical significance of chromosomal microarry analysis (CMA) for detection of chromosomal abnormalities in spontaneously aborted fetuses. METHODS: Chorionic villi samples from 431 spontaneously aborted fetuses were detected on the chromosomal abnormalities by CMA in our department form September 2014 to April 2016. RESULTS: The overall success rate of CMA was 100%,and 283 cases were detected with abnormalities (65.67%). Of these 283 cases with abnormal results,126 were common aneuploidies (trisomy 13,16,18,21,22 as well as X and Y aneuploidies) (44.52%),72 were uncommon aneuploidies (25.44%),10 were composited aneuploidies (3.53%),9 were partial aneuploidies (3.18%),29 were polyploidy (10.25%),4 were mosaicism (1.41%),31 were with multiple duplications and deletions (10.96%),and 2 were microduplication/microdeletion syndromes. CONCLUSION: CMA has great advantage for the detection of chromosomal abnormalities in spontaneously aborted fetuses comparing with fluorescence in situ hybridization (FISH). It is of great clinical significance for etiological diagnosis of spontaneous abortion and guidance on reproduction.

Lipocalin 2 promotes the migration and invasion of esophageal squamous cell carcinoma cells through a novel positive feedback loop.

Lipocalin 2 (LCN2) is a poor prognostic factor in esophageal squamous cell carcinoma (ESCC), however its functional roles and molecular mechanisms of action remain to be clarified. Here, we described the functions and signaling pathways for LCN2 in ESCC. Overexpression of LCN2 in ESCC cells accelerated cell migration and invasion in vitro, and promoted lung metastasis in vivo. Blocking LCN2 expression inhibited its pro-oncogenic effect. Either overexpression of LCN2 or treatment with recombinant human LCN2 protein enhanced the activation of MEK/ERK pathway, which in turn increases endogenous LCN2 to increase MMP-9 activity. The decreased p-cofilin and increased p-ERM induced by pERK1/2 cause the cytoskeleton F-actin rearrangement and alter the behavior of ESCC cells mediated by LCN2. As a consequence, activation of MMP-9 and the rearrangement of F-actin throw light on the mechanisms for LCN2 in ESCC. These results imply that LCN2 promotes the migration and invasion of ESCC cells through a novel positive feedback loop.