BRG1 promotes liver cancer cell proliferation and metastasis by enhancing mitochondrial function and ATP5A1 synthesis through TOMM40.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors worldwide. Brahma-related gene 1 (BRG1), as a catalytic ATPase, is a major regulator of gene expression and is known to mutate and overexpress in HCC. The purpose of this study was to investigate the mechanism of action of BRG1 in HCC cells. In our study, BRG1 was silenced or overexpressed in human HCC cell lines. Transwell and wound healing assays were used to analyze cell invasiveness and migration. Mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) detection were used to evaluate mitochondrial function in HCC cells. Colony formation and cell apoptosis assays were used to evaluate the effect of BRG1/TOMM40/ATP5A1 on HCC cell proliferation and apoptosis/death. Immunocytochemistry (ICC), immunofluorescence (IF) staining and western blot analysis were used to determine the effect of BRG1 on TOMM40, ATP5A1 pathway in HCC cells. As a result, knockdown of BRG1 significantly inhibited cell proliferation and invasion, promoted apoptosis in HCC cells, whereas BRG1 overexpression reversed the above effects. Overexpression of BRG1 can up-regulate MMP level, inhibit mPTP opening and activate TOMM40, ATP5A1 expression. Our results suggest that BRG1, as an oncogene, promotes HCC progression by regulating TOMM40 affecting mitochondrial function and ATP5A1 synthesis. Targeting BRG1 may represent a new and effective way to prevent HCC development.

Ganoderma lucidum spores-derived particulate ß-glucan treatment improves antitumor response by regulating myeloid-derived suppressor cells in triple-negative breast cancer.

Granular ß-1,3-glucan extracted from the wall of Ganoderma lucidum spores, named GPG, is a bioregulator. In this study, we investigated the structural, thermal, and other physical properties of GPG. We determined whether GPG ameliorated immunosuppression caused by Gemcitabine (GEM) chemotherapy. Triple-negative breast cancer mice with GPG combined with GEM treatment had reduced tumor burdens. In addition, GEM treatment alone altered the tumor microenvironment(TME), including a reduction in antitumor T cells and a rise in myeloid-derived suppressor cells (MDSC) and regulatory T cells (Tregs). However, combined GPG treatment reversed the tumor immunosuppressive microenvironment induced by GEM. GPG inhibited bone marrow (BM)-derived MDSC differentiation and reversed MDSC expansion induced by conditioned medium (CM) in GEM-treated E0771 cells through a Dectin-1 pathway. In addition, GPG downgraded PD-L1 and IDO1 expression on MDSC while boosting MHC-II, CD86, TNF-α, and IL-6 expression. In conclusion, this study demonstrated that GPG could alleviate the adverse effects induced by GEM chemotherapy by regulating TME.

Light-Quality-Adapted Carotenoid Photoprotection in the Photosystem of Roseiflexus castenholzii.

The photosystem of filamentous anoxygenic phototroph Roseiflexus (Rfl.) castenholzii comprises a light-harvesting (LH) complex encircling a reaction center (RC), which intensely absorbs blue-green light by carotenoid (Car) and near-infrared light by bacteriochlorophyll (BChl). To explore the influence of light quality (color) on the photosynthetic activity, we compared the pigment compositions and triplet excitation dynamics of the LH-RCs from Rfl. castenholzii was adapted to blue-green light (bg-LH-RC) and to near-infrared light (nir-LH-RC). Both LH-RCs bind γ-carotene derivatives; however, compared to that of nir-LH-RC (12%), bg-LH-RC contains substantially higher keto-γ-carotene content (43%) and shows considerably faster BChl-to-Car triplet excitation transfer (10.9 ns vs 15.0 ns). For bg-LH-RC, but not nir-LH-RC, selective photoexcitation of Car and the 800 nm-absorbing BChl led to Car-to-Car triplet transfer and BChl-Car singlet fission reactions, respectively. The unique excitation dynamics of bg-LH-RC enhances its photoprotection, which is crucial for the survival of aquatic anoxygenic phototrophs from photooxidative stress.

High-Performance Gel-Free and Label-Free Size Fractionation of Extracellular Vesicles with Two-Dimensional Electrophoresis in a Microfluidic Artificial Sieve.

Extracellular vesicles (EVs) are cell-derived particles that exhibit diverse sizes, molecular contents, and clinical implications for various diseases depending on their specific subpopulations. However, fractionation of EV subpopulations with high resolution, efficiency, purity, and yield remains an elusive goal due to their diminutive sizes. In this study, we introduce a novel strategy that effectively separates EV subpopulations in a gel-free and label-free manner, using two-dimensional (2D) electrophoresis in a microfluidic artificial sieve. The microfabricated artificial sieve consists of periodically arranged micro-slit-well structures in a 2D array and generates an anisotropic electric field pattern to size fractionate EVs into discrete streams and steer the subpopulations into designated outlets for collection within a minute. Along with fractionating EV subpopulations, contaminants such as free proteins and short nucleic acids can be simultaneously directed to waste outlets, thus accomplishing both size fractionation and purification of EVs with high performance. Our platform offers a simple, rapid, and versatile solution for EV subpopulation isolation, which can potentially facilitate the discovery of biomarkers for specific EV subtypes and the development of EV-based therapeutics.

Development of a machine learning-based model for predicting risk of early postoperative recurrence of hepatocellular carcinoma.

BACKGROUND: Surgical resection is the primary treatment for hepatocellular carcinoma (HCC). However, studies indicate that nearly 70% of patients experience HCC recurrence within five years following hepatectomy. The earlier the recurrence, the worse the prognosis. Current studies on postoperative recurrence primarily rely on postoperative pathology and patient clinical data, which are lagging. Hence, developing a new pre-operative prediction model for postoperative recurrence is crucial for guiding individualized treatment of HCC patients and enhancing their prognosis. AIM: To identify key variables in pre-operative clinical and imaging data using machine learning algorithms to construct multiple risk prediction models for early postoperative recurrence of HCC. METHODS: The demographic and clinical data of 371 HCC patients were collected for this retrospective study. These data were randomly divided into training and test sets at a ratio of 8:2. The training set was analyzed, and key feature variables with predictive value for early HCC recurrence were selected to construct six different machine learning prediction models. Each model was evaluated, and the best-performing model was selected for interpreting the importance of each variable. Finally, an online calculator based on the model was generated for daily clinical practice. RESULTS: Following machine learning analysis, eight key feature variables (age, intratumoral arteries, alpha-fetoprotein, pre-operative blood glucose, number of tumors, glucose-to-lymphocyte ratio, liver cirrhosis, and pre-operative platelets) were selected to construct six different prediction models. The XGBoost model outperformed other models, with the area under the receiver operating characteristic curve in the training, validation, and test datasets being 0.993 (95% confidence interval: 0.982-1.000), 0.734 (0.601-0.867), and 0.706 (0.585-0.827), respectively. Calibration curve and decision curve analysis indicated that the XGBoost model also had good predictive performance and clinical application value. CONCLUSION: The XGBoost model exhibits superior performance and is a reliable tool for predicting early postoperative HCC recurrence. This model may guide surgical strategies and postoperative individualized medicine.

SIRT1 Inhibition-Induced Mitochondrial Damage Promotes GSDME-Dependent Pyroptosis in Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is a malignant tumor that affects the liver and poses a significant threat to human health. Further investigation is necessary to fully understand the role of SIRT1, a protein linked to tumorigenesis, in HCC development. To investigate the effect of SIRT1 on HCC and elucidate the underlying mechanism. Eight pairs of HCC and paracancerous normal tissue specimens were collected. The levels of SIRT1 and GSDME in tissue samples were assessed using immunohistochemistry and western blotting. SIRT1 levels were determined in HCC (Huh7, HepG2, SNU-423, SNU-398, and HCCLM3) and L-02 cells using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. SNU-423 and HCCLM3 cells were transfected with si-SIRT1 and/or si-GSDME to knock down SIRT1 or GSDME expression. RT-qPCR and western blotting were performed to measure the expression of SIRT1, pro-casp-3, cl-casp-3, GSDME, GSDME-N, PGC-1α, Bax, and cytochrome c (Cyto C). Cell proliferation, migration, invasion, and apoptosis were assessed using the cell counting kit-8 (CCK-8), wound healing assay, Transwell invasion assay, and flow cytometry, respectively. The release of lactate dehydrogenase (LDH) was evaluated using an LDH kit. SIRT1 was upregulated in HCC tissues and cells, and a negative correlation was observed between SIRT1 and GSDME-N. SIRT1 silencing suppressed the proliferation, migration, and invasion of HCC cells while also promoting apoptosis and inducing mitochondrial damage. Additionally, the silencing of SIRT1 resulted in the formation of large bubbles on the plasma membrane of HCC cells, leading to cellular swelling and aggravated GSDME-dependent pyroptosis, resulting in an increase in LDH release. Inhibition of GSDME reduced SIRT1 silencing-induced cell swelling, decreased LDH release rate, and promoted apoptosis. SIRT1 silencing promotes GSDME-dependent pyroptosis in HCC cells by damaging mitochondria.

Identification of a Novel CD8+ T cell exhaustion-related gene signature for predicting survival in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health concern, necessitating a deeper understanding of its prognosis and underlying mechanisms. This study aimed to investigate the mechanism and prognostic value of CD8+ T Cell exhaustion (CD8+ TEX)-related genes in HCC and construct a survival prognosis prediction model for patients with HCC. METHODS: CD8+ TEX-related genes associated with HCC prognosis were analysed and identified, and a prognostic prediction model was constructed using the 'least absolute shrinkage and selection operator' Cox regression model. Immunohistochemistry was used to verify the expression of the model genes in HCC tissues. A nomogram was constructed based on risk scores and clinical features, and its predictive efficacy was verified. The expression of STAM, ANXA5, and MAD2L2 in HCC cell lines was detected by western blotting; subsequently, these genes were knocked down in HCC cell lines by small interfering RNA, and their effects on the proliferation and migration of HCC cell lines were detected by colony formation assay, cck8, wound healing, and transwell assays. RESULTS: Six genes related to CD8+ TEX were included in the risk-prediction model. The prognosis of patients with HCC in the low-risk group was significantly better than that of those in the high-risk group. Cox regression analysis revealed that the risk score was an independent risk factor for the prognosis of patients with HCC. The differentially expressed genes in patients with high-risk HCC were mainly enriched in the nucleotide-binding oligomerization domain-containing protein-like receptor, hypoxia-inducible factor-1, and tumour programmed cell death protein (PD)-1/PD-L1 immune checkpoint pathways. The CD8+ TEX-related genes STAM, ANXA5, and MAD2L2 were knocked down in HCC cell lines to significantly inhibit cell proliferation and migration. The prediction results of the nomogram based on the risk score showed a good fit and application value. CONCLUSION: The prediction model based on CD8+ TEX-related genes can predict the prognosis of HCC and provide a theoretical basis for the early identification of patients with poor HCC prognosis.

Accelerated Electrophoretic Focusing and Purification of DNA Based on Synchronous Coefficient of Drag Alteration.

Synchronous coefficient of drag alteration refers to a multidimensional transport mechanism where a net drift of molecules is achieved under a zero-time-average alternating motive force by perturbing their drag coefficient synchronously with the applied force. An electrophoretic form of the method is often applied to focus and purify nucleic acids in a gel under rotating electric fields. However, this method requires lengthy operation due to the use of limited field strengths. Here, using DNA as target molecules, we demonstrate that the operation time can be reduced from hours to minutes by replacing polymer gel with a microfabricated artificial sieve. We also describe an electrophoretic protocol that facilitates the collection of purified DNA from the sieve, which is shown to yield amplifiable DNA from crude samples including the lysates of cultured cells and whole blood. The sieve can be further equipped with nucleic acid amplification and detection functions for a point-of-care diagnostic application.

Endoscopic Ruler for varix size measurement: A multicenter pilot study.

BACKGROUND: We invented Endoscopic Ruler, a new endoscopic device to measure the size of varices in patients with cirrhosis and portal hypertension. AIM: To assess the feasibility and safety of Endoscopic Ruler, and evaluate the agreement on identifying large oesophageal varices (OV) between Endoscopic Ruler and the endoscopists, as well as the interobserver agreement on diagnosing large OV using Endoscopic Ruler. METHODS: We prospectively and consecutively enrolled patients with cirrhosis from 11 hospitals, all of whom got esophagogastroduodenoscopy (EGD) with Endoscopic Ruler. The primary study outcome was a successful measurement of the size of varices using Endoscopic Ruler. The secondary outcomes included adverse events, operation time, the agreement of identifying large OV between the objective measurement of Endoscopic Ruler and the empirical reading of endoscopists, together with the interobserver agreement on diagnosing large OV by Endoscopic Ruler. RESULTS: From November 2020 to April 2022, a total of 120 eligible patients with cirrhosis were recruited and all of them underwent EGD examinations with Endoscopic Ruler successfully without any adverse event. The median operation time of Endoscopic Ruler was 3.00 min [interquartile range (IQR): 3.00 min]. The kappa value between Endoscopic Ruler and the endoscopists while detecting large OV was 0.52, demonstrating a moderate agreement. The kappa value for diagnosing large OV using Endoscopic Ruler among the six independent observers was 0.77, demonstrating a substantial agreement. CONCLUSION: The data demonstrates that Endoscopic Ruler is feasible and safe for measuring the size of varices in patients with cirrhosis and portal hypertension. Endoscopic Ruler is potential to promote the clinical practice of the two-grade classification system of OV.

Continuous-flow label-free size fractionation of extracellular vesicles through electrothermal fluid rolls and dielectrophoresis synergistically integrated in a microfluidic device.

Extracellular vesicles (EVs) are cell-derived bioparticles that play significant roles in various biological processes including cell-to-cell communication and intercellular delivery. Additionally, they hold great potential as liquid biopsy biomarkers for pre-diagnostic applications. However, the isolation of EV subpopulations, especially exosomes from a biological fluid remains a challenge due to their submicron range. Here, we demonstrate continuous-flow label-free size fractionation of EVs for the first time through a synergistic combination of electrothermal fluid rolls and dielectrophoresis in a microfluidic device. The device features three dimensional microelectrodes with unique sidewall contours that give rise to effective electrothermal fluid rolls in cooperation with dielectrophoretic forces for the electrokinetic manipulation and size separation of submicron particles. We first validate the device functionality by separating submicron polystyrene particles from binary mixtures with a cut-off size of ∼200 nm and then isolate intact exosomes from cell culture medium or blood serum with a high recovery rate and purity (∼80%). The device operation in a high-conductivity medium renders the method ideal for the purification of target bioparticles directly from physiological fluids, and may offer a robust and versatile platform for EV related diagnostic applications.

Pan-cancer analysis of the prognostic and immunological role of ANLN: An onco-immunological biomarker.

Anillin actin-binding protein (ANLN) is crucially involved in cell proliferation and migration. Moreover, ANLN is significantly in tumor progression in several types of human malignant tumors; however, it remains unclear whether ANLN acts through common molecular pathways within different tumor microenvironments, pathogeneses, prognoses and immunotherapy contexts. Therefore, this study aimed to perform bioinformatics analysis to examine the correlation of ANLN with tumor immune infiltration, immune evasion, tumor progression, immunotherapy, and tumor prognosis. We observed increased ANLN expression in multiple tumors, which could be involved in tumor cell proliferation, migration, infiltration, and prognosis. The level of ANLN methylation and genetic alteration was associated with prognosis in numerous tumors. ANLN facilitates tumor immune evasion through different mechanisms, which involve T-cell exclusion in different cancer types and tumor-infiltrating immune cells in colon adenocarcinoma, kidney renal clear cell carcinoma, liver hepatocellular carcinoma, and prostate adenocarcinoma. Additionally, ANLN is correlated with immune or chemotherapeutic outcomes in malignant cancers. Notably, ANLN expression may be a predictive biomarker for the response to immune checkpoint inhibitors. Taken together, our findings suggest that ANLN can be used as an onco-immunological biomarker and could serve as a hallmark for tumor screening, prognosis, individualized treatment design, and follow-up.

Noncontrast-enhanced MRI-based Noninvasive Score for Portal Hypertension (CHESS1802): An International Multicenter Study.

BACKGROUND AND AIMS: This study aimed to determine the performance of the non-invasive score using noncontrast-enhanced MRI (CHESS-DIS score) for detecting portal hypertension in cirrhosis. METHODS: In this international multicenter, diagnostic study (ClinicalTrials.gov, NCT03766880), patients with cirrhosis who had hepatic venous pressure gradient (HVPG) measurement and noncontrast-enhanced MRI were prospectively recruited from four university hospitals in China (n=4) and Turkey (n=1) between December 2018 and April 2019. A cohort of patients was retrospectively recruited from a university hospital in Italy between March 2015 and November 2017. After segmentation of the liver on fat-suppressed T1-weighted MRI maps, CHESS-DIS score was calculated automatically by an in-house developed code based on the quantification of liver surface nodularity. RESULTS: A total of 149 patients were included, of which 124 were from four Chinese hospitals (training cohort) and 25 were from two international hospitals (validation cohort). A positive correlation between CHESS-DIS score and HVPG was found with the correlation coefficients of 0.36 (p<0.0001) and 0.55 (p<0.01) for the training and validation cohorts, respectively. The area under the receiver operating characteristic curve of CHESS-DIS score in detection of clinically significant portal hypertension (CSPH) was 0.81 and 0.9 in the training and validation cohorts, respectively. The intraclass correlation coefficients for assessing the inter- and intra-observer agreement were 0.846 and 0.841, respectively. CONCLUSIONS: A non-invasive score using noncontrast-enhanced MRI was developed and proved to be significantly correlated with invasive HVPG. Besides, this score could be used to detect CSPH in patients with cirrhosis.

Sub-pixel position estimation algorithm based on Gaussian fitting and sampling theorem interpolation for wafer alignment.

Wafer alignment is the core technique of lithographic tools. Image-processing-based wafer alignment techniques are commonly used in lithographic tools. An alignment algorithm is used to analyze the alignment mark image for obtaining the mark position. The accuracy and speed of the alignment algorithm are very important for guaranteeing the overlay and throughput of lithographic tools. The most commonly used algorithm in image-processing-based alignment techniques is the self-correlation method. This method has a high accuracy, but the calculation is complex, and the calculation speed is slow. In this paper, we propose a sub-pixel position estimation algorithm based on Gaussian fitting and sampling theorem interpolation. The algorithm first reconstructs the alignment signal by sampling theorem interpolation and then obtains the sub-pixel position of the mark by Gaussian fitting. The accuracy and robustness of the algorithm are verified by testing the simulated marks and experimentally captured marks. The repeat accuracy can reach 1/100 pixels, which is in the same level with the self-correlation method. The calculation speed is highly improved compared with the self-correlation method, which needs only about 1/3 of even short calculation time.

Effects of Lipid Deposition on Viscoelastic Response in Human Hepatic Cell Line HepG2.

Hepatic steatosis is associated with various liver diseases. The main pathological feature of steatosis is the excessive lipid accumulation. Ultrasound has been extensively used for the diagnosis of hepatic steatosis. However, most ultrasound-based non-invasive methods are still not accurate enough for cases with light lipid infiltration. One important reason is that the extent to which lipid infiltration may affect mechanical properties of hepatocytes remains unknown. In this work, we used atomic force microscope and in vitro dose-dependent lipid deposition model to detect the quantitative changes of mechanical properties under different degrees of steatosis in a single-cell level. The results show that hepatic cells with lipid deposition can be treated as linear viscoelastic materials with the power law creep compliance and relaxation modulus. Further analysis showed that even slight accumulation of lipid can lead to measurable decrease of stiffness and increased fluidity in liver cells. The accurate detection of viscoelastic properties of hepatocytes and the analysis methods may provide novel insights into hepatic steatosis grading, especially in the very early stage with reversible liver lesion. The application of viscoelasticity index for grading fat deposition might be a new detection indicator in future clinical diagnosis.

Dual roles of WISP2 in the progression of hepatocellular carcinoma: implications of the fibroblast infiltration into the tumor microenvironment.

The dismal outcome of hepatocellular carcinoma (HCC) patients is attributable to high frequency of metastasis and. Identification of effective biomarkers is a key strategy to inform prognosis and improve survival. Previous studies reported inconsistent roles of WISP2 in carcinogenesis, while the role of WISP2 in HCC progression also remains unclear. In this study, we confirmed that WISP2 was downregulated in HCC tissues, and WISP2 was acting as a protective factor, especially in patients without alcohol intake using multiple online datasets. In addition, we reported that upregulation of WISP2 in HCC was related to inhibition of the malignant phenotype in vitro, but these alterations were not observed in vivo. WISP2 also negatively correlated with tumour purity, and increased infiltration of fibroblasts promoted malignant progression in HCC tissues. The enhanced infiltration ability of fibroblasts was related to upregulated HMGB1 after overexpression of WISP2 in HCC. The findings shed light on the anticancer role of WISP2, and HMGB1 is one of the key factors involved in the inhibition of the efficiency of WISP2 through reducing the tumour purity with fibroblast infiltration.

Measurement algorithm for wafer alignment based on principal component analysis.

We propose a novel measurement algorithm for wafer alignment technology based on principal component analysis (PCA) of a mark image. The waveform of the mark is extracted from the enlarged mark image, which is collected by CCD. The position of the mark center on the CCD can be calculated based on the extracted waveform. By applying PCA to the mark image, the first principal component containing position information of the mark can be obtained. Therefore PCA can be used to extract the waveform from the mark image. Compared with the typical waveform extraction method (the summed projection (SP) method), the proposed PCA method can use the position information contained in the mark image more effectively. Through simulation and experiment, it is proved that the proposed PCA method can improve the contrast of the normalized waveform, and then improve the alignment accuracy.

OSCAR facilitates malignancy with enhanced metastasis correlating to inhibitory immune microenvironment in multiple cancer types.

Cross talk between tumors and the immune microenvironment play a critical role in the malignant progression. The osteoclast-associated receptor (OSCAR) is a regulator of lymphocyte differentiation and maturation, but little is known about the role of OSCAR in multiple cancer types. We comprehensively analyzed OSCAR expression and explored its correlation with prognosis in multiple cancer types using Oncomine, TIMER, Gene GEPIA2 and CCLE. We examined OSCAR expression correlations with lymph node metastasis and pathological stage across tumor samples using UALCAN and GEPIA2. We analyzed the effects of OSCAR on survival using the Kaplan Meier plotter. We explored genes co-expressed with OSCAR using the LinkedOmics database and analyzed associated gene ontologies using Metascape. Further, we examined the correlation between OSCAR expression and immunocyte infiltration, markers of epithelial-mesenchymal transition, and lymphocyte subtypes using TIMER. OSCAR mRNA levels were upregulated in most cancer types compared with adjacent normal tissues. Higher expression of OSCAR correlated with lymph node metastasis or advanced stage subgroups. High expression of OSCAR was related to low tumor purity, with increased levels of M2 macrophage polarization, T cells exhaustion, and mesenchymal phenotype in most cancer types. We also showed that the strength of OSCAR expression influence in malignant progression and inhibitory immune microenvironment is mitigated by the infiltration of natural killer cells. These findings shed light on the pro-carcinogenic role of OSCAR in most cancer types and indicate OSCAR could be targeted in future therapeutics to reverse the inhibitory immune microenvironment.

Depletion of MRPL35 inhibits gastric carcinoma cell proliferation by regulating downstream signaling proteins.

BACKGROUND: Gastric carcinoma (GC) is a digestive system disease with high morbidity and mortality. However, early clinical detection is difficult, and the therapeutic effect for advanced disease is not satisfactory. Thus, finding new tumor markers and therapeutic targets conducive to the treatment of GC is imperative. MRPL35 is a member of the large subunit family of mitochondrial ribosomal protein. MRPL35 shows the characteristic of oncogene in colorectal cancer and esophageal cancer, which promotes the exploration of the correlation between MRPL35 and GC. We proposed that the expression of MRPL35 might be critical in GC. AIM: To study the effect of MRPL35 knockdown on GC cell proliferation. METHODS: The expression of MRPL35 in GC was evaluated based on data from the public tumor database UALCAN (www.ualcan.path.uab.edu). The effect of the expression of MRPL35 on the prognosis was evaluated with KMplot (www.kmplot.com). The expression of MRPL35 was assessed on the tissue microarray by immunohistochemistry and the level of MRPL35 mRNA in 25 pairs of clinical GC tissues and matched adjacent tissues was detected by quantitative reverse transcription-polymerase chain reaction. Celigo cell count assay, colony formation assay, and flow cytometry were used to assess the role of MRPL35 in GC cell proliferation and apoptosis in vitro. Additionally, tumor formation experiment in BALB/c nude mice was utilized to determine the effect of MRPL35 on GC cell proliferation. After knockdown of MRPL35, related proteins were identified by isobaric tags for relative and absolute quantification analysis, and the expression of related proteins was detected by Western blot. RESULTS: The expression of MRPL35 was up-regulated in GC (P = 1.77 × 10-4). The Kaplan-Meier plots of the overall survival indicated that high expression of MRPL35 was associated with a poor survival in GC. Compared with adjacent tissues, the expression of MRPL35 in GC tissues was increased, which was related to age (P = 0.03), lymph node metastasis (P = 0.007), and pathological tumor-node-metastasis stage (P = 0.024). Knockdown of MRPL35 inhibited GC cell proliferation and colony formation and induced apoptosis. Animal experiment results showed that knockdown of MRPL35 inhibited tumor formation in BALB/c nude mice. Western blotting analysis showed that after knockdown of MRPL35, the expression of PICK1 and BCL-XL proteins decreased, and that of AGR2 protein increased. CONCLUSION: Collectively, our findings demonstrate that knockdown of MRPL35 inhibits GC cell proliferation through related proteins including PICK1, BCL-XL, and AGR2.

Evaluation of the clinical application of the Postpartum Depression Predictors Inventory-Revised for postpartum women in China.

AIM: This study was designed to assess the clinical applicability of the Postpartum Depression Predictors Inventory-Revised (PDPI-R) during the 1st month following delivery among women in China and to survey the prevalence of postpartum depression (PPD)-related risk factors included in the PDPI-R in this population. METHODS: This was a cross-sectional study which recruited 447 women from the People's Liberation Army Hospital in Hefei of Anhui province. All participants completed the Chinese version of the PDPI-R (PDPI-R-C) and the Chinese version of the Edinburgh Postnatal Depression Scale (C-EPDS) within 1 month of delivery. The predictive ability of the PDPI-R was then evaluated through receiver operating characteristic (ROC) curve analyses. RESULTS: The PDPI-R-C was able to accurately predict 73.2% of PPD cases (area under the ROC curve = 0.732; 95% CI 0.69-0.78) using a cut-off score of 5.5, as defined by a C-EPDS score of ≥10 (sensitivity = 62.8%; specificity = 73.5%; positive predictive value = 74.5%; negative predictive value = 61.5%). All 13 risk factors in the PDPI-R-C other than socioeconomic status and marital status were associated with the risk of PPD. CONCLUSIONS: The PDPI-R-C was found to be an effective and easy-to-implement tool that has promise as a means of screening for PPD in Chinese populations.