Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells.

The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8+ T cells and accelerating apoptosis in CD8+ T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells.

Disentangled Cross-Modal Transformer for RGB-D Salient Object Detection and Beyond.

Previous multi-modal transformers for RGB-D salient object detection (SOD) generally directly connect all patches from two modalities to model cross-modal correlation and perform multi-modal combination without differentiation, which can lead to confusing and inefficient fusion. Instead, we disentangle the cross-modal complementarity from two views to reduce cross-modal fusion ambiguity: 1) Context disentanglement. We argue that modeling long-range dependencies across modalities as done before is uninformative due to the severe modality gap. Differently, we propose to disentangle the cross-modal complementary contexts to intra-modal self-attention to explore global complementary understanding, and spatial-aligned inter-modal attention to capture local cross-modal correlations, respectively. 2) Representation disentanglement. Unlike previous undifferentiated combination of cross-modal representations, we find that cross-modal cues complement each other by enhancing common discriminative regions and mutually supplement modal-specific highlights. On top of this, we divide the tokens into consistent and private ones in the channel dimension to disentangle the multi-modal integration path and explicitly boost two complementary ways. By progressively propagate this strategy across layers, the proposed Disentangled Feature Pyramid module (DFP) enables informative cross-modal cross-level integration and better fusion adaptivity. Comprehensive experiments on a large variety of public datasets verify the efficacy of our context and representation disentanglement and the consistent improvement over state-of-the-art models. Additionally, our cross-modal attention hierarchy can be plug-and-play for different backbone architectures (both transformer and CNN) and downstream tasks, and experiments on a CNN-based model and RGB-D semantic segmentation verify this generalization ability.

Orientation Cues-Aware Facial Relationship Representation for Head Pose Estimation via Transformer.

Head pose estimation (HPE) is an indispensable upstream task in the fields of human-machine interaction, self-driving, and attention detection. However, practical head pose applications suffer from several challenges, such as severe occlusion, low illumination, and extreme orientations. To address these challenges, we identify three cues from head images, namely, critical minority relationships, neighborhood orientation relationships, and significant facial changes. On the basis of the three cues, two key insights on head poses are revealed: 1) intra-orientation relationship and 2) cross-orientation relationship. To leverage two key insights above, a novel relationship-driven method is proposed based on the Transformer architecture, in which facial and orientation relationships can be learned. Specifically, we design several orientation tokens to explicitly encode basic orientation regions. Besides, a novel token guide multi-loss function is accordingly designed to guide the orientation tokens as they learn the desired regional similarities and relationships. Experimental results on three challenging benchmark HPE datasets show that our proposed TokenHPE achieves state-of-the-art performance. Moreover, qualitative visualizations are provided to verify the effectiveness of the token-learning methodology.

Echocardiography-based machine learning algorithm for distinguishing ischemic cardiomyopathy from dilated cardiomyopathy.

BACKGROUND: Machine learning (ML) can identify and integrate connections among data and has the potential to predict events. Heart failure is primarily caused by cardiomyopathy, and different etiologies require different treatments. The present study examined the diagnostic value of a ML algorithm that combines echocardiographic data to automatically differentiate ischemic cardiomyopathy (ICM) from dilated cardiomyopathy (DCM). METHODS: We retrospectively collected the echocardiographic data of 200 DCM patients and 199 ICM patients treated in the First Affiliated Hospital of Guangxi Medical University between July 2016 and March 2022. All patients underwent invasive coronary angiography for diagnosis of ICM or DCM. The data were randomly divided into a training set and a test set via 10-fold cross-validation. Four ML algorithms (random forest, logistic regression, neural network, and XGBoost [ML algorithm under gradient boosting framework]) were used to generate a training model for the optimal subset, and the parameters were optimized. Finally, model performance was independently evaluated on the test set, and external validation was performed on 79 patients from another center. RESULTS: Compared with the logistic regression model (area under the curve [AUC] = 0.925), neural network model (AUC = 0.893), and random forest model (AUC = 0.900), the XGBoost model had the best identification rate, with an average sensitivity of 72% and average specificity of 78%. The average accuracy was 75%, and the AUC of the optimal subset was 0.934. External validation produced an AUC of 0.804, accuracy of 78%, sensitivity of 64% and specificity of 93%. CONCLUSIONS: We demonstrate that utilizing advanced ML algorithms can help to differentiate ICM from DCM and provide appreciable precision for etiological diagnosis and individualized treatment of heart failure patients.

MIF/SCL3A2 depletion inhibits the proliferation and metastasis of colorectal cancer cells via the AKT/GSK-3ß pathway and cell iron death.

This study investigated the mechanisms of migration inhibitory factor (MIF) and solute carrier family 3 member 2 (SLC3A2) in colorectal cancer progression. The levels of MIF and SLC3A2 expression in cells were measured by RT-qPCR. SW480 and SW620 cells were transfected with sh-MIF and sh-SLC3A2, respectively. MIF, SLC3A2, GPX4, E-cadherin and N-cadherin expression were detected by immunofluorescence (IF). CCK8 and Transwell assays were performed to detect cell proliferation and migration. Co-immunoprecipitation (CoIP) was used to measure the binding activity of MIF and SLC3A2. Finally, a nude mouse tumorigenicity assay was used to confirm the functions of MIF and SLC3A2 in colorectal cancer. Results showed that the levels of MIF and SLC3A2 expression were up-regulated in colorectal cancer cells. Inhibition of MIF or SLC3A2 expression prevented cell proliferation, migration, epithelial-mesenchymal transition (EMT) and invasion. In addition, knockdown of MIF and SLC3A2 promoted iron death in SW480 and SW620 cells. CoIP results showed that MIF and SLC3A2 directly interact with each other. Knockdown of both MIF and SLC3A2 inhibited tumour growth and metastasis via the AKT/GSK-3ß pathway in vivo. The Akt/GSK-3ß pathway was found to participate in regulating MIF and SLC3A2 both in vivo and in vitro. MIF and SLC3A2 might be potential biomarkers for monitoring the treatment of colorectal cancer.

Thymic hypoplasia induced by copy number variations contributed to explaining sudden infant death based on forensic autopsies.

Thymic hypoplasia is a primary cellular immunodeficiency that causes susceptibility to serious infections leading to sudden death in infants. Some genetic disorders in humans could result in the evident permanent hypoplasia or occasional aplasia of the thymus at birth. However, determining the genetic etiology of thymic hypoplasia is challenging for the sudden infant death due to primary cellular immunodeficiency. In this study, in order to find the fundamental reasons for sudden death of infants with thymic hypoplasia, 5 infants with suspected thymic hypoplasia and 10 control infants were assessed, and the immunohistochemistry and DNA analysis were used to investigate whether the infants with thymic hypoplasia had DiGeorge syndrome (DGS) with copy number variations (CNVs) in 22q11.2 and other chromosomes. The results showed that the weight of the thymus was significantly lower than the normal except the case 4, and that all the infants had hypocalcemia and a significant decrease or even absence of the markers CD1a, CD2, CD3, CD4 and CD8, which are related to T-cell maturation. In addition, multiplex ligation-dependent probe amplification (MLPA) analysis showed that these infants carried CNVs in 22q11.2 and other associated chromosomes with deletion and duplication of 25 genes. The results of thymus weight, histopathology, molecular pathology and MLPA analysis suggested that DGS predominantly with thymic hypoplasia induced by CNVs caused the sudden death of these infants under various infections or other unexplained reasons, which may provide new insights into the diagnosis of sudden infant death and could help the parents of deceased infants to attach more importance of genetic screening and thymus ultrasound to reduce the postnatal mortality of the infant, and demonstrates the value of genetic diagnosis in the forensic pathology.

Learning From Images: A Distillation Learning Framework for Event Cameras.

Event cameras have recently drawn massive attention in the computer vision community because of their low power consumption and high response speed. These cameras produce sparse and non-uniform spatiotemporal representations of a scene. These characteristics of representations make it difficult for event-based models to extract discriminative cues (such as textures and geometric relationships). Consequently, event-based methods usually perform poorly compared to their conventional image counterparts. Considering that traditional images and event signals share considerable visual information, this paper aims to improve the feature extraction ability of event-based models by using knowledge distilled from the image domain to additionally provide explicit feature-level supervision for the learning of event data. Specifically, we propose a simple yet effective distillation learning framework, including multi-level customized knowledge distillation constraints. Our framework can significantly boost the feature extraction process for event data and is applicable to various downstream tasks. We evaluate our framework on high-level and low-level tasks, i.e., object classification and optical flow prediction. Experimental results show that our framework can effectively improve the performance of event-based models on both tasks by a large margin. Furthermore, we present a 10K dataset (CEP-DVS) for event-based object classification. This dataset consists of samples recorded under random motion trajectories that can better evaluate the motion robustness of the event-based model and is compatible with multi-modality vision tasks.

Modulating microbiota metabolism via bioaugmentation with Lactobacillus casei and Acetobacter pasteurianus to enhance acetoin accumulation during cereal vinegar fermentation.

Acetoin, giving a creamy yogurt aroma and buttery taste, exists in cereal vinegar as an important flavor substance and is mainly produced by the metabolism of Lactobacillus and Acetobacter during multispecies solid-state acetic acid fermentation. However, the impacts of Lactobacillus-Acetobacter interactions on acetoin accumulation and the microbial metabolism during acetic acid fermentation are not completely clear. Here, six strains isolated from vinegar fermentation culture and associated with acetoin metabolism, namely, Lactobacillus reuteri L-0, L. buchneri F2-6, L. brevis 4-20, L. fermentum M10-7, L. casei M1-6 and Acetobacter pasteurianus G3-2, were selected for microbial growth and metabolism analysis in monoculture and coculture fermentations. Lactobacillus sp. and A. pasteurianus G3-2 respectively utilized glucose and ethanol preferentially. In monocultures, L. casei M1-6 (183.7 mg/L) and A. pasteurianus G3-2 (121.0 mg/L) showed better acetoin-producing capacity than the others. In the bicultures with Lactobacillus sp. and A. pasteurianus G3-2, biomass analysis in the stationary phase demonstrated that significant growth depressions of Lactobacillus sp. occurred compared with monocultures, possibly due to intolerance to acetic acid produced by A. pasteurianus G3-2. Synergistic effect between Lactobacillus sp. and A. pasteurianus G3-2 on enhanced acetoin accumulation was identified, however, cocultures of two Lactobacillus strains could not apparently facilitate acetoin accumulation. Coculture of L. casei M1-6 and A. pasteurianus G3-2 showed the best performance in acetoin production amongst all mono-, bi- and triculture combinations, and the yield of acetoin increased from 1827.7 to 7529.8 mg/L following optimization of culture conditions. Moreover, the interactions of L. casei M1-6 and A. pasteurianus G3-2 regulated the global metabolism of vinegar microbiota during fermentation through performing in situ bioaugmentation, which could accelerate the production of acetic acid, lactic acid, acetoin, ethyl acetate, ethyl lactate, ligustrazine and other important flavoring substances. This work provides a promising strategy for the production of acetoin-rich vinegar through Lactobacillus sp.-A. pasteurianus joint bioaugmentation.

Deciphering the d-/l-lactate-producing microbiota and manipulating their accumulation during solid-state fermentation of cereal vinegar.

Symphony orchestra of multi-microorganisms characterizes the solid-state acetic acid fermentation process of Chinese cereal vinegars. Lactate is the predominant non-volatile acid and plays indispensable roles in flavor formation. This study investigated the microbial consortia driving the metabolism of D-/l-lactate during fermentation. Sequencing analysis based on D-/l-lactate dehydrogenase genes demonstrated that Lactobacillus (relative abundance: > 95%) dominated the production of both d-lactate and l-lactate, showing species-specific features between the two types. Lactobacillus helveticus (>65%) and L. reuteri (~80%) respectively dominated l- and d-lactate-producing communities. D-/l-lactate production and utilization capabilities of eight predominant Lactobacillus strains were determined by culture-dependent approach. Subsequently, D-/l-lactate producer L. plantarum M10-1 (d:l ≈ 1:1), l-lactate producer L. casei 21M3-1 (D:L ≈ 0.2:9.8) and D-/l-lactate utilizer Acetobacter pasteurianus G3-2 were selected to modulate the metabolic flux of D-/l-lactate of microbial consortia. The production ratio of D-/l-lactate was correspondingly shifted coupling with microbial consortia changes. Bioaugmentation with L.casei 21M3-1 merely enhanced l-lactate production, displaying ~4-fold elevation at the end of fermentation. Addition of L.plantarum M10-1 twice increased both D- and l-lactate production, while A. pasteurianus G3-2 decreased the content of D-/l-isomer. Our results provided an alternative strategy to specifically manipulate the metabolic flux within microbial consortia of certain ecological niches.

Regulatory T-cell expansion in oral and maxillofacial Langerhans cell histiocytosis.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare myeloid-origin neoplasm characterized by the expansion and dissemination of CD1 a+/CD207+ dendritic cells (LCH cells), but the rarity of its occurrence has long impeded progress in understanding its pathology. We focus on the potentially important role that regulatory T cells (T-reg) play in the oral and maxillofacial LCH tumor microenvironment (TME). STUDY DESIGN: Nine cases of oral and maxillofacial LCH, diagnosed from 2009 to 2019, were collected retrospectively from the affiliated hospitals of Southern Medical University. Immunohistochemistry was conducted characterizing T cells and T-reg phenotype. Data were evaluated by 1-sample Wilcoxon's test. RESULTS: Significantly increased frequency and abnormal distributions of T-reg were identified in all the LCH lesion sections. Proliferating T-reg account for a mean average of 11.5% of the total T-cell subsets, with significant difference (Wilcoxon's test; P < .05). CONCLUSIONS: T-reg expansion in the localized inflammatory TME leads to a failure of immune regulation by suppressing antitumor response, which can be a latent and significant factor contributing to LCH progression. However, T-reg may also acquire the capability for aiding in initiating T-cell responses under the "cytokine storm" at the beginning of LCH onset. T-reg might contribute to the augmentation of tissue repair by transforming growth factor-ß (TGF-ß), explaining the self-limiting character of LCH.

RGBD Salient Object Detection via Disentangled Cross-modal Fusion.

Depth is beneficial for salient object detection (SOD) for its additional saliency cues. Existing RGBD SOD methods focus on tailoring complicated cross-modal fusion topologies, which although achieve encouraging performance, are with a high risk of over-fitting and ambiguous in studying cross-modal complementarity. Different from these conventional approaches combining cross-modal features entirely without differentiating, we concentrate our attention on decoupling the diverse cross-modal complements to simplify the fusion process and enhance the fusion sufficiency. We argue that if cross-modal heterogeneous representations can be disentangled explicitly, the cross-modal fusion process can hold less uncertainty, while enjoying better adaptability. To this end, we design a disentangled cross-modal fusion network to expose structural and content representations from both modalities by cross-modal reconstruction. For different scenes, the disentangled representations allow the fusion module to easily identify, and incorporate desired complements for informative multi-modal fusion. Extensive experiments show the effectiveness of our designs and a large outperformance over state-of-the-art methods.

Cdc42 subcellular relocation in response to VEGF/NRP1 engagement is associated with the poor prognosis of colorectal cancer.

Microscopic indications of malignancy and hallmark molecules of cancer are pivotal to determining cancer patient prognosis and subsequent medical intervention. Here, we found that compared to apical expression of Cdc42, which indicated that basal expression of Cdc42 occurred at the migrating cell front, glandular basal expression of Cdc42 (cell division cycle 42) in tissues indicated poorer prognoses for colorectal cancer (CRC) patients. The current study shows that activated Cdc42 was rapidly recruited to the migrating CRC cell front after VEGF stimulation through engagement of membrane-anchored neuropilin-1 (NRP1). When VEGF signalling was blocked with NRP1 knockdown or ATWLPPR (A7R, antagonist of VEGF/NRP1 interaction), Cdc42 activation and relocation to the cell front was attenuated, and filopodia and invadopodia formation was inhibited. The VEGF/NRP1 axis regulates directional migration, invasion, and metastasis through Cdc42 activation and relocation resulting from actin filament polymerisation of the extensions of membrane protrusions. Collectively, the immuno-micromorphological pattern of subcellular Cdc42 at the cell front indicated aggressive behaviours and predicted poor prognosis in CRC patients. Disruption of the intra- and extracellular interactions of the VEGF/NRP1 axis or Cdc42 relocation could be performed in clinical practice because it might inhibit cancer cell motility and metastasis.

High expression of PRKDC promotes breast cancer cell growth via p38 MAPK signaling and is associated with poor survival.

BACKGROUND: DNA-Dependent Protein Kinase Catalytic Subunit (PRKDC), a key component of the DNA damage repair pathway, is associated with chemotherapy resistance and tumor progression. METHODS: Here we analyzed transcriptome data of ~2,000 breast cancer patients and performed functional studies in vitro to investigate the function of PRKDC in breast cancer. RESULTS: Our results revealed overexpression of PRKDC in multiple breast cancer subtypes. Consistent with patients' data, overexpression of PRKDC was also observed in breast cancer cell lines compared to normal breast epithelial cells. Knockdown of PRKDC in MCF-7 and T47D breast cancer cell lines resulted in proliferation inhibition, reduced colony formation and G2/M cell cycle arrest. Furthermore, we showed that PRKDC knockdown induced proliferation inhibition through activation of p38 MAPK, but not ERK MAPK, signaling pathway in breast cancer cells. Blockage of p38 MAPK signaling could largely rescue proliferation inhibition and cell cycle arrest induced by PRKDC knockdown. Moreover, we analyzed gene expression and clinical data from six independent breast cancer cohorts containing ~1,000 patients. In all cohorts, our results consistently showed that high expression of PRKDC was significantly associated with poor survival in both treated and untreated breast cancer patients. CONCLUSION: Together, our results suggest that high expression of PRKDC facilitates breast cancer cell growth via regulation of p38 MAPK signaling, and is a prognostic marker for poor survival in breast cancer patients.

[Primary intraosseous hematopoietic pseudotumor: clinicopathological analysis and 9-year follow-up of 3 cases].

We analyzed the clinicopathological data of 3 cases of primary intraosseous hematopoietic pseudotumor (IHPT), which had been previously misdiagnosed as malignancies or metastases both clinically and pathologically. Two of the patients received close follow-up for 132 and 100 months, and one patient was lost to follow-up, and the tumors were confirmed to be benign in all the 3 cases. IHPT is a rare benign intraosseous solid lesion consisting of tissues resembling normal hematopoietic tissue, and can be easily misdiagnosed as malignancy. Understanding the clinicopathological features and the outcomes of the disease can facilitate the clinical decisions on individualized diagnosis and therapeutic regimens.

PRKDC is a prognostic marker for poor survival in gastric cancer patients and regulates DNA damage response.

A hallmark of gastric cancer is the high rate of genomic instability associated with deregulation of DNA damage repair pathways. DNA-Dependent Protein Kinase Catalytic Subunit (PRKDC) is a key component of the non-homologous end-joining (NHEJ) pathway. By reanalyzing transcriptome data of 80 pairs of gastric cancer tumors and the adjacent normal tissues from non-treated patients, we identified PRKDC as the top upregulated DNA damage repair genes in gastric cancer. High expression of PRKDC is associated with poor survival of gastric cancer patients, and genomic amplification of the gene is frequently observed across most gastric cancer subtypes. Knockdown of PRKDC in gastric cell lines resulted in reduced proliferation and cell cycle arrest. Furthermore, we showed that loss of PRKDC induced DNA damage and enhanced gastric cancer cell chemosensitivity to DNA-damaging reagents. Together, our results suggest that PRKDC is a prognostic marker of poor survival and is a putative target to overcome chemoresistance in gastric cancer.

[Culture and identification of tumor stem cells from surgically resected colorectal cancer tissues].

OBJECTIVE: To obtain cancer stem cells (CSCs) from surgically resected colorectal cancer specimens and identify their stem cell characteristics. METHODS: Colorectal cancer tissue specimen obtained from a patient undergoing radical resection of colorectal cancer were implanted in nude mice, and the xenograft was harvested 1 month later to obtain purified tumor cells by enzyme digestion and adherent culture. The CSCs were screened by limiting dilution method and serum-free culture to identify their phenotypes. Soft agar colony assay was used to assess the proliferative ability of the CSCs and human colorectal cancer cell line SW480. The tumorigenic ability of the isolated CSCs and SW480 cells was evaluated by observing their subcutaneous tumor formation in nude mice. Western blotting and immunofluorescence assay were used to detect the immunophenotype of the CSCs and SW480 cells. RESULTS: The primary cultured CSCs from clinical specimens of colorectal cancer underwent differentiation in the presence of serum in the culture. Soft agar colony formation assay showed that the CSCs had a colony formation rate above 50%, significantly higher than the rate of colorectal cancer SW480 cells (4.41%; P < 0.01). In nude mice, subcutaneous injection of 500 CSCs was sufficient to result in subcutaneous tumor formation, while the injection of 500 SW480 cells failed to form any subcutaneous tumors. The CSCs expressed CD133 and CD44 but not CK7, while SW480 cells expressed CK7 but not CD133 or CD44. CONCLUSIONS: CSCs can be derived by primary culture of cancer cells obtained from surgically resected colorectal cancer tissue followed by serum-free culture, and the CSCs obtained have self-renewal and differentiation abilities.

Application whole exome sequencing for the clinical molecular diagnosis of patients with Duchenne muscular dystrophy; identification of four novel nonsense mutations in four unrelated Chinese DMD patients.

BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common form of inherited muscular dystrophy. Germline mutations in dystrophin (DMD) gene cause DMD, with a X-linked recessive mode of inheritance. Patients with DMD are usually characterized by weakness of muscle, usually started since childhood and gradually the patient will unable to stand and walk. METHODS: In our present study, we identified four unrelated Chinese patients with DMD from four Chinese families. Whole exome sequencing was performed for genetic molecular analysis for these probands. RESULTS: Whole exome sequencing and confirmatory Sanger sequencing identified four novel nonsense mutations in these four unrelated Chinese patients, respectively. All these four mutations lead to the formation of a truncated DMD protein by formation of a premature stop codon. According to the variant interpretation guidelines of American College of Medical Genetics and Genomics (ACMG), these four novel nonsense mutations are categorized as "likely pathogenic" variants. CONCLUSION: Our present finding not only identified four novel loss-of-function mutations in dystrophin (DMD) gene but also strongly emphasized the significance of whole exome sequencing as the most efficient way of identifying the candidate genes and mutations which enables us for easy and rapid clinical diagnosis, follow-up, and management of DMD patients.

ERp29 counteracts the suppression of malignancy mediated by endoplasmic reticulum stress and promotes the metastasis of colorectal cancer.

Endoplasmic reticulum protein 29 (ERp29), an endoplasmic reticulum (ER) protein, participates in ER stress (ERS), but little is known about the association of ERp29 with ERS in the metastasis and prognosis of cancerous diseases. The present study revealed that ERp29 was important to ERS and interfered with the malignant behaviors of colorectal cancer (CRC). Experiments in in vitro and in animal models revealed that ERS inhibited the cell growth and suppressed the metastatic capacity of CRC cells, but ERp29 counteracted these effects. Furthermore, it was demonstrated that ERp29 recovered the migration and metastatic behaviors of CRC cells suppressed by ERS, mediated only when it combined with cullin5 (CUL5). ERp29 also relied on CUL5 to promote epithelial­mesenchymal transition. From the immunohistochemical examination of CRC tissues, the high expression of ERp29 was revealed to predict the poor prognosis of 457 CRC cases. The retrospective analysis of the clinicopathological data of patients with CRC was consistent with the results of the in vitro and in vivo experiments. Thus, ERp29 protected CRC cells from ERS­mediated reduction of malignancy to promote metastasis and may be a potential target of medical intervention for CRC therapy.

Telepathology consultation for frozen section diagnosis in China.

BACKGROUND: Telepathology (TP) provides remote pathology services for primary diagnosis practices, including intraoperative consultation of surgical pathology; it has not been widely implemented in China. In this study, the results of an implementation were reported, which lasted for two and a half years, and demonstrated the experience of the diagnosis of the intraoperative frozen sections by using TP consultation platform of Southern Medical University and Guangzhou Huayin Medical Laboratory Center (SMU-HUAYIN TP) in China. METHODS: The SMU-HUAYIN TP consultation platform connects 71 participating basic hospitals and 11 senior pathologists. Nanfang Hospital is a high-level hospital located in a large city in China. This retrospective study summarizes the experience and results of TP for frozen section diagnosis by comparing the data of the platform and Nanfang Hospital over a period of 2.5 years from January 2015 to June 2017. RESULTS: A total of 5233 cases were submitted to the platform, including 1019 cases in 2015, 2320 cases in 2016, and 1894 cases in 2017. The most common cases were breast (30.42%), followed by thyroid (29.05%) and gynecological (24.86%). Average turn-around time (TAT) of the cases from the platform in 2015 and 2016 was controlled within 30 min. In most TP cases (90.31%) and cases from Nanfang Hospital (86.14%), a definitive diagnosis was provided. The coincidence rate was 99.77% in the TP cases and 99.35% in the cases from Nanfang Hospital. The false positive and false negative rates of TP cases were 0.04 and 0.19%, respectively and no significant difference was found among different senior pathologists (P = 0.974, P = 0.989, P > 0.05). Similarly, there was no significant difference between TP cases and cases from Nanfang Hospital that were diagnosed by the same senior pathologist (P > 0.05). CONCLUSIONS: Our results indicate that TP in frozen section diagnosis could improve patient care and solve the problem of unevenly distributed pathology resources in China. We believe that in the near future, TP in frozen section diagnosis will become an important component of telemedicine and will play a significant role in health care reform in China.

Stomatin-like protein 2 is overexpressed in cervical cancer and involved in tumor cell apoptosis.

Stomatin-like protein 2 (SLP-2) is overexpressed in numerous types of human cancer and previous studies revealed that SLP-2 may function in mitochondria. The purpose of the present study was to evaluate the expression of SLP-2 in cervical cancer and the association between SLP-2 expression and clinical features, in addition to investigating the role of SLP-2 in the apoptosis of cervical cancer cells. The expression profile of SLP-2 was determined by quantitative polymerase chain reaction, western blotting and immunohistochemical staining. The effect of SLP-2 on cell apoptosis induced by chemotherapeutics in cervical cancer cells was evaluated using Annexin V staining and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assays. The results indicated that SLP-2 expression in cervical cancer was significantly upregulated at the mRNA and protein levels, compared with that in normal cervical tissues. Immunohistochemical analysis revealed significant correlation between SLP-2 protein expression and clinical characteristics, including the squamous cell carcinoma antigen (P=0.003), deep stromal invasion (P=0.021), lymphovascular space involvement (P=0.044) and pelvic lymph node metastasis (P<0.001), which served as independent prognostic factors for predicting the shortening of overall survival time in patients with early-stage cervical cancer. In addition, TUNEL and Annexin V binding assays revealed that silencing SLP-2 expression significantly enhanced the sensitivity of cervical cancer cells to apoptosis induced by chemotherapeutics. Taken together, the results of the present study suggest that SLP-2 may be a progressive gene in the development of cervical cancer. Overexpression of SLP-2 serves an important role in the apoptosis of human cervical cancer cells.