Search

Acquired resistance to chemotherapeutic drugs in gallbladder cancer (GBC) results in therapy failure. This study is aimed to establish oxaliplatin (OXA)-resistant GBC cell lines and uncover their gene expression profiles. First, two OXA-resistant GBC cell lines (GBC-SD/OXA and SGC996/OXA) were established by gradually increasing the drug concentration, and the resistance index was 4–5. The two resistant cell lines showed slower proliferation and higher stemness, colony formation, and migration abilities. Epithelial mesenchymal transformation and increased levels of P-glycoprotein were also detected. Next RNA-sequence analysis identified 4,675 dysregulated genes (DGs) in resistant cells, and most of the 12 randomly selected DGs were verified to be consistent with the sequence results. Kyoto Encyclopedia of Genes and Genomes analysis indicated that several DGs were involved in resistance- and phenotype-related pathways, of which the activations of PD-L1 and ERK1/2 were both verified in resistant cell lines. In conclusion, this study is the first to report the gene expression profile of OXA-resistant GBC cells and provides a useful database for target development.

Objective To investigate the short-term outcome and safety of laparoscopic splenectomy combined with peripheral cardia disconnection in treatment of portal hypertension. Methods A retrospective analysis was done with clinical data of 23 patients who underwent laparoscopic splenectomy combined with peripheral cardia disconnection in our hospital from September 2018 to December 2020. Comparison was performed using the clinical data of 13 cases with the method of open surgery, which were comparable to the clinical pathological baseline. Results Less blood loss, longer operative time, and earlier both exhaust time and feeding time were found in the patients of laparoscopic group compared with those in open group. There were no statistically significant differences in postoperative hospital stay and postoperative complications including bleeding, pleural effusion, deep vein thrombosis, gastroparesis, and incision infection between two groups(P>0.05). Conclusions Laparoscopic splenectomy combined with peripheral cardia disconnection can treat portal hypertension which is safe, less blood loss, early postoperative feeding and the short-term outcome similar to open surgery.

Mobile edge computing (MEC) is receiving more attention than centralized cloud computing due to the massive increase in transmission and compute requirements in 5G vehicle networks. It offers a significant amount of processing and storage resources to the edge of networks, offloading applications from vehicle terminals that are computation-intensive and delay-sensitive. For devices with limited resources, it uses edge resources to provide computationally heavy operations while conserving energy. This paper proposes a novel approach for computing offloading in MEC. To effectively optimize the MEC resources, this paper proposes a novel algorithm. First, the joint optimization and service cache decision subproblems were determined from continuous and discrete variables. Then, the near-optimal solution is determined from the subproblems through convex optimization and Karush–Kuhn–Tucker method. Simulation results show that the proposed algorithm has better computational offloading and resource allocation performance as compared to existing algorithms. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?What are the morphological features and microRNA (miRNA) expression features of extracellular vesicles (EVs) from haemorrhoids (Hae‐EVs) and normal tissues? What are the potential functions of the differentially expressed (DE) miRNAs in Hae‐EVs?What is the main finding and its importance?We present, for the first time, the morphological features and miRNA profile of human Hae‐EVs. Four hundred and forty‐seven significant DE‐miRNAs were identified. Gene ontology and pathway analysis of the DE‐miRNAs indicated diverse roles of the Hae‐EVs through different pathways. Our findings provide EV‐based pathological features and the underlying mechanism of haemorrhoids. Extracellular vesicles (EVs) play important roles in many pathophysiologies as cell‐to‐cell communication vehicles. However, the features and potential functions of the EVs in haemorrhoids remain unclear. Therefore, we performed microRNA (miRNA) microarray analysis in EVs derived from haemorrhoid tissue to identify the profile of miRNAs in these EVs and predict their potential functions. We obtained typical EVs from both haemorrhoid and control tissues. Microarray analysis identified 447 miRNAs with significant differential expresssion (DE): 245 upregulated and 202 downregulated. The top three upregulated miRNAs in haemorrhoid EVs (Hae‐EVs), namely miR‐6741‐3p, miR‐6834‐3p and miR‐4254, were detected by RT‐qPCR in both Hae‐EVs and haemorrhoid tissues. Interestingly, we found a different expression pattern in the haemorrhoid tissues from that in Hae‐EVs. The potential target genes of these DE‐miRNAs were predicted by the miRWalk and miRDB databases. Gene ontology (GO) analysis of the target genes showed that the DE‐miRNAs contributed mainly to protein kinase activity, transcriptional activity and ubiquitin‐protein function. KEGG search found that the DE‐miRNAs might regulate the MAPK and Ras signalling pathways. These findings revealed, for the first time, the miRNA profiles in Hae‐EVs and provided potential targets and pathways involved in the pathological process. [ABSTRACT FROM AUTHOR]

We aimed to examine whether prognostic nutritional index (PNI) could serve as an auxiliary predictor for major cardiovascular events (MCEs) in patients undergoing invasive coronary angiography (ICA). A total of 485 participants were enrolled, divided into low-PNI (≥47.40) and high-PNI (<47.40) groups. ICA determined the stenotic vessels of coronary artery disease. The primary outcome was incidental MCEs, a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or rehospitalization of in-stent restenosis. There were 47 (9.69%) MCEs during the 3.78-years follow-up. The cumulative incidence of MCEs was significantly higher in the low-PNI patients compared with the high-PNI patients (17.07% vs. 7.18%, p = 0.001). Malnutrition risk (low PNI) was significantly and independently associated with a higher risk of MCEs (hazard ratios: 2.593, 95% confidence intervals [CI]: 1.418–4.742). Combined use of the number of stenotic vessels with malnutrition risk showed a higher capacity to predict the MCEs than the presence of stenotic vessels alone (areas under the receiver operator characteristic curve: 0.696 [95% CI, 0.618–0.775] vs. 0.550 [95% CI, 0.466–0.633], p = 0.013). In conclusion, lower PNI levels may predict a higher risk of cardiovascular events in patients undergoing ICA, which supports the necessity of the risk assessment of nutrition status and guide the clinical treatment on strengthening nutritional support before ICA is performed, as well as nutritional intervention after ICA. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that hypermethylation of HOXD10 plays an important role in human cancers. However, the biological and clinical impacts of HOXD10 overmethylation and its downstream targets in colorectal cancer remain unknown. We evaluated the methylation level of HOXD10 in paired cancer and normal tissues (n = 42) by using pyrosequencing, followed by validation of the methylation status of HOXD10 from The Cancer Genome Atlas (TCGA) datasets with 302 cancer tissues and 38 normal tissues. The biological function of HOXD10 was characterized in cell lines. We further evaluated the effects of HOXD10 and its targets on chemoresistance in our established resistant cell lines and clinical cohort (n = 66). HOXD10 was found frequently methylated in colorectal cancer, and its hypermethylation correlates with its low expression level, advanced disease, and lymph node metastasis. Functionally, HOXD10 acts as a tumor suppressor gene, in which HOXD10 -expressing cells showed suppressed cell proliferation, colony formation ability, and migration and invasion capacity. Mechanistically, DNMT1, DNMT3B, and MeCP2 were recruited in the HOXD10 promoter, and demethylation by 5-Aza-2′-deoxycytidine (5-Aza-CdR) treatment or MeCP2 knockdown can sufficiently induce HOXD10 expression. HOXD10 regulates the expressions of miR-7 and IGFBP3 in a promoter-dependent manner. Restoration of the expression of HOXD10 in 5-fluorouracil (5-FU)-resistant cells significantly upregulates the expressions of miR-7 and IGFBP3 and enhances chemosensitivity to 5-FU. In conclusion, we provide novel evidence that HOXD10 is frequently methylated, silenced, and contributes to the development of colorectal cancers. Restoration of HOXD10 activates the expressions of miR-7 and IGFBP3 and results in an inhibited phenotype biologically, suggesting its potential therapeutic relevance in colorectal cancer (CRC). [ABSTRACT FROM AUTHOR]

Background: Anaplastic diffuse large B-cell lymphoma(A-DLBCL) is a rare morphological subtype characterized by the presence of polygonal, bizarre-shaped tumor cells. Our previous research found that A-DLBCL displays many genetic alterations and biological features that differ greatly from those of ordinary DLBCL. However, the status of tumor immune microenvironment components and checkpoint molecules in A-DLBCL remains unclear. Methods: Thirty A-DLBCL patients were enrolled to study tumor immune microenvironment components and checkpoint molecules and their associations with clinicopathological features and prognosis. Results: Patients with A-DLBCL presented higher expression of PD-L1 (40% vs 10%, P=0.004) than patients with ordinary DLBCL. FISH analysis showed that extra copies of PD-L1 were more frequent in A-DLBCL cases than in ordinary DLBCL cases (23.3% vs 4.0%, P=0.001). The numbers of PD-1+ TILs (tumor infiltrating lymphocytes) and CD8+T cells were significantly lower in A-DLBCL versus ordinary DLBCL. In contrast, the numbers of GATA3+ Th2 cells, FOXP3+ Tregs and CD33+ myeloid-derived suppressor cells (MDSCs) were significantly higher in A-DLBCL than in ordinary DLBCL. The associations between clinicopathological features and tumor immune microenvironment cell frequency were analyzed in A-DLBCL patients. Briefly, the number of PD-1+ TILs was lower and the number of CD33+ MDSCs was higher in patients with mutated TP53 compared to those with wild-type TP53. The number of FOXP3+ Tregs was much lower in patients with a noncomplete response (CR) to chemotherapy than in those with a complete response. The number of CD8+ T cells showed a decreasing trend in patients with high International Prognostic Index (IPI) scores and in those with concurrent MYC and BCL2 and/or BCL6 abnormalities. Univariate survival analysis showed that patients with PD-L1+, mPD-L1+(PD-L1+ nonmalignant stromal cells) or mPD-L1+ status had a significantly poorer overall survival (OS) than those with PD-L1- status. An increase in the number of CD3+ T cells, FOXP3+ Treg cells and T-bet+ Th1 cells was significantly associated with prolonged OS in patients with A-DLBCL. Conclusion: Our study suggests that A-DLBCL displays a distinct pattern of tumor immune microenvironment components and checkpoint molecules that distinguish it from ordinary DLBCL. The analysis of tumor immune microenvironment components and checkpoint molecules could help in predicting the prognosis of A-DLBCL patients and determining therapeutic strategies targeting the tumor immune microenvironment. [ABSTRACT FROM AUTHOR]

Primary gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common gastrointestinal lymphoma, but its genetic features are poorly understood. We performed whole-exome sequencing of 25 primary tumor samples from patients with GI-DLBCL and 23 matched normal tissue samples. Oncogenic mutations were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. Twenty-five patients with GI-DLBCL were enrolled in the genetic mutation analysis with a median of 184 (range 79–382) protein-altering variants per patient. We identified recurrent oncogenic mutations in GI-DLBCL, including those in TP53, MUC16, B2M, CCND3, HIST1H1C, NEB , and ID3. Compared with nodal DLBCL, GI-DLBCL exhibited an increased mutation frequency of TP53 and reduced mutation frequencies of PIM1, CREBBP, BCL2, KMT2D , and EZH2. Moreover, GI-DLBCL exhibited fewer MYD88 and CD79B mutations than DLBCL in the testis and central nervous system. GI-DLBCLs with HLA-B, MEF2A, RHOA , and NAV3 mutations exhibited a tendency toward a high proliferation index. MUC16 and ETV6 mutations often occurred in tumors with early clinical staging. Our data provide a comprehensive understanding of the landscape of mutations in a small subset of GI-DLBCLs. The genetic mutation profiles of GI-DLBCL differ from those of nodal DLBCL and DLBCL in immune-privileged sites. The different mutated genes are related to the NF-κB and JAK-STAT pathways, and the different pathogenetic mechanisms leading to the development of DLBCL may be influenced by the tissue microenvironment. Differences in genetic alterations might influence the clinicopathological characteristics of GI-DLBCL. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) is one of the most common types of malignancies, and radiochemotherapy (RCT) followed by surgery is the recommended approach for CRC treatment. However, some cases do not respond to first-line conventional chemotherapy or even progress further after treatment. Moreover, there is a risk of severe side effects, such as radiodermatitis. Therefore, identifying predictors for RCT sensitivity is an essential step toward predicting and eventually overcoming resistance. Materials and Methods: We used integrative bioinformatics analysis and experimental validation to show that regenerating family member 4 (REG4) may be a potential biomarker for RCT sensitivity in CRC. Results: REG4, whose expression is upregulated in some CRC tissues and downregulated in RCT-sensitive CRC cells, was identified as a potential genetic marker for RCT sensitivity in CRC. Immunohistochemistry-based tissue microarray of human CRC was used to experimentally validate REG4 data obtained from the bioinformatics analysis. Conclusion: Collectively, these results indicate that REG4 may be a potential biomarker for RCT sensitivity in CRC. [ABSTRACT FROM AUTHOR]

In the present paper, we introduce our experience with the novel method during laparoscopic anterior resection of upper rectal or sigmoid colon cancer by transrectal natural orifice specimen extraction (NOSE). A prospective randomized controlled trial was performed from June 2016 to May 2019. Patients with upper rectal or sigmoid colon cancer were randomized in a 1:1 ratio to the NOSE group and the non-NOSE group. Preoperative and postoperative clinical variables were analyzed and compared between groups. Postoperative pain was analyzed utilizing a visual analog scale. Postoperative overall survival was analyzed using a Kaplan–Meier curve. A total of 276 patients were enrolled, of whom 254 were randomly divided into the NOSE group (n = 122) and the conventional laparoscopic group (n = 119). NOSE failed in 22 cases, which were converted to transabdominal specimen extraction. Intention-to-treat analysis was performed, and these 22 cases were included in the NOSE group. The incidence of postoperative complications was significantly lower in the NOSE group (11/122, 9%) than in the non-NOSE group (25/119, 21%). The NOSE group had a longer operation time, less blood loss, and a lower postoperative visual analog scale score than the non-NOSE group. The time for intestinal function recovery (ventilation) and the length of hospital stay were significantly longer in the non-NOSE group. The Kaplan–Meier survival curve showed no statistically significant difference in the disease-free survival rate between the NOSE group and the non-NOSE group. The novel NOSE method is safe and feasible to use in patients having colorectal cancer. Compared with traditional laparoscopic surgery, the postoperative complication rates of NOSE surgery were lower with an improved short-term clinical recovery. [ABSTRACT FROM AUTHOR]

A variety of 0–20 mol% of molybdenum ions (Mo3+)-doped sodium rare-earth (RE) fluoride upconversion nanowires (UCNW) were prepared by Coprecipitate–Solvothermal Ion-Exchange (CSIE) method. In this study, the Mo3+-doped rare-earth hydroxide [REMo(OH)3] precursors were synthesized by the coprecipitation–solvothermal method. Following, the hexagonal phase of the Mo3+-doped sodium rare-earth fluoride (β-NaGdF4: Yb3+/Tm3+/Mo3+, abbreviated as NaREMoF4) nanowires were successfully prepared by ion-exchange reaction, and checked by XRD data analysis. As shown in the EDS results, Mo3+ was uniformly distributed in the β-NaREMoF4. The controlled diameter (20–50 nm) and aspect ratio (20–500) values of β-NaGdF4: Yb3+/Tm3+/Mo3+ nanowires strongly depend on the amount of Mo doping according to TEM images. The upconversion luminescence intensity (UC) of 10 mol% Mo3+-doped β-NaREMoF4 nanowires was increased by one order of magnitude under the 980 nm near-infrared (NIR) excitation in regard to the undoped sample. One-dimensional (1D) upconversion nanowires (UCNW) with 10 mol% Mo3+ doping gives the upconversion polyurethane (UCPU) excellent luminescent performance and about 99% of enhanced tensile strength. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide. As a high-risk factor for CRC, ulcerative colitis (UC) has been demonstrated to lead to epithelial dysplasia, DNA damage, and eventually cancer. There are approximately 18% of patients with UC may develop CRC. Patients and methods: The gene expression profiles were retrieved from the Gene Expression Omnibus. The Database for Annotation, Visualization and Integrated Discovery was employed to conduct gene annotations. Protein-protein interaction network was constructed by the Search Tool for the Retrieval of Interacting Genes, and further analysed by the Molecular Complex Detection. The correlation between TIMP1 and prognosis was evaluated by the Gene Expression Profiling Interactive Analysis. To predict the potential functions of TIMP1, the GeneMANIA, Coremine, and FunRich were employed. After transfection with small interfering RNA targeting TIMP1, cell proliferation, migration, and apoptosis were determined by CCK-8, scratch wound, and Annexin V-FITC/PI assays, respectively. Results: TIMP1, consistently overexpressed in the initiation and progression of UC-associated CRC (ucaCRC), was identified to be a potential biomarker for the prognosis of patients with CRC. Experimental results showed knockdown of TIMP1 could increase the migration, while did not affect the proliferation and apoptosis of RKO cells. The role of TIMP1 in the malignant transformation of ucaCRC was confirmed by using the protein/gene interactions and biological process annotation and validated by analysing the transcription factors targeting TIMP1. Conclusion: TIMP1 is consistently upregulated in the pathological process of ucaCRC and can be a potential biomarker for the worse prognosis of CRC. [ABSTRACT FROM AUTHOR]

Burkitt lymphoma (BL), which is characterized by high invasiveness, is a subgroup of non-Hodgkin lymphoma. Although BL is regarded as a highly curable disease, especially for children, some patients unfortunately still do not respond adequately. The understanding of the etiology and molecular mechanisms of BL is still limited, and targeted therapies are still lacking. Here, we found that T-LAK cell-derived protein kinase (TOPK) and phosphorylated Janus kinase 2 (p-JAK2) are highly expressed in the tissues of BL patients. We report that TOPK directly binds to and is phosphorylated at Tyr74 by JAK2. Histone H3, one of the downstream targets of TOPK, is also phosphorylated in vivo and in vitro. Furthermore, we report that the phosphorylation of TOPK at Tyr74 by JAK2 plays a vital role in the proliferation of BL cells and promotes BL tumorigenesis in vivo. Phosphorylation of TOPK at Tyr74 by JAK2 enhances the stability of TOPK. Collectively, our results suggest that the JAK2/TOPK/histone H3 axis plays a key role in the proliferation of BL cells and BL tumorigenesis in vivo. [ABSTRACT FROM AUTHOR]

Aims: To explore the feasibility of sleeve gastrectomy (SG) as a treatment for polycystic ovary syndrome (PCOS) and its potential to improve clinical efficacy in PCOS patients with symptoms of oligomenorrhea. Patients and Methods: Twenty-four obese patients with PCOS underwent laparoscopic SG. Simultaneously, 24 obese patients with PCOS received lifestyle modification therapy (LMT). Follow-ups were conducted at 3-6 months. Weight loss, menstruation, and improvements in hirsutism and metabolic symptoms were compared. Results: In the SG group, 20 patients were restored to normal menstrual cycles and ovulation at 3-6 months after surgery. Their average androgen levels decreased significantly following surgery ( P=.012). Conversely, only 6 patients in the LMT group were restored to normal menstrual cycles and ovulation after receiving 3 months of treatment. Their average preoperative and postoperative androgen levels showed a nonstatistically significant decrease ( P>.05). Compared with the LMT group, the SG group showed more pronounced improvements in menstruation. Additionally, body mass and body mass index were significantly reduced in patients in the SG group 3 months after the surgeries, with maximum weight loss observed at approximately 6 months after surgery. Patients who received LMT showed a gradual weight reduction such that body mass decreased significantly after 3 months ( P<. 001). Compared with patients in the LMT group, patients in the SG group showed greater weight loss results ( P<.0001). Conclusions: In patients with PCOS, SG resulted in more marked weight loss and better improvements in clinical symptoms compared with LMT. [ABSTRACT FROM AUTHOR]

Guanyu Cai, Qingyun Xiong and Bruno Viana agree with this retraction. Reference 1 Cai G, Xiong J. Enhanced luminescence of Mo3+-doped -NaREF4 (RM = Gd3+, Yb3+, Tm3+) nanowires synthesized by coprecipitation-solvothermal ion-exchange. Retraction Note to: Enhanced luminescence of Mo3+-doped -NaREF4 nanowires prepared via coprecipitation-solvothermal ion-exchange method and their application in upconversion polyurethane composite. [Extracted from the article]

This research focuses on exploring RSK4 protein expression within Clear Cell Renal Cell Carcinoma (ccRCC), based on these investigations on level of expressions coupled with the relevance to clinicopathologic features and clinical outcomes. The expression of RSK4 in 48 ccRCC and 20 hydronephrosis samples were under the detection of immunohistochemistry; besides, its relevance to the combination of clinicopathologic features with prognosis was committed in virtue of statistical approaches. The 48 ccRCC samples included 36 (75%, 36/48) positive for RSK4, while the positive rate in hydronephrosis samples were 5 (25%, 5/20). Statistical analysis showed that RSK4 in ccRCC samples express higher expression the hydronephrosis samples (P < 0.05). Furthermore, the expression of RSK4 in ccRCC samples weren't correlated with ages and genders (P > 0.05), while WHO/ISUP nucleolar grade harboured relevance to low survival rate (P = 0.018). Molecular researches demonstrated that over-expression of RSK4 was able to upgrade the proliferation capability of ccRCC cell lines. According to the expression pattern and molecular systems featured RSK4 in ccRCCs, it performed the function of a latent independent prognostic factor performing the function of a newly built latent therapeutic aim oriented with the patients undergoing RCC. Moreover, the specific mechanism of action is expected to be revealed in the future research. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is a multifactorial disease and the sixth leading cause of death from cancer worldwide. Patients with ESCC usually have a short survival period due to the late stage at diagnosis. Incidence rates of ESCC remain high among the elderly. With recent advances, it has been demonstrated that ESCC tumors display a unique genetic profile. This study aimed to examine the possible function of OTX1 in ESCC. We collected paraffin-embedded tumor tissues from 107 patients originally diagnosed with ESCC at Xijing Hospital and fresh-harvested and paired adjacent normal esophageal tissues from 15 ESCC patients undergoing curative resection. The expression level of OTX1 was evaluated through immunohistochemistry and western blot. Prognostic and survival analyses were conducted using univariate/multivariate analysis and log-rank analysis with SPSS 23.0. Cell models and xenograft models were used to examine the overexpression of OTX1 in vivo and in vitro. OTX1 was overexpressed in ESCC tissues compared with normal esophageal tissues. Both the mRNA expression level and protein level of OTX1 were higher than they were in paired normal tissue. Prognostic and OS analyses showed that the OTX1 expression level was an individual prognostic factor in ESCC patients. Cell viability was significantly promoted when OTX1 was overexpressed in ESCC cell, Furthermore, downregulating OTX1 in EC109 cell significantly attenuated the cell proliferation migration and invasion. Flow cytometric detection showed that cells overexpressing OTX1 were predominantly in the S and G2&M phases. In the xenograft model, both tumor size and weight in the OTX1 overexpression group were significantly larger than those in the control group. OTX1 is an independent prognostic factor of ESCC and contributes to tumorigenesis both in vivo and in vitro. [ABSTRACT FROM AUTHOR]

RSK4 refers to one Ser/Thr protein kinase functioning downstream pertaining to the signaling channel of protein kinase (MAPK) stimulated by Ras/mitogen. RSK4 can regulate numerous substrates impacting cells' surviving state, growing processes and proliferating process. Thus, dysregulated RSK4 active state display a relationship to several carcinoma categories, covering breast carcinoma, esophageal squamous cell carcinoma, glioma, colorectal carcinoma, lung carcinoma, ovarian carcinoma, leukemia, endometrial carcinoma, and kidney carcinoma. Whether RSK4 is a tumor suppressor gene or one oncogene remains controversial. No specific inhibiting elements for RSK4 have been found. This review briefs the existing information regarding RSK4 activating process, the function and mechanism of RSK4 in different tumors, and the research progress and limitations of existing RSK inhibitors. RSK4 may be a potential target of molecular therapy medicine in the future. [ABSTRACT FROM AUTHOR]

Primary biliary cholangitis (PBC) is characterized by nonsuppurative destructive cholangitis and is thought to be an autoimmune disorder. Currently, ursodeoxycholic acid (UDCA) is the only FDA approved first-line therapy for PBC, but up to nearly one-third of patients do not achieve a complete response to this treatment. Adaptive immune cells, including T cells and B cells, have been found in the portal tracts and the bile duct epithelium and play a role in the pathogenesis of PBC, but the importance of these cells for evaluating the therapeutic response to UDCA in PBC has not yet been studied. In this study, we collected liver puncture biopsy specimens from 34 matched patients with PBC before and after UDCA treatment and investigated the relationship between the infiltration of adaptive immune cells and the treatment response to UDCA. The extent of immune cell infiltration was determined by immunohistochemical analysis. Responses were defined based on Paris-I criteria. After 1 year of treatment, 25/34 patients responded to UDCA treatment according to Paris-I criteria (responders), and 9/34 patients were nonresponders. Immunohistochemical analysis showed that UDCA responders exhibited significantly less CD4+ T cell infiltration after UDCA treatment than before (50.4 ± 7.5/HPF vs 30.0 ± 7.9/HPF, P = 0.002). In contrast, UDCA nonresponders exhibited significantly more CD4+ T cell infiltration after UDCA treatment than before (32.2 ± 8.0/HPF vs 75.0 ± 13.9/HPF, P = 0.045). Moreover, patients who exhibited a reduction in CD4+ T cell infiltration after UDCA treatment had a higher response rate than those that exhibited an increase in CD4+ T cell infiltration (85.7 % vs 53.8 %, P = 0.041). However, CD3+ T cell, CD8+ T cell, and CD20+ B cell infiltration was not significantly different before and after treatment in either UDCA responders or nonresponders. Furthermore, we found that the number of infiltrating T-bet+ Th1 cells was much lower after UDCA treatment than before in responders (10.5 ± 5.7/HPF vs. 5.16 ± 4.0/HPF, P = 0.0214) but much higher in nonresponders after treatment than before (1.89±1.2/HPF vs. 12.3±5.4/HPF, P = 0.043). However, there was no difference in the extent of GATA3+ Th2 or FOXP3+ Treg infiltration before and after treatment in either UDCA responders or nonresponders. Collectively, our results suggest that a decrease in the number of liver-infiltrating CD4+ Th1 cells is associated with a good response of PBC patients to UDCA treatment. Immunohistochemical analysis of CD4 and T-bet in PBC liver specimens may be a potential approach for evaluating the therapeutic response to UDCA. [ABSTRACT FROM AUTHOR]

• The amino acid position 200 in HA1 of H9N2 AIVs is a newly identified multi-functional site. • The D200N substitution of HA1 changed antigenicity of H9N2 AIVs. • D200N increased the HA cleavage efficiency and reduced acid and thermal stability of HA protein. • Residue 200N increased the replication of H9N2 viruses in both chicken embryo fibroblast cells and chicken embryonated eggs. Influenza virus hemagglutinin (HA) plays an important role in viral antigenicity, replication and host range. However, few amino acid positions in HA were reported to play multiple functions in both viral antigenicity and replication. In the present study, through analyzing the amino acid sequences of H9N2 avian influenza viruses (AIVs) isolated from China, we identified a multi-functional substitution of D200N in HA1 protein. Firstly, the substitution of D200N changed the antigenicity of H9N2 AIVs. Secondly, the D200N increased the HA cleavage efficiency and reduced acid and thermal stability of HA protein, which triggered viral-endosomal membrane fusion whereby promoted the release of viral genome into the host cytoplasm. Finally, residue 200-N increased the replication of H9N2 viruses in both chicken embryo fibroblast (CEF) cells and chicken embryonated eggs. In summary, the D200N substitution is a newly identified antigenicity and replication determinant of H9N2 AIVs, which should be paid more attention during surveillance. [ABSTRACT FROM AUTHOR]

Triple-negative breast carcinoma (TNBC) is a subtype of breast carcinoma defined by negativity for estrogen receptor (ER) or progesterone receptor (PR) by immunohistochemical analysis and negativity for human epidermal growth factor receptor (Her2) by immunohistochemistry or in situ hybridization. TNBC is clinically marked by its high aggressiveness, particularly poor outcomes including a low survival rate, and the lack of specific and effective treatments. Therefore, new potential targets for the treatment of TNBC must be identified. This review summarizes recent evidence supporting novel targets and possible therapeutic regimens in the treatment of TNBC. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to evaluate changes in nutritional status as measured by the prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI) scores, and their abilities to predict clinical prognosis in patients with pacemaker implantation (PMI)., Methods: A total of 595 patients who underwent permanent PMI from January 2011 to December 2020 were included. PNI and GNRI scores were separately calculated at the beginning day of PMI operation and at the end of 12-month follow-up, and their net changes (Δ) were calculated by PNI or GNRI scores at follow-up minus the corresponding scores on admission. The cohort patients were divided into low risk of malnutritional status (ΔPNI or ΔGNRI scores ≥ 0) and high risk of malnutritional status (ΔPNI or ΔGNRI scores < 0) groups. Primary outcome measure was a composite major adverse cardiovascular event (MCE), defined as heart failure hospitalization (HFH), myocardial infarction (MI), stroke, or death from any cause, presented as hazard ratios (HR) with 95% confidence intervals (CI) calculated by MCE in the crude or multivariate-adjusted Cox Proportional Hazards models. Receiver operating characteristic (ROC) curve analysis was used to compare the differential ability to predict incident MCEs betweenΔPNI andΔGNRI scores., Results: In total, 16% of patients developed the MCE during the follow-up. The cumulative event rates determined by Kaplan-Meier analysis were significantly higher in the high risk of malnutritional patients compared to the low risk of malnutritional patients ( P < 0.05). Adjusted multivariate analysis showed that decreased PNI scores (HR: 2.228, 95% CI: 1.482-3.350) and decreased GNRI scores (HR: 2.178, 95% CI: 1.439-3.295) were independently associated with favorable outcomes. ROC curve analysis revealed an area under curve (AUC) of 0.586 forΔPNI scores and AUC of 0.592 for ΔGNRI scores, but their predictive abilities were not statistically different., Conclusion: Either positive change of PNI or GNRI scores were associated with reduced risk of MCEs in patients with PMI, and they have similar ability to predict clinical cardiometabolic risk. Additional enhancing nutritional status during follow-up may help to prevent unfavorable prognosis in clinical practices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Lian, Chen, Wang, Chen and Hu.)

Pancreatic ductal adenocarcinoma (PDAC) is one of most lethal cancers and is projected to be the second leading cause of cancer deaths in the United States by 2030. The lack of effective treatment and increased incidence in PDAC encourage a deeper knowledge of PDAC progression. By analyzing a long noncoding RNA (lncRNA) dataset, we found that increased LINC00941 expression led to poor outcomes in PDAC patients. Furthermore, in vitro and in vivo experiments revealed that LINC00941 promoted PDAC cancer cell growth by enhancing aerobic glycolysis. Mechanistically, LINC00941 was found to interact with mammalian STE20-like protein kinase 1 (MST1), which facilitated the protein phosphatase 2A (PP2A)-mediated dephosphorylation of MST1, resulting in Hippo pathway activation and consequently, enhanced glycolysis in PDAC. These results suggest that LINC00941 plays a key role in regulating PDAC tumorigenesis, potentially highlighting novel avenues for PDAC therapy., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Melatonin, which is synthesized by the pineal gland and released into the blood, exhibits antitumor properties. However, the mechanisms underlying these effects, particularly in stomach cancer, remain unknown. In the present study, the effect of melatonin on the nuclear factor (NF)-κB signaling pathway and the mitogen-activated protein kinase signaling pathway, involving p38 and c-Jun-N-terminal kinase (JNK), were investigated in SGC7901 gastric cancer cells. In addition, the effect of melatonin on the survival, migration and apoptosis of these cells was investigated in vitro in order to evaluate the use of melatonin for the treatment of gastric cancer. The results of the present study revealed that melatonin decreased the viability and migration of SGC7901 cells. Furthermore, melatonin induced apoptosis. Melatonin was identified to elevate the expression levels of phosphorylated (p)-p38 and p-JNK protein, and decrease the expression level of nucleic p-p65. These results suggest that the protein levels of p65, p38 and JNK are associated with the survival of SGC7901 cells following treatment with melatonin. The optimal concentration of melatonin was demonstrated to be 2 mM, which significantly induced apoptosis following a 24 h treatment period. These findings suggest that conflicting growth signals in cells may inhibit the efficacy of melatonin in the treatment of gastric cancer. Therefore, adjunct therapy would be required to improve the efficacy of melatonin in the treatment of cancer.

Background: The aim of this study was to investigate and interpret the expression level and potential function of TCEA3 in gastric cancer., Material and Methods: qRT-PCR was used to determine the expression level of TCEA3 in gastric cancer tissues. Pearson χ2 test was performed to clarify the correlation between TCEA3 expression and patients' clinicopathologic characteristics. Biological function of TCEA3 was tested by proliferation assay and colony formation assay. Flow cytometry was used to study the potential function of TCEA3 in apoptosis induction., Results: TCEA3 expression was significantly downregulated in gastric cancer tissues compared with paired normal tissues. Poor prognoses were observed in the low TCEA3 expression group of patients in contrast to the high TCEA3 expression group. Functionally, upregulation of TCEA3 inhibited gastric cancer cell proliferation and colony formation. We also found that TCEA3 may attenuate cell growth through apoptosis induction., Conclusions: Our findings suggest that TCEA3 attenuates the proliferation and induces apoptosis of gastric cancer cells.

Aim: To study the impact of sleeve gastrectomy plus side-to-side jejunoileal anastomosis on weight loss and the remission of type 2 diabetes mellitus., Methods: Thirty-three 7 weeks old male Zucker diabetic fatty rats were randomized into three groups: sleeve gastrectomy plus side-to-side jejunoileal anastomosis (JI-SG group), sleeve gastrectomy (SG group), sham surgery (Control group)., Results: The weight of rats in JI-SG group and SG group was significantly lower than control group at 2 weeks postoperatively, and body weight in JI-SG group was lower than SG group since 4 week postoperatively. The blood Glucose was significantly improved for both JI-SG group and SG group, and increased in Control group at 2 weeks after surgery. The serum ghrelin level of rats in JI-SG, SG group was significantly decreased, but without difference between two groups; compared with that preoperatively, the GLP-1 level of rats in JI-SG group was significantly higher at 12 weeks postoperatively; SG group and SO group had no difference in the GLP-1. The serum insulin level in rats was also decreased in JI-SG group and SG group at 6 weeks postoperatively, and plasma insulin level in JI-SG group was significantly lower than those in the SG group at 12 weeks postoperatively., Conclusions: JI-SG is superior to SG as the treatment of type 2 diabetes mellitus and weight control in obese diabetic rodents.