Effect of 3-Dimensional Imaging Device on Polyp and Adenoma Detection During Colonoscopy: A Randomized Controlled Trial.

INTRODUCTION: To evaluate the effect of 3-dimensional (3D) imaging device on polyp and adenoma detection during colonoscopy. METHODS: In a single-blind, randomized controlled trial, participants aged 18-70 years who underwent diagnostic or screening colonoscopy were consecutively enrolled between August 2019 and May 2022. Each participant was randomized in a 1:1 ratio to undergo either 2-dimensional (2D-3D) colonoscopy or 3D-2D colonoscopy through computer-generated random numbers. Primary outcome included polyp detection rate (PDR) and adenoma detection rate (ADR), defined as the proportion of individuals with at least 1 polyp or adenoma detected during colonoscopy. The primary analysis was intention-to-treat. RESULTS: Of 1,196 participants recruited, 571 in 2D-3D group and 583 in 3D-2D group were finally included after excluding those who met the exclusion criteria. The PDR between 2D and 3D groups was separately 39.6% and 40.5% during phase 1 (odds ratio [OR] = 0.96, 95% confidence interval [CI]: 0.76-1.22, P = 0.801), whereas PDR was significantly higher in 3D group (27.7%) than that of 2D group (19.9%) during phase 2, with a 1.54-fold increase (1.17-2.02, P = 0.002). Similarly, the ADR during phase 1 between 2D (24.7%) and 3D (23.8%) groups was not significant (OR = 1.05, 0.80-1.37, P = 0.788), while ADR was significantly higher in 3D group (13.8%) than that of 2D group (9.9%) during phase 2, with a 1.45-fold increase (1.01-2.08, P = 0.041). Further subgroup analysis confirmed significantly higher PDR and ADR of 3D group during phase 2, particularly in midlevel and junior endoscopists. DISCUSSION: The 3D imaging device could improve overall PDR and ADR during colonoscopy, particularly in midlevel and junior endoscopists. Trial number: ChiCTR1900025000.

Tet2-mediated DNA demethylation regulates the proliferation and apoptosis of human leukemia K562 cells.

TET2 is a member of the TET protein family which is responsible for active DNA demethylation through catalyzing the successive oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), and mutations of Tet2 frequently lead to hematological malignancies. However, the relationship between Tet2-mediated demethylation and hematological malignancies is unclear. The human leukemia K562 cell line is an immortalized leukemia line that serves as an in vitro model of erythroleukemia. In this study, we investigated the effect of Tet2-mediated demethylation on the apoptosis and proliferation of human leukemia K562 cells and found that knockdown of Tet2 promoted and inhibited K562 cell proliferation and apoptosis, respectively, while upregulation of TET2 enzymatic activity via alpha-ketoglutaric acid (α-KG) had the opposite effects. Therefore, the Tet2 gene acts as a potential target for the treatment of leukemia, and small molecules that target the Tet2 gene may be used to screen antitumor drugs for hematological malignancies.

Multimorbidity in patients with monoclonal gammopathy of undetermined significance.

Monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma, is present in over 5% of adults aged 70 and older, a population with a high prevalence of multimorbidity. MGUS is often diagnosed incidentally when patients seek care for unrelated conditions. Our study sought to examine patterns of multimorbidity among MGUS patients, as overall health may impact patient care and the prioritization of MGUS surveillance. We examined patterns of comorbidities in 429 patients diagnosed with MGUS (2007-2015) and 1287 matched controls. Twenty-seven conditions were defined at diagnosis/index date using algorithms developed by the Centers for Medicare and Medicaid Chronic Conditions Warehouse. Patterns of common comorbidities were identified individually, in dyads and triads, and compared between MGUS cases and controls. We conducted a latent class analysis to identify comorbidity patterns among cases only. We also examined comorbidity patterns among a subset of 32 MGUS cases who progressed to cancer during the study period. The most common comorbidities among both MGUS cases and controls included hypertension and hyperlipidemia. Anemia (cases: 43%; controls: 16%) and chronic kidney disease (CKD; cases: 36%; controls: 18%), and dyads and triads containing those conditions, were more common among cases. Latent class analysis identified three classes of comorbidity among MGUS cases: hypertension-hyperlipidemia plus anemia and CKD (31%); low comorbidity burden (17%); and hypertension-hyperlipidemia alone (52%). The higher prevalence among cases of anemia and CKD, which may be involved in the pathogenesis of, or surveillance for, MGUS, warrants additional investigation.

Weight Loss in Newly Admitted Nursing Home Residents With Obesity.

BACKGROUND: The prevalence of obesity (body mass index ≥ 30) among nursing home residents has been increasing, but there has been little research on weight change in this population. We examined resident characteristics associated with substantial weight loss among nursing home residents with obesity. METHODS: Using data from the Minimum Data Set 3.0, this retrospective study included long-stay nursing home residents with obesity newly admitted to a facility in 2014 who had annual assessments in 2015. Substantial weight loss was defined as a loss of ≥10% body weight within a year. Multivariate regression analyses were conducted to identify factors associated with weight loss, including demographic characteristics, medical conditions, and functional limitations in activities of daily living (ADL). RESULTS: Among 59782 newly admitted nursing home residents with obesity, 23% experienced substantial weight loss during their first year in the nursing home. Moderate ADL dependency (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.31-1.53), severe ADL dependency (OR = 1.83; 95% CI: 1.67-1.99), severe mobility impairment (OR = 1.15; 95% CI: 1.04-1.23), and severe cognitive impairment (OR = 1.13; 95% CI: 1.07-1.19), as well as cancer (OR = 1.10; 95% CI: 1.01-1.20), heart failure (OR = 1.06; 95% CI: 1.01-1.11), end-stage renal disease (OR = 1.17; 95% CI: 1.11-1.23), and bowel incontinence (OR = 1.19; 95% CI: 1.14-1.25) were associated with weight loss. CONCLUSION: Substantial weight loss is common among nursing home residents with obesity over a 1-year period following admission, and these residents have a greater burden of functional and cognitive impairment and specific medical conditions. These findings suggest the need to further elucidate the clinical implications of weight loss among this population.

RNF219 Promotes Nasopharyngeal Carcinoma Progression by Activating the NF-κB Pathway.

In Southeast Asia, the prevalence of nasopharyngeal carcinoma (NPC) is high; however, the molecular mechanism governing the progression of NPC is unclear. The results of the present study revealed upregulation of ring finger protein 219 (RNF219) expression in NPC tissues and cells. Overexpression of RNF219 enhanced NPC cell invasion, migration, and proliferation; whereas knockdown of RNF219 had the opposite effects. Mechanistically, RNF219 activated the nuclear factor kappa B (NF-κB) pathway, mainly reflected by increased p65 nuclear translocation, and increased NF-κB pathway target gene expression. NF-κB pathway inhibition in cells overexpressing RNF219 resulted in reduced invasion, migration, and proliferation, confirming that progression of NPC was promoted by RNF219-mediated NF-κB pathway activation. In addition, the expression of RNF219 correlated positively with the activity of the NF-κB pathway, verifying that RNF219 regulates the activity of the NF-κB pathway in the clinical setting. Our results identified a novel therapeutic target that could promote the development of novel treatments for NPC.

Differences in Hospital, Emergency Room and Outpatient Visits Among Adults With and Without Monoclonal Gammopathy of Undetermined Significance.

INTRODUCTION: This study evaluated the impact of receiving a monoclonal gammopathy of undetermined significance (MGUS) diagnosis on healthcare utilization from patients at a community-based multispecialty provider organization. METHODS: A cohort of patients with MGUS (n = 429) were matched on sex, age, and length of enrollment to a cohort of patients without MGUS (n = 1286). Healthcare utilization was assessed: 1-12 months before, 1 month before and after, and 1-12 months after diagnosis/index date. Multivariable conditional Poisson models compared change in utilization of each service in patients with and without MGUS. RESULTS: During the 2 months around diagnosis/index date, the rates of emergency room, hospital and outpatient visits were higher for patients with MGUS than patients without MGUS. In the year before MGUS diagnosis, the association was still elevated, although attenuated. CONCLUSION: Understanding the care of MGUS patients is important given that multiple myeloma patients with a pre-existing MGUS diagnosis may have a better prognosis.

Occupational health risk assessment of the benzene exposure industries: a comprehensive scoring method through 4 health risk assessment models.

Benzene is one of the most common occupational hazards in the working environment which was in the list of group 1 carcinogens. This study applied four occupational health risk assessment models: EPA model; MOM model of Singapore; the International Council on Mining and Metals (ICMM) model, and the Technical guide WS/T 777-2021 of China. The models assessed both non-carcinogenic and carcinogenic effects of benzene for 1629 employees in 50 factories in Jiangsu Province (China) who were exposed to benzene in the working environment and analysis the risk between industries by principal component analysis (PCA) method. The highest occupational health hazard of benzene among the five industries is petroleum processing industry, then followed by chemical products manufacturing industry, special equipment manufacturing industry, wood processing and products industry, and at last the pharmaceutical manufacturing industry. The population of abnormal routine blood parameters in the subjects was mostly in the "wood products industry" group, and the concentration of benzene in "wood products industry" group is the lowest in 5 groups. The industries with low exposure concentration have higher blood abnormality rates; this may be caused by the fact that blood damage is more secretive under low occupational health risk.

The efficacy of adding hyperthermia to the treatment of advanced NSCLC patients based on the states of EGFR.

BACKGROUND: The study aims to explore the efficacy of adding hyperthermia to the treatment of advanced NSCLC patients based on the states of epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: We included 205 advanced NSCLC patients who were received hyperthermia plus other treatment (hyperthermia group) or non- hyperthermia and other treatments (non- hyperthermia group). The OS and progression free survival (PFS) were retrospectively estimated. Using Kaplan-Meier and the log-rank test compare the OS and PFS between the groups. RESULTS: The median follow-up was 22 months. The Univariate analysis have shown that 1-year OS and PFSfirst rates in the hyperthermia group and non- hyperthermia group were 83.3% vs 71.5% (P=0.010) and 62.0% vs 42.7% (P=0.001). The subgroup analyses revealed that patients didn't have EGFR mutant who received hyperthermia had significantly higher 1 year OS and PFSfirst rates than those treated with non- hyperthermia (OS: 79.1% vs 65.2% P=0.037, PFS: 64.2% vs 36.5%, P=0.001). For patients with EGFR mutation, there was no significant difference between the two groups. The PFSfirst in first-line and PFSpost in posterior-line was no significant difference between the groups. CONCLUSIONS: This retrospective study revealed that adding hyperthermia to the treatment of NSCLC patients without EGFR mutation had better prognosis than those who did not adding hyperthermia to the regimen. Moreover, adding hyperthermia in first-line or in posterior-line treatment was no significant difference. However, these results need more prospective studies to confirm the conclusions.

Multi-trajectory models of serum biomarkers among patients with monoclonal gammopathy of undetermined significance.

Understanding the progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) is needed to identify patients who would benefit from closer clinical surveillance. Given that two of the defining criteria of MM are renal failure and anemia, we described the trajectories of creatinine (Cr) and hemoglobin (Hgb) over time in patients with a diagnosis of MGUS. Patients diagnosed with MGUS (n = 424) were identified by a previously validated case-finding algorithm using health claims and electronic health record data (2007-2015) and followed through 2018. Group-based trajectory modeling identified patients with distinct laboratory value trajectories of Cr (mg/dl) and Hgb (g/dl). Most patients were non-Hispanic White (97.6%) with a mean age of 75 years at MGUS diagnosis. Three multi-trajectory groups were identified: (1) Normal Cr/Hgb (n = 225; 53.1%)-stable serum Cr levels and decreasing, normal Hgb levels; (2) Normal Cr/lower-normal Hgb group (n = 188; 44.3%)-stable, slightly elevated levels of Cr and decreasing levels of Hgb; and (3) High Cr/borderline Hgb group (n = 11; 2.6%)-increased Cr levels and stable low levels of Hgb. Patients with MGUS in Group 2 were older than patients in other groups, and patients in group 3 had more comorbidities than participants in all other groups. Few patients developed MM during the study period. We were able to identify distinct biomarker trajectories in patients with MGUS over time. Future research should investigate how these trajectories may be related to the risk of progression to MM, including M-protein levels.

The Efficacy of Hematoporphyrin Monomethyl Ether Photodynamic Therapy in Adult Patients with Port-Wine Stains: A Retrospective Study.

INTRODUCTION: Hematoporphyrin monomethyl ether-photodynamic therapy (HMME-PDT) has been showing promising results in the treatment of port-wine stains (PWSs). We evaluated the clinical efficacy and treatment response of HMME-PDT in adult Chinese patients with PWSs. METHODS: A single-center retrospective study recruited adult PWS patients with negative HMME skin test results from December 2017 to May 2020. Patients received an intravenous injection of 5 mg/kg HMME and the lesions were exposed to 532 nm LED green light with an irradiation power density of 85-95 mW/cm2 for 20-25 min. Digital photographs were taken before and after two therapy sessions and observed by three blinded dermatologists for clinical response. RESULTS: A total of 72 patients aged between 18 and 55 years were recruited. There were 65 patients of the flat purple type, 5 of the hypertrophic type, and 2 of the nodular thickening type. Of the 65 patients, 7 showed excellent efficacy (10.77%), 13 patients indicated good efficacy (20.00%), 47 patients showed fair efficacy (64.62%), while 3 cases displayed no improvement (4.62%). All five patients of the purple and hypertrophic type showed fair efficacy (100%), and no improvement was observed in patients of the nodular thickening type (100%). Pain, pruritus, and a burning sensation were observed during treatment. Edema was noted on the treated areas post-treatment. No other obvious systemic adverse reactions were observed. CONCLUSION: HMME-PDT is an effective and safe treatment for adult patients with purple PWSs. Multiple HMME-PDT treatments can improve the response and cure rate.

NK cell-derived exosomes enhance the anti-tumor effects against ovarian cancer by delivering cisplatin and reactivating NK cell functions.

Exosomes are membranous vesicles actively secreted by almost all cells and they deliver certain intracellular molecules, including nucleic acids, proteins, and lipids, to target cells. They are also considered to be good carriers for drug delivery due to their biocompatibility, high permeability, low immunogenicity, and low toxicity. Exosomes from immune cells were also reported to have immunomodulatory activities. Herein we evaluated the application of exosomes derived from expanded natural killer cells (eNK-EXO) for the treatment of ovarian cancer (OC). We demonstrate that eNK-EXO express typical protein markers of natural killer (NK) cells, can be preferentially uptaken by SKOV3 cells, and display cytotoxicity against OC cells. Furthermore, eNK-EXO loaded with cisplatin could sensitize drug-resistant OC cells to the anti-proliferation effect of cisplatin. In addition, we show that eNK-EXO could activate NK cells from immunosuppressive tumor microenvironment, the mechanism of which is explored by transcriptional analysis. In summary, eNK-EXO exhibit anti-tumor activity against OC on its own, could be used to deliver cisplatin and enhance its cytotoxic effect against drug-resistant OC cells and also reverse the immunosuppression of NK cells, which may lead to great prospect of using eNK-EXO in the treatment of OC in the clinic. Our work also builds a strong foundation for further evaluation of eNK-EXO in other solid tumor therapies.

Characteristics of endoscopic and pathological findings of amebic colitis.

BACKGROUND: The clinical features of amoebic colitis resemble those of inflammatory bowel disease (IBD), and therefore the risk of misdiagnosis is very high. The aim of this study was to analyse the characteristics of the endoscopic and pathological findings of amebic colitis and the lessons from our patients, which were useful for diagnosing the amebic colitis timely and avoiding the serious complication. METHODS: We retrospectively reviewed data of all amebic colitis admitted to Beijing Friendship Hospital from January 2015 to January 2020. Cases were diagnosed by clinical presentation, laboratory examinations, and colonoscopy with biopsy and histological examination, no ELISA stool antigen or PCR tests were used. RESULTS: 16 patients were diagnosed with amebic colitis by the colonoscopy accompanied by biopsy and microscopic examination. At first time, 12 (75%) patients were misdiagnosed as IBD. Cecum was the most common site of amebic colitis (100%), and the caecum and rectum were also involved in many lesions (68.75%). Multiple lesions of erosion and/or ulcer were recognized in all patients (100%).The endoscopic findings included multiple irregular shaped ulcers and erosions with surrounding erythema, and the ulcers and erosions were covered by the white or yellow exudates. The intervening mucosae between the ulcers or erosions were normal. The features of rectums can be divided to 2 types: in 6 patients (54.5%), the irregular ulcer or erosions covered with white or yellow exudates were observed in rectum and cecum, and the bloody exudates in rectum were more severe than those in cecum; in other 5 patients (45.5%), rectal lesions were much less severe than those in cecum, the small superficial erosion or reddened mucosa were observed in the rectal ampulla. All patients were diagnosed as detection of amebic trophozoites from HE-stained biopsy specimens. The number of trophozoites ranged from 1/HPF to > 50/HPF. Among 16 cases, mild architectural alteration of colon crypt were observed in 10 cases (62.5%), and serious architectural alteration of colon crypt was found which had crypt branch in 1 case (16.7%). Cryptitis was observed in 12 cases (75%) and its severity was mild or moderate. No crypts abscess was observed in all cases. CONCLUSIONS: The colonoscopy with histological examination are very important to diagnose the amebic colitis. Detect the amoebic trophozoites in the exudates by histological examination is the vital. Sometimes a negative biopsy does not rule out amebiasis, repeated biopsies may be needed to make the diagnosis.

Decreased microRNA-768-3p expression indicates a poor prognosis in patients with breast cancer and promotes breast cancer cell viability, migration and invasion.

Breast cancer is the most common malignancy in women and microRNA-768-3p (miR-768-3p) is abnormally expressed in hepatocellular carcinoma, non-small cell lung carcinomas and melanoma. The aim of the present study was to evaluate the prognostic value and biological function of miR-768-3p in breast cancer. The expression of miR-768-3p in tumor tissues and adjacent tissues of 116 patients with breast cancer obtained by surgery and normal breast cell lines MCF-10A and breast cancer cell lines (MCF-7, MDA-MB-231, T-47D and SK-BR-3) were detected by reverse transcription-quantitative PCR. The association between miR-768-3p expression and the clinicopathological characteristics of patients was analyzed using the χ2 test. In addition, the Kaplan-Meier method was used for survival analysis. A Cox regression model was used to examine the effect of miR-768-3p on the prognosis of patients with breast cancer. Hemocytometer cell counting and Transwell assays were used to detect the effects of miR-768-3p on the characteristics of breast cancer cells. The target genes of miR-768-3p in breast cancer were identified by bioinformatics software and detected by luciferase reporter assay. Compared with normal tissues and normal breast cancer cells, miR-768-3p was significantly decreased in breast cancer tissues and cancer cells (P<0.001). The reduction in miR-768-3p was significantly associated with lymph node metastasis (P=0.040), Tumor Node Metastasis stage (P=0.035), and cancer subtype (P=0.008). In addition, patients with low miR-768-3p expression had a shorter overall survival time (log-rank P=0.022) compared with those with high expression and miR-768-3p may be a potential prognostic marker (hazard ratio=4.637; 95% confidence interval=1.296-16.597; P=0.018). When transfected with miR-768-3p inhibitor, cell viability, migration and invasion were significantly promoted compared with the control group (P<0.05). In addition, eukaryotic translation initiation factor 4E (eIF4E) was the target gene of miR-768-3p in breast cancer. All experiments confirmed that miR-768-3p, a tumor suppressor, inhibited the viability, migration and invasion of breast cancer cells through eIF4E. miR-768-3p may be a potential prognostic marker of breast cancer and may participate in the progression of breast cancer.

Gender differences in hematotoxicity of benzene-exposed workers, three cross-sectional studies on 218,061 subjects.

Our aim was to analyze the effects of benzene exposure on hematotoxicity in workers, with a focus on gender differences. The study was divided into three parts, and the survey included 218,061 workers. Since 2017, some workers are selected from the total workers each year to explore the possible influencing factors (age, duration of benzene exposure, TWA (8-h time-weighted average) of benzene, SPMA (S-phenylmercapturic acid), MDA (malondialdehyde), 8-OHdG (8-hydroxy-2'-deoxyguanosine) of different hematotoxicity of different genders). The abnormal rate of WBC (white blood cell), ANC (absolute neutrophil count), and platelets of female workers in the benzene exposure group was higher than that of males in the benzene exposure group and also higher than that of the female workers in the control group. Research results in 2019 showed increased SPMA as well as increases their DNA damage including 8-OHdG and MDA in benzene-exposed female workers compared to those in the control female group (all p < 0.05. SPMA, 8-OHdG, and MDA in benzene exposure female workers increased 555%, 183%, and 33.3%, respectively). Female workers are at significantly higher risk for blood system effects of benzene exposure. Therefore, more stringent standards and guidelines may be needed to protect the changing professional population, especially for females.

Design, synthesis, and biological evaluation of 2,4-diamino pyrimidine derivatives as potent FAK inhibitors with anti-cancer and anti-angiogenesis activities.

A series of 2,4-diamino pyrimidine (DAPY) derivatives were designed, synthesized, and evaluated as inhibitors of focal adhesion kinase (FAK) with antitumor and anti-angiogenesis activities. Most compounds effectively suppressed the enzymatic activities of FAK, and the IC50s of 11b and 12f were 2.75 and 1.87 nM, respectively. 11b and 12f exhibited strong antiproliferative effects against seven human cancer cells, with IC50 values against two FAK-overexpressing pancreatic cancer cells (PANC-1 and BxPC-3) of 0.98 µM, 0.55 µM, and 0.11 µM, 0.15 µM, respectively. Moreover, 11b and 12f obviously suppressed the colony formation, migration, and invasion of PANC-1 cells in a dose-dependent manner. Meanwhile, these two compounds could induce the apoptosis of PANC-1 cells and arrest the cell cycle in G2/M phase according to the flow cytometry assay. Western blot revealed that 11b and 12f effectively inhibited the FAK/PI3K/Akt signal pathway and significantly decreased the expression of cyclin D1 and Bcl-2. In addition, compounds 11b and 12f potently inhibited the antiproliferative of HUVECs and obviously altered the cell morphology. 11b and 12f also significantly inhibited the migration, tube formation of HUVECs and severely impaired the angiogenesis in the zebrafish model. Overall, these results revealed the potential of compounds 11b and 12f as promising candidates for further preclinical studies.

Genetic variants modify the associations of concentrations of methylmalonic acid, vitamin B-12, vitamin B-6, and folate with bone mineral density.

BACKGROUND: Elevated plasma homocysteine has been found to be associated with an increased risk of osteoporosis, especially hip and vertebral fractures. The plasma concentration of homocysteine is dependent on the activities of several B vitamin-dependent enzymes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and cystathionine ß-synthase (CBS). OBJECTIVES: We investigated whether genetic variants in some of the genes involved in 1 carbon metabolism modify the association of B vitamin-related measures with bone mineral density (BMD) and strength. METHODS: We measured several B vitamins and biomarkers in participants of the Framingham Offspring Study, and performed analyses of methylmalonic acid (MMA) continuously and <210 nmol/L; pyridoxal-5'-phosphate; vitamin B-12 continuously and ≥258 pmol/L; and folate. The outcomes of interest included areal and volumetric BMD, measured by DXA and quantitative computed tomography (QCT), respectively. We evaluated associations between the bone measures and interactions of single nucleotide polymorphism with a B vitamin or biomarker in Framingham participants (n = 4310 for DXA and n = 3127 for QCT). For analysis of DXA, we validated the association results in the B-PROOF cohort (n = 1072). Bonferroni-corrected locus-wide significant thresholds were defined to account for multiple testing. RESULTS: The interactions between rs2274976 and vitamin B-12 and rs34671784 and MMA <210 nmol/L were associated with lumbar spine BMD, and the interaction between rs6586281 and vitamin B-12 ≥258 pmol/L was associated with femoral neck BMD. For QCT-derived traits, 62 interactions between genetic variants and B vitamins and biomarkers were identified. CONCLUSIONS: Some genetic variants in the 1-carbon methylation pathway modify the association of B vitamin and biomarker concentrations with bone density and strength.  These interactions require further replication and functional validation for a mechanistic understanding of the role of the 1-carbon metabolism pathway on BMD and risks of fracture.

Bioinformatics and integrated analyses of prognosis-associated key genes in lung adenocarcinoma.

BACKGROUND: The objective of the present study was to predict candidate genes with prognostic information for lung adenocarcinoma (LUAD). METHODS: Weighted correlation network analysis (WGCNA) was utilized to build the co-expression network of deferentially expressed genes (DEGs) in GSE32863. Key genes were identified as the intersecting genes of the modules of WGCNA and DEGs. Kaplan-Meier plotter was employed to conduct survival analysis. Enrichment analysis was performed. The expression of key genes in LUAD was validated. Then, we performed in vitro experiments to explore functions of key genes. We overexpressed DYNLRB2 in A549 cell. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were test expression levels and functional analyses were performed, including cell viability, apoptosis. RESULTS: A total of 1,587 DEGs in GSE32863 were identified, including 649 up-regulated genes and 938 down-regulated genes. In coexpression analysis, there were 1,271 hubgenes from the modules that were chosen for further analysis. 15 key genes were identified as the intersecting genes of the modules of WGCNA and DEGs. The expressions of dynein light chain roadblock-type 2 (DYNLRB2) and mouse homolog of ß1 spectrin (SPTBN1) were lower in LUAD, and were associated with survival time of LUAD patients. GSEA results showed that high expressed DYNLRB2 and SPTBN1 were enriched in Drug metabolism cytochrome P450, Cardiac muscle contraction, Retinol metabolism. Down-regulated DYNLRB2 and SPTBN1 were associated with Homologous recombination, Progesterone mediated oocyte maturation, Base excision repair. The in vitro experiment confirmed the overexpression of DYNLRB2 in A549 transferred cells. The overexpress DYNLRB2 inhibited cell viability and induced apoptosis. CONCLUSIONS: Our study suggested that DYNLRB2 and SPTBN1 might be potential tumor suppressor genes and could serve as biomarkers for predicting the prognosis of LUAD patients.

Mesenchymal stem cell carriers enhance antitumor efficacy induced by oncolytic reovirus in acute myeloid leukemia.

Chemotherapy is the main treatment for acute myeloid leukemia (AML), but the therapeutic efficacy is modest, and most commonly manifests as relapse from remission. Thus, improving long-term AML survival is a crucial clinical challenge. In recent years, oncolytic virotherapy has provided an alternative approach for AML treatment. The use of oncolytic reoviruses has been explored in more than 30 clinical trials for safety and feasibility issues. However, like other oncolytic viruses, neutralizing antibodies (NAbs) reduce therapeutic efficacy. To tackle this problem, human umbilical cord mesenchymal stem cells (hUC-MSCs) were used to deliver reovirus using in vitro and in vivo models. Human UC-MSCs were successfully loaded with reovirus, without impairing biological function.We also observed in vitro protective effects of hUC-MSCs on reovirus in the presence of NAbs. In the immunocompromised AML mouse model, hUC-MSCs effectively carried reoviruses to tumor lesions and significantly prolonged the survival of AML xenografts in mice in the presence of a high titer anti-reovirus antibody (p = 0.001). However, reovirus-induced activation of AKT, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and NF-κB signaling led to the maintenance of intrinsic migratory properties and secretion of pro-inflammatory cytokines from hUC-MSCs, particularly CXCL10. In immuno-competent AML mice, MSCs carrying reovirus triggered immune responses, and eventually inhibited tumor growth. Therefore, these results suggest that MSCs as carriers of oncolytic reoviruses can enhance the antitumor efficacy of virotherapy.

A comprehensive bioinformatics analysis to identify a candidate prognostic biomarker for ovarian cancer.

BACKGROUND: This study aimed to investigate prognostic genes in ovarian cancer (OC) and to explore their potential underlying biological mechanisms through a comprehensive bioinformatics analysis. METHODS: Common differentially expressed genes (DEGs) in 3 OC datasets from the Gene Expression Omnibus (GEO) (GSE26712, GSE18520, and GSE14407) were screened out. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by Metascape. The protein-protein interaction (PPI) network of the DEGs was constructed using the STRING database. The prognostic value of DEGs were determined using the Kaplan-Meier plotter. The ONCOMINE and Human Protein Atlas databases were used to verify the expression levels of prognostic genes in OC. Genomic analysis of prognostic genes were also investigated by cBio Cancer Genomics Portal (cBioPortal) database, UCSC Xena browser and UALCAN. Gene set enrichment analysis (GSEA) was used to predict the possible pathways and biological processes of the prognostic genes. RESULTS: Integration of the 3 datasets have found 879 common DEGs. A high expression of structural maintenance of chromosomes protein 4 (SMC4) was revealed in the Kaplan-Meier plotter analysis to be meaningful for the prognosis of OC and was verified at both the mRNA and protein levels. The results from cBioPortal showed that SMC4 alterations accounted for 7 to 18% of genetic alterations in OC, and the majority alterations were copy number amplifications. Finally, the GSEA results showed that samples with SMC4 overexpression were mainly enriched in the cell cycle, spliceosome, ubiquitin mediated proteolysis, and adherens junctions. CONCLUSIONS: High SMC4 expression is linked with a poor prognosis in patients with OC and might serve as a prognostic biomarker for the disease.