Interleukin 35: protective role and mechanism in type 1 diabetes.

Interleukin 35 (IL-35), a cytokine secreted by regulatory T (Treg) cells from the differentiation of conventional CD4+ T cells, is a member of the IL-12 family. The IL-12 family of cytokines exhibits an anti-inflammatory property. IL-35 has recently been shown to influence the immune modulation in various diseases, including inflammatory bowel disease, Graves' disease, rheumatoid arthritis, colitis, psoriasis, and type 1 diabetes (T1D). T1D is an immune-related disease caused by destruction of pancreatic ß cells, characterized by an absolute lack of insulin. Recently, studies have suggested that protective effects of IL-35 work by improving blood glucose levels and preventing an attack of inflammatory factors on the islets. The protective mechanism may be closely related to the anti-inflammatory properties of IL-35, which include regulating macrophage phenotype, suppressing T cell proliferation, decreasing the differentiation of Th17 cells, increasing the Treg cell population, and inducing IL-35-producing regulatory T cells (iTr35). Here, we review the protective effects and mechanisms of action of IL-35 in T1D.

The role of histone chaperone spty2d1 in human colorectal cancer.

Colorectal cancer (CRC) remains a major public health concern, associated with a high rate of morbidity and mortality. Several factors have been implicated in its occurrence and development, which includes histone chaperones. The role of spty2d1 (spt2)-a novel histone chaperone protein-has rarely been investigated in CRC. Therefore, we demonstrated in this study that spt2 undergoes different genetic alterations in colorectal adenocarcinoma datasets and that it was associated with the proliferation of colon carcinoma. Spt2 silencing can reduce the ability of proliferation and increase the rate of apoptosis of LoVo cells. Regarding the overall survival associated with spt2, only the quartile disease-free survival of colon adenocarcinoma (COAD) was found to be statistically significant, while that of rectum adenocarcinoma (READ) was not. The positive (+++) expression of spt2 was correlated with a deeper invasion depth in colorectal adenocarcinoma, and this effect was more pronounced in COAD. These data collectively suggest that spt2 can influence the progression and prognosis in some subtypes of colorectal adenocarcinoma. Therefore, we propose spt2 as a potential target for application in enhancing the overall therapeutic efficacy in some specific subtypes of colorectal adenocarcinoma.

Non-destructive characterization of egg odor and fertilization status by SPME/GC-MS coupled with electronic nose.

BACKGROUND: Early and non-destructive identification of fertile (F) eggs is a difficult task in the process of breeding laying hens. The odors emitted from unfertilized (UF), infertile (IF), and fertile (F) eggs were characterized by solid-phase microextraction / gas chromatograph-mass spectrometry (SPME/GC-MS) and electronic nose (E-nose) to determine their differences by principal component, partial least squares, and canonical discriminant analyses. RESULTS: A total of 14 volatiles were identified in unhatched shell white Leghorn eggs, such as nonanal, decanal, 6-methyl-5-hepten-2-one, and 6,10-dimethyl-5,9-undecadien-2-one. Cedrene and decanal contributed greatly to the classification of UF and fertilized (Fd)/IF eggs; cedrene, decanal, 1-octanol and hexanal contributed greatly to the distinction between UF and IF eggs; heptanal might be the potential marker to determine F/IF eggs. P40/1, P10/2, P10/1, TA/2, T40/2 and T30/1, P30/1, P40/2, PA/2, T40/2 mostly contributed to the distinction between UF and Fd eggs and between F and IF eggs, respectively. Canonical discriminant analysis presented superior differentiating efficiency for almost all groups, and the odor differences between UF and Fd eggs were significantly larger than the differences between F and IF eggs. CONCLUSION: Solid-phase microextraction / gas chromatograph-mass spectrometer combined with E-nose may have the potential to non-destructively distinguish UF, F, and IF eggs, which will provide a new perspective to understand the differences among them. © 2018 Society of Chemical Industry.

Establishment of Liquid Chromatography Retention Index Based on Chemical Labeling for Metabolomic Analysis.

Chemical labeling (CL) in combination with liquid chromatography-mass spectrometry (LC-MS) analysis has been demonstrated to be a promising technology in metabolomic analysis. However, identification of chemically labeled metabolites remains to be challenging. Retention time (RT) is one of the most important parameters for the identification of metabolites, but it could vary greatly in LC-MS analysis. In this work, we developed a chemical labeling-based HPLC retention index (CL-HPLC RI) strategy to facilitate the identification of metabolites. In this CL-HPLC RI strategy, a series of 2-dimethylaminoethylamine (DMED)-labeled fatty acids were used as calibrants to establish RIs for DMED-labeled carboxylated compounds and a series of 4-( N, N-dimethylamino)phenyl isothiocyanate (DMAP)-labeled fatty amines were used as calibrants for DMAP-labeled amine compunds. To calculate the RIs, the whole LC chromatogram was divided into 24 time intervals by 23 DMED-labeled fatty acid standards or 15 time intervals by 14 DMAP-labeled fatty amine standards. Then, we established the RIs of 854 detected DMED-labeled carboxylated metabolites and 1057 DMAP-labeled amine metabolites in fecal samples and demonstrated that RIs were highly reproducible under different elution gradients, columns, and instrument systems. Finally, we applied this strategy to the identification of metabolites in human serum. Using RIs, 267 DMED-labeled carboxylated metabolites and 273 DMAP-labeled amine metabolites in human serum matched well with the fecal metabolome database. Taken together, the developed CL-HPLC RI strategy was demonstrated to be a promising method to facilitate the identification of metabolites in metabolomic analysis.

Comprehensive Profiling of Fecal Metabolome of Mice by Integrated Chemical Isotope Labeling-Mass Spectrometry Analysis.

Gut microbiota plays important roles in the host health. The host and symbiotic gut microbiota coproduce a large number of metabolites during the metabolism of food and xenobiotics. The analysis of fecal metabolites can provide a noninvasive manner to study the outcome of the host-gut microbiota interaction. Herein, we reported the comprehensive profiling of fecal metabolome of mice by an integrated chemical isotope labeling combined with liquid chromatography-mass spectrometry (CIL-LC-MS) analysis. The metabolites are categorized into several submetabolomes based on the functional moieties (i.e., carboxyl, carbonyl, amine, and thiol) and then analysis of the individual submetabolome was performed. The combined data from the submetabolome form the metabolome with relatively high coverage. To this end, we synthesized stable isotope labeling reagents to label metabolites with different groups, including carboxyl, carbonyl, amine, and thiol groups. We detected 2302 potential metabolites, among which, 1388 could be positively or putatively identified in feces of mice. We then further confirmed 308 metabolites based on our established library of chemically labeled standards and tandem mass spectrometry analysis. With the identified metabolites in feces of mice, we established mice fecal metabolome database, which can be used to readily identify metabolites from feces of mice. Furthermore, we discovered 211 fecal metabolites exhibited significant difference between Alzheimer's disease (AD) model mice and wild type (WT) mice, which suggests the close correlation between the fecal metabolites and AD pathology and provides new potential biomarkers for the diagnosis of AD.

4-Phenylaminomethyl-Benzeneboric Acid Modified Tip Extraction for Determination of Brassinosteroids in Plant Tissues by Stable Isotope Labeling-Liquid Chromatography-Mass Spectrometry.

Monitoring brassinosteroids (BRs) has been of major interest of researchers as these substances play a crucial role in a variety of phytological processes in plants. However, the determination of endogenous BRs in plant tissue is still a challenging task due to their low abundance and the complex matrix of plant tissues. In this study, a single step strategy by combining tip extraction and in situ derivatization was proposed for BR analysis. In the proposed strategy, a mixed mode sorbent (C8-SO3H) in tip was modified with 4-phenylaminomethyl-benzeneboric acid (4-PAMBA) through cation exchange and hydrophobic interactions, and then used as a boronate affinity media to selectively capture and purify BRs from plant extract through the reaction of boric acid groups of 4-PAMBA and cis-diol on BRs. The BRs-4-PAMBA derivatives formed were easily eluted from the C8-SO3H tip by nullifying the ion exchange and hydrophobic interactions using ammonia acetonitrile, followed by LC-MS/MS analysis. BR standards, isotopically labeled with d5-4-phenylaminomethyl-benzeneboric acid (4-PAMBA-d5) were introduced to improve the assay precision of LC-MS/MS. Under the optimized conditions, the overall process could be completed within 1 h, which is greatly improved in speed compared with previously reported protocols. In addition, the detection sensitivities of labeled BRs were improved by over 2000-fold compared with unlabeled BRs, thus the consumption of plant materials was reduced to 50 mg. Finally, the proposed method was applied for the investigation of BRs response in rice toward Cd stress.

Tubb3 regulation by the Erk and Akt signaling pathways: a mechanism involved in the effect of arginine ADP-ribosyltransferase 1 (Art1) on apoptosis of colon carcinoma CT26 cells.

The influence of the most important classical mono-ADP-ribosyltransferase, arginine ADP-ribosyltransferase 1 (Art1), on survival and apoptosis of colon carcinoma cells and the potential mechanisms have been partly discussed in our previous study but still need to be further studied. In this present study, Art1 of colon carcinoma CT26 cells was silenced with lentiviral vector-mediated short hairpin RNA (shRNA) or overexpressed with lentiviral vector-mediated complementary DNA (cDNA) and allograft transplant tumors are established in Balb/c mice. We verified Art1 knockdown increases apoptosis of CT26 cells transplant tumor; Art1 overexpression acts oppositely. Accordingly, growth of transplant tumors is inhibited in Art1 knockdown transplant tumors and increases in Art1 overexpression transplant tumors. Furthermore, activity of Akt and Erk cell signal pathways and expression of an apoptosis biomarker, ßIII-tubulin (Tubb3), decrease when Art1 was silenced and increase when Art1 was overexpressed. Inhibiting Akt pathway or Erk pathway both downregulates expression of Tubb3 on protein and messenger RNA (mRNA) level, indicating that Tubb3 could be regulated by both Akt and Erk pathways, and plays a role in the influence of Art1 on apoptosis of Balb/c mice allograft transplant tumor. We also demonstrated that Bcl-2 family is not the responsible downstream factor of the Erk pathway in colon carcinoma cells which is undergoing apoptosis. These findings enrich the molecular mechanism for the function of Art1 in colon carcinoma and provide a complementary support for Art1 to be a potential therapeutic target of the treatment of this kind of malignant tumor.

Profiling of aldehyde-containing compounds by stable isotope labelling-assisted mass spectrometry analysis.

We developed a strategy for non-targeted profiling of aldehyde-containing compounds by stable isotope labelling in combination with liquid chromatography-double neutral loss scan-mass spectrometry (SIL-LC-DNLS-MS) analysis. A pair of stable isotope labelling reagents (4-(2-(trimethylammonio)ethoxy)benzenaminium halide, 4-APC and d4-4-(2-(trimethylammonio)ethoxy)benzenaminium halide, 4-APC-d4) that can selectively label aldehyde-containing compounds were synthesized. The 4-APC and 4-APC-d4 labelled compounds were capable of generating two characteristic neutral fragments of 87 Da and 91 Da, respectively, under collision induced dissociation (CID). Therefore, double neutral loss scans were carried out simultaneously to record the signals of the potential aldehyde-containing compounds. In this respect, the aldehyde-containing compounds from two samples labelled with 4-APC and 4-APC-d4 were ionized at the same time but recorded separately by mass spectrometry. The peak pairs with characteristic mass differences (n × 4 Da) can be readily extracted from the DNLS spectra and assigned as potential aldehyde-containing candidates, which facilitates the identification of the target aldehydes. 4-APC and 4-APC-d4 labelling also dramatically increased detection sensitivities of the derivatives. Using the SIL-LC-DNLS-MS strategy, we successfully profiled the aldehyde-containing compounds in human urine and white wine. Our results showed that 16 and 19 potential aldehyde-containing compounds were discovered in human urine and white wine, respectively. In addition, 5 and 4 aldehyde-containing compounds in human urine and white wine were further identified by comparison with aldehyde standards. Altogether, SIL-LC-DNLS-MS demonstrated to be a promising approach in the identification and relative quantification of aldehyde-containing compounds from complex samples.

Discussion on the Influence of Gpx 4 Target in the Field of Cancer.

The current review was undertaken to collate data on Gpx4 inhibitors and the regulatory proteins related to Gpx4. Gpx4 plays an essential role in ferroptosis; it can be used to determine the Gpx4 as an indicator for determining tumor occurrence and as a means of treating cancer. Although there is no market for Gpx4 inhibitors, many researchers have conducted extensive research, and some compounds have entered clinical research. This article summarizes all papers related to Gpx4; hope this review can provide some new insights and ideas for researchers aiming to develop efficient and low-- toxicity Gpx4 inhibitors and provide some new ideas for cancer treatment.

Clinical usefulness of the baby vision test in young children and its correlation with the Snellen chart.

AIM: To investigate the efficacy of a new visual acuity (VA) screening method, the baby vision test for young children. METHODS: A total 105 eyes of 65 children aged 2-8y were included in the study. Acuity testing was conducted using a standardized recognition acuity chart (Snellen visual chart: at 3 m) and the baby vision model assessment. The baby vision device includes a screen, a near infrared camera and a computer. Children were seated at a measured distance of 33-40 cm from a display for testing. VA was estimated according to the highest resolution the children could follow. Decimal VA data were converted to logarithm of the minimum angle of resolution (logMAR) for statistical analysis. The VA results for each child were recorded and analyzed for consistency. RESULTS: The mean VA measured using the Snellen visual chart was 0.62±0.32, and that assessed using the baby vision test was 0.66±0.27. The 95% limit of agreement was -0.609 to 0.695, with 95.2% (100/105) plots within the 95% limits of agreement. VA values of the baby vision test were significantly correlated with those of the Snellen chart (R=0.274, P=0.005). CONCLUSION: The baby vision test can be used as a relatively reliable method for estimating VA in young children. This new acuity assessment might be a valid predictor of optotype-measured acuity later in preverbal children.

Uterine Burkitt Lymphoma with Rare Extranodal Deposits in the Bone, Breast, and Sacral Canal: A Case Report.

Burkitt lymphoma is a highly invasive non-Hodgkin lymphoma. Sporadic Burkitt's lymphoma is commonly found in the abdomen. However, Burkitt lymphoma infiltrating the uterus is uncommon in occurrence. We report the results of 18F-FDG PET/CT examination of a 36-year-old woman. The report indicates that in addition to the strong uptake of FDG imaging agent in the uterus, bilateral cervical and abdominal lymph nodes also have strong activity. At the same time, it was also found that bilateral small breast nodules, sacral canal and multiple bones in the whole body showed a radiation uptake pattern similar to that of the uterus. 18F-FDG PET/CT imaging can help determine the extent of the disease and the affected body area, which is helpful to guide the treatment decision. This case report shows the application of 18F-FDG PET/CT imaging in the diagnosis, staging and post-treatment evaluation of Burkitt lymphoma of the uterus. It provides very useful information for clinicians and helps to improve the accuracy of diagnosis and treatment effect.

SPC25 as a novel therapeutic and prognostic biomarker and its association with glycolysis, ferroptosis and ceRNA in lung adenocarcinoma.

OBJECTIVE: Spindle pole body component 25 (SPC25) is an important cyclin involved in chromosome segregation and spindle dynamics regulation during mitosis. However, the role of SPC25 in lung adenocarcinoma (LAUD) is unclear. MATERIALS AND METHODS: The differential expression of SPC25 in tumor samples and normal samples was analyzed using TIMER, TCGA, GEO databases, and the correlation between its expression and clinicopathological features and prognosis in LUAD patients. Biological pathways that may be enriched by SPC25 were analyzed using GSEA. In vitro cell experiments were used to evaluate the effect of knocking down SPC25 expression on LUAD cells. Correlation analysis and differential analysis were used to assess the association of SPC25 expression with genes related to cell cycle, glycolysis, and ferroptosis. A ceRNA network involving SPC25 was constructed using multiple database analyses. RESULTS: SPC25 was highly expressed in LUAD, and its expression level could guide staging and predict prognosis. GSEA found that high expression of SPC25 involved multiple cell cycles and glycolytic pathways. Knocking down SPC25 expression significantly affected the proliferation, migration and apoptosis of LUAD cells. Abnormal SPC25 expression levels can affect cell cycle progression, glycolytic ability and ferroptosis regulation. A ceRNA network containing SPC25, SNHG15/hsa-miR-451a/SPC25, was successfully predicted and constructed. CONCLUSIONS: Our findings reveal the association of up-regulation of SPC25 in LUAD and its expression with clinical features, prognosis prediction, proliferation migration, cell cycle, glycolysis, ferroptosis, and ceRNA networks. Our results indicate that SPC25 can be used as a biomarker in LUAD therapy and a target for therapeutic intervention.

TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association.

Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.

Pan-cancer analysis reveals correlation between RAB3B expression and tumor heterogeneity, immune microenvironment, and prognosis in multiple cancers.

RAB3B is essential for the transportation and secretion within cells. Its increased expression is linked to the development and progression of various malignancies. However, understanding of RAB3B's involvement in carcinogenesis is mostly limited to specific cancer subtypes. Hence, exploring RAB3B's regulatory roles and molecular mechanisms through comprehensive cancer datasets might offer innovative approaches for managing clinical cancer. To examine the potential involvement of RAB3B in the development of cancer, we analyzed data from various sources including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, HPA, UALCAN, and tissue microarray (TAM). Using bioinformatics techniques, we examined the correlation between RAB3B expression and prognosis, tumor heterogeneity, methylation modifications, and immune microenvironment across different cancer types. Our findings indicate that elevated RAB3B expression can independently predict prognosis in many tumors and has moderate accuracy for diagnosing most cancers. In most cancer types, we identified RAB3B mutations that showed a significant correlation with tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and microsatellite instability (MSI). Abnormal DNA methylation patterns were also observed in most cancers compared to normal tissues. Additionally, we found significant correlations between RAB3B expression, immune cell infiltration, and immune scores across various cancers. Through pan-cancer analysis, we observed significant differences in RAB3B expression levels between tumors and normal tissues, making it a potential primary factor for cancer diagnosis and prognosis. The IHC results revealed that the expression of RAB3B in six types of tumors was consistent with the results of the pan-cancer analysis of the database. Furthermore, RAB3B showed potential associations with tumor heterogeneity and immunity. Thus, RAB3B can be utilized as an auxiliary diagnostic marker for early tumor detection and a prognostic biomarker for various tumor types.

ART1 silencing enhances apoptosis of mouse CT26 cells via the PI3K/Akt/NF-κB pathway.

BACKGROUND/AIMS: Colorectal carcinoma is one of the most common cancers world-wide, with high morbidity and mortality rates. Arginine ADP-ribosyltransferase 1(ART1) is an important ecto-ADP-ribose transferase and has been proven to be intimately involved in a number of biological processes. However, the influence of ART1 on survival and apoptosis of colorectal carcinoma cells and the potential mechanism of action of ART1 remain uncharacterized. METHODS: ART1 was silenced via lentiviral vector-mediated short hairpin RNA (shRNA) in CT26 colon carcinoma cells, and cisplatin (CDDP) was applied to induce apoptosis. Survival and apoptosis rate of CT26 cells was assessed by CCK8 assay, flow cytometry and Hoechst 33342 staining. Expression and activity of signaling proteins were detected by Western blot. RESULTS: ART1 knockdown enhanced the inhibition of cell survival and increased the apoptosis induced by CDDP. Furthermore, the reduced survival rate correlated with reduced levels of phos-Akt(Thr308) and phos-IκBα and reduced NF-κB p65 nuclear translocation. A decline in Bcl-2 and Bcl-xl expression and an increase in Bax expression may explain the enhanced apoptosis. CONCLUSION: This study provides a molecular mechanism for the function of ART1 in colorectal carcinoma and defines a potential therapeutic target for the enhanced treatment of this prominent world-wide disease.

Symmetric and asymmetric Au-AgCdSe hybrid nanorods.

This paper describes a facile method for synthesis of Au-AgCdSe hybrid nanorods with controlled morphologies and spatial distributions. The synthesis involved deposition of Ag tips at the ends of Au nanorod seeds, followed by selenization of the Ag tips and overgrowth of CdSe on these sites. By simply manipulating the pH value of the system, the AgCdSe could selectively grow at one end, at both the ends or on the side surface of a Au nanorod, generating a mike-like, dumbbell-like, or toothbrush-like hybrid nanorod, respectively. These three types of Au-AgCdSe hybrid nanorods displayed distinct localized surface plasmon resonance and photoluminescence properties, demonstrating an effective pathway for maneuvering the optical properties of nanocrystals.

Synthesis and evaluation of in vitro and in vivo anti-Toxoplasma gondii activity of tetraoxane-substituted ursolic acid derivatives.

A series of derivatives of ursolic acid (UA) were synthesised, the anti-Toxoplasma gondii activity was tested, and the selectivity index (SI) of these compounds was calculated to determine the derivative with the best anti-Toxoplasma gondii activity. Compound A7 showed the best activity against the Toxoplasma gondii (IC50 in T. gondii infected GES-1 cells: 9.1 ± 7.2 µM), better than the lead compound UA and the positive control drug Spiramycin. Compound A7 was selected for further in vivo research: A7 was tested for its effect on the inhibition rate of tachyzoites in mice and its biochemical parameters, such as alanine aminotransferase, aspartate aminotransferase, glutathione, and malondialdehyde were determined. Compound A7 was evaluated for its anti-Toxoplasma activity and partial damage to the liver. Therefore, the results show that compound A7 could be a potential lead compound for developing a novel anti-Toxoplasma gondii molecule.

Real-world treatment and outcome patterns of patients with mantle cell lymphoma in China: A large, multicenter retrospective analysis.

BACKGROUND: Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non-Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not uniform between countries or regions within Asia and China, and Asian patient-specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China. METHODS: A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0. RESULTS: The median age of the cohort was 60.0 years with a male-to-female ratio of 3.36:1. Five-year progression-free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High-intermediate/high-risk group according to MIPI-c, without high-dose cytarabine, lack of Auto-SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high-intermediate/high risk group according to MIPI-c, without high-dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA. CONCLUSIONS: First-line high dose cytarabine exposure, auto-SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients.

RNA interference of PARG could inhibit the metastatic potency of colon carcinoma cells via PI3-kinase/Akt pathway.

AIMS: To investigate the role and mechanism of PARG inhibition of metastatic behavior in colonic carcinoma cells. METHODS: We examined the effects of PARG protein knockdown by RNA interference on invasion, migration and matrix adhesion of colon carcinoma cell lines in vitro and using a murine in vivo model of liver metastasis. Metastasis related genes were detected using mRNA and protein levels. Moreover, LY294002, an Akt phosphorylation inhibitor, was used to determine whether the suppression of metastatic behavior of colon carcinoma cells was mediated by Akt phosphorylation that was confirmed by EMSA. Pyrrolidine dithiocarbamate (PDTC) was used as a selective NFκ-B inhibitor to clarify the relationship between PARG, PARP and NF-κB. RESULTS: PARG protein was undetectable following specific shRNA transfection; mRNA and protein levels of PARP were significantly decreased. PARG-shRNA cells showed high levels of phosphorylated Akt with decreased expression of NF-κB (both total & nuclear), MMP2 and MMP9. However, no additional changes were noted following inhibition of PI3K/Akt pathway by LY294002 in the PARG-shRNA cells; these cells displayed reduced number of liver metastases when characterized in the murine in vivo model. CONCLUSION: PARG knockdown, concomitant with inhibition of PARP, suppressed the metastatic potency of colon carcinoma cells by activation of PI3K/Akt signaling pathway.

Magnetic resonance imaging and 18F-fludeoxyglucose positron emission tomography/computed tomography findings of retroperitoneal clear cell carcinoma with an unknown primary site: A case report.

Herein, we report a case of retroperitoneal clear cell carcinoma (RCCC) with an unknown primary site that was confirmed via pathology. A 46-year-old man presented with low-grade fever, hyperhidrosis, and nightly fatigue that had occurred for the last 20 days. His weight had decreased significantly within the past 2 months (approximately 12 kg). On abdominal ultrasound, a mass was observed near the left renal hilum. In addition, enhanced magnetic resonance imaging (MRI) of the abdomen revealed a retroperitoneal nodular mass; however, no abnormalities in either kidney or adrenal glands were observed. 18F-fludeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) demonstrated an intensely FDG-avid retroperitoneal mass, the maximum standardized uptake value (SUVmax) was 19.6. On March 8, 2021, left retroperitoneal lesion resection, retroperitoneal lymph node dissection, and double kidney exploration were performed under general anesthesia. A post-operative pathological examination revealed Poorly differentiated clear cell carcinoma (left retroperitoneal) and metastatic lymph nodes. Immunohistochemical findings showed that the tumor originated from the kidney. At 6-month follow-up, reexamination of the patient revealed retroperitoneal lesion recurrence; however, no abnormalities were observable via enhanced computed tomography (CT) of both kidneys. To our knowledge, there have been no previous reports of RCCC of unknown origin.