Metabolomics to identify fingerprints of carotid atherosclerosis in nonobese metabolic dysfunction-associated fatty liver disease.

BACKGROUND/AIMS: Nonobese metabolic dysfunction-associated fatty liver disease (MAFLD) is paradoxically associated with improved metabolic and pathological features at diagnosis but similar cardiovascular diseases (CVD) prognosis to obese MAFLD. We aimed to utilize the metabolomics to identify the potential metabolite profiles accounting for this phenomenon. METHODS: This prospective multicenter cross-sectional study was conducted in China enrolling derivation and validation cohorts. Liquid chromatography coupled with mass spectrometry and gas chromatography-mass spectrometry were applied to perform a metabolomics measurement. RESULTS: The study involved 120 MAFLD patients and 60 non-MAFLD controls in the derivation cohort. Controls were divided into two groups according to the presence of carotid atherosclerosis (CAS). The MAFLD group was further divided into nonobese MAFLD with/without CAS groups and obese MAFLD with/without CAS groups. Fifty-six metabolites were statistically significant for discriminating the six groups. Among the top 10 metabolites related to CAS in nonobese MAFLD, only phosphatidylethanolamine (PE 20:2/16:0), phosphatidylglycerol (PG 18:0/20:4) and de novo lipogenesis (16:0/18:2n-6) achieved significant areas under the ROC curve (AUCs, 0.67, p = 0.03; 0.79, p = 0.02; 0.63, p = 0.03, respectively). The combination of these three metabolites and liver stiffness achieved a significantly higher AUC (0.92, p < 0.01). In obese MAFLD patients, cystine was found to be significant with an AUC of 0.69 (p = 0.015), followed by sphingomyelin (SM 16:1/18:1) (0.71, p = 0.004) and de novo lipogenesis (16:0/18:2n-6) (0.73, p = 0.004). The combination of these three metabolites, liver fat content and age attained a significantly higher AUC of 0.91 (p < 0.001). The AUCs of these metabolites remained highly significant in the independent validation cohorts involving 200 MAFLD patients and 90 controls. CONCLUSIONS: Diagnostic models combining different metabolites according to BMI categories could raise the accuracy of identifying subclinical CAS. Trial registration The study protocol was approved by the local ethics committee and all the participants have provided written informed consent (Approval number: [2014] No. 112, registered at the Chinese Clinical Trial Registry, ChiCTR-ChiCTR2000034197).

Gingival metastasis from primary hepatocellular carcinoma: a case report and literature review of 30 cases.

BACKGROUND: Gingival metastasis from primary hepatocellular cancer (HCC) is rare, highly malignant, and generally has no distinct symptoms. Not performing a biopsy can lead to misdiagnosis. This article reports an 87-year-old male with gingival metastasis from HCC. To gain a better insight into this disease, we also conducted a literature review of 30 cases and discussed the clinical and pathological characteristics, diagnosis, treatment and prognosis of this unusual form of liver cancer. CASE PRESENTATION: An 87-year-old man was hospitalized with a chief complaint of chronic constipation and diffuse lower extremity edema. His past medical history included a three-year hepatitis B infection and a cerebral infarction 17 years prior. Imaging examination detected a massive hepatocellular carcinoma in the right liver lobe and multiple metastases in the lungs. Oral examinations revealed a reddish, cherry-sized exophytic mass on the right upper gum. The mass was tentatively diagnosed as a primary gingival tumor and was ultimately confirmed by biopsy as a metastatic carcinoma originating in the liver. The patient decided, with his guardians, to receive palliative care and not to remove the mass. Unfortunately, the patient accidentally bit the mass open; profuse bleeding ensued and local pressure exerted a poor hemostatic effect. The patient's condition worsened, and he eventually died of multiple organ failure. We also performed a literature review and discussed 30 cases of gingival metastases from HCC. The findings indicated that these lesions affected males more than females, with a ratio of 6:1, and infiltrated the upper gingivae (63.1%) more than the lower gingivae (36.7%). Survival analysis indicated that the overall survival for patients with upper gingival metastasis was worse than for those with lower gingival metastasis, and patients receiving treatments for primary liver cancer or metastatic gingival tumors had better overall or truncated survival times. CONCLUSION: Gingival metastasis from primary hepatocellular carcinoma is rare, and its diagnosis has presented challenges to clinicians. To avoid a potential misdiagnosis, a biopsy is mandatory regardless of whether a primary cancer is located. Early diagnosis and treatment for primary liver cancer or metastatic gingival lesions may improve survival expectations.

The Glucagon-Like Peptide-1 Analogue Liraglutide Inhibits Oxidative Stress and Inflammatory Response in the Liver of Rats with Diet-Induced Non-alcoholic Fatty Liver Disease.

Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been demonstrated to reduce hepatic steatosis. However, the mechanism of the lipid-lowering effect of liraglutide in the liver remains unclear. The aim of the present study was to investigate the beneficial effect of liraglutide on diet-induced non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism in rats. NAFLD was induced in Sprague-Dawley rats by feeding a high fat and high cholesterol (HFHC) diet. Liraglutide (0.6 mg/kg body weight/d) was injected intraperitoneally to the rats subjected to HFHC diet four weeks before sacrificing the animals. Body and liver weight, fasting blood glucose (FBG), fasting insulin, serum aminotransferase (ALT) and lipid accumulation in the liver were determined. Markers of oxidative stress, such as malondialdehyde (MDA), free fatty acid (FFAs), superoxide dismutase (SOD), and pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) were detected by colorimetric detection or enzyme-linked immunosorbent assay (ELISA). Serum and hepatic adiponectin were measured by ELISA. The expression of c-Jun N-terminal kinase-1 (JNK-1) and phosphorylated JNK-1 were examined by Western blotting. Liraglutide improved insulin resistance, decreased hepatic steatosis and reversed liver dysfunction. The hepatic levels of MDA, FFAs, and TNF-α were significantly decreased versus controls. Meanwhile, administration of liraglutide significantly increased SOD and adiponectin levels in the liver and inhibited the expression of JNK-1 and phosphorylated JNK-1 versus control rats. Liraglutide exerted anti-oxidative and anti-inflammatory effects in the liver and consequently reversed hepatic steatosis and insulin resistance. Such effects might be mediated by the elevation of adiponectin levels and the inactivation of JNK-1.

The Prognostic Value of Serum Calcium Levels in Elderly Dilated Cardiomyopathy Patients.

Background: It is unclear whether serum calcium on admission is associated with clinical outcomes in dilated cardiomyopathy (DCM). In this study, we conducted a retrospective study spanning a decade to investigate the prognostic value of baseline calcium in elderly patients with DCM. Methods: A total of 1,089 consecutive elderly patients (age ≥60 years) diagnosed with DCM were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to investigate the association of serum calcium with their clinical outcomes. Results: In this study, the average age of the subjects was 68.36 ± 6.31 years. Receiver operating characteristic (ROC) curve analysis showed that serum calcium level had a great sensitivity and specificity for predicting in-hospital death, with an AUC of 0.732. Kaplan-Meier survival analysis showed that patients with a serum calcium >8.62 mg/dL had a better prognosis than those with a serum calcium ≤8.62 mg/dL (log-rank χ2 40.84, p < 0.001). After adjusting for several common risk factors, a serum calcium ≤8.62 mg/dL was related to a higher risk of long-term mortality (HR: 1.449; 95% CI: 1.115~1.882; p = 0.005). Conclusions: Serum calcium level could be served as a simple and affordable tool to evaluate patients' prognosis in DCM.

Extracellular vesicle-packaged lncRNA from cancer-associated fibroblasts promotes immune evasion by downregulating HLA-A in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterised by immune evasion that contribute to poor prognosis. Cancer-associated fibroblasts (CAFs) play a pivotal role in orchestrating the PDAC tumour microenvironment. We investigated the role of CAF-derived extracellular vesicle (EV)-packaged long non-coding RNAs (lncRNAs) in immune evasion and explored gene therapy using engineered EVs loading small interfering RNAs (siRNAs) as a potential therapeutic strategy. Our findings highlight the significance of EV-packaged lncRNA RP11-161H23.5 from CAF in promoting PDAC immune evasion by downregulating HLA-A expression, a key component of antigen presentation. Mechanistically, RP11-161H23.5 forms a complex with CNOT4, a subunit of the mRNA deadenylase CCR4-NOT complex, enhancing the degradation of HLA-A mRNA by shortening its poly(A) tail. This immune evasion mechanism compromises the anti-tumour immune response. To combat this, we propose an innovative approach utilising engineered EVs as natural and biocompatible nanocarriers for siRNA-based gene therapy and this strategy holds promise for enhancing the effectiveness of immunotherapy in PDAC. Overall, our study sheds light on the critical role of CAF-derived EV-packaged lncRNA RP11-161H23.5/CNOT4/HLA-A axis in PDAC immune evasion and presents a novel avenue for therapeutic intervention.

Sarcopenia in liver cirrhosis: perspectives from epigenetics and microbiota.

Sarcopenia is characterized by the loss of muscle mass and function. It is well known that sarcopenia is often associated with aging, while in recent years, sarcopenia comorbid with chronic diseases such as cirrhosis has attracted widespread attention, whose underlying molecular mechanisms remain unclear. Since cirrhosis and sarcopenia are assumed to be closely interrelated in terms of pathogenesis, this review innovatively discussed the role of epigenetic modifications and microecological dysregulation in sarcopenia in the context of liver cirrhosis. Here we illustrated the relationship between sarcopenia and cirrhosis in the aspect of epigenetics, dysbiosis, and the crosstalk between gene modifications and intestinal microecology. Furthermore, the alterations in cirrhosis patients with sarcopenia, such as inflammatory response and oxidative stress, are found to present synergistic effects in the pathways of epigenetics and dysbiosis leading to sarcopenia. This review proposes that microbiome-based therapies are promising to break the vicious cycle between epigenetic modification and dysbiosis, providing strong support for the use of intestinal microecological interventions to prevent sarcopenia in cirrhotic patients.

Characteristics of the gut microbiome and metabolic profile in elderly patients with sarcopenia.

Introduction: There is growing evidence of research indicating that the gut microbiota is involved in the development of sarcopenia. Nevertheless, there exists a notable deficiency in comprehension concerning the connection between irregularities in the intestinal microbiome and metabolic processes in older individuals suffering from sarcopenia. Methods: To analyze fecal samples obtained from a cohort of 30 older patients diagnosed with sarcopenia as well as 30 older patients without sarcopenia, this study employed 16S rDNA sequencing and liquid chromatography-mass spectrometry (LC-MS)-based non-targeted metabolomics profiling techniques. Results: As a result, we found that 29 genera and 172 metabolites were significantly altered in the sarcopenic patients. Among them, Blautia, Lachnospiraceae_unclassified, and Subdoligranulum were the bacteria with a potential diagnostic value for sarcopenia diagnosis. Correlation analysis between clinical indices and these gut bacteria suggested that the IL-6 level was negatively correlated with Blautia. Function prediction analysis demonstrated that 17 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways differ significantly between sarcopenic and non-sarcopenic patients. The primary classes of metabolites identified in the study included lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds. KEGG enrichment analysis showed that purine metabolism, arginine and proline metabolism, alanine, aspartate, and glutamate metabolism, butanoate metabolism, and histidine metabolism may contribute to the development of sarcopenia. The correlation study on gut microbiota and metabolites found that Lachnospiraceae_unclassified was positively associated with seven metabolites that were more abundant in the non-sarcopenia group and negatively correlated with three metabolites that were more abundant in the sarcopenia group. In addition, Subdoligranulum was positively correlated with seven metabolites that were lacking in sarcopenia and negatively correlated with two metabolites that were enriching in sarcopenia. Moreover, Blautia was positively associated with xanthosine. Discussion: We conducted a study on the intestinal microbiota and metabolic profile of elderly individuals with sarcopenia, offering a comprehensive analysis of the overall ecosystem. Through this investigation, we were able to validate existing research on the gut-muscle axis and further investigate potential pathogenic processes and treatment options for sarcopenia.

An Optimized Strategy Based on Conventional Ultrasound for Diagnosing Metabolic Dysfunction-Associated Steatotic Liver Disease.

The inherent drawbacks of the conventional B-mode ultrasound for metabolic dysfunction-associated steatotic liver disease (MASLD) are poorly understood. We aimed to investigate the impact factors and optimize the screening performance of ultrasound in MASLD. In a prospective pilot cohort recruited from July 2020 to January 2022, subjects who had undergone magnetic resonance imaging-based proton density fat fraction (MRI-PDFF), ultrasound, and laboratory test-based assessments were included in the deprivation cohort. A validation cohort including 426 patients with liver histologic assessments from five medical centers in South China was also recruited. A total of 1489 Chinese subjects were enrolled in the deprivation cohort, and ultrasound misdiagnosed 62.2% of the non-MASLD patients and failed to detect 6.1% of the MASLD patients. The number of metabolic dysfunction components and the alanine aminotransferase (ALT) level were associated with a missed diagnosis by ultrasound (OR = 0.67, 95% CI 0.55-0.82 p < 0.001; OR = 0.50, 95% CI 0.31-0.79, p = 0.003, respectively). Compared with ultrasound alone, the new strategy based on ultrasound, in combination with measurements of the number of metabolic dysfunction components and ALT and uric acid levels, significantly improved the AUROC both in the research cohort and the validation cohort (0.66 vs. 0.84, 0.83 vs. 0.92, respectively). The number of metabolic dysfunction components and ALT and uric acid levels improved the screening efficacy of ultrasound for MASLD.

Serum albumin and prognosis in elderly patients with nonischemic dilated cardiomyopathy.

AIMS: Hypoalbuminemia was extensively used to diagnose malnutrition in older adults. Malnutrition was associated with mortality in elderly patients with cardiovascular diseases. The relationship between hypoalbuminemia and clinical outcomes in elderly patients with nonischemic dilated cardiomyopathy (NIDCM) remains unknown. METHODS: A total of 1058 consecutive patients with NIDCM (age ≥60 years) were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to assess the association of hypoalbuminemia with clinical outcomes. RESULTS: Patients with hypoalbuminemia were older (69.29 ±â€Š6.67 vs. 67.61 ±â€Š5.90 years, P  < 0.001) and had higher prevalence of in-hospital and long-term death than those without (6.9 vs. 1.7%, 50.7 vs. 35.2%, P  < 0.001). Logistic regression analysis showed that hypoalbuminemia was significantly related to in-hospital death [odds ratio (OR): 4.334, 95% confidence interval (CI): 2.185-8.597, P  < 0.001]. Kaplan-Meier survival analysis showed that patients with hypoalbuminemia had worse prognosis than those with nonhypoalbuminemia (log-rank χ2 28.96, P  < 0.001). After adjusting for age, serum creatinine, HDL-C, AST/ALT hypoalbuminemia, LVEF and diabetes, hypoalbuminemia remained an independent predictor for long-term death (hazard ratio 1.322, 95% CI 0.046-1.670, P  = 0.019). CONCLUSION: Hypoalbuminemia was associated with increased risk of in-hospital and long-term mortality in elderly patients with NIDCM.

Applications of functionalized magnetic biochar in environmental remediation: A review.

Magnetic biochar (MBC) is extensively applied on contaminants removal from environmental medium for achieving environmental-friendly remediation with reduction of secondary pollution owing to its easy recovery and separation. However, the summary of MBC synthesis methods is still lack of relevant information. Moreover, the adsorption performance for pollutants by MBC is limited, and thus it is imperative to adopt modification techniques to enhance the removal ability of MBC. Unfortunately, there are few reviews to present modification methods of MBC with applications for removing hazardous contaminants. Herein, we critically reviewed (i) MBC synthetic methods with corresponding advantages and limitations; (ii) adsorption mechanisms of MBC for heavy metals and organic pollutants; (iii) various modification methods for MBC such as functional groups grafting, nanoparticles loading and element doping; (iv) applications of modified MBC for hazardous contaminants adsorption with deep insight to relevant removal mechanisms; and (v) key influencing conditions like solution pH, temperature and interfering ions toward contaminants removal. Finally, some constructive suggestions were put forward for the practical applications of MBC in the near future. This review provided a comprehensive understanding of using functionalized MBC as effective adsorbent with low-cost and high-performance characteristics for contaminated environment remediation.

Preoperative Prognostic Nutrition Index as a Prognostic Indicator of Survival in Elderly Patients Undergoing Gastric Cancer Surgery.

PURPOSE: Gastric cancer is a common tumor type associated with nutritional and immune status. The aim of the current study was to investigate the prognostic value of a preoperative prognostic nutritional index (PNI), composed of nutritional factors and immune factors in elderly patients undergoing gastric cancer surgery. PATIENTS AND METHODS: A total of 454 patients undergoing gastric cancer surgery were divided into two groups based on preoperative PNI scores: ≤45.1 (n = 307) and >45.1 (n = 147). Survival analysis was performed using the Kaplan-Meier method and Log rank tests. Univariate and multivariate analyses were conducted to identify independent prognostic factors using a Cox proportional hazards model. RESULTS: According to the X-tile program, the optimal cutoff value for predicting overall survival (OS) with the PNI was 45.1. The receiver operating characteristic analysis revealed that PNI exhibited 70.6% sensitivity and 56.5% specificity for predicting death during long-term follow-up. The cumulative incidence of postoperative 4-year mortality indicated that the risk of death increased significantly for PNI ≤45.1. In multivariate analysis, preoperative PNI was a significant independent predictor of mortality. In the age-stratified subgroup analysis, preoperative PNI was more sensitive for the old elderly subgroup than for the young elderly subgroup. CONCLUSION: Preoperative PNI is a sensitive and specific prognostic predictor among elderly patients undergoing gastric cancer surgery.

BARX2 expression is downregulated by CpG island hypermethylation and is associated with suppressed cell proliferation and invasion of gastric cancer cells.

BarH­like homeobox 2 (BARX2), a homeobox gene, is associated with several types of cancers. The present study aimed to determine whether DNA methylation downregulates BARX2 expression and whether BARX2 is associated with suppression of gastric carcinogenesis. BARX2 protein expression in normal and cancerous gastric tissues and various gastric cancer (GC) cell lines was detected using immunohistochemical and western blot assays. BARX2 mRNA levels were detected using both reverse transcription­polymerase chain reaction (RT­PCR) and quantitative PCR (qPCR). Promoter hypermethylation in GC cells was detected using methylation­specific PCR or bisulfite DNA sequencing PCR. Effects of BARX2 expression on GC cell proliferation, clonal formation, and migration were evaluated after lentivirus­BARX2 transfection. The effect of stable BARX2 transfection on tumor formation was assessed in a nude xenograft mouse model. BARX2 was strongly expressed in the normal gastric mucosa, but weakly or not expressed in GC tissues and most GC cell lines. BARX2 expression was negatively correlated with DNMT (a marker for DNA methylation) expression in the gastric tissues. The BARX2 promoter fragment was hypermethylated in the GC cell lines. Overexpression of BARX2 significantly inhibited GC cell proliferation, clonal formation, and migration. Stable BARX2 transfection inhibited tumor formation in xenograft mice, which was correlated with decreased expression of E­cadherin, proliferation markers, and matrix metalloproteinases. In conclusion, BARX2 expression is aberrantly reduced in GC, which is associated with increased DNA methylation of its promoter. BARX2 inhibits GC cell proliferation, migration, and tumor formation, suggesting that BARX2 acts as a tumor suppressor in gastric carcinogenesis.

MicroRNA-17 promotes cell proliferation and migration in human colorectal cancer by downregulating SIK1.

Purpose: There is mounting evidence to indicate that microRNA-17 (miR-17) is expressed and functionally involved in human cancers. However, the molecular mechanism underlying the role of miR-17 in colorectal cancer (CRC) remains largely unclear. This study aims to reveal the biological function of miR-17 in colorectal cancer. Materials and methods: The expression of miR-17 in CRC cells and tissues was examined using qRT-PCR. Cell proliferation and migration assays were performed after transfection with an miR-17 mimic and inhibitors. The potential gene targets of miR-17 were predicted by bioinformatics analysis and further validated by PCR, Western blot and dual luciferase reporter assays. Results: The expression of miR-17 was significantly upregulated in CRC cell lines and tissues and may imply poor prognosis. miR-17 upregulation promoted cell invasion and migration in CRC cell lines in vitro, while downregulation of miR-17 inhibited tumor progression. SIK1 was identified as a potential direct target of miR-17 by dual luciferase reporter assay, and its downregulation in CRC may suggest poor prognosis. Conclusions: Our study indicated that upregulated miR-17 may promote the progression of CRC and may exert its function as a tumor suppressor miRNA by targeting SIK1.

Upregulation of c-mesenchymal epithelial transition expression and RAS mutations are associated with late lung metastasis and poor prognosis in colorectal carcinoma.

The present study aimed to investigate whether c-mesenchymal epithelial transition factor (C-MET) overexpression combined with RAS (including KRAS, NRAS and HRAS) or BRAF mutations were associated with late distant metastases and the prognosis of patients with colorectal cancer (CRC). A total of 374 patients with stage III CRC were classified into 4 groups based on RAS/BRAF and C-MET status for comprehensive analysis. Mutations in RAS/BRAF were determined using Sanger sequencing and C-MET expression was examined using immunohistochemistry. The associations between RAS/BRAF mutations in combination with C-MET overexpression and clinicopathological variables including survival were evaluated. In addition, their predictive value for late distant metastases were statistically analyzed via logistic regression and receiver operating characteristic analysis. Among 374 patients, mutations in KRAS, NRAS, HRAS, BRAF and C-MET overexpression were observed in 43.9, 2.4, 0.3, 5.9 and 71.9% of cases, respectively. Considering RAS/BRAF mutations and C-MET overexpression, vascular invasion (P=0.001), high carcino-embryonic antigen level (P=0.031) and late distant metastases (P<0.001) were more likely to occur in patients of group 4. Furthermore, survival analyses revealed RAS/BRAF mutations may have a more powerful impact on survival than C-MET overexpression, although they were both predictive factors for adverse prognosis. Further logistic regression suggested that RAS/BRAF mutations and C-MET overexpression may predict late distant metastases. In conclusion, RAS/BRAF mutations and C-MET overexpression may serve as predictive indicators for metastatic behavior and poor prognosis of CRC.

Potential involvement of heat shock proteins in pancreatic-duodenal homeobox-1-mediated effects on the genesis of gastric cancer: A 2D gel-based proteomic study.

AIM: To identify functional proteins involved in pancreatic-duodenal homeobox-1 (PDX1)-mediated effects on gastric carcinogenesis. METHODS: A PDX1-overexpressed model was established by transfecting gastric cancer cell line SGC7901 with pcDNA3.1(+)-PDX1 vector (SGC-PDX1). Transfection with empty pcDNA3.1 vector (SGC-pcDNA) served as control. Comparative protein profiles of the two groups were analyzed by two-dimensional electrophoresis based-proteomics (2DE gel-based proteomics). The differential proteins identified by 2DE were further validated by qRT-PCR and immunoblotting. Finally, co-immunoprecipitation was used to determine any direct interactions between PDX1 and the differential proteins. RESULTS: 2DE gel proteomics identified seven differential proteins in SGC-PDX1 when compared with those in SGC-pcDNA. These included four heat shock proteins (HSPs; HSP70p1B, HSP70p8, HSP60, HSP27) and three other proteins (ER60, laminin receptor 1, similar to epsilon isoform of 14-3-3 protein). Immunoblotting validated the expression of the HSPs (HSP70, HSP60, HSP27). Furthermore, their expressions were lowered to 80%, 20% and 24%, respectively, in SGC-PDX1, while PDX1 exhibited a 9-fold increase, compared to SGC-pcDNA. However, qRT-PCR analysis revealed that mRNA levels of the HSPs were increased in SGC-PDX1, suggesting that the expression of the HSPs was post-translationally regulated by the PDX1 protein. Finally, co-immunoprecipitation failed to identify any direct interaction between PDX1 and HSP70 proteins. CONCLUSION: This study demonstrates the potential involvement of HSPs in PDX1-mediated effects on the genesis of gastric cancer.

Primary Gastrointestinal Lymphoma: A Retrospective Multicenter Clinical Study of 415 Cases in Chinese Province of Guangdong and a Systematic Review Containing 5075 Chinese Patients.

Primary gastrointestinal lymphoma (PGIL) is a rare malignant tumor without standard diagnosis and treatment methods. This study is aimed to systematically analyze its clinical characteristics and draw out an appropriate flow chart of diagnosis and treatment process for PGIL in China.This study retrospectively analyzed the clinicopathological characteristics, diagnostic approaches, prognostic factors, and therapeutic modalities in 415 cases of PGIL in Chinese province of Guangdong. A systematic review was conducted in 118 studies containing 5075 patients to further identify clinical manifestations and mortalities of therapeutic modalities.The most common clinical presentations were abdominal pain and bloody stools. Endoscopic biopsy was an important diagnostic means, and usually more than once to make a definite diagnosis. Retrospective multicenter clinical study showed that younger onset age (<60 years), female, one region involved, one lesion, early stage, International Prognostic Index (IPI ≤1), normal lactate dehydrogenase (LDH), normal albumin, and nonemergency operation were significant prognostic factors for B-cell lymphoma; non-B symptom, tumor restricted to gastric or ileocecal region, one lesion, performance status (PS ≤1), normal LDH, and nonsurgery alone were significant prognostic factors for T-cell lymphoma. Site of origin and IPI were independent prognostic factors for B-cell lymphoma; PS was the independent prognostic factor for T-cell lymphoma. And T-cell lymphoma had worse overall survival (OS) and progression-free survival (PFS) than B-cell lymphoma. Among different therapeutic modalities, chemotherapy alone or combined with surgery showed better OS and PFS than surgery alone for diffuse large B-cell lymphoma (DLBCL) of stage I/II E and T-cell lymphoma. For DLBCL of stage III E/IV and mucosa-associated lymphoid tissue lymphoma, OS and PFS did not differ among different therapeutic groups. In meta-analysis, surgery plus chemotherapy showed lowest mortality.Chemotherapy alone or combined with surgery may be the first-line treatment for DLBCL of stage I/II E and T-cell lymphoma. A flow chart of diagnosis and treatment process for PGIL was approximately drew out.

[Effects of glucagon-like peptide-1 on liver oxidative stress, TNF-α and TGF-ß1 in rats with non-alcoholic fatty liver disease].

OBJECTIVE: To investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress, TNF-α and TGF-ß1 in rats with diet-induced non-alcoholic fatty liver disease (NAFLD). METHODS: Thirty male rats were randomly divided into 3 equal groups and fed for 16 weeks with normal diet (ND), high-fat diet (HFD), or high-fat diet with intraperitoneal injection of liraglutide (GLP-1, administered in the later 4 weeks). The rats were then sacrificed to obtain blood samples and liver tissues for analyzing the levels of blood aminotransferase (ALT), triglyceride (TG), and total-cholesterol (TC) using an automatic biochemical analyzer and the levels of superoxide dismutase (SOD), malondial-dehyde (MAD), free fatty acid (FFAs), TNF-α in the liver homogenates and TGF-ß1 in serum by radioimmunoassay or ELISA. RESULTS: Compared with ND group, HFD group showed significantly increased body weight, liver index, serum levels of ALT, TG, TC, and TGF-ß1, and TG, TC, MAD, FFAs, and TNF-α in the liver homogenates, with also significantly increased degree of hepatic steatosis and inflammation activity (P<0.05) and lowered level of SOD. All these changes were markedly ameliorated in GLP-1 group (P<0.05). CONCLUSION: Liraglutide can reduce high-fat diet-induced hepatic steatosis, improve oxidative stress and lipid peroxidation, and decrease TGF-ß1 and TNF-α levels in serum and liver homogenates, suggesting its potential as a therapeutic agent for NAFLD.

[Preparation of As2O3 nanoparticles and its drug release characteristics in vitro].

OBJECTIVE: To prepare arsenic trioxide (As2O3)-loaded biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles (NPS) and evaluate the glomeration ability, appearance, structure, surface and release characteristics of the NPs. METHODS: With PLGA as the carrier material, As2O3 NPs (As2O3-NPS) were prepared with the method of matrix and ultrasound emulsification. According to the criteria of the diameter of the NPs, drug loading (DL) and embedding ratio (ER), the process of NP preparation was optimized by scanning electron microscopy (SEM), ultraviolet spectroscopy (UV), and XPS. RESULTS: The As2O3-NPS prepared were uniformly spherical with an average diameter of 210-/+23 nm, DL of 29.6% and ER of 82.1%. The drug release assay in vitro showed a sustained drug-release capacity of the preparation. CONCLUSION: As2O3-NPS may serve as a carrier of As2O3 to change the pharmacokinetics of As2O3 in vivo, allow slow drug release, and prolong the drug circulation time after intravenous injection, thereby producing better antitumor effects.

[Clinical features of panereatic disease-associated portal hypertension].

OBJECTIVE: To investigate the clinical features and management of pancreatic disease-associated portal hypertension. METHODS: A retrospective analysis was carried out in patients with portal hypertension and concurrent pancreatic diseases. The medical records of these patients were reviewed including the data of demographics, etiologies, venous involvement, clinical presentations, laboratory tests, imaging studies, therapeutic modalities and outcomes. RESULTS: Fifty-two patients with portal hypertension resulting from pancreatic diseases were found in our hospital, accounting for 4% of all the patients with portal hypertension in 11 years. The underlying pancreatic diseases were chronic pancreatitis (21 cases, 35.6%), pancreatic carcinoma (20 cases, 33.9%), acute pancreatitis (8 cases, 13.6%), pancreatic pseudocyst (3 cases, 5.1%). Of the 40 patients whose venous involvement was identified, splenic vein obstruction occurred in 27 cases (67.5%) and portal vein obstruction in 16 cases (40.0%). Mild or moderate splenomegaly was present in 48 cases (81.4%), with leukocytopenia as the most common manifestation of the 31 cases (52.5%) with concomitant hypersplenism. Forty-five patients (76.3%) developed gastroesophageal varices (including 35 with isolated gastricvarices), and among them 22 experienced bleeding (42.3%). Conservative treatment was effective in controlling acute bleeding, but could not prevent re-bleeding. Splenectomy was performed in 18 patients mainly due to gastrointestinal hemorrhage. No postoperative bleeding occurred during the follow-up ranging from 8 months to 9 years. CONCLUSION: Pancreatic diseases may compromise portal vein and its tributaries, leading to generalized or regional portal hypertension. Pharmacological therapy can effectively control acute variceal bleeding, while surgical treatment is the appropriate procedure of choice in case of hemorrhagic recurrence.