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OBJECTIVE:Little is known about metabolic factors in cirrhotic patients in China. Therefore, we aimed to quantify the prevalence of both metabolic factors and non-alcoholic steatohepatitis-related liver cirrhosis in China.METHODS:The medical records of 1,582 patients diagnosed with liver cirrhosis from June 2003 to July 2013 at Daping Hospital (Chongqing, China) were retrospectively reviewed through a computer-generated search.RESULTS:Serum hepatitis B virus surface antigen was present in 1,083 (68.5%) patients, and hepatitis B was found to be the only etiological factor in 938 (59.3%) of all patients. Obesity, diabetes mellitus, and arterial hypertension were observed in 229 (14.5%), 159 (10.1%), and 129 (8.2%) patients, respectively. From 2012-2013, the proportion of non-alcoholic steatohepatitis-related liver cirrhosis increased to 3.2%, whereas the average proportion of non-alcoholic steatohepatitis-related liver cirrhosis in the previous ten years was 1.9%. The incidence of hepatocellular carcinoma was much higher in males than in females (6.3% vs. 3.7%, respectively, p=0.036). Obesity and diabetes mellitus did not significantly increase the incidence of hepatocellular carcinoma in the whole cirrhotic group. The presence of hepatitis B virus was the only risk factor for hepatocellular carcinoma in cirrhotic patients (p<0.001).CONCLUSIONS:Although hepatitis B virus remains the main etiology of liver cirrhosis in China, steatohepatitis-related liver cirrhosis is increasing in frequency. Hepatitis B virus was the sole significant risk factor for hepatocellular carcinoma in the whole cirrhotic group in the present study, in contrast to obesity and diabetes mellitus, for which only a trend of increased hepatocellular carcinoma was found.

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INTRODUCTION The expression profiles of different immune checkpoint molecules are promising for triaging personalized targeted immunotherapy. Our study was performed to determine co-expression levels of 2 major B7 immune molecules, PD-L1 and B7-H4, in gliomas where both have demonstrated to inhibit antitumor host immunity. METHODS We assessed tumor issues from primary gliomas stage II to IV (n = 505) by immunohistochemistry (IHC) for protein levels of both PD-L1 and B7-H4. Gene co-expression analysis assessing clusters based on extent of PD-L1/B7-H4 classifier genes expression were investigated in 2 transcriptome datasets (TCGA and CGGA) to validate IHC expression profiles and explore properties of the glioma immune microenvironment among specific co-expression PD-L1/B7-H4 cluster groups. RESULTS PD-L1 was detected in 61% of patients whereby 23% expressed high levels. B7-H4 was expressed in 54% whereby 20% were identified as high expression. Co-expression of PD-L1 and B7-H4 in high levels was limited to 2% cases. Comparable results were seen in RNA-sequencing datasets when PD-L1 mRNA expression level corelated negatively with B7-H4. Gene co-expression modules clustered in each grade gliomas without double-high modules (gliomas cluster with high mRNA expression of both PD-L1 and B7-H4 classifier genes) also verified restricted coexpression pattern. B7-H4 mRNA expression level had negative correlation with extent of immune cell infiltration, including tumor-infiltrating lymphocytes (TILs), and high-B7-H4 module gliomas (high B7-H4 but low PD-L1 classifier genes expression) was related to a cold tumor with less TILs. CONCLUSION The majority of gliomas express PD-L1 or B7-H4, however, co-expression of both at high levels is minimal. The high-B7-H4 module was significantly lacking in TILs, suggesting that B7-H4 might inhibit T cell trafficking into the central nervous system (CNS). This study demonstrates that PD-L1 expression alone is not fully informative in gliomas for immune targeted or active-specific immunotherapy, and PD-L1 and B7-H4 probably inhibit different aspects of the T cell functions.

Purpose: Diffuse midline glioma (DMG), H3K27M mutant is a new entity that has become widely recognized. However, studies concerning DMG in adult patients remains rare. We did a retrospective study covering the largest amount of patients to date to analyze the clinicopathological characteristics of DMG in adult. Methods: We reviewed 117 cases of adult DMG, collected their clinical and imaging data along with pathological results including H3K27M. Summarized their features and the connection with overall survival in different age groups.Results: Among 117 cases, most tumors were located at the thalamus, 39 patients had H3K27M mutation, of whom 38 demonstrated down regulation of H3K27me3. The average overall survival of H3K27M-mutant gliomas was 13 months, while that of 78 H3K27M wild-type gliomas were 11.8 months. For young patients (age＜35), The median survival time of the H3K27M-mutant was 20.1 months, while that of the H3K27M wild-type was 39.5 months. For older patients (age≥35), the median survival time of the H3K27M-mutant was 22.3 months, while that of the H3K27M wild-type was 17.1 months. The OS of patients who received biopsies, subtotal resections, and total resections were 15.8, 17.6, and 11.6 months respectively. Conclusion: The DMG in adults mainly occurred in the thalamus. H3K27M mutations tend to happen more frequently in young adults, and this genetic alteration results in a worse outcome only in young patients. For old patients, age and the approach of surgery are independent prognostic factors. Patients received biopsy instead of total resection had a better prognosis.

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