FKBP5 associated CD8 T cell infiltration is a novel prognostic biomarker in luminal B breast cancer.

OBJECTIVE: To investigate the relationship between FKBP prolyl isomerase 5 (FKBP5) gene expression and CD8 T cells in tumour progression and immunology of the luminal B subtype of breast cancer (LBBC) using bioinformatics analyses. METHODS: The Gene Expression Profiling Interactive Analysis 2, Human Protein Atlas and breast cancer gene-expression miner v4.5 databases were used for data mining and analysing FKBP5, its co-expressed genes and CD8 T cell-related markers. The Tumor IMmune Estimation Resource 2.0 database was used for analysing the correlation and prognosis of FKBP5 and CD8 T cell infiltration level in LBBC. RESULTS: Upregulated FKBP5 expression was correlated with improved survival in LBBC. Upregulated FKBP5-related CD8 T cell markers were also demonstrated to be significantly correlated with better survival in LBBC and might play a role in the biological activity of FKBP5. CONCLUSION: These findings suggest that FKBP5 and its associated CD8 T cell infiltration are potential benign prognostic indicators for LBBC.

Comparison of lobectomy and sublobar resection for stage I non-small cell lung cancer: a meta-analysis based on randomized controlled trials.

Background: This meta-analysis aimed to compare the prognostic between lobectomy and sublobar resection in patients with stage I non-small cell lung cancer (NSCLC). Methods: We conducted a detailed search in PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) comparing the prognosis of lobectomy and sublobar resection for stage I NSCLC, with the primary outcomes being overall survival (OS) and disease-free survival (DFS). Results: A total of 2222 patients were included in the 5 RCTs. The results showed no statistical difference in OS (HR=0.87, p=0.445) and DFS (HR=0.99, p=0.918) between patients who underwent lobectomy and sublobar resection during the total follow-up period. In terms of dichotomous variables, there were no statistical differences in OS (relative ratio [RR]=1.05, p=0.848) and DFS (RR=1.21, p=0.075) between the two groups during the total follow-up period, as well as 5-year OS (RR=0.96, p=0.409) and 5-year DFS (RR=0.95, p=0.270). In addition, subgroup analysis showed a better prognosis for non-adenocarcinoma patients with sublobar resection than lobectomy (HR=0.53, p=0.037), but also an increased cause of cancer death (not limited to lung cancer) (RR=1.56, p=0.004). Conclusion: Our results showed that for stage I NSCLC, lobectomy is usually not a justified operation. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023407301, identifier CRD42023407301.

Prognostic significance of CTNNB1 mutation in hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUNDS: Hepatocellular Carcinoma (HCC) is one of the most common malignant cancers in humans and has a high fatality rate. In recent years, researchers have verified that the Wnt/ß-catenin signaling pathway affects the clinicopathological features and prognosis of patients with HCC. Although many studies have investigated the relationship between Wnt/ß-catenin signaling pathway and HCC, the prognostic value of ß-catenin in HCC remains inconclusive. CTNNB1 (Catenin Beta-1) is an important factor in the Wnt/ß-catenin signaling pathway. However, no consensus has been reached on the clinical and prognostic significance of CTNNB1 mutations in HCCs. METHODS: Eligible studies and relevant data were obtained from PubMed, Web of Science, Elsevier, Cochrane Library, Ovid, and Embase databases. The correlation between CTNNB1 mutations and clinical/prognosis of patients were evaluated. A fixed- or random-effects model was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Seventeen studies matched the selection criteria, and 1828 patients were included. This meta-analysis demonstrated that patients with HCC with CTNNB1 mutations had favorable clinicopathological features and survival. The combined ORs of 1-, 3- and 5-year overall survival were0.52 (n = 6 studies, 95% CI: 0.34-0.81, Z = 2.89, P =0.004, 0.28 (n =6 studies, 95% CI: 0.18-0.42, Z = 6.03, P<0.00001), -0.22 (n = 6 studies, 95% CI: 0.37-0.06, Z = 2.78, P = 0.005), respectively. Additionally, CTNNB1 mutation might be significantly associated with differentiation (OR = 0.54, 95% CI:0.36-0.81, Z = 2.98, P = 0.003), TMN stages (Tumor, Node, Metastasis staging classification) (OR = -0.25, 95% CI:-0.33--0.18, Z = 6.60, P<0.00001), liver cirrhosis (OR = 0.21, 95% CI:0.11-0.39, Z = 4.94, P< = 0.00001), and HBV (Hepatitis B Virus) infection (OR = 0.44, 95% CI:0.31-0.64, Z = 4.37, P<0.0001), but not with tumor size, metastasis, vascular invasion, and HCV infection. CONCLUSIONS: CTNNB1 mutation can serve as an indicator of favorable prognosis as well as a novel target for treatment in HCC.

[Role of hydrogen sulfide on expression of phosphatidylinositol 3 kinase/protein kinase B signal pathway in rats with intestinal ischemia/reperfusion injury].

OBJECTIVE: To explore the effect of hydrogen sulfide (H2S) on expression of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signal pathway in rats with intestinal ischemia/reperfusion (IRI) injury. METHODS: Thirty male Wistar rats were divided into sham operation group (Sham group), IRI group, and H2S precursor sodium hydrosuphide (NaHS) intervention group (IRI+NaHS group) by random number table method, with 10 rats in each group. The animal model of IRI was established by 60 minutes superior mesenteric artery (SMA) blockage with non-invasive vascular clamp and 120 minutes reflow. SMA was dissociated and peritoneum cavity was closed in Sham group. The rats in IRI+NaHS group was received NaHS (100 µmol/kg bolus+1.07 mmol×kg-1×h-1 infusion) 10 minutes prior to the onset of reperfusion, while the rats in IRI group and Sham group were received equal volume of normal sodium. Blood in vena cava was collected. H2S was detected by sensitive sulfide electrode. Rats were sacrificed after blood collection. Histopathology change was observed by hematoxylin-eosin (HE) staining, ileal pathological score was studied by Chiu score. The protein expressions of phosphated Akt (p-Akt), Akt, PI3K, cleaved caspase-9, mammalian target of rapamycin (mTOR) were determined by Western Blot. RESULTS: Compared with the Sham group, there was intestinal mucosa structure disorder edema and shedding villous fracture in the IRI group. Ileal pathological score in IRI group was significantly increased (4.21±0.15 vs. 0.15±0.03, P < 0.01), while plasma H2S in IRI group was significantly decreased (µmol/L: 26.72±3.17 vs. 38.34±5.24, P < 0.01). Ileal p-Akt, PI3K, caspase-9 and mTOR protein in IRI group were significantly increased (p-Akt/GAPDH: 2.67±0.12 vs. 0.24±0.05, PI3K/GAPDH: 1.42±0.07 vs. 0.57±0.08, caspase-9/GAPDH: 4.23±0.61 vs. 0.13±0.02, mTOR/GAPDH: 2.17±0.23 vs. 0.23±0.02, all P < 0.01). Compared with the IRI group, pathological changes of intestinal mucosa in the IRI+NaHS group was improved, ileal pathological score was significantly decreased (1.56±0.02 vs. 4.21±0.15, P < 0.01), plasma H2S was significantly increased (µmol/L: 32.36±2.45 vs. 26.72±3.17, P < 0.01) and ileal p-Akt, PI3K were significantly increased (p-Akt/GAPDH: 5.12±0.08 vs. 2.67±0.12, PI3K/GAPDH: 3.14±0.05 vs. 1.42±0.07, both P < 0.01), while caspase-9, mTOR in IRI+NaHS group were significantly decreased (caspase-9/GAPDH: 2.12±0.24 vs. 4.23±0.61, mTOR/GAPDH: 1.37±0.28 vs. 2.17±0.23, both P < 0.01). CONCLUSIONS: H2S attenuates intestinal injury in IRI rats by up-regulating PI3K/Akt signal pathway and down-regulating caspase-9 and mTOR.

[Change in endogeous hydrogen sulfide in patients with acute pancreatitis and its relationship to coagulation function].

Objective: To study the change in endogenous hydrogen sulfide (H2S) in patients with acute pancreatitis and its relationship to coagulation function. Methods: A prospective case control study was conducted. Forty patients with mild acute pancreatitis (MAP group) and 40 with severe acute pancreatitis (SAP group) admitted to Yiwu Central Hospital in Zhejiang Province from December 2002 to March 2015 were enrolled. Forty healthy persons served as control (healthy control group). Blood was collected to determine the levels of H2S, blood coagulation factor Ⅷ (FⅧ), von Willebrand factor (vWF), plasminogen (PLG), antithrombin (AT), platelet count (PLT), tissue factor (TF), tumor necrosis factor-α (TNF-α), and protease activated receptor-1 (PAR-1). The correlations among the above parameters were analyzed. Results: There was no statistical significance in sex, age, body weight and time of disease among three groups, indicating it was comparable among the groups. Compared with healthy control group, the levels of H2S, FⅧ, vWF, TF, TNF-α, and PAR-1 in MAP and SAP groups were significantly elevated [H2S (µmol/L): 67.42±6.34, 112.47±12.69 vs. 42.57±4.18, FⅧ: (67.5±5.8)%, (82.3±4.7)% vs. (57.2±6.4)%, vWF: (112.6±9.7)%, (142.5±12.5)% vs. (76.4±8.2)%, TF (ng/L): 45.27±4.34, 64.76±6.25 vs. 18.15±1.89, TNF-α (ng/L): 197.67±13.62, 324.72±25.54 vs. 20.08±2.57, PAR-1 (fluorescence intensity): 32.16±4.43, 56.12±7.07 vs. 12.27±2.12, all P < 0.01], and PLG and AT activity were significantly decreased [PLG: (52.4±4.7)%, (36.7±3.2)% vs. (62.1±5.6)%, AT: (43.2±6.9)%, (35.5±5.4)% vs. (53.6±6.1)%, all P < 0.01]. The changes in the parameters in SAP group were more remarkable than those in MAP group (all P < 0.01). PLT in SAP group was significantly lower than that in healthy control and MAP groups (×109/L: 8.5±1.1 vs. 15.7±2.8, 12.4±1.9, both P < 0.01). H2S was positively correlated with FⅧ, vWF, TF, TNF-α, and PAR-1 (r value was 0.56, 0.61, 0.72, 0.66, 0.64, respectively, all P < 0.01), and it was negatively correlated with PLG and AT (r value was -0.64, -0.57, both P < 0.01). Conclusion: As an inflammatory factor, endogenous H2S deteriorates coagulation function in patients with acute pancreatitis by up-regulating TF, TNF-α, and PAR-1.