The most bioactive fraction of stir-fried Radix Paeoniae Alba regulating IL-6/STAT3 signaling pathway in allergic asthma mouse.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Paeoniae Alba (RPA), a traditional Chinese medicine, has been used frequently in the treatment of asthma. Previous studies demonstrated the dichloromethane fraction of Stir-Frying RPA (FDCM) enhanced the effect of anti-allergic asthma compared with the dichloromethane fraction of RPA (DCM). AIM OF THE STUDY: The significant increasing of Paeoniflorin (PF), ethyl gallate (EG), 1,2,3,4,6-pentagalloylglucose (PGG) had been observed in FDCM. This study aimed to investigate the effects and mechanisms of these compounds from FDCM in ovalbumin (OVA)-induced allergic asthma mouse model. MATERIALS AND METHODS: The significant difference contents compounds fraction (FB-40) and other fractions in FDCM were enriched by Medium Pressure Liquid Chromatography (MPLC). The pharmacodynamics was verified among all fractions in OVA-induced allergic asthma mice. Moreover, the drug dose dependence of FB-40 (0.42 mg/kg, 0.21 mg/kg, and 0.07 mg/kg), which were the most active fraction from FDCM for anti-allergic asthma, was explored. The expression of IL-6, p-STAT3, and STAT3 was analyzed by Western blot analysis. In addition, the main components of FB-40 were identified by UPLC with standards. Finally, the anti-inflammatory effects of the main components from FB-40 were detected by LPS-stimulated BEAS-2B cells using an Elisa assay. RESULTS: The results showed that FB-40 was the most active fraction from FDCM, which could significantly improve the lung tissue pathological condition, and decrease the number of inflammatory cells in bronchoalveolar lavage fluid (BALF). It had greater pharmacological activity than its main component PF. FB-40 also showed dose dependence and regulated the IL-6/STAT3 signaling pathway in allergic asthma mice. Besides, PF, Albiflorin (AF), PGG, EG, and 1,2,3,6-Tetra-O-galloyl-ß-D-glucose (TGG) from FB-40 were identified by UPLC with the standard. At last, in the LPS-induced BEAS-2B cell experiments, EG, PGG, 1,2,3,6-Tetra-O-galloyl-ß-D-glucose (TGG) showed stronger inhibiting activities of cytokine than the monoterpenoid glycosides (PF and AF). CONCLUSION: The research proved that FB-40 was an active fraction in FDCM, which regulates IL-6/STAT3 Signaling Pathway to ameliorate allergic asthma. Gallic acids including TGG and PGG, and EG also play a role in the treatment of allergic asthma in FB-40.

CircASPH Promotes Hepatocellular Carcinoma Progression Through Methylation and Expression of HAO2.

CircRNAs have been reported to be related to hepatocellular carcinoma (HCC) development. Limited studies have revealed the expression profile of circRNAs in tumor and para-tumor normal samples in HCC patients. We found that circASPH was significantly increased in HCC tumor samples and that the level of circASPH was closely related to the overall survival of HCC patients. Mechanistically, circASPH could regulate the methylation of the promoter and expression of hydrocyanic oxidase 2 (HAO2) to promote HCC progression by acting as a sponge for miR-370-3p, and miR-370-3p could target DNMT3b and increase the 5mC level. In summary, our study determined that circASPH could regulate the methylation and expression of HAO2 and it could be considered an important epigenetic regulator in HCC progression.

Surgical Strategy for Resecting Hepatocellular Carcinoma in the Caudate Lobe: Isolated or Combined Lobectomy? A Single-Center Study and Meta-Analysis.

BACKGROUND: Resection of hepatocellular carcinoma (HCC) originating in the caudate lobe remains challenging, while the optimal extent of resection is debated. We aimed to evaluate the relative benefits of combined caudate lobectomy (CCL) versus isolated caudate lobectomy (ICL) for caudate HCC. METHODS: Patients who underwent curative-intent resection for caudate HCC between January 2010 and December 2018 were identified from a single-center database. Surgical outcomes of the two strategy groups were analyzed before and after propensity score matching. A systematic review with meta-analysis was also performed to compare outcomes of CCL versus ICL for caudate HCC. RESULTS: A total of 28 patients were included: 11 in the CCL and 17 in the ICL group. Compared with ICL, the CCL group contained patients with larger tumors and a higher incidence of vascular invasion. After propensity score matching, 6 pairs of patients were selected. In the well-matched cohort, CCL demonstrated significantly improved recurrence-free survival (RFS) (P = 0.047) compared with ICL; no significant differences were noted for overall survival (OS), operation time, blood loss and morbidity rate. A total of 227 patients from nine eligible studies and ours were involved in the systematic review. Meta-analysis revealed that CCL provided better RFS (hazard ratio 0.54, 95% confidence interval 0.31-0.92) than ICL; no significant differences were observed in OS, operation time, blood loss and morbidity rate. CONCLUSION: CCL confers superior RFS over ICL without compromise of perioperative outcomes and should be prioritized for patients with caudate HCC when feasible, especially for those with large-sized tumors.

Analysis of the efficacy and prognostic factors of PD-1 inhibitors in advanced gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) is highly malignant, its early diagnosis is difficult, and the 5-year survival rate is less than 5%. For patients with advanced GBC (GBCa), combined chemotherapy, radiotherapy, targeted therapy, and immunotherapy are needed to improve the overall survival (OS) rate of patients. METHODS: Data were collected from 53 patients with GBCa who had volunteered to receive programmed death protein-1 (PD-1)-based treatment at the First Affiliated Hospital of Nanjing Medical University from February 2018 to February 2021. Statistical analysis of the collected data, including Kaplan-Meier method, log-rank test, Cox proportional hazard regression model and other methods. RESULTS: The objective response rates (ORRs) and disease control rates (DCRs) of 53 participants 3 months after receiving immunotherapy were 30.2% and 79.2%, respectively. The ORRs and DCRs of the combined treatment group were higher than those of the camrelizumab group (CG) (P<0.05). The DCRs of the camrelizumab plus apatinib group (CAG) at 3 and 6 months were 90.9% and 45.5% (P=0.003), respectively, while the DCRs at 3 and 6 months of the camrelizumab plus chemotherapy group (CCG) were 85.7% and 71.4% (P=0.450), respectively. After treatment, there were statistically significant differences before and after CA199 for each group (P<0.05). The median progression-free survival (mPFS) of the 53 participants was 7 months, and the median overall survival (mOS) was 12 months. The mPFS and mOS of the CAG and the CCG were greater than those in the CG (6 vs. 3 months, P<0.001, 12 vs. 8 months, P=0.019; 9 vs. 3 months, P<0.001, 13 vs. 8 months, P<0.001, respectively). A total of 16 cases had grade 1 or 2 adverse events, and 3 cases had grade 3 and higher adverse events. CONCLUSIONS: For GBCa patients, PD-1 combined with targeted therapy or chemotherapy is more effective than immunotherapy alone. The targeted therapy group has more obvious early effects on the disease control rate, and combined chemotherapy can achieve sustained effects, providing new ideas for the future GBCa application of immune, targeted, and chemotherapy sequential therapy.

Identification and validation of a six immune-related gene signature for prediction of biochemical recurrence in localized prostate cancer following radical prostatectomy.

BACKGROUND: Prostate cancer (PCa) is the second lethal heterogeneous cancer among males worldwide, and approximately 20% of PCa patients following radical prostatectomy (RP) will undergo biochemical recurrence (BCR). This study is aimed to identify the immune-related gene signature that can predict BCR in localized PCa following RP. METHODS: Expression profile of genes together with clinical parameters from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database (GEO) and the immune-related genes from the Molecular Signatures Database v4.0 were applied to construct and validate the gene signature. The Cox regression analyses were conducted to identify the candidate genes and establish the gene signature. To estimate the prognostic power of the risk score, the time-dependent receiver operating characteristic (ROC) analysis and Harrell's index of concordance (C-index) were utilized. We also established a nomogram to forecast the probability of patients' survival. RESULTS: A total of 268 patients from the TCGA and 77 patients from GSE70770 and six immune-related genes (SCIN, THY1, TBX1, NOTCH4, MAL, BNIP3L) were eventually selected. The Kaplan-Meier analysis demonstrated that patients in the low-risk group had a significantly longer recurrence-free survival (RFS) compared to those in the high-risk group. In the multivariate Cox model, the signature was identified as an independent prognostic factor, which was significantly associated with RFS (TCGA: HR =5.232, 95% CI: 1.762-15.538, P=0.003; GSE70770: HR =2.158, 95% CI: 1.051-4.432, P=0.036). Moreover, the C-index got improved after incorporating the risk score into original clinicopathological parameters. In addition, the novel nomogram was constructed to better predict the 1-, 3- and 5-year RFS. CONCLUSIONS: This signature could serve as an independent prognostic factor for BCR. Incorporation of our signature into traditional risk classification might further stratify patients with different prognosis, which could assist practitioners in developing clinical decision-making.

Complete response to immunotherapy combined with an antiangiogenic agent in multiple hepatic metastases after radical surgery for advanced gallbladder cancer: a case report.

Most advanced gallbladder cancers (GBCa) are unresectable or metastatic once diagnosed, and even patients who undergo surgery have a high risk of recurrence and metastasis. Immunotherapy, especially immune checkpoint inhibitors (ICIs), combined with an antiangiogenic agent, is an emerging prospective treatment for GBCa. However, the efficacy and safety of this combination therapy have not yet been investigated. We report the case of a 70-year-old female patient with recurrent metastatic GBCa (stage IVB) after radical surgery. Immunohistochemical examination revealed that 10% of the tumor cells expressed programmed cell death protein-1 (PD-1) and programmed cell death receptor ligand 1 (PD-L1). Whole-exome sequencing showed cancer tissues with a low tumor mutational burden (TMB) and microsatellite stability (MSS). The patient received Camrelizumab (200 mg, every three weeks) and Apatinib (40 mg/d). The clinical and immunological responses were observed, and the patient achieved a complete response after five cycles. This is the first case describing the efficacy and safety of Camrelizumab plus Apatinib in a GBCa patient with weak PD-1 and PD-L1 expression, and low TMB and MSS. The treatment had a tolerable safety profile and a complete response in the patient. Also, we found that the cluster of differentiation (CD)16+CD56+natural killer (NK) cell ratio in peripheral blood was increased after the combined treatment. Immunotherapy with antiangiogenic drugs may be a potential treatment option for patients with recurrent GBC or GBCa.