Aims. The aim of this study was to examine the effects of Xiaoaiping on the stemness of hepatocellular carcinoma (HCC) cells in vivo and to investigate the underlying molecular mechanism. Methods. A subcutaneous xenograft nude mouse model was established using Hep3B-derived HCC cells. The mice were randomly assigned to the 100 mg/kg Xiaoaiping or 100 μL/20 g normal saline (control) groups (n =3/sex/group) for daily intragastric administration for 14 days. The tumor size was closely monitored during the dosing phase. After the treatment period, the tumor tissues were weighed and harvested for mRNA and protein isolation. qPCR and Western blotting were used to evaluate the expression of cancer stemness markers (epithelial cell adhesion molecule [EpCAM], cluster of differentiation [CD13], CD90, aldehyde dehydrogenase 1 [ALDH1], CD44, and CD45), totipotency factors (sex determining region Y-box 2 [Sox2], Nanog, and octamer-binding transcription factor 4 [Oct4]), and genes involved in the Notch, Wnt/β-catenin, Hedgehog, and Hippo signaling pathways. Key Findings. The tumor size and weight were significantly reduced in the nude mice treated with 100 mg/kg Xiaoaiping when compared with the controls. The Xiaoaiping effects on the stemness markers and totipotency factors included decreased expression of EpCAM, CD24, CD47, Sox2, Oct4, and sal-like protein 4 (SALL4), as well as increased expression of CD13 and ALDH1. In addition, Xiaoaiping inhibited the Hippo, Wnt, and Hedgehog signaling pathways. Conclusion. Xiaoaiping significantly inhibited the growth of HCC xenograft in nude mice. These antitumor effects may be mediated by modulating the expression of multiple stemness markers and totipotency factors and inhibition of the Hippo, Wnt, and Hedgehog signaling pathways.
Previous studies have revealed that the peritumoral environment has a profound influence on tumor initiation and progression. Zinc-binding protein-89 (ZBP-89) has been observed to be involved with tumor development, recurrence, and metastasis. High intratumoral expression of ZBP-89 has been associated with improved prognosis in several tumor types. However, the prognostic values of peritumoral expression of ZBP-89 remain to be elucidated in patients with hepatocellular carcinoma (HCC) following curative resection. In the present study, peritumoral ZBP-89 expression was examined using immunohistochemistry in 102 HCC patients who had received curative hepatectomy. Expression of ZBP-89 protein was positive in 66.3% of the peritumoral samples from 102 HCC patients. HCC patients with high peritumoral ZBP-89 expression exhibited significantly shorter disease-free survival (DFS) times (P=0.012) than those patients with low peritumoral ZBP-89 expression. Additionally, high ZBP-89 expression in peritumoral HCC tissue was positively associated with the presence of liver cirrhosis. Univariate and multivariate Cox proportional hazard regression analyses demonstrated that albumin levels ≤35 g/l, multiple tumors, tumor sizes ≥5 cm, and macroscopic vascular invasion may serve as independent prognostic factors for overall survival (OS) [hazard ratio (HR)=2.031; P=0.014] in patients with HCC. The multivariate Cox regression model identified that high ZBP-89 expression, multiple tumors and macroscopic vascular invasion were independent prognostic factors for shorter DFS durations. High expression of ZBP-89 in peritumoral HCC tissues was associated with a shorter DFS in HCC patients following curative hepatectomy. Additionally, high ZBP-89 expression in peritumoral HCC tissue was positively associated with the presence of liver cirrhosis in HCC patients, indicating that cirrhosis accompanied by high ZBP-89 expression may be a contributing factor to the poor prognosis of patients with HCC. Therefore, peritumoral ZBP-89 expression may be a good prognostic marker to predict DFS time in HCC patients following curative hepatectomy and may provide novel insights into the molecular mechanisms of HCC initiation.
Background Double-expressor lymphoma (DEL), defined as cases with concurrent MYC and BCL2 proteins overexpression, is associated with poor prognosis when treated with R-CHOP alone. Prognostic data on DEL treated with intensive treatment are limited and controversial.Methods We retrospectively report our experiences about 221 consecutive de-novo diffuse large B cell lymphoma patients and analyze the role of intensive therapies for 65 patients with DEL.Results No significant difference in clinical characteristics and survival outcomes between DEL and non-DEL was observed. Overall, 32 (76.2%) and 20 (87.0%) patients with DEL received R-CHOP and intensive treatment achieved partial response or complete response, respectively. Intensive therapies may improve the prognosis over R-CHOP in patients with DEL (P = 0.029 for PFS, P = 0.026 for OS). Subgroup analysis according to clinical characteristics showed intensive therapies resulted in better prognosis than R-CHOP regimen in DEL patients aged under 60 years (P = 0.004 for PFS; P =0.090 for OS), whereas no significant superiority was found in DEL patients aged over 60 years (P = 0.646 for PFS; P = 0.361 for OS).Conclusions This second Chinese cohort study suggests that intensive immunochemotherapy may have the ability to improve the prognosis of young patients with DEL.
Double-expressor lymphoma (DEL) is associated with a poor prognosis. The standard treatment for patients with DEL remains controversial. A comparison of the safety and feasibility of R-CHOP and DA-EPOCH-R as the first-line therapy for patients with DEL is urgently needed.Methods: The clinical and treatment outcomes of 75 DEL patients were retrospectively analyzed. The role of DA-EPOCH-R was determined and compared to that of R-CHOP in DEL patients. PubMed, Embase, the Cochrane Central Library, and ClinicalTrials. gov were systematically searched up to November 1, 2021 and were evaluated by Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Articles comparing DA-EPOCH-R versus R-CHOP in patients with DEL were included.Results: Overall, 49 and 26 DEL patients received R-CHOP and DA-EPOCH-R, respectively. Although the difference in response for patients who received R-CHOP and DA-EPOCH-R was not significant (P = .347), DA-EPOCH-R may improve the prognosis compared to R-CHOP (P = .056 for progression-free survival [PFS], P = .009 for overall survival [OS]). A systematic review and meta-analysis including 412 DEL patients in six articles were conducted. The event rate for 3-year PFS was significantly lower in patients receiving DA-EPOCH-R treatment than in those undergoing R-CHOP treatment (OR = 0.63, 95% CI = 0.42-0.94, P = .02), whereas no statistically significant difference was found in the HRs for both PFS and OS or the event rate for 3-year OS. Conclusion:The results of this study indicated that DA-EPOCH-R might improve the prognosis of DEL patients compared with R-CHOP.
Background: Although the axillary web syndrome (AWS) is a common post-mastectomy complication. A small number of studies have reported treatment strategies for the AWS that showed interventions for one month were an effective strategy. The current study in AWS patients investigated the clinical efficacy of short-term massage manipulation (STMM) combined with remote guided self-exercise (RGS).Method: The patients were randomized into either short-term massage manipulation combine with remote guided self-exercise group (STMM+RGS group) or treatment without massage manipulation and remote guided self-exercise group (T- STMM+RGS group). STMM+RGS group received massage manipulation for 20 min per day for 7 days as total hospitalized therapy and then received telephone-guided therapy for 9 weeks, rehabilitation gymnastics provided during hospitalization.T- STMM+RGS group received rehabilitation gymnastics only. The primary outcome was changes in upper limb range of movement (ROM), assessed at 3, 6, and 9 weeks after intervention. The secondary outcomes were scores of visual analog scales (VAS), disability of arm, shoulder and hand (DASH) index, and activities of daily living (ADL) index assessed at 3, 6, 9 weeks of follow-up.Results: 106 patients were enrolled in the trial, 86 were randomized to treatment groups, with 79 completing the trial (41 in STMM+RGS group, 38 in T-STMM+RGS group). At 6 and 9 weeks of follow-up ROM had improved in STMM+RGS group compared with that observed in T-STMM+RGS group(p<0.05). This improvement was more pronounced and significantly different at 9 weeks(p<0.01).. There was also a significant difference in VAS at 6 and 9 weeks between the two groups. The DASH score improved significantly in STMM+RGS group compared with that in T-STMM+RGS group at 3, 6, and 9 weeks of follow-up(p<0.01), while the ADL score was significantly different (p<0.05) in the two groups at 3 and 6 weeks , but showed no significant difference after 9 weeks of follow-up.Conclusion: The combination of STMM and RGS improves upper limb ROM, relieves upper limb pain, and reduces the occurrence of disabilities in post-mastectomy patients with the AWS.
Background: To compare the necessity between Fine-needle aspiration (FNA) biopsy and ultrasound examination in the diagnosis of different sizes of the thyroid nodules. Does the FNA biopsy have to do it all? Methods: A retrospective analysis was performed to 8352 thyroid patients who underwent thyroid operations between 2011 and 2016 in our hospital. Results: In FNA(+) group, the nodule was more smaller, the increment speed of the amount of operation increased more faster. In no FNA group, the increment speed decreased not obvious in nodules ≥10mm sub-group, but tremendous in both nodules 5mm-10mm sub-group and nodules ≤ 5mm sub-group no matter the nodules were malignant or benign. Over the six years, the total operation number increased, but operation of patients with nodules ≥10mm decreased slightly and operation of patients with nodules <10mm increased markedly especially in nodules ≤ 5mm sub-group. In no FNA group, to compare the malignancy or benign tumor after surgery between nodules 5mm-10mm sub-group and nodules ≥10mm sub-group, χ2=12.000,P=0.001, and between nodules ≤ 5mm sub-group and nodules ≥10mm sub-group, χ2=7.968,P=0.005, but between nodules 5mm-10mm sub-group and nodules ≤ 5mm sub-group, χ2=0.669,P=0.414. Further pairwise comparison showed, in nodules 5mm-10mm sub-group and nodules ≤ 5mm sub-group, the probability of benign tumor was greater than nodules ≥10mm sub-group. Conclusions: In thyroid nodules ≥10mm sub-group, there is no statistical difference between ultrasound diagnosis and biopsy. In nodules <10mm sub-groups, FNA biopsy has the great significance in the diagnosis to add more references for the subsequent treatment.
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