Efficacy and safety of anlotinib as an adjuvant therapy in hepatocellular carcinoma patients with a high risk of postoperative recurrence.

Objective: Hepatocellular carcinoma (HCC) has a high rate of postoperative recurrence and lacks an effective treatment to prevent recurrence. This study aims to investigate the efficacy and safety of anlotinib in postoperative adjuvant therapy for HCC patients with high-risk recurrence factors. Methods: For this multicenter, retrospective study, we recruited 63 HCC patients who received either anlotinib (n=27) or transcatheter arterial chemoembolization (TACE) (n=36) from six research centers in China between March 2019 and October 2020. The primary endpoint was disease-free survival (DFS) and the secondary endpoints were overall survival (OS) and safety. Results: In this study, the median follow-up time was 25.9 and 26.8 months in the anlotinib and TACE groups, respectively. There was no significant difference in the median DFS between the anlotinib [26.8 months, 95% confidence interval (95% CI): 6.8-NE] and TACE groups (20.6 months, 95% CI: 8.4-NE). The 12-month OS rates in the anlotinib and TACE groups were 96.3% and 97.2%, respectively. In the anlotinib group, 19 of 27 patients (70.4%) experienced treatment-emergent adverse events, with the most common events (≥10%) being hypertension (22.2%) and decreased platelet count (22.2%). Conclusions: The results indicate that anlotinib, as a new, orally administered tyrosine kinase inhibitor, has the same efficacy as TACE, and side effects can be well controlled.

Prevalence of malocclusion in Chinese schoolchildren from 1991 to 2018: A systematic review and meta-analysis.

BACKGROUND: Malocclusion is a common oral health problem in schoolchildren. Literature describing the prevalence of malocclusion varies substantially across China. AIM: This study identified the epidemiological characteristics of malocclusion among Chinese schoolchildren from 1991 to 2018. DESIGN: Six English and Chinese electronic databases were searched through November 2018. The search was supplemented by hand searching to identify relevant surveys. The overall prevalence of malocclusion was estimated by a random-effects meta-analysis model, and variations in different groups were assessed by subgroup meta-analysis. RESULTS: Thirty-seven eligible articles describing 117 682 samples were investigated. The pooled national prevalence for malocclusion was 47.92% (95% CI: 58.6%-71.9%). For the Angle classification, the overall prevalence rates were 30.07% (95% CI: 25.37%-35.48%), 9.91% (95% CI: 7.41%-13.79%), and 4.76% (95% CI: 3.85%-6.54%) for Class I, Class II, and Class III malocclusion, respectively. A deep overbite (16.67%, 95% CI: 11.50%-23.08%) was shown to be the most common trait of malocclusion. When stratified by sex, males had a slightly higher prevalence than females (RR = 1.04, 95% CI: 1.01-1.06). More importantly, an ascending trend and substantial variations across the country were observed. CONCLUSIONS: Our results confirmed that malocclusion has become a serious oral health problem in Chinese schoolchildren, highlighting the need for proactive interventions at an early age. Moreover, high-quality epidemiological studies on malocclusion are still required.

Simultaneous Activation of Immunogenic Cell Death and cGAS-STING Pathway by Liver- and Mitochondria-Targeted Gold(I) Complexes for Chemoimmunotherapy of Hepatocellular Carcinoma.

Induction of immunogenic cell death (ICD) and activation of the cyclic GMP-AMP synthase stimulator of interferon gene (cGAS-STING) pathway are two potent anticancer immunotherapeutic strategies in hepatocellular carcinoma (HCC). Herein, 12 liver- and mitochondria-targeting gold(I) complexes (9a-9l) were designed and synthesized. The superior complex 9b produced a considerable amount of reactive oxygen species (ROS) and facilitated DNA excretion, the ROS-induced ICD and DNA activated the cGAS-STING pathway, both of which evoked an intense anticancer immune response in vitro and in vivo. Importantly, 9b strongly inhibited tumor growth in a patient-derived xenograft model of HCC. Overall, we present the first case of simultaneous ICD induction and cGAS-STING pathway activation within the same gold-based small molecule, which may provide an innovative strategy for designing chemoimmunotherapies for HCC.

Spontaneous rupture of primary splenic angiosarcoma: a case report and literature review.

BACKGROUND: Primary angiosarcoma of the spleen is a rare mesenchymal malignant tumor of vascular origin often with a poor prognosis, due to its high metastatic potential. This disease often presents with atraumatic rupture and lethal hemorrhage. CASE PRESENTATION: We report a case of a 65-year-old man who presented with abdominal pain, anemia, thrombocytopenia, and palpable abdominal mass with unstable blood pressure. Laparotomy revealed a huge actively bleeding spleen, thus splenectomy was performed. Some liver metastasis foci were also found during the procedure. Histopathology diagnosis of the removed spleen was primary splenic angiosarcoma. The patient was discharged on the 10th day post operation with no complication. CONCLUSIONS: Splenic angiosarcoma should be considered one of the differential diagnoses in patients with spleen parenchymal lesions. Definitive diagnosis requires laparotomy followed by splenectomy. In the majority of the patients with spleen angiosarcoma, metastatic diseases have already occurred at the time of laparotomy, so splenectomy is an approach more for diagnostic purpose rather than curative purpose.

HMOX1 Attenuates the Sensitivity of Hepatocellular Carcinoma Cells to Sorafenib via Modulating the Expression of ABC Transporters.

Hepatocellular carcinoma (HCC) represents a common malignancy, and mechanisms of acquired sorafenib resistance during the treatment of HCC patients remain elusive. The present study performed integrated bioinformatics analysis and explored the potential action of heme oxygenase 1 (HMOX1) in sorafenib-resistant HCC cells. Differentially expressed genes (DEGs) of the sorafenib-resistant group as compared to the sorafenib-sensitive group from GSE140202 and GSE143233 were extracted. Fifty common DEGs between GSE140202 and GSE143233 were extracted. Ten hub genes were identified from the protein-protein interaction network based on common DEGs. Experimental results revealed the upregulation of HMOX1 in sorafenib-resistant HCC cells. HMOX1 silence promoted the sensitivity to sorafenib in sorafenib-resistant HCC cells; overexpression of HMOX1 attenuated the sensitivity. In addition, HMOX1 silence downregulated the mRNA expression of ABC transporters in sorafenib-resistant HCC cells, while HMOX1 overexpression upregulated mRNA expression of ABC transporter expression in HCC cells. Further analysis also revealed that high expression of HMOX1 was associated with shorter OS and DSS in HCC patients. In conclusion, our analysis identified ten hub genes associated with sorafenib resistance in HCC. Further validation studies demonstrated that HMOX1 promoted sorafenib resistance of HCC cells via modulating ABC transporter expression.

Global burden of primary liver cancer by five etiologies and global prediction by 2035 based on global burden of disease study 2019.

BACKGROUND: Using data from the global burden of disease (GBD) between 1990 and 2019 to report the leading etiological factors and hazards for liver cancer by HBV (LCHB), HCV (LCHC), alcoholic use (LCAL), NASH (LCNA), and other causes (LCOT). METHOD: The estimated annual percentage change (EAPC) and age-standardized incidence rate (ASR) in different districts, sex, and age are used to quantify the change of etiologies of liver cancer. Age-period-cohort models were performed to predict the primary liver cancer incidence and case numbers. RESULTS: Based on the GBD database of the whole world for the five etiologies of liver cancer in 2019, the percentage of incidence of LCAL, LCHB, LCHC, LCNA, and LCOT are 18.4%, 41%, 28.5%, 6.8%, and 5.3%, respectively. Fiver etiologies of liver cancer show gender differences, with LCHB and LCAL being more prevalent in men, and LCHC, LCNA being more prevalent in women. Besides, live cancer of males is because of alcohol using and smoking, while the reason of liver cancer of females is drug use, high BMI and high fasting plasma glucose. Interestingly, the incidence of LCHC in women over 85 years old, LCNA in women over 75 years old, and LCOT in women over 75 years old were all higher than that in men. According to the future prediction, the incidence rate of liver cancer itself, as well as the five causes of liver cancer, tends to decrease gradually after 2019, while the incidence rate of LCNA in males will continue to increase until 2025. CONCLUSIONS: The incidence of liver cancer has been increasing and its major causes vary considerably at global, regional, or national levels, also vary by gender and age group.

Triptolide alleviates hepatic ischemia/reperfusion injury by attenuating oxidative stress and inhibiting NF-κB activity in mice.

BACKGROUND: Hepatic I/R injury is unavoidable in liver transplantation and surgery. This remains a significant problem in surgical procedures. The purpose of this study was to investigate the effects of triptolide on liver ischemia/reperfusion (I/R) injury and related mechanisms in mice. MATERIALS AND METHODS: Male C57BL/6 mice were randomized into four groups: (1) sham group; (2) sham-triptolide group; (3) I/R group; and (4) I-R/triptolide group. Ninety minutes of warm ischemia was induced and flow by 24 h reperfusion. Serum alanine aminotransferase and aspartate aminotransferase were assayed, pathologic alterations and (NF)-κB p65 immunohistochemistry were observed. Liver malondialdehyde (MDA) level, activity of endogenous antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and activity of neutrophil accumulation marker myeloperoxidase (MPO) were measured. TNF-α, IL-6, and IL-1ß mRNA were detected by RT-PCR, whereas nuclear factor (NF)-κB p65 and IκBα were assessed with Western blotting. RESULTS: Plasma aminotransferase activity was higher in the I/R group than in the I/R-triptolide group. MDA level and neutrophil infiltration were also markedly reduced, while SOD, CAT, and GSH-Px levels increased in I/R-triptolide group compared with I/R group. In group 4, histopathologic changes were significantly attenuated in triptolide-treated livers. In comparison with group 3, triptolide reduced NF-κB p65 nuclear and IκBα expression, and effectively suppressed pro-inflammatory cytokine level during the I/R. CONCLUSIONS: These results suggest that triptolide has protective effects against hepatic I/R injury. Its mechanisms might be related to reduction of oxidative stress and neutrophil infiltration and inhibition NF-κB p65 activity.

Non-Coding RNA m6A Modification in Cancer: Mechanisms and Therapeutic Targets.

Recently, N6-methyl-adenosine (m6A) ribonucleic acid (RNA) modification, a critical and common internal RNA modification in higher eukaryotes, has generated considerable research interests. Extensive studies have revealed that non-coding RNA m6A modifications (e.g. microRNAs, long non-coding RNAs, and circular RNAs) are associated with tumorigenesis, metastasis, and other tumour characteristics; in addition, they are crucial molecular regulators of cancer progression. In this review, we discuss the relationship between non-coding RNA m6A modification and cancer progression from the perspective of various cancers. In particular, we focus on important mechanisms in tumour progression such as proliferation, apoptosis, invasion and metastasis, tumour angiogenesis. In addition, we introduce clinical applications to illustrate more vividly that non-coding RNA m6A modification has broad research prospects. With this review, we aim to summarize the latest insights and ideas into non-coding RNA m6A modification in cancer progression and targeted therapy, facilitating further research.

Low expression of KIF20A suppresses cell proliferation, promotes chemosensitivity and is associated with better prognosis in HCC.

This study analysed the microarray datasets from Gene Expression Omnibus (GEO) database, and aimed to identify novel potential hub genes associated with the progression of HCC via bioinformatics analysis and experimental validation. The common differentially expressed genes (DEGs) from five GEO datasets were screened using GEO2R tool. The expression and survival analysis of hub genes in HCC were performed using Gene Expression Profiling Interactive Analysis, UALCAN and Kaplan-Meier plotter tools. In vitro functional assays were used to determine the caspase-3, -9, cell proliferation and chemo-sensitivity of HCC cells. A total of 177 common DEGs were identified between normal liver and HCC tissues among these datasets. Functional enrichment and PPI network analysis identified 22 hub genes from the common DEGs. The mRNA expression of 22 hub genes was all significantly up-regulated in HCC tissues compared to that in normal liver tissues. Further survival analysis showed that 10 hub genes predicted poor prognosis of patients with HCC. More importantly, the in vitro functional studies demonstrated that KIF20A knockdown suppressed the HCC cell proliferation and promoted the chemosensitivity of HCC cells to cisplatin and sorafenib. In conclusion, the present study identified a total of 177 common DEGs among 5 GEO microarray datasets and found that 10 hub genes could predict the poor prognosis of patients with HCC using the comprehensive bioinformatics analysis. Furthermore, KIF20A silence suppressed cell proliferation and enhanced chemosensitivity in HCC cells. Further studies may be required to determine the mechanistic role of these hub genes in HCC progression.

Enucleation is Better for a Giant Hemangioma Proximal to the Hepatic Portal Vascular Structures.

The aim of this study is to compare the effect of liver enucleation with resection of a giant hemangioma proximal to the hepatic portal vascular structures. From 2008 to 2014, 53 patients with giant hemangiomas proximal to the hepatic portal vascular structures underwent surgery in our hospital by the same surgical team. The indications for surgery included a tumor size greater than 8 cm, a middle size greater than 4 cm but with abdominal pain, a rapidly increased tumor size with uncertain malignancy, or tumor rupture. Thirty-two patients (60 %) had pain only, 15 (29 %) had pain with tumor growth, 5 patients (9 %) had an uncertain diagnosis, and 1 patient (2 %) had tumor rupture. Enucleation was performed in 31 patients and liver resection was performed in 22 patients. There were no significant differences in the size of the hemangioma (13.9 ± 3.1 vs 12.3 ± 5.5 cm; P > 0.05), preoperative liver function tests, hemoglobin levels, and platelet counts between the enucleation and resection groups. The mean intraoperative blood loss was significantly less in the enucleation group compared with the resection group (350.9 ± 89.8 vs 988 ± 91.7 mL; P < 0.01), and the enucleation group had a significantly shorter mean operative time (1.7 ± 0.4 vs 2.9 ± 0.9 h; P < 0.01) and significantly shorter duration of hospital stay (9.6 ± 4.2 vs 14.7 ± 3.7 days; P < 0.05). Five patients in the resection group and only 1 patient in the enucleation group had major postoperative complications. Compared to liver resection, enucleation is safer and faster for liver hemangiomas proximal to the hepatic portal vascular structures and is associated with fewer complications.

Rare case of omentum-wrapped abscess caused by a fish bone penetrating the terminal ileum.

Accidentally ingested foreign bodies, for the most part, pass through the gastrointestinal tract, but can cause several complications. Perforation is rare, but can occur in any segment of the gastrointestinal tract. Intestinal perforations due to foreign bodies are rarely diagnosed preoperatively as clinical symptoms are non-specific and they can mimic other abdominal conditions. We describe a case of a 48-year-old patient who was admitted to the emergency room because of severe abdominal pain of 5 d duration. A computed tomography scan showed an undefined liquid collection involving a linear image 35 mm in size, suggestive of a foreign body. On laparotomy, an abscess containing a fish bone was resected. As fish bone ingestion is usually not remembered by the patient, the diagnosis can be delayed. The preoperative diagnosis is frequently acute abdomen of unknown cause. A low threshold of suspicion along with a good clinical history and radiological studies are extremely important in order to make a correct diagnosis.

Triptolide protects mice from ischemia/reperfusion injury by inhibition of IL-17 production.

Ischemia and reperfusion have been identified as a complex cascade of inflammatory mediators that are involved in the pathogenesis of hepatic injury. Triptolide (diterpenoid triepoxide), was extracted from a purified component of a traditional Chinese Medicine, Tripterygium wilfondii Hook F. Currently, triptolide has been shown to have anti-inflammatory, immunosuppressive, and antineoplastic activity. Accumulated data have shown that Th17 cells might contribute to the pathogenesis of liver diseases. Triptolide has been shown to reduce interleukin (IL)-17 expression in inflammatory bowel disease and arthritis. However, the role of triptolide in liver ischemia/reperfusion (I/R) and whether it can attenuate injury and the potential mechanism have not been investigated. Mice were treated with triptolide (0.1mg/kg) for 1 week or IL-17 antibody (50 µg/mouse) 2 days before ischemic insult. Partial warm ischemia was produced in the hepatic lobes of C57BL/6 mice for 90 min, followed by various periods of reperfusion. We demonstrated that IL-17 was involved in the inflammatory response to hepatic I/R injury, and that triptolide inhibited IL-17 generation and suppressed neutrophil migration after liver I/R injury through downregulation of signal transducer and activator of transcription 3 (STAT3) transcription. Also, triptolide pretreatment protected the liver from warm I/R injury, at least in part, mediated by the upregulation of Foxp3 expression. These results could pave the way for the use of triptolide as a novel agent to attenuate I/R injury.