Undifferentiated carcinoma of the liver with osteoclast-like giant cells: a case report and literature review.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Osteoclast-like giant cells (OGCs) are relatively more common in pancreatic cancer, but extremely rare in HCC. Currently, there have been only a few reported cases of OGCs in HCC, and their presence indicates an aggressive clinical course. Here, we present a case of primary undifferentiated carcinoma of the liver with OGCs in a 49-year-old male patient, and through a literature review, we summarize 20 similar cases to further understand the diagnosis, treatment, and clinical course of this disease entity.

Preliminary Mechanism of Glial Maturation Factor ß on Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.

Recent evidence suggests that glia maturation factor ß (GMFß) is important in the pathogenesis of pulmonary arterial hpertension (PAH), but the underlying mechanism is unknown. To clarify whether GMFß can be involved in pulmonary vascular remodeling and to explore the role of the IL-6-STAT3 pathway in this process, the expression of GMFß in PAH rats is examined and the expression of downstream molecules including periostin (POSTN) and interleukin-6 (IL-6) is measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The location and expression of POSTN is also tested in PAH rats using immunofluorescence. It is proved that GMFß is upregulated in the lungs of PAH rats. Knockout GMFß alleviated the MCT-PAH by reducing right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and pulmonary vascular remodeling. Moreover, the inflammation of the pulmonary vasculature is ameliorated in PAH rats with GMFß absent. In addition, the IL-6-STAT3 signaling pathway is activated in PAH; knockout GMFß reduced POSTN and IL-6 production by inhibiting the IL-6-STAT3 signaling pathway. Taken together, these findings suggest that knockout GMFß ameliorates PAH in rats by inhibiting the IL-6-STAT3 signaling pathway.

Risk Factors of the Occurrence and Treatment Failure of Refractory Peritoneal Dialysis-Associated Peritonitis: A Single-Center Retrospective Study From China.

BACKGROUND: This study aimed to investigate the clinical characteristics and prognosis of refractory peritoneal dialysis (PD)-associated peritonitis as well as the risk factors of its occurrence and treatment failure. METHODS: A single-center retrospective cohort study was conducted among 519 patients undergoing PD from January 2007 to October 2021. According to the International Society for Peritoneal Dialysis guidelines, all episodes occurred in our center were divided into two groups: refractory and nonrefractory. Demographic, biochemical, and pathogenic bacteria and treatment outcome data were collected. RESULTS: During the 15-year period, 282 episodes of peritonitis occurred in 166 patients undergoing PD. The refractory rate was 34.0% (96/282). Gram-positive organisms were the leading cause of peritonitis (47.9%); however, gram-negative organisms were predominant in refractory peritonitis (34.4%, p = 0.002). Multiple logistic regression revealed that gram-negative organism-based peritonitis, longer PD duration, and female sex were the significant independent predictors of refractory peritonitis. Among 96 refractory episodes, white blood cell (WBC) count, dialysate WBC on Day 3, and PD duration ≥5 years were the independent risk factors of treatment failure. CONCLUSIONS: Gram-negative organism-based peritonitis, longer PD duration, and female sex were the independent risk factors of refractory peritonitis. Refractory peritonitis with higher WBC count, higher dialysate WBC on Day 3, and PD duration ≥5 years increased treatment failure risk and required immediate PD catheter removal. The timely identification of refractory peritonitis with high risk of treatment failure as well as timely PD catheter removal is important.

SUMOylation of GMFB regulates its stability and function in retinal pigment epithelial cells under hyperglycemia.

BACKGROUND: Glia maturation factor beta (GMFB) is a growth and differentiation factor that acts as an intracellular regulator of signal transduction pathways. The small ubiquitin-related modifier (SUMO) modification, SUMOylation, is a posttranslational modification (PTM) that plays a key role in protein subcellular localization, stability, transcription, and enzymatic activity. Recent studies have highlighted the importance of SUMOylation in the inflammation and progression of numerous diseases. However, the relationship between GMFB and SUMOylation is unclear. RESULTS: Here, we report for the first time that GMFB and SUMO1 are markedly increased in retinal pigment epithelial (RPE) cells at the early stage of diabetes mellitus (DM) under hyperglycemia. The GMFΒ protein could be mono-SUMOylated by SUMO1 at the K20, K35, K58 or K97 sites. SUMOylation of GMFB led to its increased protein stability and subcellular translocation. Furthermore, deSUMOylation of GMFΒ downregulates multiple signaling pathways, including the Jak-STAT signaling pathway, p38 pathway and NF-kappa B signaling pathway. CONCLUSIONS: This work provides novel insight into the role of SUMOylated GMFB in RPE cells and provides a novel therapeutic target for diabetic retinopathy (DR).

The identification of a novel shared therapeutic target and drug across all insulin-sensitive tissues under insulin resistance.

Background: To identify key and shared insulin resistance (IR) molecular signatures across all insulin-sensitive tissues (ISTs), and their potential targeted drugs. Methods: Three datasets from Gene Expression Omnibus (GEO) were acquired, in which the ISTs (fat, muscle, and liver) were from the same individual with obese mice. Integrated bioinformatics analysis was performed to obtain the differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was carried out to determine the "most significant trait-related genes" (MSTRGs). Enrichment analysis and PPI network were performed to find common features and novel hub genes in ISTs. The shared genes of DEGs and genes between DEGs and MSTRGs across four ISTs were identified as key IR therapeutic target. The Attie Lab diabetes database and obese rats were used to verify candidate genes. A medical drug-gene interaction network was conducted by using the Comparative Toxicogenomics Database (CTD) to find potential targeted drugs. The candidate drug was validated in Hepa1-6 cells. Results: Lipid metabolic process, mitochondrion, and oxidoreductase activity as common features were enriched from ISTs under an obese context. Thirteen shared genes (Ubd, Lbp, Hp, Arntl, Cfd, Npas2, Thrsp., Tpx2, Pkp1, Sftpd, Mthfd2, Tnfaip2, and Vnn3) of DEGs across ISTs were obtained and confirmed. Among them, Ubd was the only shared gene between DEGs and MSTRGs across four ISTs. The expression of Ubd was significantly upregulated across four ISTs in obese rats, especially in the liver. The IR Hepa1-6 cell models treated with dexamethasone (Dex), palmitic acid (PA), and 2-deoxy-D-ribose (dRib) had elevated expression of Ubd. Knockdown of Ubd increased the level of p-Akt. A lowing Ubd expression drug, promethazine (PMZ) from CTD analysis rescued the decreased p-Akt level in IR Hepa1-6 cells. Conclusion: This study revealed Ubd, a novel and shared IR molecular signature across four ISTs, as an effective biomarker and provided new insight into the mechanisms of IR. PMZ was a candidate drug for IR which increased p-Akt level and thus improved IR by targeting Ubd and downregulation of Ubd expression. Both Ubd and PMZ merit further clinical translational investigation to improve IR.

Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial.

Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

A Real-time augmented reality robot integrated with artificial intelligence for skin tumor surgery - experimental study and case series.

BACKGROUND: Skin tumors affect many people worldwide, and surgery is the first treatment choice. Achieving precise preoperative planning and navigation of intraoperative sampling remains a problem and is excessively reliant on the experience of surgeons, especially for Mohs surgery for malignant tumors. MATERIALS AND METHODS: To achieve precise preoperative planning and navigation of intraoperative sampling, we developed a real-time augmented reality (AR) surgical system integrated with artificial intelligence (AI) to enhance three functions: AI-assisted tumor boundary segmentation, surgical margin design, and navigation in intraoperative tissue sampling. Non-randomized controlled trials were conducted on manikin, tumor-simulated rabbits, and human volunteers in xxx Laboratory to evaluate the surgical system. RESULTS: The results showed that the accuracy of the benign and malignant tumor segmentation were 0.9556 and 0.9548, respectively, and the average AR navigation mapping error was 0.644 mm. The proposed surgical system was applied in 106 skin tumor surgeries, including intraoperative navigation of sampling in 16 Mohs surgery cases. Surgeons who have used this system highly recognize it. CONCLUSIONS: The surgical system highlighted the potential to achieve accurate treatment of skin tumors and to fill the gap in global research on skin tumor surgery systems.

Wnt5a/ß-catenin-mediated epithelial-mesenchymal transition: a key driver of subretinal fibrosis in neovascular age-related macular degeneration.

BACKGROUND: Neovascular age-related macular degeneration (nAMD), accounts for up to 90% of AMD-associated vision loss, ultimately resulting in the formation of fibrotic scar in the macular region. The pathogenesis of subretinal fibrosis in nAMD involves the process of epithelial-mesenchymal transition (EMT) occurring in retinal pigment epithelium (RPE). Here, we aim to investigate the underlying mechanisms involved in the Wnt signaling during the EMT of RPE cells and in the pathological process of subretinal fibrosis secondary to nAMD. METHODS: In vivo, the induction of subretinal fibrosis was performed in male C57BL/6J mice through laser photocoagulation. Either FH535 (a ß-catenin inhibitor) or Box5 (a Wnt5a inhibitor) was intravitreally administered on the same day or 14 days following laser induction. The RPE-Bruch's membrane-choriocapillaris complex (RBCC) tissues were collected and subjected to Western blot analysis and immunofluorescence to examine fibrovascular and Wnt-related markers. In vitro, transforming growth factor beta 1 (TGFß1)-treated ARPE-19 cells were co-incubated with or without FH535, Foxy-5 (a Wnt5a-mimicking peptide), Box5, or Wnt5a shRNA, respectively. The changes in EMT- and Wnt-related signaling molecules, as well as cell functions were assessed using qRT-PCR, nuclear-cytoplasmic fractionation assay, Western blot, immunofluorescence, scratch assay or transwell migration assay. The cell viability of ARPE-19 cells was determined using Cell Counting Kit (CCK)-8. RESULTS: The in vivo analysis demonstrated Wnt5a/ROR1, but not Wnt3a, was upregulated in the RBCCs of the laser-induced CNV mice compared to the normal control group. Intravitreal injection of FH535 effectively reduced Wnt5a protein expression. Both FH535 and Box5 effectively attenuated subretinal fibrosis and EMT, as well as the activation of ß-catenin in laser-induced CNV mice, as evidenced by the significant reduction in areas positive for fibronectin, alpha-smooth muscle actin (α-SMA), collagen I, and active ß-catenin labeling. In vitro, Wnt5a/ROR1, active ß-catenin, and some other Wnt signaling molecules were upregulated in the TGFß1-induced EMT cell model using ARPE-19 cells. Co-treatment with FH535, Box5, or Wnt5a shRNA markedly suppressed the activation of Wnt5a, nuclear translocation of active ß-catenin, as well as the EMT in TGFß1-treated ARPE-19 cells. Conversely, treatment with Foxy-5 independently resulted in the activation of abovementioned molecules and subsequent induction of EMT in ARPE-19 cells. CONCLUSIONS: Our study reveals a reciprocal activation between Wnt5a and ß-catenin to mediate EMT as a pivotal driver of subretinal fibrosis in nAMD. This positive feedback loop provides valuable insights into potential therapeutic strategies to treat subretinal fibrosis in nAMD patients.

Clinicopathological Analysis of Densely and Sparsely Granulated Somatotroph Tumors of Pituitary.

OBJECTIVE: Somatotroph tumors are the second most common type of pituitary neuroendocrine tumors, which can be further classified into 2 subtypes-densely granulated somatotroph tumors (DGSTs) and sparsely granulated somatotroph tumors (SGSTs). The aim of this study was to investigate the clinical significance of the 2 subtypes in a retrospective analysis. METHODS: From the database of the Ningbo Clinical Pathology Diagnosis Center, we collected patients diagnosed with pituitary somatotroph tumors. We then compiled pertinent clinical and radiological data and proceeded with histopathological examination involving hematoxylin-eosin staining and immunohistochemical staining. Subsequent analysis compared the 2 subtypes using either χ2 test or Fisher exact test. RESULTS: We analyzed 40 cases of somatotroph tumors, 18 cases DGSTs and 22 SGSTs. Male-to-female ratio was 5:4 for DGSTs and 4:7 for SGSTs. Mean age was 52.83 years for DGSTs and 47.18 years for SGSTs. Statistically significant differences were observed between the DGST and SGST groups in invasiveness (P = 0.0267) and postoperative remission (P = 0.007). Cells of both DGSTs and SGSTs exhibited coexpression of PIT1, growth hormone, and CAM5.2, although the patterns of CAM5.2 expression differed between the 2 subtypes. CONCLUSIONS: The efficacy of CAM5.2 staining in distinguishing between DGSTs and SGSTs was demonstrated. SGSTs, with their increased invasiveness and lower remission rate, are a high-risk subtype. The histological subtype of somatotroph tumors plays a crucial role in guiding treatment decisions and prognostic evaluation in affected patients.

A comprehensive stem cell laboratory module with blended learning for medical students at Tongji University.

The laboratory practice "Primary culture and directional differentiation of rat bone marrow mesenchymal stem cells (BMSCs)" is part of a required course for sophomore medical students at Tongji university, which has been conducted since 2012. Blended learning has been widely applied in medical courses. Based on a student-centered teaching philosophy, we reconstructed a comprehensive stem cell laboratory module with blended learning in 2021, aiming to facilitate students in enhancing their understanding of the multi-lineage differentiation potential of stem cells and improve their experimental skills, self-directed learning ability, and innovative thinking. First, we constructed in-depth online study resources, including videos demonstrating laboratory procedures, a PowerPoint slide deck, and published literature on student self-learning before class. In class, students performed a primary culture of BMSCs, freely chose among adipogenic, osteogenic, or chondrogenic differentiation, and used cytochemical or immunofluorescence staining for identification. After class, the extracurricular part involved performing quantitative polymerase chain reaction to examine the expression of multi-lineage differentiation marker genes, which was designed as an elective. After 2 years of practice, positive feedback was obtained from both students and faculty members who achieved, the learning goal as expected. The reconstructed stem cell laboratory module provides comprehensive practice opportunities for students. Students have a better understanding of BMSC at the molecular, cellular, and functional levels and have improved their experimental skills, which forms a basis for scientific research for medical students. Introducing blended learning into other medical laboratory practices thus seems valuable.

GMFB/AKT/TGF-ß3 in Müller cells mediated early retinal degeneration in a streptozotocin-induced rat diabetes model.

Retinal degeneration, characterized by Müller cell gliosis and photoreceptor apoptosis, is considered an early event in diabetic retinopathy (DR). Our previous study proposed that GMFB may mediate diabetic retinal degeneration. This study identified GMFB as a sensitive and functional gliosis marker for DR. Compared to the wild type (WT) group, Gmfb knockout (KO) significantly improved visual function, attenuated gliosis, reduced the apoptosis of neurons, and decreased the mRNA levels of tumor necrosis factor α (Tnf-α) and interleukin-1ß (Il-1ß) in diabetic retinas. Tgf-ß3 was enriched by hub genes using RNA sequencing in primary WT and KO Müller cells. Gmfb KO significantly upregulated the transforming growth factor (TGF)-ß3 protein level via the AKT pathway. The protective effect of TGF-ß3 in the vitreous resulted in significantly improved visual function and decreased the number of apoptotic cells in the diabetic retina. The protection of Gmfb KO in primary Müller cells against high glucose (HG)-induced photoreceptor apoptosis was partially counteracted by TGF-ß3 antibody and administration of TGFBR1/2 inhibitors. Nuclear receptor subfamily 3 group C member 1 (NR3C1) binds to the promoter region of Gmfb and regulates Gmfb mRNA at the transcriptional level. NR3C1 was increased in the retinas of early diabetic rats but decreased in the retinas of late diabetic rats. N'-[(1E)-(3-Methoxyphenyl)Methylene]-3-Methyl-1H-Pyrazole-5-Carbohydrazide (DS-5) was identified as an inhibitor of GMFB, having a protective role in DR. We demonstrated that GMFB/AKT/TGF-ß3 mediated early diabetic retinal degeneration in diabetic rats. This study provides a novel therapeutic strategy for treating retinal degeneration in patients with DR.

A Case of Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorder.

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder is indolent clinical behaviour and uncertain malignant potential. Histologically, these lesions show a predominance of small to medium-size CD4+ pleomorphic T-cell expressing follicular helper T-cell markers. We report the case of a 59-year-old female who presented with nodules on the left chest for 3 years. Dermatological examination showed four red nodules localized on the left chest with angiotelectasis without tenderness. The histopathological manifestation was consistent with the diagnosis of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder. We focus on the clinical appearance, histopathological features, diagnosis, and differential diagnosis of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder.

Signaling pathways and targeted therapies for psoriasis.

Psoriasis is a common, chronic, and inflammatory skin disease with a high burden on individuals, health systems, and society worldwide. With the immunological pathologies and pathogenesis of psoriasis becoming gradually revealed, the therapeutic approaches for this disease have gained revolutionary progress. Nevertheless, the mechanisms of less common forms of psoriasis remain elusive. Furthermore, severe adverse effects and the recurrence of disease upon treatment cessation should be noted and addressed during the treatment, which, however, has been rarely explored with the integration of preliminary findings. Therefore, it is crucial to have a comprehensive understanding of the mechanisms behind psoriasis pathogenesis, which might offer new insights for research and lead to more substantive progress in therapeutic approaches and expand clinical options for psoriasis treatment. In this review, we looked to briefly introduce the epidemiology, clinical subtypes, pathophysiology, and comorbidities of psoriasis and systematically discuss the signaling pathways involving extracellular cytokines and intracellular transmission, as well as the cross-talk between them. In the discussion, we also paid more attention to the potential metabolic and epigenetic mechanisms of psoriasis and the molecular mechanistic cascades related to its comorbidities. This review also outlined current treatment for psoriasis, especially targeted therapies and novel therapeutic strategies, as well as the potential mechanism of disease recurrence.

Subconjunctival injection of human umbilical cord mesenchymal stem cells alleviates experimental allergic conjunctivitis via regulating T cell response.

BACKGROUND: T helper 2 (Th2) cells are thought to play critical roles in allergic conjunctivitis (AC). They release inflammatory cytokines to promote an allergic response in AC. Due to individual heterogeneity and long-term chronic management, current therapies do not always effectively control AC. Mesenchymal stem cells (MSCs) have been shown to be effective in treating allergy-related disorders, but it is unclear how exactly the Th2-mediated allergic response is attenuated. This study aims to elucidate the therapeutic effect and mechanism of the human umbilical cord MSCs (hUCMSCs) in a mouse model of experimental AC (EAC). METHODS: A mouse EAC model was established by inoculating short ragweed (SRW) pollen. After the SRW pollen challenge, the mice received a single subconjunctival or tail vein injection of 2 × 106 hUCMSCs, or subconjunctival injection of hUCMSCs conditioned medium (hUCMSC-CM), and dexamethasone eye drops was used as positive control; subsequent scratching behavior and clinical symptoms were assessed. Immunostaining and flow cytometry were carried out to show allergic reactions and the activation of CD4 + T cell subsets in the conjunctiva and cervical lymph nodes (CLNs). Gene expression was determined by RNA-seq and further verified by qRT-PCR and Western blot. Co-culture assays were performed to explore the regulatory role of hUCMSCs in the differentiation of CD4 + naive T cells (Th0) into Th2 cells. RESULTS: Subconjunctival administration of hUCMSCs resulted in fewer instances of scratching and lower inflammation scores in EAC mice compared to the tail vein delivery, hUCMSC-CM and control groups. Subconjunctival administration of hUCMSCs reduced the number of activated mast cells and infiltrated eosinophils in the conjunctiva, as well as decreased the number of Th2 cells in CLNs. After pretreatment with EAC mouse serum in vitro to mimic the in vivo milieu, hUCMSCs were able to inhibit the differentiation of Th0 into Th2 cells. Further evidence demonstrated that repression of Th2 cell differentiation by hUCMSCs is mediated by CRISPLD2 through downregulation of STAT6 phosphorylation. Additionally, hUMCSCs were able to promote the differentiation of Th0 cells into regulatory T cells in CLNs of EAC mice. CONCLUSIONS: Subconjunctival injection of hUCMSCs suppressed the Th2-allergic response and alleviated clinical symptoms. This study provides not only a potential therapeutic target for the treatment of AC but also other T cell-mediated diseases.

Discrimination of SARS-CoV-2 omicron variant and its lineages by rapid detection of immune-escape mutations in spike protein RBD using asymmetric PCR-based melting curve analysis.

BACKGROUND: The SARS-CoV-2 Omicron strain has multiple immune-escape mutations in the spike protein receptor-binding domain (RBD). Rapid detection of these mutations to identify Omicron and its lineages is essential for guiding public health strategies and patient treatments. We developed a two-tube, four-color assay employing asymmetric polymerase chain reaction (PCR)-based melting curve analysis to detect Omicron mutations and discriminate the BA.1, BA.2, BA.4/5, and BA.2.75 lineages. METHODS: The presented technique involves combinatory analysis of the detection of six fluorescent probes targeting the immune-escape mutations L452R, N460K, E484A, F486V, Q493R, Q498R, and Y505H within one amplicon in the spike RBD and probes targeting the ORF1ab and N genes. After protocol optimization, the analytical performance of the technique was evaluated using plasmid templates. Sensitivity was assessed based on the limit of detection (LOD), and reliability was assessed by calculating the intra- and inter-run precision of melting temperatures (Tms). Specificity was assessed using pseudotyped lentivirus of common human respiratory pathogens and human genomic DNA. The assay was used to analyze 40 SARS-CoV-2-positive clinical samples (including 36 BA.2 and 4 BA.4/5 samples) and pseudotyped lentiviruses of wild-type and BA.1 viral RNA control materials, as well as 20 SARS-CoV-2-negative clinical samples, and its accuracy was evaluated by comparing the results with those of sequencing. RESULTS: All genotypes were sensitively identified using the developed method with a LOD of 39.1 copies per reaction. The intra- and inter-run coefficients of variation for the Tms were ≤ 0.69% and ≤ 0.84%, with standard deviations ≤ 0.38 °C and ≤ 0.41 °C, respectively. Validation of the assay using known SARS-CoV-2-positive samples demonstrated its ability to correctly identify the targeted mutations and preliminarily characterize the Omicron lineages. CONCLUSION: The developed assay can provide accurate, reliable, rapid, simple and low-cost detection of the immune-escape mutations located in the spike RBD to detect the Omicron variant and discriminate its lineages, and its use can be easily generalized in clinical laboratories with a fluorescent PCR platform.

[Acteoside promotes autophagy and apoptosis of hepatoma cells by regulating JNK signaling pathway].

This study explored the molecular mechanism of acteoside against hepatoma 22(H22) tumor in mice through c-Jun N-terminal kinase(JNK) signaling pathway. H22 cells were subcutaneously inoculated in 50 male BALB/c mice, and then the model mice were classified into model group, low-dose, medium-dose, and high-dose acteoside groups, and cisplatin group. The administration lasted 2 weeks for each group(5 consecutive days/week). The general conditions of mice in each group, such as mental status, diet intake, water intake, activity, and fur were observed. The body weight, tumor volume, tumor weight, and tumor-inhibiting rate were compared before and after administration. Morphological changes of liver cancer tissues were observed based on hematoxylin and eosin(HE) staining, and the expression of phosphorylated(p)-JNK, JNK, B-cell lymphoma-2(Bcl-2), Beclin-1, and light chain 3(LC3) in each tissue was detected by immunohistochemistry and Western blot. qRT-PCR was performed to detect the mRNA expression of JNK, Bcl-2, Beclin-1, and LC3. The general conditions of mice in model and low-dose acteoside groups were poor, while the general conditions of mice in the remaining three groups were improved. The body weight of mice in medium-dose acteoside group, high-dose acteoside group, and cisplatin group was smaller than that in model group(P<0.01). The tumor volume in model group was insignificantly different from that in low-dose acteoside group, and the volume in cisplatin group showed no significant difference from that in high-dose acteoside group. Tumor volume and weight in medium-dose and high-dose acteoside groups and cisplatin group were lower than those in the model group(P<0.001). The tumor-inhibiting rates were 10.72%, 40.32%, 53.79%, and 56.44% in the low-dose, medium-dose, and high-dose acteoside groups and cisplatin group, respectively. HE staining showed gradual decrease in the count of hepatoma cells and increasing sign of cell necrosis in the acteoside and cisplatin groups, and the necrosis was particularly obvious in the high-dose acteoside group and cisplatin group. Immunohistochemical results suggested that the expression of Beclin-1, LC3, p-JNK, and JNK was up-regulated in acteoside and cisplatin groups(P<0.05). The results of immunohistochemistry, Western blot, and qRT-PCR indicated that the expression of Bcl-2 was down-regulated in the medium-dose and high-dose acteoside groups and cisplatin group(P<0.01). Western blot showed that the expression of Beclin-1, LC3, and p-JNK was up-regulated in acteoside and cisplatin groups(P<0.01), and there was no difference in the expression of JNK among groups. qRT-PCR results showed that the levels of Beclin-1 and LC3 mRNA were up-regulated in the acteoside and cisplatin groups(P<0.05), and the level of JNK mRNA was up-regulated in medium-dose and high-dose acteoside groups and cisplatin group(P<0.001). Acteoside promotes apoptosis and autophagy of H22 cells in mice hepatoma cells by up-regulating the JNK signaling pathway, thus inhibiting tumor growth.

Case report of hepatic retiform hemangioendothelioma: A rare tumor treated with ultrasound-guided microwave ablation.

Retiform hemangioendothelioma (RH) is a type of low-grade malignant angiosarcoma. It commonly involves the skin and subcutaneous tissue of the lower extremities, but a few cases have been reported in the gut. However, hepatic RH has not been previously reported. This report presents the case of RH of the liver in a 61-year-old woman who was admitted to the hospital having presented with liver space-occupying lesions of 2 months evolution. The patient underwent an abdominal ultrasound examination, which indicated a hemangioma, but abdominal computed tomography diagnosed a liver abscess. In order to determine the nature of the lesion, an ultrasound-guided liver biopsy was performed, after which a pathological diagnosis confirmed the presence of RH in the liver. The patient underwent ultrasound-guided microwave ablation three times and has been followed up for 8 years with no tumor recurrence or metastasis. Surgical excision is still the first choice for the treatment of hepatic RH. As shown in this case, however, for patients who refuse to undergo surgery or have surgical contraindications, ultrasound-guided microwave ablation is an alternative treatment option. The report of this case expands the scope of liver tumors to a certain extent and provides a reference for clinical diagnosis and treatment.