Regional intra-arterial vs. systemic chemotherapy for the treatment of advanced pancreatic cancer: a systematic review and meta-analysis.

Introduction: Pancreatic cancer is a highly aggressive malignancy with limited response to chemotherapy. This research aims to compare the effectiveness and safety of regional intra-arterial chemotherapy (RIAC) with conventional systemic chemotherapy in treating advanced stages of pancreatic cancer. Methods: A comprehensive literature review was conducted using databases such as PubMed, Embase, Web of Science, and the Cochrane Library. Studies assessing the comparative outcomes of RIAC and systemic chemotherapy were included. Data extraction and quality evaluation were performed independently by two researchers. Statistical analysis was conducted using STATA16 software, calculating odds ratios (OR), risk differences (RD), and 95% confidence intervals (CI). Results: Eleven studies, comprising a total of 627 patients, were included in the meta-analysis. The findings showed that patients undergoing RIAC had significantly higher rates of partial remission (PR) compared to those receiving systemic chemotherapy (OR = 2.23, 95% CI: 1.57, 3.15, I2= 0%). Additionally, the rate of complications was lower in the RIAC group (OR = 0.45, 95% CI: 0.33, 0.63, I2= 0%). Moreover, patients treated with RIAC had notably longer median survival times. Discussion: The results of this research indicate that RIAC is associated with a higher rate of partial remission, improved clinical benefits, and fewer complications compared to systemic chemotherapy in the management of advanced pancreatic cancer. These findings suggest that RIAC may be a more effective and safer treatment option for patients with advanced stages of pancreatic cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023404637.

Palliative care and Chinese medicine in a centenarian with primary hepatocellular carcinoma and 27-month follow-up: A case report.

The number of centenarians with cancer is increasing as the global population ages. The diagnosis and treatment for centenarians with tumor sometimes are specific, and there are currently less appropriate guidelines as references. We report a 104-year-old man with asymptomatic primary liver cancer (PLC) whose family decided to receive conservative and palliative care. The patient has been followed up for 27 months. He has been mainly received Chinese herbal medicine (CHM), nutritional support and thymalfasin injection intermittently, etc. During the 27-month follow-up, the patient has showed good compliance and tolerance without any complications of the tumor. Conclusion: Individualized palliative care and complementary medicine, based on multidisciplinary evaluation, traditional Chinese medicine, consultation with patients and their families about treatment options, etc., may help improve the life quality of centenarians with end-stage tumors.

Germline Mutation of PLCD1 Contributes to Human Multiple Pilomatricomas through Protein Kinase D/Extracellular Signal-Regulated Kinase1/2 Cascade and TRPV6.

Pilomatricoma, a benign skin appendage tumor, also known as calcifying epithelioma, consists of islands of epithelial cells histologically that contain anucleated cells in the center surrounded by basophilic cells and partial calcification. Sporadic pilomatricomas commonly have somatic mutations in the gene CTNNB1, but causative genes from germline and the underlying pathophysiology are unclear. In this study, we identified a germline missense variant of PLCD1 encoding PLCδ1, c.1186G>A (p.Glu396Lys), in a large Chinese family with autosomal dominant multiple pilomatricomas. Phospholipase C, a key enzyme playing critical roles in intracellular signal transduction, is essential for epidermal barrier integrity. The p.Glu396Lys variant increased the enzymatic activity of PLCδ1, leading to protein kinase C/protein kinase D/extracellular signal-regulated kinase1/2 pathway activation and TPRV6 channel closure, which not only resulted in excessive proliferation of keratinocytes in vitro and in vivo but also induced local accumulation of calcium in the pilomatricoma-like tumor that developed spontaneously in the skin of Plcd1E396K/E396K mice. Our results implicate this p.Glu396Lys variant of PLCD1 from germline leading to gain-of-function of PLCδ1 as a causative genetic defect in familial multiple pilomatricomas.

[Preparation and in vitro evaluation of tissue engineered osteochondral integration of multi-layered scaffold].

Objective: The tissue engineered osteochondral integration of multi-layered scaffold was prepared and the related mechanical properties and biological properties were evaluated to provide a new technique and method for the repair and regeneration of osteochondral defect. Methods: According to blend of different components and proportion of acellular cartilage extracellular matrix of pig, nano-hydroxyapatite, and alginate, the osteochondral integration of multi-layered scaffold was prepared by using freeze-drying and physical and chemical cross-linking technology. The cartilage layer was consisted of acellular cartilage extracellular matrix; the middle layer was consisted of acellular cartilage extracellular matrix and alginate; and the bone layer was consisted of nano-hydroxyapatite, alginate, and acellular cartilage extracellular matrix. The biological and mechanics characteristic of the osteochondral integration of multi-layered scaffold were evaluated by morphology observation, scanning electron microscope observation, Micro-CT observation, porosity and pore size determination, water absorption capacity determination, mechanical testing (compression modulus and layer adhesive strength), biocompatibility testing [L929 cell proliferation on scaffold assessed by MTT assay, and growth of green fluorescent protein (GFP)-labeled Sprague Dawley rats' bone marrow mesenchumal stem cells (BMSCs) on scaffolds]. Results: Gross observation and Micro-CT observation showed that the scaffolds were closely integrated with each other without obvious discontinuities and separation. Scanning electron microscope showed that the structure of the bone layer was relatively dense, while the structure of the middle layer and the cartilage layer was relatively loose. The pore structures in the layers were connected to each other and all had the multi-dimensional characteristics. The porosity of cartilage layer, middle layer, and bone layer of the scaffolds were 93.55%±2.90%, 93.55%±4.10%, and 50.28%±3.20%, respectively; the porosity of the bone layer was significantly lower than that of cartilage layer and middle layer ( P<0.05), but no significant difference was found between cartilage layer and middle layer ( P>0.05). The pore size of the three layers were (239.66±35.28), (153.24±19.78), and (82.72±16.94) µm, respectively, showing significant differences between layers ( P<0.05). The hydrophilic of the three layers were (15.14±3.15), (13.65±2.98), and (5.32±1.87) mL/g, respectively; the hydrophilic of the bone layer was significantly lower than that of cartilage layer and middle layer ( P<0.05), but no significant difference was found between cartilage layer and middle layer ( P>0.05). The compression modulus of the three layers were (51.36±13.25), (47.93±12.74), and (155.18±19.62) kPa, respectively; and compression modulus of the bone layer was significantly higher than that of cartilage layer and middle layer ( P<0.05), but no significant difference was found between cartilage layer and middle layer ( P>0.05). The osteochondral integration of multi-layered scaffold was tightly bonded with each layer. The layer adhesive strength between the cartilage layer and the middle layer was (18.21±5.16) kPa, and the layer adhesive strength between the middle layer and the bone layer was (16.73±6.38) kPa, showing no significant difference ( t=0.637, P=0.537). MTT assay showed that L929 cells grew well on the scaffolds, indicating no scaffold cytotoxicity. GFP-labeled rat BMSCs grew evenly on the scaffolds, indicating scaffold has excellent biocompatibility. Conclusion: The advantages of three layers which have different performance of the tissue engineered osteochondral integration of multi-layered scaffold is achieved double biomimetics of structure and composition, lays a foundation for further research of animal in vivo experiment, meanwhile, as an advanced and potential strategy for osteochondral defect repair.

Responses of the Toll-like receptor and melanoma differentiation-associated protein 5 signaling pathways to avian infectious bronchitis virus infection in chicks.

Avian infectious bronchitis virus (IBV) is a Gammacoronavirus in the family Coronaviridae and causes highly contagious respiratory disease in chickens. Innate immunity plays significant roles in host defense against IBV. Here, we explored the interaction between IBV and the host innate immune system. Severe histopathological lesions were observed in the tracheal mucosa at 3-5 days post inoculation (dpi) and in the kidney at 8 dpi, with heavy viral loads at 1-11 and 1-28 dpi, respectively. The expression of mRNAs encoding Toll-like receptor (TLR) 3 and TLR7 were upregulated at 3-8 dpi, and that of TIR-domain-containing adapter-inducing interferon (IFN) ß (TRIF) was upregulated at 21 dpi in the trachea and kidney. Myeloid differentiation primary response protein 88 (MyD88) was upregulated in the trachea during early infection. Tumor necrosis factor receptor-associated factor (TRAF) 3 and TRAF6 were upregulated expression in both tissues. Moreover, melanoma differentiation-associated protein 5 (MDA5), laboratory of genetics and physiology 2 (LGP2), stimulator of IFN genes (STING), and mitochondrial antiviral signaling protein (MAVS), as well as TANK binding kinase 1 (TBK1), inhibitor of kappaB kinase (IKK) ε, IKKα, IKKß, IFN regulatory factor (IRF) 7, nuclear factor of kappaB (NF-ĸB), IFN-α, IFN-ß, various interleukins(ILs), and macrophage inflammatory protein-1ß (MIP-1ß) were significantly upregulated in the trachea and downregulated in the kidney. These results suggested that the TLR and MDA5 signaling pathways and innate immune cytokine were induced after IBV infection. Additionally, consistent responses to IBV infection were observed during early infection, with differential and complicated responses in the kidney.

[Nasal endoscopy-assisted bulboprostatic anastomosis for posterior urethral stricture].

OBJECTIVE: To study the clinical value and operation skills of nasal endoscopy-assisted bulboprostatic anastomosis in the treatment of posterior urethral stricture. METHODS: Between January 2012 and November 2014, we performed nasal endoscopy-assisted bulboprostatic anastomosis for 12 male patients with posterior urethral stricture. We recorded the operation time, blood loss, exposure of operation visual field, and success rate of anastomosis and summarized the operation skills. RESULTS: Eight of the patients experienced first-stage recovery. Two underwent a urethral dilation at 3 months postoperatively, 1 received 10 urethral dilations within 5 months after surgery, and 1 underwent internal urethrotomy after failure in urethral dilation, but all the 4 cases were cured. CONCLUSION: Nasal endoscopy can significantly improve the operation field exposure, elevate the precision, reduce the difficulty, and enhance the efficiency of bulboprostatic anastomosis in the treatment of posterior urethral stricture.

Calcification of the intervertebral disc and posterior longitudinal ligament in children.

STUDY DESIGN: Case report. OBJECTIVE: To report the clinical features, radiographic findings, treatments, and results of 2 children with cervical intervertebral disc calcification combined with ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: The calcification of the intervertebral disc, which is more frequent in males with predominant localization to cervical spine, was first reported by Baron in 1924. OPLL of the cervical spine, which is found approximately in the 5th to 7th decade of life, is a disease-causing spinal canal stenosis and spinal cord compression. The etiologies of these 2 diseases still remain unclear. METHODS: An 8-year-old girl presented with progressive neck pain and complained of weakness and numbness of the upper left extremity, and a 6-year-old boy presented with complains of neck pain. X-ray, computed tomography, and magnetic resonance imaging findings of 2 patients confirmed the presence of cervical intervertebral disc calcification combined with OPLL. RESULTS: Two children were treated using conservative treatment. The girl was observed up for 2 years and the boy was observed up for 18 months, respectively. Computed tomography and magnetic resonance imaging revealed that cervical intervertebral disc calcification and OPLL at the C6/7 (case 1) and C3/4 (case 2) level have disappeared completely, only a small calcification at the C2/3 intervertebral disc remained in the second case and both of them were asymptomatic. CONCLUSIONS: Cervical intervertebral disc calcification combined with OPLL was rarely observed in children. Conservative management was carried out and the patients had a full recovery. Our experience suggests that the conservative treatment is an acceptable method.

Apelin stimulates glucose uptake through the PI3K/Akt pathway and improves insulin resistance in 3T3-L1 adipocytes.

Apelin, a cytokine mainly secreted by adipocytes, is closely related with insulin resistance. The underlying molecular mechanisms of how apelin affects insulin resistance, however, are poorly understood. This study aimed to investigate the effect of apelin on glucose metabolism and insulin resistance in 3T3-L1 adipocytes. After 10 ng/ml TNF-α treatment for 24 h, insulin-stimulated glucose uptake was reduced by 47% in 3T3-L1 adipocytes. Apelin treatment improved glucose uptake in a time- and dose-dependent manner. Treatment of 1,000 nM apelin for 60 min maximally augmented glucose uptake in insulin-resistant 3T3-L1 adipocytes. Furthermore, apelin pre-incubation also increased adipocytes' insulin-stimulated glucose uptake, and PI3K/Akt pathway were involved in these effects. In addition, immunocytochemistry staining and western blotting analysis indicated that apelin could increase glucose transporter 4 translocation from the cytoplasm to the plasma membrane. Apelin also increased the anti-inflammatory adipokine adiponectin mRNA expression while reducing that of pro-inflammatory adipokine interleukin-6 in insulin-resistant 3T3-L1 adipocytes. These results suggest that apelin stimulates glucose uptake through the PI3K/Akt pathway, promotes GLUT4 translocation from the cytoplasm to the plasma membrane, and modulates inflammatory responses in insulin-resistant 3T3-L1 adipocytes.