The role of the hepatitis B virus genome and its integration in the hepatocellular carcinoma.

The integration of Hepatitis B Virus (HBV) is now known to be closely associated with the occurrence of liver cancer and can impact the functionality of liver cells through multiple dimensions. However, despite the detailed understanding of the characteristics of HBV integration and the mechanisms involved, the subsequent effects on cellular function are still poorly understood in current research. This study first systematically discusses the relationship between HBV integration and the occurrence of liver cancer, and then analyzes the status of the viral genome produced by HBV replication, highlighting the close relationship and structure between double-stranded linear (DSL)-HBV DNA and the occurrence of viral integration. The integration of DSL-HBV DNA leads to a certain preference for HBV integration itself. Additionally, exploration of HBV integration hotspots reveals obvious hotspot areas of HBV integration on the human genome. Virus integration in these hotspot areas is often associated with the occurrence and development of liver cancer, and it has been determined that HBV integration can promote the occurrence of cancer by inducing genome instability and other aspects. Furthermore, a comprehensive study of viral integration explored the mechanisms of viral integration and the internal integration mode, discovering that HBV integration may form extrachromosomal DNA (ecDNA), which exists outside the chromosome and can integrate into the chromosome under certain conditions. The prospect of HBV integration as a biomarker was also probed, with the expectation that combining HBV integration research with CRISPR technology will vigorously promote the progress of HBV integration research in the future. In summary, exploring the characteristics and mechanisms in HBV integration holds significant importance for an in-depth comprehension of viral integration.

Comprehensive profiling of lipid metabolic reprogramming expands precision medicine for HCC.

BACKGROUND AND AIMS: Liver HCC is the second leading cause of cancer-related deaths worldwide. The heterogeneity of this malignancy is driven by a wide range of genetic alterations, leading to a lack of effective therapeutic options. In this study, we conducted a systematic multi-omics characterization of HCC to uncover its metabolic reprogramming signature. APPROACH AND RESULTS: Through a comprehensive analysis incorporating transcriptomic, metabolomic, and lipidomic investigations, we identified significant changes in metabolic pathways related to glucose flux, lipid oxidation and degradation, and de novo lipogenesis in HCC. The lipidomic analysis revealed abnormal alterations in glycerol-lipids, phosphatidylcholine, and sphingolipid derivatives. Machine-learning techniques identified a panel of genes associated with lipid metabolism as common biomarkers for HCC across different etiologies. Our findings suggest that targeting phosphatidylcholine with saturated fatty acids and long-chain sphingolipid biosynthesis pathways, particularly by inhibiting lysophosphatidylcholine acyltransferase 1 ( LPCAT1 ) and ceramide synthase 5 ( CERS5 ) as potential therapeutic strategies for HCC in vivo and in vitro. Notably, our data revealed an oncogenic role of CERS5 in promoting tumor progression through lipophagy. CONCLUSIONS: In conclusion, our study elucidates the metabolic reprogramming nature of lipid metabolism in HCC, identifies prognostic markers and therapeutic targets, and highlights potential metabolism-related targets for therapeutic intervention in HCC.

Modified Biejia Jianwan decoction restrains PD-L1-mediated immune evasion through the HIF-1α/STAT3/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Biejia Jianwan (M-BJJW), a Traditional Chinese Medicine (TCM) decoction, has exhibited great potential in treating hepatocellular carcinoma (HCC). However, its underlying functional mechanism still remains unknown. AIM OF THE STUDY: The study aimed to explore the anti-hepatocarcinogenic effects of M-BJJW, specifically its influence on PD-L1-mediated immune evasion in hypoxic conditions, and elucidate the related molecular mechanisms in HCC. MATERIALS AND METHODS: To investigate the therapeutic efficacy and mechanisms underlying M-BJJW's effects on HCC, we employed a diethylnitrosamine (DEN)-induced rat model maintained for 120 days. Following model establishment, flow cytometry was utilized to assess the distribution of immune cell populations in peripheral blood, spleens, and tumor tissues after M-BJJW administration. Simultaneously, enzyme-linked immunosorbent assays (ELISA) were conducted to analyze cytokine profiles in serum samples. Immunohistochemistry was employed to determine the expression levels of crucial proteins within tumor tissues. Furthermore, HCC cells exposed to CoCl2 underwent Western blot analysis to validate the expression levels of HIF-1α, PD-L1, STAT3, and nuclear factor kappa B (NF-κB) p65. The modulatory effects of STAT3 and NF-κB p65 were investigated using specific inhibitors and activators in wild-type cell lines. High-performance liquid chromatography coupled with mass spectrometry (HPLC/MS) was utilized to identify the chemical constituents present in M-BJJW-medicated serum. The immunomodulatory properties and the anti-tumor activities of M-BJJW were evaluated by co-culturing with peripheral blood mononuclear cells (PBMC) and the CCK-8 assay. Additionally, we assessed M-BJJW's impact on hypoxia-induced alterations in HCC cell lines using immunofluorescence and Western blot assessments. RESULTS: M-BJJW exhibited substantial therapeutic advantages by effectively alleviating pathological deterioration within the HCC microenvironment. In the DEN-induced rat model, M-BJJW administration notably reduced tumor growth. Flow cytometry analyses revealed an increased proportion of Cytotoxic T lymphocytes (CTLs) accompanied by a simultaneous decrease in regulatory T cells (Tregs). ELISA data supported a marked decrease in pro-inflammatory cytokines, including interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor α (TNF-α). Immunohistochemistry confirmed the suppressive effect of M-BJJW on the expression of HIF-1α and PD-L1. Notably, western blotting unveiled the role of HIF-1α in regulating PD-L1 expression via the STAT3 and NF-κB signaling pathways in HCC cell lines, which was validated using activators and inhibitors of STAT3 and NF-κB. The CCK-8 assay and co-culture techniques demonstrated the anti-tumor activity of M-BJJW. Immunofluorescence and western blotting further confirmed that M-BJJW-containing serum dose-dependently inhibited HIF-1α, PD-L1, p-STAT3, and p-p65 in hypoxic HCC cell lines. CONCLUSIONS: M-BJJW demonstrates significant therapeutic potential against HCC by influencing the hypoxic microenvironment, thereby regulating the immunosuppressive milieu. Specifically, M-BJJW modulates the HIF-1α/STAT3/NF-κB signaling pathway, leading to reduced PD-L1 expression and an elevated ratio of cytotoxic T lymphocytes (CTLs), while concurrently decreasing T regulatory cells (Tregs) and immunosuppressive factors. These synergistic effects aid in countering PD-L1-mediated immune evasion, presenting compelling pharmacological evidence supporting the clinical application of M-BJJW as a therapeutic approach for HCC.

Therapeutic effect and transcriptome-methylome characteristics of METTL3 inhibition in liver hepatocellular carcinoma.

Methyltransferase-like 3 (METTL3) is the key subunit of methyltransferase complex responsible for catalyzing N6-methyladenosine (m6A) modification on mRNA, which is the most prevalent post-transcriptional modification in eukaryotes. In this study, we utilized online databases to analyze the association between METTL3 expression and various aspects of tumorigenesis, including gene methylation, immunity, and prognosis. Our investigation revealed that METTL3 serves as a prognostic marker and therapeutic target for liver hepatocellular carcinoma (LIHC). Through experimental studies, we observed frequent upregulation of METTL3 in LIHC tumor tissue and cells. Subsequent inhibition of METTL3 using a novel small molecule inhibitor, STM2457, significantly impeded tumor growth in LIHC cell lines, spheroids, and xenograft tumor model. Further, transcriptome and m6A sequencing of xenograft bodies unveiled that inhibition of METTL3-m6A altered genes enriched in SMAD and MAPK signaling pathways that are critical for tumorigenesis. These findings suggest that targeting METTL3 represents a promising therapeutic strategy for LIHC.

Insights into the role of nucleotide methylation in metabolic-associated fatty liver disease.

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease characterized by fatty infiltration of the liver. In recent years, the MAFLD incidence rate has risen and emerged as a serious public health concern. MAFLD typically progresses from the initial hepatocyte steatosis to steatohepatitis and then gradually advances to liver fibrosis, which may ultimately lead to cirrhosis and carcinogenesis. However, the potential evolutionary mechanisms still need to be clarified. Recent studies have shown that nucleotide methylation, which was directly associated with MAFLD's inflammatory grading, lipid synthesis, and oxidative stress, plays a crucial role in the occurrence and progression of MAFLD. In this review, we highlight the regulatory function and associated mechanisms of nucleotide methylation modification in the progress of MAFLD, with a particular emphasis on its regulatory role in the inflammation of MAFLD, including the regulation of inflammation-related immune and metabolic microenvironment. Additionally, we summarize the potential value of nucleotide methylation in the diagnosis and treatment of MAFLD, intending to provide references for the future investigation of MAFLD.

The emerging role of circular RNAs in drug resistance of non-small cell lung cancer.

Due to the characteristics of aggressiveness and high risk of postoperative recurrence, non-small cell lung cancer (NSCLC) is a serious hazard to human health, accounting for 85% of all lung cancer cases. Drug therapies, including chemotherapy, targeted therapy and immunotherapy, are effective treatments for NSCLC in clinics. However, most patients ultimately develop drug resistance, which is also the leading cause of treatment failure in cancer. To date, the mechanisms of drug resistance have yet to be fully elucidated, thus original strategies are developed to overcome this issue. Emerging studies have illustrated that circular RNAs (circRNAs) participate in the generation of therapeutic resistance in NSCLC. CircRNAs mediate the modulations of immune cells, cytokines, autophagy, ferroptosis and metabolism in the tumor microenvironment (TME), which play essential roles in the generation of drug resistance of NSCLC. More importantly, circRNAs function as miRNAs sponges to affect specific signaling pathways, directly leading to the generation of drug resistance. Consequently, this review highlights the mechanisms underlying the relationship between circRNAs and drug resistance in NSCLC. Additionally, several therapeutic drugs associated with circRNAs are summarized, aiming to provide references for circRNAs serving as potential therapeutic targets in overcoming drug resistance in NSCLC.

Link of sorafenib resistance with the tumor microenvironment in hepatocellular carcinoma: Mechanistic insights.

Sorafenib, a multi-kinase inhibitor with antiangiogenic, antiproliferative, and proapoptotic properties, is the first-line treatment for patients with late-stage hepatocellular carcinoma (HCC). However, the therapeutic effect remains limited due to sorafenib resistance. Only about 30% of HCC patients respond well to the treatment, and the resistance almost inevitably happens within 6 months. Thus, it is critical to elucidate the underlying mechanisms and identify effective approaches to improve the therapeutic outcome. According to recent studies, tumor microenvironment (TME) and immune escape play critical roles in tumor occurrence, metastasis and anti-cancer drug resistance. The relevant mechanisms were focusing on hypoxia, tumor-associated immune-suppressive cells, and immunosuppressive molecules. In this review, we focus on sorafenib resistance and its relationship with liver cancer immune microenvironment, highlighting the importance of breaking sorafenib resistance in HCC.

Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis.

Ubiquitination is a critical type of protein post-translational modification playing an essential role in many cellular processes. To date, more than eight types of ubiquitination exist, all of which are involved in distinct cellular processes based on their structural differences. Studies have indicated that activation of the ubiquitination pathway is tightly connected with inflammation-related diseases as well as cancer, especially in the non-proteolytic canonical pathway, highlighting the vital roles of ubiquitination in metabolic programming. Studies relating degradable ubiquitination through lys48 or lys11-linked pathways to cellular signaling have been well-characterized. However, emerging evidence shows that non-degradable ubiquitination (linked to lys6, lys27, lys29, lys33, lys63, and Met1) remains to be defined. In this review, we summarize the non-proteolytic ubiquitination involved in tumorigenesis and related signaling pathways, with the aim of providing a reference for future exploration of ubiquitination and the potential targets for cancer therapies.

Bone-targeted nanoplatform enables efficient modulation of bone tumor microenvironment for prostate cancer bone metastasis treatment.

As there is currently no effective therapy for patients with prostate cancer (PCa) bone metastasis, it was stringent to explore the relevant treatment strategies. Actually, the interaction between cancer cells and bone microenvironment plays important role in prostate cancer bone metastasis, especially the Sonic hedgehog protein (SHH) signaling in the bone microenvironment. The SHH promotes osteoblast maturation and osteoblast then secretes RANKL to induce osteoclastogenesis. Herein, this study develops bone-targeting calcium phosphate lipid hybrid nanoparticles (NPs) loaded with docetaxel (DTXL) and SHH siRNA for PCa bone metastasis treatment. For bone targeting purposes, the nanoplatform was modified with alendronate (ALN). (DTXL + siRNA)@NPs-ALN NPs effectively change the bone microenvironment by inhibiting the SHH paracrine and autocrine signaling, enhancing the anti-tumor effects of DTXL. Besides showing good in vitro cellular uptake, the NPs-ALN also inhibited tumor growth both in vitro and in vivo by inducing apoptosis, cell cycle arrest, and autophagy. This DDS comprised of (DTXL + siRNA)-loaded NPs provides an excellent strategy to treat PCa bone metastasis.

Isorhamnetin inhibited migration and invasion via suppression of Akt/ERK-mediated epithelial-to-mesenchymal transition (EMT) in A549 human non-small-cell lung cancer cells.

In the present study, we investigated the potential effects of Isorhamnetin on the growth and metastasis of A549 human lung cancer cells, as well as the underlying mechanism. Treatment with Isorhamnetin exhibited a dose- and time-dependent inhibition on A549 cell proliferation. Furthermore, the cell adhesion and Transwell assay showed that treatment with Isorhamnetin (2.5, 5, and 10 µM) for 48 h resulted in a significant inhibition effect on cell adhesion, invasion and migration of A549 cells, depending on concentration, which was associated with the suppression of matrix metalloproteinase (MMP)-2 and MMP-9 activity and protein expression. Moreover, Isorhamnetin effectively suppressed the expressions of epithelial-to-mesenchymal transition (EMT) markers, as evidenced by the down-regulation of N-cadherin, vimentin and snail, as well as up-regulation of E-cadherin protein expression. Additionally, these inhibitions were mediated by interrupting AKT/ERK1/2 signaling pathways. Taken together, the results of the current study demonstrated that Isorhamnetin may become a good anti-metastastic agent against lung cancer A549 cell line by the suppression of EMT via interrupting Akt/ERK1/2 signaling pathway.

Bis(imino)pyridines fused with 6- and 7-membered carbocylic rings as N,N,N-scaffolds for cobalt ethylene polymerization catalysts.

The unsymmetrical diketone, 1,2,3,7,8,9,10-heptahydrocyclohepta[b]quinoline-4,6-dione, based on a central pyridine unit fused by both 6- and 7-membered rings, has been synthesized via a sequence of reactions including ruthenium-catalyzed coupling cyclization. Templating this diketone with a mixture of cobalt(ii) chloride hexahydrate and the corresponding aniline in acetic acid at reflux afforded five examples of carbocyclic-fused bis(arylimino)pyridine-cobalt(ii) chlorides (aryl = 2,6-Me2Ph Co1, 2,6-Et2Ph Co2, 2,6-i-Pr2Ph Co3, 2,4,6-Me3Ph Co4, 4-Me-2,6-Et2Ph Co5) in good yield. All cobalt complexes have been fully characterized including by 1H NMR spectroscopy which reveals broad but assignable paramagnetically shifted peaks. The molecular structures of Co1, Co3 and Co4 highlight the inequivalency of the two fused rings with the cobalt center adopting a distorted trigonal bipyramidal geometry. Treatment of Co1-Co5 with MAO gave highly active catalysts (up to 5.03 × 106 g PE mol-1 (Co) h-1 at 40 °C, with Co4 > Co5 > Co1 > Co2 > Co3) for ethylene polymerization generating strictly linear vinyl-terminated polymers with low molecular weights (Mw range: 1.53-22.77 kg mol-1). By comparison, polymerizations conducted using Co1-Co5/MMAO were less active and displayed a lower selectivity for unsaturated polymers. Common to both MAO and MMAO, the most sterically hindered precatalyst Co3 gave the highest molecular weight polymer of the series (up to 22.77 kg mol-1) but exhibited the lowest activity.

Passive smoking induces pediatric asthma by affecting the balance of Treg/Th17 cells.

BACKGROUND: We aimed to explore the effects of passive smoking on the severity of pediatric asthma and associated molecular mechanisms. METHODS: A total of 378 children with asthma were assigned into four groups according to asthma severity (from grades I to IV). Univariate and multivariate regression analyses were used to analyze possible factors associated with asthma severity in children. Environmental tobacco smoke (ETS) exposure was measured via cotinine concentration in urine. Serum levels of immunoglobulin E (IgE) and cytokines were measured using allergen diagnostic and ELISA (enzyme-linked immunosorbent assay) kits. The percentage of T-regulatory (Treg) and T-helper type 17 (Th17) cells in peripheral blood mononuclear cells (PMBCs) were measured by flow cytometry. Treg- and Th17-associated transcription factors from PMBCs were measured by using ELISA kits. RESULTS: The levels of ETS and serum IgE, and the duration and amounts of passive smoking were closely associated with asthma severity. Passive smoking significantly reduced the levels of FoxP3 (Forkhead/winged helix transcription factor) and tumor growth factor-ß, which were associated with Treg cells, and increased the levels of interleukin-17A and interleukin-23, which were associated with Th17 cells. Meanwhile, passive smoking significantly reduced the ratio of Treg/Th17 cells (P < 0.05). CONCLUSIONS: Passive smoking was closely associated with the severity of childhood asthma by affecting the balance of Treg/Th17 cells.

Fusing Carbocycles of Inequivalent Ring Size to a Bis(imino)pyridine-Iron Ethylene Polymerization Catalyst: Distinctive Effects on Activity, PE Molecular Weight, and Dispersity.

The 4,6-bis(arylimino)-1,2,3,7,8,9,10-heptahydrocyclohepta[b]quinoline-iron(II) chlorides (aryl = 2,6-Me2C6H3 Fe1; 2,6-Et2C6H3 Fe2; 2,6-i-Pr2C6H3 Fe3; 2,4,6-Me3C6H2 Fe4; and 2,6-Et2-4-Me2C6H2 Fe5) have been prepared in good yield by a straightforward one-pot reaction of 2,3,7,8,9,10-hexahydro-1H-cyclohepta[b]quinoline-4,6-dione, FeCl2·4H2O, and the appropriate aniline in acetic acid. All ferrous complexes have been characterized by elemental analysis and FT-IR spectroscopy. In addition, the structure of Fe3 has been determined by single crystal X-ray diffraction, which showed the iron center to adopt a distorted square pyramidal geometry with the saturated sections of the fused six- and seven-membered carbocycles to be cis-configured. In combination with either MAO or MMAO, Fe1-Fe5 exhibited exceptionally high activities for ethylene polymerization (up to 15.86 × 106 g(PE) mol-1 (Fe) h-1 at 40°C (MMAO) and 9.60 × 106 g(PE) mol-1 (Fe) h-1 at 60°C (MAO)) and produced highly linear polyethylene (HLPE, T m ≥ 128°C) with a wide range in molecular weights; in general, the MMAO-promoted polymerizations were more active. Irrespective of the cocatalyst employed, the 2,6-Me2-substituted Fe1 and Fe4 proved the most active while the more sterically hindered 2,6-i-Pr2 Fe3 the least but afforded the highest molecular weight polyethylene (M w : 65.6-72.6 kg mol-1). Multinuclear NMR spectroscopic analysis of the polymer formed using Fe4/MMAO at 40°C showed a preference for fully saturated chain ends with a broad bimodal distribution a feature of the GPC trace (M w/M n = 13.4). By contrast, using Fe4/MAO at 60°C a vinyl-terminated polymer of lower molecular weight (M w = 14.2 kg mol-1) was identified that exhibited a unimodal distribution (M w/M n = 3.8). Moreover, the amount of aluminoxane cocatalyst employed, temperature, and run time were also found to be influential on the modality of the polymer.

Indoor air pollution aggravates asthma in Chinese children and induces the changes in serum level of miR-155.

Indoor air pollution is associated with childhood asthma but the molecular mechanism remains unclear. We aimed to explore the relationship between indoor air pollution and pediatric asthma, and the potential molecular mechanism. The serum level of miR-155 was measured by real-time qPCR in 180 Chinese children with asthma caused by air pollution (an asthma group). Meanwhile, 180 healthy subjects were selected as a control group. HCHO, NO2, and particles (PM10, PM2.5, and PM1) were measured. Univariate and multivariate logistic regression were analyzed to assess the relationship between air pollutants and asthma risk. A rank correlation test was used to explore the relationship between serum level of miR-155 and the level of PM2.5 or HCHO. Serum level of miR-155 was higher in the asthma group than the control group (p < 0.001). The history of childhood allergy, breastfeeding, environmental tobacco smoke, PM2.5, and HCHO were significantly different between two groups (p < 0.05). Serum level of miR-155 was closely associated with the levels of indoor PM2.5 and HCHO in the asthma group (p < 0.05) but not in the control group (p > 0.05). Indoor air pollution aggravates the asthma in Chinese children and induces the changes in the serum level of miR-155. Abbreviation: DEP: Diesel exhaust particles; PAHs: Polycyclic aromatic hydrocarbons; THBS1: thrombospondin 1; ISAAC: International Study of Asthma and Allergies in Childhood; PFTs: Pulmonary Function Tests; FEV1: The first second of forced expiration; EDTA, ethylenediaminetetraacetic acid; RT-qPCR, Reverse transcription quantitative real-time PCR; ETS: environmental tobacco smoke; PAEs: phthalate esters.

Essential role of Na+/Ca2+ exchanger 1 in smoking-induced growth and migration of esophageal squamous cell carcinoma.

Tobacco-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a major environmental risk factor for the pathogenesis of human esophageal squamous cell carcinoma (ESCC). However, the molecular mechanisms by which tobacco induces ESCC are not well understood. Na+/Ca2+ exchanger 1 (NCX1) is a plasma membrane transporter protein that plays an essential role in maintaining cytosolic Ca2+ ([Ca2+]cyt) homeostasis under physiological conditions and is implicated in tumorigenesis as well. In this study, we found that NCX1 expression was significantly higher in ESCC primary tissues compared to the noncancerous tissues and was overexpressed in tumor samples from the smoking patients. The expression of NCX1 proteins was also significantly higher in human ESCC cell lines compared to normal esophageal epithelial cell line. Moreover, NNK potentiated the [Ca2+]cyt signaling induced by removal of extracellular Na+, which was abolished by KB-R7943 or SN-6. NNK dose-dependently promoted proliferation and migration of human ESCC cells induced by NCX1 activation. Therefore, NCX1 expression correlates with the smoking status of ESCC patients, and NNK activates the Ca2+ entry mode of NCX1 in ESCC cells, leading to cell proliferation and migration. Our findings suggest NCX1 protein is a novel potential target for ESCC therapy.

Functional interaction of CCAAT/enhancer-binding-protein-α basic region mutants with E2F transcription factors and DNA.

The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) regulates cell cycle arrest and terminal differentiation of neutrophils and adipocytes. Mutations in the basic leucine zipper domain (bZip) of C/EBPα are associated with acute myeloid leukemia. A widely used murine transforming C/EBPα basic region mutant (BRM2) entails two bZip point mutations (I294A/R297A). BRM2 has been discordantly described as defective for DNA binding or defective for interaction with E2F. We have separated the two BRM2 mutations to shed light on the intertwined reciprocity between C/EBPα-E2F-DNA interactions. Both, C/EBPα I294A and R297A retain transactivation capacity and interaction with E2F-DP. The C/EBPα R297A mutation destabilized DNA binding, whereas the C/EBPα I294A mutation enhanced binding to DNA. The C/EBPα R297A mutant, like BRM2, displayed enhanced interaction with E2F-DP but failed to repress E2F-dependent transactivation although both mutants were readily suppressed by E2F1 for transcription through C/EBP cis-regulatory sites. In contrast, the DNA binding enhanced C/EBPα I294A mutant displayed increased repression of E2F-DP mediated transactivation and resisted E2F-DP mediated repression. Thus, the efficient repression of E2F dependent S-phase genes and the activation of differentiation genes reside in the balanced DNA binding capacity of C/EBPα.

Surgical treatment and rehabilitation of medial Hoffa fracture fixed by locking plate and additional screws: A retrospective cohort study.

PURPOSE: Hoffa fracture fixed by only using a single plate or lag screws might be not strong enough to achieve direct stability. The goal of this study is to determine the functional outcome of the surgical treatment and rehabilitation of medial Hoffa fracture by a locking plate combined with cannulated or lag screws. METHODS: A total of 13 patients suffering isolated medical Hoffa fractures were identified during the study period (2005.February-2013.February) and retrospectively analyzed. All the fractures were treated by open reduction via the medial approach, and internal fixation by a locking plate combined with cannulated or lag screws. Early active rehabilitation including tele-rehabilitation for rural patients with restricted weight bearing was instituted after the surgical treatment. The radiological and functional outcome analysis was performed by using Knee Society Score (KSS), the range of movement (ROM), and the stability of fixation of the patients during 24 month follow-up. RESULTS: The bone union of medial Hoffa fractures was achieved in all patients. The articular surface of medial femoral condyle was anatomically reduced. There was no loss of reduction and fixation. All patients achieved satisfactory knee joint function and regained their walking ability with good clinical results through early postsurgical rehabilitation. Ten patients (77%) had 0°-130° range of motion with full extension; two patients (15%) had 0°-115° range of motion; one patient (8%) had 0°-110° range of motion. The KSS of all the patients were more than 80, and the scores of seven patients (54%) were more than 85. CONCLUSION: Fixation with a locking plate and cannulated or lag screws for medial Hoffa fracture seemed to be effective and reliable for achieving anatomical reduction, and gave satisfactory functional results when coupled with aggressive rehabilitation.

Comprehensive transcriptome analysis of mesenchymal stem cells in elderly patients with osteoporosis.

OBJECTIVE: To explore the role of aging in the pathogenesis of osteoporosis, several differentially expressed genes (DEGs) and altered biological pathways were identified in mesenchymal stem cells (MSCs) in elderly patients with osteoporosis. METHODS: Raw data were downloaded from Gene Expression Omnibus database. A total of 14 human MSC samples were available, including five samples from elderly patients suffering from osteoporosis, five controls from young non-osteoporotic donors and five controls from old non-osteoporotic donors. The DEGs were identified using LIMMA package among the three groups. Gene ontology and KEGG pathway analysis were carried out using DAVID. A protein-protein interaction (PPI) network of DEGs was constructed with STRING and then visualized with Cytoscape. RESULTS: A total of 3179 DEGs were screened, including 1071 up- and 2108 down-regulated genes. Compared with young and old controls, 271 and 781 genes were up-regulated in osteoporosis, respectively, and 17 genes were shared. Function and pathway enrichment showed that the up-regulated genes in osteoporosis were involved in extracellular matrix (ECM)-receptor interaction, focal adhesion and mammalian target of rapamycin signaling pathway. Moreover, a range of genes linked to cell adhesion, ECM-receptor interaction and cell cycle were revealed in the PPI network, such as transforming growth factor beta 1, insulin-like growth factor 2 and integrin beta 2. CONCLUSION: A number of DEGs and altered pathways were screened in osteoporosis. Our study provided insights into the role of aging in the pathogenesis of osteoporosis and some DEGs might be potential biomarkers for osteoporosis.

Synthesis, characterization and ethylene polymerization behaviour of binuclear nickel halides bearing 4,5,9,10-tetra(arylimino)pyrenylidenes.

Pyrene-4,5,9,10-tetraone was prepared via the oxidation of pyrene, and reacted with various anilines to afford a series of 4,5,9,10-tetra(arylimino)pyrenylidene derivatives (L1-L4). The tetraimino-pyrene compounds L1 and L2 were reacted with two equivalents of (DME)NiBr2 in CH2Cl2 to afford the corresponding dinickel bromide complexes (Ni1 and Ni2). The organic compounds were fully characterized, whilst the bi-metallic complexes were characterized by FT-IR spectra and elemental analysis. The molecular structures of representative organic and nickel compounds were confirmed by single-crystal X-ray diffraction studies. These nickel complexes exhibited high activities towards ethylene polymerization in the presence of either MAO or Me2AlCl, maintaining a high activity over a prolonged period (longer than previously reported dinickel complex pre-catalysts). The polyethylene obtained was characterized by GPC, DSC and FT-IR spectroscopy and was found to possess branched features.

Nickel(II) complexes bearing 4,5-bis(arylimino)pyrenylidenes: synthesis, characterization, and ethylene polymerization behaviour.

A series of nickel(II) dihalides complexes bearing 4,5-bis(arylimino)pyrenylidenes, NiX2(2,6-R(1)-4-R(2)C6H2N)2C16H8, was synthesized and characterized by FT-IR spectroscopy, elemental analysis, and single crystal X-ray diffraction for the organic compounds (L2 and L3) and the nickel complexes (C1 and C2). The molecular structures of C1 (R(1) = Me, R(2) = H, X = Br) and C2 (R(1) = R(2) = Me, X = Br) revealed a distorted tetrahedral geometry around the nickel centre. Upon treatment with the co-catalysts MAO, EASC and MMAO, all the nickel pre-catalysts exhibited high activities (of up to 4.42 × 10(6) g(PE) mol(Ni)(-1) h(-1)) for ethylene polymerization, and produced polyethylene products with a high degree of branching (up to 130 branched per 1000 carbons) and narrow molecular weight distribution. The influence of the reaction parameters and the nature of the ligands on the catalytic behavior of the title nickel complexes have been investigated.