Relationships between apolipoprotein E and insulin resistance in patients with obstructive sleep apnoea: a large-scale cross-sectional study.

BACKGROUND: Obstructive sleep apnoea (OSA) is commonly associated with insulin resistance (IR) and dyslipidaemia. Apolipoprotein E (APOE) plays important roles in lipid metabolism. The study aimed to disentangle the multifactorial relationships between IR and APOE based on a large-scale population with OSA. METHODS: A total of 5,591 participants who underwent polysomnography for OSA diagnosis were finally enrolled. We collected anthropometric, fasting biochemical and polysomnographic data for each participant. Linear regression analysis was performed to evaluate the relationships between APOE, IR, and sleep breathing-related parameters. Logistic regression, restricted cubic spline (RCS) and mediation analyses were used to explore relationships between APOE and IR in patients with OSA. RESULTS: Increasing OSA severity was associated with greater obesity, more obvious dyslipidaemia, and higher levels of APOE and IR. APOE was positively correlated with the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and microarousal index (MAI) even after adjusting for age, sex, body mass index, and smoking and drinking levels (ß = 0.107, ß = 0.102, ß = 0.075, respectively, all P < 0.001). The risks of IR increased from the first to fourth quartiles of APOE (odds ratio (OR) = 1.695, 95% CI: 1.425-2.017; OR = 2.371, 95% confidence interval (CI): 2.009-2.816; OR = 3.392, 95% CI: 2.853-4.032, all P < 0.001) after adjustments. RCS analysis indicated non-linear and dose response relationships between APOE, AHI, ODI, MAI and insulin resistance. Mediation analyses showed that HOMA-IR explained 9.1% and 10% of the association between AHI, ODI and APOE. The same trends were observed in men, but not in women. CONCLUSIONS: This study showed that APOE is a risk factor for IR; moreover, IR acts as a mediator between OSA and APOE in men. APOE, IR, and OSA showed non-linear and multistage relationships. Taken together, these observations revealed the complex relationships of metabolic disorders in patients with OSA, which could lead to the development of new treatment modalities and a deeper understanding of the systemic impact of OSA.

Gpbar-1/cAMP/PKA signaling mitigates macrophage-mediated acute cholestatic liver injury via antagonizing NLRP3-ASC inflammasome.

Acute cholestatic liver injury (ACLI) is a disease associated with bile duct obstruction that causes liver inflammation and apoptosis. Although G protein-coupled bile acid receptor1 (Gpbar-1) has diverse metabolic roles, its involvement in ACLI-associated immune activation remains unclear. Liver tissues and blood samples from 20 patients with ACLI and 20 healthy individuals were analyzed using biochemical tests, H&E staining, western blotting, and immunohistochemistry to verify liver damage and expression of Gpbar-1. The expression of Gpbar-1, cAMP/PKA signaling, and the NLRP3 inflammasome was tested in wild-type (WT) and Gpbar-1 knockdown (si-Gpbar-1) mice with ACLI induced by bile duct ligation (BDL) and in primary Kupffer cells (KCs) with or without Gpbar-1-siRNA. The results showed that total bile acids and Gpbar-1 expressions were elevated in patients with ACLI. Gpbar-1 knockdown significantly worsened BDL-induced acute hepatic damage, inflammation, and liver apoptosis in vivo. Knockdown of Gpbar-1 heightened KC sensitivity to lipopolysaccharide (LPS) stimulation. Gpbar-1 activation inhibited LPS-induced pro-inflammatory responses in normal KCs but not in Gpbar-1-knockdown KCs. Notably, NLRP3-ASC inflammasome expression was effectively enhanced by Gpbar-1 deficiency. Additionally, Gpbar-1 directly increased intracellular cAMP levels and PKA phosphorylation, thus disrupting the NLRP3-ASC inflammasome. The pro-inflammatory characteristic of Gpbar-1 deficiency was almost neutralized by the NLRP3 inhibitor CY-09. In vitro, M1 polarization was accelerated in LPS-stimulated Gpbar-1-knockdown KCs. Therapeutically, Gpbar-1 deficiency exacerbated BDL-induced ACLI, which could be rescued by inhibition of the NLRP3-ASC inflammasome. Our study reveal that Gpbar-1 may act as a novel immune-mediated regulator of ACLI by inhibiting the NLRP3-ASC inflammasome.

Role of T cells in liver metastasis.

The liver is a major metastatic site (organ) for gastrointestinal cancers (such as colorectal, gastric, and pancreatic cancers) as well as non-gastrointestinal cancers (such as lung, breast, and melanoma cancers). Due to the innate anatomical position of the liver, the apoptosis of T cells in the liver, the unique metabolic regulation of hepatocytes and other potential mechanisms, the liver tends to form an immunosuppressive microenvironment and subsequently form a pre-metastatic niche (PMN), which can promote metastasis and colonization by various tumor cells(TCs). As a result, the critical role of immunoresponse in liver based metastasis has become increasingly appreciated. T cells, a centrally important member of adaptive immune response, play a significant role in liver based metastases and clarifying the different roles of the various T cells subsets is important to guide future clinical treatment. In this review, we first introduce the predisposing factors and related mechanisms of liver metastasis (LM) before introducing the PMN and its transition to LM. Finally, we detail the role of different subsets of T cells in LM and advances in the management of LM in order to identify potential therapeutic targets for patients with LM.

Advances in the pathogenesis of vulvar lichen sclerosus.

Vulvar lichen sclerosus (VLS) is a chronic non-neoplastic skin lesion characterized by vulvar itching, pain, atrophy, whitening of the skin and mucous membranes, and gradual atrophy and disappearance of the labia minora, which can eventually lead to vulvar scarring, causing functional impairment and seriously affecting the patient's physical and mental health. VLS can occur at any age, however, its pathogenesis and etiology are not fully understood. Considerable progress has been made in related research on genetic susceptibility factors, autoimmune disorders, collagen metabolism abnormalities, and their triggering factors in disease formation and progression. This article reviews the etiology of vulvar lichen sclerosus.

Application of Laennec extrathecal blockade combined with indocyanine green fluorescence imaging in laparoscopic anatomic hepatectomy.

OBJECTIVE: To investigate the safety and application value of combining Laennec extracapsular occlusion with ICG fluorescence imaging in laparoscopic anatomic hepatectomy. METHODS: Complete laparoscopic dissection was performed outside the Laennec sheath, blocking Glisson's pedicle of the corresponding liver segment or lobe. An appropriate amount of indocyanine green (ICG) dye was intravenously injected, and the boundary line between the pre-cut liver segment and liver lobe was identified using fluorescence laparoscopy. Complete resection of the liver segment or lobe was performed based on anatomical markers. Clinical data, including operation time, intraoperative blood loss, postoperative hospital stay, and postoperative complications, were collected. RESULTS: A total of 14 cases were included in the study, including seven cases of primary liver cancer, three cases of metastatic liver cancer, three cases of intrahepatic bile duct calculi, and one case of hepatic hemangioma. All 14 patients underwent anatomic hepatectomy under fluorescent laparoscopy, with four cases involving the right liver, seven cases involving the left liver, two cases involving the right anterior lobe, and one case involving the right posterior lobe. CONCLUSION: Combining laparoscopic follow-up of the Laennec membrane with Glisson outer sheath block and intraoperative ICG fluorescence imaging provides real-time guidance for locating the resection boundaries during anatomic hepatectomy. This approach helps in controlling intraoperative bleeding, reducing operation time, and ensuring high safety. It holds significant value in clinical application.

Cadmium influence on lipid metabolism in Sprague-Dawley rats through linoleic acid and glycerophospholipid metabolism pathways.

Cadmium (Cd) is widely distributed in the environment and easy adsorbed by living organisms with adverse effects. Exposure to Cd-contaminated food may disrupt lipid metabolism and increase human health risk. To study the perturbation effect of Cd on lipid metabolism in vivo, 24 male Sprague-Dawley (SD) rats were randomly assigned four groups and treated by Cd chloride solution (0, 1.375 mg/kg, 5.5 mg/kg, 22 mg/kg) for 14 days. The characteristic indexes of serum lipid metabolism were analyzed. Afterwards, untargeted metabolomics analysis was applied to explore the adverse effects of Cd on rats by liquid chromatography coupled with mass spectrometry (LC-MS). The results revealed that Cd exposure obviously decreased the average serum of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and caused an imbalance of endogenous compounds in the 22 mg/kg Cd-exposed group. Compared with the control group, 30 metabolites with significant differences were identified in the serum. Our results indicated that Cd caused lipid metabolic disorders in rats by disrupting linoleic acid and glycerophospholipid metabolism pathways. Furthermore, there were three kinds of remarkable differential metabolites-9Z,12Z-octadecadienoic acid, PC(20:4(8Z,11Z,14Z,17Z)/0:0), and PC(15:0/18:2(9Z,12Z)), which enriched the two significant metabolism pathways and could be the potential biomarkers.

UHRF2 promotes the malignancy of hepatocellular carcinoma by PARP1 mediated autophagy.

Autophagy have critical implications in the proliferation and metastasis of HCC. In the current study, we aimed to explore the underlying mechanisms of UHRF2 regulates HCC cells autophagy and HCC progression. We initially determined the relationship between UHRF2 and HCC autophagy, oncogenicity and patient survival through GSEA database and TCGA database. We mainly investigated the effect of UHRF2 on HCC development and autophagy through western blot, electron microscopy, and immunofluorescence. Functionally, UHRF2 was positively involved in the autophagy activation. Overexpression of UHRF2 reduced apoptosis in HCC cells, and promoted the malignancy phenotype of HCC both in vitro and in vivo. Mechanistically, PRDX1 bound to UHRF2 and upregulated its protein expression to facilitate the biological function of UHRF2 in HCC. Meanwhile, UHRF2 bound to autophagy-related protein PARP1 and upregulated PARP1 protein level. The results showed that UHRF2 promoted autophagy and contributed to the malignant phenotype of HCC by regulating PARP1 protein level. In summary, a novel interaction between PRDX1, UHRF2, and PARP1 was revealed, suggesting that UHRF2 could inspire a potential biomarker and potential therapeutic target for HCC.

Construction of HBV-HCC prognostic model and immune characteristics based on potential genes mining through protein interaction networks.

OBJECTIVE: To search for human protein-coding genes related to hepatocellular carcinoma (HCC) in the context of hepatitis B virus (HBV) infection, and perform prognosis risk assessment. METHODS: Genes related to HBV-HCC were selected through literature screening and protein-protein interaction (PPI) network database analysis. Prognosis potential genes (PPGs) were identified using Cox regression analysis. Patients were divided into high-risk and low-risk groups based on PPGs, and risk scores were calculated. Kaplan-Meier plots were used to analyze overall survival rates, and the results were predicted based on clinicopathological variables. Association analysis was also conducted with immune infiltration, immune therapy, and drug sensitivity. Experimental verification of the expression of PPGs was done in patient liver cancer tissue and normal liver tissue adjacent to tumors. RESULTS: The use of a prognosis potential genes risk assessment model can reliably predict the prognosis risk of patients, demonstrating strong predictive ability. Kaplan-Meier analysis showed that the overall survival rate of the low-risk group was significantly higher than that of the high-risk group. There were significant differences between the two subgroups in terms of immune infiltration and IC50 association analysis. Experimental verification revealed that CYP2C19, FLNC, and HNRNPC were highly expressed in liver cancer tissue, while UBE3A was expressed at a lower level. CONCLUSION: PPGs can be used to predict the prognosis risk of HBV-HCC patients and play an important role in the diagnosis and treatment of liver cancer. They also reveal their potential role in the tumor immune microenvironment, clinical-pathological characteristics, and prognosis.

De novo design of modular peptide-binding proteins by superhelical matching.

General approaches for designing sequence-specific peptide-binding proteins would have wide utility in proteomics and synthetic biology. However, designing peptide-binding proteins is challenging, as most peptides do not have defined structures in isolation, and hydrogen bonds must be made to the buried polar groups in the peptide backbone1-3. Here, inspired by natural and re-engineered protein-peptide systems4-11, we set out to design proteins made out of repeating units that bind peptides with repeating sequences, with a one-to-one correspondence between the repeat units of the protein and those of the peptide. We use geometric hashing to identify protein backbones and peptide-docking arrangements that are compatible with bidentate hydrogen bonds between the side chains of the protein and the peptide backbone12. The remainder of the protein sequence is then optimized for folding and peptide binding. We design repeat proteins to bind to six different tripeptide-repeat sequences in polyproline II conformations. The proteins are hyperstable and bind to four to six tandem repeats of their tripeptide targets with nanomolar to picomolar affinities in vitro and in living cells. Crystal structures reveal repeating interactions between protein and peptide interactions as designed, including ladders of hydrogen bonds from protein side chains to peptide backbones. By redesigning the binding interfaces of individual repeat units, specificity can be achieved for non-repeating peptide sequences and for disordered regions of native proteins.

Changes in the oral and nasal microbiota in pediatric obstructive sleep apnea.

Background: Several clinical studies have demonstrated that pediatric obstructive sleep apnea (OSA) is associated with dysbiosis of airway mucosal microbiota. However, how oral and nasal microbial diversity, composition, and structure are altered in pediatric OSA has not been systemically explored. Methods: 30 polysomnography-confirmed OSA patients with adenoid hypertrophy, and 30 controls who did not have adenoid hypertrophy, were enrolled. Swabs from four surface oral tissue sites (tongue base, soft palate, both palatine tonsils, and adenoid) and one nasal swab from both anterior nares were collected. The 16S ribosomal RNA (rRNA) V3-V4 region was sequenced to identify the microbial communities. Results: The beta diversity and microbial profiles were significantly different between pediatric OSA patients and controls at the five upper airway sites. The abundances of Haemophilus, Fusobacterium, and Porphyromonas were higher at adenoid and tonsils sites of pediatric patients with OSA. Functional analysis revealed that the differential pathway between the pediatric OSA patients and controls involved glycerophospholipids and amino acid metabolism. Conclusions: In this study, the oral and nasal microbiome of pediatric OSA patients exhibited certain differences in composition compared with the controls. However, the microbiota data could be useful as a reference for studies on the upper airway microbiome.

Therapeutic efficacy of programmed spatial anatomy of the myopectineal orifice in total extraperitoneal hernioplasty: a retrospective study.

This study aimed to investigate the therapeutic efficacy of programmed spatial anatomy of myopectineal orifice technique in laparoscopic total extraperitoneal hernioplasty (TEP) surgery. A total of 121 adult male patients with unilateral inguinal hernias who underwent TEP in the Department of General Surgery, Wujin Hospital, affiliated with Jiangsu University, from January 2019 to December 2020 were selected. Patients were divided into the procedural (63 cases) and traditional groups (58 cases) according to the surgical methods adopted. The procedural group underwent programmed spatial anatomy of the myopectineal orifice combined with TEP, and the traditional group underwent traditional TEP. The perioperative evaluation indicators and postoperative complications were observed and compared between the two groups. Compared with the traditional group, the time of handling hernia, the intraoperative operation time, intraoperative blood loss, postoperative ambulation time, and postoperative hospital stay in the procedural group were significantly reduced (P < 0.05). The incidence of postoperative complications such as sensory nerve abnormalities and chronic pain was significantly decreased (P < 0.05), and the total incidence of complications in the procedural group was significantly lower than that in the traditional group (P < 0.05). While there was no significant difference in postoperative incision infection (P > 0.05). The programmed spatial anatomy of the myopectineal orifice can significantly improve the treatment outcome of TEP, significantly improve the patients' intraoperative and postoperative indicators, and reduce the incidence of postoperative complications. It is worthy of being promoted among young physicians and basic hospitals.

The deubiquitinase OTUD1 noncanonically suppresses Akt activation through its N-terminal intrinsically disordered region.

Akt is commonly activated and serves as a valuable target in human cancer. In this study, OTUD1 is identified as an Akt-associated protein and is downregulated upon Akt activation. Ectopic OTUD1 inhibits Akt phosphorylation; however, its deubiquitinase activity contributes only slightly to this effect. A short peptide (OUN-36) located in the OTUD1 N-terminal intrinsically disordered region strongly binds to the Akt PH domain. The residues in the PH domain, which are required for PtdIns(3,4,5)P3 recognition, are also essential for OUN-36 binding. OUN-36 preferentially inhibits Akt-hyperactive tumor cells' proliferation and interferes with Akt cell membrane localization, presumably by disrupting PH domain-PIP3 interaction. Importantly, OUN-36-based therapy efficiently abrogates Akt feedback reactivation in response to MK-2206 treatment and sensitizes cancer cells to chemotherapy and immunotherapy. We therefore show a mechanism by which OTUD1 modulates Akt activity and suggest a potential peptide-based cancer therapeutic strategy implemented by targeting the Akt PH domain.

Phosphorylation of UHRF2 affects malignant phenotypes of HCC and HBV replication by blocking DHX9 ubiquitylation.

Hepatitis B virus (HBV) infection is one of main contributors to poor prognosis and rapid progression of hepatocellular cancer (HCC). We previously identified the important role of the phosphorylation of ubiquitin-like with PHD and ring finger domains (UHRF2) in HBV-associated HCC. In this study we identify upregulated UHRF2 protein levels in HBV-associated HCC cells and tissues. UHRF2 overexpression promotes the viability, proliferation, migration and invasiveness of HBV-positive HCC cell lines, and enhances HBV DNA replication. To obtain a comprehensive understanding of the interaction networks of UHRF2 and their underlying mechanism, this study suggests that UHRF2 facilitates the ubiquitin-proteasome-mediated proteolysis of DExD/H (Asp-Glu-Ala-His) -box helicase enzyme 9 (DHX9). However, phosphorylation of UHRF2 by HBx at S643 inhibits E3 ubiquitin ligase activity of UHRF2 and improves DHX9 protein stability. Furthermore, results suggest that HBx promotes phosphorylation of UHRF2 by the ETS1-CDK2 axis through the downregulation of miR-222-3p in HBV-associated HCC specimens and cells. Our findings suggest that HBx-induced phosphorylation of UHRF2 S643 acts as a "switch" in HBV-associated HCC oncogenesis, activating the positive feedback between phosphorylated UHRF2 and HBV, provide evidence that UHRF2 is a new regulator and a potential prognostic indicator of poor prognosis for HBV-associated HCC.

A signalling pathway for transcriptional regulation of sleep amount in mice.

In mice and humans, sleep quantity is governed by genetic factors and exhibits age-dependent variation1-3. However, the core molecular pathways and effector mechanisms that regulate sleep duration in mammals remain unclear. Here, we characterize a major signalling pathway for the transcriptional regulation of sleep in mice using adeno-associated virus-mediated somatic genetics analysis4. Chimeric knockout of LKB1 kinase-an activator of AMPK-related protein kinase SIK35-7-in adult mouse brain markedly reduces the amount and delta power-a measure of sleep depth-of non-rapid eye movement sleep (NREMS). Downstream of the LKB1-SIK3 pathway, gain or loss-of-function of the histone deacetylases HDAC4 and HDAC5 in adult brain neurons causes bidirectional changes of NREMS amount and delta power. Moreover, phosphorylation of HDAC4 and HDAC5 is associated with increased sleep need, and HDAC4 specifically regulates NREMS amount in posterior hypothalamus. Genetic and transcriptomic studies reveal that HDAC4 cooperates with CREB in both transcriptional and sleep regulation. These findings introduce the concept of signalling pathways targeting transcription modulators to regulate daily sleep amount and demonstrate the power of somatic genetics in mouse sleep research.

Immunodeficiency, autoimmunity, and increased risk of B cell malignancy in humans with TRAF3 mutations.

Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a central regulator of immunity. TRAF3 is often somatically mutated in B cell malignancies, but its role in human immunity is not defined. Here, in five unrelated families, we describe an immune dysregulation syndrome of recurrent bacterial infections, autoimmunity, systemic inflammation, B cell lymphoproliferation, and hypergammaglobulinemia. Affected individuals each had monoallelic mutations in TRAF3 that reduced TRAF3 expression. Immunophenotyping showed that patients' B cells were dysregulated, exhibiting increased nuclear factor-κB 2 activation, elevated mitochondrial respiration, and heightened inflammatory responses. Patients had mild CD4+ T cell lymphopenia, with a reduced proportion of naïve T cells but increased regulatory T cells and circulating T follicular helper cells. Guided by this clinical phenotype, targeted analyses demonstrated that common genetic variants, which also reduce TRAF3 expression, are associated with an increased risk of B cell malignancies, systemic lupus erythematosus, higher immunoglobulin levels, and bacterial infections in the wider population. Reduced TRAF3 conveys disease risks by driving B cell hyperactivity via intrinsic activation of multiple intracellular proinflammatory pathways and increased mitochondrial respiration, with a likely contribution from dysregulated T cell help. Thus, we define monogenic TRAF3 haploinsufficiency syndrome and demonstrate how common TRAF3 variants affect a range of human diseases.

Prevalence and Outcomes of Unilateral Versus Bilateral Oophorectomy in Women With Ovarian Cancer: A Population-Based Study.

Background: Unilateral oophorectomy has the benefits of preserving the ovarian function of fertility and hormone secretion, but the precise inclusion criteria for candidates for this procedure remain controversial. This study aimed to compare the prevalence and therapeutic efficiency of unilateral oophorectomy in women with ovarian cancer who underwent bilateral oophorectomy; moreover, it aimed to identify the appropriate candidates for unilateral oophorectomy. Methods: Female patients diagnosed with stage I-III ovarian cancer between 2000 and 2017 were retrospectively identified from the Surveillance, Epidemiology, and End Results program database. Overall survival (OS) and disease-specific survival (DSS) after unilateral or bilateral (salpingo-) oophorectomy were estimated. Cumulative mortality rates (CMRs) for non-cancer comorbidities were also estimated. Results: A total of 28,480 women with ovarian cancer were included in this study, of whom 11,517 died during the study period. Of the patients, 7.5% and 48.0% underwent unilateral and bilateral oophorectomy, respectively. Overall, for stage-Ia tumors, unilateral oophorectomy was associated with remarkably better OS and DSS than bilateral oophorectomy (OS: p < 0.001; DSS: p = 0.01). For stage-Ib and stage-Ic ovarian tumor, there was no significant difference between the OS and DSS of patients treated by unilateral oophorectomy and those treated by bilateral oophorectomy. For stage-II and stage-III ovarian cancer, unilateral oophorectomy was associated with remarkably worse OS and DSS than bilateral oophorectomy. Among the reproductive-age women younger than 50 years, the OS and DSS of patients with stage-I tumors receiving unilateral oophorectomy were comparable to those receiving bilateral oophorectomy, even for high-grade stage-Ic tumors (all p > 0.05). For those aged 50 years and older, OS and DSS of patients with stage-I tumor receiving unilateral oophorectomy were significantly worse than those receiving bilateral oophorectomy, even for low-grade stage-Ia ovarian tumor (OS: p < 0.001; DSS: p = 0.02). Conclusion: Unilateral oophorectomy exhibited excellent oncological superiority and was equivalent to bilateral oophorectomy for stage-I ovarian tumors among women of reproductive age. For women of reproductive age, the criteria of unilateral oophorectomy can be appropriately broadened to high-grade stage-Ic diseases because of the better performance of unilateral oophorectomy in this population.

Green tea polyphenols inhibit malignant melanoma progression via regulating circ_MITF/miR-30e-3p/HDAC2 axis.

Green tea polyphenols (GTPs) are regarded as anticancer substances and have been revealed to play significant roles in the development of malignant melanoma. However, the mechanisms by which GTPs perform anticarcinogenic activity are not well elucidated. Cellular function assays revealed that GTPs inhibited melanoma cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted apoptosis in vitro. Circ_MITF expression was elevated in melanoma tissues and cells but was decreased by GTPs in cells. Functional experiments indicated circ_MITF overexpression reversed the anticancer effects of GTPs on melanoma cells. Then the underlying mechanism analysis suggested that circ_MITF served as a sponge for miR-30e-3p to upregulate the level of HDAC2. MiR-30e-3p reexpression attenuated the regulatory effects of circ_MITF on GTPs-treated melanoma cells. Silencing of miR-30e-3p promoted the malignant phenotypes in GTPs-treated melanoma cells, which were reversed by HDAC2 knockdown. Preclinically, administration of GTPs suppressed the expression of downstream target genes and repressed tumorigenesis of xenografts in nude mice. In all, GTPs suppressed melanoma progression by regulating circ_MITF/miR-30e-3p/HDAC2 axis, providing a potential therapeutic strategy for human malignant melanoma intervention.

Treatment of hepatic venous system hemorrhage and carbon dioxide gas embolization during laparoscopic hepatectomy via hepatic vein approach.

With the improvement of laparoscopic surgery, the feasibility and safety of laparoscopic hepatectomy have been affirmed, but intraoperative hepatic venous system hemorrhage and carbon dioxide gas embolism are the difficulties in laparoscopic hepatectomy. The incidence of preoperative hemorrhage and carbon dioxide gas embolism could be reduced through preoperative imaging evaluation, reasonable liver blood flow blocking method, appropriate liver-breaking device, controlled low-center venous pressure technology, and fine-precision precision operation. In the case of blood vessel rupture bleeding in the liver vein system, after controlling and reducing bleeding, confirm the type and severity of vascular damage in the liver and venous system, take appropriate measures to stop the bleeding quickly and effectively, and, if necessary, transfer the abdominal treatment in time. In addition, to strengthen the understanding, prevention and emergency treatment of severe CO2 gas embolism in laparoscopic hepatectomy is also the key to the success of surgery. This study aims to investigate the methods to deal with hepatic venous system hemorrhage and carbon dioxide gas embolization based on author's institutional experience and relevant literature. We retrospectively analyzed the data of 60 patients who received laparoscopic anatomical hepatectomy of hepatic vein approach for HCC. For patients with intraoperative complications, corresponding treatments were given to cope with different complications. After the operation, combined with clinical experience and literature, we summarized and discussed the good treatment methods in the face of such situations so that minimize the harm to patients as much as possible.

An artificially designed elastin-like recombinant polypeptide improves aging skin.

BACKGROUND: As a substrate for cell growth, elastin can promote the regeneration and remodeling of the epidermis, which plays an important role in delaying skin aging. However, elastin proteins are more than 700 amino acids long and cannot be absorbed through the skin, which prevents the direct utilization of elastin in the prevention and treatment of aging skin. METHODS: We designed an elastin-like recombinant polypeptide (ELR) which could be absorbed through the skin based on the property of hexapeptide VGVAPG. Thirty healthy Chinese Han female participants which met the criteria were enrolled in this study and all of them completed the tests including elasticity, tightness, and wrinkle detection. The participants used this polypeptide for 4 weeks and were tested in three visits: one day before trial started (D0), and 14 and 28 days after the trial (D14 and D28, respectively). Paired t-tests or Wilcoxon signed-rank tests for non-parametric measures were used to determine the difference between D0 and D14, or D0 and D28. RESULTS: The skin elasticity level in the thirty participants was significantly increased after using ELR for 28 days (P=0.024), and the average value of skin firmness (Uf) declined from 3.313 (D0) to 3.292 (D14) and 3.265 (D28), although there was no statistically significant difference between treatment and pre-treatment. Furthermore, the wrinkle count (D14: P<0.001; D28: P<0.001), wrinkles volume (D14: P<0.001; D28: P=0.008), and wrinkles area (D14: P<0.001; D28: P<0.001) of Crow's feet were significantly improved by using ELR for 14 days or 28 days. CONCLUSION: Continuous use of ELR could significantly improve skin elasticity and reduce wrinkles.

UHRF2 promotes Hepatocellular Carcinoma Progression by Upregulating ErbB3/Ras/Raf Signaling Pathway.

Emerging evidence revealed that UHRF2 was implicated in a variety of human diseases, especially in cancer. However, the biological function, clinical significance and underly mechanisms of UHRF2 in hepatocellular carcinoma (HCC) is largely unknown. We analyzed the expression of UHRF2 in 371 HCC tissues and 50 para-cancerous tissues of TCGA database. We found that UHRF2 was significantly upregulated in HCC tissues, which was further confirmed in HCC cells and tissues by western blot. More importantly, the level of UHRF2 was correlated with pathological grade and clinical stage, and the patients with high level of UHRF2 had lower overall survival, disease-free survival and higher recurrence rate than those with low UHRF2 level. Univariate and multivariate Cox regression analysis revealed that high level of UHRF2 might be an independent prognostic factor for HCC patients. Functional investigations suggested that ectopic expression of UHRF2 could promote the proliferation, migration and invasion of HCC cell lines, whereas knock down of UHRF2 exhibited an opposite effect. Additionally, gene set enrichment analysis indicated that ERBB signaling pathway was upregulated in patients with high level of UHRF2. Pearson correlation analysis indicated that the expression of UHRF2 was positively correlated with ErbB3 and its downstream targets SOS1, Ras and Raf-1. Furthermore, we found that overexpression of UHRF2 could upregulate the expression of ErbB3, SOS1, Ras and Raf-1. Our findings suggested that UHRF2 might accelerate HCC progression by upregulating ErbB3/Ras/Raf signaling pathway and it might serve as a diagnostic marker and therapeutic target for HCC patients.