SRY is a Key Mediator of Sexual Dimorphism in Hepatic Ischemia/Reperfusion Injury.

OBJECTIVES: To identify the role and mechanism of a male specific gene, SRY, in I/R-induced hepatic injury. BACKGROUND: Males are more vulnerable to I/R injury than females. However, the mechanism of these sex-based differences remains poorly defined. METHODS: Clinicopathologic data of patients who underwent hepatic resection were identified from an international multi-institutional database. Liver specific SRY TG mice were generated, and subjected to I/R insult with their littermate WT controls in vivo. In vitro experiments were performed by treating primary hepatocytes from TG and WT mice with hypoxia/reoxygen-ation stimulation. RESULTS: Clinical data showed that postoperative aminotransferase level, incidence of overall morbidity and liver failure were markedly higher among 1267 male versus 508 female patients who underwent hepatic resection. SRY was dramatically upregulated during hepatic I/R injury. Overexpression of SRY in male TG mice and ectopic expression of SRY in female TG mice exacerbated liver I/R injury compared with WTs as manifested by increased inflammatory reaction, oxidative stress and cell death in vivo and in vitro. Mechanistically, SRY interacts with Glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin, and promotes phosphorylation and degradation of ß-catenin, leading to suppression of the downstream FOXOs, and activation of NF-κBand TLR4 signaling. Furthermore, activation of ß-catenin almost completely reversed the SRYoverexpression-mediated exacerbation of hepatic I/R damage. CONCLUSIONS: SRY is a novel hepatic I/R mediator that promotes hepatic inflammatory reaction, oxidative stress and cell necrosis via inhibiting Wnt/ß-catenin signaling, which accounts for the sex-based disparity in hepatic I/R injuries.

Combined fenestrated/chimney thoracic endovascular repair for the treatment of blunt traumatic aortic injury: A case report.

Blunt traumatic thoracic aortic injury (BTAI) is an extremely serious medical condition with a high rate of associated mortality. Recent advances in techniques such as thoracic endovascular repair offer new opportunities to manage the critical BTAI patients in an efficacious yet less invasive manner. A 65 year-old-male suffered from multiple injuries after a fall, including BTAI in the aortic arch, which resulted in dissection of the descending thoracic-abdominal aorta and iliac artery, development of an intimal flap in the left common carotid artery, and dissection of the left subclavian artery. Based on the imaging information of this patient and our clinical experience, the combined treatment of fenestrated thoracic endovascular repair and a chimney technique was immediately planned to fully repair these dissections and moreover prevent further dissection of the branching vessels, additionally to ensure sufficient blood flow in the left subclavian artery and left common carotid artery. The intervention yielded satisfactory early outcomes. Follow-up assessment at six months reported no symptoms or complications associated with the stent-graft. Computed tomography angiography further confirmed adequate stent-graft coverage of the aortic injury.

Cancer­associated fibroblast­derived exosomal miR­382­5p promotes the migration and invasion of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC), with high potential for metastasis, is the most common malignant tumor of the head and neck. Cancer­associated fibroblasts (CAFs) are the main stromal cells in the microenvironment and aggravate tumor progression. However, whether CAFs are associated with the progression of OSCC remains unknown and the underlying mechanism remains unclear. In the present study, the role of CAFs in mediating OSCC cell migration and invasion was investigated, and the participation of exosomal miR­382­5p in this process was elucidated. In this study, according to the α­SMA staining with immunohistochemistry, 47 OSCC patients were divided into CAFs­rich and CAFs poor groups, and association of CAF density and clinicopathologic features of the OSCC patients were analyzed with Pearson χ2 test. Transwell assay was used for evaluating cell migration and invasion ability of OSCC cells after being co­cultured with NFs or CAFs, or after added exosomes. qPCR was used to detect the expression of miR­382­5p. Western blot analysis was used to measure the expression of migration and invasion­associated proteins. In the present study, the CAF density in tumor tissues was found to be relevant to OSCC lymph node metastasis and TNM stage. Furthermore, we revealed that miR­382­5p was overexpressed in CAFs compared with that in fibroblasts of adjacent normal tissue and miR­382­5p overexpression was responsible for OSCC cell migration and invasion. Finally, we demonstrated that CAF­derived exosomes transported miR­382­5p to OSCC cells. The present study confirmed a new mechanism of CAF­facilitated OSCC progression and may be beneficial for identifying new cancer therapeutic targets.

Prognostic value of long non-coding RNA plasmacytoma variant translocation1 in human solid tumors: A meta-analysis.

Plasmacytoma variant translocation 1 (PVT1) is highly expressed in a variety of cancer tissues and is related to the clinicopathological features and prognosis. However, the prognostic value of PVT1 is still controversial. Therefore, this systematic evaluation and meta-analysis were performed to evaluate the relationship between PVT1 expression and clinicopathological features.PubMed, EMBASE, Web of science, and Cochrane library databases were searched for literature collection according to inclusion criteria and exclusion criteria. The pooled hazard ratios (HRs) or odds ratios (ORs) were used to evaluate the association between PVT1 expression and overall survival, tumor size, tumor-node-metastasis (TNM) stage, lymph node metastasis, and distant metastasis.A total of 39 articles including 3974 patients were included in the study. The results showed that the expression of PVT1 was closely related to the overall survival rate of cancers (HR = 1.64, 95% confidence interval [CI]: 1.50-1.78, P < .000001). Subgroup analysis showed that the high expression of PVT1 was closely related to the low overall survival rate of patients with clear cell renal cell carcinoma, breast cancer, cervical cancer, colon cancer, epithelial ovarian cancer, gastric cancer, lung cancer, and osteosarcoma. In addition, the high expression of PVT1 was positively correlated with tumor size (OR = 1.50, 95% CI: 1.14-1.96, P = .004), TNM stage (OR = 3.39, 95% CI: 2.73-4.20, P < .00001), lymph node metastasis (OR = 2.60, 95% CI: 1.76-3.84, P < .00001), and distant metastasis (OR = 2.94, 95% CI: 1.90-4.56, P < .00001).PVT1 could serve as a marker for the size, TNM stage, metastasis, and prognosis of different type of cancers.

Metformin inhibits metastatic breast cancer progression and improves chemosensitivity by inducing vessel normalization via PDGF-B downregulation.

BACKGROUND: Vascular maturity and functionality are closely associated with tumor progression and chemosensitivity. The antidiabetic agent metformin has shown its ability to inhibit tumor angiogenesis in metastatic breast cancer models. However, it remains unclear if or how metformin remodels the abnormal vasculature of metastatic breast cancer, while inhibiting angiogenesis. METHODS: Metastatic breast cancer models were constructed to compare microvessel density (MVD), vascular maturity and function, lung metastasis and chemosensitivity in metformin-treated or untreated mice. Protein array assay and transcriptome sequencing were performed for genetic screening. Lentiviral shRNA-PDGF-B transfection was used for observing the contribution of PDGF-B knockdown to metformin's vascular effects. RESULTS: Metastatic breast cancers were characterized by an excessively angiogenic, immature and morphologically abnormal vasculature. Compared to control, metformin significantly reduced MVD, leakage and hypoxia, and increased vascular mural cells coverage and perfusion, namely, "vessel normalization". Metformin at human blood concentrations had no direct effect on the migration and proliferation of cancer cells. Based on that, reduced lung metastasis of the primary tumor and improved chemosensitization by metformin were assumed to be mediated via metformin's vascular effects. Further results of genetic screening and in vivo experiments showed that the downregulation of platelet-derived growth factor B (PDGF-B) greatly contributed to the metformin-induced vessel normalization. CONCLUSIONS: These findings provide pre-clinical evidences for the vascular mechanism of metformin-induced metastasis inhibition and the chemosensitization of metastatic breast cancers.

Identification of key candidate genes and pathways in oral squamous cell carcinoma by integrated Bioinformatics analysis.

Oral squamous cell carcinoma (OSCC) is one of the most common types of malignant head and neck tumor, which poses a serious threat to human health. In recent years, the incidence of OSCC has been increasing, while the prognosis has not significantly improved. Elucidation of the molecular mechanisms underlying the development of OSCC may provide novel therapeutic strategies. In the present study, the gene expression profiles from 4 datasets, including 244 OSCC and 95 normal oral mucosa samples, were subjected to statistical and Bioinformatics analysis. A total of 34 differentially expressed genes (DEGs) were identified, among which 14 were upregulated and 20 were downregulated in OSCC compared with normal oral mucosa tissues. Gene Ontology enrichment analysis indicated that the DEGs were mainly involved in regulation of the immune response, cell adhesion and cell proliferative processes. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were mainly associated with the phosphoinositide-3 kinase Akt and Toll-like receptor signaling pathway. The key candidate DEGs were identified from the complex protein-protein interaction network, and secreted phosphoprotein 1 (SPP1), integrin subunit α 3 and plasminogen activator, urokinase (PLAU) were confirmed to be significantly associated with the survival rate. Cell Counting Kit-8 and Transwell assays demonstrated that SPP1 and PLAU regulate cell proliferation, migration and invasion. The candidate genes/pathways identified in the present study may include promising diagnostic biomarkers or therapeutic targets for OSCC.

The efficacy of polidocanol sclerotherapy in mucocele of the minor salivary gland.

OBJECTIVES: Mucocele of the minor salivary gland is usually caused when the duct is injured, mucus leaks into the tissue space and the mucous gland are obstructed, which lead to cystic lesion formation and dilatation. Currently, there are multiple therapeutic methods available with various outcomes. This study aims to provide clinical evidence of polidocanol sclerotherapy for the treatment of mucocele of the minor salivary gland. METHODS: In this study, we injected polidocanol into 112 patients who were diagnosed with mucocele of the minor salivary gland and evaluated the treatment efficacy and safety systematically. RESULTS: Of the 122 cases, 102 cases were cured, eight cases showed remarkable remission, and two cases had partial remission. No recurrence was found during follow-up, and none of the cases showed an invalid effect, resulting in a total cure rate of 91.07%. No severe side effects were observed during treatment or the follow-up period. No significant difference in efficacy between different genders was found (P = 0.490). Polidocanol sclerotherapy for mucocele on the lower lip was more effective compared to mucocele on the inferior surface of the lingual apex (P = 0.035). CONCLUSION: Polidocanol sclerotherapy showed satisfying curative effects for mucocele of the minor salivary gland without causing side effects of anesthesia, trauma, or severe pain.

Metformin's antitumour and anti-angiogenic activities are mediated by skewing macrophage polarization.

Beneficial effects of metformin on cancer risk and mortality have been proved by epidemiological and clinical studies, thus attracting research interest in elucidating the underlying mechanisms. Recently, tumour-associated macrophages (TAMs) appeared to be implicated in metformin-induced antitumour activities. However, how metformin inhibits TAMs-induced tumour progression remains ill-defined. Here, we report that metformin-induced antitumour and anti-angiogenic activities were not or only partially contributed by its direct inhibition of functions of tumour and endothelial cells. By skewing TAM polarization from M2- to M1-like phenotype, metformin inhibited both tumour growth and angiogenesis. Depletion of TAMs by clodronate liposomes eliminated M2-TAMs-induced angiogenic promotion, while also abrogating M1-TAMs-mediated anti-angiogenesis, thus promoting angiogenesis in tumours from metformin treatment mice. Further in vitro experiments using TAMs-conditioned medium and a coculture system were performed, which demonstrated an inhibitory effect of metformin on endothelial sprouting and tumour cell proliferation promoted by M2-polarized RAW264.7 macrophages. Based on these results, metformin-induced inhibition of tumour growth and angiogenesis is greatly contributed by skewing of TAMs polarization in microenvironment, thus offering therapeutic opportunities for metformin in cancer treatment.

A Comparison of Concomitant Tributary Laser Ablation and Foam Sclerotherapy in Patients Undergoing Truncal Endovenous Laser Ablation for Lower Limb Varicose Veins.

PURPOSE: To compare outcomes of patients who received simultaneous tributary endovenous laser ablation (EVLA) or foam sclerotherapy (FS) with EVLA of the great saphenous vein (GSV) trunk. METHODS AND MATERIALS: This study recruited 418 patients (542 legs) with diagnosed varicose veins. Patients in the EVLA/FS group (255 patients, 327 legs) received concomitant FS for the tributaries with truncal lasering. For the EVLA-alone group (163 patients, 215 legs), tributaries (8W) were ablated with EVLA in addition to the GSV trunk (14W). Complications, Aberdeen Varicose Vein Questionnaire (AVVQ), EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D), numerical rating scale (NRS) scores, and condition of residual varicosities were assessed at 3 days, 4 weeks, and 6 months after procedure. All residual varicosities were identified and treated with a staged FS at 6 months. RESULTS: Except for ecchymosis, incidence of other complications was not significantly different between both groups at 6 months. Pain NRS scores of the EVLA/FS group were remarkably elevated at 4 weeks and then, at 6 months, declined to a level similar to the EVLA-alone group. The EVLA/FS group exhibited more significant improvement in both AVVQ and EQ-5D scales than the EVLA group at 6 months, while exhibiting poor improvement at 4 weeks. The EVLA/FS group had a significantly lower rate of residual varicosities than the EVLA group, thus reducing the need for the staged FS. CONCLUSIONS: These results confirm the feasibility and safety of simultaneous tributary EVLA and FS. In addition, they indicate better early quality-of-life improvement and a reduced reoperation rate of simultaneously combined truncal EVLA and tributary FS.

Garcinone E induces apoptosis and inhibits migration and invasion in ovarian cancer cells.

Ovarian cancer remains the most lethal gynecological malignant tumor. In this study, 24 xanthones were isolated and identified from the pericarps of mangosteen (Garcinia mangostana), and their anti-proliferative activities were tested in ovarian cancer cells. Garcinone E (GE) was found to exhibit excellent anti-proliferative effects among the tested xanthones. It significantly inhibited the proliferation in HEY, A2780, and A2780/Taxol cells as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, Hoechst 33342 staining, annexin V/PI staining, and JC-1 staining. It induced endoplasmic reticulum (ER) stress and activated the protective inositol-requiring kinase (IRE)-1α pathway. Knocking down IRE-1α further activated the caspase cascade and caused an increase in cell death. Moreover, GE eliminated the migratory ability of HEY cells by reducing the expression of RhoA and Rac. It also blocked the invasion, which might be related to downregulation of matrix metalloproteinases (MMPs), i.e., MMP-9 and MMP-2, and upregulation of tissue inhibitors of metalloproteinase (TIMP) -1 and TIMP-2. In summary, GE exerts anticancer activities by inducing apoptosis and suppressing migration and invasion in ovarian cancer cells, which indicates its therapeutic potential for ovarian cancer.

[Emodin ameliorates the peritoneal dialysis-related peritoneal fibrosis via inhibiting the activation of Notch pathway].

Long term peritoneal dialysis (PD) is often associated with peritoneal fibrosis. The aim of this study was to explore the effect of emodin on PD-related peritoneal fibrosis and its related cellular and molecular mechanism. PD-related peritoneal fibrosis rats and cultured rat peritoneal mesothelial cells were recruited in the experiment. PD-related peritoneal fibrosis was induced by intraperitoneal injection of lactate-buffered solution containing 4.25% glucose. The peritoneal equilibrium test (PET) was performed at the end of 2 weeks, 4 weeks, and 6 weeks, respectively. HE staining and Masson staining were used for histopathological evaluation. Enzyme linked immunosorbent assay (ELISA) was used to measure the plasma N-terminal procollagen III propeptide (PIIINP) level. Real-time PCR technique was used to detect the mRNA levels of Notch1, Jagged-1, and Hes-1 in peritoneal tissue. Western blot was applied to identify the protein levels of Notch1, Jagged-1, Hes-1, and Notch intracellular domain (NICD). In vitro, Notch1 overexpressing or knockdown rat peritoneal mesothelial cells were established and Western blot was used to examine the effect of emodin on the expressions of Hes-1 and Hey. Compared with the control group, HE staining revealed that PD rats suffered from decreasing in mesothelial cells, or detaching from surface of parietal peritoneum, accompanied by infiltration of inflammatory cells; Masson staining result showed thickened peritonea (P < 0.01), and the collagen deposition in the parietal peritoneum was increased; also, PIIINP level in plasma was elevated (P < 0.01). Treatment of the PD rats with emodin increased mesothelial cells in peritoneal tissue, and decreased the peritoneal thickness (P < 0.01), collagen depositions, as well as the plasma PIIINP level (P < 0.05). The expressions of Notch1, Jagged-1, Hes-1 and NICD in peritoneal tissue were also attenuated (P < 0.05 or P < 0.01). In cultured rat peritoneal mesothelial cells, compared with emodin group, emodin further inhibited the expressions of Hes-1 and Hey induced by Notch1-overexpression (P < 0.05), but not the expressions of Hes-1 and Hey induced by Notch1-knockdown (P > 0.05). Therefore, the activation of Notch pathway may be involved in the pathological process of PD-induced peritoneal fibrosis. Emodin may ameliorate the PD-related peritoneal fibrosis through inhibiting the activation of Notch pathway.

Are incidence and severity of clubfoot related to the season of birth?

BACKGROUND: This study was designed to determine whether the occurrence of clubfoot follows a seasonal pattern in neonates from eastern and south-eastern China and to speculate the potential etiology of clubfoot. METHODS: We reviewed 239 neonates with clubfeet during a period of 4 years as well as the monthly neonatal population of the Sixth National Population Census. Seasonal variations in terms of month of birth and severity were analyzed. RESULTS: The incidence of clubfoot in neonates from eastern and south-eastern China showed seasonal variations, and the incidence was higher in autumn with a reference to the average birth rate in this corresponding area. No significant difference was found in severity of clubfoot. CONCLUSIONS: This seasonal pattern is of significant value to further understanding the etiology and pathogenesis of clubfoot in the corresponding area of China.

Penthorin A and B, two unusual 2,4'-epoxy-8,5'-neolignans from Penthorum chinese.

Two new 2,4'-epoxy-8,5'-neolignans (1 and 2), together with five known 7,9';7',9-diepoxylignans (3-7), were isolated from an ethyl acetate soluble portion of a hepatoprotective water decoction of Penthorum chinese. Their structures and absolute configurations were elucidated by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. This is the second report of 2,4'-epoxy-8,5'-neolignans from plants. Compounds 2, 6, and 7 showed in vitro protective activities against acetaminophen-induced hepatocyte injury at 5 µM.

Regression based state space adaptive model of two-phase anaerobic reactor.

In this paper, a linear state space model for the two-phase anaerobic reactor system was developed based on historical data. Subsequently, the model was used to predict its future behavior. The state space model developed involved correlation analysis and model development. The model would be updated at every time point when a new data set became available, giving it an "adaptive" feature. The model was then applied to monitor two-phase anaerobic co-digestion of a feed comprising 2 industrial secondary sludges and 2 industrial wastewaters. The case study showed the proposed model was able to provide good predictions of various process parameters. In addition, it also predicted impending process failure and this would have allowed the operator to take necessary measures to prevent or reduce impact of such failure during plant operation.

New amino butenolides from the bulbs of Fritillaria unibracteata.

Five new amino γ-butenolides, fritenolide A (1), B (2), C (3), D (4), and E (5), along with four known compounds, were isolated from the bulbs of Fritillaria unibracteata. Their structures were determined by spectroscopic analysis, including 1D NMR, 2D NMR, HRESIMS, HRESIMS/MS, IR, and CD techniques. All isolates were evaluated for the protective activity on injured hepatocytes and cytotoxic activity on human cancer cells in vitro. The unusual amino butenolides were isolated from the Liliaceae family for the first time.

Adhesion of a vesicle on an elastic substrate: 2D analysis.

Cell or vesicle adhesion plays an essential role in a plethora of physiological activities. In this study, we established a theoretical model to explore the adhesion behavior of a vesicle adhering on an elastic substrate. Based upon the free energy functional of the system, the governing equation set and the transversality boundary conditions were derived. The morphology of the vesicle-substrate system and the phase diagram were presented, and it was found that there exist different wrapping states depending on the work of adhesion and bending stiffness. Finally, the adhesion behavior of a vesicle to a rigid substrate was investigated. These analyses are beneficial to understanding the mechanism of cell motility, and cast a new light on the droplet wrapped by a membrane when input the voltage.

A follow-up study on newer anti-epileptic drugs as add-on and monotherapy for partial epilepsy in China.

BACKGROUND: Recently, new anti-epileptic drugs (AEDs) have been more frequently selected to treat epilepsy. In the present study, we evaluated the dynamic changes of efficacy and safety of three newer AEDs for treating partial epilepsy in China. METHODS: Patients were collected sequentially and were divided into three groups which accepted oxcarbazepine (OXC), lamotrigine (LTG) or topiramate (TPM) therapy. Each group included monotherapy and add-on therapy subgroups. We followed all patients for one year and recorded the indexes of efficacy and safety in detail. RESULTS: A total of 909 patients finished the follow-up observation. No significant difference was found in proportion of patients with > or = 50% reduction, > or = 75% reduction and 100% seizure reduction in the LTG and OXC groups between the first and the second six months. In the TPM group there was a statistical difference between the first and the second six months in proportion of patients with > or = 50% reduction (P = 0.002), > or = 75% reduction (P < 0.0001) and 100% seizure reduction (P = 0.009) in the monotherapy subgroup, and about > or = 75% reduction and 100% seizure reduction in the add-on therapy subgroup (P < 0.0001). The efficacy between the add-on and monotherapy subgroups showed a statistical difference. The safety of the three newer AEDs was good. CONCLUSIONS: The three newer AEDs all showed good efficacy and tolerability for partial epilepsy. And the efficacy can be maintained for at least one year.

Elasticity-driven droplet movement on a microbeam with gradient stiffness: a biomimetic self-propelling mechanism.

Directional movement of liquid droplets is of significance not only for certain physiological processes in nature but also for design of some microfluidic devices. In this study, we report a novel way to drive directional movement of liquid droplets on a microbeam with a varying or gradient stiffness. We use the energy method to theoretically analyze the interaction between a droplet and the elastic microbeam. The system tends to have the minimum potential energy when the droplet moves to the softer end of the beam. Therefore, a gradient change of the bending stiffness may be utilized to help the directional motion of droplets. Similarly, one can also drive droplets to move in a designed direction by varying the cross sectional geometry of the beam. Finally, some possible applications of this self-propelling mechanism are suggested.

[Comparative study of Modified Xiaoyao Pill combining amitriptyline on therapeutic effect and compliance in treating patients with depression].

OBJECTIVE: To comparatively observe the curative effect, adverse reaction and compliance of Modified Xiaoyao Pill combining amitriptyline (MXP-At) in treating patients with depression. METHODS: Sixty-four patients with diagnosis of depression matched to the Chinese Classification of Mental Disorders (CCMD-3) were randomly assigned to 2 groups, the treatment group treated with MXP-At and the control group with fluoxeline, 32 cases in each group. The curative effect was evaluated by Hamilton depression (HAMD) scale and the adverse reaction was recorded before treatment and at the 2nd, 4th and 12th week of the treatment. Patients were regularly followed up from the 12th week to the 24 th week. The curative effect and compliance in the two groups were compared. RESULTS: The HAMD score dropped in both groups from the 2nd week of the treatment, and at that time, it was lower in the control group than that in the treatment group (P < 0.05); but at the 4th week, no significant difference was found in the therapeutic effect and the HAMD score between the two groups. However, 3 and 14 cases in the treatment and the control group were relapsed during the 12 weeks of follow-up respectively. CONCLUSION: MXP-At shows a curative effect similar to fluoxetine on depression but with less adverse reaction, and is not expensive.