Spatial response of urban land use intensity to ecological networks: a case study of Xi'an Metropolitan Region, China.

In the face of the persistent degradation of ecological environments and fragmentation of ecological networks brought about by rapid urbanization, this study focuses on examining the interaction between urban land use intensity and ecological networks in the Xi'an Metropolitan Region (XAMR), China, and their impact on ecological equilibrium and sustainable development. By comprehensively evaluating the changes in land use intensity in XAMR from 2010 to 2020, the aim is to underscore the pivotal role of ecological networks in maintaining urban ecological balance and promoting sustainable development. The findings indicate a transition in land use intensity in the XAMR from low to high concentration, reflecting an intensification in land resource utilization during urbanization. However, the establishment and management of ecological networks can significantly enhance urban ecological security and biodiversity. Notably, this research identified crucial ecological corridors and source areas, augmenting the connectivity of urban green infrastructure and providing vital support for urban biodiversity. Additionally, a significant finding of this study is the spatial spillover effects generated by socioeconomic factors such as the proportion of tertiary and secondary industries and per capita GDP through the ecological network, which have profound impacts on land use intensity in the surrounding areas. These insights offer a novel understanding of the complex interactions within urban ecosystems, emphasizing the importance of incorporating ecological network construction in urban planning. Overall, through a comprehensive analysis of the relationship between the ecological network and land use intensity in the XAMR, this study proposes new directions for urban ecosystem management and land use planning, highlighting the significance of scientific ecological network planning and management in achieving long-term sustainable development in urbanization processes.

Exosomal lncRNA XIST promotes perineural invasion of pancreatic cancer cells via miR-211-5p/GDNF.

Perineural invasion (PNI) is an essential form of tumor metastasis in multiple malignant cancers, such as pancreatic cancer, prostate cancer, and head and neck cancer. Growing evidence has revealed that pancreatic cancer recurrence and neuropathic pain positively correlate with PNI. Therefore, targeting PNI is a proper strategy for pancreatic cancer treatment. Exosomal lncRNA derived from pancreatic cancer cells is an essential component of the tumor microenvironment. However, whether exosomal lncXIST derived from pancreatic cancer cells can promote PNI and its exact mechanism remains to be elucidated. We show that lncXIST mediates nerve-tumor crosstalk via exosomal delivery. Our data reveal that exosomal lncXIST derived from pancreatic cancer cells is delivered to neural cells and promotes their release of glial-cell-line-derived neurotrophic factor (GDNF), essential in facilitating the PNI of pancreatic cancer. Mechanistically, microRNA-211-5p negatively regulates GDNF, and lncXIST serves as a miR-211-5p sponge. The function of exosomes in the dynamic interplay between nerves and cancer is confirmed in both in vivo and in vitro PNI models. Therefore, targeting pancreatic cancer cell-derived exosomal lncXIST may provide clues for a promising approach for developing a new strategy to combat PNI of pancreatic cancer.

HCV Reactivation in a Patient with Hepatocellular Carcinoma Due to Sorafenib: A Case Report.

The global prevalence of hepatitis C virus (HCV) infection is approximately 3%, with a post-infection chronicity rate of up to 50%-85%. HCV reactivation can occur when anti-HCV positive individuals receive antineoplastic therapy. In this study, we report a case of an anti-HCV positive patient with negative HCV RNA after 12 weeks of direct antiviral therapy. Two months later, sorafenib was used to treat hepatocellular carcinoma, and HCV reactivation occurred after 8 months of the treatment. HCV RNA was negative after 12 weeks of antiviral treatment with Sofosbuvir-velpatasvir. We also discussed the mechanism of HCV reactivation caused by sorafenib and the antiviral treatment regimen after HCV reactivation with the relevant literature.

Sulforaphane alleviated vascular remodeling in hypoxic pulmonary hypertension via inhibiting inflammation and oxidative stress.

Hypoxic pulmonary hypertension (HPH) is a cardiopulmonary disease featured by pulmonary vascular remodeling, which is due to abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunction of endothelial cells (ECs). Sulforaphane (SFN) is a natural isothiocyanate extracted from cruciferous vegetables with promising anti-inflammatory and anti-oxidative activities. This study aimed to explore the effect and mechanism of SFN on HPH. Male mice were exposed to persistent chronic hypoxia for 4 weeks to induce HPH. The results demonstrated that SFN repressed the increased right ventricular systolic pressure (RVSP) and attenuated the right ventricular hypertrophy and pulmonary arteries remodeling in HPH mice. In particular, after SFN treatment, the CD68 positive cells in lung sections were reduced; TNF-α and IL-6 levels in lungs and serum declined; activation of NF-κB in PASMCs was inhibited in response to hypoxia. Besides, SFN enhanced the superoxide dismutase (SOD) activity in serum, SOD2 expression, total glutathione levels, and GSH/GSSG ratio in PASMCs, along with a decrease in malondialdehyde (MDA) contents in serum and ROS production in PASMCs after hypoxia exposure. Notably, SFN, as an Nrf2 activator, reversed the reduction in Nrf2 expression in hypoxic PASMCs. In vitro, SFN treatment inhibited hyperproliferation and promoted apoptosis of PASMCs under hypoxia conditions. SFN also prevented the apoptosis of pulmonary microvascular ECs caused by hypoxia. Therefore, these data suggested that SFN could significantly restrain the inflammation and oxidative stress, thereby inhibiting PASMCs proliferation, promoting PASMCs apoptosis, and reversing hypoxia injury in ECs to improve pulmonary vascular remodeling.

Melatonin Attenuates Mitochondrial Damage in Aristolochic Acid-Induced Acute Kidney Injury.

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Interferon α-2b spray shortened viral shedding time of SARS-CoV-2 Omicron variant: An open prospective cohort study.

Background: The Omicron SARS-CoV-2 variant has spread quickly worldwide due to its effects on virus transmission and vaccine effectiveness. Interferon(IFN) has been shown to have a protective effect against SARS-CoV because of its broad antiviral activity. This study aimed to analyze the treatment effects of IFN α-2b spray in virus clearance of the Omicron SARS-CoV-2 variant. Methods: We examined the effectiveness and safety of IFN α-2b spray in Shanghai, China, with participants infected with the Omicron SARS-CoV-2 variant in an open, prospective cohort study from April 16th to May 5th, 2022. Results: A total of 871 confirmed patients were enrolled in this study. Four hundred and thirteen patients were allocated to the IFN α-2b spray group, and 458 patients were allocated to the control group. The viral shedding time was significantly different between experimental group and control group (11.90 vs.12.58, P <0.05). In the experimental group, the median administration time since the first positive test for SARS-CoV-2 was three days, ranging from 0 to 15 days. There was no obvious adverse effect associated with the spray of IFN α-2b. The univariate Cox regression analysis revealed that the administration time since the first positive test ≤3 days was a protective factor associated with viral shedding time (HR 0.81 95% CI 0.74-0.87, P <0.05). Subgroup analysis showed that the viral shedding time was 10.41 (4.00-16.00) days in the ≤3 days group, which was significantly less than that in the control group (12.58, 95% CI: 7.00-19.15, P <0.0001) and in the >3 days group (13.56, 95%CI: 7.00-22.25, P <0.0001). Conclusions: IFN α-2b spray shortened the viral shedding time of the Omicron SARS-CoV-2 variant when administrated within three days since the first positive test for SARS-CoV-2.

Observation of Voriconazole in the Treatment of Liver Failure Complicated With Invasive Pulmonary Fungal Infection Induced by Chinese Patent Medicine in Teenagers: 2 Case Reports.

Background: Drug-induced liver injury (DILI) caused by Chinese patent medicines is increasing in China. The incidence of invasive fungal infections (IFIs) is increasing due to the suppression of the immune function in greater numbers of patients. Invasive procedures such as deep vein catheterization and the use of glucocorticoids are also predisposing factors to IFIs. The clinical presentation of IFI in teenagers is often atypical, challenging to diagnose, difficult to treat, and associated with a high fatality rate. Case presentation: Herein, we report 2 teenagers with liver failure after receiving oral Chinese patent medicines. Case 1 was a 14-year-old boy who presented with subacute liver failure who had been administered a Chinese patent medicine that included acetaminophen. Administration of glucocorticoids and non-bioartificial liver treatment improved his condition. Subsequently, invasive pulmonary Aspergillus (IPA) was diagnosed and was successfully treated with voriconazole for 85 days. Case 2 was a 17-year-old girl who presented with acute liver failure after taking the Chinese patent medicine QubaiBabuqi tablets for vitiligo. Chest computed tomography (CT) revealed multiple pulmonary nodules with an intermittent low-grade fever, and she was diagnosed with IPA. She was initially treated with caspofungin (23 days) and then voriconazole (406 days) for 429 days. Her liver function returned to normal, and lung lesions were absorbed in 2 patients. At the same time, two to three histopathological examinations of the liver biopsy showed that the drug-induced autoimmune-like phenomena could be improved by glucocorticoid therapy. Conclusion: To the best of our knowledge, this is the first report of the successful treatment of 2 cases of liver failure (Child-Pugh class C) caused by Chinese patent medicines complicated with IPA in teenagers. Drug-induced autoimmune-like phenomena could be improved by glucocorticoid therapy.

Melatonin Attenuates Dasatinib-Aggravated Hypoxic Pulmonary Hypertension via Inhibiting Pulmonary Vascular Remodeling.

Dasatinib treatment is approved as first-line therapy for chronic myeloid leukemia. However, pulmonary hypertension (PH) is a highly morbid and often fatal side-effect of dasatinib, characterized by progressive pulmonary vascular remodeling. Melatonin exerts strong antioxidant capacity against the progression of cardiovascular system diseases. The present work aimed to investigate the effect of melatonin on dasatinib-aggravated hypoxic PH and explore its possible mechanisms. Dasatinib-aggravated rat experimental model of hypoxic PH was established by utilizing dasatinib under hypoxia. The results indicated that melatonin could attenuate dasatinib-aggravated pulmonary pressure and vascular remodeling in rats under hypoxia. Additionally, melatonin attenuated the activity of XO, the content of MDA, the expression of NOX4, and elevated the activity of CAT, GPx, and SOD, the expression of SOD2, which were caused by dasatinib under hypoxia. In vitro, dasatinib led to decreased LDH activity and production of NO in human pulmonary microvascular endothelial cells (HPMECs), moreover increased generation of ROS, and expression of NOX4 both in HPMECs and primary rat pulmonary arterial smooth muscle cells (PASMCs) under hypoxia. Dasatinib up-regulated the expression of cleaved caspase-3 and the ratio of apoptotic cells in HPMECs, and also elevated the percentage of S phase and the expression of Cyclin D1 in primary PASMCs under hypoxia. Melatonin ameliorated dasatinib-aggravated oxidative damage and apoptosis in HPMECs, meanwhile reduced oxidative stress level, proliferation, and repressed the stability of HIF1-α protein in PASMCs under hypoxia. In conclusion, melatonin significantly attenuates dasatinib-aggravated hypoxic PH by inhibiting pulmonary vascular remodeling in rats. The possible mechanisms involved protecting endothelial cells and inhibiting abnormal proliferation of smooth muscle cells. Our findings may suggest that melatonin has potential clinical value as a therapeutic approach to alleviate dasatinib-aggravated hypoxic PH.

[An overview on sleep research based on functional near infrared spectroscopy].

Sleep is a complex physiological process of great significance to physical and mental health, and its research scope involves multiple disciplines. At present, the quantitative analysis of sleep mainly relies on the "gold standard" of polysomnography (PSG). However, PSG has great interference to the human body and cannot reflect the hemodynamic status of the brain. Functional near infrared spectroscopy (fNIRS) is used in sleep research, which can not only meet the demand of low interference to human body, but also reflect the hemodynamics of brain. Therefore, this paper has collected and sorted out the related literatures about fNIRS used in sleep research, concluding sleep staging research, clinical sleep monitoring research, fatigue detection research, etc. This paper provides a theoretical reference for scholars who will use fNIRS for fatigue and sleep related research in the future. Moreover, this article concludes the limitation of existing studies and points out the possible development direction of fNIRS for sleep research, in the hope of providing reference for the study of sleep and cerebral hemodynamics.

[Application of "process management and evaluation" in resident standardization training plan in acupuncture-moxibustion department of hospital for postgraduates of non-acupuncture- moxibustion speciality].

The teaching effect of "process management and evaluation" was assessed in resident standardization training plan in acupuncture-moxibustion department of hospital for postgraduates of non-acupuncture-moxibustion speciality. A total of 120 postgraduates of non-acupuncture-moxibustion speciality participating in resident standardization training were randomized into an observation group (60 cases) and a control group (60 cases, 1 case dropped off). In the control group, the conventional training mode was used. In the observation group, the "process management and evaluation" was adopted, in which, the syllabus was refined, various teaching modes were cooperated and the summary was conducted once a week. The training results were evaluated at the end of 1-month shift test and questionnaire was issued in all of the postgraduates of the two groups. In the observation group, the score for theory and the score of each of the items for technical ability, named differentiation and treatment, technical manipulation and physician-patient communication, as well as the total score were all higher than the control group successively (P<0.05, P<0.01). The results of the student questionnaire showed that in the items as "being liable to the memory of relevant knowledge" "connection of theory with practical ability" "stimulating students' interest and subjective initiative" "self-learning ability" "clinical question handling ability" and "communication ability with patients" as well as the total score in the observation group were all higher than the control group successively (P<0.01, P<0.05). The teaching effect of "process management and evaluation" is obviously better than the conventional teaching mode.

SPT6 recruits SND1 to co-activate human telomerase reverse transcriptase to promote colon cancer progression.

Human telomerase reverse transcriptase (hTERT) plays an extremely important role in cancer initiation and development, including colorectal cancer (CRC). However, the precise upstream regulatory mechanisms of hTERT in different cancer types remain poorly understood. Here, we uncovered the candidate transcriptional factor of hTERT in CRC and explored its role and the corresponding molecular mechanisms in regulating hTERT expression and CRC survival with an aim of developing mechanism-based combinational targeting therapy. The possible binding proteins at the hTERT promoter were uncovered using pull-down/mass spectrometry analysis. The regulation of SPT6 on hTERT expression and CRC survival was evaluated in human CRC cell lines and mouse models. Mechanistic studies focusing on the synergy between SPT6 and staphylococcal nuclease and Tudor domain containing 1 (SND1) in controlling hTERT expression and CRC progression were conducted also in the above two levels. The expression correlation and clinical significance of SPT6, SND1, and hTERT were investigated in tumor tissues from murine models and patients with CRC in situ. SPT6 was identified as a possible transcriptional factor to bind to the hTERT promoter. SPT6 knockdown decreased the activity of hTERT promoter, downregulated the protein expression level of hTERT, suppressed proliferation, invasion, and stem-like properties, promoted apoptosis induction, and enhanced chemotherapeutic drug sensitivity in vitro. SPT6 silencing also led to the delay of tumor growth and metastasis in mice carrying xenografts of human-derived colon cancer cells. Mechanistically, SND1 interacted with SPT6 to co-control hTERT expression and CRC cell proliferation, stemness, and growth in vitro and in vivo. SPT6, SND1, and hTERT were highly expressed simultaneously in CRC tissues, both from the murine model and patients with CRC in situ, and pairwise expression among these three factors showed a significant positive correlation. In brief, our research demonstrated that SPT6 synergized with SND1 to promote CRC development by targeting hTERT and put forward that inhibiting the SPT6-SND1-hTERT axis may create a therapeutic vulnerability in CRC.

Steroid receptor coactivator-1 enhances the stemness of glioblastoma by activating long noncoding RNA XIST/miR-152/KLF4 pathway.

Glioblastoma (GBM) recurrence is attributed to the presence of therapy-resistant glioblastoma stem cells. Steroid receptor coactivator-1 (SRC-1) acts as an oncogenic regulator in many human tumors. The relationship between SRC-1 and GBM has not yet been studied. Herein, we investigate the role of SRC-1 in GBM. In this study, we found that SRC-1 expression is positively correlated with grades of glioma and inversely correlated with glioma patient's prognosis. Steroid receptor coactivator-1 promotes the proliferation, migration, and tumor growth of GBM cells. Notably, SRC-1 knockdown suppresses the stemness of GBM cells. Mechanistically, long noncoding RNA X-inactive specific transcript (XIST) is regulated by SRC-1 at the posttranscriptional level and mediates the function of SRC-1 in promoting stemness-like properties of GBM. Steroid receptor coactivator-1 can promote the expression of Kruppel-like factor 4 (KLF4) through the XIST/microRNA (miR)-152 axis. Additionally, arenobufagin and bufalin, SRC small molecule inhibitors, can reduce the proliferation and stemness of GBM cells. This study reveals SRC-1 promotes the stemness of GBM by activating the long noncoding RNA XIST/miR-152/KLF4 pathway and provides novel markers for diagnosis and therapy of GBM.

Aspirin enhances the sensitivity of colon cancer cells to cisplatin by abrogating the binding of NF-κB to the COX-2 promoter.

Cisplatin is one of the most potent chemotherapeutic agents for the treatment of colon cancer. Nevertheless, the unavoidability of the notable toxicity and the development of the acquired resistance severely restricted its clinical application. Aspirin and some other non-steroidal anti-inflammatory drugs have been used to prevent colon tumorigenesis as chemopreventive agents. Here, we explored the possibility of aspirin as an adjuvant drug to boost the anti-cancer effect of cisplatin for colon cancer. We found that aspirin significantly enhanced the cisplatin-mediated inhibitions of cell proliferation, migration and invasion and the induction of apoptosis in colon cancer cells. The combined treatment of aspirin and cisplatin suppressed the expression of the anti-apoptotic protein Bcl-2 and the EMT-related proteins, up-regulated the levels of the cleaved PARP and Bax, and blocked the PI3K/AKT and RAF-MEK-ERK signaling pathway. In addition, we demonstrated that the enhanced effect of aspirin on the cisplatin-induced inhibition of tumor cell growth was also mediated through the suppression of the binding activity of NF-κB to the COX-2 promoter. The combination of aspirin and cisplatin effectively attenuated the translocation of NF-κB p65/p50 from the cytoplasm to the nucleus, and abrogated the binding of NF-κB p65/p50 to the COX-2 promoter, thereby down-regulating COX-2 expression and PGE2 synthesis. Moreover, the in vivo study also verified the enhanced anti-tumor activity of such combined therapy in colon cancer by targeting the NF-κB/COX-2 signaling. Our results provided new insights into understanding the molecular mechanisms of aspirin in sensitizing cisplatin-mediated chemotherapeutic effect in colon cancer and indicated a great potential of this combined therapy for cancer treatment.

Significance of MUC2 gene methylation detection in pancreatic cancer diagnosis.

PURPOSE: This study was conducted to explore the diagnostic value of MUC2 gene methylation in pancreatic cancer. METHODS: Methylation restriction enzyme digestion (Msp I/Hap II) and polymerase chain reaction (PCR) were performed to detect methylation of the MUC2 gene in fecal and blood specimens from seven study subjects with pancreatic cancer (PC), chronic pancreatitis (CP), or normal controls (CON). Simultaneously, blood CA 19-9 levels were detected as a positive indicator of PC. RESULTS: MUC2 methylation was detected in 50% of PC cell lines. In fecal samples, the MUC2 methylation rate in PC (n = 30) was 43.3%, which was significantly higher than those in CP (n = 8, 0%, P < 0.05) and CON (n = 20, 5.0%, P < 0.05). In blood samples, the MUC2 methylation rate in PC (n = 40) was 52.5%, which was significantly higher than those in CP (n = 15, 0%, P < 0.01) and CON (n = 25, 4.0%, P < 0.01). For PC diagnosis, MUC2 gene methylation in blood samples showed higher specificity and positive predictive value than CA 19-9. The combined detection in the feces and blood showed a 60% MUC2 methylation rate in PC (n = 10), which was higher than those in the CP (n = 5, 0%, P < 0.01) and CON (n = 12, 0%, P < 0.01). CONCLUSIONS: The study can clearly indicate that combined detection of MUC2 gene methylation in the peripheral blood and feces could be used as a new screening and early diagnosis method for pancreatic cancer.

Cleavage and polyadenylation specific factor 4 promotes colon cancer progression by transcriptionally activating hTERT.

CPSF4 was identified as a crucial tumorigenic factor in lung cancer development. However, its precise function and the underlying molecular mechanisms in colon cancer progression remain completely unknown. Here, we demonstrate CPSF4 was highly expressed in human colon cancer cells and tissues. Its knockdown inhibited colorectal cancer progression in vitro, including cell proliferation, migration, invasion and stemness maintenance. In contrast, the ectopic overexpression of CPSF4 had the opposite effects in vitro and in vivo. Further mechanistic studies demonstrated that CPSF4 facilitated colorectal tumorigenesis and development partially through transcriptionally regulating hTERT expression by cooperating with NF-kB1 and co-anchoring at hTERT promoter -321 to -234 fragment. In addition, clinical samples analysis indicated that CPSF4 expression was positively correlated with hTERT, and the simultaneously high expression of CPSF4 and hTERT predicted poor patient outcome. Overall, our findings established CPSF4 as a pro-tumorigenic factor in colorectal cancer progression, and suggested that targeting CPSF4-hTERT axis may represent a promising therapeutic strategy in colon cancer treatment.

Aqp-1 Gene Knockout Attenuates Hypoxic Pulmonary Hypertension of Mice.

Objective- Hypoxic pulmonary hypertension (HPH) is characterized by proliferative vascular remodeling. Abnormal pulmonary artery smooth muscle cells proliferation and endothelial dysfunction are the primary cellular bases of vascular remodeling. AQP1 (aquaporin-1) is regulated by oxygen level and has been observed to play a role in the proliferation and migration of pulmonary artery smooth muscle cells. The role of AQP1 in HPH pathogenesis has not been directly determined to date. To determine the possible roles of AQP1 in the pathogenesis of HPH and explore its possible mechanisms. Approach and Results- Aqp1 knockout mice were used, and HPH model was established in this study. Primary pulmonary artery smooth muscle cells, primary mouse lung endothelial cells, and lung tissue sections from HPH model were used. Immunohistochemistry, immunofluorescence and Western blot, cell cycle, apoptosis, and migration analysis were performed in this study. AQP1 expression was upregulated by chronic hypoxia exposure, both in pulmonary artery endothelia and medial smooth muscle layer of mice. Aqp1 deficiency attenuated the elevation of right ventricular systolic pressures and mitigated pulmonary vascular structure remodeling. AQP1 deletion reduced abnormal cell proliferation in pulmonary artery and accompanied with accumulation of HIF (hypoxia-inducible factor). In vitro, Aqp1 deletion reduced hypoxia-induced proliferation, apoptosis resistance, and migration ability of primary cultured pulmonary artery smooth muscle cells and repressed HIF-1α protein stability. Furthermore, Aqp1 deficiency protected lung endothelial cells from apoptosis in response to hypoxic injury. Conclusions- Our data showed that Aqp1 deficiency could attenuate hypoxia-induced vascular remodeling in the development of HPH. AQP1 may be a potential target for pulmonary hypertension treatment.

Gab2 Ablation Reverses the Stemness of HER2-Overexpressing Breast Cancer Cells.

BACKGROUND/AIMS: HER2 has been implicated in mammary tumorigenesis as well as aggressive tumor growth and metastasis. Its overexpression is related to a poor prognosis and chemoresistance in breast cancer patients. Although Grb2-associated binding protein 2 (Gab2) is important in the development and progression of human cancer, its effects and mechanisms in HER2-overexpressing breast cancer are unclear. METHODS: Clone formation and MTT assays were used to examine cell proliferation. To detect the effect of Gab2 on the stemness of breast cancer cells, we used flow cytometry, a sphere formation assay, real-time PCR, and western blot. An animal model was created to validate the effect of Gab2 on tumor growth in vivo. Tissue slides were analyzed by immunohistochemistry. RESULTS: Knockdown of Gab2 suppressed PI3K/AKT and MAPK/ERK pathway activity. Gab2 ablation also reduced the stemness of HER2-overexpressing breast cancer cells. In vivo, knockdown of Gab2 inhibited tumor growth. CONCLUSION: This study unveils a potential function of Gab2 in HER2-overexpressing breast cancer cells. Gab2 might be a potential target in the clinical therapy of HER2-overexpressing breast carcinoma.

Melatonin inhibits the proliferation of breast cancer cells induced by bisphenol A via targeting estrogen receptor-related pathways.

BACKGROUND: Background: Bisphenol A (BPA) is an estrogen-like chemical widely contained in daily supplies. There is evidence that environmental exposure to BPA could contribute to the development of hormone-related cancers. As is reported in numerous studies, melatonin, an endogenous hormone secreted by the pineal gland, could markedly inhibit estrogen-induced proliferation of breast cancer (BC) cells. In this study, we intended to reveal the effects of melatonin on BPA-induced proliferation of estrogen receptor-positive BC cells. METHODS: Methods: We used methyl thiazolyl tetrazolium, luciferase reporter gene and western blotting assays to testify the effect of melatonin on BPA-mediated proliferation of MCF-7 and T47D cells. RESULTS: Methyl thiazolyl tetrazolium and colony formation assays showed that melatonin could significantly abolish BPA-elevated cell proliferation. Meanwhile, BPA-upregulated phosphorylation of ERK and AKT was decreased by melatonin treatment. Mechanistically, we found that BPA was capable of upregulating the protein levels of steroid receptor coactivators (SRC-1, SRC-3), as well as promoting the estrogen response element activity. However, the addition of melatonin could remarkably block the elevation of steroid receptor coactivators expression and estrogen response element activity triggered by BPA. CONCLUSION: Conclusions: Therefore, these results demonstrated that melatonin could abrogate BPA-induced proliferation of BC cells. Therapeutically, melatonin could be regarded as a potential medication for BPA-associated BC.

Ultra-high b-value diffusion-weighted imaging features of the prostatic leiomyoma-case report.

BACKGROUND: Leiomyoma of the prostate is a rare benign tumor arising from smooth muscle fibers. Most cases are incidental findings observed during pathological examinations after resection of the prostate. To the best of our knowledge, only few studies have reported the conventional magnetic resonance imaging (MRI) findings of such tumors; however, no reports have described the ultra-high b-value diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) findings of prostatic leiomyomas. CASE PRESENTATION: We report MR imaging characteristics and surgical pathologic findings of a case of prostatic leiomyoma treated by robot-assisted transperitoneal laparoscopic approach. Typical MR features showed a homogeneous lesion with slightly hypointense signal compared to the skeletal muscle on T2-weighted images, and isointense signal relative to the muscle on T1-weighted images with fat suppression, which collectively demonstrate apparent homogeneous enhancement with a non-enhanced envelope. A slightly hyperintense signal compared to the skeletal muscle was observed on ultra-high b-value DWI, and higher ADC values were observed as compared to the prostate cancer. CONCLUSIONS: Prostatic leiomyoma is a benign tumor. This case indicates that MRI features of prostatic leiomyoma are helpful for the differential diagnosis of prostate cancer.

[Research on vigilance detection based on pulse wave].

This paper studied the rule for the change of vigilance based on pulse wave. 10 participants were recruited in a 95-minute Mackworth clock test (MCT) experiment. During the experiment, the vigilance of all participants were evaluated by Karolinska sleepiness scale (KSS) and Stanford sleepiness scale (SSS), and behavior data (the reaction time and the accuracy of target) and pulse wave signal of the participants were recorded simultaneously. The result indicated that vigilance of the participants can be divided into 3 classes: the first 30 minutes for high vigilance level, the middle 30 minutes for general vigilance level, and the last 30 minutes for low vigilance level. Besides, time domain features such as amplitude of secondary peak, amplitude of peak and the latency of secondary peak decreased with the decrease of vigilance, while the amplitude of troughs increased. In terms of frequency domain features, the energy of 4 frequency band including 8.600 ~ 9.375 Hz, 11.720 ~ 12.500 Hz, 38.280 ~ 39.060 Hz and 39.060 ~ 39.840 Hz decreased with the decrease of vigilance. Finally, under the recognition model established by the 8 characteristics mentioned above, the average accuracy of three-classification results over the 10 participants was as high as 88.7%. The results of this study confirmed the feasibility of pulse wave in the evaluation of vigilance, and provided a new way for the real-time monitoring of vigilance.