Diagnostic efficacy of FibroScan for liver inflammation in patients with chronic hepatitis B: a single-center study with 1185 liver biopsies as controls.

BACKGROUND: Noninvasive diagnostic technologies that can dynamically monitor changes in liver inflammation are highly important for the management of chronic hepatitis B (CHB) patients and thus warrant further exploration. This study assessed the diagnostic efficacy of FibroScan for liver inflammation in CHB patients. METHODS: A total of 1185 patients were selected, and ultrasound-guided liver biopsy was performed within 1 month after the FibroScan test. The liver stiffness measurement (LSM), the reliability criteria (IQR/M) of LSM, the quality of liver biopsy (complete portal area, PA), and the liver inflammation grades were the main observation items of this study. With liver biopsy as the control, the diagnostic efficacy of FibroScan for liver inflammation in CHB patients was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The grade of liver inflammation was positively correlated with the stage of fibrosis (rho = 0.829, P < 0.001). Different grades of inflammation will have significant rise in LSM values within the same fibrosis stage, and LSM values were positively correlated with liver inflammation grade and fibrosis stage, and the rho is 0.579 and 0.593 respectively (P < 0.001). Significant differences in the LSM of FibroScan were observed among different grades of liver inflammation (P < 0.0001). Liver biopsy (PA > 10) served as the control, and the cutoff point and the area under ROC curves (AUCs) of the LSMs for different inflammation grades were as follows: G2, 8.6 kPa, 0.775; G3 9.8 kPa, 0.818; and G4, 11.0 kPa; 0.832. With LSM cutoff values of 8.6 kPa, 9.8 kPa and 11.0 kPa, FibroScan showed certain diagnostic value for CHB patients with G2, G3 and G4 liver inflammation, especially those with G4 inflammation. CONCLUSIONS: The grade of liver inflammation was positively correlated with the stage of fibrosis, different grades of inflammation will have significant rise in LSM values within the same fibrosis stage. In addition to liver fibrosis, FibroScan could evaluate liver inflammation in CHB patients in a noninvasive manner.

17ß-Estradiol Promotes Angiogenesis of Rat Cardiac Microvascular Endothelial Cells In Vitro.

BACKGROUND The formation of new blood vessels, known as angiogenesis, is critical for recovery from ischemic heart disease, and estrogen is considered an important factor in this process. Here, we investigated the effects of 17ß-estradiol (17ß-E2) on proliferation and migration of cardiac microvascular endothelial cells (CMECs) in vitro. MATERIAL AND METHODS Rat CMECs were isolated and cultured with 17ß-E2 (0.001-1 µmol/l) in the absence or presence of the estrogen antagonist tamoxifen. Then, the expression level of estrogen receptor alpha was evaluated by using immunofluorescence assay, RT-PCR, and Western blot. Cell proliferation was detected by methyl thiazolyl tetrazolium analysis and the cell migration was verified by a scraping assay and quantified by a Transwell chamber assay. CMEC differentiation was examined using a tube formation assay. Vascular endothelial growth factor (VEGF) secretion was detected by enzyme-linked immunosorbent assay. RESULTS CMECs exhibited homogenous, polygonal, exhibited contact inhibition, and had characteristically ovoid nuclei with 1 or 2 nucleoli, and the cytoplasm exhibited red fluorescence after staining for von Willebrand factor. 17ß-E2 treatment upregulated estrogen receptor alpha expression in CMECs. 17ß-E2 treatment significantly promoted the proliferation, migration, tubular structure formation, and VEGF secretion in CMECs. The maximal proliferation occurred in the presence of 0.01 µmol/l 17ß-E2. Furthermore, estrogen and VEGF were found to synergistically stimulate angiogenesis. CONCLUSIONS Our data show that 17ß-E2 promotes angiogenesis in vitro and suggests that estrogen treatment as a novel therapeutic modality in the management of arterial insufficiency.

FgSKN7 and FgATF1 have overlapping functions in ascosporogenesis, pathogenesis and stress responses in Fusarium graminearum.

Fusarium head blight caused by Fusarium graminearum is one of the most destructive diseases of wheat and barley. Deoxynivalenol (DON) produced by the pathogen is an important mycotoxins and virulence factor. Because oxidative burst is a common defense response and reactive oxygen species (ROS) induces DON production, in this study, we characterized functional relationships of three stress-related transcription factor genes FgAP1, FgATF1 and FgSKN7. Although all of them played a role in tolerance to oxidative stress, deletion of FgAP1 or FgATF1 had no significant effect on DON production. In contrast, Fgskn7 mutants were reduced in DON production and defective in H2 O2 -induced TRI gene expression. The Fgap1 mutant had no detectable phenotype other than increased sensitivity to H2 O2 and Fgap1 Fgatf1 and Fgap1 Fgskn7 mutants lacked additional or more severe phenotypes than the single mutants. The Fgatf1, but not Fgskn7, mutant was significantly reduced in virulence and delayed in ascospore release. The Fgskn7 Fgatf1 double mutant had more severe defects in growth, conidiation and virulence than the Fgatf1 or Fgskn7 mutant. Instead of producing four-celled ascospores, it formed eight small, single-celled ascospores in each ascus. Therefore, FgSKN7 and FgATF1 must have overlapping functions in intracellular ROS signalling for growth, development and pathogenesis in F. graminearum.

Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening.

Mitochondria are key regulators of hematopoietic stem cell (HSC) homeostasis. Our research identifies the transcription factor Nynrin as a crucial regulator of HSC maintenance by modulating mitochondrial function. Nynrin is highly expressed in HSCs under both steady-state and stress conditions. The knockout Nynrin diminishes HSC frequency, dormancy, and self-renewal, with increased mitochondrial dysfunction indicated by abnormal mPTP opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. By contrast, Nynrin overexpression in HSCs diminishes irradiation (IR)-induced lethality. The deletion of Nynrin activates Ppif, leading to overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies such as Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring HSC function in Nynrin-deficient mice. This study identifies Nynrin as a critical regulator of mitochondrial function in HSCs, highlighting potential therapeutic targets for preserving stem cell viability during cancer treatment.

[A cohort study on the relationship between cerebrovascular hemodynamic changing and risk of stroke].

OBJECTIVE: To study the role of cerebrovascular hemodynamic indexes (CVHI) changing in stroke and to provide reference for stroke prevention and risk factor study. METHODS: From 2003 to 2004, participants aged 40 years and above in two communities in Fengxian district were recruited by cluster sampling. Risk factors of stroke and CVHI were investigated and checked during baseline investigation. A total of 10 565 individuals completed the survey and met the inclusion criterion. After baseline investigation, the cohort was followed up for stroke occurrence. Relative risk (RR) of CVHI and common risk factors were estimated by cohort study design. RESULTS: Age of the cohort was (56.2 ± 11.4) years. 4444 (42.1%) were males and 6121 (57.9%) were females. Total follow-up duration was 67 885.7 person-years. A total of 195 stroke cases occurred and incidence density of stroke was 287.2 per 100 000 person-years. Stroke incidence in exposure groups of hypertension, heart disease and alcohol drinking was 3.47% (108/3118), 2.96% (21/710) and 2.50% (47/1882), respectively. The incidence in corresponding non-exposure group was 1.17% (87/7448), 1.77% (174/9855) and 1.70% (148/8683) respectively. There was significant difference between 2 groups (χ(2) value was 62.72, 4.56 and 4.94, respectively, P < 0.05). Stroke incidence in CVHI score < 25, 25 - 49, 50 - 74 and ≥ 75 groups was 9.12% (59/647), 5.68% (44/775), 2.52% (39/1545) and 0.72% (53/7403)(χ(2)trend = 273.57, P < 0.05), respectively. Incidence of stroke in 40 - 49, 50 - 59, 60 - 69, ≥ 70 years age group was 0.22% (8/3565), 1.28% (43/3357), 2.71% (50/1848) and 5.88% (94/1600) (χ(2)trend = 181.48, P < 0.05), respectively. Multiple Cox regression analysis indicated that RR (95%CI) value of hypertension and cigarette smoking was 1.40(1.02 - 1.92) and 1.59(1.19 - 2.12), respectively when comparing with non-exposure group. RR (95%CI) value in CVHI score < 25, 25 - 49 and 50 - 74 points group were 6.15 (4.08 - 9.26), 4.55 (2.98 - 6.96) and 2.68 (1.75 - 4.09), respectively when comparing with the score ≥ 75 points group. RR (95%CI) value in age 50 - 59, 60 - 69 and ≥ 70 years group was 4.61 (2.16 - 9.82), 7.81 (3.67 - 16.60) and 13.49(6.44 - 28.24), respectively when comparing with below 40 years group. CONCLUSION: CVHI score is the strong independent predictive factor and hypertension, cigarette smoking and age are the independent risk factors of stroke.

Silencing MARCH2 Inhibits the Invasion, Migration, and EMT Transformation of Human Colorectal Cancer SW480 Cells.

Aim: This study aimed to investigate the role of MARCH2 (membrane-associated RING-CH2) in the progression, invasion, and migration of colorectal cancer (CRC). Methods: In this study, the expression levels of MARCH2 and E-cadherin in CRC tissues were detected by immunohistochemistry through retrospective study, and their correlation was analyzed. After silencing the MARCH2 gene using SiRNA MARCH2-1/-2, the invasion and migration abilities of SW480 cells were detected using Transwell and Scratch assay, respectively. Quantitative real-time PCR (qRT-PCR) and Western blotting assays were performed to detect the expression levels of epithelial-mesenchymal transition (EMT) related markers. Results: As compared to adjacent tissues, the MARCH2 expression level was significantly overexpressed in the CRC tissues, and correlated with tumor size, pathological grade, lymph node metastasis, and survival time. MARCH2 was negatively correlated with E-cadherin. MARCH2 silencing significantly restrained the invasion and migration abilities of SW480 cells in vitro. Meanwhile, the MARCH2 silencing also upregulated the mRNA and protein expression levels of E-cadherin and downregulated those of Vimentin. Conclusions: The high expression of MARCH2 was unfavorable for patients' survival. Thus, MARCH2 might be an independent predictor for CRC patients, affecting the invasion and metastasis of CRC through EMT.

Effectiveness of Teriparatide for Spine Fusion in Osteoporotic Patient: A Systematic Review and Meta-Analysis of Comparative Studies.

OBJECTIVE: Our goal was to assess teriparatide's (TP) effectiveness in improving radiographic and functional outcomes after spinal fusion surgery. This meta-analysis included randomized controlled trials (RCTs) and comparative cohort studies. The findings provide valuable insights and guidance for surgeons treating osteoporotic patients undergoing spinal fusion surgery. METHODS: We conducted a systematic review to assess TP's efficacy in spinal fusion surgery for osteoporosis. Through thorough selection, data extraction, and quality assessment, we employed network meta-analysis to evaluate radiographic outcomes (fusion rate, screw loosening, vertebral fracture) and changes in bone mineral density measured by Hounsfield units. Functional outcomes were assessed using the Oswestry Disability Index scales. Our study aims to comprehensively understand TP's impact and effectiveness in spinal fusion surgery. RESULTS: A total of 868 patients were included in the analysis. All patients underwent thoracolumbar internal fixation fusion surgery and were divided into following 2 groups: the TP treatment group and the control group. The results revealed significant differences in radiological outcomes. The fusion rate showed a significant difference, as well as screw loosening, and bone mineral density measured in Hounsfield units. However, there was no significant difference in vertebral fracture. The TP group demonstrated favorable effects with statistical significance. In terms of functional outcomes, there was no significant difference in the assessment of Oswestry Disability Index scores between the 2 treatment groups. CONCLUSIONS: The meta-analysis demonstrated that the TP group exhibited significantly better outcomes, particularly in radiological measures, when compared to the control group. The use of TP in spinal fusion surgery shows promise in reducing postoperative complications and providing overall benefits.

Fabrication of Transparent and Flexible Digital Microfluidics Devices.

This study proposed a fabrication method for thin, film-based, transparent, and flexible digital microfluidic devices. A series of characterizations were also conducted with the fabricated digital microfluidic devices. For the device fabrication, the electrodes were patterned by laser ablation of 220 nm-thick indium tin oxide (ITO) layer on a 175 µm-thick polyethylene terephthalate (PET) substrate. The electrodes were insulated with a layer of 12 µm-thick polyethylene (PE) film as the dielectric layer, and finally, a surface treatment was conducted on PE film in order to enhance the hydrophobicity. The whole digital microfluidic device has a total thickness of less than 200 µm and is nearly transparent in the visible range. The droplet manipulation with the proposed digital microfluidic device was also achieved. In addition, a series of characterization studies were conducted as follows: the contact angles under different driving voltages, the leakage current density across the patterned electrodes, and the minimum driving voltage with different control algorithms and droplet volume were measured and discussed. The UV-VIS spectrum of the proposed digital microfluidic devices was also provided in order to verify the transparency of the fabricated device. Compared with conventional methods for the fabrication of digital microfluidic devices, which usually have opaque metal/carbon electrodes, the proposed transparent and flexible digital microfluidics could have significant advantages for the observation of the droplets on the digital microfluidic device, especially for colorimetric analysis using the digital microfluidic approach.

Comparison of Neoadjuvant Chemotherapy Efficiency in Advanced Ovarian Cancer Patients Treated With Paclitaxel Plus Carboplatin and Intraperitoneal Bevacizumab vs. Paclitaxel With Carboplatin.

Objective: This study evaluated the role of neoadjuvant chemotherapy (NACT) with bevacizumab intraperitoneal perfusion in advanced ovarian cancer (AOC). Methods: In this study, 80 patients with advanced epithelial ovarian cancer (stage IIIc or IV) who received NACT at the Central Hospital of Zhuzhou between February 2019 and October 2020 were enrolled. Patients were randomized to receive paclitaxel plus carboplatin (TC) or TC plus intraperitoneal perfusion of bevacizumab (TCB). The effect of chemotherapy was assessed following two cycles of chemotherapy. Cancer antigen 125 (CA125), tumor size, ascites volume, bleeding volume, duration of operation, surgical satisfaction rate, complication rate, and residual tumor were assessed to monitor response to chemotherapy. Results: Treatment with TCB regimen significantly reduced serum levels of CA125 and ascites volume (p < 0.001). Meanwhile, the TCB group had significantly lower intraoperative blood loss and shorter operation time (p < 0.001). Most importantly, patients treated with TCB regimen had a higher surgical satisfaction rate (p < 0.01). Moreover, the incidence of postoperative wound infection, hypoproteinemia, abdominal distension, and fever was lower in the TCB group compared with the TC group. Assessment of adverse reactions during chemotherapy showed no severe complications between the two groups. Conclusions: The results demonstrated that the TCB regimen is superior to the TC regimen alone in the treatment of AOC. These findings could help improve the surgical satisfaction rate, provide more effective treatment strategies to prolong progression-free survival and reduce postoperative complications, and promote surgical recovery in AOC.

Restoration of Aberrant Shape of Caudate Subregions Associated with Cognitive Function Improvement in Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is an important but less recognized public health concern. Research shows that altered subcortical structures mediate cognitive impairment in patients with mTBI. This has been performed mostly using voxel-based morphometry methods and traditional volume measurement methods, which have certain limitations. In this study, we conducted a vertex-wise shape analysis to understand the aberrant patterns of caudate subregions and recovery from mTBI. The study involved 36 patients with mTBI and 34 matched healthy controls (HCs) observed at seven days (acute phase) and followed up for one month (subacute phase) post-injury. Different aberrant shapes of the caudate subregions were observed at the acute phase, which revealed atrophy in the bilateral dorsal medial caudate, and increase in the size of the right ventral anterior caudate in patients with mTBI related to HCs. Moreover, specific and significant shape restoration of right dorsal medial caudate in mTBI was observed at the subacute phase, which significantly associated with the cognitive function improvement of the patients. These findings suggest that the restoration of the aberrant shape atrophy of the right dorsal medial caudate plays a vital role in the improvement of cognitive function of patients with mTBI, providing an alternative clinical target for these patients.

Abdominopelvic Lymphatic Drainage Area Irradiation for Consolidative Radiotherapy of Advanced Ovarian Carcinoma: Analysis of Clinical Application Efficacy and Dosimetric Verification.

Background: The aim of the study was to evaluate the efficacy of abdominopelvic lymphatic drainage area irradiation (APLN), instead of whole abdominal radiotherapy (WART), in the consolidative radiotherapy of advanced ovarian carcinoma patients. Methods: We conducted a retrospective analysis collecting 99 patients with locally advanced ovarian cancer treated by APLN with 45 - 50 Gy/25- 28 fractions/5-7#, instead of WART. We evaluated the clinical outcome of APLN. Five patients were selected for dosimetric verifications verses WART (30 Gy/20 fractions). The normal tissue complication probability (NTCP) was calculated for the two treatment methods. Results: The mean follow-up time was 64.10 months (5.5 - 113.2 months), after APLN consolidative radiotherapy, 1-, 3-, and 5-year overall survival (OS) was 87.9%, 81.3%, and 61.5%, median disease-free survival (DFS) was 40.8 months, 5-year local recurrence free survival (LRFS) was 75.9%, and 5-year distant metastasis free survival (DMFS) was 49.2%. One patient died due to intestinal perforation. Local recurrence in the area between WART and APLN was rare (3/99 patients). The number of surgical procedures < 2 was an independent risk factor for LRFS (P = 0.023). Dosimetric comparison showed that comparing with WART, APLN significantly reduced the organ at risk (OAR) dose: 25.37 ± 3.63 Gy (25%) for liver, 8.77 ± 5.03 Gy (25%) for kidney, 8.14 ± 1.51 Gy (25%) for small intestine, etc. NTCP was reduced by 0.04-1.04% for liver, kidney, and small intestine. Conclusion: For consolidative radiotherapy in locally advanced ovarian cancer, APLN (intensity-modulated radiotherapy 45 - 50 Gy/25 - 28 fractions) could be an alternative to WART, resulting in excellent LRFS and DFS, with acceptable toxicities, comparing with previous literature reports. Dosimetric analysis also showed the benefits of APLN in NTCP.

Modulation effect of acupuncture treatment on chronic neck and shoulder pain in female patients: Evidence from periaqueductal gray-based functional connectivity.

AIMS: Chronic neck and shoulder pain (CNSP) is a common neurological disorder, which females are more likely to suffer from. The periaqueductal gray (PAG) plays a key role in the descending modulation of pain. This study aimed to investigate altered PAG-based functional connectivity (FC) in female patients with CNSP related to healthy controls (HCs) and the effect of acupuncture for female patients with CNSP using PAG-based FC biomarkers. METHODS: PAG-based FC value was calculated based on resting-state functional images and then compared between patients with CNSP at pre-acupuncture, post-acupuncture, and HCs. Then, correlational analyses were performed to examine the relationships between increased PAG-based FC strength and improved clinical parameters in patients after acupuncture treatment. RESULTS: Before acupuncture treatment, compared to HCs, patients with CSNP showed altered PAG-based FC with widely distributed brain regions, including the left medial superior frontal gyrus, bilateral posterior insula (pIns), and cingulate gyrus. After treatment, patients with CNSP exhibited specially improved PAG-pIns FC compared to that before treatment, and no significant difference was observed in the increased PAG-pIns FC strength between HCs and patients with CNSP after treatment. Furthermore, pain catastrophizing reduction was significantly correlated with the increased PAG-pIns FC strength in patients after treatment. CONCLUSION: The effect of acupuncture treatment may relate to the increased PAG-pIns FC, which significantly correlated with pain catastrophizing reduction after treatment. These findings shed important mechanistic information on the role of therapeutic approaches in treating chronic neck and shoulder pain.

Invasive Mole Resulting in Uterine Rupture: A Case Report.

Uterine surgery is a common predisposing factor for uterine rupture, while an invasive mole that leads to uterine rupture is a rare clinical occurrence. Here, we report a case of a 31-year-old childless woman who underwent abortion after 53 days of pregnancy. She still experienced abdominal pain and scanty vaginal bleeding after the abortion. Her levels of human chorionic gonadotropin (HCG) were high, while ultrasound and MRI results revealed an enlarged uterus and a mass in the myometrium. During preparation for treatment, the gynecologist ruptured the uterus of the patient, leaving her shocked. Eventually the patient's uterus was removed the uterus and pathologically diagnosed as result is the an invasive mole.

Neuroimaging in the Understanding of Acupuncture Analgesia: A Review of Acupuncture Neuroimaging Study Based on Experimental Pain Models.

With the development of real-time and visualized neuroimaging techniques, the studies on the central mechanism of acupuncture analgesia gain increasing attention. The experimental pain models have been widely used in acupuncture-analgesia neuroimaging studies with quantitative and controlled advantages. This review aimed to analyze the study design and main findings of acupuncture neuroimaging studies to provide reference for future study. The original studies were collected and screened in English databases (PubMed, EMBASE, and Cochrane Library) and Chinese databases (Chinese Nation Knowledge Infrastructure, Chinese Biomedical Literature Database, the Chongqing VIP Database, and Wanfang Database). As a result, a total of 27 articles were included. Heat stimulation and electroacupuncture were the mostly used pain modeling method and acupuncture modality, respectively. The neuroimaging scanning process can be divided into two models and five subtypes. The anterior cingulate cortex and insula were the most commonly reported brain regions involved in acupuncture analgesia with experimental pain models.

Alterations of White Matter Network Properties in Patients With Functional Constipation.

Background: The abnormalities in brain function and structure of patients with functional constipation (FC) have been identified using multiple neuroimaging studies and have confirmed the abnormal processing of visceral sensation at the level of the central nervous system (CNS) as an important reason for FC. As an important basis for central information transfer, the role of the white matter (WM) networks in the pathophysiology of FC has not been investigated. This study aimed to explore the topological organization of WM networks in patients with FC and its correlation with clinical variables. Methods and Analysis: In this study, 70 patients with FC and 45 age- and gender-matched healthy subjects (HS) were recruited. Diffusion tensor imaging (DTI) data and clinical variables were acquired from each participant. WM networks were constructed using the deterministic fiber tracking approach, and the global and nodal properties of the WM networks were compared using graph theory analysis between patients with FC and HS. The relationship between the representative nodal characteristics-nodal betweenness and clinical parameters was assessed using partial correlation analysis. Results: Patients with FC showed increased nodal characteristics in the left superior frontal gyrus (orbital part), right middle frontal gyrus (orbital part), and right anterior cingulate and paracingulate (P < 0.05, corrected for false discovery rate) and decreased nodal characteristics in the left caudate and left thalamus (P < 0.05, corrected for false discovery rate) compared with HS. The duration of FC was negatively correlated with the nodal betweenness of the left thalamus (r = -0.354, P = 0.04, corrected for false discovery rate). Conclusion: The results indicated the alternations in WM networks of patients with FC and suggested the abnormal visceral sensation processing in the CNS from the perspective of large-scale brain WM network.

Phenomic Analysis of Chronic Granulomatous Disease Reveals More Severe Integumentary Infections in X-Linked Compared With Autosomal Recessive Chronic Granulomatous Disease.

Background: Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI), characterised by recurrent bacterial and fungal infections. It is inherited either in an X-linked (XL) or autosomal recessive (AR) mode. Phenome refers to the entire set of phenotypes expressed, and its study allows us to generate new knowledge of the disease. The objective of the study is to reveal the phenomic differences between XL and AR-CGD by using Human Phenotype Ontology (HPO) terms. Methods: We collected data on 117 patients with genetically diagnosed CGD from Asia and Africa referred to the Asian Primary Immunodeficiency Network (APID network). Only 90 patients with sufficient clinical information were included for phenomic analysis. We used HPO terms to describe all phenotypes manifested in the patients. Results: XL-CGD patients had a lower age of onset, referral, clinical diagnosis, and genetic diagnosis compared with AR-CGD patients. The integument and central nervous system were more frequently affected in XL-CGD patients. Regarding HPO terms, perianal abscess, cutaneous abscess, and elevated hepatic transaminase were correlated with XL-CGD. A higher percentage of XL-CGD patients presented with BCGitis/BCGosis as their first manifestation. Among our CGD patients, lung was the most frequently infected organ, with gastrointestinal system and skin ranking second and third, respectively. Aspergillus species, Mycobacterium bovis, and Mycobacteirum tuberculosis were the most frequent pathogens to be found. Conclusion: Phenomic analysis confirmed that XL-CGD patients have more recurrent and aggressive infections compared with AR-CGD patients. Various phenotypic differences listed out can be used as clinical handles to distinguish XL or AR-CGD based on clinical features.

Effective treatment of advanced cholangiocarcinoma by hepatic arterial infusion chemotherapy combination with sorafenib: one case report from China.

BACKGROUND/AIMS: Cholangiocarcinoma, especially intrahepatic type, is difficult to be found early and diagnosed at early stages. Although it was reported as rare to happen, it is a well-known devastating malignancy with little treatment effects. As a result, most of the patients suffer from poor prognosis. On the other hand, the incidence of intrahepatic cholangiocarcinoma arises worldwide. Radical surgical resection was regarded as the most effective treatment, in spite of recurrence. Unfortunately, only 30 percent of patients qualify for this at the time of diagnosis. Hence, for advanced cholangiocarcinoma, chemotherapy is the only modality left to be chosen. Recently LaRocca and Kudoh reported about effective chemotherapy for cholangiocarcinoma. Even so, because of no randomized study, no standard chemotherapy for cholangiocarcinoma has been accepted, and most of the projects were based on 5-Fu. Sorafenib, a multikinase inhibitor, which can competitively inhibit RAF/MEK/ERK pathway, human vascular endothelial growth factor receptors (VEGFR2, VEGFR3) platelet-derived growth factor receptor beta (PDGFR), Flt3, and C-kit receptors, has been successfully applied for solid tumors such as renal cancer and hepatocellular carcinoma. Sorafenib used alone or in combinations, can induce growth-inhibition and apoptosis in vitro experiments. Application of sorafenib alone for cholangiocarcinoma has also been published. The role of combination with other chemotherapy drugs in advanced cholangiocarcinoma still needs to be defined. METHODOLOGY: A patient admitted for exploratory operation was demonstrated to be suffering from unresectable, biopsy-proven intrahepatic cholangiocarcinoma. A pump was placed inside hepatic artery, for the purpose of infusion chemotherapy. Program of chemotherapy was scheduled and hepatic arterial infusion of 5-Fu/LV +oxaliplatin +hydroxycamptothecine was performed. Three months later, no effect was discovered, so sorafenib was suggested to combine with infusion chemotherapy. For the first time we applied sorafenib combination to hepatic arterial infusion chemotherapy RESULT: After lower dosage of sorafenib was used as a combination with hepatic arterial infusion chemotherapy, size of hepatic lesions and level CA19-9 of peripheral blood count were decreased, without any damage to the hepatic function, except for temporary skin hyperkeratosis as well as vomit. Efficacy of treatment was demonstrated by computed tomography (CT) scan. CONCLUSION: So far as in our patient, the application of sorafenib combination with other agents through hepatic arterial infusion chemotherapy may be an effective way for cholangiocarcinoma, but the definite mechanism has to be confirmed by methods of molecular biology.

Definition of a novel vascular invasion-associated multi-gene signature for predicting survival in patients with hepatocellular carcinoma.

The aim of the present study was to identify a vascular invasion-associated gene signature for predicting prognosis in patients with hepatocellular carcinoma (HCC). Using RNA-sequencing data of 292 HCC samples from The Cancer Genome Atlas (TCGA), the present study screened differentially expressed genes (DEGs) between patients with and without vascular invasion. Feature genes were selected from the DEGs by support vector machine (SVM)-based recursive feature elimination (RFE-SVM) algorithm to build a classifier. A multi-gene signature was selected by L1 penalized (LASSO) Cox proportional hazards (PH) regression model from the feature genes selected by the RFE-SVM to develop a prognostic scoring model. TCGA set was defined as the training set and was divided by the gene signature into a high-risk group and a low-risk group. Involvement of the DEGs between the two risk groups in pathways was also investigated. The presence and absence of vascular invasion between patients of training set was 175 DEGs. A classification model of 42 genes performed well in differentiating patients with and without vascular invasion on the training set and the validation set. A 14-gene prognostic model was built that could divide the training set or the validation set into two risk groups with significantly different survival outcomes. A total of 762 DEGs in the two risk groups of the training set were revealed to be significantly associated with a number of signaling pathways. The present study provided a 42-gene classifier for predicting vascular invasion, and identified a vascular invasion-associated 14-gene signature for predicting prognosis in patients with HCC. Several genes and pathways in HCC development are characterized and may be potential therapeutic targets for this type of cancer.

Circular RNA circNRIP1 Sponges microRNA-138-5p to Maintain Hypoxia-Induced Resistance to 5-Fluorouracil Through HIF-1α-Dependent Glucose Metabolism in Gastric Carcinoma.

BACKGROUND: Hypoxia-induced chemoresistance is recognized as a major obstacle to the successful treatment of gastric cancer (GC). Circular RNAs (circRNAs) have been proposed to implicate in resistance to chemotherapeutic drugs. However, whether circNRIP1 is involved in the development of hypoxia-induced 5-fluorouracil (5-FU) resistance remains largely unknown. METHODS: Gene expression was evaluated using quantitative real-time polymerase chain reaction and Western blot. The impact of circNRIP1 on hypoxia-induced resistance to 5-FU was investigated by determining glucose consumption, lactate production and glucose-6-phosphate (G6P) levels. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolim bromide assay was performed to assess cell survival. RESULTS: circNRIP1 was upregulated in GC cells. Hypoxia induced the upregulation of circNRIP1 and reduced the sensitivity of GC cells to 5-FU, as evidenced by the increase in multidrug resistance 1 gene, P-glycoprotein, hypoxia-inducible factor-1α (HIF-1α) and G6P levels, glucose consumption, lactate production, as well as cell survival. Silencing of circNRIP1 enhanced the sensitivity of GC cells to 5-FU under a hypoxic condition. microRNA (miR)-138-5p was confirmed as a downstream target gene of circNRIP1, and upregulation of miR-138-5p could reverse the effect of circNRIP1 on hypoxia-induced 5-FU resistance. Additionally, HIF-1α was a target gene of miR-138-5p. More significantly, the effect of circNRIP1 on hypoxia-induced 5-FU resistance was markedly blocked by 2-DG treatment. CONCLUSION: circNRIP1 functioned as a miR-138-5p sponge to enhance hypoxia-induced resistance to 5-FU through modulation of HIF-1α-dependent glycolysis, which provides a novel potential approach to overcome hypoxia-induced 5-FU resistance in GC.

Bioinformatics Analysis of Key Genes and Pathways of Cervical Cancer.

BACKGROUND AND OBJECTIVE: Globally, cervical cancer (CC) is the fourth most common cancer affecting women. Although effective screening reduces its incidence, it remains one of the most serious cancers threatening the health of women. Therefore, the purpose of this study is to find new genes that can be used as potential biomarkers for the prognosis of CC. METHODS AND RESULTS: After downloading three datasets such as GSE6791, GSE63678, and GSE63514 from the Gene Expression Omnibus (GEO), we combined the expression matrixes and analyzed them to obtain the differential expressed genes (DEGs). Next, using the STRING website, we performed the protein interaction network analysis. Subsequently, hub genes were screened using the R and Cytoscape software. Then, the expression difference and survival analyses of the hub genes were confirmed using GIPIA. Here, we established that the KNTC1 gene was correlated to the overall survival prognosis of CC. Besides, the expression of the KNTC1 gene in the GSE63514 dataset was significantly different from that of the normal cervix, cervical pre-cancerous lesions, and CC. Consequently, immunohistochemistry analysis showed that the results have a definite diagnostic value. CONCLUSION: The KNTC1 gene could be linked with the pathophysiology of CC and maybe one of the early diagnostic markers for the diagnosis of cervical pre-cancerous lesions.