Clinical predictors of severe radiation pneumonitis in patients undergoing thoracic radiotherapy for lung cancer.

Background: Severe radiation pneumonitis (RP), one of adverse events in patients with lung cancer receiving thoracic radiotherapy, is more likely to lead to more mortality and poor quality of life, which could be predicted by clinical information and treatment scheme. In this study, we aimed to explore the clinical predict model for severe RP. Methods: We collected information on lung cancer patients who received radiotherapy from August 2020 to August 2022. Clinical features were obtained from 690 patients, including baseline and treatment data as well as radiation dose measurement parameters, including lung volume exceeding 5 Gy (V5), lung volume exceeding 20 Gy (V20), lung volume exceeding 30 Gy (V30), mean lung dose (MLD), etc. Among them, 621 patients were in the training cohort, and 69 patients were in the test cohort. Three models were built using different screening methods, including multivariate logistics regression (MLR), backward stepwise regression (BSR), and random forest regression (RFR), to evaluate their predictive power. Overoptimism in the training cohorts was evaluated by four validation methods, including hold-out, 10-fold, leave-one-out, and bootstrap methods, and test cohort was used to evaluate the predictive performance of the model. Model calibration, decision curve analysis (DCA), and evaluation of the nomograms for the three models were completed. Results: Severe RP was up to 9.4%. The results of multivariate analysis of logistics regression in all patients showed that patients with subclinical (untreated and asymptomatic) interstitial lung disease (ILD) could increase the risk of severe RP, and patients with a better lung diffusion function and received standardized steroids treatment could decrease the risk of severe RP. The three models built by MLR, BSR, and RFR all had good accuracy (>0.850) and moderate κ value (>0.4), and the model 2 built by BSR had the highest area under the receiver operating characteristic (ROC) curve (AUC) in three models, which was 0.958 [95% confidence interval (CI): 0.932-0.985]. The calibration curve showed good agreement between the predicted and actual values, and the DCA showed a positive net benefit for the model 2 which drew the nomogram. The model 2 included subclinical ILD, diffusing capacity of the lung for carbon monoxide (DLCO), ipsilateral lung V20, and standardized steroid treatment, which could affect the incidence of severe RP. Conclusions: Subclinical ILD, DLCO, ipsilateral lung V20, and with or not standardized steroid treatment could affect the incidence of severe RP. Strict lung dose limitation and standardized steroid treatment could contribute to a decrease in severe RP.

Accuracy of implant placement using CAD-CAM tooth-supported surgical guides for an auricular prosthesis in vitro.

PURPOSE: To evaluate the accuracy of tooth-supported surgical guides used to place implants in auricular prostheses. The accuracy (trueness and precision) of the implant positions was evaluated, and the difference between the surgical guide with and without retention of the external auditory canal (EAC) was compared. MATERIALS AND METHODS: This study simulated implant placement in vitro for the treatment of right auricle malformation. Surgical guides and other casts were fabricated using additive manufacturing technology. The casts were divided into 2 groups according to the surgical guide, with 10 bone blocks in each group (with or without the EAC plug (Guides 1 and 2)). Three implant positions (Implants 1-3) were prepared for each bone block using surgical guides. Implant positions were registered using light-body silicone impressions combined with optical surface scans to measure the coronal, apical, depth, and angular deviations. Four deviations of trueness and precision were reported as the mean ± standard deviation, which was analyzed by Student's t-test. RESULTS: Each group of 10 bone blocks with 30 implant positions was successfully prepared and digitally reproduced as implants. The accuracies of implant position with surgical guides were acceptable when compared with the preoperatively planned implant positions. Compared with the Guide 2 group, there was a significant difference in the apical, depth, and angular deviations of Guide 1 group in terms of precision (p = 0.001). There was a significant difference in the depth deviation of Implant 1 (p = 0.028) and apical deviation of Implant 2 (p < 0.001) compared two groups in terms of trueness. In terms of precision, there was a significant difference in the coronal (p = 0.002), apical (p = 0.001), and depth (p < 0.001) deviation of Implant 1; apical (p = 0.036) and angular (p < 0.001) deviation of Implant 2 also existed significant difference; the coronal deviation of Implant 3 (p = 0.018) also existed significant difference. Moreover, the group with the EAC plug showed lower deviation in precision and a smaller volume in the 95% confidence ellipsoid. CONCLUSION: Both types of tooth-supported surgical guides can provide acceptable accuracy. A surgical guide with an EAC plug was considered to be more precise.

Correlation between intraosseous thermal change and drilling impulse data during osteotomy within autonomous dental implant robotic system: An in vitro study.

OBJECTIVES: This study aims at examining the correlation of intraosseous temperature change with drilling impulse data during osteotomy and establishing real-time temperature prediction models. MATERIALS AND METHODS: A combination of in vitro bovine rib model and Autonomous Dental Implant Robotic System (ADIR) was set up, in which intraosseous temperature and drilling impulse data were measured using an infrared camera and a six-axis force/torque sensor respectively. A total of 800 drills with different parameters (e.g., drill diameter, drill wear, drilling speed, and thickness of cortical bone) were experimented, along with an independent test set of 200 drills. Pearson correlation analysis was done for linear relationship. Four machining learning (ML) algorithms (e.g., support vector regression [SVR], ridge regression [RR], extreme gradient boosting [XGboost], and artificial neural network [ANN]) were run for building prediction models. RESULTS: By incorporating different parameters, it was found that lower drilling speed, smaller drill diameter, more severe wear, and thicker cortical bone were associated with higher intraosseous temperature changes and longer time exposure and were accompanied with alterations in drilling impulse data. Pearson correlation analysis further identified highly linear correlation between drilling impulse data and thermal changes. Finally, four ML prediction models were established, among which XGboost model showed the best performance with the minimum error measurements in test set. CONCLUSION: The proof-of-concept study highlighted close correlation of drilling impulse data with intraosseous temperature change during osteotomy. The ML prediction models may inspire future improvement on prevention of thermal bone injury and intelligent design of robot-assisted implant surgery.

Accuracy and Feasibility of Synthetic CT for Lung Adaptive Radiotherapy: A Phantom Study.

OBJECTIVES: The respiratory variations will lead to inconsistency between the actual delivery dose and the planning dose. How the minor interfractional amplitude changes affect the geometry and dose delivery accuracy remains to be investigated in the context of lung adaptive radiotherapy. METHODS: Planning 4-dimensional-computed tomography and kV-cone beam computed tomography were scanned based on the Computerized Imaging Reference Systems phantom, which was employed to simulate the minor interfractional amplitude variations. The corresponding synthetic computed tomography for a particular motion pattern can be generated from Velocity program. Then a clinically meaningful synthetic computed tomography was analyzed through the geometrical and dosimetric assessment. RESULTS: The image quality of synthetic computed tomography was improved obviously compared with cone beam computed tomography. Mean absolute error was minimized when no significant interfractional motion occurs and Velocity can be qualified for dealing with the regular breathing motion patterns. The mean percent hounsfield unit difference of the synthetic hounsfield unit values per organ relative to the planning 4-dimensional-computed tomography image was 22.3%. Under the same conditions, the mean percent hounsfield unit difference of the cone beam computed tomography hounsfield unit values per organ, relative to the planning 4-dimensional-computed tomography image was 83.9%. Overall, the accuracy of hounsfield unit in synthetic computed tomography was improved obviously and the variability of the synthetic image correlates with the planning 4-dimensional-computed tomography image variability. Meanwhile, the dose-volume histograms between planning 4-dimensional-computed tomography and synthetic computed tomography almost coincided each other, which indicates that Velocity program can qualify lung adaptive radiotherapy well when there were no interfractional respiratory variations. However, for cases with obvious interfractional amplitude change, the volume covered at least by 100% of the prescription dose was only 59.6% for that synthetic image. CONCLUSION: The synthetic computed tomography images generated from Velocity were close to the real images in anatomy and dosimetry, which can make clinical lung adaptive radiotherapy possible based on the actual patient anatomy during treatment.

MicroRNA miR-34a-5p inhibition restrains oxidative stress injury of macrophages by targeting MDM4.

OBJECTIVE: Atherosclerosis is a chronic cardiovascular disease associated with oxidative stress damage, which is caused by excessive oxidation of low-density lipoprotein (ox-LDL). The role of microRNA miR-34a-5p on oxidative stress in ox-LDL-treated macrophages was investigated in this study. METHODS: Flow cytometry was prepared for assessing THP1-derived macrophage apoptosis. The protein and expression levels of miR-34a-5p and MDM4 were examined by Western blot and RT-qPCR, respectively. We also measured the levels of total cholesterol (TC) and triglyceride to determine the lipid accumulation. Subsequently, the activities of superoxide dismutase, malondialdehyde, and reactive oxygen species revealed the level of oxidative stress injury after miR-34a-5p and MDM4 knockdown. RESULTS: After ox-LDL treatment, cell apoptosis of macrophages increased in a dose-dependent and time-dependent manner. With the increase of ox-LDL treatment and the prolongation of treatment time, the expression level of miR-34a-5p was upregulated. Next, interfering with miR-34a-5p inhibited lipid accumulation and oxidative stress injury in ox-LDL-stimulated macrophages. MDM4 was a target gene of miR-34a-5p and was upregulated in ox-LDL-stimulated macrophages. With the increase of ox-LDL treatment and the prolongation of treatment time, the expression level of MDM4 was downregulated. Importantly, MDM4 knockdown partially counteracted the inhibitory effect of miR-34a-5p on oxidative stress injury. CONCLUSION: MicroRNA miR-34a-5p knockdown suppressed oxidative stress injury via MDM4 in ox-LDL-treated macrophages.

Effects of sponge iron dosage on nitrogen removal performance and microbial community structure in sequencing batch reactors.

The application of sponge iron (SI) carriers can improve the biochemical treatment performance of sequencing batch reactors (SBR) during wastewater treatment. This study used SBR reactors to explore the effects of SI dosage on the nitrogen removal performance and reactor stability and microbial community structure under low temperature and ultra-low load. In contrast to conventional SBR, the average removal rate of total nitrogen (TN) in the biological sponge iron system (BSIS) was increased by 5.38 % for 45 g/L, 18.93 % for 90 g/L, and 13.52 % for 135 g/L, respectively. The nitrogen removal performance and reactor stability showed the best performance under the SI dosage of 90 g/L. The addition of SI formed the anaerobic-anoxic-aerobic microenvironments, which facilitate the propagation of denitrifying bacteria (Saccharimonadales, Hydrogenophaga) and iron bacteria (Rhodoferax and Acinetobacter) in the BSIS. This study provides a new insight on the application of SI in the wastewater treatment.

A digital workflow for fabricating an interim obturator after partial maxillary resection.

This article describes a digital workflow for fabricating an interim obturator after partial maxillectomy which utilizes the radiopacity of iodoform gauze, a common surgical packing material, to simulate postoperative oronasal defect cavities through a computer-aided design and computer-aided manufacturing (CAD-CAM) workflow and to generate the interim obturator by 3-dimensional printing. This technique may serve as a promising alternative technique for the fabrication of an interim obturator and, in particular, benefit patients who have not seen a prosthetic specialist before surgery and present without a surgical obturator.

The association between disruption of the circadian rhythm and aggravation of colitis in mice.

Delayed recovery from ulcerative colitis is mainly due to impaired healing of the intestinal epithelium after inflammation. The circadian rhythm controls cell proliferation and energy metabolism. However, the role of circadian genes in inflammatory bowel disease is largely unknown. The purpose of this study was to investigate whether disrupting the circadian rhythm in mice can worsen colitis by altering mitochondrial energy metabolism. Mice in the experimental groups were under physiologic stress with an 8-h light shift jet-lag schedule every 3 days, whereas those in the control group were not. Subsequently, half of the mice in the control and jet-lagged groups were given dextran sodium sulfate (DSS) to induce colitis. Mice in each group were euthanized at zeitgeber time (ZT)0, ZT4, ZT8, ZT12, ZT16, and ZT20. To investigate the effects of jet lag on the mice, colon specimens were subjected to hematoxylin and eosin staining to analyse mRNA and protein expression of core circadian clock genes (Bmal1, Clock, Per1, Per2, Cry1, Cry2, and Nr1d1). We analysed the mitochondrial morphology, adenosine triphosphate (ATP) levels, and the expression of dynamin-related protein 1 (Drp1) and ser637-phosphorylated (p)-Drp1, which are closely related to ATP production. We further investigated the effect of PER2 knock-down in the colon epithelial cells (CCD 841 CoN) by measuring ATP and cell proliferation levels. Disrupting the circadian rhythm changed the oscillation of clock genes in the colon of mice, altered the mitochondrial morphology of the colon specimens, decreased the expression of p-Drp1, reduced ATP production, and exacerbated inflammatory responses in mice with DSS-induced colitis. Additionally, silencing of PER2 in the colon epithelial cells reduced ATP production and cell proliferation. Disrupting the circadian rhythm in mice decreases mitochondrial energy metabolism in the colon and exacerbates symptoms of colitis.

Low-activity 125I implantation into VX2 tumor rabbits and quantitative evaluation of the precise therapeutic effect.

There is still controversy about quantitatively evaluating the therapeutic effect of radioactive low-activity iodine-125 seeds (125I seeds). In the present study, a paired VX2 tumor model in a rabbit hind leg muscle was established, which is virus-induced anaplastic squamous cell carcinoma characterized by hypervascularity, rapid growth and easy propagation in the skeletal muscle. 125I seeds with 0.4 and 0.7 mCi activity were implanted into the left and right legs, respectively, using a radiation treatment planning system under positron emission tomography (PET)/computed tomography (CT) guidance. PET/CT scans and hematoxylin and eosin staining were observed at 72 h and 2 and 4 weeks after implantation to assess the therapeutic effect. The results showed that the average tumor length and standard uptake value (SUV) decreased over time, and both 125I seed groups achieved therapeutic effects at 4 weeks post-implantation. Quantitative evaluation of tumor inhibition rate, SUV variation and tumor marker ratio (Bcl-2/Bax) suggested that 0.7 mCi 125I seeds were more suitable than 0.4 mCi seeds in a clinical setting.

Production of viable chicken by allogeneic transplantation of primordial germ cells induced from somatic cells.

The allogeneic transplantation of primordial germ cells (PGCs) derived from somatic cells overcomes the limitation of avian cloning. Here, we transdifferentiate chicken embryo fibroblasts (CEFs) from black feathered Langshan chickens to PGCs and transplant them into White Plymouth Rock chicken embryos to produce viable offspring with characteristics inherited from the donor. We express Oct4/Sox2/Nanog/Lin28A (OSNL) to reprogram CEFs to induced pluripotent stem cells (iPSCs), which are further induced to differentiate into PGCs by BMP4/BMP8b/EGF. DNA demethylation, histone acetylation and glycolytic activation elevate the iPSC induction efficiency, while histone acetylation and glycolytic inhibition facilitate PGCs formation. The induced PGCs (iPGCs) are transplanted into the recipients, which are self-crossed to produce 189/509 somatic cells derived chicken with the donor's characteristics. Microsatellite analysis and genome sequencing confirm the inheritance of genetic information from the donor. Thus, we demonstrate the feasibility of avian cloning from somatic cells.

Naringenin promotes cell autophagy to improve high-fat-diet-induced atherosclerosis in ApoE-/- mice.

Naringenin (NAR) is a major flavanone in citrus fruits that has multiple pharmacological attributes such as anticancer and antiatherogenic. This study aims to investigate the mechanism of NAR in high-fat-diet (HFD)-induced atherosclerosis (AS) in apolipoprotein E-knockout (ApoE-/-) mice. A HFD-induced AS ApoE-/- mouse model was established. The mice were treated with HFD, different doses of NAR and simvastatin (Simv). After drug treatment, the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD), and alanine aminotransferase (ALT) were determined. The expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected using qRT-PCR and enzyme-linked immunosorbent assay. The plaque area of the aorta of AS mice was determined using oil red O staining. Western blot analysis was applied to measure the levels of autophagy-related proteins [protein 1 light chain 3B (LC3B), beclin 1, and p62]. The TC, TG, LDL-C, TNF-α, ALT, and MDA levels were significantly increased while the HDL-C, SOD, and GSH-Px levels were decreased in the HFD-induced AS ApoE-/- mice. NAR treatment reversed the expression of the above indicators in mice. After they were treated with different doses of NAR, the LC3B and beclin 1 levels were improved while the p62 protein level was decreased. This study suggested that NAR could promote cell autophagy to improve HFD-induced AS in ApoE-/- mice.

Naringenin promotes cell autophagy to improve high-fat-diet-induced atherosclerosis in ApoE-/- mice

Naringenin (NAR) is a major flavanone in citrus fruits that has multiple pharmacological attributes such as anticancer and antiatherogenic. This study aims to investigate the mechanism of NAR in high-fat-diet (HFD)-induced atherosclerosis (AS) in apolipoprotein E-knockout (ApoE-/-) mice. A HFD-induced AS ApoE-/- mouse model was established. The mice were treated with HFD, different doses of NAR and simvastatin (Simv). After drug treatment, the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD), and alanine aminotransferase (ALT) were determined. The expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected using qRT-PCR and enzyme-linked immunosorbent assay. The plaque area of the aorta of AS mice was determined using oil red O staining. Western blot analysis was applied to measure the levels of autophagy-related proteins [protein 1 light chain 3B (LC3B), beclin 1, and p62]. The TC, TG, LDL-C, TNF-α, ALT, and MDA levels were significantly increased while the HDL-C, SOD, and GSH-Px levels were decreased in the HFD-induced AS ApoE-/- mice. NAR treatment reversed the expression of the above indicators in mice. After they were treated with different doses of NAR, the LC3B and beclin 1 levels were improved while the p62 protein level was decreased. This study suggested that NAR could promote cell autophagy to improve HFD-induced AS in ApoE-/- mice.

Comparison between curcumin and all-trans retinoic acid in the osteogenic differentiation of mouse bone marrow mesenchymal stem cells.

The use of bone marrow mesenchymal stem cells (BMSCs) has great potential in cell therapy, particularly in the orthopedic field. BMSCs represent a valuable renewable cell source that have been successfully utilized to treat damaged skeletal tissue and bone defects. BMSCs can be induced to differentiate into osteogenic lineages via the addition of inducers to the growth medium. The present study examined the effects of all-trans retinoic acid (ATRA) and curcumin on the osteogenic differentiation of mouse BMSCs. Morphological changes, the expression levels of the bone-associated gene markers bone morphogenetic protein 2, runt-related transcription factor and osterix during differentiation, an in vitro mineralization assay, and changes in osteocalcin expression revealed that curcumin supplementation promoted the osteogenic differentiation of BMSCs. By contrast, the application of ATRA increased osteogenic differentiation during the early stages, but during the later stages, it decreased the mineralization of differentiated cells. In addition, to the best of our knowledge, the present study is the first to examine the effect of curcumin on the osteogenic potency of mouse embryonic fibroblasts (MEFs) after reprogramming with human lim mineralization protein (hLMP-3), which is a positive osteogenic regulator. The results revealed that curcumin-supplemented culture medium increased hLMP-3 osteogenic potency compared with that of MEFs cultured in the non-supplemented medium. The present results demonstrate that enrichment of the osteogenic culture medium with curcumin, a natural osteogenic inducer, increased the osteogenic differentiation capacity of BMSCs as well as that of MEFs reprogrammed with hLMP-3.

Direct conversion of mouse embryonic fibroblast to osteoblast cells using hLMP-3 with Yamanaka factors.

Large bone defects and bone loss after fractures remain significant challenges for orthopedic surgeons. Our study aims to find an available, applicable and biological treatment for bone regeneration overcoming the limitations in ESC/iPSC technology. We directly reprogrammed the mouse embryonic fibroblast (MEF) into osteoblast cells using different combinations of Yamanaka factors with human lim mineralization protein-3 (hLMP-3). LMP is an intracellular LIM-domain protein acting as an effective positive regulator of the osteoblast differentiation. After transduction, cells were cultured in osteogenic medium, and then examined for osteoblast formation. The expression of osteogenic markers (BMP2, Runx2 and Osterix) during reprogramming and in vitro mineralization assay revealed that the best reprogramming cocktail was (c-Myc - Oct4) with hLMP-3. In addition, both immunofluorescent staining and western blot analysis confirmed that osteocalcin (OCN) expression increased in the cells treated with the c-Myc/Oct4/hLMP3 cocktail than using hLMP-3 alone. Furthermore, this reprogramming cocktail showed efficient healing in an induced femoral bone defect in rat animal model one month after transplantation. In the present study, we reported for the first time the effect of combining Yamanaka factors with hLMP-3 to induce osteoblast cells from MEF both in vitro and in vivo.

The establishment of clonally derived chicken embryonic fibroblast cell line (CSC) with high transfection efficiency and ability as a feeder cell.

This study established a single cloned chicken embryonic fibroblast (CEF) cell line. It solves the main problem of the instability of a cultured primary cell and its impact on the experiment. In this study, CEF pass through this crisis and formed a continuous cell line after subculture. We isolated single postcrisis CEF by a mouth pipette under a convert microscope then established a single cloned cell line named CSC-1-5 which passaged continuously from 96-well plates to 60 mm culture plates. CSC has a normal chicken diploid karyotype, no tumorigenicity, and a high G2/M phase cell ratio. We found that Fugene could mediate the transfection of CSCs efficiently; it was significantly improved compared with the primary cells. It could also promote the proliferation of chicken embryonic stem cell as a feeder layer.

CREPT and p15RS regulate cell proliferation and cycling in chicken DF-1 cells through the Wnt/ß-catenin pathway.

The CREPT (cell cycle-related and expression elevated protein in tumor, also known as RPRD1B) and p15RS (p15INK4b -related sequence, also known as RPRD1A) have been shown to regulate cell proliferation and alter the cell cycle through Wnt/ß-catenin pathway downstream genes in human. Although several studies have revealed the mechanism by which CREPT and p15RS regulate cell proliferation in human and mammals, it is still unclear how these genes function in poultry. In order to determine the function of CREPT and p15RS in chicken, we examined the expression of CREPT and p15RS in a variety of chicken tissues and DF-1 cells. Then, we determined the effect of overexpression or depletion of CREPT or p15RS, by transiently transfecting chicken DF-1 cells with overexpression and short hairpin RNA (shRNA) vectors respectively, on the regulation of cell proliferation. The results showed that CREPT and p15RS had different expression patterns and opposite effects on the cell cycling and proliferation. Knockdown of p15RS expression or overexpression of CREPT facilitated cell proliferation by promoting the cell-cycle transition from G0/G1 to S-phase and G2/M, whereas knockdown of CREPT or overexpression of p15RS inhibited cell proliferation. Mechanistically, CREPT and p15RS control DF-1 cell proliferation by regulating the expression of Wnt/ß-catenin pathway downstream regulatory genes, including ß-catenin, TCF4, and Cyclin D1. In conclusion, CREPT and p15RS regulate cell proliferation and the cell-cycle transition in chicken DF-1 cells by regulating the transcription of Wnt/ß-catenin pathway downstream regulatory genes.

CYP1A1 based on metabolism of xenobiotics by cytochrome P450 regulates chicken male germ cell differentiation.

This study aimed to explore the regulatory mechanism of metabolism of xenobiotics by cytochrome P450 during the differentiation process of chicken embryonic stem cells (ESCs) into spermatogonial stem cells (SSCs) and consummate the induction differentiation system of chicken embryonic stem cells (cESCs) into SSCs in vitro. We performed RNA-Seq in highly purified male ESCs, male primordial germ cells (PGCs), and SSCs that are associated with the male germ cell differentiation. Thereinto, the metabolism of xenobiotics by cytochrome P450 was selected and analyzed with Venny among male ESC vs male PGC, male PGC vs SSC, and male ESC vs SSC groups and several candidates differentially expressed genes (DEGs) were excavated. Finally, quantitative real-time PCR (qRT-PCR) detected related DEGs under the condition of retinoic acid (RA) induction in vitro, and the expressions were compared with RNA-Seq. By knocking down CYP1A1, we detected the effect of CYP1A1-mediated metabolism of xenobiotics by cytochrome P450 on male germ cell differentiation by qRT-PCR and immunocytochemistry. Results showed that 17,742 DEGs were found during differentiation of ESCs into SSCs and enriched in 72 differently significant pathways. Thereinto, the metabolism of xenobiotics by cytochrome P450 was involved in the whole differentiation process of ESCs into SSCs and several candidate DEGs: CYP1A1, CYP3A4, CYP2D6, ALDH3B1, and ALDH1A3 were expressed with the same trend with RNA-Seq. Knockdown of CYP1A1 caused male germ cell differentiation under restrictions. Our findings showed that the metabolism of xenobiotics by cytochrome P450 was significantly different during the process of male germ cell differentiation and was persistently activated when we induced cESCs to differentiate into SSCs with RA in vitro, which illustrated that the metabolism of xenobiotics by cytochrome P450 played a crucial role in the differentiation process of ESCs into SSCs.

Inferior mesenteric arteriovenous fistula with nonpulsatile abdominal mass: A case report and a mini-review.

RATIONALE: Inferior mesenteric arteriovenous fistula (IMAVF) is a rare condition principally characterized by portal hypertension and ischemic bowel disease. Up to now, only 30 cases have been reported. Presented here is an IMAVF patient with nonpulsatile abdominal mass as the main manifestation. PATIENT CONCERNS: A 62-year-old Chinese male who complained of abdominal discomfort for a month was admitted to our hospital. Physical examination revealed a hard and hardly mobile mass. DIAGNOSES: Space-occupying lesions were first suspected but endoscopy did not reveal any masses. The computed tomography angiography exhibited no definite boundary between the inferior mesenteric artery and vein. The patient was diagnosed with IMAVF. INTERVENTIONS: The treatment of IMAVF mainly includes intra-arterial embolization and surgery. In our case, fistulas were complex and the patient had symptoms of colon ischemia, so we suggested a surgical resection instead of embolization. And the postoperative biopsy also confirmed the diagnosis. OUTCOMES: After surgery, gastrointestinal symptoms disappeared and the patient began to gain weight gradually. During the follow-up, colonoscopy showed that the anastomotic astium and colonic mucosa were normal. LESSONS: Analysis of the case showed that computed tomography angiography is an important auxiliary examination for establishing the diagnosis of IMAVF and surgery is an effective treatment.

Endoscopic ultrasonography with fine-needle aspiration for histological diagnosis of solid pancreatic masses: a meta-analysis of diagnostic accuracy studies.

BACKGROUND: Previous studies have demonstrated that endoscopic ultrasound-fine needle aspiration (EUS-FNA) is a reliable tool for diagnosing pancreatic lesions; however, the reported sensitivity and specificity vary greatly across studies. The aim of this study was to pool the existing literature and assess the overall performance of EUS-FNA in the diagnosis of solid pancreatic lesions. METHODS: A systematic search of MEDLINE, Cochrane Database for Systematic Reviews, and EMBASE was performed to identify original and review articles published between January 1995 and January 2014 that reported the accuracy of EUS-FNA in the diagnosis of pancreatic masses. Quality of the included studies was assessed using the quality assessment of diagnosis accuracy studies score tool. Meta-DiSc software was used to calculate the pooled sensitivity and specificity, positive and negative likelihood ratios, and to construct the summary receiver operating characteristics curve. RESULTS: Twenty studies involving a total of 2,761 patients were included in the study. The pooled sensitivity and specificity of EUS-FNA in the diagnosis of solid pancreatic lesions were 90.8 % [95 % confidence interval (CI), 89.4-92 %] and 96.5 % (95 % CI, 94.8-97.7 %), respectively. The positive and negative likelihood ratios were 14.8 (95 % CI, 8.0-27.3) and 0.12 (95 % CI, 0.09-0.16), respectively. The overall diagnostic accuracy was 91.0 %. CONCLUSIONS: Our findings suggest that EUS-FNA has high sensitivity and specificity in the diagnosis of solid pancreatic lesions.

Comparison of the values of MRI diffusion kurtosis imaging and diffusion tensor imaging in cerebral astrocytoma grading and their association with aquaporin-4.

OBJECTIVE: To compare the value of MRI diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in grading cerebral astrocytomas and to analyze the correlation of respective parameters with aquaporin-4 (AQP4) expression. METHODS: Sixty patients with cerebral astrocytoma, including low-grade astrocytomas (LGA, n = 25) and high-grade astrocytomas (HGA, n = 35), were studied. The values of DKI parameters (mean kurtosis [MK], radial kurtosis [Kr], and axial kurtosis [Ka]) and DTI parameters (fractional anisotropy, mean diffusivity [MD]) corrected by contralateral normal-appearing white matter in the solid parts of the tumors and peritumoral edema were compared. Receiver operating characteristic curves were used to identify the best parameters. Spearman correlation analysis was conducted to assess the correlation of AQP4 expression with each parameter value. RESULTS: MK, Ka, and Krvalues were significantly higher whereas MD values were significantly lower in the solid parts of HGA, as compared to those of LGA. MK value in peritumoral edematous tissue was significantly higher in HGA as compared to that in LGA. Ka (0.889) had the largest area under the curve (AUC), followed by MK (0.840), Kr (0.750), and MD (0.764). The AUC of Kaand MK was significantly higher than that of MD. Optimal thresholds for MK, Ka, Kr, and MD for differentiating the two groups were 0.490, 0.525, 0.432, and 1.493, respectively. The AQP4 expression in the solid parts of the tumors was significantly higher in HGAs. MK, Kr, Kavalues positively correlated with the AQP4 expression, whereas MD showed a slight negative correlation with AQP4. CONCLUSION: Use of DKI improved grading of cerebral astrocytomas when compared with DTI. DKI parameters appeared to reflect the level of AQP4 expression in astrocytomas.