Comparison of Lower and Upper Extremity Arteriovenous Graft: A Retrospective Clinical Analysis with 5-Year Follow-Up.

BACKGROUND: For patients in whom an upper extremity (UE) vascular access cannot be established, the lower extremity (LE) arteriovenous graft (AVG) could be selected. However, the application of LE AVG is limited owing to its high infection rate, uncertain patency time, and technical difficulties. This study aimed to compare the long-term patency rates and the incidence of vascular access complications of AVG in the LE and UE to provide a reference for the applications of AVG, especially in the LEs. METHODS: This was a retrospective analysis of patients who successfully underwent LE or UE AVG placement from March 2016 to October 2021. Patient characteristics were collected and compared using parameter or nonparameter tests according to data type. Postoperative patency was evaluated using Kaplan-Meier test. Postoperative complication incidence density and intergroup comparison were estimated using the Poisson distribution. RESULTS: Twenty-two patients with LE AVG and 120 patients with UE AVG were included. The 1-year primary patency rate was 67.4% (±11.0% standard error [SE]) in the LE group and 30.1% (±4.5% SE) in the UE group (P = 0.031). The assisted primary patency rate at postoperative months 12, 24, and 36 was respectively 78.6% (±9.6% SE), 65.5% (±14.4% SE), and 49.1% (±17.8% SE) in the LE group and 63.3% (±4.6% SE), 47.5% (±5.4% SE), and 30.4% (±6.1% SE) in the UE group (P = 0.137). The secondary patency rate at postoperative months 12, 24, and 36 remains 95.5% (±4.4% SE) in the LE group and 89.3% (±2.9% SE), 83.7% (±3.9% SE), and 73.0% (±6.2% SE), respectively, in the UE group (P = 0.200). Postoperative complications included stenosis, occlusion/thrombosis, infection, steal syndrome, pseudoaneurysm, severe postoperative serum swelling, and AVG exposure. The total incidence rates of postoperative complications were 0.87 (95% confidence interval [CI] 0.59-1.23) versus 1.61 (95% CI 1.45-1.79) (P = 0.001) cases/person-year, the incidence rates of stenosis were 0.45 (95% CI 0.26-0.73) versus 0.92 (95% CI 0.80-1.06) (P = 0.005) cases/person-year and the incidence rates of occlusion/thrombosis were 0.34 (95% CI 0.17-0.59) versus 0.62 (95% CI 0.52-0.74) cases/person-year in the LE group compared to those in the UE group (P = 0.041). CONCLUSIONS: LE AVG had higher primary patency rate and lower postoperative complication incidence than UE AVG. With the development of interventional technology, both LE AVG and UE AVG exhibited high secondary patency rates. LE AVG can be a reliable and long-term alternative for appropriately selected patients with unusable UE vessels.

The function of Foxo1 in spermatogonia development is independent of PI3K/PTEN signaling.

Spermatogenesis is a highly coordinated process that initiates shortly after birth and continues throughout the lifespan of male animals. Foxo1 is a transcription factor and is involved in many biological processes. It has been reported that the inactivation of Foxo1 in gonocytes during the embryonic stage causes the defects of spermatogenesis. In the present study, we found that the inactivation of Foxo1 in spermatogonia after birth also caused germ cell loss and male infertility. We found that the initiation of meiosis was not affected; however, the germ cell development was arrested after meiosis and lack of mature spermatozoa in the cauda epididymis. We also found that the proliferation of Foxo1-deficient spermatogonia stem cells was significantly reduced under in vitro conditions. Further study revealed that inactivation of Pten in postnatal spermatogonia using Stra8-Cre did not affect germ cell development and the subcellular location of FOXO1 in Pten-deficient spermatogonia. This study demonstrated that Foxo1 was involved in the development of spermatogonia after birth and the function of Foxo1 was probably not regulated by PI3K/PTEN signaling.

Fancb deficiency causes premature ovarian insufficiency in mice†.

Fanconi anemia complementation group B (FANCB) protein is a major component of the Fanconi anemia (FA) core complex and plays an important role in hematopoiesis and germ cell development. Deletion of Fancb gene causes the defect of primordial germ cell (PGC) development and infertility in male mice. However, it remains unknown whether Fancb is required for female germ cell development. In this study, we found that the fertility of Fancb knockout male mice in C57/ICR mixed backgrounds was not affected. Female Fancb-/- mice were obtained by crossing Fancb+/- females with Fancb-/Y males. The number of PGCs was dramatically decreased in Fancb-/- females. Very few oocytes were observed after birth and the primordial follicle pool was completely depleted at 6 weeks of age in Fancb-/- females. However, the remained oocytes from Fancb-/- mice were normal in fertilization and embryonic development from 2-cell to the blastocyst stage. We also found that Fancb and Fancl double-knockout males were also fertile and the number of sperm in epididymis was not reduced as compared to that of Fancb-/- and Fancl-/- single-knockout mice. Taken together, these results showed that Fancb is also essential for female germ cell development. Inactivation of Fancb causes massive germ cell loss and infertility in adult females. We also found that Fancb and Fancl do not act synergistically in regulating germ cell development.

Automated quality assessment of chest radiographs based on deep learning and linear regression cascade algorithms.

OBJECTIVES: Develop and evaluate the performance of deep learning and linear regression cascade algorithms for automated assessment of the image layout and position of chest radiographs. METHODS: This retrospective study used 10 quantitative indices to capture subjective perceptions of radiologists regarding image layout and position of chest radiographs, including the chest edges, field of view (FOV), clavicles, rotation, scapulae, and symmetry. An automated assessment system was developed using a training dataset consisting of 1025 adult posterior-anterior chest radiographs. The evaluation steps included: (i) use of a CNN framework based on ResNet - 34 to obtain measurement parameters for quantitative indices and (ii) analysis of quantitative indices using a multiple linear regression model to obtain predicted scores for the layout and position of chest radiograph. In the testing dataset (n = 100), the performance of the automated system was evaluated using the intraclass correlation coefficient (ICC), Pearson correlation coefficient (r), mean absolute difference (MAD), and mean absolute percentage error (MAPE). RESULTS: The stepwise regression showed a statistically significant relationship between the 10 quantitative indices and subjective scores (p < 0.05). The deep learning model showed high accuracy in predicting the quantitative indices (ICC = 0.82 to 0.99, r = 0.69 to 0.99, MAD = 0.01 to 2.75). The automatic system provided assessments similar to the mean opinion scores of radiologists regarding image layout (MAPE = 3.05%) and position (MAPE = 5.72%). CONCLUSIONS: Ten quantitative indices correlated well with the subjective perceptions of radiologists regarding the image layout and position of chest radiographs. The automated system provided high performance in measuring quantitative indices and assessing image quality. KEY POINTS: • Objective and reliable assessment for image quality of chest radiographs is important for improving image quality and diagnostic accuracy. • Deep learning can be used for automated measurements of quantitative indices from chest radiographs. • Linear regression can be used for interpretation-based quality assessment of chest radiographs.

PRMT7 is involved in regulation of germ cell proliferation during embryonic stage.

Arginine methylation is one of the most important post-translational modifications which is catalyzed by protein arginine methyltransferases (PRMTs). Previous studies have demonstrated that Prmt5 plays important role in germ cell development. Prmt7 is the only family member responsible for mono-methylation of arginine residue. However, whether Prmt7 is also involved in germ cell development remains unclear. In this study, we find that PRMT7 is abundantly expressed in the male germ cells during embryonic stage (from E10.5). Depletion of Prmt7 results in the defect of germ cell proliferation during embryonic stage and the number of primordial germ cells is significantly reduced in Prmt7-/- mice at E11.5. We also find that the size of testes is reduced in Prmt7-/- mice at P5 with reduced germ cell number and the diameter of seminiferous tubules. Further study reveals that the expression of BMPs and TGF-ß singling pathway is significantly changed in germ cells of Prmt7-/- mice at E12.5. However, no defect of testes development is observed in adult Prmt7-/flox; Mvh-Cre mice. Collectively, this study demonstrates that Prmt7 plays roles in male germ cell proliferation during embryonic stages and it is not required for germ cell development postnatally.

Treatment of anastomotic stricture after rectal cancer operation by magnetic compression technique: A case report.

BACKGROUND: The treatment of postoperative anastomotic stenosis (AS) after resection of colorectal cancer is challenging. Endoscopic balloon dilation is used to treat stenosis in such cases, but some patients do not show improvement even after multiple balloon dilations. Magnetic compression technique (MCT) has been used for gastrointestinal anastomosis, but its use for the treatment of postoperative AS after colorectal cancer surgery has rarely been reported. CASE SUMMARY: We report a 72-year-old man who underwent radical resection of colorectal cancer and ileostomy one year ago. An ileostomy closure was prepared six months ago, but colonoscopy revealed a narrowing of the rectal anastomosis. Endoscopic balloon dilation was performed three times, but colonoscopy showed no significant improvement in stenosis. The AS was successfully treated using MCT. CONCLUSION: MCT is a minimally invasive method that can be used for the treatment of postoperative AS after colorectal cancer surgery.

Magnetic compression anastomosis to restore biliary tract continuity after obstruction following major abdominal trauma: A case report.

BACKGROUND: The combination of magnetic compression anastomosis (MCA) and endoscopy has been used to treat biliary stricture after liver transplantation. However, its use for the treatment of complex biliary obstruction after major abdominal trauma has not been reported. This case report describes the successful use of MCA for the treatment of biliary obstruction resulting from major abdominal trauma. CASE SUMMARY: A 23-year-old man underwent major abdominal surgery (repair of liver rupture, right half colon resection, and ileostomy) following a car accident one year ago. The abdominal drainage tube, positioned at the Winslow foramen, was draining approximately 600-800 mL of bile per day. During the two endoscopic retrograde cholangiopancreatography procedures, the guide wire was unable to enter the common bile duct, which prevented placement of a biliary stent. MCA combined with endoscopy was used to successfully achieve magnetic anastomosis of the peritoneal sinus tract and duodenum, and then a choledochoduodenal stent was placed. Finally, the external biliary drainage tube was removed. The patient achieved internal biliary drainage leading to the removal of the external biliary drainage tube, which improved the quality of life. CONCLUSION: Magnetic compression technique can be used for the treatment of complex biliary obstruction with minimal operative trauma.

Novel magnetic compression technique for the treatment of postoperative anastomotic stenosis in rectal cancer: A case report.

BACKGROUND: The treatment of postoperative anastomotic stenosis after excision of rectal cancer is challenging. Endoscopic balloon dilation and radial incision are not effective in all patients. We present a new endoscopy-assisted magnetic compression technique (MCT) for the treatment of rectal anastomotic stenosis. We successfully applied this MCT to a patient who developed an anastomotic stricture after radical resection of rectal cancer. CASE SUMMARY: A 50-year-old man had undergone laparoscopic radical rectal cancer surgery at a local hospital 5 months ago. A colonoscopy performed 2 months ago indicated that the rectal anastomosis was narrow due to which ileostomy closure could not be performed. The patient came to the Magnetic Surgery Clinic of the First Affiliated Hospital of Xi'an Jiaotong University after learning that we had successfully treated patients with colorectal stenosis using MCT. We performed endoscopy-assisted magnetic compression surgery for rectal stenosis. The magnets were removed 16 d later. A follow-up colonoscopy performed after 4 months showed good anastomotic patency, following which, ileostomy closure surgery was performed. CONCLUSION: MCT is a simple, non-invasive technique for the treatment of anastomotic stricture after radical resection of rectal cancer. The technique can be widely used in clinical settings.

Magnetic compression anastomosis for sigmoid stenosis treatment: A case report.

BACKGROUND: Endoscopic balloon dilation is a minimally invasive treatment for colorectal stenosis. Magnetic compression anastomosis can be applied against gastrointestinal anastomosis. When combined with endoscopy, it offers a unique approach to the recanalization of colorectal stenosis. CASE SUMMARY: We have reported here the case of a 53-year-old female patient who underwent a descending colostomy due to sigmoid obstruction. Postoperative fistula restoration was not possible in her due to sigmoid stenosis. Accordingly, endoscopic-assisted magnetic compression anastomosis for sigmoid stenosis was performed, and the sigmoid stenosis was recanalized 15 d after the surgery. Subsequently, a reduction colostomy was successfully performed after 10 d. CONCLUSION: This case report proposes a novel minimally invasive treatment approach for colorectal stenosis.

Clinical study of extrahepatic biliary adenoma.

BACKGROUND: Biliary adenomas that occur in the extrahepatic biliary tree are rare. It is difficult to distinguish it from cholangiocarcinoma or cholangiolithiasis by various imaging examinations, and it is very easy to be misdiagnosed. AIM: To evaluate the cumulative experiences including clinical characteristics and treatments of nine patients diagnosed with extrahepatic biliary adenoma admitted to the First Affiliated Hospital of Xi'an Jiaotong University from 2016 to 2022. METHODS: A total of nine patients were included in our study. The laboratory examinations, disease diagnosis, therapy and pathological characteristics, and follow-up of every patient were evaluated. RESULTS: Our cohort consisted of six females and three males with an average diagnosis age of 65.1 years (range 46-87). Six extrahepatic biliary adenomas were located in the common bile ducts and three in the hepatic duct. On initial presentation, all of the patients have symptom of biliary origin, including obstructive jaundice (4/9, 44.4%), abdominal pain (6/9, 66.7%), and fever (3/9, 33.3%). Preoperative imaging examination considered bile duct carcinoma in 6 cases and bile duct calculi in 3 cases. All the patients received surgical treatment and were confirmed by pathology as biliary adenoma. The symptoms improved significantly in all 9 patients after surgery. Seven of nine patients recovered well at follow-up without tumor recurrence. One patient died 2 mo after the surgery due to heart failure. One patient developed jaundice again 8 mo after surgery, underwent endoscopic retrograde cholangiopancreatography and biliary stent placement. CONCLUSION: Benign extrahepatic biliary tumors are rare and difficult to diagnosis preoperatively. Intraoperative choledochoscopy and timely biopsy may offer great advantages.

[The relationship between hypoxia-inducible factor-1α and cartilage degeneration in osteoarthritis: a review].

Osteoarthritis is one of the most common diseases seen in clinical practice. Cartilage survives in the hypoxic microenvironment. Hypoxia-inducible factor-1α (HIF-1α) is a key nuclear transcription factor which mediates the hypoxic response of cells. HIF-1α gene is an important regulator for the adaptation of articular cartilage to the hypoxic environment. It is important for formation of articular cartilage, energy metabolism and matrix synthesis. If the HIF-1α gene is knocked out, the cartilage can not maintain their normal morphology and function, which may lead to cartilage degeneration, and result in diseases such as osteoarthritis. Chinese herbal medicines can regulate the expression of HIF-1α gene and supply a therapy method for osteoarthritis. In this paper, the authors review the situation of the correlation between HIF-1α and osteoarthritis cartilage degeneration examined in recent years.

Application of Convolutional Neural Network to GIS and Physics.

Human life and property are often seriously threatened and lost due to natural disasters such as earthquakes. As a spatial information system, the geographic information system (GIS) can collect, store, and manage the local or whole related physical data of the surface space to be measured with the support of software and hardware. The physical data is collected through GIS for performance testing. The data are collected from the aftershock event records of the Wenchuan earthquake. Among them, 14,000 Wenchuan earthquake events are used as the original data set, and 8,800 aftershock events are used as the test data set. Seismic data involves the detection of multiple physical quantities, which makes the seismic data gradually increase, many data have no obvious linear relationship, and traditional detection methods are difficult to meet the detection requirements. The artificial intelligence method led by a convolutional neural network (CNN) can perform pattern matching on complex nonlinear variables, and models with general characteristics can be generated from different seismic waveforms for the prediction of seismic waveforms. The results show that GIS can effectively intercept and collect seismic physical signals. The training and detection accuracy of CNN combined with GIS physical data is higher than 90%. Compared with traditional training methods, CNN is obviously superior in detection accuracy and recall rate. At the same time, a large number of microseismic events that are easily missed by manual selection can also be found.

A non-cooperative game approach to the robust control design for a class of fuzzy dynamical systems.

Aiming at the time-varying bounded uncertainty in the mechanical system and the problem of excessive control gain caused by the "worst case", a robust control with tunable parameters that can be used to compensate for the uncertainty is proposed. The proposed control can guarantee that the system has uniform boundedness and uniform ultimate boundedness. Besides, the fuzzy set theory is used to describe the uncertainty to avoid introducing any IF-THEN fuzzy logic rules or probability theory. Based on the non-cooperative game theory, the parameters of the proposed control are optimized. We treat mutually independent parameters to be optimized as players, then design performance indexes for each parameter as its cost function, and solve the optimal result by the definition of Nash equilibrium. Finally, taking the trajectory tracking control of omnidirectional mobile platform as an example, the feasibility of the optimization method and the effectiveness of the control are verified by comparing with the other two control methods.

Therapeutic effect of alternating red and blue light irradiation combined with collagen in patients with acne vulgaris and the risk factors of short-term recurrence.

OBJECTIVE: To explore the therapeutic effect of alternating red and blue light irradiation combined with collagen in patients with acne vulgaris and the risk factors of short-term recurrence. METHOD: A retrospective analysis was conducted on 105 patients with acne vulgaris treated in Baoji Hospital of Traditional Chinese Medicine from January 2019 to February 2020. 50 patients received conventional treatment (Pumen red and blue light) were taken as the control group, and the other 55 patients treated with collagen dressing on the basis of control group were taken as the research group. Clinical efficacy, changes of serum interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) before and after treatment, and the occurrence of adverse reactions were compared between the two groups of patients. The scores of inflammatory skin lesions, facial seborrhea scores, stratum corneum water content and transepidermal water loss (TEWL) were compared before and after the treatment. The 1-year review records of patients were queried, and they were divided into a relapse group and a non-relapse group according to the recurrence situation. Logistic regression was used to analyze the risk factors affecting the recurrence of the patients. RESULTS: The clinical efficacy of the patients in research group after treatment was significantly higher than that in the control group (P<0.05). IL-1ß and IL-6 in the serum of patients after treatment were markedly decreased, and such decline in the research group was more evident after treatment (P<0.05). The incidence of adverse reactions, the scores of inflammatory skin lesions, and facial seborrhea and TEWL in the research group after treatment were all lower than those in the control group (all P<0.05), while the water content of the stratum corneum was higher comparatively (P<0.05). 17 patients were confirmed with recurrence within 1 year after treatment. Logistic regression analysis found that age, monthly income, pre-treatment IL-1ß and pre-treatment IL-6 were risk factors for recurrence. CONCLUSION: Alternating red and blue light irradiation combined with collagen can improve the treatment efficacy in patients with acne vulgaris. And indexes like age, monthly income, pre-treatment IL-1ß and pre-treatment IL-6 are risk factors affecting the recurrence of patients.

CRAUNet: A cascaded residual attention U-Net for retinal vessel segmentation.

Retinal vessels play an important role in judging many eye-related diseases, so accurate segmentation of retinal vessels has become the key to auxiliary diagnosis. In this paper, we present a Cascaded Residual Attention U-Net (CRAUNet) that can be regarded as a set of U-Nets, that allows coarse-to-fine representations. In the CRAUNet, we introduce a DropBlock regularization similar to the frequently-used dropout, which greatly reduces the overfitting problem. In addition, we propose a multi-scale fusion channel attention (MFCA) module to explore helpful information, and then merge this information instead of using a direct skip-connection. Finally, to prove the effectiveness of our method, we conduct extensive experiments on DRIVE and CHASE_DB1 datasets. The proposed CRAUNet achieves area under the receiver operating characteristic curve (AUC) of 0.9830 and 0.9865, respectively, for the two datasets. Compared to other state-of-the-art methods, the experimental results demonstrate that the performance of the proposed method is superior to that of others.

Generalized Multiphase Dynamic Modeling and Precision Interaction Force Control of a Walking Lower Limb Hydraulic Exoskeleton.

Wearable lower limb hydraulic exoskeletons can be used to augment the human performance in heavy load transportation. Nonlinear and walking phase-dependent dynamics make the lower limb hydraulic exoskeleton become difficult to be modeled. This paper presents a generalized multiphase dynamic modeling method in which the dynamic model of each walking phase can all be solved based on a general higher dimensional dynamic model and different holonomic constraints. Compared to traditional lower limb exoskeleton modeling methods where the modeling of each walking phase is done independently, the proposed method is simple and applicable to arbitrary walking phases, especially for double leg support phase (closed-chain dynamics). Based on the established dynamic models, MIMO adaptive robust cascade force controllers (ARCFC) are designed both for double leg support phase and single leg support phase to effectively address high-order nonlinearities and various modeling uncertainties in hydraulic exoskeletons. An additional torque allocation method is proposed to deal with the overactuated characteristic in double leg support. Comparative simulations are conducted to verify the excellent human-machine interaction force control performance of the proposed scheme.

Catch-up fat in male adults induces low testosterone and consequently promotes metabolic abnormalities and cognitive impairment.

BACKGROUND: Catch-up fat in adults (CUFA) caused by rapid nutrition promotion after undernutrition plays an important role in the epidemic of insulin resistance (IR)-related diseases in developing societies. Insulin resistance is considered to be closely associated with reduced testosterone levels and cognitive function. However, the effects of CUFA on testosterone levels and cognitive function are unclear in males. OBJECTIVES: To investigate the changes in testosterone levels and cognitive function in CUFA in male humans and rats, and explore their probable relationship and mechanisms in rats. MATERIALS AND METHODS: The blood testosterone levels, fasting glucose, and blood insulin (FINS) were measured in subpopulation 1 (27 CUFA individuals, 61 controls without CUFA) aged 40-50 years to show the characteristics of sex hormone levels and the metabolic status in CUFA men. Cognitive Flexibility Inventory was conducted in subpopulation 2 (54 CUFA individuals, 214 controls) over 20 years to investigate the associations between sex hormone levels, cognitive function, and CUFA. Male rats (n = 27) were randomly allocated to the NC group (normal chow controls), RN group (CUFA, refeeding after caloric restriction), and RT group (RN with testosterone intramuscular injected while refeeding). The blood testosterone levels, intraperitoneal insulin tolerance test (IPITT), and FINS were measured, and the attentional set-shifting task test (ASST) for the assessment of cognitive function was performed in these animals. Insulin signaling pathway, N-methyl-d-aspartate receptors subtype 2A (NR2A) and 2B (NR2B) expression levels were determined in the rat cerebral cortex. RESULTS: The total testosterone levels decreased (medium [inter-quartile ranges], 13.43 [9.87-18.96] vs. 15.58 [13.37-24.96], p = 0.036), and HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) elevated (1.61 [1.08-2.33] vs. 1.24 [0.87-1.87], P = 0.037) in CUFA men in subpopulation 1. Additionally, cognitive impairment was observed in CUFA men in subpopulation 2. Moreover, our results indicated decreases in total and free testosterone levels, elevations in visceral lipid accumulation, FINS, HOMA-IR, blood glucose, and the area under the curve after IPITT, increases in the number of trials required to achieve the criterion of the first reversal of discrimination (R1) in ASST, and downregulation of IRS-1 mRNA expression, AKT phosphorylation, and the NR2A and NR2B expression in brain tissue in male CUFA rats. Notably, testosterone supplementation improved visceral lipid accumulation and IR-related metabolic disorders, cognitive dysfunction, decreases in IRS-1 mRNA expression, Akt phosphorylation, and NR2A and NR2B expression in brain tissue in male CUFA rodents. DISCUSSION AND CONCLUSION: CUFA was characterized by reduced testosterone levels, metabolic abnormalities, and cognitive dysfunction in males, and testosterone supplementation attenuated these changes, as well as the alteration in insulin signaling and NR2A and NR2B expression in male CUFA rodents. Herein, we tentatively put forward that CUFA in males induces low testosterone, consequently promoting metabolic abnormalities and cognitive impairment probably mediated by defects in insulin signaling and NR2A, NR2B pathway in brain tissue.

PRMT5 regulates ovarian follicle development by facilitating Wt1 translation.

Protein arginine methyltransferase 5 (Prmt5) is the major type II enzyme responsible for symmetric dimethylation of arginine. Here, we found that PRMT5 was expressed at high level in ovarian granulosa cells of growing follicles. Inactivation of Prmt5 in granulosa cells resulted in aberrant follicle development and female infertility. In Prmt5-knockout mice, follicle development was arrested with disorganized granulosa cells in which WT1 expression was dramatically reduced and the expression of steroidogenesis-related genes was significantly increased. The premature differentiated granulosa cells were detached from oocytes and follicle structure was disrupted. Mechanism studies revealed that Wt1 expression was regulated by PRMT5 at the protein level. PRMT5 facilitated IRES-dependent translation of Wt1 mRNA by methylating HnRNPA1. Moreover, the upregulation of steroidogenic genes in Prmt5-deficient granulosa cells was repressed by Wt1 overexpression. These results demonstrate that PRMT5 participates in granulosa cell lineage maintenance by inducing Wt1 expression. Our study uncovers a new role of post-translational arginine methylation in granulosa cell differentiation and follicle development.

Infertility in women can be caused by many factors, such as defects in the ovaries. An important part of the ovaries for fertility are internal structures called follicles, which house early forms of egg cells. A follicle grows and develops until the egg is finally released from the ovary into the fallopian tube, where the egg can then be fertilised. In the follicle, an egg is surrounded by other types of cells, such as granulosa cells. The egg and neighbouring cells must maintain healthy contacts with each other, otherwise the follicle can stop growing and developing, potentially causing infertility. The development of a follicle depends on an array of proteins. For example, the transcription factor WT1 controls protein levels by activating other genes and their proteins and is produced in high numbers by granulosa cells at the beginning of follicle development. Although WT1 levels dip towards the later stages of follicle development, insufficient levels can lead to defects. So far, it has been unclear how levels of WT1in granulose cells are regulated. Chen, Dong et al. studied mouse follicles to reveal more about the role of WT1 in follicle development. The researchers measured protein levels in mouse granulosa cells as the follicles developed, and discovered elevated levels of PRMT5, a protein needed for egg cells to form and survive in the follicles. Blocking granulosa cells from producing PRMT5 led to abnormal follicles and infertility in mice. Moreover, mice that had been engineered to lack PRMT5 developed abnormal follicles, where the egg and surrounding granulosa cells were not attached to each other, and the granulosa cells had low levels of WT1. Further experiments revealed that PRMT5 controlled WT1 levels by adding small molecules called methyl groups to another regulatory protein called HnRNPA1. The addition of methyl groups to genes or their proteins is an important modification that takes place in many processes within a cell. Chen, Dong et al. reveal that this activity also plays a key role in maintaining healthy follicle development in mice, and that PRMT5 is necessary for controlling WT1. Identifying all of the intricate mechanism involved in regulating follicle development is important for finding ways to combat infertility.

PRMT5 Is Involved in Spermatogonial Stem Cells Maintenance by Regulating Plzf Expression via Modulation of Lysine Histone Modifications.

Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of mono- or symmetric dimethylarginine residues on histones and non-histone substrates and has been demonstrated to play important roles in many biological processes. In the present study, we observed that PRMT5 is abundantly expressed in spermatogonial stem cells (SSCs) and that Prmt5 deletion results in a progressive loss of SSCs and male infertility. The proliferation of Prmt5-deficient SSCs cultured in vitro exhibited abnormal proliferation, cell cycle arrest in G0/G1 phase and a significant increase in apoptosis. Furthermore, PLZF expression was dramatically reduced in Prmt5-deficient SSCs, and the levels of H3K9me2 and H3K27me2 were increased in the proximal promoter region of the Plzf gene in Prmt5-deficient SSCs. Further study revealed that the expression of lysine demethylases (JMJD1A, JMJD1B, JMJD1C, and KDM6B) was significantly reduced in Prmt5-deficient SSCs and that the level of permissive arginine methylation H3R2me2s was significantly decreased at the upstream promoter region of these genes in Prmt5-deficient SSCs. Our results demonstrate that PRMT5 regulates spermatogonial stem cell development by modulating histone H3 lysine modifications.

Segmentation and classification of thyroid follicular neoplasm using cascaded convolutional neural network.

In this paper, we present a segmentation and classification method for thyroid follicular neoplasms based on a combination of the prior-based level set method and deep convolutional neural network. The proposed method aims to discriminate thyroid follicular adenoma (TFA) and follicular thyroid carcinoma (FTC) in ultrasound images. In their appearance, these two kinds of tumours have similar shapes, sizes and contrasts. Therefore, it is difficult for even ultrasound specialists to distinguish them. Because of the complex background in thyroid ultrasound images, before distinguishing TFA and FTC, we need to segment the lesions from the whole image for each patient. The main challenge of segmentation is that the images often have weak edges and heterogeneous regions. The main issue of classification is that the accuracy depends on the features extracted from the segmentation results. To solve these problems, we conduct the two tasks, i.e. segmentation and classification, by a cascaded learning architecture. For segmentation, to obtain more accurate results, we exploit the Res-U-net framework and the prior-based level set method to enhance their respective abilities. Then, the classification network is trained by sharing shallow layers of the segmentation network. Testing the proposed method on real patient data shows that it is able to segment the lesion areas in thyroid ultrasound images with a Dice score of 92.65% and to distinguish TFA and FTC with a classification accuracy of 96.00%.