Prenatal restraint stress is associated with demethylation of corticotrophin releasing hormone (CRH) promoter and enhances CRH transcriptional responses to stress in adolescent rats.

Maternal stress can disturb normal fetal neurodevelopmental progress, and lead to negative behavioral and neuroendocrine consequences for the offspring. These effects may be related to alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Early life events disrupting the function of the HPA axis may be associated with epigenetic modification. This study investigated the effect of maternal stress on the methylation rate of the corticotrophin-releasing hormone (CRH) promoter and HPA axis response to acute stress in the adolescent offspring of Sprague-Dawley rats. Pregnant dams were randomly assigned to two groups: restraint stress group and normal control group. Adolescent male and female offspring were used from each group. The results showed that prenatal stress is associated with the demethylation of the CRH promoter, and leads to anxiety-like behaviors in adolescent life stages, as well as hyper-responsiveness of the HPA axis. Together, these results imply that prenatal stress alters the normal HPA function, which may be via the epigenetic mechanism.

Heterocyclic core analogs of a direct thrombin inhibitor.

Thrombin is a serine protease that plays a key role in blood clotting. Pyrrolidine 1 is a potent thrombin inhibitor discovered at Merck several years ago. Seven analogs (2-8) of 1 in which the pyrrolidine core was replaced with various heterocycles were prepared and evaluated for activity against thrombin, clotting factors VIIa, IXa, Xa, and XIIa, and trypsin. The thiomorpholine analog 6 was the most active, essentially matching the thrombin inhibitory activity of 1 with slightly improved selectivity over trypsin.

Sample-Based Continuous Approximate Method for Constructing Interval Neural Network.

In safety-critical engineering applications, such as robust prediction against adversarial noise, it is necessary to quantify neural networks' uncertainty. Interval neural networks (INNs) are effective models for uncertainty quantification, giving an interval of predictions instead of a single value for a corresponding input. This article formulates the problem of training an INN as a chance-constrained optimization problem. The optimal solution of the formulated chance-constrained optimization naturally forms an INN that gives the tightest interval of predictions with a required confidence level. Since the chance-constrained optimization problem is intractable, a sample-based continuous approximate method is used to obtain approximate solutions to the chance-constrained optimization problem. We prove the uniform convergence of the approximation, showing that it gives the optimal INN consistently with the original ones. Additionally, we investigate the reliability of the approximation with finite samples, giving the probability bound for violation with finite samples. Through a numerical example and an application case study of anomaly detection in wind power data, we evaluate the effectiveness of the proposed INN against existing approaches, including Bayesian neural networks, highlighting its capability to significantly improve the performance of applying INNs for regression and unsupervised anomaly detection.

Identification of immune-associated biomarker for predicting lung adenocarcinoma: bioinformatics analysis and experiment verification of PTK6.

BACKGROUND: Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. OBJECTIVE: The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. METHODS: The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. RESULTS: PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-ß signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. CONCLUSION: PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

Effects of small interfering RNA-mediated hepatic glucagon receptor inhibition on lipid metabolism in db/db mice.

Hepatic glucose overproduction is a major characteristic of type 2 diabetes. Because glucagon is a key regulator for glucose homeostasis, antagonizing the glucagon receptor (GCGR) is a possible therapeutic strategy for the treatment of diabetes mellitus. To study the effect of hepatic GCGR inhibition on the regulation of lipid metabolism, we generated siRNA-mediated GCGR knockdown (si-GCGR) in the db/db mouse. The hepatic knockdown of GCGR markedly reduced plasma glucose levels; however, total plasma cholesterol was increased. The detailed lipid analysis showed an increase in the LDL fraction, and no change in VLDL HDL fractions. Further studies showed that the increase in LDL was the result of over-expression of hepatic lipogenic genes and elevated de novo lipid synthesis. Inhibition of hepatic glucagon signaling via siRNA-mediated GCGR knockdown had an effect on both glucose and lipid metabolism in db/db mice.

Sample-Based Neural Approximation Approach for Probabilistic Constrained Programs.

This article introduces a neural approximation-based method for solving continuous optimization problems with probabilistic constraints. After reformulating the probabilistic constraints as the quantile function, a sample-based neural network model is used to approximate the quantile function. The statistical guarantees of the neural approximation are discussed by showing the convergence and feasibility analysis. Then, by introducing the neural approximation, a simulated annealing-based algorithm is revised to solve the probabilistic constrained programs. An interval predictor model (IPM) of wind power is investigated to validate the proposed method.

Case report of 18F-FDG PET/CT features of hypoglycemic encephalopathy.

RATIONALE: Hypoglycemia may cause diverse neurological manifestations, ranging from focal neurological deficits to irreversible coma. Severe and persistent hypoglycemia can lead to hypoglycemic encephalopathy (HE). Imaging findings of HE at different stages of 18F-FDG positron emission tomography/computed tomography (PET/CT) have rarely been reported. Herein, we describe a case of HE occurring in the medial frontal cortex, cerebellar cortex, and dentate nucleus using 18F-FDG PET/CT images from different periods. 18F-FDG PET/CT has a high value in displaying the lesion range and indicating the prognosis. PATIENT CONCERNS: A 57-year-old male patient with type 2 diabetes (T2D) was transferred to the hospital with a history of unconsciousness for 1 night. The patient showed a significant decrease in blood glucose levels. DIAGNOSES: The patient was initially diagnosed with a hypoglycemic coma. INTERVENTIONS: The patient subsequently underwent a comprehensive treatment. The 18F-FDG PET/CT examination on the fifth day after admission revealed a significant symmetrical fluorodeoxyglucose (FDG)-positive accumulation in the bilateral medial frontal gyrus, cerebellar cortex, and dentate nucleus. A follow-up PET/CT examination 6 months later revealed hypometabolism in the bilateral medial frontal gyrus and no abnormalities in FDG uptake in the bilateral cerebellar cortex and dentate nucleus. OUTCOMES: The patient condition was stable 6 months later, with a slow response, memory deterioration, occasional dizziness, and episodes of hypoglycemia. LESSONS: HE lesions with a high metabolic status may be related to a metabolic compensation mechanism in response to gray matter loss. Some of the more severely damaged cells eventually die even after the blood sugar levels return to normal. Less damaged nerve cells can be recovered. 18F-FDG PET/CT has high value in indicating the lesion range and prognosis of HE.

Bone marrow mesenchymal stem cell exosome-derived lncRNA TUC339 influences the progression of osteoarthritis by regulating synovial macrophage polarization and chondrocyte apoptosis.

Osteoarthritis (OA) is an extremely common type of chronic progressive disease in clinical practice. lncRNA TUC339 has a close association with bone marrow mesenchymal stem cell (BMSC) and an important impact on organismal inflammation. However, the mechanism of BMSC-derived lncRNA TUC339 on OA was poorly understood. In this study, we found that TUC339 was lower in the research group than in the control group and it was negatively correlated with IL-6, IL-8 and TNF-α. Prognosis TUC339 was lower in patients with recurrent OA than in those without recurrence, and ROC analysis manifested that TUC339 had a better predictive value for recurrence of OA. Phenotypic identification revealed elevated expression of CD29 and CD44 in BMSCs and TSG101, CD63 and CD81 in BMSCs-exosome (BMSCs-exo), with a stem cell versus exosome phenotype. Finally, animal experiments improved significantly in joint injury in the BMSCs-exo and TUC339-overexpression vector groups compared with control groups. Similarly, the activity of chondrocytes was enhanced, and apoptosis was reduced in the BMSCs-exo group versus the TUC339-overexpression vector group of rats. Study demonstrated that BMSCs-exo improves OA by elevating the expression of TUC339 to promote M1-type mø to M2-type polarization, suppressing inflammation and promoting chondrocyte activity, which provides a reliable basis for future transplantation therapy of MSCs for OA.

Early outcomes, associated factors and predictive values of clinical outcomes of tandospirone in generalized anxiety disorder: a post-hoc analysis of a randomized, controlled, multicenter clinical trial.

OBJECTIVE: To examine the early outcomes, associated factors and predictive values of clinical outcomes of different tandospirone doses in patients with a generalized anxiety disorder (GAD). METHODS: This was a posthoc analysis of "a randomized, controlled multicenter clinical trial of the efficacy and safety of different doses of tandospirone on GAD". A total of 274 patients with GAD were included and randomized into the high-dose (tandospirone 60 mg/d) and low-dose (tandospirone 30 mg/d) groups for a 6-week treatment. The Hamilton Anxiety (HAMA), Clinical Global Impression-Severity (CGI-S), Short-Form-12 (SF-12) scales were used for assessment. The trial was registered at clinical trail.gov (NCT01614041). RESULTS: (1) In the first week of treatment, 35.8% of patients in the high-dose group fulfilled the early onset criteria, which was significantly higher than 19.0% found in the low-dose group (p = 0.002). In the second week of treatment, 22.6% of patients in the high-dose group achieved an early response, versus 12.4% in the low-dose group, indicating a significant difference (p = .026). (2) Factors associated with early onset at week 1 included baseline HAMA total score (OR = 0.916, 95%CI 0.882-0.952), age (OR = 0.974, 95%CI 0.950-0.998), drug dose (30 mg vs. 60 mg; OR = 0.298, 95%CI 0.156-0.568) and SF-12 physiological total score (OR = 1.030, 95%CI 1.010-1.050). (3) Early onset was significantly associated with response rate (OR = 18.34, 95%CI 12.10-27.81), remarkable response rate (OR = 27.56, 95%CI 11.65-65.17) and recovery rate (OR = 11.85, 95%CI 4.98-28.18). Group (high dose group vs. low dose group) (χ2 = 8.535, p = .003) and baseline HAMA total score (χ2 = 70.840, p < .001) were independent predictors of onset time. CONCLUSIONS: The early outcomes of high-dose tandospirone in the treatment of GAD are better than those of the low-dose group. Patients with younger age at onset, milder anxiety symptoms and better physiological functions administered high-dose tandospirone showed rapid onset, great early outcomes, high recovery rate and good prognosis. Drug onset time had a good predictive effect on treatment outcome.

Statistical models of near-accident event and pedestrian behavior at non-signalized intersections.

This paper proposes an innovative framework of modeling the statistical properties of the near-accident event and pedestrian behavior at non-signalized intersections based on Poisson process and logistic regression. The first contribution of this study is that the predictive intensity model of the near-accident event is established by regarding the near-accident event as a Poisson process on space of the vehicle velocity, distance to the intersection and lateral distance to the pedestrian at the time when pedestrian appears. Besides, logistic regression is used to build the model which can predict the probability of pedestrian behavior. The two proposed models are validated in a generative simulation. The simulated pedestrian behavior data is generated by the proposed models and compared with the real data. The real data set is from the drive recorder data base of Smart Mobility Research Center (SMRC) at Tokyo University of Agriculture and Technology. Accident and near-accident data has been collected in the city streets with an image-captured drive recorder mounted on a taxi since 2006. The findings in this study are expected to be useful for constructions of traffic simulators or safety control design which considers the pedestrian-vehicle interaction.

A plasmonic ELISA for multi-colorimetric sensing of C-reactive protein by using shell dependent etching of Ag coated Au nanobipyramids.

The etching of gold nanorods/nanobipyramid, or silver-coated nanorods/nanobipyramid inducing plasmon changes represents an efficient strategy to improve the performance of enzyme-linked immunosorbent assay (ELISA). However, the effect of shape on the sensitivity was negligible, especially the thickness of coated silver shell. Here, we propose a plasmonic ELISA for multi-colorimetric detection of CRP based on the etching of Ag-coated Au nanobipyramid (Au NBP@Ag). The effect of silver shell thickness on the sensitivity of plasmon peak shifting was investigated by experiments and DDA calculations. The relationship between the Ag shell thickness and the sensitivity of plasmon peak shifting was obtained. Our results reveal that the thickness of coated Ag shell acts as a key factor in the multi-color change of Au NBP@Ag etching. It is found that Au NBP@Ag with medium Ag shell thickness and rod-like shape has the higher sensitivity and is suitable for sensing. At the optimized most sensitive Ag shell, the detection limit of proposed plasmonic ELISA for CRP was determined to be 0.09 ng/mL with a spectrometer in the range from 0.09 ng/mL to 25 ng/mL. Importantly, the visual detection limit was 0.78 ng/mL, which allows the differential diagnosis with the naked eye. Compared with traditional ELISA with the monochromatic intensity variations, the multi-color ELISA proposed in this study has a large linear range and rich color variation for high-sensitivity and naked-eye semi-quantitative detection.

Efficacy and long-term results of endovascular embolization and surgical clipping for posterior communicating artery unruptured aneurysms complicated with oculomotor nerve palsy.

THIS STUDY AIMED: to investigate the efficacy and long-term outcomes of endovascular embolization and surgical clipping for patients with posterior communicating artery unruptured aneurysms (PcomAs) concomitant with oculomotor nerve palsy (ONP). No significant (P > .05) difference existed in the age, gender, proportion of complete ONP, and size of eye fissure and pupil before treatment between 2 groups. After compared with before treatment, the eye fissure was widened significantly (P < .05) and the pupil narrowed significantly (P < .05), but no significant (P > .05) differences existed between the 2 groups. Complete ONP recovery was observed in 32 (80%) patients in the embolization group and 31 (77.5%) in the microsurgical group, partial ONP recovery occurred in 6 (15%) in the embolization group and 8 (20%) in the microsurgical group. The recovery rate was 95% in the embolization group and 97.5% in the microsurgical group, with no significant (P > .05) difference between 2 groups. The recovery rate of the ONP was significantly (P < .01) greater in the microsurgical group than that in the embolization group at follow-up of 1 month, 3 months, six and 12 months, respectively. At 18 months, the ONP recovery rate was not significantly different between 2 groups (95% vs 97.5%) Surgical clipping may have a faster effect on the recovery of oculomotor nerve palsy than endovascular embolization for patients with posterior communicating artery unruptured aneurysms complicated with oculomotor nerve palsy, but both approaches may result in a similar effect on the nerve recovery in the long run.Eighty patients treated with endovascular embolization or surgical clipping were retrospectively enrolled into the endovascular embolization group or surgical clipping and analyzed.

Accuracy of behavioral health variables in Oregon national violent death reporting system data: a linked cohort study.

BACKGROUND: The National Violent Death Reporting System (NVDRS) collects data on the circumstances of violent deaths, and all firearm-related deaths, across states and territories in the USA. This surveillance system is critical to understanding patterns and risk factors for these fatalities, thereby informing targets for prevention. NVDRS variables include behavioral health conditions among decedents, but the validity of the reported behavioral health data is unknown. Using Department of Veterans Affairs (VA) healthcare records as a criterion standard, we examined the accuracy of NVDRS-reported behavioral health variables for veteran decedents in a sample state (Oregon) between 2003 and 2017. METHODS: We linked Oregon NVDRS data to VA healthcare data to identify veteran decedents who used VA services within two years of death. Veterans' VA diagnoses within this time frame, including depression, post-traumatic stress disorder (PTSD), anxiety, and substance use disorders, were compared to behavioral health variables identified in the Oregon NVDRS. Concordance, sensitivity, and correlates of sensitivity were examined over time and by decedent characteristics. RESULTS: We identified 791 VA-using veterans with violent and/or firearm-related fatal injuries documented in the Oregon NVDRS between 2003 and 2017. In this cohort, the Oregon NVDRS accurately identified only 49% of decedents who were diagnosed with depression, 45% of those diagnosed with PTSD, and 17% of those diagnosed with anxiety by the VA. Among 211 veterans diagnosed by the VA with a substance use disorder, the Oregon NVDRS coded only 56% as having a substance use problem. In general, the sensitivity of behavioral health variables in the Oregon NVDRS remained the same or decreased over the study period; however, the sensitivity of PTSD diagnoses increased from 21% in 2003-2005 to 54% in 2015-2017. Sensitivity varied by some decedent characteristics, but not consistently across behavioral health variables. CONCLUSIONS: NVDRS data from one state missed more than half of behavioral health diagnoses among VA-using veterans who died from violence or from firearm injuries. This suggests that reports of behavioral health conditions among decedents nationally may be severely undercounted. Efforts to improve validity of these variables in state NVDRS data are needed.

Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate osteoarthritis of the knee in mice model by interacting with METTL3 to reduce m6A of NLRP3 in macrophage.

BACKGROUND: Osteoarthritis (OA) is a prevalent degenerative joint disease that not only significantly impairs the quality of life of middle-aged and elderly individuals but also imposes a significant financial burden on patients and society. Due to their significant biological properties, extracellular vesicles (EVs) have steadily received great attention in OA treatment. This study aimed to investigate the influence of EVs on chondrocyte proliferation, migration, and apoptosis and their protective efficacy against OA in mice. METHODS: The protective impact of EVs derived from human umbilical cord mesenchymal stem cells (hucMSCs-EVs) on OA in mice was investigated by establishing a mouse OA model by surgically destabilizing the medial meniscus (DMM). Human chondrocytes were isolated from the cartilage of patients undergoing total knee arthroplasty (TKA) and cultured with THP-1 cells to mimic the in vivo inflammatory environment. Levels of inflammatory factors were then determined in different groups, and the impacts of EVs on chondrocyte proliferation, migration, apoptosis, and cartilage extracellular matrix (ECM) metabolism were explored. N6-methyladenosine (m6A) level of mRNA and methyltransferase-like 3 (METTL3) protein expression in the cells was also measured in addition to microRNA analysis to elucidate the molecular mechanism of exosomal therapy. RESULTS: The results indicated that hucMSCs-EVs slowed OA progression, decreased osteophyte production, increased COL2A1 and Aggrecan expression, and inhibited ADAMTS5 and MMP13 overexpression in the knee joint of mice via decreasing pro-inflammatory factor secretion. The in vitro cell line analysis revealed that EVs enhanced chondrocyte proliferation and migration while inhibiting apoptosis. METTL3 is responsible for these protective effects. Further investigations revealed that EVs decreased the m6A level of NLRP3 mRNA following miR-1208 targeted binding to METTL3, resulting in decreased inflammatory factor release and preventing OA progression. CONCLUSION: This study concluded that hucMSCs-EVs inhibited the secretion of pro-inflammatory factors and the degradation of cartilage ECM after lowering the m6A level of NLRP3 mRNA with miR-1208 targeting combined with METTL3, thereby alleviating OA progression in mice and providing a novel therapy for clinical OA treatment.

A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo.

Proprotein convertase subtilisin-like/kexin type 9 (PCSK9) regulates LDL cholesterol levels by inhibiting LDL receptor (LDLr)-mediated cellular LDL uptake. We have identified a fragment antigen-binding (Fab) 1D05 which binds PCSK9 with nanomolar affinity. The fully human antibody 1D05-IgG2 completely blocks the inhibitory effects of wild-type PCSK9 and two gain-of-function human PCSK9 mutants, S127R and D374Y. The crystal structure of 1D05-Fab bound to PCSK9 reveals that 1D05-Fab binds to an epitope on the PCSK9 catalytic domain which includes the entire LDLr EGF(A) binding site. Notably, the 1D05-Fab CDR-H3 and CDR-H2 loops structurally mimic the EGF(A) domain of LDLr. In a transgenic mouse model (CETP/LDLr-hemi), in which plasma lipid and PCSK9 profiles are comparable to those of humans, 1D05-IgG2 reduces plasma LDL cholesterol to 40% and raises hepatic LDLr protein levels approximately fivefold. Similarly, in healthy rhesus monkeys, 1D05-IgG2 effectively reduced LDL cholesterol 20%-50% for over 2 weeks, despite its relatively short terminal half-life (t(1/2) = 3.2 days). Importantly, the decrease in circulating LDL cholesterol corresponds closely to the reduction in free PCSK9 levels. Together these results clearly demonstrate that the LDL-lowering effect of the neutralizing anti-PCSK9 1D05-IgG2 antibody is mediated by reducing the amount of PCSK9 that can bind to the LDLr.

Roles of phospholipase D in phorbol myristate acetate-stimulated neutrophil respiratory burst.

The phorbol myristate acetate (PMA) stimulated nutrophil respiratory burst has been considered to simply involve the activation of protein kinase C (PKC). However, the PLD activity was also increased by 10-fold in human neutrophils stimulated with 100 nM PMA. Unexpectedly, U73122, an inhibitor of phospholipase C, was found to significantly inhibit PMA-stimulated respiratory burst in human neutrophils. U73122 at the concentrations, which were sufficient to inhibit the respiratory burst completely, caused partial inhibition of the PLD activity but no inhibition on PKC translocation and activation, suggesting that PLD activity is also required in PMA-stimulated respiratory burst. Using 1-butanol, a PLD substrate, to block phosphatidic acid (PA) generation, the PMA-stimulated neutrophil respiratory burst was also partially inhibited, further indicating that PLD activation, possibly its hydrolytic product PA and diacylglycerol (DAG), is involved in PMA-stimulated respiratory burst. Since GF109203X, an inhibitor of PKC that could completely inhibit the respiratory burst in PMA-stimulated neutrophils, also caused certain suppression of PLD activation, it may suggest that PLD activation in PMA-stimulated neutrophils might be, to some extent, PKC dependent. To further study whether PLD contributes to the PMA stimulated respiratory burst through itself or its hydrolytic product, 1,2-dioctanoyl-sn-glycerol, an analogue of DAG , was used to prime cells at low concentration, and it reversed the inhibition of PMA-stimulated respiratory burst by U73122. The results indicate that U73122 may act as an inhibitor of PLD, and PLD activation is required in PMA-stimulated respiratory burst.

A proprotein convertase subtilisin-like/kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake.

PCSK9 binds to the low density lipoprotein receptor (LDLR) and leads to LDLR degradation and inhibition of plasma LDL cholesterol clearance. Consequently, the role of PCSK9 in modulating circulating LDL makes it a promising therapeutic target for treating hypercholesterolemia and coronary heart disease. Although the C-terminal domain of PCSK9 is not involved in LDLR binding, the location of several naturally occurring mutations within this region suggests that it has an important role for PCSK9 function. Using a phage display library, we identified an anti-PCSK9 Fab (fragment antigen binding), 1G08, with subnanomolar affinity for PCSK9. In an assay measuring LDL uptake in HEK293 and HepG2 cells, 1G08 Fab reduced 50% the PCSK9-dependent inhibitory effects on LDL uptake. Importantly, we found that 1G08 did not affect the PCSK9-LDLR interaction but inhibited the internalization of PCSK9 in these cells. Furthermore, proteolysis and site-directed mutagenesis studies demonstrated that 1G08 Fab binds a region of beta-strands encompassing Arg-549, Arg-580, Arg-582, Glu-607, Lys-609, and Glu-612 in the PCSK9 C-terminal domain. Consistent with these results, 1G08 fails to bind PCSK9DeltaC, a truncated form of PCSK9 lacking the C-terminal domain. Additional studies revealed that lack of the C-terminal domain compromised the ability of PCSK9 to internalize into cells, and to inhibit LDL uptake. Together, the present study demonstrate that the PCSK9 C-terminal domain contribute to its inhibition of LDLR function mainly through its role in the cellular uptake of PCSK9 and LDLR complex. 1G08 Fab represents a useful new tool for delineating the mechanism of PCSK9 uptake and LDLR degradation.

Primary follicular lymphoma in the renal pelvis: A rare case report.

BACKGROUND: Follicular lymphoma (FL) is more common in lymph nodes, while primary extranodal lymphomas are rare. Urinary tract lymphoid neoplasms are extremely rare, accounting for less than 5% of all extranodal lymphomas. Only one case of FL from the renal pelvis has previously been reported. CASE SUMMARY: A 70-year-old male patient with a history of esophageal cancer visited our hospital for follow-up examination. Abdominal computed tomography revealed a malignant mass in the right renal pelvis. The whole-body positron emission tomography/computed tomography showed a significant increase in fluorodeoxyglucose uptake of this soft tissue mass and no abnormal fluorodeoxyglucose uptake in the esophageal wall. The patient underwent radical resection of a malignant tumor in the right kidney, which was confirmed by postoperative pathology to be FL. The patient received no radiation or chemotherapy after surgery, and no recurrence of lymphoma or other malignant tumors was found at the 1-year follow-up. CONCLUSION: Extranodal FL is more common in the skin and gastrointestinal tract but rarely occurs in the urinary tract. This is the second report of primary renal FL. Localized extranodal FL is expected to have a favorable prognosis and can be cured by local resection.

18F-FDG PET/CT imaging for aggressive melanotic schwannoma of the L3 spinal root: A case report.

RATIONALE: Melanotic schwannoma (MS) is an unusual variant of a nerve sheath neoplasm that accounts for less than 1% of all primary peripheral nerve sheath tumors. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has unique value in detecting malignant MS lesions. To date, only 4 cases of MS with hepatic metastasis have been reported. Herein, we report the fifth case, which is the first reported patient with MS of Asian ethnicity with hepatic metastasis. PATIENT CONCERNS: A 29-year-old woman with a 1-day history of backache was admitted to our hospital. PET/CT showed a paravertebral heterogeneous soft tissue mass along the spinal nerve at the L2-L3 level with strong FDG uptake, and a nodule with increased FDG uptake in the lateral lobe of the left liver. DIAGNOSIS: A puncture biopsy of the L3 bony destruction and surrounding soft tissue mass was performed. The final diagnosis was spinal MS with hepatic metastasis. INTERVENTIONS: The patient underwent 6 courses of systemic chemotherapy. OUTCOMES: The patient did not receive further treatment for half a year after the end of chemotherapy and recovered well. LESSONS: Unlike conventional schwannomas, which are completely benign, MS has an unpredictable prognosis. It is thought to have low malignant potential, and the malignant type tends to metastasize. FDG PET/CT has a unique and important value in the differential diagnosis of benign and malignant lesions, in detecting occult metastases, monitoring the treatment response, and assessing the prognosis of MS.

Pulmonary mucinous cystadenoma complicated with infection: A rare case report.

RATIONALE: Mucinous cystadenoma is a benign tumor that is commonly found in the pancreas, ovaries, or appendix, but is rarely encountered in the lungs. Worldwide, only a few reported cases of these tumors originate in the lungs. Herein, we analyzed the imaging features of a case of pulmonary mucinous cystadenoma (PMCA). To the best of our knowledge, this is the first reported case of PMCA complicated by significant infection. PATIENT CONCERNS: A 57-year-old man was admitted to our hospital with blood in sputum for more than 2 months. Serum laboratory examination showed significantly elevated leukocyte and tumor marker, carcinoembryonic antigen. Enhanced thoracic computed tomography and whole-body positron emission tomography/computed tomography showed a cystic-solid ill-defined mass in the right upper lung. DIAGNOSIS: The tumor was considered malignant, both clinically and radiologically. INTERVENTIONS: The patient underwent right upper lobe tumor resection and mediastinal lymph node dissection. OUTCOMES: Postoperative specimen pathology was diagnosed as PMCA with infection. The patient was not administered any further treatment. The patient was alive without any recurrence or metastasis of the tumor after 2 years of follow-up. LESSONS: Preoperative diagnosis of PMCA with atypical imaging and clinical manifestations is extremely difficult. This is the first reported case of PMCA complicated by a significant infection that was misdiagnosed preoperatively as a malignancy.