Effects of Liver Fibrosis on Islet Function in Patients with Chronic Hepatitis B Complicated with Impaired Fasting Glucose.

Background: Patients with chronic hepatitis B (CHB) and cirrhosis often have impaired fasting glucose (IFG). This study sought to investigate the impact of liver fibrosis on islet function in individuals diagnosed with CHB and IFG. Material and Methods: Patients with chronic hepatitis B (CHB) and impaired fasting glucose (IFG) were selected for this study. They were divided into low-risk (L-R), intermediate-risk (M-R), and high-risk (H-R) liver fibrosis groups based on the FIB-4 score. The study compared islet function among different risk groups of liver fibrosis and analyze the correlation between liver fibrosis and islet function. Additionally, the patients were divided into a diabetes mellitus (DM) group and a non-DM (NDM) group based on the development of DM. The cumulative risk of progression to DM in patients with L-R, M-R, and H-R liver fibrosis was analyzed using the Kaplan-Meier method. Hazard ratios (HRs) and confidence intervals (CIs) were calculated for DM development through Cox regression analysis. Results: In this study of 228 individuals, higher FIB-4 scores were observed in the DM group compared to the NDM group. Patients with H-R liver fibrosis displayed lower islet function and had a significantly higher risk of developing DM. The FIB-4 score and fasting plasma glucose (FPG) were identified as independent risk factors for DM progression in CHB patients with IFG. Conclusion: Among patients with CHB and IFG, the severity of liver fibrosis is associated with islet function, and the FIB-4 score is a significant risk factor for DM development.

Capsaicin functions as a selective degrader of STAT3 to enhance host resistance to viral infection.

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.

Role of OAS gene family in COVID-19 induced heart failure.

BACKGROUND: COVID-19, the current global pandemic caused by SARS-CoV-2 infection, can damage the heart and lead to heart failure (HF) and even cardiac death. The 2',5'-oligoadenylate synthetase (OAS) gene family encode interferon (IFN)-induced antiviral proteins which is associated with the antiviral immune responses of COVID-19. While the potential association of OAS gene family with cardiac injury and failure in COVID-19 has not been determined. METHODS: The expression levels and biological functions of OAS gene family in SARS-CoV-2 infected cardiomyocytes dataset (GSE150392) and HF dataset (GSE120852) were determined by comprehensive bioinformatic analysis and experimental validation. The associated microRNAs (miRNAs) were explored from Targetscan and GSE104150. The potential OAS gene family-regulatory chemicals or ingredients were predicted using Comparative Toxicogenomics Database (CTD) and SymMap database. RESULTS: The OAS genes were highly expressed in both SARS-CoV-2 infected cardiomyocytes and failing hearts. The differentially expressed genes (DEGs) in the two datasets were enriched in both cardiovascular disease and COVID-19 related pathways. The miRNAs-target analysis indicated that 10 miRNAs could increase the expression of OAS genes. A variety of chemicals or ingredients were predicted regulating the expression of OAS gene family especially estradiol. CONCLUSION: OAS gene family is an important mediator of HF in COVID-19 and may serve as a potential therapeutic target for cardiac injury and HF in COVID-19.

Congenital radioulnar synostosis: is prenatal diagnosis possible? - A case report.

OBJECTIVES: The main objectives of this case report are to discuss prenatal ultrasound findings of congenital radioulnar synostosis and to review the literature. CASE REPORT: A patient was diagnosed with congenital radioulnar synostosis at eight months old when parents noticed limited motions in the child's left forearm. The parent denied any traumatic or family history of bony malformations. Physical examination by a pediatric orthopedics specialist and digital radiography revealed proximal radioulnar synostosis. The case report includes perinatal course, comparison between the postnatal radiography and fetal ultrasound images. CONCLUSION: Congenital radioulnar synostosis is often associated with sex chromosome abnormalities and congenital musculoskeletal disorders or syndromes affecting limbs. Isolated congenital radioulnar synostosis is hardly diagnosed before birth, in some cases even have been neglected postnatally. Knowing the developmental milestones of the forearm and specified high-risk groups might help develop a targeted screening strategy to increase the possibility of early detection and intervention.

Orexin-A aggravates cognitive deficits in 3xTg-AD mice by exacerbating synaptic plasticity impairment and affecting amyloid ß metabolism.

Dementia is the main clinical feature of Alzheimer's disease (AD). Orexin has recently been linked to AD pathogenesis, and exogenous orexin-A (OXA) aggravates spatial memory impairment in APP/PS1 mice. However, the effects of OXA on other types of cognitive deficits, especially in 3xTg-AD mice exhibiting both plaque and tangle pathologies, have not been reported. Furthermore, the potential electrophysiological mechanism by which OXA affects cognitive deficits and the molecular mechanism by which OXA increases amyloid ß (Aß) levels are unknown. In the present study, the effects of OXA on cognitive functions, synaptic plasticity, Aß levels, tau hyperphosphorylation, BACE1 and NEP expression, and circadian locomotor rhythm were evaluated. The results showed that OXA aggravated memory impairments and circadian rhythm disturbance, exacerbated hippocampal LTP depression, and increased Aß and tau pathologies in 3xTg-AD mice by affecting BACE1 and NEP expression. These results indicated that OXA aggravates cognitive deficits and hippocampal synaptic plasticity impairment in 3xTg-AD mice by increasing Aß production and decreasing Aß clearance through disruption of the circadian rhythm and sleep-wake cycle.

Scoparone suppresses mitophagy-mediated NLRP3 inflammasome activation in inflammatory diseases.

Recent evidence shows that targeting NLRP3 inflammasome activation is an important means to treat inflammasome-driven diseases. Scoparone, a natural compound isolated from the Chinese herb Artemisia capillaris Thunb, has anti-inflammatory activity. In this study we investigated the effect of scoparone on NLRP3 inflammasome activation in inflammatory diseases. In LPS-primed, ATP or nigericin-stimulated mouse macrophage J774A.1 cells and bone marrow-derived macrophages (BMDMs), pretreatment with scoparone (50 µM) markedly restrained canonical and noncanonical NLRP3 inflammasome activation, evidenced by suppressed caspase-1 cleavage, GSDMD-mediated pyroptosis, mature IL-1ß secretion and the formation of ASC specks. We then conducted a transcriptome analysis in scoparone-pretreated BMDMs, and found that the differentially expressed genes were significantly enriched in mitochondrial reactive oxygen species (ROS) metabolic process, mitochondrial translation and assembly process, as well as in inflammatory response. We demonstrated in J774A.1 cells and BMDMs that scoparone promoted mitophagy, a well-characterized mechanism to control mitochondrial quality and reduce ROS production and subsequent NLRP3 inflammasome activation. Mitophagy blockade by 3-methyladenine (3-MA, 5 mM) reversed the protective effects of scoparone on mitochondrial damage and inflammation in the murine macrophages. Moreover, administration of scoparone (50 mg/kg) exerted significant preventive effects via inhibition of NLRP3 activation in mouse models of bacterial enteritis and septic shock. Collectively, scoparone displays potent anti-inflammatory effects via blocking NLRP3 inflammasome activation through enhancing mitophagy, highlighting a potential action mechanism in treating inflammasome-related diseases for further clinical investigation.

Using the Apriori Algorithm to Explore Caregivers' Depression by the Combination of the Patients with Dementia and Their Caregivers.

PURPOSE: The purpose of this study was to identify the caring scenarios that result in severe depression in caregivers caring for dementia patients. PATIENTS AND METHODS: A cross-sectional study with 1111 dementia patients and their caregivers in Taiwan from October 2015 to January 2020 was conducted. Gender, age, type of dementia, clinical dementia rating, walking ability, mood symptoms, behavioral symptoms, and psychological symptoms were the variables from the dementia patients. Age, relation to the patient, employment, type of primary care, frequency of care, mood symptoms, and the score from the Center for Epidemiologic Studies Depression Scale were the variables from the caregivers. A comprehensive viewpoint of both dementia patients and their caregivers was evaluated by the Apriori algorithm to find the attributes resulting in different caregiving depressions. RESULTS: Forty-seven rules were found with 18 rules of mild depressive symptomatology, 17 rules of moderate depressive symptomatology, and 12 rules of severe depressive symptomatology. A total of 7 general rules were summarized to be the severe depressive symptomatology. The results showed that an unemployed or retired caregiver with the mood symptoms such as helplessness, anger, emotional liability, or anxiety who took care of AD patients or AD patients with a moderate severity would have severe depression. Increased care frequencies (≥6 days per week) and multiple mood problems from caregivers result in severe depression. The composition of adult children, patients' aggression, and caregivers' helplessness as well as the combinations of male patients aged 75-84 years with the caregiver's mood of helplessness or nervousness and hopelessness were highly associated with severe depression. CONCLUSION: For those caring for AD patients, severe depression was associated with the combination of different parameters to constitute each of these seven scenarios. Unlike previous studies which often evaluated one or two variables related to caregiver's depression, this study provided a more comprehensive viewpoint that enabled the collaborative team to efficiently identify and manage different scenarios by summarizing the rules of caregivers with severe depression from a systematic viewpoint.

Suvorexant ameliorates cognitive impairments and pathology in APP/PS1 transgenic mice.

Cognitive impairments and circadian rhythm disorders are the main clinical manifestations of Alzheimer's disease (AD). Orexin has been reported as abnormally elevated in the cerebrospinal fluid of AD patients, accompanied with cognitive impairments. Our recent research revealed that suvorexant, a dual orexin receptor antagonist, could improve behavioral circadian rhythm disorders in 9-month-old APP/PS1 mice. Here we further observed whether suvorexant could ameliorate the cognitive decline in APP/PS1 mice by using behavioral tests, and investigated the possible mechanisms by in vivo electrophysiological recording, western blot, and immunochemistry. The results showed that suvorexant treatment effectively ameliorated the cognitive impairments, alleviated in vivo hippocampal long-term potentiation suppression, restored the circadian phosphorylated CREB expression in the hippocampus, and reduced amyloid-ß protein deposition in the hippocampus and cortex in APP/PS1 mice. These results indicate that the neuroprotective effects of suvorexant against AD are involved in the reduction of amyloid-ß plaques, improvement of synaptic plasticity, and circadian expression of phosphorylated CREB, suggesting that suvorexant could be beneficial to the prevention and treatment of AD.

[A case report of multiple dentigerous cyst of mandible and review of literature].

Dentigerous cyst belongs to one kind of odontogenic cysts, and is also known as follicular cyst. After the formation of the crown or root of the tooth, liquid exudates between the residual enamel epithelium and the crown surface to form odontogenic cysts. Multiple odontogenic cysts are rare in the oral and maxillofacial regions, especially in different areas of the jaw. In this paper, we reported case with multiple odontogenic cysts and discussed its etiology,pathological classification,differential diagnosis and treatment.

Prenatal diagnosis of coarctation of the aorta with ventricular septal defect: A case report.

OBJECTIVE: To present an accurate prenatal diagnosis of coarctation of the aorta with ventricular septal defect and to illustrate how early diagnosis in prenatal period with proper referral and counseling can optimize management. CASE REPORT: A case with coarctation of the aorta with ventricle septal defect was found to have an abnormal three vessel view at 12 weeks, and with close follow-ups, coarctation of the aorta with ventricle septal defect was diagnosed at 24 weeks. Following the support from a multidisciplinary team that provided counseling, diagnosis, and follow-ups, the pregnant woman decided to continue with the pregnancy and had a vaginal delivery at a medical center. The newborn made an uneventful recovery after undergoing cardiac surgery on day 9. CONCLUSION: The case demonstrates the role a fetal medicine team plays in diagnosing, supporting, and seamlessly transferring the congenital heart disease case from the first line obstetrician to the cardiac surgeon. A multi-disciplinary team approach was able to lead to improved perinatal outcome of the congenital heart disease case.

Dandy-Walker syndrome with duplex kidney abnormalities in trisomy 18 - A rare case report.

OBJECTIVE: Trisomy 18 is one of the major numerical chromosomal disorders. The incidence of trisomy 18 is approximately one in 6000 live births. Dandy-Walker malformation (DWM) is the most common congenital malformation of the cerebellum, with an incidence of about one in 5000 live births. The incidence of trisomy 18 associated with DWM is rare and long-term survival rate is very low. CASE REPORT: A case involving a 39-year-old pregnant female with a case of trisomy 18 associated with DWM. CONCLUSION: The incidence of trisomy 18 associated with DWM is rare, and our report presents an unusual case that supplements our knowledge of this condition. We report a case involving a 39-year-old pregnant female with a case of trisomy 18 associated with Dandy-Walker malformation (DWM). Fetal ultrasonography showed hypoplasia of the cerebellar vermis and dilatation of the fourth ventricle and was characterized by an enlarged posterior fossa. Fetal magnetic resonance imaging showed inferior vermian hypoplasia and a large posterior fossa cyst communicating with the fourth ventricle causing high insertion of the torcular herophili, which was compatible with DWM. Furthermore, the karyotyping report revealed trisomy 18. The incidence of trisomy 18 associated with DWM is rare, and our report presents an unusual case that supplements our knowledge of this condition.

Prenatal Diagnosis of Persistent Left Superior Vena Cava is Associated with Coarctation of the Aorta - A Case Report.

A singleton pregnant woman was found to have persistent left superior vena cava (PLSVC) of the fetus at 22 weeks by ultrasound. Follow-up scans revealed PLSVC, dilated coronary sinus, dominant right heart, some pericardial effusion, and hypertrophy of the right ventricular wall. The woman had an abdominal delivery at 34 weeks due to rupture of membranes. The baby was found to have coarctation of the aorta postnatally and had aortic reconstruction at 31 days of age. A prenatal ultrasound finding of PLSVC might be associated with coarctation of the aorta and it warrants specialist follow-ups and complete workup of echocardiography prenatally and postnatally.

ZnFe2 O4 Leaves Grown on TiO2 Trees Enhance Photoelectrochemical Water Splitting.

TiO2 has excellent electrochemical properties but limited solar photocatalytic performance in light of its large bandgap. One important class of visible-wavelength sensitizers of TiO2 is based on ZnFe2 O4 , which has shown fully a doubling in performance relative to pure TiO2 . Prior efforts on this important front have relied on presynthesized nanoparticles of ZnFe2 O4 adsorbed on a TiO2 support; however, these have not yet achieved the full potential of this system since they do not provide a consistently maximized area of the charge-separating heterointerface per volume of sensitizing absorber. A novel atomic layer deposition (ALD)-enhanced synthesis of sensitizing ZnFe2 O4 leaves grown on the trunks of TiO2 trees is reported. These new materials exhibit fully a threefold enhancement in photoelectrochemical performance in water splitting compared to pristine TiO2 under visible illumination. The new materials synthesis strategy relies first on the selective growth of FeOOH nanosheets, 2D structures that shoot off from the sides of the TiO2 trees; these templates are then converted to ZnFe2 O4 with the aid of a novel ALD step, a strategy that preserves morphology while adding the Zn cation to achieve enhanced optical absorption and optimize the heterointerface band alignment.

Psychometric evaluation of the Simplified Chinese Version of the Posttraumatic Growth Inventory for assessing breast cancer survivors.

PURPOSE: Due to the rapid increase in the number of breast cancer survivors in China, it is important to have a valid instrument to assess their posttraumatic growth. We carried out a study to validate the psychometric testing of the Simplified Chinese Version of the Posttraumatic Growth Inventory (PTGI-SC) in breast cancer survivors. METHODS AND SAMPLE: A convenience sampling method was used to collect data from 1227 breast cancer survivors at eight tertiary hospitals and some anticancer groups in Beijing between April 2010 and April 2012. We tested the item discrimination, content validity, construct validity, and internal consistency of the PTGI-SC. KEY RESULTS: The difficulties of the items ranged from 0.432 to 0.737, and their discrimination correlation coefficients ranged from 0.324 to 0.721. The content validity index of the inventory was 0.98. Five factors were extracted using exploratory factor analysis, and their cumulative contribution was determined to be 68.3%. The results of the confirmatory factor analysis include χ(2)/df=3.912, SRMR = 0.046, RMSEA = 0.055, IFI = 0.932, CFI = 0.932, and Cronbach's α = 0.90. CONCLUSION: The validity and reliability of the PTGI-SC support its use for evaluating Chinese breast cancer survivors. This reliable and valid inventory can be used in practice to measure PTG in breast cancer survivors and provide information about their psychological adjustment. It can also facilitate further psychological research among Chinese breast cancer survivors.

Posttraumatic growth and associated socio-demographic and clinical factors in Chinese breast cancer survivors.

PURPOSE: The factors that affect posttraumatic growth (PTG) in breast cancer survivors have been discussed for many years, but it remains unclear which are most influential. The purpose of this study was to determine the level of PTG and identify associated socio-demographic and clinical factors in Chinese breast cancer survivors. METHODS AND SAMPLE: A descriptive research design with a convenience sampling method was employed to collect data using the simplified Chinese version of the Posttraumatic Growth Inventory (PTGI-SC). This questionnaire was administered to 1227 participants recruited from eight tertiary hospitals and cancer survivor groups in Beijing between April 2010 and April 2012. KEY RESULTS: PTG is present in Chinese breast cancer survivors, with an average PTGI-SC score of 70.18 ± 15.85. There were five variables in the regression model: exercise, other chronic disease, income, education level, and work status. Exercise showed the strongest positive association with PTG after breast cancer. Household income and educational level also positively influenced PTG. Survivors with other accompanying chronic diseases had lower PTG. Retired survivors had the highest PTG, those working had moderate PTG, and those on sick leave had the lowest PTG. CONCLUSIONS: PTG is common among Chinese breast cancer survivors. It is positively associated with exercise, income, education, and retirement, and negatively associated with the presence of other chronic diseases and working. The results may provide information on how to promote the development of PTG while nursing breast cancer survivors.

[Role of stress in depression insomnia and sleep characteristics of commonly used animal stress models].

Depression and insomnia are intimately related. Depressed patients usually manifest sleep discontinuity and early awakening, reduced or no slow wave sleep (SWS) and shortened latency of rapid eye movement (REM) sleep. These sleep abnormalities are very similar to those caused by over activated hypothalamic-pituitary-adrenal (HPA) axis with stress. Therefore, the animal models developed by post-traumatic stress disorder or chronic unpredictable mild stress could be used to evaluate drugs which have effects of both anti-depression and improvement of sleep quality, and to provide a more reliable platform for further studis on the mechanisms of depression and accompanied insomnia. This review mainly focuses on the typical features of sleep disturbance of depression, possible pathophysiological mechanisms, establishment of animal stress models and analysis of their abnormal sleep characteristics.