Inherited chromosomally-integrated human herpes virus 6 confounding test results in a patient with myelitis and optic neuritis - A case report.

A case of the 'perfect storm' of myelin oligodendrocyte glycoprotein (MOG) antibody-mediated myelitis, human herpesvirus 6 (HHV-6) reactivation, and COVID-19 infection was reported in 2021. This article reports a case of a similarly observed clinical triad, but with a different conclusion and explanation supported by laboratory test results and evidence from our literature review.

Performance Optimization in Frequency Estimation of Noisy Signals: Ds-IpDTFT Estimator.

This research presents a comprehensive study of the dichotomous search iterative parabolic discrete time Fourier transform (Ds-IpDTFT) estimator, a novel approach for fine frequency estimation in noisy exponential signals. The proposed estimator leverages a dichotomous search process before iterative interpolation estimation, which significantly reduces computational complexity while maintaining high estimation accuracy. An in-depth exploration of the relationship between the optimal parameter p and the unknown parameter δ forms the backbone of the methodology. Through extensive simulations and real-world experiments, the Ds-IpDTFT estimator exhibits superior performance relative to other established estimators, demonstrating robustness in noisy conditions and stability across varying frequencies. This efficient and accurate estimation method is a significant contribution to the field of signal processing and offers promising potential for practical applications.

Comorbidity Patterns of Older Lung Cancer Patients in Northeast China: An Association Rules Analysis Based on Electronic Medical Records.

PURPOSES: This study aims to identify the comorbidity patterns of older men with lung cancer in China. METHODS: We analyzed the electronic medical records (EMRs) of lung cancer patients over age 65 in the Jilin Province of China. The data studied were obtained from 20 hospitals of Jilin Province in 2018. In total, 1510 patients were identified. We conducted a rank-frequency analysis and social network analysis to identify the predominant comorbidities and comorbidity networks. We applied the association rules to mine the comorbidity combination with the values of confidence and lift. A heatmap was utilized to visualize the rules. RESULTS: Our analyses discovered that (1) there were 31 additional medical conditions in older patients with lung cancer. The most frequent comorbidities were pneumonia, cerebral infarction, and hypertension. (2) The network-based analysis revealed seven subnetworks. (3) The association rules analysis provided 41 interesting rules. The results revealed that hypertension, ischemic cardiomyopathy, and pneumonia are the most frequent comorbid combinations. Heart failure may not have a strong implicating role in these comorbidity patterns. Cerebral infarction was rarely combined with other diseases. In addition, glycoprotein metabolism disorder comorbid with hyponatremia or hypokalemia increased the risk of anemia by more than eight times in older lung cancer patients. CONCLUSIONS: This study provides evidence on the comorbidity patterns of older men with lung cancer in China. Understanding the comorbidity patterns of older patients with lung cancer can assist clinicians in their diagnoses and contribute to developing healthcare policies, as well as allocating resources.

Comorbidity in Older Patients Hospitalized with Cancer in Northeast China based on Hospital Discharge Data.

Patients with cancer often carry the dual burden of the cancer itself and other co-existing medical conditions. The problems associated with comorbidities among elderly cancer patients are more prominent compared with younger patients. This study aimed to identify common cancer-related comorbidities in elderly patients through routinely collected hospital discharge data and to use association rules to analyze the prevalence and patterns of these comorbidities in elderly cancer patients at different cancer sites. We collected the discharge data of 80,574 patients who were diagnosed with cancers of the esophagus, stomach, colorectum, liver, lung, female breast, cervix, and thyroid between 2016 and 2018. The same number of non-cancer patients were randomly selected as the control group and matched with the case group by age and gender. The results showed that cardiovascular diseases, metabolic diseases, digestive diseases, and anemia were the most common comorbidities in elderly patients with cancer. The comorbidity patterns differed based on the cancer site. Elderly patients with liver cancer had the highest risk of comorbidities, followed by lung cancer, gastrointestinal cancer, thyroid cancer, and reproductive cancer. For example, elderly patients with liver cancer had the higher risk of the comorbid infectious and digestive diseases, whereas patients with lung cancer had the higher risk of the comorbid respiratory system diseases. The findings can assist clinicians in diagnosing comorbidities and contribute to the allocation of medical resources.

Patterns of Comorbidity in Hepatocellular Carcinoma: A Network Perspective.

Hepatocellular carcinoma (HCC) is a common and fatal cancer. People with HCC report higher odds of comorbidity compared with people without HCC. To explore the association between HCC and medical comorbidity, we used routinely collected clinical data and applied a network perspective. In the network perspective, we used correlation analysis and community detection tests that described direct relationships among comorbidities. We collected 14,891 patients with HCC living in Jilin Province, China, between 2016 and 2018. Cirrhosis was the most common comorbidity of HCC. Hypertension and renal cysts were more common in male patients, while chronic viral hepatitis C, hypersplenism, hypoproteinemia, anemia and coronary heart disease were more common in female patients. The proportion of chronic diseases in comorbidities increased with age. The main comorbidity patterns of HCC were: HCC, cirrhosis, chronic viral hepatitis B, portal hypertension, ascites and other common complications of cirrhosis; HCC, hypertension, diabetes mellitus, coronary heart disease and cerebral infarction; and HCC, hypoproteinemia, electrolyte disorders, gastrointestinal hemorrhage and hemorrhagic anemia. Our findings provide comprehensive information on comorbidity patterns of HCC, which may be used for the prevention and management of liver cancer.

Iterative Trajectory Optimization for Physical-Layer Secure Buffer-Aided UAV Mobile Relaying.

With the fast development of commercial unmanned aerial vehicle (UAV) technology, there are increasing research interests on UAV communications. In this work, the mobility and deployment flexibility of UAVs are exploited to form a buffer-aided relaying system assisting terrestrial communication that is blocked. Optimal UAV trajectory design of the UAV-enabled mobile relaying system with a randomly located eavesdropper is investigated from the physical-layer security perspective to improve the overall secrecy rate. Based on the mobility of the UAV relay, a wireless channel model that changes with the trajectory and is exploited for improved secrecy is established. The secrecy rate is maximized by optimizing the discretized trajectory anchor points based on the information causality and UAV mobility constraints. However, the problem is non-convex and therefore difficult to solve. To make the problem tractable, we alternatively optimize the increments of the trajectory anchor points iteratively in a two-dimensional space and decompose the problem into progressive convex approximate problems through the iterative procedure. Convergence of the proposed iterative trajectory optimization technique is proved analytically by the squeeze principle. Simulation results show that finding the optimal trajectory by iteratively updating the displacements is effective and fast converging. It is also shown by the simulation results that the distribution of the eavesdropper location influences the security performance of the system. Specifically, an eavesdropper further away from the destination is beneficial to the system's overall secrecy rate. Furthermore, it is observed that eavesdropper being further away from the destination also results in shorter trajectories, which implies it being energy-efficient as well.

Effect of alcohol extract of Acanthus ilicifolius L. on anti-duck hepatitis B virus and protection of liver.

ETHNOPHARMACOLOGICAL RELEVANCE: Acanthus ilicifolius L. is an important medicinal mangrove plant. It is popularly used for its anti-inflammatory, antioxidant activity and hepatoprotective effects. The present study was conducted to evaluate the effect of treatment with alcohol extract of Acanthus ilicifolius L. on duck hepatitis B. MATERIALS AND METHODS: One-day-old Guangxi shelducks injected intraperitoneally with strong positive duck hepatitis B virus (DHBV) serum were used to establish a duck hepatitis B animal model in the study. The ducks were respectively administered in different groups with low-, middle- and high-dose alcohol extracts of Acanthus ilicifolius L., the positive control drug acyclovir (ACV) and double-distilled water. The levels of serum DHBV DNA were detected by fluorescence quantitative PCR (FQ-PCR). Duck hepatitis B surface antigen (DHBsAg) and duck hepatitis B e antigen (DHBeAg) OD values in the serum were measured by ELISA. The activity of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) in the serum was measured, and the livers were taken for histopathological examination. RESULTS: The levels of serum DHBV DNA and the values of DHBsAg and DHBeAg OD were not significant in any of the dose extract groups. However, the ALT activity was obviously lower in the middle- and high-dose extract groups. It was also found that a high dose of alcohol extract could reduce the activity of AST significantly and significantly improve hepatic pathological effects. CONCLUSIONS: High-dose alcohol extract of Acanthus ilicifolius L. has an obvious protective effect on the liver function and liver tissue. However, the present study finds that Acanthus ilicifolius L. cannot inhibit the replication of duck hepatitis B virus.

Insufficient screening knowledge in Chinese interns: a survey in ten leading medical schools.

OBJECTIVE: This study aimed to investigate Chinese medical interns' cancer knowledge and associated factors, focusing on cancer screening. METHODS: A questionnaire survey was conducted in ten leading Chinese medical schools from June to July in 2011. Medical interns were invited to fill the questionnaire. RESULTS: Out of the 1350 copies sent, 1135 eligible responses were returned. Around 50% of interns had positive attitude toward oncology, but the knowledge score was low, particularly in screening. The percentages of scores were 44.8% (8.95/20) for overall and only 29.6% (2.07/7) for screening. The majority of internship length in oncology department was eight to fourteen days. Screening and prevention was ranked as third most taught, following diagnosis and treatment. Multivariate analysis showed that positive attitude to oncology correlated with positive self-evaluated overall (OR = 1.76, 95% CI (1.45, 2.12)) and screening (OR = 1.62, 95% CI (1.35, 1.95)) competence, but unexpectedly predicted lower screening score (OR = 0.77, 95% CI (0.61, 0.97)). Interns with positive self-evaluated screening competence were not found to possess higher cancer screening knowledge. CONCLUSION: Current medical education in Chinese medical schools fails to equip interns with optimal cancer knowledge, particularly in screening, even in interns who hold positive view to oncology. Interns' self-evaluated competence is not proportional to their knowledge scores.

Stage dependent and androgen inductive expression of orphan receptor TR4 in rat testis.

In this study, we investigated the expression of TR4 in different stages of seminiferous tubules and the relationship between TR4 and androgen in rat testis. We found that TR4 was stage-dependently expressed in rat seminiferous tubules, T withdrawal induced by high doses of testosterone undecanoate and ethane dimethane sulfonate inhibit TR4 expression in rat testis, and testosterone induced TR4 expression in co-cultured primary germ/Sertoli cells. Furthermore, we demonstrated that androgen receptor could enhance TR4-mediated transactivation activity in testis cells in the presence of testosterone. Together, these data indicate that the expression of TR4 in rat testis is stage dependent and androgen inductive, and suggest the important role of orphan receptor TR4 in spermatogenesis.

Targeted inactivation of testicular nuclear orphan receptor 4 delays and disrupts late meiotic prophase and subsequent meiotic divisions of spermatogenesis.

Testicular orphan nuclear receptor 4 (TR4) is specifically and stage-dependently expressed in late-stage pachytene spermatocytes and round spermatids. In the developing mouse testis, the highest expression of TR4 can be detected at postnatal days 16 to 21 when the first wave of spermatogenesis progresses to late meiotic prophase. Using a knockout strategy to delete TR4 in mice, we found that sperm production in TR4(-/-) mice is reduced. The comparison of testes from developing TR4(+/+) and TR4(-/-) mice shows that spermatogenesis in TR4(-/-) mice is delayed. Analysis of the first wave of spermatogenesis shows that the delay can be due to delay and disruption of spermatogenesis at the end of late meiotic prophase and subsequent meiotic divisions. Seminiferous tubule staging shows that stages X to XII, where late meiotic prophase and meiotic divisions take place, are delayed and disrupted in TR4(-/-) mice. Histological examination of testis sections from TR4(-/-) mice shows degenerated primary spermatocytes and some necrotic tubules. Testis-specific gene analyses show that the expression of sperm 1 and cyclin A1, which are genes expressed at the end of meiotic prophase, was delayed and decreased in TR4(-/-) mouse testes. Taken together, results from TR4(+/+) and TR4(-/-) mice indicate that TR4 is essential for normal spermatogenesis in mice.

TR2 orphan receptor functions as negative modulator for androgen receptor in prostate cancer cells PC-3.

BACKGROUND: Both androgen receptor (AR) and orphan receptor TR2 (TR2) belong to the steroid nuclear receptor superfamily and are expressed in prostate cancer tissue and cell lines. AR has been known to be involved in prostate proliferation and prostate cancer progression. AR binds to androgen response elements and regulates target gene expression via a mechanism involving coregulators. However, the function of TR2 in prostate and prostate cancer and the relationship between TR2 and AR in the prostate cancer is unclear. METHODS: Transient transfection and CAT reporter gene assays were employed to assess AR-mediated transactivation. The expression level of prostate specific antigen (PSA) was measured by Northern blot analysis. The interaction between AR and TR2 was assessed by glutathione-S-transferase (GST) pull-down assay and mammalian two-hybrid system assay. RESULTS: Orphan nuclear receptor TR2 suppressed androgen-mediated transactivation in prostate cancer PC-3 cells, and over-expression of TR2 suppressed PSA expression. The suppression of AR mediated transactivation by TR2 is not due to competition for the limited coregulator availability by these two receptors, but possibly through the interaction between TR2 and AR nuclear receptors. CONCLUSIONS: TR2 may function as a negative modulator to suppress AR function in prostate cancer. Further studies on how to control TR2 function may result in the ability to modulate AR function in prostate cancer.

Disruption of TR4 orphan nuclear receptor reduces the expression of liver apolipoprotein E/C-I/C-II gene cluster.

Apolipoprotein E (apoE) is synthesized in many tissues, and the liver is the primary site from which apoE redistributes cholesterol and other lipids to peripheral tissues. Here we demonstrate that the TR4 orphan nuclear receptor (TR4) can induce apoE expression in HepG2 cells. This TR4-mediated regulation of apoE gene expression was further confirmed in vivo using TR4 knockout mice. Both serum apoE protein and liver apoE mRNA levels were significantly reduced in TR4 knockout mice. Gel shift and luciferase reporter gene assays further demonstrated that TR4 can induce apoE gene expression via a TR4 response element located in the hepatic control region that is 15 kb downstream of the apoE gene. Furthermore our in vivo data from TR4 knockout mice prove that TR4 can also regulate apolipoprotein C-I and C-II gene expression via the TR4 response element within the hepatic control region. Together our data show that loss of TR4 down-regulates expression of the apoE/C-I/C-II gene cluster in liver cells, demonstrating important roles of TR4 in the modulation of lipoprotein metabolism.

TR3 orphan nuclear receptor mediates apoptosis through up-regulating E2F1 in human prostate cancer LNCaP cells.

Early studies suggested both TR3 orphan receptor (TR3) and apoptosis mediator E2F1 might play an important role in mediating prostate cancer cell apoptosis. Their linkage and relationship, however, remain unclear. Here we found that 12-O-tetradecanoylphorbol-13-acetate (TPA) could induce cell apoptosis via induction of TR3 and E2F1 expression in LNCaP prostate cancer cells. Addition of antisense E2F1 could partially rescue the TR3-mediated cell apoptosis, and transfection of the TR3 dominant-negative plasmid could block the TR3-induced E2F1 expression. These data suggest that TPA is able to induce LNCaP cell apoptosis via induction of TR3 resulting in the induction of E2F1. Promoter reporter assays show that TR3 can induce E2F1 expression via binding to the TR3 response element (TR3RE) in the E2F1 promoter -316 to -324 bp region. TR3 can bind specifically to this TR3RE with a Kd of 6.29 nm, and mutations of this E2F1-TR3RE can partially block the TR3-mediated E2F1 expression. Taken together, these data suggest that TPA is able to induce cell apoptosis via a TPA --> TR3 --> E2F1 --> apoptosis pathway in LNCaP cells. Further studies of how to modulate this pathway may allow us to better understand how to control the prostate cancer growth.

Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues.

By using a cre-lox conditional knockout strategy, we report here the generation of androgen receptor knockout (ARKO) mice. Phenotype analysis shows that ARKO male mice have a female-like appearance and body weight. Their testes are 80% smaller and serum testosterone concentrations are lower than in wild-type (wt) mice. Spermatogenesis is arrested at pachytene spermatocytes. The number and size of adipocytes are also different between the wt and ARKO mice. Cancellous bone volumes of ARKO male mice are reduced compared with wt littermates. In addition, we found the average number of pups per litter in homologous and heterozygous ARKO female mice is lower than in wt female mice, suggesting potential defects in female fertility and/or ovulation. The cre-lox ARKO mouse provides a much-needed in vivo animal model to study androgen functions in the selective androgen target tissues in female or male mice.

Suppression of estrogen receptor-mediated transcription and cell growth by interaction with TR2 orphan receptor.

The transcriptional activity of the estrogen receptor (ER) is known to be highly modulated by the character and amount of coregulator proteins present in the cells. TR2 orphan receptor (TR2), a member of the nuclear receptor superfamily without identified ligands, is found to be expressed in the breast cancer cell lines and to function as a repressor to suppress ER-mediated transcriptional activity. Utilizing an interaction blocker, ER-6 (amino acids 312-340), responsible for TR2 interaction, the suppression of ER by TR2 could be reversed, suggesting that this suppression is conferred by the direct protein-protein interaction. Administration of antisense TR2, resulting in an enhancement of ER transcriptional activity in MCF7 cells, indicates that endogenous TR2 normally suppresses ER-mediated signaling. To gain insights into the molecular mechanism by which TR2 suppresses ER, we found that TR2 could interrupt ER DNA binding via formation of an ER-TR2 heterodimer that disrupted the ER homodimerization. The suppression of ER transcription by TR2 consequently caused the inhibition of estrogen-induced cell growth and G(1)/S transition in estrogen-dependent breast cancer cells. Taken together in addition to the potential roles in spermatogenesis and neurogenesis, our data provide a novel biological function of TR2 that may exert an important repressor in regulating ER activity in mammary glands.

Spermatogenesis and testis development are normal in mice lacking testicular orphan nuclear receptor 2.

Early in vitro cell culture studies suggested that testicular orphan nuclear receptor 2 (TR2), a member of the nuclear receptor superfamily, may play important roles in the control of several pathways including retinoic acids, vitamin D, thyroid hormones, and ciliary neurotrophic factor. Here we report the surprising results showing that mice lacking TR2 are viable and have no serious developmental defects. Male mice lacking TR2 have functional testes, including normal sperm number and motility, and both male and female mice lacking TR2 are fertile. In heterozygous TR2(+/-) male mice we found that beta-galactosidase, the indicator of TR2 protein expression, was first detected at the age of 3 weeks and its expression pattern was restricted mainly in the spermatocytes and round spermatids. These protein expression patterns were further confirmed with Northern blot analysis of TR2 mRNA expression. Together, results from TR2-knockout mice suggest that TR2 may not play essential roles in spermatogenesis and normal testis development, function, and maintenance. Alternatively, the roles of TR2 may be redundant and could be played by other close members of the nuclear receptor superfamily such as testicular orphan receptor 4 (TR4) or unidentified orphan receptors that share many similar functions with TR2. Further studies with double knockouts of both orphan nuclear receptors, TR2 and TR4, may reveal their real physiological roles.