VIRMA promotes nasopharyngeal carcinoma, tumorigenesis, and metastasis by upregulation of E2F7 in an m6A-dependent manner.

The N6-methyladenosine (m6A) modification possesses new and essential roles in tumor initiation and progression by regulating mRNA biology. However, the role of aberrant m6A regulation in nasopharyngeal carcinoma (NPC) remains unclear. Here, through comprehensive analyses of NPC cohorts from the GEO database and our internal cohort, we identified that VIRMA, an m6A writer, is significantly upregulated in NPC and plays an essential role in tumorigenesis and metastasis of NPC, both in vitro and in vivo. High VIRMA expression served as a prognostic biomarker and was associated with poor outcomes in patients with NPC. Mechanistically, VIRMA mediated the m6A methylation of E2F7 3'-UTR, then IGF2BP2 bound, and maintained the stability of E2F7 mRNA. An integrative high-throughput sequencing approach revealed that E2F7 drives a unique transcriptome distinct from the classical E2F family in NPC, which functioned as an oncogenic transcriptional activator. E2F7 cooperated with CBFB-recruited RUNX1 in a non-canonical manner to transactivate ITGA2, ITGA5, and NTRK1, strengthening Akt signaling-induced tumor-promoting effect.

m6A-enriched lncRNA LINC00839 promotes tumor progression by enhancing TAF15-mediated transcription of amine oxidase AOC1 in nasopharyngeal carcinoma.

Dysregulation of long noncoding RNAs (lncRNAs) contributes to tumorigenesis by modulating specific cancer-related pathways, but the roles of N6-methyladenosine (m6A)-enriched lncRNAs and underlying mechanisms remain elusive in nasopharyngeal carcinoma (NPC). Here, we reanalyzed the previous genome-wide analysis of lncRNA profiles in 18 pairs of NPC and normal tissues as well as in ten paired samples from NPC with or without post-treatment metastases. We discerned that an oncogenic m6A-enriched lncRNA, LINC00839, which was substantially upregulated in NPC and correlated with poor clinical prognosis, promoted NPC growth and metastasis both in vitro and in vivo. Mechanistically, by using RNA pull-down assay combined with mass spectrometry, we found that LINC00839 interacted directly with the transcription factor, TATA-box binding protein associated factor (TAF15). Besides, chromatin immunoprecipitation and dual-luciferase report assays demonstrated that LINC00839 coordinated the recruitment of TAF15 to the promoter region of amine oxidase copper-containing 1 (AOC1), which encodes a secreted glycoprotein playing vital roles in various cancers, thereby activating AOC1 transcription in trans. In this study, potential effects of AOC1 in NPC progression were first proposed. Moreover, ectopic expression of AOC1 partially rescued the inhibitory effect of downregulation of LINC00839 in NPC. Furthermore, we showed that silencing vir-like m6A methyltransferase-associated (VIRMA) and insulin-like growth factor 2 mRNA-binding proteins 1 (IGF2BP1) attenuated the expression level and RNA stability of LINC00839 in an m6A-dependent manner. Taken together, our study unveils a novel oncogenic VIRMA/IGF2BP1-LINC00839-TAF15-AOC1 axis and highlights the significance and prognostic value of LINC00839 expression in NPC carcinogenesis.

Thyroid dysfunction in Chinese nasopharyngeal carcinoma after anti-PD-1 therapy and its association with treatment response.

BACKGROUND: Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated efficacy in nasopharyngeal carcinoma (NPC). Thyroid dysfunction is among the most common immune-related adverse events. This study aimed to explore the clinical pattern of thyroid dysfunction and its relationship with survival marker in nonmetastatic NPC after immunotherapy. METHODS: From January 1, 2019, to December 31, 2021, 165 pairs of nonmetastatic NPC patients (165 with and 165 without anti-PD-1 immunotherapy) matched by the propensity score matching method were included in this study. Thyroid function was assessed retrospectively before the first treatment and during each immunotherapy cycle. RESULTS: The spectrum of thyroid dysfunction was different between the immunotherapy and control groups (P < 0.001). Compared with the control group, patients in the immunotherapy group developed more hypothyroidism (14.545% vs. 7.273%), less hyperthyroidism (10.909% vs. 23.636%), and a distinct pattern, biphasic thyroid dysfunction (3.030% vs. 0%). Immunotherapy also accelerates the onset of hypothyroidism, which was earlier with a median onset time difference of 32 days (P < 0.001). Patients who acquired thyroid dysfunction during immunotherapy had better complete biological response to treatment (OR, 10.980; P = 0.042). CONCLUSIONS: For nonmetastatic NPC, thyroid dysfunction was associated with better response to treatment in immunotherapy but not in routine treatment. Thyroid function could be used as a predictor for survival and should be under regular and intensive surveillance in clinical practice of anti-PD-1 immunotherapy for nonmetastatic NPC.

Liquid biopsy posttreatment surveillance in endemic nasopharyngeal carcinoma: a cost-effective strategy to integrate circulating cell-free Epstein-Barr virus DNA.

BACKGROUND: The optimal posttreatment surveillance strategy for nasopharyngeal carcinoma (NPC) remains unclear. Circulating cell-free Epstein-Barr virus (cfEBV) DNA has been recognized as a promising biomarker to facilitate early detection of NPC recurrence. Therefore, we aim to determine whether integrating circulating cfEBV DNA into NPC follow-up is cost-effective. METHODS: For each stage of asymptomatic nonmetastatic NPC patients after complete remission to primary NPC treatment, we developed a Markov model to compare the cost-effectiveness of the following surveillance strategies: routine follow-up strategy, i.e., (1) routine clinical physical examination; routine imaging strategies, including (2) routine magnetic resonance imaging plus computed tomography plus bone scintigraphy (MRI + CT + BS); and (3) routine 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT); cfEBV DNA-guided imaging strategies, including (4) cfEBV DNA-guided MRI + CT + BS and (5) cfEBV DNA-guided PET/CT. Clinical probabilities, utilities, and costs were derived from published studies or databases. Sensitivity analyses were performed. RESULTS: For all disease stages, cfEBV DNA-guided imaging strategies demonstrated similar survival benefits but were considerably more economical than routine imaging strategies. They only required approximately one quarter of the number of imaging studies compared with routine imaging strategies to detect one recurrence. Specifically, cfEBV DNA-guided MRI + CT + BS was most cost-effective for stage II (incremental cost-effectiveness ratio [ICER] $57,308/quality-adjusted life-year [QALY]) and stage III ($46,860/QALY) patients, while cfEBV DNA-guided PET/CT was most cost-effective for stage IV patients ($62,269/QALY). However, routine follow-up was adequate for stage I patients due to their low recurrence risk. CONCLUSIONS: The cfEBV DNA-guided imaging strategies are effective and cost-effective follow-up methods in NPC. These liquid biopsy-based strategies offer evidence-based, stage-specific surveillance modalities for clinicians and reduce disease burden for patients.

Changes of T lymphocyte subsets in patients with HIV-negative symptomatic neurosyphilis.

OBJECTIVES: The host immune response could be an imperative factor in the pathogenesis of neurosyphilis, but the role of T lymphocyte subsets remains unclear. In the present study, we assessed the CD4+ T and CD8+ T cell subsets in the peripheral blood of patients with HIV-negative symptomatic neurosyphilis and then explored the clinical application value of neurosyphilis. METHODS: In total, 24 patients with HIV-negative symptomatic neurosyphilis and 22 patients with syphilis/non-neurosyphilis were included in this study and cerebrospinal fluid (CSF) and blood samples were obtained. Th1, Th2, Th17, Th9, CD8+IFN-γ+, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells were identified by flow cytometry. RESULTS: The levels of CD8+IFN-γ+ were significantly increased in the peripheral blood of neurosyphilis patients compared to that in syphilis/non-neurosyphilis patients, but it was opposite to Th2, Th9, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells. Dendritic cells (DCs) of neurosyphilis matured by T. pallidum induced the development of a combination of IFN-γ-producing Th1 cells. The number of CD8+IL-17 + cells was significantly correlated with the CSF RPR and CSF TPPA levels. ROC curve analysis revealed that the number of CD8+IFN-γ+ cells could be a potential biomarker for neurosyphilis from non-neurosyphilis/syphilis. CONCLUSIONS: High expression of CD8+IFN-γ+ cells and low expression of CD8+IL-17 + cells in patients with symptomatic neurosyphilis, which explains the pathogenesis of symptomatic neurosyphilis, meanwhile CD8+IFN-γ+ cells may be a better indicator in classifying symptomatic neurosyphilis from non-neurosyphilis/syphilis among patients without HIV infection.

Molecular Docking and Molecular Dynamics (MD) Simulation of Human Anti-Complement Factor H (CFH) Antibody Ab42 and CFH Polypeptide.

An understanding of the interaction between the antibody and its targeted antigen and knowing of the epitopes are critical for the development of monoclonal antibody drugs. Complement factor H (CFH) is implied to play a role in tumor growth and metastasis. An autoantibody to CHF is associated with anti-tumor cell activity. The interaction of a human monoclonal antibody Ab42 that was isolated from a cancer patient with CFH polypeptide (pCFH) antigen was analyzed by molecular docking, molecular dynamics (MD) simulation, free energy calculation, and computational alanine scanning (CAS). Experimental alanine scanning (EAS) was then carried out to verify the results of the theoretical calculation. Our results demonstrated that the Ab42 antibody interacts with pCFH by hydrogen bonds through the Tyr315, Ser100, Gly33, and Tyr53 residues on the complementarity-determining regions (CDRs), respectively, with the amino acid residues of Pro441, Ile442, Asp443, Asn444, Ile447, and Thr448 on the pCFH antigen. In conclusion, this study has explored the mechanism of interaction between Ab42 antibody and its targeted antigen by both theoretical and experimental analysis. Our results have important theoretical significance for the design and development of relevant antibody drugs.

Dual role of polyamines in heart ischemia/reperfusion injury through regulation of mitochondrial permeability transition pore.

Polyamines (putrescine, spermidine, and spermine) are essential polycations that play important roles in various physiological and pathophysiological processes in mammalian cells. The study was to investigate their role in cardioprotection against ischemia/reperfusion (I/R) injury and the underlying mechanism. Isolated hearts from male Sprague-Dawley rats were Langendorff-perfused and cardiac I/R was achieved by 30 min of global ischemia followed by 120 min of reperfusion. Different concentrations of polyamines (0.1, 1, 10, and 15 µmol/L of putrescine, spermidine, and spermine), cyclosporin A (0.2 µmol/L), or atractyloside (20 µmol/L) were given 10 min before the onset of reperfusion. The hemodynamics were monitored; the lactate dehydrogenase (LDH) levels in the coronary effluent were measured spectrophotometrically; infarct size was determined by the 2,3,5-triphenyltetrazolium chloride staining method; and mitochondrial permeability transition pore (MPTP) opening was determined spectrophotometrically by the Ca2+-induced swelling of isolated cardiac mitochondria. The results showed that compared to I/R alone, 0.1 and 1 µmol/L polyamines treatment improved heart function, reduced LDH release, decreased infarct size, and these effects were inhibited by atractyloside (MPTP activator). In isolated mitochondria from normal rats, 0.1 and 1 µmol/L polyamines treatment inhibited MPTP opening. However, 10 and 15 µmol/L polyamines treatment had the opposite effects, and these effects were inhibited by cyclosporin A (MPTP inhibitor). Our findings showed that polyamines may have either protective or damaging effects on hearts suffering from I/R by inhibiting or activating MPTP opening.

Comparison of Clinical and Laboratory Characteristics of General Paresis and Non-Neurosyphilis Dementia.

BACKGROUND: The differential diagnosis of general paresis (GP) and non-neurosyphilis (NS) dementia is not clearly defined. The present study examined the differences in clinical and laboratory features of GP and non-NS dementia. MATERIALS AND METHODS: We retrospectively examined clinical and laboratory features of 85 GP patients and 196 non-NS dementia patients. Data were collected from Zhongshan Hospital between June 2005 and June 2014. RESULTS: The GP group had a higher percentage of males (83.53%, 71/85) and younger median age ([52 [interquartile range 47.0-61.0] vs. 76 [68.3-82.0] years) than the non-NS dementia group. GP have higher Mini-Mental State Examination (MMSE; Z = -5.809; p = 0.000) than non-NS dementia. Distribution of CDR scores were significantly higher in the non-NS group than GP group (χ2 = 29.153; p = 0.000). The laboratory findings showed significantly different total cholesterol (CH), low-density lipoprotein CH and homocysteine levels between the 2 groups. Serologic testing for syphilis revealed that the GP group had higher seropositive rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) rates than the non-NS dementia group (96.47% [82/85] vs. 0.51% [1/196], Z = -2.663, p = 0.008; 100% [85/85] vs. 1.02% [2/196], Z = -2.663, p = 0.008). Interestingly, cerebrospinal fluid (CSF) biochemical indices, including pleocytosis rates, increased protein levels, and positive RPR and TPPA rates in the GP group were higher than that in the non-NS dementia group. CONCLUSIONS: Based on these preliminary data, patients with clinically evident symptoms of dementia, especially middle-aged males, should undergo blood tests for syphilis. All patients with positive serology results should undergo CSF examinations to diagnose GP dementia before further pharmaceutical and behavioral interventions.

Temperature and photoperiod as environmental cues affect body mass and thermoregulation in Chinese bulbuls, Pycnonotus sinensis.

Seasonal changes in temperature and photoperiod are important environmental cues used by small birds to adjust their body mass (Mb) and thermogenesis. However, the relative importance of these cues with respect to seasonal adjustments in Mb and thermogenesis is difficult to distinguish. In particular, the effects of temperature and photoperiod on energy metabolism and thermoregulation are not well known in many passerines. To address this problem, we measured the effects of temperature and photoperiod on Mb, energy intake, resting metabolic rate (RMR), organ mass and physiological and biochemical markers of metabolic activity in the Chinese bulbul (Pycnonotus sinensis). Groups of Chinese bulbuls were acclimated in a laboratory to the following conditions: (1) warm and long photoperiod, (2) warm and short photoperiod, (3) cold and long photoperiod, and (4) cold and short photoperiod, for 4 weeks. The results indicate that Chinese bulbuls exhibit adaptive physiological regulation when exposed to different temperatures and photoperiods. Mb, RMR, gross energy intake and digestible energy intake were higher in cold-acclimated than in warm-acclimated bulbuls, and in the short photoperiod than in the long photoperiod. The resultant flexibility in energy intake and RMR allows Chinese bulbuls exposed to different temperatures and photoperiods to adjust their energy balance and thermogenesis accordingly. Cold-acclimated birds had heightened state-4 respiration and cytochrome c oxidase activity in their liver and muscle tissue compared with warm-acclimated birds indicating the cellular mechanisms underlying their adaptive thermogenesis. Temperature appears to be a primary cue for adjusting energy budget and thermogenic ability in Chinese bulbuls; photoperiod appears to intensify temperature-induced changes in energy metabolism and thermoregulation.

Novel predictors of neurosyphilis among HIV-negative syphilis patients with neurological symptoms: an observational study.

BACKGROUND: Known predictors of neurosyphilis were mainly drawn from human immunodeficiency virus (HIV)-infected syphilis patients, which may not be applicable to HIV-negative populations as they have different characteristics, particularly those with neurological symptoms. This study aimed to identify novel predictors of HIV-negative symptomatic neurosyphilis (S-NS). METHODS: From June 2005 to June 2015, 370 HIV-negative syphilis patients with neurological symptoms were recruited, consisting of 191 S-NS patients (including 123 confirmed neurosyphilis and 68 probable neurosyphilis patients) and 179 syphilis/non-neurosyphilis (N-NS) patients. Clinical and laboratory characteristics of S-NS were compared with N-NS to identify factors predictive of S-NS. Serum rapid plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and their parallel testing format for screening S-NS were evaluated. RESULTS: The likelihood of S-NS was positively associated with the serum RPR and TPPA titers. The serum TPPA titers performed better than the serum RPR titers in screening S-NS. The optimal cut-off points to recognize S-NS were serum RPR titer ≥1:4 and serum TPPA titer ≥1:2560 respectively. A parallel testing format of a serum RPR titer ≥1:2 and serum TPPA titer ≥1:1280 screened out 95.8% of S-NS and all confirmed cases of neurosyphilis. S-NS was independently associated with male sex, serum RPR titer ≥1:4, serum TPPA titer ≥1:2560, and elevated serum creatine kinase. Concurrence of these factors increased the likelihood of S-NS. CONCLUSIONS: Quantitation of serum TPPA is worthwhile and performs better than serum RPR in screening S-NS. Serum RPR, serum TPPA, male sex, and serum creatine kinase can predict S-NS. Moreover, patients with both a serum RPR titer <1:2 and a serum TPPA titer <1:1280 have a low probability of S-NS, suggesting that it is reasonable to reduce lumbar punctures in such individuals.

A comparative study on postoperative mortality prediction of SFLI scoring system and Child-Pugh classification in patients with hepatocellular carcinoma.

PURPOSE: In our previous study, we have established the clinical significance of the SFLI (scoring formula of liver injury), the purpose of this study was to compare the SFLI system and the Child-Pugh grading system in the prediction of postoperative mortality in patients with hepatocellular carcinoma (HCC). METHODS: 114 patients with HCC who underwent surgical treatment were enrolled. According to the requirement of the indicators for the Child-Pugh classification, various indices (including albumin [ALB], total bilirubin [TBIL], prothrombin time [PT], ascites, and hepatic encephalopathy) were considered in these patients before surgery, and then Child-Pugh grading was performed. Similarly, the serum biochemical markers including ALB, pre-albumin (PA), TBIL, serum creatining (SCR), international normalized ratio (INR), alanine transminase (ALT), aspartate transaminase (AST), γ-glutamyl transpeptidase (ggr;-GT), alkaline phosphatase (ALP), PT, activated partial thromboplastin time (APTT), and thrombine time (TT) were collected before surgery for SFLI analysis. The predicted postoperative mortality rates of these two scoring models and their diagnostic efficacy were analyzed and compared. RESULTS: According to the Child-Pugh grading system, in level A, B and C were 75, 35, and 4 cases respectively, and the corresponding mortality rates were 1.3% (1/75), 17.1% (6/35) and 75% (3/4). Meanwhile, according to the SLFI classification, the number of patients in the grade I, I+, II, and III were 36, 29, 28, and 21, respectively, and the corresponding mortality rates were 0, 0, 14.3% (4/28), and 28.6% (6/21), respectively. The patient mortality rate increased significantly with increasing grading (p<0.01). These two classification methods were further compared using ROC analysis, in which the area under the curve (AUC) for the Child-Pugh method was 10.2% with a 95% confidence interval (95% CI) 17-18, and the AUC of SFLI was 88.2% with a 95% CI 80-96. CONCLUSION: The SFLI scoring system is very useful in the assessment of liver function and postoperative mortality, and its grading standard is much better than the traditional Child-Pugh classification in many aspects.

Phenotypic flexibility of thermogenesis in the hwamei (Garrulax canorus): responses to cold acclimation.

Cold acclimation in birds involves a comprehensive array of physiological and morphological adjustment ranging from changes in aerobic enzyme activity to metabolic rate and organ mass. In the present study, we investigated phenotypic variation in thermogenic activity in the hwamei (Garrulax canorus) under normal (35°C) or cold (15°C) ambient temperature conditions. Acclimation to an ambient temperature of 15°C for 4 wk significantly increased the body mass, basal metabolic rate (BMR), and energy intake, including both gross energy intake and digestible energy intake, compared with birds kept at 35°C. Furthermore, birds acclimated to 15°C increased the dry mass of their liver and kidneys, but not their heart and pectoral muscles, and displayed higher state-4 respiration in the liver, kidneys, heart, and pectoral muscles, and higher cytochrome-c oxidase (COX) activity in liver, kidney, and pectoral muscle, compared with those kept at 35°C. There was a positive correlation between BMR and state-4 respiration in all of the above organs except the liver, and between BMR and COX activity in all of the above organs. Taken together, these data illustrate the morphological, physiological, and enzymatic changes associated with cold acclimation, and support the notion that the hwamei is a bird species from temperate climates that exhibits high phenotypic flexibility of thermogenic capacity.

Evaluation of the boson chemiluminescence immunoassay as a first-line screening test in the ECDC algorithm for syphilis serodiagnosis in a population with a high prevalence of syphilis.

We developed a new Boson chemiluminescence immunoassay (CIA) and evaluated its application with cross-sectional analyses. Our results indicated that the Boson CIA demonstrated strong discriminatory power in diagnosing syphilis and that it can be used as a first-line screening test for syphilis serodiagnosis using the European Centre for Disease Prevention and Control algorithm or as a confirmatory test when combined with a patient's clinical history.

Seasonal variation in body mass, body temperature and thermogenesis in the Hwamei, Garrulax canorus.

The basal thermogenesis of birds is beginning to be viewed as a highly flexible physiological trait influenced by environmental fluctuations, particularly changes in ambient temperature (Ta). Many birds living in regions with seasonal fluctuations in Ta typically respond to cold by increasing their insulation and adjusting their metabolic rate. To understand these metabolic adaptations, body temperature (Tb), metabolic rate (MR), thermal neutral zone (TNZ) and thermal conductance were measured within a range of temperatures from 5 to 40°C in free-living Hwamei, Garrulax canorus, in both winter and summer. Body mass was 61.2±0.3g in winter and 55.5±1.0g in summer, and mean Tb was 41.6±0.1°C in winter and 42.3±0.1°C in summer. TNZ was between 28.3 and 35.1°C in winter and between 28.7 and 33.2°C in summer. The mean basal metabolic rate (BMR) within TNZ was 203.32±11.81ml O2 h(-1) in winter and 168.99±6.45ml O2 h(-1) in summer. Minimum thermal conductance was 3.73±0.09joulesg(-1)h(-1)°C(-1) in winter and 3.26±0.06joulesg(-1)h(-1)°C(-1) in summer. Birds caught in winter had higher body mass, MR, and more variable TNZ than those in summer. The increased winter BMR indicates improved ability to cope with cold and maintenance of a high Tb. These results show that the Hwamei's metabolism is not constant, but exhibits pronounced seasonal phenotypic flexibility associated with maintenance of a high Tb.

Psychiatric manifestations as primary symptom of neurosyphilis among HIV-negative patients.

This study characterizes psychiatric manifestations as a primary symptom of neurosyphilis (NS). Fifty-two of the 169 NS patients presented with psychiatric manifestations, many patients had characteristics of more than one syndrome, including cognitive impairment, personality disorders, delirium, hostility, dysarthria, confusion, disruption of their sleep-wake cycle, fecal and urinary incontinence, dysphoria, paranoia, hallucinations, expansive mood, and mania. Fifty-two patients had positive sera RPR and T. pallidum particle agglutination (TPPA), 75% had positive CSF RPR, 96.2% had positive CSF TPPA, 44.2% had CSF pleocytosis and elevated CSF proteins, and 70.0% had nonspecific, abnormal brain MRIs. These results indicate that NS mimics almost all psychiatric disorders.

Clinical spectrum of neurosyphilis among HIV-negative patients in the modern era.

BACKGROUND: The clinical spectrum of neurosyphilis (NS) has changed over time. OBJECTIVE: To describe the clinical spectrum and characteristics of NS in HIV-negative patients. METHODS: A retrospective chart review was performed for 149 in patients with NS. RESULT: All patients were >25 years old, including 16.8% asymptomatic for NS, 15.4% with syphilitic meningitis, 24.2% with meningovascular NS, 38.9% with general paresis, 4.0% with tabes dorsalis and 0.7% with gummatous NS. The original misdiagnosis rate was 84.6%. All 149 patients had positive serum Treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR). The overall positive rates of cerebrospinal fluid RPR (CSF-RPR) and CSF-TPPA were 57.0 and 89.9%, respectively. CSF pleocytosis and elevated CSF protein were found in 40.3% of patients. Nonspecific abnormal brain magnetic resonance imaging and electroencephalography findings were present in 60.4 and 54.8% of NS patients, respectively. CONCLUSIONS: NS has various clinical manifestations, laboratory findings and magnetic resonance imaging and electroencephalography findings, but all studies lack specificity. Every patient with neurological or psychiatric symptoms that are without unambiguous causes should have blood tests for syphilis. When serology proves positive, patients should undergo CSF examination.

Neuropsychiatric disorders secondary to neurosyphilis in elderly people: one theme not to be ignored.

BACKGROUND: Neurosyphilis (NS) may present with neuropsychiatric disorders characterized by cognitive impairment, personality disorders, and confusion, among others. Very few studies have focused on neuropsychiatric disorders secondary to NS in elderly people. METHOD: A retrospective chart review was performed to characterize the psychiatric findings, clinical signs and symptoms, laboratory findings, and brain magnetic resonance imaging results of ten elderly inpatients with NS. RESULTS: In these ten patients, the most common presenting symptoms included a wide variety of psychiatric manifestations. The serum rapid plasma regain (RPR) and Treponema pallidum particle agglutination assay (TPPA) of the ten patients were positive, with positive CSF TPPA and RPR rates of 100% and 60%, respectively. In addition, 90% of the patients demonstrated abnormal imaging, including cerebral atrophy, infarct ischemic stroke, and hydrocephalus. CONCLUSIONS: Our findings support the importance of serological tests for syphilis as a routine component of the evaluation of patients with clinically evident neurological or psychiatric symptoms. If the serology is positive, all of the patients should be examined with a lumbar puncture. Moreover, psychiatric illnesses secondary to NS in the elderly also deserve medical attention.

Geographic variation in basal thermogenesis in little buntings: relationship to cellular thermogenesis and thyroid hormone concentrations.

Acclimatization to different ambient conditions is an essential prerequisite for survival of small passerine birds. Long-distance migration and winter acclimatization induce similar physiological and biochemical adjustments in passerines. To understand metabolic adaptations, the resting metabolic rate (RMR), the thermogenic properties of mitochondria in liver and muscle, and the activity of thyroid hormones were examined in field-captured little buntings (Emberiza pusilla) between Southeastern (Wenzhou) and Northeastern (Qiqihar) China from March to May in 2008 during their migration. Twelve birds were trapped from March to April in Wenzhou region, Zhejiang Province (27°29'N, 120°51'E) and eleven birds originated from April to May in Qiqihar region, Heilongjiang Province (47°29'N, 124°02'E). We found that RMRs of little buntings were significantly higher in Qiqihar than in Wenzhou. Consistently, mitochondrial state-4 respiration capacities and cytochrome c oxidase activities (COX) in liver and muscle, and circulating levels of plasma triiodothyronine (T(3)) of little buntings were also significantly higher in Qiqihar than in Wenzhou. Variation in metabolic biochemical markers of liver and muscle, such as state-4 respiration and COX, and variation in thyroid hormone levels were correlated with variation in RMR. There was also a positive relationship between T(3) and metabolic biochemical markers. Little buntings mainly coped with a cold environment by enhancing thermogenic capacities through enhanced respiratory enzyme activities and plasma T(3). These results support the view that the primary means by which small birds meet energetic challenges of cold conditions is through metabolic adjustments.

MicroRNA-575 targets Derlin 1 to regulate proliferation, migration and invasion of human thyroid cancer cells.

Introduction: This study was undertaken to examine the expression of miR-575 in thyroid cancer tissues and to explore its therapeutic potential. Material and methods: Expression analysis was carried out by qRT-PCR. The MTT assay was used for cell viability. DAPI and annexin V/PI assays were used to detect apoptosis. Wound healing and Transwell assays were used for cell migration and invasion respectively. Western blot analysis was used to determine the expression of proteins. Results: The results showed significant downregulation of miR-575 in thyroid cancer tissues and cell lines. The role of miR-575 was deciphered by overexpression of miR-575 in MDA-T32 and MDA-T68 thyroid cancer cells. The results showed that overexpression of miR-575 caused significant inhibition of the proliferation of the MDA-T32 and MDA-T68 cells via induction of apoptotic cell death. The expression of Bax was also enhanced while that of Bax was decreased upon miR-575 overexpression in MDA-T32 and MDA-T68 cells. Additionally, miR-575 overexpression inhibited the migration and invasion of the MDA-T32 and MDA-T68 thyroid cancer cells. Bioinformatic approaches and the dual luciferase assay indicated Derlin 1 (DERL1) to be the potential target of miR-575 in thyroid cancer. DERL1 was significantly upregulated in thyroid cancer tissues and cell lines and overexpression of miR-575 caused suppression of DERL1 in MDA-T68 cells. Silencing of DERL1 inhibited the proliferation of the MDA-T68 cells while overexpression of DERL1 could abolish the effects of miR-575 overexpression on the proliferation of MDA-T68 thyroid cancer cells. Conclusions: miR-575 may be used as a therapeutic target for thyroid cancer treatment.

Prognostic models for early and late tumor progression prediction in nasopharyngeal carcinoma: An analysis of 8292 endemic cases.

OBJECTIVES: The time for posttreatment tumor progression differs between nasopharyngeal carcinoma (NPC) patients. Herein, we established effective nomograms for predicting early tumor progression (ETP) and late tumor progression (LTP) in NPC patients. METHODS: We retrospectively enrolled 8292 NPC patients (training cohort: n = 6219; validation cohort: n = 2073). The ELP and LTP were defined as the time to tumor progression ≤24 and >24 months after treatment, respectively. RESULTS: The ETP and LTP accounted for 52.6 and 47.4% of the total patient cohort, respectively. Patients who developed ETP had markedly worse overall survival (OS) versus patients who suffered from LTP (5-year OS: 26.2% vs. 59.7%, p < 0.001). Further, we identified 10/6 predictive factors significantly associated with ETP/LTP via logistic regression analyses. These indicators were used separately to construct two predictive nomograms for ETP and LTP. In the training group, the ETP nomogram [Harrell Concordance Index (C-index) value: 0.711 vs. 0.618; p < 0.001] and LTP nomogram (C-index value: 0.701 vs. 0.612; p < 0.001) were significantly superior for risk stratification than the TNM staging. These results were supported in the validation group with a C-index value of 0.753 and 0.738 for the ETP and LTP nomograms, respectively. High-risk patients defined by ETP/LTP nomograms had shorter progression-free survival than low-risk patients (all p < 0.001). CONCLUSION: The established nomograms can help in ELP or LTP risk stratification for NPC patients. Our current results might also provide insights into individualized treatment decisions and designing surveillance strategies for NPC patients.