Clinical manifestations of severe enterovirus 71 infection and early assessment in a Southern China population.

BACKGROUND: Enterovirus 71 (EV-A71) shows a potential of rapid death, but the natural history of the infection is poorly known. This study aimed to examine the natural history of EV-A71 infection. METHODS: This was a prospective longitudinal observational study performed between January 1st and October 31st, 2012, at three hospitals in Guangdong, China. Subjects with positive EV-A71 RNA laboratory test results were included. Disease progression was documented with MRI, autopsies, and follow-up. Symptoms/signs with potential association with risk of death were analyzed. RESULTS: Among the 288 patients, neurologic symptoms and signs were observed (emotional movement disorders, dyskinesia, involuntary movements, autonomic dysfunction, and disturbance of consciousness). Some of them occurred as initial symptoms. Myoclonic jerks/tremors were observed among >50% of the patients; nearly 40% of patients presented fatigue and 25% were with vomiting. Twenty-eight patients (9.7%) presented poor peripheral perfusion within 53.4 ± 26.1 h; 23 patients (8.0%) presented pulmonary edema and/or hemorrhage within 62.9 ± 28.6 h. Seventeen (5.9%) patients were in a coma. Seven (2.4%) patients died within 62.9 ± 28.6 h. Seventy-seven survivors underwent head and spinal cord MRI and 37.7% (29/77) showed abnormalities. Two fatal cases showed neuronal necrosis, softening, perivascular cuffing, colloid, and neuronophagia phenomenon in the brainstem. CONCLUSIONS: Patients with EV-A71 infection showed high complexity of symptoms and onset timing. Death risk may be indicated by autokinetic eyeball, eyeball ataxia, severe coma, respiratory rhythm abnormality, absent pharyngeal reflex, ultrahyperpyrexia, excessive tachycardia, pulmonary edema and/or hemorrhage, and refractory shock and ataxic respiration. Early assessment of these symptoms/signs is important for proper management.

The constitutive activation of Egr-1/C/EBPa mediates the development of type 2 diabetes mellitus by enhancing hepatic gluconeogenesis.

The sequential secretion of insulin and glucagon delicately maintains glucose homeostasis by inhibiting or enhancing hepatic gluconeogenesis during postprandial or fasting states, respectively. Increased glucagon/insulin ratio is believed to be a major cause of the hyperglycemia seen in type 2 diabetes. Herein, we reveal that the early growth response gene-1 (Egr-1) can be transiently activated by glucagon in hepatocytes, which mediates glucagon-regulated gluconeogenesis by increasing the expression of gluconeogenesis genes. Blockage of Egr-1 function in the liver of mice led to lower fasting blood glucose, better pyruvate tolerance, and higher hepatic glycogen content. The mechanism analysis demonstrated that Egr-1 can directly bind to the promoter of C/EBPa and regulate the expression of gluconeogenesis genes in the later phase of glucagon stimulation. The transient increase of Egr-1 by glucagon kept the glucose homeostasis after fasting for longer periods of time, whereas constitutive Egr-1 elevation found in the liver of db/db mice and high serum glucagon level overactivated the C/EBPa/gluconeogenesis pathway and resulted in hyperglycemia. Blockage of Egr-1 activation in prediabetic db/db mice was able to delay the progression of diabetes. Our results suggest that dysregulation of Egr-1/C/EBPa on glucagon stimulation may provide an alternative mechanistic explanation for type 2 diabetes.

Altered regional brain activity and functional connectivity in primary intravaginal anejaculation patients revealed by resting-state fMRI.

ABSTRACT: Ejaculation is regulated by the central nervous system. However, the central pathophysiology of primary intravaginal anejaculation (PIAJ) is unclear. The present study aimed to examine the changes in regional brain activity and functional connectivity underlying PIAJ. A total of 20 PIAJ patients and 16 healthy controls (HCs) were enrolled from September 2020 to September 2022 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Magnetic resonance imaging data were acquired from all participants and then were preprocessed. The measures of fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) were calculated and compared between the groups. PIAJ patients showed increased fALFF values in the left precuneus compared with HCs. Additionally, PIAJ patients showed increased ReHo values in the left precuneus, left postcentral gyrus, left superior occipital gyrus, left calcarine fissure, right precuneus, and right middle temporal gyrus, and decreased ReHo values in the left inferior parietal gyrus, compared with HCs. Finally, brain regions with altered fALFF and ReHo values in PIAJ patients showed increased FC with widespread cortical regions, which included the frontal, parietal, temporal, and occipital regions, compared with HCs. In conclusion, increased regional brain activity in the parietal, temporal, and occipital regions, and increased FC between these brain regions, may be associated with PIAJ occurrence.

Abnormal cortical surface-based spontaneous and functional connectivity in the whole brain in lifelong premature ejaculation patients.

Recent research has highlighted structural and functional abnormalities in the cerebral cortex of patients with premature ejaculation (PE). These anomalies could play a pivotal role in the physiological mechanisms underlying PE. This study leveraged functional magnetic resonance imaging (fMRI), a noninvasive technique, to explore these neural mechanisms. We conducted resting-state fMRI scans on 36 PE patients and 22 healthy controls (HC), and collected data on Premature Ejaculation Diagnostic Tool (PEDT) scores and intravaginal ejaculation latency time (IELT). Employing a surface-based regional homogeneity (ReHo) approach, we analyzed local neural synchronous spontaneous activity, diverging from previous studies that utilized a volume-based ReHo method. Areas with significant ReHo differences between PE and HC groups underwent surface-based functional connectivity (FC) analysis. Significant discrepancies in ReHo and FC across the cortical surface were observed in the PE cohort. Notably, PE patients exhibited decreased ReHo in the left triangular inferior frontal gyrus and enhanced ReHo in the right middle frontal gyrus. The latter showed heightened connectivity with the left lingual gyrus and the right orbital superior frontal gyrus. Furthermore, a correlation between ReHo and FC values with PEDT scores and IELT was found in the PE group. Our findings, derived from surface-based fMRI data, underscore specific brain regions linked to the neurobiological underpinnings of PE.

Simulating Fractures With Bonded Discrete Element Method.

Along with motion and deformation, fracture is a fundamental behaviour for solid materials, playing a critical role in physically-based animation. Many simulation methods including both continuum and discrete approaches have been used by the graphics community to animate fractures for various materials. However, compared with motion and deformation, fracture remains a challenging task for simulation, because the material's geometry, topology and mechanical states all undergo continuous (and sometimes chaotic) changes as fragmentation develops. Recognizing the discontinuous nature of fragmentation, we propose a discrete approach, namely the Bonded Discrete Element Method (BDEM), for fracture simulation. The research of BDEM in engineering has been growing rapidly in recent years, while its potential in graphics has not been explored. We also introduce several novel changes to BDEM to make it more suitable for animation design. Compared with other fracture simulation methods, the BDEM has some attractive benefits, e.g., efficient handling of multiple fractures, simple formulation and implementation, and good scaling consistency. But it also has some critical weaknesses, e.g., high computational cost, which demand further research. A number of examples are presented to demonstrate the pros and cons, which are then highlighted in the conclusion and discussion.

[Study on the four-year retention rate and influencing factors for 2,353 AIDS patients by Chinese medicine].

OBJECTIVE: To analyze the retention rate and its influencing factors of HIV/AIDS patients by Chinese medicine (CM) maintenance treatment in the first 5 provinces in China. METHODS: Kaplan-Meier method was used to analyze the retention rate of treatment in patients. Cox hazard regression model was used to assess factors that might influence the treatment time of Chinese medication. RESULTS: Totally 2,353 patients took part in this four-year study. Of them, 1,156 (49. 1%) were male, 2,344 (99. 6%) were Han nationality, 2,260 (96%) were married, 2,219 (94.3%) had junior middle-schooling or below, the average age was 41.52 +/- 8.98 years, 1,758 (74.7%) received paid blood donation, 478 (20.3%) received blood transfusion, 737 (31.3%) were absent of symptoms, 963 (40.9%) received combined treatment of CM and Western medicine. The median time within the four years was 44.84 months. The average retention rate for 1, 2, 3, 4 years of CM treatment were 86.6%, 78.4%, 72.2%, 65.6%, respectively. The results of Cox model indicated that the drop-out risk could be reduced in combined treatment of CM and Western medicine patients (HR=0. 805, P<0.01) and AIDS patients (HR=0. 769, P<0.01). The drop-out risk could be increased by the infection route of paid blood donation (HR =1. 373, P<0.01). CONCLUSIONS: The four-year retention rate of the 2 353 patients by CM treatment in the first 5 provinces in China was 65. 6%. Route of infection, whether or not in combination of Western medicine, and staging showed influence on CM maintenance treatment time.

Cobalt-Catalyzed Direct C-H Carbonylative Synthesis of Free (NH)-Indolo[1,2-a]quinoxalin-6(5H)-ones.

A cobalt-catalyzed direct C-H carbonylative reaction of N-(2-(1H-indol-1-yl)phenyl)picolinamides for the synthesis of (NH)-indolo[1,2-a]quinoxalin-6(5H)-one skeletons has been developed. Using benzene-1,3,5-triyl triformate (TFBen) as the CO source and picolinamide as the traceless directing group, various free (NH)-indolo[1,2-a]quinoxalin-6(5H)-ones were obtained in good yields (up to 88%). Additionally, a series of product derivatizations were demonstrated, and the core fragment of PARP-1 inhibitor C can be readily constructed by this protocol.