[Study on the prognostic value of preoperative anti hepatitis B virus therapy in patients with hepatocellular carcinoma complicated with microvascular tumor thrombus and establishment of survival prediction model].

Objective: To explored the effect of preoperative antiviral therapy on the prognosis of microvascular tumor thrombi patients, and to established a prognostic prediction model for these patients after radical resection of liver cancer. Methods: The clinicopathological and survival data of hepatocellular carcinoma patients with microvascular tumor thrombus who underwent radical resection in the Third Affiliated Hospital of Sun Yat-sen University from January 1, 2013 to December 31, 2015 were retrospectively collected. Kaplan-Meier method was used to calculate the survival curve, and log-rank test was used to compare the prognosis of patients with and without antiviral treatment before operation. Univariate and multivariate Cox proportional hazard regression model was used to screen predictive factors. R software was used to make predictive nomogram, and discrimination and calibration degree were used to evaluate the prediction model. Results: Among all 153 patients, 22 were female and 131 were male, aged (51.3±11.7) years. The preoperative antiviral therapy significantly improved overall survival and recurrence-free survival (χ2=41.423, 54.389; both P<0.001). According to the results of multivariate and regression analysis, preoperative antiviral therapy (HR=0.301,95%CI:0.171-0.532,P<0.001), alpha fetoprotein (HR=1.226,95%CI:1.157-1.776,P=0.032) and tumor size (HR=1.008,95%CI:1.001-1.016,P=0.02) were important prognostic factors for overall survival. The area under curve value of 3-year survival prediction model was 0.749(95%CI: 0.712-0.782), and that of 5-year survival prediction model was 0.755(95%CI: 0.724-0.793), with good calibration. Conclusions: Preoperative anti hepatitis B virus(HBV) therapy can significantly improve the prognosis of patients with hepatocellular carcinoma complicated with microvascular tumor thrombus, we develope the prediction models of 3-year and 5-year survival rate that can improve the reference for clinical work and benefit patients.

Neurobiological mechanisms of TENS-induced analgesia.

Pain inhibition by additional somatosensory input is the rationale for the widespread use of Transcutaneous Electrical Nerve Stimulation (TENS) to relieve pain. Two main types of TENS produce analgesia in animal models: high-frequency (∼50-100 Hz) and low-intensity 'conventional' TENS, and low-frequency (∼2-4 Hz) and high-intensity 'acupuncture-like' TENS. However, TENS efficacy in human participants is debated, raising the question of whether the analgesic mechanisms identified in animal models are valid in humans. Here, we used a sham-controlled experimental design to clarify the efficacy and the neurobiological effects of 'conventional' and 'acupuncture-like' TENS in 80 human volunteers. To test the analgesic effect of TENS we recorded the perceptual and brain responses elicited by radiant heat laser pulses that activate selectively Aδ and C cutaneous nociceptors. To test whether TENS has a long-lasting effect on brain state we recorded spontaneous electrocortical oscillations. The analgesic effect of 'conventional' TENS was maximal when nociceptive stimuli were delivered homotopically, to the same hand that received the TENS. In contrast, 'acupuncture-like' TENS produced a spatially-diffuse analgesic effect, coupled with long-lasting changes both in the state of the primary sensorimotor cortex (S1/M1) and in the functional connectivity between S1/M1 and the medial prefrontal cortex, a core region in the descending pain inhibitory system. These results demonstrate that 'conventional' and 'acupuncture-like' TENS have different analgesic effects, which are mediated by different neurobiological mechanisms.

Somatotopic Representation of Second Pain in the Primary Somatosensory Cortex of Humans and Rodents.

There is now compelling evidence that selective stimulation of Aδ nociceptors eliciting first pain evokes robust responses in the primary somatosensory cortex (S1). In contrast, whether the C-fiber nociceptive input eliciting second pain has an organized projection to S1 remains an open question. Here, we recorded the electrocortical responses elicited by nociceptive-specific laser stimulation of the four limbs in 202 humans (both males and females, using EEG) and 12 freely moving rats (all males, using ECoG). Topographical analysis and source modeling revealed in both species, a clear gross somatotopy of the unmyelinated C-fiber input within the S1 contralateral to the stimulated side. In the human EEG, S1 activity could be isolated as an early-latency negative deflection (C-N1 wave peaking at 710-730 ms) after hand stimulation, but not after foot stimulation because of the spatiotemporal overlap with the subsequent large-amplitude supramodal vertex waves (C-N2/P2). In contrast, because of the across-species difference in the representation of the body surface within S1, S1 activity could be isolated in rat ECoG as a C-N1 after both forepaw and hindpaw stimulation. Finally, we observed a functional dissociation between the generators of the somatosensory-specific lateralized waves (C-N1) and those of the supramodal vertex waves (C-N2/P2), indicating that C-fiber unmyelinated input is processed in functionally distinct somatosensory and multimodal cortical areas. These findings demonstrated that C-fiber input conveys information about the spatial location of noxious stimulation across the body surface, a prerequisite for deploying an appropriate defensive motor repertoire.SIGNIFICANCE STATEMENT Unmyelinated C-fibers are the evolutionarily oldest peripheral afferents responding to noxious environmental stimuli. Whether C-fiber input conveys information about the spatial location of the noxious stimulation to the primary somatosensory cortex (S1) remains an open issue. In this study, C-fibers were activated by radiant heat stimuli delivered to different parts of the body in both humans and rodents while electrical brain activity was recorded. In both species, the C-fiber peripheral input projects to different parts of the contralateral S1, coherently with the representation of the body surface within this brain region. These findings demonstrate that C-fiber input conveys information about the spatial location of noxious stimulation across the body surface, a prerequisite for deploying an appropriate defensive motor repertoire.

Cold exposure induces the acquisition of brown adipocyte gene expression profiles in cattle inguinal fat normalized with a new set of reference genes for qRT-PCR.

The last few years have seen great advances in our understanding of browning in white adipose tissue (WAT) where white adipocytes take on characteristics of brown adipocytes. At present, the economic significance of browning for animal husbandry is beginning to be realized with the emerging evidence that browning affects body weight not only in human and rodent but in farm animals. Quantitative RT-PCR provides a quick and sensitive way to preliminary determine browning of WAT. However, there have been no established condition specific reference genes for browning of cattle WAT. As the results showed, the most two stable reference genes for diet treatment were Wdr33 (M=0.38) and Hdac3 (M=0.43), while the most three internal controls for temperature treatment were Hdac3 (M=0.28), Wdr33 (M=0.32), and Hprt1 (M=0.39) among the ten candidates. The mRNA relative expression levels of selective marker genes were normalized by normalization factor (geometric mean of control genes quantities). Cold exposure rather than high energy diet induced transcript elevations of brite specific markers (Cited1, Tbx1), thermoregulatory markers (brown and beige versus white markers, i.e., Cidea, Cox7a1, Ucp1), mitochondrial biogenesis markers (Nrf1, Nrf2, Tfam), and transcription regulators (brown and beige versus white markers, i.e., Pgc1α) (P<0.05) in cattle inguinal fat (iWAT). Quantitative RT-PCR is a preliminary study for WAT browning. In conclusion, cattle inguinal fat acquired brown adipocyte gene expression features upon cold acclimation with prerequisite identification of stable reference genes.

Biological mechanism of post-herpetic neuralgia: Evidence from multiple patho-psychophysiological measures.

BACKGROUND: Post-herpetic neuralgia (PHN), which develops after the resolution of a herpes zoster eruption, is an exceptionally drug-resistant neuropathic pain. The unsatisfactory management of PHN partly results from the difficulty in dissecting out its contributing factors due to the complexity of PHN mechanism. METHODS: Here, to elaborate our understanding of the PHN mechanism and to establish a basis for effective therapeutic strategies, we comprehensively investigated the contributions of multiple factors to PHN severity. RESULTS: Based on the comparison of somatosensory detection thresholds (C, Aδ and Aß fibre thresholds) between affected and unaffected sides, 16 PHN patients with significant sensory deficits and 13 PHN patients without significant sensory deficits were identified and assigned to different groups. The different extents of lesions in the nociceptive system between patients with and without sensory deficits were confirmed using laser-evoked brain responses. Moreover, patients with sensory deficits had more severe pain and psychological disorders, e.g. anxiety and depression. Importantly, chronic pain severity was significantly influenced by various psychophysiological factors (sleep disturbances, psychological disorders and hypothalamic-pituitary-adrenal axis dysfunction) for patients with sensory deficits. CONCLUSIONS: Our findings demonstrated the contribution of multiple patho-psychophysiological factors to PHN severity, which could help establish a basis for the development of a rational, patient-centred therapeutic strategy. SIGNIFICANCE: This study revealed the contribution of multiple patho-psychophysiological factors to PHN severity, which expanded our understanding of the underlying PHN mechanism, and helped develop a rational, patient-centred therapeutic strategy targeting towards the corresponding etiology and psychophysiological disorders for individual patient.

Laser-evoked cortical responses in freely-moving rats reflect the activation of C-fibre afferent pathways.

The limited success of translating basic animal findings into effective clinical treatments of pain can be partly ascribed to the use of sub-optimal models. Murine models of pain often consist in recording (1) threshold responses (like the tail-flick reflex) elicited by (2) non-nociceptive specific inputs in (3) anaesthetized animals. The direct cortical recording of laser-evoked potentials (LEPs) elicited by stimuli of graded energies in freely-moving rodents avoids these three important pitfalls, and has thus the potential of improving such translation. Murine LEPs are classically reported to consist of two distinct components, reflecting the activity of Aδ- and C-fibre afferent pathways. However, we have recently demonstrated that the so-called "Aδ-LEPs" in fact reflect the activation of the auditory system by laser-generated ultrasounds. Here we used ongoing white noise to avoid the confound represented by the early auditory response, and thereby comprehensively characterized the physiological properties of C-fibre LEPs recorded directly from the exposed surface of the rat brain. Stimulus-response functions indicated that response amplitude is positively related to the stimulus energy, as well as to nocifensive behavioral score. When displayed using average reference, murine LEPs consist of three distinct deflections, whose polarity, order, and topography are surprisingly similar to human LEPs. The scalp topography of the early N1 wave is somatotopically-organized, likely reflecting the activity of the primary somatosensory cortex, while topographies of the later N2 and P2 waves are more centrally distributed. These results indicate that recording LEPs in freely-moving rats is a valid model to improve the translation of animal results to human physiology and pathophysiology.

Insulator-metal transition of VO2 ultrathin films on silicon: evidence for an electronic origin by infrared spectroscopy.

We report on the first simultaneous observations of both electronic and structural temperature-induced insulator-to-metal transition (IMT) in VO2 ultrathin films, made possible by the use of broad range transmission infrared spectroscopy. Thanks to these techniques, the infrared phonon structures, as well as the appearance of the free carrier signature, were resolved for the first time. The temperature-resolved spectra allowed the determination of the temperature hysteresis for both the structural (monoclinic-to-rutile) and electronic (insulator-to-metallic) transitions. The combination of these new observations and DFT simulations for the monoclinic structure allows us to verify the direct transition from monoclinic (M1) to rutile and exclude an intermediate structural monoclinic form (M2). The delay in structural modification compared to the primer electronic transition (325 K compared to 304 K) supports the role of free charges as the transition driving force. The shape of the free charge hysteresis suggests that the primer electronic transition occurs first at 304 K, followed by both its propagation to the heart of the layer and the structural transition when T increases. This study outlines further the potential of VO2 ultrathin films integrated on silicon for optoelectronics and microelectronics.

Follow-up study of acute hepatitis C.

An extended follow-up study of hepatitis C virus (HVC) infection was conducted in Guangzhou and its nearby regions on patients hospitalized with acute hepatitis. Routine screening of blood donors for HCV was not yet instituted at the time of this study. HCV was found to be a common cause of the disease, and the infection had a close association with recent histories of blood transfusion. Sequential sera obtained from patients during hospitalization and after discharge were tested for the presence of HCV antibodies by the first and the second generation of commercial test kits, for levels of alanine aminotransferase (ALT), and for the presence of HCV-RNA. The development of HCV antibodies in some of the patients may be delayed for protracted period following clinical onset. HCV-RNA was only intermittently detectable both before and after seroconversion. Six of 33 patients studied showed seroreversion and 5 of them were accompanied by loss of HCV-RNA and serum ALT returned to normal levels. The disease persisted in 24 of 27 patients without seroreversion, accompanied by intermittent detection of HCV-RNA throughout the protracted course of the infection. Our results indicate that both EIA for detection of HCV antibodies and PCR for serum HCV-RNA should be used in combination for reliable diagnosis of HCV infection and screening of blood for transfusion.

Development of a monoclonal antibody against a tumor-associated antigen.

A monoclonal antibody-producing hybrid cell line was obtained by fusing mouse myeloma cells with spleen cells from a mouse immunized with C6 glioma cells. This antibody binds to a specific cell-surface antigen that is present on C6 rat glioma cells, transformed astrocytes and oligodendrocytes, and a human glioma cell line but is absent on a normal glial cell line, fibroblasts, and primary cultures of astrocytes and oligodendrocytes. The antigen also appears on tumor tissue of transformed oligodendrocytes but not on normal brain tissue.