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Drug-induced liver injury influencing factors are complex and have diverse clinical manifestations. Simple and reliable diagnostic methods are still deficient, and further classification of toxicological mechanisms is required. There are numerous pertinent discrepancies between domestic and international guidelines aimed at drug-induced liver injury diagnosis and treatment, with partial to no consensus on the content. The American Gastroenterological Association's 2021 Clinical Guidelines, the Asia-Pacific Association for the Study of the Liver's 2021 Consensus Guidelines, the Council for International Organizations of Medical Sciences' 2020 International Consensus, the European Society's Hepatology Committee's 2019 Clinical Practice Guidelines, and the 2015 Chinese Medical Association Guidelines are five influential clinical guidelines on drug-induced liver injury at home and abroad. The epidemiology, risk factors, diagnosis and evaluation, treatment management, and other contents, particularly traditional Chinese medicine, were compared and analyzed using other relevant consensus opinions or guidelines in order to improve understanding and provide a reference for clinical diagnosis and treatment of drug-induced liver injury.
Subject(s)
Humans , Chemical and Drug Induced Liver Injury/therapy , Medicine, Chinese TraditionalABSTRACT
The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCNVm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCNVm neurons' function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.
Subject(s)
Animals , Mice , Blinking , Cerebellar Nuclei/physiology , Cerebellum , Neurons/physiology , ThalamusABSTRACT
While the hippocampus has been implicated in supporting the association among time-separated events, the underlying cellular mechanisms have not been fully clarified. Here, we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning (tEBC) task. We found that the hippocampal interneurons exhibited conditioned stimulus (CS)-evoked sustained activity, which predicted the performance of conditioned eyeblink responses (CRs) in the early acquisition of the tEBC. Consistent with this, greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC. Moreover, optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC. In contrast, suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs. Our findings highlight the role of hippocampal interneurons in the tEBC, and point to a potential cellular mechanism subserving associative learning.
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As a novel transdermal drug delivery technology of minimally invasive, safe and efficient, microneedles have received increasing attention. The microchannels formation by microneedles onto the skin is a prerequisite and key for microneedles to deliver drugs. However, there is still a lack of systematic evaluation in skin microchannels. This review summarized influencing factors and evaluation methods in microchannels formation and healing by microneedles, including geometric parameters, materials for preparation, drugs, penetration parameters, differences among the skin of subjects, and presence or absence of occlusion. This review provides reference for other scholars to further study the effectiveness and security of microneedle applications.
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To investigate the influence factors and effects of metal or dissolving microneedles on the formation and healing of skin microchannels, the pencil-shaped or conical stainless steel microneedles with different lengths, tip to tip space and base area, and the pencil-shaped dissolving microneedles with different tip to tip space were used. The microneedles were applied to the skin of epilatory mice and rats, and the effects of various microneedle parameters, application parameters, and animals on the microchannels were explored by the transepidermal water loss (TEWL) and methylene blue staining. Visually observe the skin local irritation caused by the microneedles. The animal experiments were approved by the Animal Experiments Welfare and Ethical Committee of Zhejiang University of Technology. The application time of the microneedle should be maintained at 30 s or more. When the insertion forces were 2, 4, 8 N, and the TEWL initial values of the formed microchannels were 12.9, 33.0, 40.4 g·m-2·h-1, respectively. When the length of metal microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 37.1, 40.4, 49.5 g·m-2·h-1, respectively. When the tip to tip space of metal microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 33.2, 40.4, 55.8 g·m-2·h-1, respectively. When the base area of metal microneedle were 0.16, 0.35, 0.62 cm2, and the TEWL initial values of the formed microchannels were 35.1, 40.4, 67.1 g·m-2·h-1, respectively. The effects of conical and pencil-shaped microneedles are similar. When the tip to tip space of pencil shaped dissolving microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 49.8, 60.5, 70.5 g·m-2·h-1, respectively. The TEWL baseline values of animal skins of different genders and series are different, but the tendency of microchannels formation and closure is similar. Visual inspection revealed that the slight erythema caused by the microneedles subsided within 24 h. Microneedles of different parameters have different effects on microchannels. The microchannels closed within 24 or 48 h, and the skin local irritation caused by microneedle was mild.
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It is to determine the effect mechanism and therapeutic method of the idea as "guiding meridian sinew
Subject(s)
Acupuncture Points , Acupuncture Therapy , Meridians , Qi , RunningABSTRACT
Objective: To analyze the inorganic elements composition of Naozhenning Granules (NG) by inductively coupled plasma spectrometer (ICP-MS), in order to evaluate the uniformity and safety of NG. Methods The sample of NG was prepared using the microwave digestion method, and the levels of 18 inorganic elements in 10 batches of NG were determined by ICP-MS. Then the results were analyzed by Heatmaps and Pearson Correlations. The uniformity of the products was evaluated by Inorganic elemental fingerprint, principal components analysis, and Cluster analysis. Results :The main inorganic elements in NG were K, Ca, P, Na, Mg, Fe, and there was positive correlations among the different elements. The contents of five heavy metal elements, including As, Hg, Cd, Pb, and Cu, were below the limit of Chinese Pharmacopoeia 2015. The inorganic elements reference fingerprint of NG was generated using the average and median methods. The results of fingerprint similarity, cluster analysis, and principal component analysis showed that the inorganic elements of NG showed good uniformity. The results of principal component analysis showed that K, Mg, Sr, Mn, P,and Pb may be the characteristic elements influencing the quality fluctuation of inorganic elements of NG. Conclusion: This study determined the inorganic element composition of NG, which laid a foundation for its uniformity and safety evaluation of NG.
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<p><b>OBJECTIVES</b>To reveal etiologies of persistent isolated hematuria (PIH) through ultrastructural pathological examination, to disclose clinicopathological correlation in cases with PIH, and to summarize appropriate management of patients with PIH.</p><p><b>METHODS</b>we retrospectively studied 155 PIH patients receiving renal biopsy between January, 2003 and December, 2008 in Peking Union Medical College Hospital. All the clinical data and follow-up result were analyzed.</p><p><b>RESULTS</b>All subjects included 38 children and 117 adults, with mean age of 11.38±3.25 years for children and 35.17±8.44 years for adults. Thin basement membrane nephropathy (TBMN) was the most common pathology (55.3% of children and 49.6% of adults), followed by IgA nephropathy (18.4% of children and 32.5% of adults, mainly grade 2-3) and mesangial proliferative glomerulonephritis (MsPGN) without IgA deposition (13.2% of children and 12.8% of adults). Besides, Alport syndrome (2.6% of children) and membrane nephropathy (2.6% of children and 0.9% of adults) were demonstrated as other causes of PIH. Elevated mean arteral pressure or protein excretion rate, as well as episodic macrohematuria, indicated higher risk for MsPGN rather than TBMN. On the other hand, severity of microhematuria was irrelevant to pathological types of PIH. Totally, 86 patients were followed up and 37 cases therein stayed on track for long term (mean duration 41.11?28.92 months, range 8-113 months). Most cases had benign clinical course except 3 cases with TBMN, 5 cases with IgA nephropathy, 1 case with MsPGN (without IgA deposition), and 1 case with Alport syndrome, who developed hypertension or proteinuria. All of them were administered timely intervention.</p><p><b>CONCLUSIONS</b>Close follow-up should be required as the primary management for PIH. Equally important is careful monitoring for early identification of undesirable predictors; while renal biopsy and other timely intervention are warranted if there is hypertension, significant proteinuria or renal impairment.</p>
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Biopsy , Hematuria , Pathology , Kidney , PathologyABSTRACT
<p><b>OBJECTIVE</b>To study the progression of myopia in school-age children over the past 12 years and factors influencing myopia progression.</p><p><b>METHODS</b>A total of 4569 cases of 5 to 12-year-old children who had refractive examinations in the Third Xiangya Hospital, Central South University between January 2000 and December 2011 were enrolled in this study. The children had no family history of congenital high myopia or other eye diseases. Myopia progression was evaluated when the children were re-examined. The refractive state of each child was measured with cyclopiegic retinoscopy.</p><p><b>RESULTS</b>The mean spherical equivalent (SE) myopia was-2.0±1.7 D between January 2000 and December 2011. There was no statistical difference in yearly myopia progression between different years. The average age of the myopic children decreased from 10.1 in 2000 to 8.9 years old in 2011 (P<0.05). Mean myopia progression was -0.6±0.7 D per year from 2000 to 2011. Myopia progression reduced gradually in 5 to 8-year-olds (P<0.05), however, it accelerated between ages 9 and 11 years. Myopia progression in 10- and 11-year-olds was significantly greater than in 7- and 8-year-olds (P<0.01). The multiple linear regression analysis demonstrated that age and baseline myopic refraction were positively related to myopia progression.</p><p><b>CONCLUSIONS</b>There was no obvious change in the yearly myopia progression of the children over the past 12 years. The mean age of myopia occurrence became younger with time. More preventive measures are needed to ward off high myopia in children with moderate myopia, especially those aged over 10 years.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Disease Progression , Linear Models , Myopia , Retrospective StudiesABSTRACT
<p><b>OBJECTIVE</b>To study the influence of near-work and outdoor activities on myopia progression in school children.</p><p><b>METHODS</b>Eighty 7-11-year-old school children with myopia were randomly assigned into an intervention group (n=41) and a control group (n=39). The children in the intervention group did near- and middle-vision activities less than 30 hrs per week and more outdoor activities than 14-15 hrs per week. Myopia progression was observed regularly over 2 years after which ophthalmologists administered questionnaires regarding near-vision work (reading, writing and using computer), middle-vision work (watching TV and extracurricular learning activities), outdoor activities, using nature light, wearing glasses, etc.</p><p><b>RESULTS</b>The annual mean myopia progression (0.38 ± 0.15 D) in the intervention group was significantly lower than that in the control group (0.52 ± 0.19 D; P<0.01). The children in the two groups spent similar amounts of time in near-vision activities, but the children in the intervention group spent less time in middle-vision activities (P<0.01) and more outdoor activities (13.7 ± 2.4 vs 6.2 ± 1.6 hrs/wk; P<0.01). When considering all children in the study, there were 4 factors that significantly correlated with less myopia progression: more outdoor activities, more time spent wearing glasses, more time spent in natural light and less time using a computer. When analyzing the intervention group separately, more outdoor activity was inversely correlated with myopia progression (t=-2.510, P<0.05). Separate analysis of the control group indicated that more time wearing glasses was correlated with less myopia progression (t=-3.115, P<0.05).</p><p><b>CONCLUSIONS</b>Myopia progression in school children may be slowed by more outdoor activities, more time spent in natural light and more time wearing corrective glasses.</p>