ObjectiveTo study the changing law of appearance color and physicochemical properties of Angelicae Sinensis Radix Carbonisata（ASRC） during the processing by color space method combined with statistical analysis， so as to provide reference for determining the processing endpoint and evaluating the quality of the decoction pieces. MethodsTaking processing time（4， 8， 12， 16 min） and temperature（180， 200， 220， 240 ℃） as factors， ASRC decoction pieces with different processing degrees were prepared in a completely randomized design. Then， the brightness value（L^*）， red-green value（a^*）， yellow-blue value（b^*）， and total chromaticity value （E^*ab） of the decoction pieces were determined by spectrophotometer， the color difference value（ΔE） was calculated， and the data of colorimetric values were analyzed by discriminant analysis. At the same time， the pH， charcoal adsorption， and contents of tannins， 5-hydroxymethylfurfural（5-HMF）， tryptophan， chlorogenic acid， ferulic acid， senkyunolide I， senkyunolide H and ligustilide of ASRC with different processing degrees were determined by pH meter， ultraviolet and visible spectrophotometry and ultra-high performance liquid chromatography（UPLC）. Principal component analysis（PCA） was used to analyze the data of physicochemical indexes， after determining the processing technology of ASRC， the canonical discriminant function was established to distinguish the decoction pieces with different processing degrees， and leave-one-out cross validation was conducted. Finally， Pearson correlation analysis was used to explore the correlation between various physicochemical indexes and chromaticity values. ResultsWith the prolongation of the processing time， L^*， a^*， b^* and E^*ab all showed a decreasing trend， and the established discriminant model based on color parameters was able to distinguish ASRC with different processing degrees. The pH showed an increasing trend with the prolongation of processing time， and the charcoal adsorption， and the contents of tannins， 5-HMF， and tryptophan all showed an increasing and then decreasing trend. Among them， the charcoal adsorption， contents of tannin and 5-HMF reached their maximum values successively after processing for 8-12 min. While the contents of chlorogenic acid， ferulic acid， senkyunolide I， senkyunolide H and ligustilide decreased with the increase of processing time， with a decrease of 60%-80% at 8 min of processing. Therefore， the optimal processing time should be determined to be 8-12 min. PCA could clearly distinguish ASRC with different processing degrees， while temperature had no significant effect on the processing degree. The 12 batches of process validation results（10 min， 180-240 ℃） showed that except for 3 batches identified as class Ⅱ light charcoal， all other batches were identified as class Ⅲ standard charcoal， and the chromaticity values of each batch of ASRC were within the reference range of class Ⅱ-Ⅲ sample chromaticity values. The correlation analysis showed that the chromaticity values were negatively correlated with pH and charcoal adsorption， and positively correlated with contents of tryptophan， chlorogenic acid， ferulic acid， senkyunolide I， senkyunolide H， and ligustilide. And both pH and charcoal adsorption were negatively correlated with the contents of the above components， but the charcoal adsorption was positively correlated with the content of 5-HMF. ConclusionThe chromaticity values and the contents of various physicochemical indicators of ASRC undergo significant changes with the prolongation of processing time， and there is a general correlation between chromaticity values and various physicochemical indicators. Based on the changes in color and physicochemical indicators， the optimal processing time for ASRC is determined to be 8-12 min. This study reveals the dynamic changes of the relevant indexes in the processing of ASRC， which can provide a reference for the discrimination of the processing degree and the quantitative study of the processing endpoint.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Endoscopy ; Health Services Needs and Demand

Objective:To retrieve, evaluate, and integrate the best evidence of general anesthesia health education for adult patients undergoing elective surgery, so as to provide a basis for clinical health education guidance.Methods:Evidence-based questions were established based on the population, intervention, professional, outcome, setting and type of evidence (PIPOST) model. All evidence on general anesthesia health education for adult patients undergoing elective surgery were retrieved from databases or professional association websites such as Cochrane Library, British Medical Journal (BMJ) Best Practice, UpToDate, Agency for Healthcare Research and Quality, Guidelines International Network, National Institute for Health and Clinical Excellence, Clinical Guidelines Library, PubMed, China National Knowledge Infrastructure, WanFang Data, Medlive, American Society of Anesthesiologists, and Society of Anesthesiology of the Chinese Medical Association. The search period was from database establishment to June 18, 2023. Two researchers screened and evaluated the quality of the included literature, extracted and integrated the evidence to form the best evidence for general anesthesia health education in adult patients undergoing selective surgery.Results:A total of 10 articles were included, including four guidelines, three clinical decision-making, and three expert consensus. A total of 41 pieces of evidence on general anesthesia health education for adult patients undergoing elective surgery were extracted, including six aspects of anesthesia overview, pre-anesthesia evaluation, pre-anesthesia preparation, anesthesia process and cooperation, anesthesia recovery period management, and postoperative management.Conclusions:The best evidence of general anesthesia health education for adult patients undergoing selective surgery summarized can provide a basis for comprehensive and systematic education of anesthesia health educators.

Objective:To discusses the variations of 7Be, 137Cs and 210Pb activity concentrations in the air in Beijing from March 16, 2021 to March 31, 2023, and their correlation with temperature, precipitation, relative humidity, barometric pressure, PM10 (only limited to 137Cs) and other meteorological parameters. Methods:A total of 60 aerosol samples were collected using the HRHA01-SFS1000/A ultra-large flowair sampler in the automatic radiation monitoring station. The activity concentrations of 7Be, 137Cs and 210Pb in the aerosol samples were measured by GMX-60 low background anti-Compton high purity germanium gamma spectrometer. Pearson correlation coefficient was used to show the correlation of the relevant parameters. Results:The seasonal mean values of 7Be activity concentration were spring 4.31 mBq/m 3, summer 3.53 mBq/m 3, autumn 3.09 mBq/m 3 and winter 2.45 mBq/m 3, respectively, ranging from 1.17 to 7.79 mBq/m 3, with the overall mean of (3.36±1.33) mBq/m 3. The activity concentration of 137Cs ranged from 0.39 to 8.49 μBq/m 3, with an average of (0.59±1.47) μBq/m 3. The average activity concentrations of 210Pb were spring 0.53 mBq/m 3, summer 0.44 mBq/m 3, autumn 0.72 mBq/m 3 and winter 0.75 mBq/m 3, respectively, ranging from 0.21 to 1.36 mBq/m 3, with an average of (0.56±0.26) mBq/m 3. The activity concentration of 7Be was correlated with temperature and pressure ( r=0.38, -0.40), the activity concentration of 137Cs was correlated with precipitation ( r=-0.41), and the activity concentration of 210Pb was correlated with temperature and pressure ( r=-0.31, 0.37). The variation of 137Cs activity concentration in the air showed an obvious seasonal pattern, and the peak value generally appears in spring of each year (March to May), which was related to the frequent spring dust in Beijing. The activity concentration of 210Pb in the air was affected by coal combustion heating in winter, and has a peak value during November to March. Conclusions:The activity concentrations of 7Be, 137Cs and 210Pb in the air in Beijing are within the normal range, showing a seasonal trend.

Leber's hereditary optic neuropathy (LHON) is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I, which is an important contributor to blindness among young adults across the globe. However, the disorder has no available cures, since the approved drug idebenone for LHON in Europe relies on bypassing complex I defects rather than fixing them. Herein, PARKIN mRNA-loaded nanoparticle (mNP)-engineered mitochondria (mNP-Mito) were designed to replace dysfunctional mitochondria with the delivery of exogenous mitochondria, normalizing the function of complex I for treating LHON. The mNP-Mito facilitated the supplementation of healthy mitochondria containing functional complex I via mitochondrial transfer, along with the elimination of dysfunctional mitochondria with impaired complex I via an enhanced PARKIN-mediated mitophagy process. In a mouse model induced with a complex I inhibitor (rotenone, Rot), mNP-Mito enhanced the presence of healthy mitochondria and exhibited a sharp increase in complex I activity (76.5%) compared to the group exposed to Rot damage (29.5%), which greatly promoted the restoration of ATP generation and mitigation of ocular mitochondrial disease-related phenotypes. This study highlights the significance of nanoengineered mitochondria as a promising and feasible tool for the replacement of dysfunctional mitochondria and the repair of mitochondrial function in mitochondrial disease therapies.

Humans ; Cytomegalovirus ; Cytomegalovirus Infections ; Antigens, Viral ; Immunity ; Autoimmune Diseases ; CD8-Positive T-Lymphocytes

Image 1.

Objective:To investigate the clinical features and influencing factors of long-term prognosis of tuberculous meningitis(TBM), and to provide a recommendation for treatment and early intervention of TBM.Methods:Clinical data of TBM patients were retrospectively collected at Peking Union Medical College Hospital from January 2014 to December 2021. Patients who were followed-up more than one year were divided into two groups according to modified Rankin Scale (mRS). Risk factors associated with long-term prognosis were analyze by conditional logistic stepwise regression.Results:A total of 60 subjects were enrolled including 33 (55%) males and 27 (45%) females with age 15-79 (44.5±19.8) years. There were 30 cases (50%) complicated with encephalitis, 21 cases (35%) with miliary tuberculosis. The diagnosis was microbiologically confirmed in 22 patients (36.7%), including 5 cases (22.7%, 5/22) by acid-fast staining, 8 cases (36.4%, 8/22) by Mycobacterium tuberculosis (MTB) culture, and 20 cases (90.9%, 20/22) by molecular biology. The median follow-up period was 52(43, 66 ) months in 55 cases surviving more than one year. Among them, 40 cases (72.7%) were in favorable group (mRS 0-2) and 15 cases (27.3%) were in unfavorable group (mRS 3-6) with poor prognosis. The mortality rate was 20% (11/55). Elderly ( OR=1.06, P=0.048 ) , hyponatremia( OR=0.81, P=0.020), high protein level in cerebrospinal fluid (CSF) ( OR=3.32, P=0.033), cerebral infarction( OR=10.50, P=0.040) and hydrocephalus( OR=8.51, P=0.049) were associated with poor prognosis in TBM patients. Conclusions:The mortality rate is high in patients with TBM. Molecular biology tests improves the sensitivity and shorten the diagnosis time of TBM. Elderly, hyponatremia, high protein level in CSF, cerebral infarction and hydrocephalus are independent risk factors of long-term survival in TBM patients.