Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

The aim of this study was to investigate the effect of baicalein on a Drosophila model of hereditary Parkinson's disease caused by gene mutations and to preliminarily elucidate the mechanism of baicalein in delaying hereditary Parkinson's disease. In this paper, PTEN-induced putative kinase 1 (PINK1)-RNAi Parkinson's Drosophila were used as the model group and wild-type Drosophila w¹¹¹⁸ were used as the control group. Different doses of baicalein and Madopa were administered to the model group to observe their effects on the life span, motor ability, the abnormal rate of wings, dopamine content and dopaminergic neurons of PINK1-RNAi Parkinson's Drosophila and their effects on mitochondrial dysfunction including adenosine triphosphate (ATP), mitochondrial DNA (mtDNA) and reactive oxygen species (ROS) content. The results showed that the effective administration doses of baicalein were 0.8 mg·mL^-1 for low concentration, 1.6 mg·mL^-1 for medium concentration and 3.2 mg·mL^-1 for high concentration, and the optimal administration dose of the positive drug Madopa was 0.1 μg·mL^-1. Baicalein and Madopa could significantly improve the life span, exercise ability and reduce the abnormal rate of wings of PINK1-RNAi male Drosophila (P < 0.05), and low dose baicalein showed the best effect; baicalein could improve the loss of dopaminergic neurons, and the effects of low dose and high dose were the best, but Madopa showed no significant effect; baicalein and Madopa had no significant effect on dopamine content (P > 0.05). Baicalein and Madopa could increase the ATP content of PINK1-RNAi male Drosophila (P < 0.05), and low dose baicalein showed the best effect; middle dose baicalein could significantly increase the mtDNA content of PINK1-RNAi male Drosophila (P < 0.05), but Madopa had no significant effect; baicalein and Madopa had no significant effect on ROS content (P > 0.05).

OBJECTIVE: To evaluate the association between serum uric acid (SUA) and kidney function decline. METHODS: Data was obtained from the China Health and Retirement Longitudinal Study on the Chinese middle-aged and older population for analysis. The kidney function decline was defined as an annual estimated glomerular filtration rate (eGFR) decrease by > 3 mL/min per 1.73 m ². Multivariable logistic regression was applied to determine the association between SUA and kidney function decline. The shape of the association was investigated by restricted cubic splines. RESULTS: A total of 7,346 participants were included, of which 1,004 individuals (13.67%) developed kidney function decline during the follow-up of 4 years. A significant dose-response relation was recorded between SUA and the kidney function decline ( OR 1.14, 95% CI 1.03-1.27), as the risk of kidney function decline increased by 14% per 1 mg/dL increase in SUA. In the subgroup analyses, such a relation was only recorded among women ( OR 1.22, 95% CI 1.03-1.45), those aged < 60 years ( OR 1.22, 95% CI 1.05-1.42), and those without hypertension and without diabetes ( OR 1.22, 95% CI 1.06-1.41). Although the dose-response relation was not observed in men, the high level of SUA was related to kidney function decline ( OR 1.83, 95% CI 1.05-3.17). The restricted cubic spline analysis indicated that SUA > 5 mg/dL was associated with a significantly higher risk of kidney function decline. CONCLUSION The SUA level was associated with kidney function decline. An elevation of SUA should therefore be addressed to prevent possible kidney impairment and dysfunction.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; East Asian People ; Glomerular Filtration Rate ; Kidney/physiopathology* ; Longitudinal Studies ; Risk Factors ; Uric Acid/blood*

The chemical constituents from the fruits of Morinda citrifolia were systematically explored by chromatographic fractionation methods including silica gel, octadecylsilyl(ODS) gel, Sephadex LH-20 gel, and preparative high performance liquid chromatography(pre-HPLC). The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, as well as the comparisons of their physicochemical and spectroscopic data with the reported data in literature. As a result, 22 isolated compounds from the 90% ethanol extract of the fruits of M. citrifolia were identified, which were moricitritone(1), 2'-deoxythymidine(2), cyclo-(L-Pro-L-Tyr)(3), methyl-5-hydroxy-2-pyridinecarboxylate(4), methyl pyroglutamate(5), bisbenzopyran(6), epipinoresinol(7), 3, 3'-bisdemethyl pinoresinol(8), 3, 3'-bisdemethyltanegool(9), trimesic acid(10), crypticin B(11), kojic acid(12), vanillic acid(13), protocatechoic acid(14), 5-hydroxymethyl furfural(15), blumenol A(16), 1-O-(9Z, 12Z-octadecadienoyl) glycerol(17), mucic acid dimethylester(18), methyl 2-O-β-D-glucopyranosylbenzoate(19), 2-phenylethyl-O-β-D-glucoside(20), scopoletin(21), and quercetin(22). Among them, compound 1 was a new pyrone derivative, compounds 2, 4-7, 10-12, and 17 were isolated from the plants belonging to Morinda genus for the first time, and compound 18 was obtained from M. citrifolia for the first time. Moreover, on the basis of testing the activities of all isolated compounds on inhibiting the proliferation of synovial fibroblasts in vitro by MTS assay, the anti-rheumatoid arthritis activities of all isolated compounds were initially evaluated. The results showed that compounds 1-6, 9, 19, and 20 exhibited remarkable anti-rheumatoid arthritis activities, which displayed the inhibitory effects on the proliferation of MH7A synovial fibroblast cells with the IC_(50) values in the range of(3.69±0.08) to(168.96±0.98) μmol·L~(-1).
Fruit/chemistry* ; Morinda/chemistry* ; Synoviocytes ; Cell Proliferation ; Arthritis

OBJECTIVES: To establish a method for the simultaneous quantitative analysis of etomidate and its metabolite etomidate acid in blood, and to discuss its application value in actual cases. METHODS: Acetonitrile precipitate protein method was used, and C₁₈ column was selected. Gradient elution was performed with acetonitrile and 5 mmol/L ammonium acetate within 6 min. Electrospray ionization source in positive ion mode was used. The internal standard etomidate acid-d₅ was obtained by etomidate-d₅ alkaline hydrolysis reaction. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for quantitative analysis. The methodological verification was conducted. RESULTS: Etomidate and etomidate acid in blood showed good linear relationship in the quantitative linear range (r>0.999), with the lower limit of quantification was 2.5 ng/mL and 7.5 ng/mL, respectively. The accuracy, precision, recovery rate, and matrix effect of the method met the professional verification standards. The practical application results showed that etomidate and etomidate acid could be detected in the blood of the abusers, and their mass concentrations ranged from 17.24 to 379.93 ng/mL. CONCLUSIONS The method established in this study can simultaneously quantify etomidate and etomidate acid in blood, which is simple and convenient to operate with accuracy. It can meet the detection needs of actual cases and provide technical support for law enforcement to crack down on etomidate abuse.
Chromatography, High Pressure Liquid/methods* ; Chromatography, Liquid ; Etomidate ; Tandem Mass Spectrometry/methods* ; Liquid Chromatography-Mass Spectrometry ; Acetonitriles

Traditional Chinese medicine （TCM） effervescent tablets have the characteristics of rapid disintegration， good taste， and convenient taking， but there are some technical difficulties in the preparation and storage process， which are mainly reflected in the sticking， easy moisture absorption， poor compressibility， and poor stability. The basic physical properties of TCM powder （extract powder， raw powder） are the main cause of these technical problems， and also the key to control the quality of TCM effervescent tablets. Powder modification technology has shown good effects in solving the above problems. The author intended to review the research in the above aspects in recent years， and proposed the following strategies for applying powder modification technology to solve the problems in the production process of TCM effervescent tablets from the three aspects of raw materials， excipients and preparation intermediates：①The application of co-processing technology to the treatment of raw materials and auxiliary materials can solve the problems of sticking， poor compressibility， delayed disintegration， and poor stability. ②Using surface coating technology to treat raw materials and preparation intermediates can improve poor fluidity， poor compressibility and delayed disintegration. ③The hygroscopicity of the preparation can be reduced by using microencapsulation technology to treat the raw material. ④The inclusion technology can improve the clarity and stability of the preparation.

The high performance liquid chromatography(HPLC) characteristic chromatogram of Xiaoer Ganmaoning Oral Liquid(oral liquid for short) was established. The medicinal materials corresponding to characteristic peaks, their index components and ranges of similarity with the reference chromatograms were clarified. The similarity between the characteristic chromatograms of 10 batches of the oral liquid and the reference chromatogram was higher than 0.994. Eighteen characteristic peaks were identified, which were derived from different medicinal materials including Scutellariae Radix, Arctii Fructus, Lonicerae Japonicae Flos, Gardeniae Fructus and Forsythiae Fructus. Further, 11 characteristic peaks were assigned by the comparison with reference substances as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, baicalin, baicalein, wogonin, scutellarin, forsythiaside A and arctiin. Also, the characteristic chromatogram of precipitate in the oral liquid was established, and the similarity between characteristic chromatograms of 10 batches of the precipitate and the reference chromatogram was higher than 0.940. The 14 characteristic peaks originating from the precipitate and those from the oral liquid were consistent in retention time, and the content of all index components in the precipitate was lower than 5% of that in the oral liquid. Moreover, the stability of precipitate during the accelerated stability test was explored with filtration and Matlab-based image sensory evaluation. The precipitate mass and precipitation degree both increased over the stability test duration significantly. The stability of the oral liquid was used as a model system in this study to establish the integrated quality control system which related to medicinal materials, preparations and precipitate with HPLC characteristic chromatograms and image sensory evaluation, which lays a foundation for the exploration of the quantity value transfer of the oral liquid.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Scutellaria baicalensis/chemistry*

Anemia of chronic disease (ACD), complicated by various chronic inflammatory diseases, is the second most prevalent type of anemia after iron deficiency anemia in the world. ACD significantly reduces the life quality of patients with chronic diseases, and represents an independent poor prognostic factor in certain chronic diseases. A large body of studies has demonstrated that most of anemia is related to abnormal iron metabolism. In the past decade, hepcidin, as a key factor in regulating iron metabolism, has attracted enormous attention due to its important role in the pathogenesis of ACD. This article reviews the research progress on the role and underlying regulatory mechanisms of hepcidin in ACD. We also discuss the potential of hepcidin as an effective therapeutic target for ACD treatment, in order to provide a new maneuver for improving the quality of ACD patients' life.
Anemia ; Anemia, Iron-Deficiency/pathology* ; Chronic Disease ; Hepcidins ; Humans ; Iron/metabolism*

The chemical constituents from the branches and leaves of Artocarpus incisus were isolated and purified via silica gel, ODS, and Sephadex LH-20 column chromatography as well as preparative HPLC. The chemical structures of all isolated compounds were identified in the light of their physicochemical properties, spectroscopic analyses, and comparisons of their physicochemical and spectroscopic data with the reported data in literature. As a result, 20 compounds were isolated and characterized from the 90% ethanol extract of the branches and leaves of A. incisus, which were identified as tephrosin(1), 6-hydroxy-6 a, 12 a-dehydrodeguelin(2), sarcolobin(3), lupiwighteone(4), 12-deoxo-12α-methoxyelliptone(5), 6 aα,12 aα-12 a-hydroxyelliptone(6), homopterocarpin(7), 3-hydroxy-8,9-dimethoxypterocarpan(8), pterocarpin(9), maackiain(10), medicarpin(11), calycosin(12), genistein(13), formononetin(14), 5-hydroxy-4',7-dimethoxy isoflavone(15), liquiritigenin(16), 4(15)-eudesmene-1β,7α-diol(17), ent-4(15)-eudesmene-1β,6α-diol(18), 1α-hydroxyisodauc-4-en-15-al(19), and guaianediol(20). Except compounds 13 and 16, all other compounds were isolated from the Artocarpus plants for the first time. Additionally, using MTS assay, compounds 1-20 were eva-luated for their anti-rheumatoid arthritis activities by measuring their anti-proliferative effects on synoviocytes in vitro. As a consequence, compounds 1-16 showed notable anti-rheumatoid arthritis activities, which displayed inhibitory effects on the proliferation of MH7 A synovial fibroblast cells, with the IC_(50) values in range of(9.86±0.09)-(218.07±1.96) μmol·L~(-1).
Arthritis ; Artocarpus ; Cell Proliferation ; Ethanol ; Genistein ; Plant Extracts/pharmacology* ; Silica Gel ; Synoviocytes