Processing for deodorization is widely used in the production of animal-derived Chinese medicinal materials. In this study, Heracles Neo ultra-fast gas-phase electronic nose combined with chemometrics was employed to analyze the overall odor difference of Cervi Cornu Pantotrichum(focusing on that derived from Cervus nippon Temminck in this study) before and after processing. The results showed that the electronic nose effectively distinguished between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. HS-GC-MS was used to identify and quantify the volatile components in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum, and 35 and 37 volatile components were detected in the medicinal materials and decoction pieces, respectively. The medicinal materials and decoction pieces contained 28 common volatile components contributing to the odor of Cervi Cornu Pantotrichum. The odor activity value(OAV) of each volatile component was calculated based on the olfactory threshold and relative content. The results showed that there were 17 key odor substances such as isovaleraldehyde, 2-methylbutanal, isobutyraldehyde, hexanal, and methanethiol in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. All of them had bad odor and were the main source of the odor of Cervi Cornu Pantotrichum. The results of principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) showed that there were significant differences in volatile components between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. Based on the thresholds of P<0.05 and Variable Importance in Projection(VIP)>1, 21 differential volatile odor components were screened out. Among them, isopentanol, isovaleraldehyde, 2-methylbutanal, n-nonanal, and dimethylamine were the key differential odor compounds between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. The odor compounds and their relative content reduced, and some flavor substances such as esters were produced after processing with wine, which was the main reason for the reduction of the odor after processing of Cervi Cornu Pantotrichum.
Odorants/analysis* ; Electronic Nose ; Gas Chromatography-Mass Spectrometry/methods* ; Animals ; Volatile Organic Compounds/analysis* ; Deer ; Drugs, Chinese Herbal/chemistry*

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are limited.This study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum women. Methods A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this study.The urinary iodine concentration(UIC),TSH,VA,and VD were measured. Results The median UIC of total and lactating participants were 142.00 μg/L and 139.95 μg/L,respectively.The median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44 μg/mL,and 24.04 ng/mL,respectively.No differences in the UIC were found between lactating and non-lactating mothers.UIC and TSH levels were significantly different among the three provinces.The rural UIC was higher than the urban UIC.Obese mothers had a higher UIC and a higher prevalence of excessive TSH.Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group.After adjustment,no linear correlation was observed between UIC and VA/VD.No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion The mothers in the present study had no iodine deficiency.Region,area type,BMI,and VD may be related to the iodine status or TSH levels.

Objective To investigate the effect of antinuclear antibodies(ANAs)on hormone response in patients with autoimmune hepatitis(AIH)-primary biliary cholangitis(PBC)overlap syndrome(AIH-PBC OS)and AIH-only within half a year.Methods A retrospective analysis of 77 patients with autoimmune liver disease(AILD)admitted to First Clinical Medical College of Lanzhou University from January 2018 to December 2021,all of whom were confirmed by liver biopsy and receiving glucocorticoid treatment.Among them,46 patients were in AIH-PBC OS group and 31 were in AIH-only group.The general clinical characteristics,liver puncture-related indexes,autoantibodies and immunoglobulin indexes of patients in each group at the time of diagnosis were collected and compared,and the biochemical and immunoglobulin indexes of patients at the time of hormone use and at the time of review within 6 months were also collected,and the hormone response within 6 months was evaluated according to the levels of glutamic transaminase(AST),glutamic alanine transaminase(ALT)and immunoglobulin G(IgG),and the effect of ANAs on hormone response outcomes in both groups over a six-month period was analyzed.Multifactorial ordered logistic analysis was performed to evaluate the effect of ANAs on hormone response between two groups.Results There was no statistically significant difference in the percentage of AIH-PBC OS and AIH-only patients among both ANAs-positive and-negative AILD patients(55.6%vs.44.4%and 65.6%vs.34.4%,P>0.05).Among 46 patients with AIH-PBC OS,there were 25 in ANAs-positive group and 21 in ANAs-negative group.The rate of complete hormone response within 6 months was lower than that of ANAs-negative group(44.0%vs.76.2%),while the rate of hormone non-response was higher than that of ANAs-negative group(20.0%vs.0),and the difference was statistically significant(P<0.05).There were 20 cases of ANAs-positive and 11 cases of ANAs-negative in the 31 AIH-only patients.There was no statistically significant difference in the results of hormone response within 6 months between the two groups(P>0.05).Multifactorial ordered logistic analysis showed that AIH-PBC OS patients were more likely to have a higher likelihood of 6-month hormone non-response rate in ANAs-positive patients,and the difference was statistically different(P<0.05).And there was no significant effect of ANAs type on hormone response outcome in AIH-only patients(P>0.05).Conclusion AIH-PBC OS ANAs-positive patients have a poor hormone response within half a year.In AIH-only patients,ANAs have no significant effect on hormone response results.

PI3Kγ and PI3Kδ have important regulatory roles in the immune system, and targeting these two subtypes helps to reshape the tumor microenvironment. PI3Kγ and PI3Kδ are potential targets for tumor immunotherapy. In this study, a series of new pyrazolopyrimidine derivatives were designed and synthesized on the basis of our previously reported PI3K inhibitors, resulting in the discovery of compound 16l as a potent and selective PI3Kγ/δ dual inhibitor. Compound 16l demonstrated strong biochemical potencies against PI3Kγ and PI3Kδ with IC₅₀ values of 0.11 and 0.79 nmol·L^-1. In cell-based assays, it potently inhibited the PI3Kγ and PI3Kδ mediated Akt S473 phosphorylation with EC₅₀ values of 3 and 7 nmol·L^-1. In vivo, compound 16l exhibited acceptable pharmacokinetic properties in Sprague-Dawley (SD) rats and suppressed the tumor growth in a MC38 syngeneic mouse model. The animal experiments were approved by the Animal Ethics Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (approval number: DWLL-2000-06). In addition, no appreciable human ether-a-go-go-related gene (hERG) inhibition was observed for compound 16l even at 30 μmol·L^-1. These results suggested that compound 16l might be a potential research tool for studying the PI3Kγ/δ mediated signaling pathways.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

The chemical components of Huanglian Decoction were identified by ultra-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS) technology. The gradient elution was conducted in Agilent ZORBAX Extend-C_(18) column(2.1 mm×100 mm, 1.8 μm) with the mobile phase of 0.1% formic acid aqueous solution(A)-acetonitrile(B) at a flow rate of 0.3 mL·min~(-1) and the column temperature of 35 ℃. The MS adopted the positive and negative ion mode of electrospray ionization(ESI), and the MS data were collected under the scanning range of m/z 100-1 500. Through high-resolution MS data analysis, combined with literature comparison and confirmation of reference substances, this paper identified 134 chemical components in Huanglian Decoction, including 12 alkaloids, 23 flavonoids, 22 terpenes and saponins, 12 phenols, 7 coumarins, 12 amino acids, 23 organic acids, and 23 other compounds, and the medicinal sources of the compounds were ascribed. Based on the previous studies, 7 components were selected as the index components. Combined with the network pharmacology research and analysis me-thods, the protein and protein interaction(PPI) network information of the intersection targets was obtained through the STRING 11.0 database, and 20 core targets of efficacy were screened out. In this study, UPLC-Q-TOF-MS/MS technology was successfully used to comprehensively analyze and identify the chemical components of Huanglian Decoction, and the core targets of its efficacy were discussed in combination with network pharmacology, which laid the foundation for clarifying the material basis and quality control of Huanglian Decoction.
Tandem Mass Spectrometry ; Network Pharmacology ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Technology

Cortical interneurons can be categorized into distinct populations based on multiple modalities, including molecular signatures and morpho-electrical (M/E) properties. Recently, many transcriptomic signatures based on single-cell RNA-seq have been identified in cortical interneurons. However, whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown. Here, we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA (mRNA) expression of >600 interneurons in layer V of the mouse somatosensory cortex (S1). Subsequently, we identified 11 M/E subtypes, 9 neurochemical cell populations (NCs), and 20 transcriptomic cell populations (TCs) in this cortical lamina. Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically. A similar analysis of layer V interneurons of mouse primary visual cortex (V1) and motor cortex (M1) gave results largely comparable to S1. Comparison between S1, V1, and M1 suggested that, compared to V1, S1 interneurons were morpho-electrically more similar to M1. Our study reveals the presence of substantial M/E variations in cortical interneuron populations defined by molecular expression.
Mice ; Animals ; Neocortex/physiology* ; Mice, Transgenic ; Interneurons/physiology*

Objective: To explore a method for digitally designing and fabricating a sequential tooth-sectioning guide that can assist in the extraction of mandibular horizontal impacted third molars, preliminarily evaluate its feasibility and provide a reference for clinical application. Methods: Twenty patients with mandibular low level impacted third molars who visited the Department of General Dentistry, Peking University School and Hospital of Stomatology from March 2021 to January 2022 were selected. Cone-beam CT showed direct contact between the roots and mandibular canal, and full range impressions of the patients' intraoral teeth were taken and optical scans of the dental model were performed. The patients' cone-beam CT data and optical scan data were reconstructed in three dimensions, anatomical structure extraction, registration fusion, and the design of the structure of the guide (including crown-sectioning guide and root-sectioning guide) by Mimics 24.0, Geomagic Wrap 2021, and Magics 21.0 software, and then the titanium guide was three dimension printed, and the guide was tried on the dental model. After confirmation, the guide was used to assist the dentist in the operation. We observed whether the guide was in place, the number of tooth splitting, the matching of tooth splitting with the preoperative design, the operation time, and whether there were any complications. Results: In this study, 20 sectioning guides were successfully printed, all of them were well fitted in the patients' mouth, the average number of section was 3.4 times, the tooth parts was better matched with the preoperative design, and the average operative time of the guides was (29.2±9.8) minutes without complications such as perforation of the bone cortex. Conclusions: The use of sequential sectioning guides to assist in the extraction of mandibular impacted third molars was initially validated to accurately replicate the preoperative sectioning design, and is expected to provide a digital solution to improve surgical precision and ensure safety. Further studies with larger sample sizes are needed to evaluate its accuracy and safety.

Objective: To explore a simple and feasible method for the isolation and purification of hepatocytes, hepatic stellate cells (HSC), and lymphocytes from mice. Methods: The cell suspension was obtained from male C57bl/6 mice by hepatic perfusion through the portal vein digestion method and then isolated and purified by discontinuous Percoll gradient centrifugation. Trypan blue exclusion was used to determine cell viability. Glycogen staining, cytokeratin 18, and transmission electron microscopy were used to identify hepatic cells. Immunofluorescence was used to detect α-smooth muscle actin combined with desmin in HSCs. Flow cytometry was used to analyze lymphocyte subsets in the liver. Results: After isolation and purification, about 2.7×10(7) hepatocytes, 5.7×10(5) HSCS, and 4.6×106 hepatic mononuclear cells were obtained from the liver of mice with a body weight of about 22g. The cell survival rate in each group was > 95%. Hepatocytes were apparent in glycogen deposited purple-red granules and cytokeratin 18. Electron microscopy showed that there were abundant organelles in hepatocytes and tight junctions between cells. HSC had expressed α-smooth muscle actin and desmin. Flow cytometry showed hepatic mononuclear cells, including lymphocyte subsets such as CD4, CD8, NKs, and NKTs. Conclusion: The hepatic perfusion through the portal vein digestion method can isolate multiple primary cells from the liver of mice at once and has the features of simplicity and efficiency.
Male ; Mice ; Animals ; Keratin-18 ; Actins ; Desmin ; Liver ; Hepatocytes ; Hepatic Stellate Cells