This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

Objective: To investigate the prevalence of suicidal ideation among MSM, and to explore the influence of perceived social support and depression on suicidal ideation and the possible pathway. Methods: MSM who are ≥18 years, HIV-negative, and ever had sex with men (oral sex/anal sex) in the last year participated in is study. Cross-sectional survey and convenient sampling method were used to recruit MSM through a male social interaction platform Blued 7.5 software from December 2020 to March 2021, with a questionnaire survey. Demographic questionnaire, Perceived Social Support Questionnaire and Center for Epidemiologic Studies Depression Scale were employed to collect data. Mplus 8.3 was used for data analysis. Results: Among 1 394 eligible MSM participants, 25.7% (358/1 394) had suicidal ideation. Perceived social support could have a direct effect on suicidal ideation (β=-0.11, P=0.009), and an indirect effect on suicidal ideation through depression (β=-0.18, P<0.001). Conclusions: Suicidal ideation was found to be lower in MSM with a higher level of perceived social support and a lower level of depression. Using social media to improve MSM's perceived social support and reduce depressive symptoms might be an effective means to prevent suicidal ideation.
Cross-Sectional Studies ; Depression/epidemiology* ; Homosexuality, Male ; Humans ; Male ; Sexual Behavior ; Sexual and Gender Minorities ; Social Support ; Suicidal Ideation

Objective:To investigate the application value of advance care planning among patients with chronic heart failure, so as to provide reference for the clinical practice of advance care planning.Methods:A total of 62 chronic heart failure patients from October 2017 to November 2019 in Fuwai Central China Cardiovascular Hospital were assigned to control group and experimental group according to the enrolled time, with 31 cases in each group. The patients in the control group from October 2017 to October 2018 recieved routine nursing, the experimental group from November 2018 to November 2019 carried out advance care planning based on the routine care. Before and after 3 weeks of intervention, the fatigue symptom and psychological condition were assessed by the Multidimensional Fatigue Inventory (MFI-20) and Symptom Checklist 90 (SCL-90), respectively.Results:There was no significant difference in the score of MFI-20 and SCL-90 before intervention between the two groups( P>0.05). After 3 weeks of intervention, the mental fatigue scores and total scores in MFI-20 were (8.23 ± 2.77), (51.00 ± 5.03) points in the experimental group, significantly lower than those in the control group (10.23 ± 2.58), (54.06 ± 5.50) points, the differences were statistically significant ( t=2.94, 2.29, all P<0.05). After 3 weeks of intervention, the somatization, obsessive symptoms, depression, anxiety, hostility scores and total score of SCL-90 were (1.28 ± 0.14), (1.43 ± 0.09), (1.19 ± 0.12), (1.13 ± 0.08), (1.33 ± 0.07), (121.00 ± 3.68) points in the experimental group, significantly lower than those in the control group (1.82 ± 0.44), (1.73 ± 0.58), (1.69 ± 0.12), (1.78 ± 0.13), (1.39 ± 0.10), (144.69 ± 9.09) points, the differences were statistically significant ( t values were 2.76-23.06, all P<0.05). Conclusions:Advance care planning can effectively alleviate fatigue symptom and improve psychological condition of patients with chronic heart failure.

Objective:To investigate the protective effect and molecular mechanism of Angelicae Sinensis Radix-Chuanxiong Rhizoma medicated serum （ASRCRS） against oxidative damage of PC12 cells induced by H₂O₂. Method:Oxidative damage of PC12 cells was induced by H₂O₂ in vitro， and intervention was performed in the low-， medium-， and high-dose ASRCRS groups with a final volume fraction of 15%. The cell viability was determined by methyl thiazolyl tetrazolium （MTT） assay. Cell morphology was observed by an inverted fluorescence microscope. The content of lactate dehydrogenase （LDH） and malondialdehyde （MDA）， the activity of superoxide dismutase （SOD）， and the distribution of reactive oxygen species （ROS） in the cell supernatant were detected by the kits. Cell apoptosis was detected by Annexin V-FITC/PI double staining. The protein expression levels of nuclear factor E₂-related factor 2 （Nrf2）， Kelch-like epichlorohydrin associated protein-1 （Keap1）， heme oxygenase-1 （HO-1）， and SOD1 were detected by Western blot. Result:Oxidative damage was induced by 300 μmol·L^-1 H₂O₂ for 24 hours. Compared with the normal group， the model group showed abnormal cell morphology， reduced cell viability （P<0.01）， increased LDH and MDA （P<0.01）， blunted SOD activity， elevated intracellular distribution of ROS， down-regulated protein expression of Nrf2， HO-1， and SOD1 （P<0.05， P<0.05）， and up-regulated protein expression of Keap1 （P<0.01）. Compared with the model group， ASRCRS groups displayed improved cell morphology， increased cell viability， inhibited cell apoptosis， potentiated SOD activity （P<0.01）， suppressed release of LDH （P<0.01） and generation of ROS， decreased content of MDA （P<0.01）， up-regulated protein expression of Nrf2， HO-1 and SOD1 （P<0.05， P<0.01）， and down-regulated protein expression of Keap1 （P<0.01）. Conclusion:ASRCRS could protect PC12 cells from oxidative damage induced by H₂O₂ by up-regulating the expression of Nrf2 to activate the Nrf2/antioxidant response element （ARE） signaling pathway， enhancing the ability to resist oxidative damage， and inhibiting cell apoptosis.

Objective Alzheimer's disease (AD) is the most common cause of dementia. The pathophysiology of the disease mostly remains unearthed, thereby challenging drug development for AD. This study aims to screen high throughput gene expression data using weighted co-expression network analysis (WGCNA) to explore the potential therapeutic targets.Methods The dataset of GSE36980 was obtained from the Gene Expression Omnibus (GEO) database. Normalization, quality control, filtration, and soft-threshold calculation were carried out before clustering the co-expressed genes into different modules. Furthermore, the correlation coefficients between the modules and clinical traits were computed to identify the key modules. Gene ontology and pathway enrichment analyses were performed on the key module genes. The STRING database was used to construct the protein-protein interaction (PPI) networks, which were further analyzed by Cytoscape app (MCODE). Finally, validation of hub genes was conducted by external GEO datasets of GSE 1297 and GSE 28146.Results Co-expressed genes were clustered into 27 modules, among which 6 modules were identified as the key module relating to AD occurrence. These key modules are primarily involved in chemical synaptic transmission (GO:0007268), the tricarboxylic acid (TCA) cycle and respiratory electron transport (R-HSA-1428517).

Objective To analyze the characteristics of the bilateral external ears of Uygur adults by directly observing the morphological characteristics of the external ears of Uygur adults and classifying each feature. The frequency distribution of the characteristics was calculated to provide reference for forensic identification. Methods The 210 cases （75 males and 135 females） of bilateral external ear photos of Uygur adults in Xinjiang that met the inclusion criteria were collected. The frequencies of the features of the external ear were recorded and distinguished between the two sexes and the different sides. The data were statistically analyzed by SPSS 21.0 statistical software. Results The shapes of the external ears of males and females were commonly oblique or rectangular （34.67% of the left external ear of males and 41.33% of the right were oblique; 30.37% of the left and right external ear of females were rectangular）, while triangular ears were the rare variants and the least common. Sex and bilateral differences were observed as regards the form of the helix in the subjects. Normally rolled helix was the most common （58.67% males and 61.48% females for the left ear; 60.00% males and 72.59% females for the right ear）. Wide covering scapha helix was the most rare for the male left ear and flat helix was the most rare for the female right ear. Square and free earlobes were the most common （49.33% males and 62.96% females for the left ear; 40.00% males and 54.81% females for the right ear）, whereas triangular earlobes were rarely seen. Single knob tragus （40.00% males and 37.78% females for the left ear; 37.33% males and 33.33% females for the right ear） and projection type of Darwin's tubercle （50.67% males and 40.00% females for the left ear; 48.00% males and 39.26% females for the right ear） were found to be common. Conclusion The characteristics of the bilateral external ears of male and female Uygur adults have differences, which can be used for forensic identification.
Adult ; Ear, External ; Ethnicity ; Female ; Humans ; Male ; Sex Characteristics

Objective: To predict B cell and T cell epitopes of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins. Methods: The sequences of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins which were derived from Orientia tsutsugamushi were analyzed by SOPMA, DNAstar, Bcepred, ABCpred, NetMHC, NetMHC II and IEDB. The 58-kDa tertiary structure model was built by MODELLER9.17. Results: The 22-kDa B-cell epitopes were located at positions 194-200, 20-26 and 143-154, whereas the T-cell epitopes were located at positions 154-174, 95-107, 17-25 and 57-65. The 47-kDa protein B-cell epitopes were at positions 413-434, 150-161 and 283-322, whereas the T-cell epitopes were located at positions 129-147, 259-267, 412-420 and 80-88. The 56-kDa protein B-cell epitopes were at positions 167-173, 410-419 and 101-108, whereas the T-cell epitopes were located at positions 88-104, 429-439, 232-240 and 194-202. The 58-kDa protein B-cell epitopes were at positions 312-317, 540-548 and 35-55, whereas the T-cell epitopes were located at positions 415-434, 66-84 and 214-230. Conclusions: We identified candidate epitopes of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins from Orientia tsutsugamushi. In the case of 58-kDa, the dominant antigen is displayed on tertiary structure by homology modeling. Our findings will help target additional recombinant antigens with strong specificity, high sensitivity, and stable expression and will aid in their isolation and purification.

Near-infrared spectroscopy (NIRS) combined with chemometrics can achieve rapid detection in process analysis. After variable selection, the redundant information is effectively removed and the characteristic variables related to the response values are selected. Compared with global model, the complexity is significantly reduced and the prediction accuracy is also improved. In this study, near-infrared spectroscopy analysis combined with different variable selection methods was applied to achieve the rapid detection of baicalin in the extraction process of Scutellaria baicalensis. Data sets were divided based on sample set portioning based on joint x-y distance (SPXY) method. Competitive adaptive weighted resampling method (CARS), random frog (RF) and successive projections algorithm (SPA) were applied to variable selection. Partial least squares (PLS) models were constructed based on above three methods, and the prediction results were compared. After CARS, RF and SPA method, 92, 10 and 17 variables were screened out respectively. According to the performance of the models, CARS method is found to be more effective and suitable than RF and SPA. Furthermore, the characteristic variables selected by CARS method have a better correspondence with the chemical structure of baicalin. The root mean square error (RMSEC) of the calibration set and the root mean square error (RMSEP) of the prediction set are 0.528 2 and 0.720 2 respectively. Compared with the global PLS model, the correlation coefficient of the calibration set (Rc) is increased to 0.979 9 from 0.917 0, and the relative standard errors of prediction (RSEP) is reduced to 5.59% from 10.58%.

Objective:To investigate the protective effect of ferulic acid on PC12 cells injured by H₂O₂ and the molecular mechanisms. Method:The oxidative stress model was established by treating PC12 cells with H₂O₂, and then different dosages of ferulic acid (1, 10, 100 μmol·L^-1) were used for intervention. Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the cell viability,lactate dehydrogenase (LDH) and malondialdelyde (MDA) in cell supernatant, and superoxidedismutase (SOD) in cells was tested by biochemical method respectively. Insulin-like growth factors-1 (IGF-1) mRNA and protein expressions were detected by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) and Western blot. Result:The 24 h intervention with different dosages of ferulic acid (1, 10, 100 μmol·L^-1) could significantly improve the oxidative damage of PC12 cells induced by H₂O₂, compared with the model group, ferulic acid at 1,10,100 μmol·L^-1 significantly increased PC12 cells viability,significantly decreased LDH and MDA content in cell supernatant (P<0.05, P<0.01), and enhanced SOD activity(P<0.01). Real-time PCR and Western blot showed that compared with control group,IGF-1 mRNA and protein expressions in model group decreased significantly (P<0.01), compared with model group, IGF-1 mRNA and protein expressions in ferulic acid group increased significantly (P<0.01). Conclusion:Ferulic acid exerts a protective effect on H₂O₂-inducing PC12 cells injury,which might be related to insulin signaling pathways.

A large amount of nicotinamide adenine dinucleotide phosphate (NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells. Malic enzyme 1(ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool. ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis. In the present study, we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma(NPC) cells. High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells. However, there were no obvious changes in the other two pathways for glucose metabolism: glycolysis and oxidative phosphorylation. Interestingly, NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells, whereas no significant difference was observed under high-glucose condition. ME1-repressed cells had significantly decreased tolerance to low-glucose condition. Moreover, NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress. Furthermore, diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein. Collectively, these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.
Carcinoma ; Cell Line, Tumor ; Cell Movement ; Cell Survival ; Glucose ; metabolism ; Glycolysis ; Humans ; Malate Dehydrogenase ; metabolism ; NADP ; metabolism ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Invasiveness ; Oxidation-Reduction ; Oxidative Phosphorylation ; Pentose Phosphate Pathway ; Proto-Oncogene Proteins c-akt ; metabolism