Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

Objective: To investigate the detection and diagnostic efficacy of chest radiographs for ≤30 mm pulmonary nodules and the factors affecting them, and to compare the level of consistency among readers. Methods: A total of 43 patients with asymptomatic pulmonary nodules who consulted in Cancer Hospital, Chinese Academy of Medical Sciences from 2012 to 2014 and had chest CT and X-ray chest radiographs during the same period were retrospectively selected, and one nodule ≤30 mm was visible on chest CT images in the whole group (total 43 nodules in the whole group). One senior radiologist with more than 20 years of experience in imaging diagnosis reviewed CT images and recording the size, morphology, location, and density of nodules was selected retrospectively. Six radiologists with different levels of experience (2 residents, 2 attending physicians and 2 associate chief physicians independently reviewed the chest images and recorded the time of review, nodule detection, and diagnostic opinion. The CT imaging characteristics of detected and undetected nodules on X images were compared, and the factors affecting the detection of nodules on X-ray images were analyzed. Detection sensitivity and diagnosis accuracy rate of 6 radiologists were calculated, and the level of consistency among them was compared to analyze the influence of radiologists' seniority and reading time on the diagnosis results. Results: The number of nodules detected by all 6 radiologists was 17, with a sensitivity of detection of 39.5%(17/43). The number of nodules detected by ≥5, ≥4, ≥3, ≥2, and ≥1 physicians was 20, 21, 23, 25, and 28 nodules, respectively, with detection sensitivities of 46.5%, 48.8%, 53.5%, 58.1%, and 65.1%, respectively. Reasons for false-negative result of detection on X-ray images included the size, location, density, and morphology of the nodule. The sensitivity of detecting ≤30 mm, ≤20 mm, ≤15 mm, and ≤10 mm nodules was 46.5%-58.1%, 45.9%-54.1%, 36.0%-44.0%, and 36.4% for the 6 radiologists, respectively; the diagnosis accuracy rate was 19.0%-85.0%, 16.7%-6.5%, 18.2%-80.0%, and 0%-75.0%, respectively. The consistency of nodule detection among 6 doctors was good (Kappa value: 0.629-0.907) and the consistency of diagnostic results among them was moderate or poor (Kappa value: 0.350-0.653). The higher the radiologist's seniority, the shorter the time required to read the images. The reading time and the seniority of the radiologists had no significant influence on the detection and diagnosis results (P>0.05). Conclusions: The ability of radiographs to detect lung nodules ≤30 mm is limited, and the ability to determine the nature of the nodules is not sufficient, and the increase in reading time and seniority of the radiologists will not improve the diagnostic accuracy. X-ray film exam alone is not suitable for lung cancer diagnosis.
Humans ; Retrospective Studies ; Solitary Pulmonary Nodule/diagnostic imaging* ; Radiography ; Multiple Pulmonary Nodules/diagnostic imaging* ; Tomography, X-Ray Computed/methods* ; Lung Neoplasms/diagnostic imaging* ; Sensitivity and Specificity ; Radiographic Image Interpretation, Computer-Assisted/methods*

This study used UPLC-TQ-MS technology to replicate a Henoch-Schonlein purpura(HSP) model in rats by administering warm drugs by gavage and injecting ovalbumin with Freund's complete adjuvant emulsion. The distribution differences and characteristics of eight major components(ferulic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, benzoyl oxypaeoniflorin, tracheloside, loganin, and paeoniflorin) in rat liver, lung, heart, spleen, and kidney tissues were determined after oral administration of the Liangxue Tuizi Mixture at a dose of 42 g·kg~(-1) in both normal physiological and HSP states at 0.5, 1, 2, 6, and 12 hours. The results showed that the distribution patterns of the eight components of Liangxue Tuizi Mixture in the tissues of normal and HSP model rats were different. The main component, paeoniflorin, in Moutan Cortex and Paeoniae Radix Alba had higher content in all tissues. The eight components were predominantly distributed in the liver, lung, and kidney tissues, followed by spleen and heart tissues.
Rats ; Animals ; IgA Vasculitis/drug therapy* ; Monoterpenes ; Administration, Oral ; Liquid Chromatography-Mass Spectrometry

Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofission-associated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of pan-inhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynamin-related protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.

The aim of the present study was to explore the changes in some functional connectivity in the resting-state electroencephalogram (EEG) based functional brain network of depressed college students, and to understand the brain regions involved in the onset of depression and the electrophysiological activity of subcortical nerve cells, hoping to provide additional information for the diagnosis of depression. Twenty female college students with depressive symptoms were selected according to the Beck Depression Inventory-II (BDI-II) and the Self-rating Depression Scale (SDS). The EEG information of 20 female college students under resting-state was collected by using a 32-conduction EEG acquisition system (Neuroscan). Then Pearson correlation analysis, coherence analysis, phase locking value analysis, phase lag index analysis and weighted phase lag index analysis were used to construct the resting-state brain functional network. The results showed that, compared with the normal group, the depression group exhibited significantly increased correlation in θ and β bands of EEG (P < 0.05), and extremely significantly increased in α band (P < 0.01). Among them, the coherence in α and β bands was significantly increased (P < 0.05), mainly concentrated in the left hemisphere frontal lobe and temporal lobe region. The phase locking value in θ, α and β bands was significantly increased (P < 0.05), mainly concentrated in the prefrontal region and the left hemisphere from the frontal region to the temporal region, and the connectivity in α band was the most obvious. Correlation analysis showed a significant positive correlation between indicators of differential functional connectivity (coherence and phase locking value) and BDI-II scores in the depression group, and the receiver operating characteristics (ROC) curve indicated a high specificity of 85% for the differential indicators. These results suggest that the abnormal brain function of the depressed college students is related to the change of functional connectivity in the left hemisphere, especially α frequency band in the frontal region, which is of great significance for the diagnosis of depression in the future.
Brain/physiology* ; Brain Mapping/methods* ; Depression ; Electroencephalography ; Female ; Humans ; Students

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

OBJECTIVE To investigate the effect and potential mechanism of safflower polysaccharide on apoptosis and autophagy of human hepatocellular carcinoma cells. METHODS Human hepatocellular carcinoma HepG2， SMMC-7721 and Huh-7 cells were selected as subjects， and safflower polysaccharide was used as intervention drug to screen sensitive cells， intervention concentration and intervention time. The sensitive cells were selected as the object and intervened with different concentrations of safflower polysaccharide； the apoptosis， migration， clone formation， morphology and autophagy of human hepatocellular carcinoma cells were observed； the expressions of apoptosis， autophagy and phosphatidyl inositol-3-kinase （PI3K）/protein kinase B （Akt）/mammals rapamycin target protein （mTOR） signaling pathway related protein were detected. RESULTS safflower polysaccharide could inhibit the proliferation of 3 kinds of human hepatocellular carcinoma cells， and the half inhibition concentration of it to SMMC-7721 cells was significantly lower than to other two kinds of cells （P＜0.05）. After 48 h intervened with low， medium and high concentrations of safflower polysaccharide （20， 40， 80 μmol/L）， the apoptosis of SMMC-7721 cells was increased compared with the control group， and cell migration rates at 24 and 48 h （except for safflower polysaccharide low- dose group at 24 h） and clone formation rate at 24 h were significantly decreased compared with the control group （P＜0.05 or P＜ 0.01）. Compared with the control group， cell number in safflower polysaccharide groups was significantly decreased， and autophagy levels were improved to some extent； the relative expressions of cleaved caspase-3， caspase-9， Bax and beclin-1 protein and ratio of LC3Ⅱ/LC3Ⅰ were significantly increased， and the relative protein expressions of Bcl-2， p62， PI3K， mTOR and Akt were significantly decreased （P＜0.05 or P＜0.01）. CONCLUSIONS Safflower polysaccharide could effectively inhibit the proliferation and induce apoptosis and autophagy of human hepatocellular carcinoma SMMC-7721 cells， the mechanism of which may be related to the inhibition of PI3K/Akt/mTOR signaling pathway.

Cannulated Screw is a common internal fixation for the treatment of femoral neck fractures. However, the traditional implantation method has disadvantages such as inaccuracy and large radiation exposure. Based on the anatomical characteristics of the femoral neck and geometric principles, we develop a novel guide device for cannulated screws insertion. The cadaver experiment showed that it can improve the accuracy of cannulated screws implantation, reduce puncture attempts and the radiation exposure of doctors and patients.
Bone Screws ; Femoral Neck Fractures/surgery* ; Fracture Fixation, Internal ; Humans ; Robotic Surgical Procedures