Objective To provide a reference for the establishment, development and application of the adverse drug reaction （ADR） automated monitoring system, through verifying and quantifying the research hotspots and advantages of the system by CiteSpace software and systematic review. Methods Literature on ADR automated monitoring up to December 2023 were retrieved and screened from CNKI and web of science databases. CiteSpace 6.4.R1 software was used to conduct co-occurrence, clustering and emergence analysis, and to visualize and comparatively analyze the research hotspots, rules and distribution in the field of automated monitoring of ADR at home and abroad. In compliance with the preferred reporting items for systematic reviews and Meta-analyses （PRISMA）, literature covering publications in English and Chinese including detection rates of ADR collected using Incident Reporting Systems （IRSs） and/or automated monitoring systems were retrieved and screened. The advantages and disadvantages of automated monitoring systems were analyzed by comparing the differences between these two systems in terms of the number of ADR reports and the types of positive signals. Results A total of 56 articles in English and 80 articles in Chinese were indexed by CiteSpace. The research hotspots in recent years included data mining, deep learning, text classification techniques, machine learning and so on. A total of seven studies compiled with the inclusion criteria for the systematic evaluation, all of which were completed between 1991 and 2021 in hospitals in four countries. 150 526 medical records were reviewed from 15 institutions. A total of 194 ADR reports were collected by IRSs. A total of 2 090 ADR reports were collected by the automated monitoring system over the same period, indicating a 977% increase in the number of ADR reports （P=0.0156） compared with the IRSs. Conclusion The ADR automatic monitoring system had significantly improved the level of drug risk identification and reduced costs, but it was necessary to optimize the algorithm, expand the data source and carry out standardization construction to overcome the current limitations.

Feces and intestinal contents of pigs suspected with porcine epidemic diarrhea virus were collected from a farm in Minqin County,Gansu Province,China.After the suspected positive sam-ples were detected by RT-PCR,Vero cells were used to isolate and culture them in vitro.The suc-cessfully isolated virus was identified in the laboratory,and its whole genome sequence was ana-lyzed for genetic evolution.The pathogenicity was evaluated by animal regression test.The results showed that typical syncytial lesions could be observed when the PEDV-positive treatment solu-tion was inoculated with Vero cells in the 4th generation,and the virus titer in the 6th generation reached 10-4 75TCID50/mL.PEDV-like virions with a diameter of about 100 nm and a round shape with obvious capsular membranes and spikes were observed by electron microscopy.Whole genome sequencing analysis showed that the total length of this strain was 28 085 bp,which was far from the G1 subtype represented by the classical strain CV777(96.6％),and had a high homology with the G2b strains BC-2011-1,IA1,USA/Colorado/2013 and WELL(98.6％).This indicated that the strain belonged to the G2b epidemic strain.The animal regression test showed that the 5-day-old piglets developed vomiting,acute watery diarrhea,emaciation and mental depression within 12 h after the attack,and the symptoms worsened and died within 24 h.After autopsy,the infected piglets could be observed with stomach swelling,high intestinal heave,thin and transparent intesti-nal wall,and undigested milk clots inside.In summary,a PEDV G2b epidemic strain was success-fully isolated and identified in this study,and its whole genome sequence and pathogenicity were analyzed,providing research materials for future studies on PEDV gene function,pathogenic mech-anism and vaccine development.

To screen and identify the key host proteins interacting with the non-structural protein 15 (Nsp15) of porcine epidemic diarrhea virus (PEDV). The IP/pull-down assay and mass spectrometry were employed to screen and identify the host proteins interacting with Nsp15. The interaction between the host protein and Nsp15 was studied by co-immunoprecipitation and laser scanning confocal microscopy. Finally, Western blotting and RT-qPCR were employed to examine the interaction between SLC25a3 and PEDV. The recombinant eukaryotic expression vector pcDNA3.1(+)-Flag-Nsp15 was successfully constructed, and the host protein SLC25a3 interacting with PEDV Nsp15 was screened out. An interaction existed between SLC25a3 and Nsp15, and SLC25a3 significantly inhibited PEDV replication in a dose-dependent manner. SLC25a3 inhibits PEDV replication. The results of this study provide a basis for deciphering the role and mechanism of SLC25a3 in the host immune response to PEDV infection.
Porcine epidemic diarrhea virus/genetics* ; Viral Nonstructural Proteins/metabolism* ; Animals ; Swine ; Virus Replication ; Coronavirus Infections/veterinary* ; Swine Diseases/metabolism*

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.
Animals ; Cell Differentiation ; Flavanones ; Mice ; Mice, Inbred C57BL ; Myelin Sheath/metabolism* ; Oligodendroglia/metabolism* ; Rats ; Remyelination ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism*

Objective:To explore the effect of the implantation of absorbable stents on the prognosis of patients with inferior knee artery balloon dilatation.Methods:From March 2018 to January 2021, twenty-five patients with drug absorbable stent implantation after inferior knee artery balloon dilatation (stent group) and 25 patients without absorbable stent implantation after inferior knee artery balloon dilatation (control group) were included in Qingdao Haici Medical Group Affiliated to Qingdao University. The improvement of symptoms, ankle brachial index, Rutherford classification and claudication distance before and after operation were compared. The symptoms, ankle brachial index, Rutherford grade, claudication distance and patency rate of the two groups were compared 6 months after operation. The preoperative and postoperative data were analyzed by independent sample t-test, and the patency rate was analyzed by χ 2 test. Results:The ankle brachial index in the stent group and the control group on the first day after operation was significantly higher than that before operation (0.18±0.11 vs. 0.85±0.15, t=18.5, P<0.05, 0.22±0.15 vs. 0.87±0.10, t=20.8, P<0.05), and the Rutherford classification decreased significantly (4.66±0.21 vs. 2.1±0.11, t=9.2, P<0.05, 4.58±0.33 vs. 2.3±0.22, t=12.9, P<0.05), the limp distance increased significantly ((27±8) m vs. (300±43) m, t=20.8, P<0.05, (42±14) m vs. (320±18) m, t=32.6, P<0.05). There was no significant difference in preoperative ankle brachial index, postoperative ankle brachial index, Rutherford grade and claudication distance between the two groups ( P>0.05). Six months after operation, the ankle brachial index (0.72±0.03 and 0.54±0.12; t=10.2, P<0.05), Rutherford classification ((1.72±0.17) and (3.23±0.22); t=12.8, P<0.05) and claudication distance ((580.00±137.00) m and (267.00±54.00) m; t=8.2, P<0.05) in the stent group and the control group were significantly better than those in the control group. The patency rate of stent group at 6 months was 68% (17/25), which was better than that of ordinary balloon dilatation group by 56% (14/25). Conclusion:Implantation of drug absorbable stents can significantly improve the prognosis of patients undergoing arterial balloon dilatation.

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.

Objective To analyze the distribution of various genotypes of human cytomegalovirus glycoprotein N ( HCMV gN) in patients with HIV infection; to investigate the effects of HCMV-HIV co-in-fection on disease progression and the relationships between HCMV gN genotypes and disease progression. Methods Patients with active HCMV infection were screened out from 359 patients with HIV infection by using the pp65 antigenemia assay.The genes encoding HCMV gN ( UL73 ) were amplified by nested PCR ( nPCR) .The amplicons were digested by restriction enzymes including MboⅠ, ScaⅠ and SalⅠ.Then, the restricted fragment length polymorphisms were further analyzed on 4%agarose gel.The relationships be-tween HCMV genotypes and the morbidity and mortality of acquired immune deficiency syndrome ( AIDS ) were investigated via a prospective study.Results Among the 359 patients with HIV infection, 28 subjects were positive for the HCMV pp65 antigenemia assay.The HCMV gN genotypes in 20 patients with active HCMV infection were distributed as: gN-3a (4/20, 20%), gN-1 (4/20, 20%), gN-4d (1/20, 5%), gN-4b (1/20, 5%) and mixed infection (10/20, 50%).Patients with HCMV-HIV co-infection were more likely to develop AIDS during the follow-up period (RR=9.78).Patients harboring HCMV gN-1 and gN-4 genotypes would seem likely to have 4.6 times of chance leading to AIDS-associated death than those harbo-ring other HCMV gN genotypes.Conclusion HCMV infection ( especially gN-1 and gN-4 genotypes) might accelerate the progression of HIV infection.

Objective To analyze the different metabolites of the classical activated (M1) ,alternatively activated (M2) and resting BV2 cells by metabolomics method .Methods The mRNAs of several potential biomarkers were determined by real-time PCR analyses to confirm the state of BV2 cells .Static GC-MS combined with metabolomics technology was used to analyze the metabolic changes .Results There were 15 biomarkers identified between the M1 group and the resting group ,and 15 biomarkers were found in the M2 group and the resting group .Conclusion The present study provides an effective way to reveal the mechanism of the polarization of BV 2 cell ,and it might provide a theoretical basis to prevent or treat the neurodegen-erative diseases .

Objective To summarize the clinical experience about video-assisted-thoracoscopic in the treatment of thoracic surgical disease.Methods Through the video-assisted-thoracoscopic technique in the treatment of 282 cases with thoracic surgical diseases,which included the pulmonary bulla resection in 162 cases,the organizing blood thoracic dissection by trauma in 23 cases,the excision of lung-cyst in 17 cases,the empyema clearance and fibreboard stripping in 30 cases,the pulmonary nodular lesion resection in 17 cases,the peripheral lung wedge resection in 13 cases,the spontaneous pneumothorax pulmonary bulla resection and hemostasis hysterectomy in 9 cases,the pleural tumors in 6 cases,the esophageal leiomyoma in 2 cases,the removal foreign body of lung in 3 cases.Results The operative time was 30 ～ 180minutes,the volume of bleed was 20 ～650ml,the postoperative thoracic drainage was 3 ～ 16 days,the postoperative complications occurred in 11 patients,the incidence of complications was 3.9％,there was no death.Conclusion The thoracoscopic minimally invasive surgery is trauma,less bleeding,rapid recovery,and had the broader indications for thoracic surgery.

Objective To observe the dynamic changes of high mobility group protein B1 ( HMGB1 )expression in the lung of rats with Vibrio vulnificus sepsis so as to unravel the role of HMGB1 in lung injury.Methods Sixty rats of clean grade were randomly divided into normal control group ( A group, n = 10) and Vibrio vulnificus sepsis group (B group, n =50). Sepsis model was made in rats with subcutaneous injection of Vibrio vulnificus with concentration of 6 × 108 cfu/ml in dose of 0. 1 ml/100 g into left lower limb.The rats of group B were sacrificed 1 h, 6 h, 12 h, 24 h and 48 h after infection for taking lung tissues to detect the water content of lung and to observe the histopathological changes in lung under light microscope.The expression of HMGB1 mRNA and the level of HMGB1 protein in the lungs were detected by RT-PCR and Western blot, respectively. Data were analysed with ANOVA and LSD method for comparison between groups, and P ＜0.05 was considered statistically significant. Results Compared with the group A (0.652±0. 177), the expressions of HMGB1 mRNA in lung of rats of group B were significantly higher in 12 hours (1. 161 ±0.358, P=0.013), 24 hours (1.679 ±0.235, P =0.000) and 48 hours (1.258 ±0.274, P=0.004) and reached the peak in 24 h. Compared with group A (0.594 ±0. 190), the level of HMGB1 protein in rats of group B 6 h after infection ( 1. 408 ± 0. 567, P = 0. 026) was significantly increased (P＜0.05), and it reached peak in 24 h (2.415 ± 1.064, P =0.000) after infection. Compared with group A (0.699 ± 0.054), the lung water contents in rats of group B were significantly increased in 6 h (0.759±0.030, P=0.001), in 12 h (0.767 ±0.023, P =0.000), in 24 h (0.771 ±0.043, P=0.000) and in 48 h (0.789 ±0.137, P=0.000) after infection. Compared with group A, the pathological changes in the lung of rats in group B showed clearly marked pulmonary vascular congestion, interstitial edema and inflammatory cell infiltration, and those changes became more and more serious until alveolar sacs entirely collapsed and the boundaries of the alveolar septa could not be clearly identified in 48 h. Conclusions Vibrio vulnificus sepsis leads to the lung injury of infected rats, and the increase in the expression of HMGB1 mRNA in lung might be one of the mechanisms of lung injury in rats with Vibrio vulnificus sepsis.