An overview of the application of association rule mining(ARM)in real-world study(RWD)on drug safety to inform pharmacovigilance real-world data analysis.The applications of ARM in RWD of drug safety were divided into single drug/vaccine signal detection,combined medication risk mining,multidimensional risk factor analysis and adverse drug event occurrence characterization based on passive monitoring data;medication characterization pattern analysis,auxiliary epidemiological study design and risk mining of the whole dataset based on active monitoring data.In general,foreign scholars pay more attention to method rule setting,performance evaluation and application research,while domestic scholars pay more attention to multidimensional risk factor analysis,adverse drug event occurrence pattern,and clinical drug use characteristics research.With the accumulation of medical data and the continuous development of data mining technology,ARM may provide new ideas for RWD on drug safety.

Objective:To explore the key factors affecting health-related quality of life in children with brain tumors following initial diagnosis and to analyze its impact on survival and prognosis.Methods:Seventy-eight pediatric brain tumor patients who participated in a prospective cohort study between June 1st，2016 and June 30th，2021 were included for health-related quality of life assessment and long-term follow-up（median follow-up duration：52 months）.Results:The male-to-female ratio among the 78 children was 1.1：1，with a median age of 7.0（4.0，10.0）years. The scores of the Pediatric Quality of Life Inventory? 4.0 Generic Core Scales（PedsQL? 4.0）were（67.40±18.26）for parent proxy reports and（67.87±20.40）for child self-reports. Cronbach's α coefficients ranged from 0.790 to 0.927，with the intraclass correlation coefficient（ICC）was 0.673. According to the PedsQL? 4.0，impaired quality of life was observed in 50.0% of children by parent proxy report and 52.8% by child self-report，primarily affecting physical and role functioning. In addition，70% of caregivers reported impaired quality of life，with worry being the most prominent issue. Key factors affecting children's quality of life included radiotherapy，tumor stage，annual family income，and parents' marital status，while caregivers' quality of life was influenced by radiotherapy and the child's IgA levels（all P<0.05）. Children with decreased total scores，impaired physical functioning，or impaired emotional functioning on the PedsQL? 4.0 parent proxy report exhibited an increased risk of mortality（all P<0.05）. In multivariate Cox regression analysis，independent prognostic factors included a decrease in the total score on the PedsQL? 4.0 parent proxy report（ HR=6.702，95% CI：1.442-31.151， P<0.05），presence of hydrocephalus（ HR=33.602，95% CI：4.354-259.333， P<0.05），tumor recurrence（ HR=16.846，95% CI：3.158-89.852， P<0.05），and absence of hydrocephalus shunt surgery（ HR=13.428，95% CI：1.761-102.394， P<0.05）. Conclusion:The quality of life of newly diagnosed children with brain tumors is lower than that of healthy children，and quality of life is an important prognostic factor. Quality of life assessment should be an integral component of a comprehensive management program for children with brain tumors.

Objective To investigate the effect of toripalimab combined with chemoradiotherapy in patients with cervical lymph node metastasis of nasopharyngeal carcinoma on immune function.Methods A prospective study was conducted in 160 patients with nasopharyngeal carcinoma accom-panied by cervical lymph node metastasis.Patients were divided into study group and control group using block randomization,with 80 patients in each group.The control group received a standard che-moradiotherapy regimen,while the study group received toripalimab combined with chemoradiothera-py.Both groups were treated for 3 courses.The clinical efficacy,levels of immune function indica-tors,levels of tumor markers[squamous cell carcinoma antigen(SCC-Ag),high-mobility group box 1(HMGB1),pentraxin 3(PTX3),and cytokeratin 19 fragment antigen 21-1(CYFRA21-1)],and the incidenceof adverse reactions were compared between the two groups.Results The objective re-sponse rates of the primary lesion and cervical lymph nodes in the study group were higher than those in the control group(P＜0.05).After treatment,the levels of CD3+,CD4+,and natural killer cells in the study group were higher than those before treatment and in the control group,while the lev-el of CD8+was lower than that before treatment and in the control group(P＜0.05).After treatment,the levels of HMGB1,PTX3,SCC-Ag and CYFRA21-1 in the study group were lower than those before treatment and in the control group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Toripalimab combined with chemoradiotherapy has a sig-nificant efficacy in treatment of cervical lymph node metastasis of nasopharyngeal carcinoma.It can enhance the immune function of patients,improve the levels of tumor markers,and has good safety.

Objective To fabricate nanosilicate functionalized polycaprolactone(PCL/LAP)electrospun membrane and evaluate its role in bone marrow mesenchymal stem cells(BMSCs)-induced bone repairing.Methods The PCL/LAP electrospun membranes were fabricated via electrospinning technology and co-cultured with rat BMSCs.The cytocompatibility of the membranes was evaluated through cytoskeleton staining,live/dead cell staining and CCK-8 assay.The migration capacity of BMSCs was assessed using scratch assay,Transwell migration experiments and expression of migration-related genes(Pdgf and Tgfβ)was evaluated by qRT-PCR.The os-teogenic differentiation and pro-angiogenesis potential were determined by alkaline phosphatase(ALP)staining,alizarin red staining,expression levels of osteogenesis-related genes(Alp,Col1a1,Runx2,Bglap and Bmp2)and angiogenesis-related genes(Angpt1,Fgf2 and Vegfa)along with RUNX2 protein expression.PCL and PCL/LAP electrospun membranes conditioned medium was subsequently used to stimulate vascular endothelial cells(EAhy926).The expression of angiogenesis-associated genes(KDR,ENOS and HIF1A)was quantified by qRT-PCR.Results BMSCs adhered well to the surface of the PCL/LAP membranes,with no significant impact on cell viability(P＞0.05).PCL/LAP membranes not only promoted the proliferation(P＜0.05),migration(P＜0.05),but also enhanced ALP activity and mineralized nodule formation(P＜0.05),increased osteogenic differentiation gene and protein expression(P＜0.05)of BMSCs.Moreover,PCL/LAP promoted the expression of angiogenic genes of BMSCs(P＜0.05),to indirectly regulate angiogenesis-related gene expression in vascular endothelial cells(P＜0.05).Conclusion PCL/LAP electrospun membranes exhibit excellent biocompatibility and can promote proliferation,migration,osteogenic differentiation and BMSC-mediated angiogenic differentiation,showing great potential for bone defect repairing as barrier membrane.

An overview of the application of association rule mining(ARM)in real-world study(RWD)on drug safety to inform pharmacovigilance real-world data analysis.The applications of ARM in RWD of drug safety were divided into single drug/vaccine signal detection,combined medication risk mining,multidimensional risk factor analysis and adverse drug event occurrence characterization based on passive monitoring data;medication characterization pattern analysis,auxiliary epidemiological study design and risk mining of the whole dataset based on active monitoring data.In general,foreign scholars pay more attention to method rule setting,performance evaluation and application research,while domestic scholars pay more attention to multidimensional risk factor analysis,adverse drug event occurrence pattern,and clinical drug use characteristics research.With the accumulation of medical data and the continuous development of data mining technology,ARM may provide new ideas for RWD on drug safety.

Objective To fabricate nanosilicate functionalized polycaprolactone(PCL/LAP)electrospun membrane and evaluate its role in bone marrow mesenchymal stem cells(BMSCs)-induced bone repairing.Methods The PCL/LAP electrospun membranes were fabricated via electrospinning technology and co-cultured with rat BMSCs.The cytocompatibility of the membranes was evaluated through cytoskeleton staining,live/dead cell staining and CCK-8 assay.The migration capacity of BMSCs was assessed using scratch assay,Transwell migration experiments and expression of migration-related genes(Pdgf and Tgfβ)was evaluated by qRT-PCR.The os-teogenic differentiation and pro-angiogenesis potential were determined by alkaline phosphatase(ALP)staining,alizarin red staining,expression levels of osteogenesis-related genes(Alp,Col1a1,Runx2,Bglap and Bmp2)and angiogenesis-related genes(Angpt1,Fgf2 and Vegfa)along with RUNX2 protein expression.PCL and PCL/LAP electrospun membranes conditioned medium was subsequently used to stimulate vascular endothelial cells(EAhy926).The expression of angiogenesis-associated genes(KDR,ENOS and HIF1A)was quantified by qRT-PCR.Results BMSCs adhered well to the surface of the PCL/LAP membranes,with no significant impact on cell viability(P＞0.05).PCL/LAP membranes not only promoted the proliferation(P＜0.05),migration(P＜0.05),but also enhanced ALP activity and mineralized nodule formation(P＜0.05),increased osteogenic differentiation gene and protein expression(P＜0.05)of BMSCs.Moreover,PCL/LAP promoted the expression of angiogenic genes of BMSCs(P＜0.05),to indirectly regulate angiogenesis-related gene expression in vascular endothelial cells(P＜0.05).Conclusion PCL/LAP electrospun membranes exhibit excellent biocompatibility and can promote proliferation,migration,osteogenic differentiation and BMSC-mediated angiogenic differentiation,showing great potential for bone defect repairing as barrier membrane.

Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.
Humans ; Mice ; Animals ; Dysbiosis ; Anti-Bacterial Agents/pharmacology* ; Virulence ; Microbiota ; Periodontitis/chemically induced* ; Cytokines

Objective:To evaluate the role of NOD-like receptor 3 (NLRP3) inflammasome activation-mediated macrophage polarization in myocardial injury after ischemic stroke in diabetic mice.Methods:Wild-type C57BL/6J mice and NLRP3 -/- mice, aged 4-6 weeks, were fed a high fat diet combined with streptozotocin administration to develop the diabetic model. Twenty-four diabetic wild type C57BL/6J mice and 23 diabetic NLRP3 -/- mice were divided into wild type sham operation group (WT D-SHAM group, n=9) , wild type ischemic stroke group (WT D-MCAO group, n=15) , NLRP3 -/- sham operation group (NLRP3 -/-D-SHAM group, n=9) and NLRP3 -/- ischemic stroke group (NLRP3 -/-D-MCAO group, n=14). The ischemic stroke model was developed by middle cerebral artery occlusion in the animals anesthetized with isoflurane. Echocardiography and electrocardiography were carried out at 3, 7, 14 and 28 days after developing the model. Mice were sacrificed under deep anesthesia, and myocardial tissues were taken at 28 days after surgery for determination of the expression of macrophage marker F4/80 and M2 type macrophage marker CD206 mRNA (by real-time fluorescence quantitative polymerase chain reaction). Results:Compared with WT D-SHAM group, the cardiac output, mass of left ventricle and corrected mass of left ventricle were significantly decreased at 28 days after surgery, and QT interval and QTc interval were prolonged at 14 and 28 days after developing the model in WT D-MCAO group ( P<0.05). Compared with NLRP3 -/-D-SHAM group, the cardiac output, mass of left ventricle and corrected mass of left ventricle were significantly decreased, and QT interval and QTc interval were prolonged at 3 days after surgery in NLRP3 -/-D-MCAO group ( P<0.05). There was no significant difference in CD206 and F4/80 mRNA expression between WT D-SHAM group and WT D-MCAO group and between NLRP3 -/-D-SHAM group and NLRP3 -/-D-MCAO group ( P>0.05). Compared with WT D-MCAO group, the QT interval and QTC interval were significantly shortened at 14 and 28 days after developing the model, and the expression of F4/80 mRNA was down-regulated and the expression of CD206 mRNA was up-regulated at 28 days after developing the model in NLRP3 -/-D-MCAO group ( P<0.05). Conclusions:NLRP3 inflammasome activation-mediated polarization of macrophages to M2 phenotype is involved in myocardial injury after ischemic stroke in diabetic mice.

Objective:To assess the diagnostic efficacy of upper gastrointestinal endoscopic image assisted diagnosis system (ENDOANGEL-LD) based on artificial intelligence (AI) for detecting gastric lesions and neoplastic lesions under white light endoscopy.Methods:The diagnostic efficacy of ENDOANGEL-LD was tested using image testing dataset and video testing dataset, respectively. The image testing dataset included 300 images of gastric neoplastic lesions, 505 images of non-neoplastic lesions and 990 images of normal stomach of 191 patients in Renmin Hospital of Wuhan University from June 2019 to September 2019. Video testing dataset was from 83 videos (38 gastric neoplastic lesions and 45 non-neoplastic lesions) of 78 patients in Renmin Hospital of Wuhan University from November 2020 to April 2021. The accuracy, the sensitivity and the specificity of ENDOANGEL-LD for image testing dataset were calculated. The accuracy, the sensitivity and the specificity of ENDOANGEL-LD in video testing dataset for gastric neoplastic lesions were compared with those of four senior endoscopists.Results:In the image testing dataset, the accuracy, the sensitivity, the specificity of ENDOANGEL-LD for gastric lesions were 93.9% (1 685/1 795), 98.0% (789/805) and 90.5% (896/990) respectively; while the accuracy, the sensitivity and the specificity of ENDOANGEL-LD for gastric neoplastic lesions were 88.7% (714/805), 91.0% (273/300) and 87.3% (441/505) respectively. In the video testing dataset, the sensitivity [100.0% (38/38) VS 85.5% (130/152), χ2=6.220, P=0.013] of ENDOANGEL-LD was higher than that of four senior endoscopists. The accuracy [81.9% (68/83) VS 72.0% (239/332), χ2=3.408, P=0.065] and the specificity [ 66.7% (30/45) VS 60.6% (109/180), χ2=0.569, P=0.451] of ENDOANGEL-LD were comparable with those of four senior endoscopists. Conclusion:The ENDOANGEL-LD can accurately detect gastric lesions and further diagnose neoplastic lesions to help endoscopists in clinical work.

Objective:To construct a real-time artificial intelligence (AI)-assisted endoscepic diagnosis system based on YOLO v3 algorithm, and to evaluate its ability of detecting focal gastric lesions in gastroscopy.Methods:A total of 5 488 white light gastroscopic images (2 733 images with gastric focal lesions and 2 755 images without gastric focal lesions) from June to November 2019 and videos of 92 cases (288 168 clear stomach frames) from May to June 2020 at the Digestive Endoscopy Center of Renmin Hospital of Wuhan University were retrospectively collected for AI System test. A total of 3 997 prospective consecutive patients undergoing gastroscopy at the Digestive Endoscopy Center of Renmin Hospital of Wuhan University from July 6, 2020 to November 27, 2020 and May 6, 2021 to August 2, 2021 were enrolled to assess the clinical applicability of AI System. When AI System recognized an abnormal lesion, it marked the lesion with a blue box as a warning. The ability to identify focal gastric lesions and the frequency and causes of false positives and false negatives of AI System were statistically analyzed.Results:In the image test set, the accuracy, the sensitivity, the specificity, the positive predictive value and the negative predictive value of AI System were 92.3% (5 064/5 488), 95.0% (2 597/2 733), 89.5% (2 467/ 2 755), 90.0% (2 597/2 885) and 94.8% (2 467/2 603), respectively. In the video test set, the accuracy, the sensitivity, the specificity, the positive predictive value and the negative predictive value of AI System were 95.4% (274 792/288 168), 95.2% (109 727/115 287), 95.5% (165 065/172 881), 93.4% (109 727/117 543) and 96.7% (165 065/170 625), respectively. In clinical application, the detection rate of local gastric lesions by AI System was 93.0% (6 830/7 344). A total of 514 focal gastric lesions were missed by AI System. The main reasons were punctate erosions (48.8%, 251/514), diminutive xanthomas (22.8%, 117/514) and diminutive polyps (21.4%, 110/514). The mean number of false positives per gastroscopy was 2 (1, 4), most of which were due to normal mucosa folds (50.2%, 5 635/11 225), bubbles and mucus (35.0%, 3 928/11 225), and liquid deposited in the fundus (9.1%, 1 021/11 225).Conclusion:The application of AI System can increase the detection rate of focal gastric lesions.