With the development of information technology, the massive growth of pharmaceutical electronic data and the significant increase in the reports of drug adverse event reports have brought great challenges to pharmacovigilance research. Data mining techniques can automatically extract the risk signals of adverse drug reaction from real-world data. Therefore, efficient data mining of massive adverse event reporting is a necessary measure to realize the automatic detection of adverse drug reactions. By introducing the current major large-scale adverse drug event reporting databases and related data mining methods, this study reviews the application and limitations of adverse drug reaction data mining technology in pharmacovigilance, which provides reference for pharmacovigilance-related institutions and researchers.

Objective To observe the effects of a 1 470 nm semiconductor laser on vaporization cutting,coagulation,and thermal injury of ex vivo animal tissues,aiming to explore the feasibility of its application in the treatment of benign prostatic hyperplasia.Methods The experimental group and control group were treated with HANS-D1 and ML-DD01FI 1 470 nm semiconductor laser therapy equipment,respectively.Fresh ex vivo pig bladder tissue was exposed to lasers with the optical fiber placed at distances of 0.5 cm and 1 cm from the tissue for 5 s.The effects of layers at powers of 60,90,120,150,and 160 W on tissue injury were observed.Ex vivo dog prostate and pig kidney tissues were used for vaporization ablation and cutting to observe the effects of lasers at the same power levels on tissue vaporization and cutting thermal injury.Additionally,in coagulation mode,the effects of 30,40,and 50 W semiconductor lasers on tissue coagulation were observed after irradiating ex vivo pig kidney tissue for 5,10,and 15 seconds.Results When the optical fiber was placed 1 cm away from the tissue,the 1 470 nm semiconductor lasers did not cause accidental damage to adjacent normal bladder tissue.However,at a distance of 0.5 cm,the 120 W,150 W,or 160 W lasers caused slight damage to the bladder tissue.In addition,with the increase in output power,the vaporization ablation efficiency of 60-160 W lasers on dog prostate tissue gradually increased,showing a good linear correlation between vaporization volume and total energy consumption(P＜0.001).Histopathological HE staining results indicated that the coagulation layer thickness in the experimental group was 292.20-309.98 μm,and the vaporization layer depth was 1.49-4.52 mm.In the control group,the coagulation layer thickness was 289.91-303.53 μm,and the vaporization layer depth was 1.88-4.43 mm.There was no significant difference between the two groups(P＞0.05).Moreover,when performing vaporization cutting on ex vivo pig kidney tissue with a cross-sectional area of 1 cm2,the efficiency of vaporization cutting by the 60-160 W 1 470 nm semiconductor lasers increased with the increase in output power(P＜0.05).The coagulated layer thickness in the experimental group was 496.04-514.47 μm,while that in the control group was 489.39-518.53 μm.Additionally,in coagulation mode,when ex vivo pig kidney tissue was irradiated for 5,10,and 15 s with 30,40,and 50 W semiconductor lasers,the coagulation diameter,groove depth,and coagulation efficiency gradually increased with the increase in laser output power(P＜0.05).The coagulation layer thickness in the experimental group and control group was 399.10-449.98 μm and 392.97-447.65 μm,respectively,and the vaporization layer depth was 3.05-7.09 mm and 2.70-7.14 mm,respectively.There was no significant difference between the two groups(P＞0.05).Conclusion The 1 470 nm semiconductor laser shows good vaporization ablation,cutting,and coagulation effect on ex vivo tissues,with a good linear correlation between the effect and the output energy.

Objective To analyze the characteristics and malignancy of red-patch like lesion(RPL)during cystoscopy,and to explore the significance of RPL biopsy.Methods Clinical data of patients who had RPL detected in our hospital during Jan.2019 and Jun.2023 were retrospectively analyzed,including gender,age,cause of examination,presence of scars,complications and biopsy pathology.The patients were divided into the benign and malignant groups,and their clinical and RPL characteristics were analyzed.Results A total of 521 cases of RPL were enrolled including 416(79.8％)benign cases,and 105(20.2％)malignant cases.The averae age of the malignant group was higher than the benign group's[(66.8±12.2)years vs.(62.8±12.9)years,P=0.005].The malignant detection rate of RPL in postoperative follow-up patients,those with hematuria and those with lower urinary tract symptoms was 23.7％(92/389),19.6％(9/46),4.7％(4/86),respectively.According to direct observation and experience,the detection rate of pathological malignancy in the three groups of patients with high suspicion of RPL malignancy,mild suspicion of RPL malignancy and high probability of benign was 56.9％(37/65),37.0％(30/81)and 10.1％(38/375),respectively.Conclusion Once RPL is detected during cystoscopy,active biopsy should be performed.For elderly male patients undergoing postoperative follow-up,RPL biopsy is particularly important,especially when the lesion is located on or near the scar surface.

Objective:To investigate the effects of stimulator of interferon gene (STING) on ferroptosis mediated by acyl-CoA synthetase long-chain family member 4 (ACSL4) in mouse dendritic cells (DCs) under sepsis, providing a basis for improving the dysregulation of immune response in sepsis caused by factors such as wound infection.Methods:This study was an experimental research. The mouse DC line DC2.4 in the logarithmic growth phase (with passages 3-10) were divided into lipopolysaccharide (LPS) stimulation 0 h (unstimulated) group, LPS stimulation 6 h group, LPS stimulation 12 h group, LPS stimulation 18 h group, and LPS stimulation 24 h group according to the random number table (the same grouping method below), which were cultured with 1 μg/mL LPS (the same concentration below) for the corresponding time. The protein expressions of phosphorylated STING (p-STING), STING, and ACSL4 in cells were determined by Western blotting. DC2.4 successfully transfected with lentivirus containing STING gene small interfering RNA (hereinafter referred to as siSTING) were divided into siSTING+phosphate buffer solution (PBS) group and siSTING+LPS group. DC2.4 successfully transfected with empty lentivirus were divided into empty vector+PBS group and empty vector+LPS group. After being stimulated with PBS or LPS and cultured for 24 hours, the protein expressions of p-STING, STING, and ACSL4 in cells were determined as above. Cell lipid peroxidation degrees were observed using the lipid peroxidation assay kit, and cell apoptosis rates were detected using flow cytometry. The sample numbers in the above cell experiments were all 3. Eighty male C57BL/6J mice aged 6 to 8 weeks were divided into sham surgery+normal saline (NS) group, cecal ligation and puncture (CLP)+NS group, sham surgery+C-176 group, and CLP+C-176 group, with 20 mice in each group. Mice in the two C-176 groups were intraperitoneally injected with C-176, while mice in the two NS groups were intraperitoneally injected with an equivalent volume of NS. One hour later, sham surgery was performed on the mice in the two sham surgery groups, and CLP surgery was performed on the mice in the two CLP groups to establish a sepsis model. At 24 h post-surgery, 10 mice from each group were sacrificed to extract spleen DCs, and protein expression, lipid peroxidation, and apoptosis rates were detected as above ( n=3). Hematoxylin-eosin staining was performed to observe pathological damage in the heart, liver, lung, and kidney tissue. The remaining 10 mice in each group were observed for survival within 7 days after surgery. Results:The protein expressions of p-STING, STING, and ACSL4, as well as the p-STING/STING ratio in DC2.4 in LPS stimulation 24 h group were significantly higher than those in LPS stimulation 0 h group ( P<0.05). After 24 h of culture, the protein expressions of p-STING, STING, and ACSL4 in DC2.4 in siSTING+LPS group and empty vector+PBS group were significantly lower than those in empty vector+LPS group ( P<0.05); the lipid peroxidation degrees of DC2.4 in siSTING+LPS group and empty vector+PBS group were weaker than those in empty vector+LPS group. The apoptosis rates of DC2.4 in empty vector+PBS group, empty vector+LPS group, siSTING+PBS group, and siSTING+LPS group were (15.7±3.0)%, (37.8±2.9)%, (13.1±2.1)%, and (20.6±1.8)%, respectively. The apoptosis rates of DC2.4 in empty vector+PBS group and siSTING+LPS group were significantly lower than that in empty vector+LPS group ( P<0.05). At 24 h post-surgery, the protein expressions of p-STING and ACSL4, and the p-STING/STING ratio in spleen DCs of mice in CLP+NS group were significantly higher than those in sham surgery+NS group and CLP+C-176 group ( P<0.05); the protein expression of STING in spleen DCs of mice in CLP+NS group was significantly higher than that in sham surgery+NS group ( P<0.05); the lipid peroxidation degrees of spleen DCs of mice in CLP+C-176 group and sham surgery+NS group were weaker than that in CLP+NS group. The apoptosis rates of spleen DCs of mice in sham surgery+NS group and CLP+C-176 group were significantly lower than that in CLP+NS group ( P<0.05), and the apoptosis rate of spleen DCs of mice in CLP+C-176 group was significantly higher than that in sham surgery+C-176 group ( P<0.05). Pathological tissue damage in the heart, liver, lung, and kidney of mice in CLP+NS group was significantly worse than that in sham surgery+NS group, while such damage in the above organs of mice in CLP+C-176 group was significantly alleviated compared with that in CLP+NS group. The survival ratio of mice in CLP+NS group within 7 days after surgery was significantly lower than that in sham surgery+NS group ( χ2=8.30, P<0.05). Conclusions:Under sepsis, STING activation in mouse DCs is significant, which enhances ACSL4-mediated ferroptosis. Inhibiting STING activation can significantly reduce ACSL4-mediated ferroptosis level in mouse DCs under sepsis, thereby improving the survival rate of septic mice.

Objective:To investigate associations of serum low-density lipoprotein cholesterol (LDL-C) with hematoma enlargement, early neurological deterioration (END), and outcome in patients with acute spontaneous intracerebral hemorrhage (ICH).Methods:"A multi-center registration study for spontaneous intracerebral hemorrhage in Inner Mongolia" (registration number: ChiCTR2000029494) database was used to include patients with ICH who completed their first head CT scan within 6 hours after onset, underwent blood lipid examination, CT follow-up within 24 hours of onset, and accurately measured hematoma volume using 3D Slicer software between June 2020 and September 2022. HE was defined as hematoma volume increasing >33% or >6 ml at 24 hours, or ventricular hematoma volume increasing ≥1 ml compared to the baseline. END was defined as an increase of ≥4 in the National Institutes of Health Stroke Scale (NIHSS) score from the baseline or death within 24 hours after onset. The follow-up was conducted at 3 months after onset, and the modified Rankin Scale score >2 was defined as poor outcome. Multivariate logistic analysis was used to determine the independent correlation between LDL-C and HE, END, and outcome. Results:A total of 338 patients with ICH were enrolled, including 206 males (60.9%). LDL-C was 2.39±1.22 mmol/L. Eighty-eight patients (26.0%) developed HE, 67 (19.8%) developed END, and 162 (47.9%) had poor outcome at 3 months. Multivariate logistic analysis showed that after adjusting for confounding factors, there was a significant independent negative correlation between LDL-C and HE (odds ratio 0.312, 95% confidence interval 0.208-0.467; P<0.001) and END (odds ratio 0.408, 95% confidence interval 0.275-0.606; P<0.001), but not with the outcome at 3 months. Conclusion:Lower LDL-C is associated with HE and END in patients with ICH, but not with the outcome.

This study aims at developing a dataset for determining the presence of carotid artery plaques in ultrasound images,composed of 1761 ultrasound images from 1165 participants.A deep learning architecture that combines bilinear convolutional neural networks with residual neural networks,known as the single-input BCNN-ResNet model,was utilized to aid clinical doctors in diagnosing plaques using carotid ultrasound images.Following training,internal validation,and external validation,the model yielded an ROC AUC of 0.99(95%confidence interval:0.91 to 0.84)in internal validation and 0.95(95%confidence interval:0.96 to 0.94)in external validation,surpassing the ResNet-34 network model,which achieved an AUC of 0.98(95%confidence interval:0.99 to 0.95)in internal validation and 0.94(95%confidence interval:0.95 to 0.92)in external validation.Consequently,the single-input BCNN-ResNet network model has shown remarkable diagnostic capabilities and offers an innovative solution for the automatic detection of carotid artery plaques.

Objective To investigate the therapeutic effects of Isaria felina derived from Cordyceps sinensis combined with cyclophosphamide(CTX)in hepatoma H22 tumor-bearing mice.Methods An H22 tumor-bearing mouse model was established and mice were divided randomly into a normal control group(NC group,distilled water),model control group(MC group,distilled water),positive control group(CTX group,25 mg/kg),Isaria felina group(IF group,400 mg/kg),and combined administration group(IF+CTX group,IF 400 mg/kg+CTX 25 mg/kg),with 5 mice in each group.Distilled water and IF were administered by gavage,and CTX was administered by intraperitoneal injection.The administration cycle was 10 days.At the end of the experiment,the mean tumor volume and weight,tumor inhibition rate,q value,and immune organ index were calculated,and routine blood indexes and cytokine levels were determined.Histopathological changes in tumor tissues were observed by HE staining.Results The tumor volume and mass were significantly lower in mice in each treatment group compared with those in mice in the MC group(P＜0.05).The tumor inhibition rates in the CTX,IF,and IF+CTX groups were 49.3%,34.2%,and 72.8%,respectively,and the q value was 1.09.The numbers of white blood cells,Lymph,and platelets were significantly higher in the IF+CTX group than in the CTX group(P＜0.05).The spleen index was significantly higher in the MC group compared with that in the NC group,and significantly lower in the IF+CTX group compared with that in the MC group(P＜0.05).Serum interferon-γ levels were significantly lower in the MC group than in the NC group,and were significantly higher in the IF and IF+CTX groups compared with those in the MC and CTX groups(P＜0.05).Pathologically,tumor cells in the MC group grew well and were numerous and closely arranged,while cells in the CTX,IF,and IF+CTX groups were arranged loosely,with focal necrosis and nuclear pyknosis of necrotic cells in many places.Conclusions The combination of IF and CTX has an additive anti-tumor effect on H22 tumor-bearing mice,which can alleviate immunosuppression and have an immunomodulatory function.

Objective To investigate the mechanism of cartilage injury and inflammation in the WHBE rabbit KOA model and the effect of platelet-rich fibrin releasates(PRFr)treatment on the KOA process,we established a WHBE rabbit KOA model by excision of medial collateral and partial patellar ligaments and administered a PRFr solution.Methods Twenty-four WHBE rabbits were randomly divided into three groups:normal control(NC)group(n=6),model(KOA)group(n=12),and cure(PRFr)group(n=6).KOA and PRFr groups were injected with 0.5 mL saline and PRFr into both joint cavities on 7 and 14 postoperative days,respectively.At 4 and 8 weeks of modeling,the knee joint grade scoring,X-ray imaging,and gross scoring were performed.Serum levels of IL-1β,TNF-α,and MMP-13 were measured by ELISA.At 4 weeks,6 animals in the KOA group were euthanized,and at 8 weeks,the remaining animals in each group were euthanized.Pathological sections were prepared after decalcification,and then HE,toluidine blue,and safranin O-fast green staining and immunohistochemical analysis of TGF-β,BMP3,and NF-κB were conducted.Results The Lequesne MG behavioral score,Mankin's score,and Pelletier score of WHBE rabbits after the operation were significantly increased compared with the NC group(P＜0.01).Pathological observations revealed surface defects of the cartilage and partial loss of chondrocytes.These result indicated that the KOA model was established successfully.In KOA rabbits,knee joint swelling,joint pain stimulation,and movement limitation were obvious.X-rays showed a high-density soft tissue shadow,indicating more joint effusion and a rough articular surface in general.After PRFr treatment,the serum levels of proinflammatory factors IL-1β,TNF-α,and MMP-13 in KOA model rabbits were significantly reversed(P＜0.05,P＜0.01).Additionally,the cartilage surface became smooth,and most chondrocytes were neatly distributed.Expression levels of TGF-β,BMP3,and NF-κB induced by KOA were also significantly decreased(P＜0.01).Conclusions We successfully established a KOA model in WHBE rabbits,and PRFr improved the cartilage injury and inflammation of the WHBE rabbit KOA model through TGF-β/BMP and NF-κB pathways.

Objective To evaluate the effectiveness of a 1470 nm semiconductor laser therapeutic instrument(referred to as a curestar therapeutic instrument)for prostatectomy in Beagle dogs.Methods Twenty-eight adult male Beagle dogs were randomly divided into three groups:sham(n=3),experimental(n=15),and control(n=10).The experimental group was further divided into three subgroups:120 W/50 W,150 W/50 W,and 160 W/50 W for vaporization cutting/coagulation hemostasis.The control group was divided into two subgroups:120 W/50 W and 150 W/50 W with five in each subgroup.Experimental and control groups underwent canine prostatectomy through the entrance of the bladder neck under electrocision.The operational suitability and effectiveness of the product during surgery were assessed.After the operation,the general condition of the dogs was observed,and blood biochemical and hematological indicators were measured before,immediately after,and at 3,7,and 28 days after the operation.At 1 h and 4 weeks after surgery,B-ultrasound and electric resection were performed under anesthesia to observe the conditions of the urethra and prostate,and prostatic tissue was subjected to HE staining for pathological observations.The thickness of the coagulation layer at 1 h after the operation and repair of the urothelial epithelium at 4 weeks were analyzed.Results During the operation,experimental and control groups had good operability and showed good vaporization cutting and coagulation hemostasis performance.After the operation,no significant effects were observed on the general condition,and blood biochemical and hematological indicators of the dogs.Ultrasound showed that the urethral expansion was visible immediately after the operation,and the echo of the urethral epithelium was slightly enhanced.At 4 weeks,the prostate tissue had a slightly low echo with uniformly distributed small point-like echoes inside,and the capsule had a linearly high echo,consistent with the sham group.The weight of the vaporized prostate tissue in experimental and control groups was 0.91～1.33 g with a resection rate of 17.11％～20.27％.As the power of vaporization cutting increased,the laser emission time gradually decreased,while the vaporization cutting speed and efficiency both increased.However,no significant difference was found between experimental and control groups(P＞0.05).Under the electrocision microscope,a burn-like change was observed in the surgical wounds of the prostate urethra in experimental and control groups at 1 h after surgery,and the boundary between the wound and normal urothelium was visible.At 4 weeks,the urothelium of the prostate had been repaired and flattened,and the boundary with the surrounding normal urothelium was blurred.Similarly,pathological observations showed that experimental and control groups had significant damage to the prostate urethral orifice at 1 h after surgery with a small amount of carbonization and coagulative necrosis on the surface of the wound,a small amount of inflammatory cell infiltration,and a coagulation layer thickness of approximately 0.4 mm.At 4 weeks,the prostate urethral morphology of the sham group was normal,whereas experimental and control groups showed new epithelial growth covering the wound with a uniform thickness and no coagulative necrosis tissue attached to the wound.A mild inflammatory reaction was still present in the surrounding area,fibroblast proliferation was obvious,and stromal and epithelial cell proliferation was visible in the surrounding prostate,some of which showed squamous metaplasia.The prostate capsule was intact and the morphology of the surrounding nerves and blood vessels was normal.Conclusions The curestar therapy instrument is effective for prostatectomy in Beagle dogs with good vaporization cutting and coagulation hemostasis performance.No significant difference was found in postoperative physiological indicators compared with the sham group.

Objective To investigate the correlation between thyroid function,neutrophil/lymphocyte ratio(NLR),platelet/lymphocyte ratio(PLR)and diabetic ketoacidosis(DKA).Methods A total of 272 diabetic patients admitted to the Department of Endocrinology,Anhui No.2 Provincial People's Hospital were enrolled in this study from January 2021 to March 2024 and divided into DKA group(n=74),diabetic ketosis group(DK group,n=100)and simple DM group(n=98)according to their disease conditions.Serum free triiodothyronine(FT3),free tetraiodothyronine(FT4),thyroid stimulating hormone(TSH),FPG,HbA1c,anion gap(AG),white blood cells(WBC),neutrophils(N),platelets(PLT)and lymphocytes(L)were detected in each group,and NLR and PLR were calculated.The influence factors of DKA were analyzed by logistic regression,and the diagnostic value of FT3,NLR and PLR in DKA was evaluated by receiver operating characteristic(ROC)curve.Results Hospitalization days,FPG,HbA1c,incidence of LT3S,AG,WBC,N,PLT,NLR,PLR were higher in DKA group than in DM and DK groups(P<0.05),Age,FT3,FT4,TSH,L were lower in DKA group than in DM and DK groups(P<0.05).Logistic regression analysis showed that FT3,AG,NLR and PLR were the influencing factors for DKA.ROC curve showed that the area under the curve of FT3,NLR,PLR and combined detection to predict DKA were 0.961,0.938,0.810 and 0.980,the sensitivity was 87.8%,90.5%,75.7%and 98.6%,the specificity was 95.5%,92.9%,76.3%,92.4%,and the combined detection was superior to the single detection.Conclusions FT3,NLR,PLR have a certain diagnostic value for DKA,and the combined detection of the three has a high diagnostic value,which can provide a reference for clinical diagnosis of DKA.