OBJECTIVE To confirm trigger items for adverse drug reaction （ADR） induced by bevacizumab， to identify and analyze the occurrence of related ADR， and to establish a predictive model for severe adverse reaction （SAR） caused by this drug. METHODS Based on the global trigger tool （GTT） theory， and referencing the GTT White Paper， drug package inserts and relevant literature， trigger items for bevacizumab-related ADR were confirmed using a single-round Delphi method. Utilizing these established items， electronic medical records of relevant patients at Guilin People’s Hospital from January 2020 to September 2024 were actively screened via the China Hospital Pharmacovigilance System. Pharmacists then identified and tallied the occurrence of bevacizumab-induced ADR. Data from patients with any positive trigger item served as the study subjects （divided into training and test sets at a ratio of 7∶3）， candidate feature variables were selected from 39 related variables using the Boruta algorithm， and the multivariable Logistic regression analysis was performed with the occurrence of SAR as the dependent variable. Based on these candidate features， Logistic Regression， Extreme Gradient Boosting， Light Gradient Boosting Machine， Random Forest， and Categorical Boosting models were constructed. Model performance was evaluated using metrics including the area under the curve （AUC） of receiver operating characteristic curve and recall rate. The Shapley Additive exPlanations （SHAP） method was applied to analyze and interpret the contribution of each variable. A nomogram was constructed based on the optimal model. RESULTS A total of 38 trigger items for active monitoring of bevacizumab-related ADR were determined， comprising 17 laboratory indicators， 13 clinical manifestations， and 8 intervention measures. In total， 483 patients with positive trigger items were included， and 318 patients with bevacizumab-induced ADR were identified， including 83 SARs. The positive predictive values for the trigger items and cases were 43.57% （708/1 625） and 63.84% （318/483）， respectively. Bevacizumab-induced ADR involved 7 systems/organs， with the hematological system being the most frequently involved （64.15%）. The Boruta algorithm selected 7 vari ables： serum potassium， hematocrit， albumin-to-globulin ratio， prealbumin， hypertension history， age and red blood cell count. Multivariable Logistic regression showed that elevated serum potassium levels were associated with a decreased risk of bevacizumab-induced SAR （OR＝0.234， P ＝0.002）， while a history of hypertension （OR＝2.642， P ＝0.006） and increased age （OR＝1.040， P ＝0.025） were associated with an increased risk. The Logistic Regression model demonstrated superior performance with higher AUC， F1 score and recall rate （0.761， 0.447， 0.607）， compared to other models. SHAP evaluation results indicated that variables such as serum potassium， hematocrit， and age ranked highest in importance. CONCLUSIONS Totally 38 trigger entries have been successfully identified for active screening of bevacizumab-related ADR. Elevated serum potassium levels are a protective factor against bevacizumab-induced SAR， whereas the hypertension history and increased age are risk factors. The Logistic Regression model is the optimal predictive model.

AIM:To analyze the influencing factors of visual outcome after vitrectomy for polypoidal choroidal vasculopathy(PCV)combined with vitreous hemorrhage and establish a predictive model.METHODS: A retrospective analysis was conducted on the clinical data of 129 cases(129 eyes)of patients who underwent vitrectomy for PCV combined with vitreous hemorrhage from June 2021 to January 2024 in our hospital. They were divided into elevated group(71 eyes)and non-elevated group(58 eyes)according to visual outcome at early posoperative stage(within 24 mo). Another 30 cases(30 eyes)of PCV with vitreous hemorrhage undergoing vitrectomy were selected as external validation data. The predictive value of the model for the postoperative visual outcomes of both internal and external populations was evaluated.RESULTS: The non-elevated group had a higher proportion of patients aged ≥60 years, diabetes, continuous abnormalities of the ellipsoid zone(EZ)during surgery, bleeding involving the macular fovea, and postoperative retinal scar formation than the elevated group were independent factors affecting postoperative visual acuity(all P<0.05). The AUC of the predictive model for predicting the postoperative visual outcomes of internal and external populations was 0.824(95%CI: 0.750-0.898)and 0.809(95%CI: 0.723-0.865), respectively.CONCLUSION:Patients aged ≥60 years, diabetes, intraoperative continuous abnormalities of EZ, bleeding involving the macular fovea, and postoperative retinal scar formation are influencing factors for visual outcome after vitrectomy in patients with PCV combined with vitreous hemorrhage. A predictive model based on those factors has been established, which has a certain predictive value for postoperative visual outcome.

Objective: Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors. Methods: Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1). Results: The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group. Conclusions In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.

Objective: Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors. Methods: Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1). Results: The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group. Conclusions In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.

Objective To introduce the modeling method of pendulum-like modified rat abdominal heart heterotopic transplantation model and evaluate the quality of the model. Methods An operator without transplantation experience performed 15 consecutive models, recorded the time of each step, changes in body weight and modified Stanford scores, and calculated the surgical success rate, postoperative 1-week survival rate and technical success rate. Ultrasound examinations was performed in 1 week postoperatively. Results The times for donor heart acquisition, donor heart processing, recipient preparation and transplantation anastomosis were (14.3±1.4) min, (3.5±0.6) min, (13.6±2.1) min and (38.3±5.2) min respectively. The surgical success rate was 87% (13/15), and the survival rate 1 week after operative was 100% (13/13). The improved Stanford score indicated a technical success rate of 92% (12/13), and the postoperative 1-week ultrasound examination showed that grafts with Stanford scores ≥3 had detectable pulsation and blood flow signals. Conclusions The pendulum-like modified rat abdominal heart heterotopic transplantation improved model further optimizes the operational steps with a high success rate and stable quality, may be chosen as a modeling option for basic research in heart transplantation in the future.

Objective: Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors. Methods: Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1). Results: The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group. Conclusions In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.

Objective: Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors. Methods: Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1). Results: The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group. Conclusions In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.

OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Objective: Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors. Methods: Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1). Results: The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group. Conclusions In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.

Objective To investigate the correlation of solute carrier protein 17 family member 1 (SLC17A1) gene single nucleotide polymorphisms (SNPs) and susceptibility to hyperuricemia (HUA) in automotive manufacturing workers. Methods A total of 192 Han male workers diagnosed with HUA were selected as the case group, 192 Han male workers without HUA from the same enterprises were selected as the control group. These workers were determined by the matching factor of age, total length of service, and body mass index by the 1∶1 case-control study method. Peripheral venous blood from the workers was collected for DNA extraction. Two SNPs of SLC17A1 were genotyped by MassArray system. Results The gene frequency distributions of SLC17A1 rs2096386 and rs1183201 of workers in the control group were in consistent with the Hardy-Weinberg equilibrium test (both P>0.05). The allele frequency distribution of rs2096386, and the genotype and allele frequency distribution of rs1183201 were significantly different between workers in the two groups (all P<0.05). There was no significant difference in genotype frequency distribution of rs2096386 between workers in the two groups (P>0.05). The results of conditional logistic regression analysis showed that workers with G allele at rs2096386 increased the risk of HUA [odds ratio (OR)=1.43, 95% confidence interval (CI)=1.01-2.04], workers with T allele at rs1183201 increased the risk of HUA (OR=2.03, 95%CI =1.29-3.19), after adjusting for confounding factors such as serum creatinine, blood urea nitrogen, alanin aminotransferase and aspartate aminotransferase. While workers with TA and TA+AA genotypes at rs1183201 had a lower risk of HUA than those with TT genotype (OR=0.51, 95%CI =0.30-0.85; OR=0.50, 95%CI =0.30-0.83), workers with TA genotype at rs1183201 had a lower risk of HUA than those with TT+AA genotype (OR=0.53, 95%CI =0.32-0.88). Conclusion The polymorphisms at rs2096386 and rs1183201 of SLC17A1 gene may be correlated with HUA susceptibility among automobile manufacturing workers in Guangzhou City.