Objective In this study, the resistance of Blattella germanica to D-cyphenothrin in Guangdong Province was analyzed. Further, the contact activity of eight types of plant essential oils against B. germanica and their synergistic effects with D-cyphenothrin were tested and screened, providing a basis for slowing down insecticide resistance in pests and developing plant synergists. Methods The drip test method was used to measure the resistance levels of B. germanica to D-cyphenothrin in four cities of Guangdong Province:Zhongshan City, Foshan City, Zhuhai City, and Jiangmen City. In addition, the contact killing activities of eight types of plant essential oils against B. germanica, namely, garlic, cinnamon, clove, camphor, eucalyptus leaves, tea tree, Angelica dahurica and peppermint, and their synergistic activities with D-cyphenothrin were evaluated. Results Except for B. germanica in the Xiaolan area of Zhongshan, which was moderately resistant, B. germanica in the other four towns in Guangdong were all highly resistant. Among the eight essential oils tested, garlic essential oil had the strongest toxic activity against B. germanica, with LD50 values of 45.01 μg/individual. A concentration of 2% essential oil plus D-cyphenothrin (LD20)was used to screen for synergistic activity. After 24 h of treatment, Angelica dahurica, garlic, peppermint, camphor, and tea tree essential oils showed synergistic activity. Of these, A. dahurica essential oil had the strongest synergistic activity, with a synergistic coefficient of 125%. Conclusions The essential oil of garlic had the strongest toxic activity against B. germanica, and the essential oils of A. dahurica and garlic together had the strongest synergistic activity with D-cyphenothrin, thereby providing a reference for developing natural plant synergists.

Objective:To evaluate the efficacy and safety of combining third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) with brain radiotherapy in patients with newly diagnosed EGFR mutation-positive non-small cell lung cancer (NSCLC) with brain metastases. Methods:A retrospective analysis was performed on the clinical data of patients with newly diagnosed EGFR-mutant NSCLC with brain metastases who received first-line treatment with third-generation EGFR-TKI with or without brain radiotherapy at the Fourth Affiliated Hospital of Guangxi Medical University between January 2018 and December 2022. Patients treated with EGFR-TKI plus brain radiotherapy were assigned to the combination group, while those treated with EGFR-TKI alone were assigned to the monotherapy group. Intracranial progression-free survival (iPFS), progression-free survival (PFS), overall survival (OS), intracranial disease control rate (iDCR), intracranial objective response rate (iORR), and adverse events were compared between groups. Subgroup analyses were performed according to EGFR exon 19 deletion (19del) and exon 21L858R mutation status. Survival was estimated using the Kaplan-Meier method, with the log-rank test applied for group comparisons and univariate analysis, while multivariate analysis was conducted using Cox proportional hazards regression model. Results:A total of 107 patients were included: 57 (53%) in the monotherapy group and 50 (47%) in the combination group. The combination therapy significantly improved iORR (80% vs. 60%, P=0.023), prolonged median OS (37.7 vs. 31.6 months, P=0.004), and extended median iPFS (21.8 vs. 16.7 months, P=0.018). The iDCR was 100% in both groups, and the difference in median PFS was not statistically significant (18.6 vs. 15.2 months, P=0.086). In the 19del subgroup ( n=53), patients in the combination group had longer OS ( P=0.028) and iPFS ( P=0.028). In the 21L858R subgroup ( n=54), the median OS was also longer in the combination group ( P=0.050). Multivariate analysis identified TKI monotherapy and an Eastern Cooperative Oncology Group (ECOG) performance status score=2 as independent adverse prognostic factors for iPFS, while TKI monotherapy, age ≥65 years, ECOG score=2, and >3 brain metastases were the independent adverse prognostic factors for OS. The incidence of adverse events did not differ significantly between groups (all P>0.05). Conclusions:First-line combination therapy with third-generation EGFR-TKI and cranial radiotherapy provides superior efficacy and acceptable safety compared with EGFR-TKI monotherapy in patients with EGFR-mutant lung adenocarcinoma and brain metastases. Both EGFR 19del and 21L858R mutation subgroups benefit from the combined treatment approach.

Objective:To examine the safety and effectiveness of a novel domestic transcatheter aortic valve system in addressing severe aortic valve stenosis.Methods:This prospective, multicenter, single-arm target-value clinical trial enrolled patients with severe aortic stenosis meeting inclusion criteria from 13 Chinese centers between July 2021 and April 2022. The primary endpoint was all-cause mortality at 1-year post-procedure. Secondary endpoints included safety outcomes (30-day all-cause mortality, 1-year major adverse cardiovascular events, device success) and efficacy parameters (transvalvular pressure gradient, paravalvular leak severity, New York Heart Association(NYHA)class improvement, and quality of life). Survival analysis was performed using the Kaplan-Meier analysis.Results:The study included 134 patients, 85 males and 49 females, with an age of (73.6±5.6)years (range: 65.1 to 91.8 years). Bicuspid aortic valve morphology was present in 59.7% (80/134). Device success rate was 99.3%, with one case converted to open surgery due to coronary obstruction. All-cause mortality was 0.8% (95% CI: 0.1% to 5.3%) at both 30-day and 1-year follow-up, significantly lower than the 25% target value ( P<0.01). Permanent pacemaker implantation rates remained 2.2% (3/134) at both timepoints. Stroke incidence was 0.7% (1/134) at 30 days and 1.5% (2/134) at 1 year. Myocardial infarction rates were 0.7% (1/134) at both intervals. The postoperative transvalvular pressure gradient of the aortic valve was (6.6±3.1) mmHg(1 mmHg=0.133 kPa) (range: 4 to 8 mmHg). Among the patients, 32 cases (23.9%) had mild paravalvular leakage, 4 cases (3.0%) had moderate paravalvular leakage, and no severe paravalvular leakage was observed. NYHA class Ⅰ and Ⅱ patients increased from 18.7% preoperatively to 99.3% postoperatively. Conclusion:The novel domestic transcatheter aortic valve system demonstrates satisfactory 1-year safety and efficacy outcomes in treating severe aortic stenosis.

Objective:To evaluate the efficacy and safety of combining third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) with brain radiotherapy in patients with newly diagnosed EGFR mutation-positive non-small cell lung cancer (NSCLC) with brain metastases. Methods:A retrospective analysis was performed on the clinical data of patients with newly diagnosed EGFR-mutant NSCLC with brain metastases who received first-line treatment with third-generation EGFR-TKI with or without brain radiotherapy at the Fourth Affiliated Hospital of Guangxi Medical University between January 2018 and December 2022. Patients treated with EGFR-TKI plus brain radiotherapy were assigned to the combination group, while those treated with EGFR-TKI alone were assigned to the monotherapy group. Intracranial progression-free survival (iPFS), progression-free survival (PFS), overall survival (OS), intracranial disease control rate (iDCR), intracranial objective response rate (iORR), and adverse events were compared between groups. Subgroup analyses were performed according to EGFR exon 19 deletion (19del) and exon 21L858R mutation status. Survival was estimated using the Kaplan-Meier method, with the log-rank test applied for group comparisons and univariate analysis, while multivariate analysis was conducted using Cox proportional hazards regression model. Results:A total of 107 patients were included: 57 (53%) in the monotherapy group and 50 (47%) in the combination group. The combination therapy significantly improved iORR (80% vs. 60%, P=0.023), prolonged median OS (37.7 vs. 31.6 months, P=0.004), and extended median iPFS (21.8 vs. 16.7 months, P=0.018). The iDCR was 100% in both groups, and the difference in median PFS was not statistically significant (18.6 vs. 15.2 months, P=0.086). In the 19del subgroup ( n=53), patients in the combination group had longer OS ( P=0.028) and iPFS ( P=0.028). In the 21L858R subgroup ( n=54), the median OS was also longer in the combination group ( P=0.050). Multivariate analysis identified TKI monotherapy and an Eastern Cooperative Oncology Group (ECOG) performance status score=2 as independent adverse prognostic factors for iPFS, while TKI monotherapy, age ≥65 years, ECOG score=2, and >3 brain metastases were the independent adverse prognostic factors for OS. The incidence of adverse events did not differ significantly between groups (all P>0.05). Conclusions:First-line combination therapy with third-generation EGFR-TKI and cranial radiotherapy provides superior efficacy and acceptable safety compared with EGFR-TKI monotherapy in patients with EGFR-mutant lung adenocarcinoma and brain metastases. Both EGFR 19del and 21L858R mutation subgroups benefit from the combined treatment approach.

Objective:To investigate the predictive value of 18F-FDG PET related metabolic parameters on microsatellite instability-high (MSI-H) and human epidermal growth factor receptor-2(HER2) expression in colorectal cancer (CRC). Methods:The 18F-FDG PET imaging, clinical and pathological data of 101 CRC patients (58 males, 43 females; age 68.0(58.0, 75.0) years) admitted to Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2016 to March 2024 were retrospectively collected, including 17 cases in MSI-H group, 84 cases in microsatellite stability/microsatellite instability-low (MSS/MSI-L) group, 23 cases in HER2 expression group, 34 cases in non-HER2 expression group, and 44 patients without HER2 detection. Univariate analyses (independent-sample t test, Mann-Whitney U test, χ2 test) and multivariate logistic regression analysis were used to screen out independent risk factors, and ROC curve was used to evaluate the predictive efficacy. Bootstrap method was used to verify the model internally. Results:There were significant differences in metabolic tumor volume (MTV) 80% between MSI-H group and MSS/MSI-L group (2.1(1.6, 4.0) vs 1.4(1.0, 2.7) cm 3;Z=-2.10, P=0.036), and total lesion glycolysis (TLG) 80% and carcinoembryonic antigen (CEA) were significantly different between those 2 groups ( Z=-2.27, χ2=6.40, both P<0.05). There were significant differences in TLG 80% (29.0(16.1, 41.0) vs 14.3(9.4, 22.9) g; Z=-2.80, P=0.005) between HER2 expression group and non-HER2 expression group, and significant differences were also found in MTV 80%, heterogeneity index (HI) and CV ( Z=-2.24, t values: -2.26, 2.54, all P<0.05). The independent risk factors for MSI-H were MTV 80% (odds ratio ( OR)=1.326, 95% CI: 1.015-1.733, P=0.038) and CEA ( OR=0.200, 95% CI: 0.056-0.706, P=0.012), with the AUC for the combined model of 0.730 (95% CI: 0.605-0.856), and the concordance index (C-index) of 0.716. The independent risk factors for HER2 expression were TLG 80% ( OR=1.037, 95% CI: 1.001-1.073, P=0.041) and CV ( OR=1.467, 95% CI: 1.073-2.005, P=0.016), with the AUC for the combined model of 0.775 (95% CI: 0.645-0.875), and the C-index of 0.757. Conclusions:18F-FDG PET can be used as a noninvasive tool to evaluate CRC microsatellite status and HER2 gene amplification. MTV 80% and CEA are independent risk factors for MSI-H; TLG 80% and CV are independent risk factors for HER2 expression.

Objective:To evaluate the clinical prognostic value of intratumoral metabolic heterogeneity parameters of baseline 18F-FDG PET/CT in primary cutaneous malignant melanoma (CMM). Methods:From October 2015 to July 2023, the clinical data of 35 patients (24 males, 11 females, age (66.6±13.1) years) diagnosed with primary CMM who underwent baseline 18F-FDG PET/CT in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School were retrospectively analyzed. Conventional metabolic parameters (SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG)) and PET intratumoral metabolic heterogeneity parameters (area under the cumulative SUV histograms curve (AUC-CSH), linear regression slope, SUV max/ SUV mean) were assessed. Using thresholds of 30%, 40%, 50%, 60%, 70%, and 80% SUV max or thresholds of 40%, 60%, and 80% SUV max to delineate MTV, linear regression was performed, with the slopes being heterogeneity index-1 (HI-1) and heterogeneity index-2 (HI-2), respectively. Using SUV thresholds of 2.5, and 40%, 50%, 60%, and 70%SUV max to calculate AUC-CSH and SUV max/SUV mean. Kaplan-Meier survival curves and Cox proportional hazards models were used to analyze the prognostic value of primary lesion PET metabolic parameters on overall survival (OS) and progression-free survival (PFS). Results:The median follow-up time of 35 patients was 20 months, with 25 patients (71%) experiencing disease progression and 16 patients (46%) deceased. Multivariate Cox regression analysis revealed that HI-1, HI-2, MTV, SUV max/SUV mean2.5, and SUV max were the independent prognostic factors for PFS (hazard rate ( HR) (95% CI): 0.32(0.13-0.82), 0.32(0.13-0.82), 3.86(1.34-11.12), 4.61(1.33-16.02), 4.06(1.55-10.61), all P<0.05), whereas SUV max and SUV max/SUV mean2.5 were the independent prognostic factors for OS ( HR: 8.04(1.96-32.87), 2.87(1.09-7.51), P values: 0.004, 0.032). Conclusion:HI-1, HI-2, and SUV max/SUV mean2.5 have prognostic value for CMM, while the value of AUC-CSH heterogeneity parameters are not significant.

Objective:To establish a combined model of tumor heterogeneity metabolic parameters using 18F-FDG PET/CT and explore its value in differentiating benign from malignant pulmonary lesions. Methods:A total of 251 patients (157 males, 94 females; age 15-88 years) who were diagnosed with malignant lung lesions by 18F-FDG PET/CT and with definitive pathological results at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from February 2017 to February 2024 were retrospectively enrolled. Analysis was conducted on clinical data, traditional parameters (SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG)) of primary lesions on 18F-FDG PET/CT, and intra-tumoral metabolic heterogeneity index (HI; such as cumulative SUV volume histogram AUC (AUC-CSH), linear regression slope, CV). AUC-CSH and CV were calculated using SUV thresholds of 2.5 and 40%SUV max. Logistic univariate and multivariate regression analyses were used to extract independent predictors in clinical features and PET/CT parameters for the differential diagnosis of pulmonary lesions. A multi-parameter combined model was established through logistic regression and validated for diagnostic efficacy using ROC curve analysis. Results:Among 251 patients, 101 were benign and 150 were malignant. In univariate analysis, gender, age, tumor markers, spiculation sign, lobulation sign, vessel convergence sign, air bronchogram, long diameter, short diameter, SUV max, AUC-CSH 2.5, AUC-CSH 40%, CV2.5, and CV40% were predictive factors for the diagnosis of benign and malignant tumors (odds ratio ( OR): 0.57-17.39, all P<0.05). In multivariate analysis, gender, age, tumor markers, lobulation sign, vessel convergence sign, SUV max, AUC-CSH 40%, and CV40% were independent predictors for the diagnosis of benign and malignant tumors ( OR: 2.30-13.18, all P<0.05). The AUC, sensitivity, specificity, and accuracy of the multi-parameter combined model established with the above independent predictors were 0.89, 77.33%(116/150), 84.16%(85/101), 80.08%(201/251), respectively. Conclusion:18F-FDG PET/CT multi-parameter combined model has high value in the differentiation of benign and malignant pulmonary lesions.

Objective:To establish venetoclax-resistant acute myeloid leukemia(AML)cell lines,assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family,and investigate their resistance mechanisms.Methods:CCK-8 method was used to screen AML cell lines(MV4-11,MOLM13,OCI-AML2)that were relatively sensitive to venetoclax.Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines.Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry.BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients.Results:Venetoclax-resistant cell lines of MV4-11,MOLM13,and OCI-AML2 were successfully established,with IC50 values exceeding 10-fold.Under the same concentration of venetoclax,the apoptosis rate of resistant cells decreased significantly(P＜0.05).BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins(such as BIM,BID and NOXA).RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines.Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results.Conclusion:The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax.The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM,BID,and NOXA,which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.

Objective:To explore the value of preoperative 18F-fluorodeoxyglucose ( 18F-FDG) positron emission tomography (PET) metabolic heterogeneity parameters in predicting tumor deposits (TD) in colorectal cancer (CRC). Methods:A retrospective analysis was conducted on 91 CRC patients who underwent surgical treatment at the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from February 2013 to March 2024. All patients underwent preoperative 18F-FDG PET/CT examination. The LIFEx-7.5.15 software was used to delineate the primary lesion with 40% of maximum standardized uptake value (SUV max) as the relative threshold, and metabolic parameters were extracted. Intratumoral metabolic heterogeneity parameters included cumulative SUV histogram area under the curve (AUC-CSH), heterogeneity index (HI), heterogeneity factor (HF), and coefficient of variation (CV). The presence of TD was confirmed by postoperative pathological examination. Differences in data between the TD group and non-TD (NTD) group were compared. Binary logistic regression analysis was used to identify independent risk factors for TD, and receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of each parameter for TD. Results:Postoperative pathological diagnosis showed that 27 patients were included in the TD group and 64 in the NTD group. There were statistically significant differences between the TD group and NTD group in CV ( Z=-3.145, P=0.002) and the proportion of patients with carcinoembryonic antigen (CEA) >10 ng/ml (χ 2=10.751, P=0.001), while no statistically significant differences were found in HI, HF, or AUC-CSH (all P>0.05). Binary logistic regression analysis showed that CV was an independent risk factor for TD. ROC curve analysis showed that the area under the ROC curve (AUC) of CV for predicting TD was 0.709(95% CI: 0.593-0.826), which was higher than that of other metabolic heterogeneity parameters. Conclusions:The preoperative 18F-FDG PET/CT metabolic heterogeneity parameter CV has value in predicting TD in CRC patients.

Objective:To investigate the anatomical feasibility of the endoscopic transorbital approach (ETOA) to the orbital apex and lateral middle cranial fossa, to identify stable and recognizable surgical landmarks under endoscopic visualization, and to provide morphometric data for preoperative planning and intraoperative navigation.Methods:Stepwise anatomical dissection was performed on five formalin-fixed cadaveric heads and one fresh arterially injected cadaveric specimen to simulate the ETOA using a 0° endoscope. Key structures and their anatomical relationships were observed and recorded. Additionally, high-resolution CT scans of 50 adults were retrospectively analyzed. Three-dimensional reconstructions and measurements were performed using Mimics 17.0 software. Spatial validation was performed using 17 dry skulls to verify the consistency and reliability of osseous anatomical landmarks.Results:Cadaveric dissection identified the meningo-orbital band, superior orbital fissure, optic canal, foramen rotundum, and foramen ovale as reliable surgical landmarks for the ETOA. A topographic map of the surgical region was established based on the endoscopic view. CT measurements revealed the following distances (Mean±SD): the midpoint of the supraorbital rim to the foramen rotundum (57.31±3.59) mm and foramen ovale (71.46±3.42) mm; the lateral orbital rim to the lateral edge of the superior orbital fissure (37.38±2.52) mm; the distance from the superior orbital fissure to the optic canal (9.98±1.49) mm; and the distance from the anterior ethmoidal artery to the optic canal (19.98±2.05) mm. These measurements were consistent with dry skull data, indicating that these osseous landmarks had stable spatial relationships and were suitable for intraoperative localization.Conclusions:The ETOA provides favorable anatomical accessibility and clinical feasibility for lesions involving the orbital apex and lateral skull base. Key osseous structures demonstrate high identifiability and stable spatial relationships, serving as critical references for intraoperative navigation and preoperative pathway planning. The quantitative anatomical framework established in this study provides critical morphometric support for minimally invasive surgery targeting lesions in this region.