Objective:To explore the efficacy and safety of combining targeted therapy and immunotherapy with standard chemotherapy in patients with advanced pancreatic cancer.Methods:This is a single-center retrospective cohort study. A total of 123 patients with advanced pancreatic cancer who received first-line systemic treatment at the Second Hospital of Hebei Medical University between January 2022 and December 2024 were retrospectively enrolled. There were 65 males and 58 females,with a mean age of (65.1±10.1) years (range:22 to 88 years). According to whether targeted therapy combined with immunotherapy was added to chemotherapy,patients were divided into a triplet group ( n=46) and a standard chemotherapy group ( n=77). The primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included radiological efficacy indicators (objective response rate (ORR), disease control rate (DCR),clinical benefit rate,etc.) and treatment-related adverse events. Propensity score matching (PSM,caliper=0.2) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate survival,and Cox regression models were applied to analyze factors influencing OS and PFS. Results:In the original cohort,the median OS was 11 months in the triplet group and 8 months in the chemotherapy group,with no statistically significant difference ( P=0.056). The median PFS was 5 months in the triplet group and 3 months in the chemotherapy group,also without statistical significance ( P>0.05). Multivariate Cox regression analysis indicated that the triplet regimen was an independent prognostic factor for both OS and PFS ( P<0.05). After PSM,baseline balance between groups was good. The median OS was 10.0 months in the triplet group and 7.0 months in the chemotherapy group, with no significant difference ( P=0.094). In terms of efficacy, the ORR was 26.1% (12/46) in the triplet group versus 7.8% (6/77) in the chemotherapy group,with a statistically significant difference ( χ2=6.320, P=0.012). The DCR was 54.3% (25/46) in the triplet group and 33.8% (26/77) in the chemotherapy group,also statistically significant ( χ2=4.214, P=0.037). The incidence of adverse events was similar between groups,mostly grade 1 to 2. Conclusions:The triplet regimen of chemotherapy,targeted therapy,and immunotherapy shows potential in improving efficacy and prolonging survival with acceptable safety in patients with advanced pancreatic cancer. However, its definitive benefits require further investigation.

Objective:To explore the efficacy and safety of combining targeted therapy and immunotherapy with standard chemotherapy in patients with advanced pancreatic cancer.Methods:This is a single-center retrospective cohort study. A total of 123 patients with advanced pancreatic cancer who received first-line systemic treatment at the Second Hospital of Hebei Medical University between January 2022 and December 2024 were retrospectively enrolled. There were 65 males and 58 females,with a mean age of (65.1±10.1) years (range:22 to 88 years). According to whether targeted therapy combined with immunotherapy was added to chemotherapy,patients were divided into a triplet group ( n=46) and a standard chemotherapy group ( n=77). The primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included radiological efficacy indicators (objective response rate (ORR), disease control rate (DCR),clinical benefit rate,etc.) and treatment-related adverse events. Propensity score matching (PSM,caliper=0.2) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate survival,and Cox regression models were applied to analyze factors influencing OS and PFS. Results:In the original cohort,the median OS was 11 months in the triplet group and 8 months in the chemotherapy group,with no statistically significant difference ( P=0.056). The median PFS was 5 months in the triplet group and 3 months in the chemotherapy group,also without statistical significance ( P>0.05). Multivariate Cox regression analysis indicated that the triplet regimen was an independent prognostic factor for both OS and PFS ( P<0.05). After PSM,baseline balance between groups was good. The median OS was 10.0 months in the triplet group and 7.0 months in the chemotherapy group, with no significant difference ( P=0.094). In terms of efficacy, the ORR was 26.1% (12/46) in the triplet group versus 7.8% (6/77) in the chemotherapy group,with a statistically significant difference ( χ2=6.320, P=0.012). The DCR was 54.3% (25/46) in the triplet group and 33.8% (26/77) in the chemotherapy group,also statistically significant ( χ2=4.214, P=0.037). The incidence of adverse events was similar between groups,mostly grade 1 to 2. Conclusions:The triplet regimen of chemotherapy,targeted therapy,and immunotherapy shows potential in improving efficacy and prolonging survival with acceptable safety in patients with advanced pancreatic cancer. However, its definitive benefits require further investigation.

Objective To investigate the relationship between vertical laminar fracture(VLF)in thoracolumbar burst fractures and both neurological injury and dural tear.Methods A retrospective analysis was conducted on the clinical data and multi spiral computed tomography(MSCT)coronal images of 255 patients of thoracolumbar burst fractures.The patients were divided into three groups based on the presence of VLF[Ⅰ group(complete VLF group),Ⅱ group(partial VLF group),and Ⅲ group(normal lamina group)].Statistical analysis was performed using analysis of variance and Fisher's exact test to compare radiological parameters,inci-dence of dural tear,and neurological injury among the groups.Results The Ⅰ group showed significant differences in spinal canal sagittal diameter,pedicle distance,and spinal canal area compared with the other two groups(P<0.05).However,there was no sig-nificant difference in vertebral body compression rate between the Ⅰ group and the Ⅱ group(P>0.05).The Ⅰ group had the high-est incidence of severe neurological injury[American Spinal Injury Association(ASIA)impairment scale grades A and B]and dural tear(P<0.05).Conclusion The severity of VLF is closely related to dural tear and neurological injury.MSCT coronal images can clearly display the extent of VLF,providing an important basis for clinical evaluation and treatment plan.

Objective:To investigate the risk factors for dural tears in patients with thoracolumbar burst fracture (TLBF) and their predictive efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 135 TLBF patients admitted to Tianjin Fifth Central Hospital from March 2020 to February 2025, including 83 males and 52 females, aged 16-65 years [41(31, 50)years]. Among them, 31 patients had thoracic fracture and 104 lumbar fracture. The patients were divided into dural tear group ( n=82) and dural intact group ( n=53) based on the presence of dural tear. The following data of the two groups were collected including gender, age, underlying diseases, body mass index (BMI), bone density T-score, cause of injury, AO fracture classification, distribution of injured vertebrae, vertical laminar fracture (VLF) classification, radiological parameters (pedicle spacing, vertebral canal area, sagittal diameter of the vertebral canal, vertebral compression rate), and American Spinal Injury Association (ASIA) impairment scale. Univariate analysis and multivariate Logistic regression analysis were conducted to assess and identify the independent risk factors for dural tears in TLBF patients. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the predictive efficacy of each independent risk factor. Results:Univariate analysis showed statistically significant differences in VLF classification, pedicle spacing, vertebral canal area, sagittal diameter of the vertebral canal, vertebral compression rate, and ASIA impairment scale between the two groups ( P<0.05). Multivariate Logistic regression analysis revealed that VLF classification ( OR=4.16, 95% CI 1.03, 11.46, P<0.05), pedicle spacing ( OR=1.08, 95% CI 0.81, 1.16, P<0.05), and ASIA impairment scale ( OR=3.06, 95% CI 2.00, 8.48, P<0.01) were significantly associated with dural tears in TLBF patients. ROC curve analysis showed that VLF classification (AUC=0.86, 95% CI 0.62, 0.95), pedicle spacing (AUC=0.86, 95% CI 0.77, 1.00), and ASIA impairment scale (AUC=0.76, 95% CI 0.74, 0.97) had relatively high predictive efficacy for dural tear. The combination of VLF classification and pedicle spacing had the highest predictive efficacy (AUC=0.89, 95% CI 0.78, 1.01). Conclusions:VLF classification, pedicle spacing, and ASIA impairment scale are independent risk factors for dural tears in TLBF patients. VLF classification and pedicle spacing have relatively high independent predictive efficacy and their combination can further improve the predictive efficacy.

Objective To investigate the relationship between vertical laminar fracture(VLF)in thoracolumbar burst fractures and both neurological injury and dural tear.Methods A retrospective analysis was conducted on the clinical data and multi spiral computed tomography(MSCT)coronal images of 255 patients of thoracolumbar burst fractures.The patients were divided into three groups based on the presence of VLF[Ⅰ group(complete VLF group),Ⅱ group(partial VLF group),and Ⅲ group(normal lamina group)].Statistical analysis was performed using analysis of variance and Fisher's exact test to compare radiological parameters,inci-dence of dural tear,and neurological injury among the groups.Results The Ⅰ group showed significant differences in spinal canal sagittal diameter,pedicle distance,and spinal canal area compared with the other two groups(P<0.05).However,there was no sig-nificant difference in vertebral body compression rate between the Ⅰ group and the Ⅱ group(P>0.05).The Ⅰ group had the high-est incidence of severe neurological injury[American Spinal Injury Association(ASIA)impairment scale grades A and B]and dural tear(P<0.05).Conclusion The severity of VLF is closely related to dural tear and neurological injury.MSCT coronal images can clearly display the extent of VLF,providing an important basis for clinical evaluation and treatment plan.

Objective:To investigate the risk factors for dural tears in patients with thoracolumbar burst fracture (TLBF) and their predictive efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 135 TLBF patients admitted to Tianjin Fifth Central Hospital from March 2020 to February 2025, including 83 males and 52 females, aged 16-65 years [41(31, 50)years]. Among them, 31 patients had thoracic fracture and 104 lumbar fracture. The patients were divided into dural tear group ( n=82) and dural intact group ( n=53) based on the presence of dural tear. The following data of the two groups were collected including gender, age, underlying diseases, body mass index (BMI), bone density T-score, cause of injury, AO fracture classification, distribution of injured vertebrae, vertical laminar fracture (VLF) classification, radiological parameters (pedicle spacing, vertebral canal area, sagittal diameter of the vertebral canal, vertebral compression rate), and American Spinal Injury Association (ASIA) impairment scale. Univariate analysis and multivariate Logistic regression analysis were conducted to assess and identify the independent risk factors for dural tears in TLBF patients. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the predictive efficacy of each independent risk factor. Results:Univariate analysis showed statistically significant differences in VLF classification, pedicle spacing, vertebral canal area, sagittal diameter of the vertebral canal, vertebral compression rate, and ASIA impairment scale between the two groups ( P<0.05). Multivariate Logistic regression analysis revealed that VLF classification ( OR=4.16, 95% CI 1.03, 11.46, P<0.05), pedicle spacing ( OR=1.08, 95% CI 0.81, 1.16, P<0.05), and ASIA impairment scale ( OR=3.06, 95% CI 2.00, 8.48, P<0.01) were significantly associated with dural tears in TLBF patients. ROC curve analysis showed that VLF classification (AUC=0.86, 95% CI 0.62, 0.95), pedicle spacing (AUC=0.86, 95% CI 0.77, 1.00), and ASIA impairment scale (AUC=0.76, 95% CI 0.74, 0.97) had relatively high predictive efficacy for dural tear. The combination of VLF classification and pedicle spacing had the highest predictive efficacy (AUC=0.89, 95% CI 0.78, 1.01). Conclusions:VLF classification, pedicle spacing, and ASIA impairment scale are independent risk factors for dural tears in TLBF patients. VLF classification and pedicle spacing have relatively high independent predictive efficacy and their combination can further improve the predictive efficacy.

Humans ; SARS-CoV-2 ; COVID-19

Objective:To evaluate regulatory effects of fibroblast growth factor receptor 3 (FGFR3) and human papillomavirus type 2 (HPV2) E2 protein on the differentiation of an immortalized human keratinocyte line HaCaT and a normal human epidermal keratinocyte line NHEK.Methods:In both HaCaT and NHEK cells, HPV2 E2-stably transfected cell lines (HPV2 E2-transfected groups) were established by using the lentivirus transfection method, wide-type FGFR3-overexpressing cells (FGFR3-WT transfected groups) and FGFR3-K650E mutant-overexpressing cells (FGFR3-K650E transfected groups) were constructed by using the plasmid transfection method, and cells transfected with blank vectors served as control groups (blank vector control groups). Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of HPV2 E2, and Western blot analysis to determine the protein expression of HPV2 E2, FGFR3, and keratinocyte differentiation markers including loricrin, filaggrin, as well as involucrin. Laser scanning confocal microscopy was conducted to observe the spatial localization of HPV2 E2 and FGFR3 in HaCaT cells. Statistical analysis was carried out by using two-independent-sample t test for the comparison between two groups, one-way analysis of variance for the comparison among multiple groups, and Dunnett t-test for multiple comparisons. Results:The HPV2 E2-stably transfected cell lines were successfully constructed, and the expression of HPV2 E2 FLAG protein was significantly higher in the HPV2 E2-transfected groups than in the blank vector control groups in both HaCaT and NHEK cells ( t = 13.71, 25.91, respectively, both P < 0.001) ; both FGFR3-WT and FGFR3-K650E were successfully overexpressed in both HaCaT and NHEK cells, and the FGFR3 protein expression was significantly higher in the FGFR3-WT transfected groups and the FGFR3-K650E transfected groups than in the blank vector control groups ( F = 473.90, 579.90, respectively, both P < 0.001). In both HaCaT and NHEK cells, the expression of keratinocyte differentiation markers including loricrin, filaggrin, and involucrin was significantly upregulated in the HPV2 E2-transfected groups, the FGFR3-WT transfected groups, and the FGFR3-K650E transfected groups than in the blank vector control groups (all P < 0.05). In the HPV2 E2-stably transfected HaCaT and NHEK cells, the expression of loricrin, filaggrin, and involucrin was significantly down-regulated in the HPV2 E2 + FGFR3-WT transfected groups and the HPV2 E2 + FGFR3-K650E transfected groups than in the HPV2 E2 + blank vector groups (all P < 0.05). Laser scanning confocal microscopy showed the spatial co-localization of HPV2 E2 and FGFR3 in the nuclear membrane and cytoplasm of HaCaT cells. Conclusion:HPV2 E2 and FGFR3 could both induce the differentiation of HaCaT and NHEK cells, while FGFR3 could inhibit HPV2 E2-induced differentiation trend of HaCaT and NHEK cells, which may be related to the cellular spatial co-localization of HPV2 E2 and FGFR3.

OBJECTIVE To screen the potential drug targets and signaling pathways of Acanthopanax senticosus for the treatment of Alzheimer’s disease(AD) by bioinformatics and network pharmacology-based approach, and to preliminarily validate its efficacy. METHODS The ingredients of Acanthopanax senticosus were obtained through literature, the ingredients were screened by Swiss ADME, and potential targets were predicted by Swiss Target Prediction. AD’s differentially expressed genes were screened from the GSE28146 dataset. The target of Acanthopanax senticosus and AD target were mapped to construct a “drug-ingredients-potential target-disease” network and protein-protein interaction network. The DAVID database was used for GO and KEGG enrichment analysis. Autodock software was used to verify the molecular docking between key active ingredients and core targets. AD mice model was induced by D-galactose combined with aluminum chloride. Morris water maze test was performed to examine the learning memory ability of each group of mice and to observe the pathological changes in the hippocampus of mice. RESULTS Screened to obtain 24 active components and 74 potential targets of Acanthopanax senticosus for the treatment of AD. “Drug-ingredients-potential target-disease” network indicated that quercetin and kaempferol were the main components of Acanthopanax senticosus for the treatment of AD, and the protein-protein interaction network indicated that STAT3, MAPK1 and PIK3CA were the key targets. Obtained 366 GO enrichment entries(P<0.01) and 109 KEGG enrichment pathways(P<0.01). It mainly involved PI3K-AKT, AGE-RAGE, TNF and other pathways. The molecular docking results showed that the main active ingredients of Acanthopanax senticosus were able to bind well to the main targets. The in vivo pharmacological results showed that Acanthopanax senticosus could significantly improve the learning and memory ability of mice, reduce hippocampal tissue damage, and decrease the content of TNF-α, IL-6, and IL-1β in hippocampal tissue. CONCLUSION Acanthopanax senticosus may exert anti-AD effects by inhibiting the expression of inflammatory factors and reducing inflammatory damage.

Objective: To analyze the microvessel density (MVD) and lymph node metastasis in the papillary thyroid carcinoma (PTC) with punctate or sheet calcification. Methods: Fifty PTC patients in the Affiliated Hospital of Yangzhou University from May 2015 to October 2017 were retrospectively enrolled in this study. All of the 50 PTC patients were divided into punctate calcification group (38 cases) and sheet calcification group (12 cases) according to the different features of pathological calcification in microscope examination. For the two groups, the central and peripheral zone MVD and the lymph node metastasis of each PTC nodule were compared. Results: For PTC nodules of punctate calcification group, the mean central and peripheral zone MVD were (51±7)/HP and (64±8)/HP, respectively. For those of sheet calcification group, which were (35±5)/HP and (49±6)/HP, respectively. The mean MVD in both central and peripheral zone of PTC nodules of punctate calcification group were significantly higher than those of the sheet calcification group (t values were 10.183 and 12.406, both P < 0.05). The neck Ⅵ area lymph node metastasis rates of the punctate and sheet calcification groups were 42.1% (16/38) and 8.3% (1/12), respectively. The lymph node metastasis rate of the punctate calcification group was significantly higher than that of the sheet calcification group (χ ² = 4.635, P < 0.05). Conclusion PTC nodules with different type of pathological calcification may have different invasion and metastasis, and PTC with punctate calcification is more likely to undergo local metastasis than PTC with sheet calcification.