Objective To investigate the short- and long-term prognoses and the risk factors affecting “textbook outcome” (TO) after laparoscopic pancreaticoduodenectomy (LPD) for pancreatic ductal adenocarcinoma (PDAC). Methods The clinical and follow-up data of patients diagnosed with PDAC and treated with LPD from January 2019 to December 2022 were retrospectively analyzed. The prognosis was compared between TO and non-TO groups, and univariate and multivariate logistic regression analyses were used to identify independent prognostic factors for TO. Results A total of 284 patients were enrolled in this study, including 185 cases in the TO group and 99 cases in the non-TO group. The 1-, 3- and 5-year overall survival (OS) rates of the TO and non-TO groups with PDAC were 87.3% vs. 85.9%, 52.5% vs. 38.4%, and 18.0% vs. 4.5%, respectively (P=0.020); the recurrence-free survival (RFS) rates were 74.1% vs. 65.7%, 27.1% vs. 21.0%, and 10.0% vs. 0%, respectively (P=0.042). Multivariate logistic regression analysis showed that operation time >360 min (OR=0.561, 95%CI: 0.321-0.979, P=0.042), intraoperative blood loss >400 ml (OR=0.392, 95%CI: 0.175-0.879, P=0.023), hard or tough texture of pancreas (OR=2.240, 95%CI: 1.247-4.022, P=0.007), and main pancreatic duct diameter >3 mm (OR=1.931, 95%CI: 1.126-3.312, P=0.017) were independent prognostic factors for TO. Conclusion After the learning curve, more than 60% of patients with PDAC can achieve TO after LPD. The chances of achieving TO are significantly reduced when the operation time >360 min, the intraoperative blood loss >400 ml, the texture of pancreas was soft, and the diameter of the main pancreatic duct >3 mm.

Objective To investigate the short-and long-term prognoses and the risk factors affecting"text-book outcome"(TO)after laparoscopic pancreaticoduodenectomy(LPD)for pancreatic ductal adenocar-cinoma(PDAC).Methods The clinical and follow-up data of patients diagnosed with PDAC and treated with LPD from January 2019 to Dec-ember 2022 were retrospectively anal-yzed.The prognosis was compared bet-ween TO and non-TO groups,and uni-variate and multivariate logistic regre-ssion analyses were used to identify independent prognostic factors for TO.Results A total of 284 patients were enrolled in this study,including 185 cases in the TO group and 99 cases in the non-TO group.The 1-,3-and 5-year overall survival(OS)rates of the TO and non-TO groups with PDAC were 87.3%vs.85.9%,52.5%vs.38.4%,and 18.0%vs.4.5%,respectively(P=0.020);the recurrence-free survival(RFS)rates were 74.1%vs.65.7%,27.1%vs.21.0%,and 10.0%vs.0%,respectively(P=0.042).Multivariate logistic regression analysis showed that operation time>360 min(OR=0.561,95%CI:0.321-0.979,P=0.042),intraoperative blood loss>400 ml(OR=0.392,95%CI:0.175-0.879,P=0.023),hard or tough texture of pancreas(OR=2.240,95%CI:1.247-4.022,P=0.007),and main pancreatic duct dia-meter>3 mm(OR=1.931,95%CI:1.126-3.312,P=0.017)were independent prognostic factors for TO.Conclusion After the learning curve,more than 60%of patients with PDAC can achieve TO after LPD.The chances of achieving TO are significantly reduced when the operation time>360 min,the intraoperative blood loss>400 ml,the texture of pancreas was soft,and the diameter of the main pancreatic duct>3 mm.

OBJECTIVES: This study investigated the effects of a polycaprolactone (PCL)-polyethylene glycol (PEG) scaffold incorporated with concentrated growth factor (CGF) on the adhesion, proliferation, and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). METHODS: The PCL-PEG-CGF composite scaffold was fabricated using an immersion and freeze-drying technique. Its microstructure, mechanical properties, and biocompatibility were systematically characterized. The hPDLSCs were isolated through enzymatic digestion, and the hPDLSCs were identified through flow cytometry. Third-passage hPDLSCs were seeded onto the composite scaffolds, and their adhesion, proliferation and osteogenic differentiation were assessed using CCK-8 assays, 4',6-diamidino-2-phenylindole (DAPI) staining, alkaline phosphatase (ALP) staining, alizarin red staining, and Western blot analysis of osteogenesis-related proteins [Runt-related transcription factor 2 (Runx2), ALP, and morphogenetic protein 2 (BMP2)]. RESULTS: Scanning electron microscopy revealed that the PCL-PEG-CGF composite scaffold exhibited a honeycomb-like structure with heterogeneous pore sizes. The composite scaffold exhibited excellent hydrophilicity, as evidenced by a contact angle (θ) approaching 0° within 6 s. Its elastic modulus was measured at (4.590 0±0.149 3) MPa, with comparable hydrophilicity, fracture tensile strength, and fracture elongation to PCL-PEG scaffold. The hPDLSCs exhibited significantly improved adhesion to the PCL-PEG-CGF composite scaffold compared with the PCL-PEG scaffold (P<0.01). Additionally, cell proliferation was markedly improved in all the experimental groups on days 3, 5, and 7 (P<0.01), and statistically significant differences were found between the PCL-PEG-CGF group and other groups (P<0.01). The PCL-PEG-CGF group showed significantly elevated ALP activity (P<0.05), increased mineralization nodule formation, and upregulated expression of osteogenic-related proteins (Runx2, BMP2 and ALP; P<0.05). CONCLUSIONS The PCL-PEG-CGF composite scaffold exhibited excellent mechanical properties and biocompatibility, enhancing the adhesion and proliferation of hPDLSCs and promoting their osteogenic differentiation by upregulating osteogenic-related proteins.
Humans ; Polyesters/chemistry* ; Periodontal Ligament/cytology* ; Polyethylene Glycols/chemistry* ; Stem Cells/cytology* ; Tissue Scaffolds ; Cell Proliferation ; Osteogenesis ; Cell Differentiation ; Cell Adhesion ; Bone Morphogenetic Protein 2/metabolism* ; Cells, Cultured ; Alkaline Phosphatase/metabolism* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Intercellular Signaling Peptides and Proteins/pharmacology* ; Tissue Engineering/methods*

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Background::It is of great clinical significance to further explore new strategies and potential combined therapeutic targets for gastric cancer. This study aimed to investigate the synthetic lethal effect of RBBP8 molecular intervention combined with a poly ADP ribose polymerase (PARP) inhibitor in non-BRCA mutant gastric cancer and clarify the mechanism by which RBBP8 regulates homologous recombination repair.Methods::The role of RBBP8 in DNA damage repair was observed using bioinformatic analysis, western blot analysis, and immunofluorescence. The synthetic lethal effect was verified using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS)and flow cytometry apoptosis experiments.Results::Among the patients with gastric cancer treated with chemotherapy, the prognosis of patients with high RBBP8 expression levels was worse (homologous recombination [HR]= 1.54, p= 0.028). RBBP8 knockdown induced DNA damage and had a synergistic effect with PARP inhibitor treatment on cell viability inhibition and cell apoptosis in AGS (generic code for human gastric adenocarcinoma cells) ( t= 11.154, p < 0.001) and N87 ( t= 6.362, p < 0.001) cells. RBBP8 knockdown inhibited RAD51 activation and DNA terminal excision in homologous recombination repair. Conclusion::RBBP8 is involved in homologous recombination repair, and molecular intervention into RBBP8 could achieve a synthetic lethal effect with PARP inhibitor treatment in gastric cancer cells.

Background::It is of great clinical significance to further explore new strategies and potential combined therapeutic targets for gastric cancer. This study aimed to investigate the synthetic lethal effect of RBBP8 molecular intervention combined with a poly ADP ribose polymerase (PARP) inhibitor in non-BRCA mutant gastric cancer and clarify the mechanism by which RBBP8 regulates homologous recombination repair.Methods::The role of RBBP8 in DNA damage repair was observed using bioinformatic analysis, western blot analysis, and immunofluorescence. The synthetic lethal effect was verified using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS)and flow cytometry apoptosis experiments.Results::Among the patients with gastric cancer treated with chemotherapy, the prognosis of patients with high RBBP8 expression levels was worse (homologous recombination [HR]= 1.54, p= 0.028). RBBP8 knockdown induced DNA damage and had a synergistic effect with PARP inhibitor treatment on cell viability inhibition and cell apoptosis in AGS (generic code for human gastric adenocarcinoma cells) ( t= 11.154, p < 0.001) and N87 ( t= 6.362, p < 0.001) cells. RBBP8 knockdown inhibited RAD51 activation and DNA terminal excision in homologous recombination repair. Conclusion::RBBP8 is involved in homologous recombination repair, and molecular intervention into RBBP8 could achieve a synthetic lethal effect with PARP inhibitor treatment in gastric cancer cells.

Objective:To investigate the related factors of nonalcoholic steatohepatitis in children with obesity.Methods:A retrospective analysis was performed on 91 children with obesity who visited the Pediatric Obesity Clinic in the Affiliated Hospital of Hangzhou Normal University from July 2020 to January 2021. The 91 children with obesity were divided into two groups: with or without nonalcoholic steatohepatitis. Age, gender, body mass index, blood 25 hydroxyvitamin D3, fasting blood glucose, total cholesterol, triglyceride, low density lipoprotein, fasting insulin, control attenuation parameter and liver hardness value of in the 2 groups were recorded. Univariate analysis of the clinical data of the two groups was performed, and the clinical data with statistically significant differences between the two groups were included in binary logistic regression analysis to explore the related factors of nonalcoholic steatohepatitis in children with obesity. And then the receiver operating characteristic curve (ROC curve) was drawn on the relevant factors.Results:The children with obesity received treatment at the age of 6 years 1 month to 14 years 11 months, the male to female ratio was 1.33∶1. And 13 children (14.3%) were diagnosed with non-alcoholic steatohepatitis, of 46 nonalcoholic fatty liver disease, 9 were male and 4 were female. Univariate analysis showed that there were significant differences in gender, age, fasting insulin, control attenuation parameter and liver hardness value between the two groups (all P<0.05). Binary logistic regression analysis showed that control attenuation parameter ( OR=1.022, 95% CI: 1.001-1.041) and liver hardness value ( OR=1.689, 95% CI: 1.077-2.648) were the related factors of nonalcoholic steatohepatitis in children with obesity (both P<0.05). The area under the curve (AUC) values of control attenuation parameter and liver hardness value for predicting nonalcoholic steatohepatitis in children with obesity was 0.840 (95% CI: 0.748-0.931) and 0.794 (95% CI: 0.672-0.915), respectively. Conclusion:Control attenuation parameter and liver hardness value are correlated with nonalcoholic steatohepatitis in children with obesity with certain diagnostic value.

Objective:To compare the difference of low-level assisted ventilation and T-piece method on respiratory mechanics of patients with invasive mechanical ventilation during spontaneous breathing trial (SBT) within 3 days before extubation.Methods:A retrospective observational study was conducted. Twenty-five patients with difficulty in weaning or delayed weaning from invasive mechanical ventilation who were admitted to department of critical care medicine of the First Affiliated Hospital of Guangzhou Medical University from December 2018 to June 2020, and were in stable condition and entered the weaning stage after more than 72 hours of invasive mechanical ventilation were studied. A total of 119 cases of respiratory mechanical indexes were collected, which were divided into the low-level assisted ventilation group and the T-piece group according to the ventilator method and parameters used during the data collection. The different ventilation modes related respiratory mechanics indexes such as the esophageal pressure (Pes), the gastric pressure (Pga), the transdiaphragmatic pressure (Pdi), the maximum Pdi (Pdimax), Pdi/Pdimax ratio, the esophageal pressure-time product (PTPes), the gastric pressure-time product (PTPga), the transdiaphragmatic pressure-time product (PTPdi), the diaphragmatic electromyography (EMGdi), the maximum diaphragmatic electromyography (EMGdimax), PTPdi/PTPes ratio, Pes/Pdi ratio, the inspiratory time (Ti), the expiratory time (Te) and the total time respiratory cycle (Ttot) at the end of monitoring were recorded and compared between the two groups.Results:Compared with the T-piece group, Pes, PTPes, PTPdi/PTPes ratio, Pes/Pdi ratio and Te were higher in low-level assisted ventilation group [Pes (cmH 2O, 1 cmH 2O = 0.098 kPa): 2.84 (-1.80, 5.83) vs. -0.94 (-8.50, 2.06), PTPes (cmH 2O·s·min -1): 1.87 (-2.50, 5.93) vs. -0.95 (-9.71, 2.56), PTPdi/PTPes ratio: 0.07 (-1.74, 1.65) vs. -1.82 (-4.15, -1.25), Pes/Pdi ratio: 0.17 (-0.43, 0.64) vs. -0.47 (-0.65, -0.11), Te (s): 1.65 (1.36, 2.18) vs. 1.33 (1.05, 1.75), all P < 0.05], there were no significant differences in Pga, Pdi, Pdimax, Pdi/Pdimax ratio, PTPga, PTPdi, EMGdi, EMGdimax, Ti and Ttot between the T-piece group and the low-level assisted pressure ventilation group [Pga (cmH 2O): 6.96 (3.54,7.60) vs. 7.74 (4.37, 11.30), Pdi (cmH 2O): 9.24 (4.58, 17.31) vs. 6.18 (2.98, 11.96), Pdimax (cmH 2O): 47.20 (20.60, 52.30) vs. 29.95 (21.50, 47.20), Pdi/Pdimax ratio: 0.25 (0.01, 0.34) vs. 0.25 (0.12, 0.41), PTPga (cmH 2O·s·min -1): 7.20 (2.54, 9.97) vs. 7.97 (5.74, 13.07), PTPdi (cmH 2O·s·min -1): 12.15 (2.95, 19.86) vs. 6.87 (2.50, 12.63), EMGdi (μV): 0.05 (0.03, 0.07) vs. 0.04 (0.02, 0.06), EMGdimax (μV): 0.07 (0.05, 0.09) vs. 0.07 (0.04, 0.09), Ti (s): 1.20 (0.95, 1.33) vs. 1.07 (0.95, 1.33), Ttot (s): 2.59 (2.22, 3.09) vs. 2.77 (2.35, 3.24), all P > 0.05]. Conclusions:When mechanically ventilated patients undergo SBT, the use of T-piece method increases the work of breathing compared with low-level assisted ventilation method. Therefore, long-term use of T-piece should be avoided during SBT.

A 73-year-old male patient received immunotherapy (IV infusion of camrelizumab injection 200 mg once every 21 days) for mediastinal and right cervical lymph node metastasis after operation of esophageal cancer. Before immunotherapy, laboratory tests showed cardiac troponin I (cTnI) <0.01 μg/L, creatine kinase (CK) 69 U/L, and CK-MB 16 U/L. Electrocardiogram (ECG) showed no obvious abnormality. The day after the first IV infusion of camrelizumab, the patient developed fatigue, which were relieved without any treatment. The day after the second IV infusion of camrelizumab, he developed chest tightness, palpitation, and fatigue without obvious inducement. Laboratory tests showed cTnI 0.14 μg/L, CK 440 U/L, and CK-MB 39 U/L. ECG showed ST-T segment changes. Immune myocarditis due to camrelizumab was considered. An IV infusion of methylprednisolone injection (60-500 mg/d) was given. After 16 days of treatment, the patient′s chest tightness and palpitations were improved. Laboratory tests showed cTnI 0.48 μg/L, CK 94 U/L, and CK-MB 37 U/L.

A 73-year-old male patient received immunotherapy (IV infusion of camrelizumab injection 200 mg once every 21 days) for mediastinal and right cervical lymph node metastasis after operation of esophageal cancer. Before immunotherapy, laboratory tests showed cardiac troponin I (cTnI) <0.01 μg/L, creatine kinase (CK) 69 U/L, and CK-MB 16 U/L. Electrocardiogram (ECG) showed no obvious abnormality. The day after the first IV infusion of camrelizumab, the patient developed fatigue, which were relieved without any treatment. The day after the second IV infusion of camrelizumab, he developed chest tightness, palpitation, and fatigue without obvious inducement. Laboratory tests showed cTnI 0.14 μg/L, CK 440 U/L, and CK-MB 39 U/L. ECG showed ST-T segment changes. Immune myocarditis due to camrelizumab was considered. An IV infusion of methylprednisolone injection (60-500 mg/d) was given. After 16 days of treatment, the patient′s chest tightness and palpitations were improved. Laboratory tests showed cTnI 0.48 μg/L, CK 94 U/L, and CK-MB 37 U/L.