Associations of subcutaneous fat area and Systemic Immune-inflammation Index with survival in patients with advanced gastric cancer receiving dual PD-1 and HER2 blockade.

BACKGROUND: Systemic Immune-inflammation Index (SII) and body composition parameters are easily assessed, and can predict overall survival (OS) in various cancers, allowing early intervention. This study aimed to assess the correlation between CT-derived body composition parameters and SII and OS in patients with advanced gastric cancer receiving dual programmed death-1 (PD-1) and human epidermal growth factor receptor 2 (HER2) blockade. MATERIALS AND METHODS: This retrospective study enrolled patients with advanced gastric cancer treated with dual PD-1 and HER2 blockade from March 2019 to June 2022. We developed a deep learning model based on nnU-Net to automatically segment skeletal muscle, subcutaneous fat and visceral fat at the third lumbar level, and calculated the corresponding Skeletal Muscle Index, skeletal muscle density, subcutaneous fat area (SFA) and visceral fat area. SII was computed using the formula that total peripheral platelet count×neutrophil/lymphocyte ratio. Univariate and multivariate Cox regression analysis were used to determine the associations between SII, body composition parameters and OS. RESULTS: The automatic segmentation deep learning model was developed to efficiently segment body composition in 158 patients (0.23 s/image). Multivariate Cox analysis revealed that high SII (HR=2.49 (95% CI 1.54 to 4.01), p<0.001) and high SFA (HR=0.42 (95% CI 0.24 to 0.73), p=0.002) were independently associated with OS, whereas sarcopenia was not an independent prognostic factor for OS (HR=1.41 (95% CI 0.86 to 2.31), p=0.173). In further analysis, patients with high SII and low SFA had worse long-term prognosis compared with those with low SII and high SFA (HR=8.19 (95% CI 3.91 to 17.16), p<0.001). CONCLUSION: Pretreatment SFA and SII were significantly associated with OS in patients with advanced gastric cancer. A comprehensive analysis of SII and SFA may improve the prognostic stratification of patients with gastric cancer receiving dual PD-1 and HER2 blockade.

Fate and mechanistic insights into nanoscale zerovalent iron (nZVI) activation of sludge derived biochar reacted with Cr(VI).

While nanoscale zero-valent iron modified biochar (nZVI-BC) have been widely investigated for the removal of heavy metals, the corrosion products of nZVI and their interaction with heavy metals have not been revealed yet. In this paper, nZVI-BC was synthesized and applied for the removal of Cr(VI). Batch experiments indicated that the adsorption of Cr(VI) fit Langmuir isotherm, with the maximum removal capacity at 172.4 mg/g at pH 2.0. SEM-EDS, BET, XRD, FT-IR, Raman and XPS investigation suggested that reduction of Cr(VI) to Cr(III) was the major removal mechanism. pH played an important role on the corrosion of nZVI-BC, at pH 4.5 and 2.0, FeOOH and Fe3O4 were detected as the major iron oxide, respectively. Therefore, FeOOH-BC and Fe3O4-BC were further prepared and their interaction with Cr were studied. Combining with DFT calculations, it revealed that Fe3O4 has higher adsorption capacity and was responsible for the effective removal of Cr(VI) through electrostatic attraction and reduction under acidic conditions. However, Fe3O4 will continue to convert to the more stable FeOOH, which is the key to for the subsequent stabilization of the reduced Cr(III). The results showed that the oxide corrosion products of nZVI-BC were subjected to the environment, which will eventually affect the fate and transport of the adsorbed heavy metal.

[Experimental study on gradient of nerve growth factor immobilized conduits promoting peripheral nerve regeneration in rats].

OBJECTIVE: To study the effect of the loaded concentration gradient of nerve growth factor (NGF) immobilized conduit on rat peripheral nerve defect repair. METHODS: The peripheral nerve conduits made of poly (epsilon-caprolactone)-block-poly (L-lactide-co-epsilon-caprolactone) were prepared with uniform loads or concentration gradient loads by combining differential absorption of NGF/silk fibroin (SF) coating, and the gradient of NGF was immobilized in the nerve conduits. ELISA method was used to exam the NGF release for 12 weeks in vitro. Twenty-four male Sprague Dawley rats (weighing, 220-250 g) were selected to establish the right sciatic nerve defect model (14 mm in length) and randomly divided into 4 groups according to repair methods. The transected nerve was bridged by a blank conduit without NGF in group A, by a conduit containing uniform loads of NGF in group B, by a conduit concentration gradient loads of NGF in group C, and by the autogenous nerve segment in group D. The gross observation, electrophysiological examination, histological observation, and transmission electron microscope observation were carried out to assess the nerve regeneration at 12 weeks after surgery. RESULTS: The cumulative release amount of NGF was (14.2 +/- 1.4) ng/mg and (13.7 +/- 1.3) ng/mg in gradient of NGF loaded conduits and uniform NGF loaded conduits respectively at 12 weeks, showing no significant difference (t = 0.564, P=0.570). All the animals survived to completion of the experiment; plantar ulcers occurred at 4 days, which healed at 12 weeks; groups C and D were better than groups A and B in ulcerative healing. At 12 weeks after surgery, the compound muscle action potential of group A was significantly lower than that of groups B, C, and D (P < 0.05), and group B was significantly lower than groups C and D (P < 0.05), but no significant difference was found between groups C and D (P > 0.05). The axon density of group C was significantly higher that of groups A, B, and D (P < 0.05); group D was significantly higher than groups A, B, and C, and group C was significantly higher than groups A and B in the axon number, axon diameter, and area of muscle fiber (P < 0.05); the thickness of myelin sheath of groups C and D was significantly larger than that of groups A and B (P < 0.05), but no significant difference was found between groups C and D (P > 0.05). CONCLUSION: Gradient of NGF loaded nerve condnits for rat sciatic nerve defect has similar results to autogenous nerve, with a good bridge, which can promote the sciatic nerve regeneration, improve the myelinization of the regenerating nerve, and accelerate the function reconstruction of the regenerating nerve.

Preparation of PLLA/bpV(pic) microspheres and their effect on nerve cells.

In this study, we prepared PLLA/bpV(pic) microspheres, a bpV(pic) controlled release system and examined their ability to protect nerve cells and promote axonal growth. PLLA microspheres were prepared by employing the o/w single emulsification-evaporation technique. Neural stem cells and dorsal root ganglia were divided into 3 groups in terms of the treatment they received: a routine medium group (cultured in DMEM), a PLLA microsphere group (DMEM containing PLLA microspheres alone) and a PLLA/bpV(pic) group [DMEM containing PLLA/bpV(pic) microspheres]. The effects of PLLA/bpV(pic) microspheres were evaluated by the live-dead test and measurement of axonal length. Our results showed that PLLA/bpV(pic) granulation rate was (88.2±5.6)%; particle size was (16.8±3.1)%, drug loading was (4.05±0.3)%; encapsulation efficiency was (48.5±1.8)%. The release time lasted for 30 days. In PLLA/bpV(pic) microsphere group, the cell survival rate was (95.2 ±4.77)%, and the length of dorsal root ganglion (DRG) was 718±95 µm, which were all significantly greater than those in ordinary routine medium group and PLLA microsphere group. This preliminary test results showed the PLLA/bpV(pic) microspheres were successfully prepared and they could promote the survival and growth of neural cells in DRG.