Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial.

Hepatocellular carcinoma (HCC), particularly when accompanied by microvascular invasion (MVI), has a markedly high risk of recurrence after liver resection. Adjuvant immunotherapy is considered a promising avenue. This multicenter, open-label, randomized, controlled, phase 2 trial was conducted at six hospitals in China to assess the efficacy and safety of adjuvant sintilimab, a programmed cell death protein 1 inhibitor, in these patients. Eligible patients with HCC with MVI were randomized (1:1) into the sintilimab or active surveillance group. The sintilimab group received intravenous injections every 3 weeks for a total of eight cycles. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat population. Key secondary endpoints included overall survival (OS) and safety. From September 1, 2020, to April 23, 2022, a total of 198 eligible patients were randomly allocated to receive adjuvant sintilimab (n = 99) or undergo active surveillance (n = 99). After a median follow-up of 23.3 months, the trial met the prespecified endpoints. Sintilimab significantly prolonged RFS compared to active surveillance (median RFS, 27.7 versus 15.5 months; hazard ratio 0.534, 95% confidence interval 0.360-0.792; P = 0.002). Further follow-up is needed to confirm the difference in OS. In the sintilimab group, 12.4% of patients experienced grade 3 or 4 treatment-related adverse events, the most common of which were elevated alanine aminotransferase levels (5.2%) and anemia (4.1%). These findings support the potential of immune checkpoint inhibitors as effective adjuvant therapy for these high-risk patients. Chinese Clinical Trial Registry identifier: ChiCTR2000037655 .

Disrupted topological organization of the default mode network in mild cognitive impairment with subsyndromal depression: A graph theoretical analysis.

AIMS: Subsyndromal depression (SSD) is common in mild cognitive impairment (MCI). However, the neural mechanisms underlying MCI with SSD (MCID) are unclear. The default mode network (DMN) is associated with cognitive processes and depressive symptoms. Therefore, we aimed to explore the topological organization of the DMN in patients with MCID. METHODS: Forty-two MCID patients, 34 MCI patients without SSD (MCIND), and 36 matched healthy controls (HCs) were enrolled. The resting-state functional connectivity of the DMN of the participants was analyzed using a graph theoretical approach. Correlation analyses of network topological metrics, depressive symptoms, and cognitive function were conducted. Moreover, support vector machine (SVM) models were constructed based on topological metrics to distinguish MCID from MCIND. Finally, we used 10 repeats of 5-fold cross-validation for performance verification. RESULTS: We found that the global efficiency and nodal efficiency of the left anterior medial prefrontal cortex (aMPFC) of the MCID group were significantly lower than the MCIND group. Moreover, small-worldness and global efficiency were negatively correlated with depressive symptoms in MCID, and the nodal efficiency of the left lateral temporal cortex and left aMPFC was positively correlated with cognitive function in MCID. In cross-validation, the SVM model had an accuracy of 0.83 [95% CI 0.79-0.87], a sensitivity of 0.88 [95% CI 0.86-0.90], a specificity of 0.75 [95% CI 0.72-0.78] and an area under the curve of 0.88 [95% CI 0.85-0.91]. CONCLUSIONS: The coexistence of MCI and SSD was associated with the greatest disrupted topological organization of the DMN. The network topological metrics could identify MCID and serve as biomarkers of different clinical phenotypic presentations of MCI.

[Effect of electroacupuncture on renal vascular microcirculation in diabetic mice based on in vivo two-photon microscopy imaging].

OBJECTIVE: To investigate the protective effect of electroacupuncture (EA) at "Zusanli"(ST36)and "Weiwanxiashu"(EX-B3) on capillary function around the renal tubule and renal tubule structure in diabetic mice based on two-photon microscopy (TPM) imaging, so as to providing visualizable evidence for the regulatory effect of EA on diabetic renal vascular microcirculation. METHODS: Spontaneous type Ⅱ diabetes mellitus mice (db/db) were employed for this study. Twenty db/db mice were randomly divided into model group (n=10) and EA group (n=10), and 10 db/m mice used as the control group. EA was applied to bilateral ST36 and EX-B3 for 20 min/time, 6 times a week for 6 weeks. The body weight was recorded and the fasting blood glucose measured before and after the intervention. The urine production and water consumption of mice in each cage were recorded after EA. The renal in vivo imaging method based on TPM was established to display the morphological structure of renal tubules, and the mouse renal blood flow velocity was detected by injecting 500 kDa dextran-fluorescein into femoral vein after the intervention. RESULTS: Compared with the control group, the proportion of mice with decreased body mass in the model group was increased, accounting for 40%, while that in the control group was 0%; and fasting blood glucose, urine production and water consumption were significantly increased in the model group (P<0.001, P<0.000 1). A renal in vivo imaging method based on TPM was successfully established, which can be applied to quantitatively analyze the renal blood flow and renal tubular diameter of mice. Based on this method, the results showed that compared with the control group, the blood flow velocity of peritubular capillary in the model group was significantly decreased (P<0.000 1, P<0.001), renal tubular cells were slightly exfoliated and the diameter of renal tubular was significantly increased (P<0.000 1). Compared with the model group, EA reduced the body weight loss ratio from 40% to 0%, and significantly decreased the fasting blood glucose, urine production and water consumption (P<0.01, P<0.000 1, P<0.001), and the blood flow velocity of peritubular capillary in the EA group was significantly increased (P<0.001, P<0.05) and tubule dilatation significantly alleviated (P<0.0 1). CONCLUSION: EA at ST36 and EX-B3 can ameliorate renal vascular microcirculation disorder to relieve the renal structure damage and improve renal function in diabetes mice.

Evaluation of nano-silver concentrations using multi-media fate and transport models with different spatial resolutions.

Due to the complexity of the environmental matrix and the limitation of the detection level, it is important to use models to evaluate environmental exposure to nanomaterials. Based on this, this research established two multi-media fate and transport models of silver nanoparticles (AgNPs) with respective coarse and fine spatial resolutions. Using the case of the spatial distribution of AgNPs in the Xiangjiang River, China, we compared how the spatial resolution of a model impacts modeling results. The results show that the process of heterogeneous aggregation has the greatest impact on the modeled concentration of AgNPs in water, and the heterogeneous aggregation of free AgNPs with natural colloids and settling down to sediments is the dominant mechanism responsible for the loss of AgNPs. In addition, the use of different spatial resolutions gives similar trends in the modeled AgNPs concentration, despite the difference in absolute levels. Our work also shows that the reliability and accuracy of the rate constant of heterogeneous aggregation has a great influence on the modeled AgNPs concentrations.

Cloud point extraction (CPE) combined with single particle -inductively coupled plasma-mass spectrometry (SP-ICP-MS) to analyze and characterize nano-silver sulfide in water environment.

Silver Nanoparticles (Ag-NPs), an emerging type of pollutant, might occur various physical and chemical transformations, which would affect its environmental fate, transformation and biological effects. Sulfurization is the most common conversion of Ag-NPs, accompanied by the formation of nano-silver sulfide (Ag2S-NPs). The method of Ag2S-NPs analysis and characterization is of great significance for assessing the environmental risks of Ag. In this study, cloud point extraction (CPE) and Single Particle-Inductively Coupled Plasma-Mass Spectrometry (SP-ICP-MS) were used in combination to establish a simple and reliable analysis method to quantify Ag2S-NPs in water, with the morphology unchanged. Non-Ag2S-NPs were dissociated into Ag+ firstly, and Ag2S-NPs and Ag+ were separated by CPE, followed by SP-ICP-MS analysis. The extraction rate based on particle number concentration was between (76.19 ± 0.56) % to (106.35 ± 0.00) % in environmental waters. Compared with the (76.96 ± 2.18) nm Ag2S-NPs spiked, the particle size extracted increased slightly with (94.19 ± 2.72) nm- (97.25 ± 0.22) nm as the large-size Ag2S-NPs originally presented in waters, instead of agglomeration. This method could be generally applicable to the analysis of Ag2S-NPs in waters, and provide ideas for other metal sulfide nanoparticles (MS-NPs), which has certain significance.

Enzyme digestion combined with SP-ICP-MS analysis to characterize the bioaccumulation of gold nanoparticles by mustard and lettuce plants.

Plants can absorb and accumulate engineered nanomaterials (ENMs) through water and soil, providing a potential way for nanoparticles to be enriched in humans through the food chain. In this paper, a combination of enzymatic digestion method and SP-ICP-MS analysis was used to quantitatively characterize the enriched AuNPs in mustard and lettuce plants. The results showed that Macerozyme R-10 enzyme can extract AuNPs from plants without obvious aggregation/dissolution. Both mustard and lettuce plants can absorb and enrich the complete AuNPs to the above-ground organs, and the particle number concentrations detected are 1.24 × 107 particles L-1 and 4.39 × 107 particles L-1, respectively. With different exposure level of AuNPs(0.5 mg L-1,), a particle number concentration of 2.32 × 107 particles L-1 was detected in the stems of lettuce plants, while the mustard failed to transport AuNPs to the above-ground organs. The transport efficiency of Au ions by plants is higher than that of AuNPs, and the plants have stronger bioavailability for ions.

Quantitative detection of gold nanoparticles in soil and sediment.

Ever-growing application of engineering nanoparticles in many sectors of the society requires efficient methods to extract them from soil and sediment, for the sake of environmental protection. In this study, we develop a new method which uses sodium pyrophosphate solution (TSPP, Na4P2O7) as extratant to extract gold nanoparticle (AuNPs) from soil and sediment under optimized parameters through vortexing, water bath oscillation, ultrasonic bath and precipitation. SP-ICP-MS was used for the detection of number concentration, mass concentration and size distribution of AuNPs in soil. UV irradiation was innovatively used to directly degrade soil organic matter to improve the recovery of AuNPs due to their low recovery rate in rich organic soils. It could be found that the mass fraction recovery increased from 36% (without UV digestion) to 83% (with 48h UV digestion). The extraction method is versatile for different coating layers and wide-ranging particle sizes in real soil and sediment. Therefore, the rapid and efficient characterization and quantification of AuNPs in soil and sediment are achieved, and the researches on the extraction method of AuNPs and their behavior and toxicity assessment in soil environment can be enriched.

[Simultaneous detection of phenol and anionic surfactant in water based on continuous spectrum].

Phenol and anionic surfactant are important indices for water-quality. Based on improvement and optimization of standard methods (spectrophotometry) for the two indices, we integrated the respective two color-extractants into a composited reagent. Using a self-developed microspectrometer with a design of splitting behind and collection of continuous spectrum signal (340-770 nm) in real time, a compound detection system was constructed. This system could simultaneously detect phenol and anionic surfactant in water without chemical and spectral interferences, leading to great decreases in reagent amount and detection time. The detection limits for phenol and anionic surfactant are 0. 003 and 0.016 mg x L(-1), respectively. This method was applied to water-quality monitoring of real samples in comparison with standard methods, and the results indicated that its reproducibility (relative standard deviation, n=5) and accuracy (relative error to results by standard methods) were less than 5%, contenting with the related standard.