Preliminary study on diagnosis of gallbladder neoplastic polyps based on contrast-enhanced ultrasound and grey scale ultrasound radiomics.

Objective: Neoplastic gallbladder polyps (GPs), including adenomas and adenocarcinomas, are considered absolute indications for surgery; however, the distinction of neoplastic from non-neoplastic GPs on imaging is often challenging. This study thereby aimed to develop a CEUS radiomics nomogram, and evaluate the role of a combined grey-scale ultrasound and CEUS model for the prediction and diagnosis of neoplastic GPs. Methods: Patients with GPs of ≥ 1 cm who underwent CEUS between January 2017 and May 2022 were retrospectively enrolled. Grey-scale ultrasound and arterial phase CEUS images of the largest section of the GPs were used for radiomics feature extraction. Features with good reproducibility in terms of intraclass correlation coefficient were selected. Grey-scale ultrasound and CEUS Rad-score models were first constructed using the Mann-Whitney U and LASSO regression test, and were subsequently included in the multivariable logistic regression analysis as independent factors for construction of the combined model. Results: A total of 229 patients were included in our study. Among them, 118 cholesterol polyps, 68 adenomas, 33 adenocarcinomas, 6 adenomyomatoses, and 4 inflammatory polyps were recorded. A total of 851 features were extracted from each patient. Following screening, 21 and 15 features were retained in the grey-scale and CEUS models, respectively. The combined model demonstrated AUCs of 0.88 (95% CI: 0.83 - 0.93) and 0.84 (95% CI: 0.74 - 0.93) in the training and testing set, respectively. When applied to the whole dataset, the combined model detected 111 of the 128 non-neoplastic GPs, decreasing the resection rate of non-neoplastic GPs to 13.3%. Conclusion: Our proposed combined model based on grey-scale ultrasound and CEUS radiomics features carries the potential as a non-invasive, radiation-free, and reproducible tool for the prediction and identification of neoplastic GPs. Our model may not only guide the treatment selection for GPs, but may also reduce the surgical burden of such patients.

Dynamic Contrast-Enhanced Ultrasonography Combined With LR-M Classification Criteria for Differentiating Malignant Liver Nodules at High Risk for Hepatocellular Carcinoma.

OBJECTIVE: We aimed to investigate the value of quantitative parameters derived from dynamic contrast-enhanced ultrasonography (DCE-US) and a combination of these quantitative parameters with the LR-M classification criteria in distinguishing hepatocellular carcinoma (HCC) nodules and non-HCC malignancies. METHODS: HCC and non-HCC malignant nodules were grouped using pathologic results, and each nodule was classified using CEUS LI-RADS 2017. Quantitative CEUS analysis of each nodule was performed using VueBox, and quantitative parameters were compared between the HCC and non-HCC groups. The diagnostic efficacy of the LR-5 category for HCC was analyzed using the LR-M classification criteria along with time-related quantitative parameters. RESULTS: Of the 190 malignant liver nodules, 137 and 53 were HCCs and non-HCC malignancies, respectively. The median values of quantitative parameters RT (rise time), TTP (time to peak), mTTl (mean transit time local), and FT (fall time) in the non-HCC malignant group were lower than those in the HCC group, with p < 0.05. There was a statistically significant difference in WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve), WiWoAUC (wash-in and wash-out area under the curve), and WoR (wash-out rate) values between HCC and non-HCC malignant groups, with p < 0.05. Using LR-M washout time <60 s and FT ≤21.2 s as the new diagnostic standard, the LR-5 category showed a sensitivity of 83.9%, specificity of 96.2%, and positive predictive value of 98.3% for HCC diagnosis. CONCLUSION: DCE-US can facilitate the distinction of HCCs and non-HCC malignancies. Non-HCC malignancies present with earlier peak enhancement and more rapid and marked washout than HCC nodules. The combination of the LR-M classification criteria and FT ≤21.2 s can significantly improve the diagnostic sensitivity of the LR-5 category for HCC.

Hippocampal BAIAP2 prevents chronic mild stress-induced depression-like behaviors in mice.

Background: The pathogenesis of depression is closely related to changes in hippocampal synaptic plasticity; however, the underlying mechanism is still unclear. Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2), a postsynaptic scaffold protein in excitatory synapses important for synaptic plasticity, is highly expressed in the hippocampus and has been implicated in several psychiatric disorders. However, the role of BAIAP2 in depression remains poorly understood. Methods: In the present study, a mouse model of depression was established via exposure to chronic mild stress (CMS). An adeno-associated virus (AAV) vector expressing BAIAP2 was injected into the hippocampal brain region of mice and a BAIAP2 overexpression plasmid was transfected into HT22 cells to upregulate BAIAP2 expression. Depression- and anxiety-like behaviors and dendritic spine density were examined in mice using behavioral tests and Golgi staining, respectively. In vitro, hippocampal HT22 cells were treated with corticosterone (CORT) to simulate the stress state, and the effect of BAIAP2 on CORT-induced cell injury was explored. Reverse transcription-quantitative PCR and western blotting were employed to determine the expression levels of BAIAP2 and those of the synaptic plasticity-related proteins glutamate receptor ionotropic, AMPA 1 (GluA1), and synapsin 1 (SYN1). Results: Mice exposed to CMS exhibited depression- and anxiety-like behaviors accompanied by decreased levels of BAIAP2 in the hippocampus. In vitro, the overexpression of BAIAP2 increased the survival rate of CORT-treated HT22 cells and upregulated the expression of GluA1 and SYN1. Consistent with the in vitro data, the AAV-mediated overexpression of BAIAP2 in the hippocampus of mice significantly inhibited CMS-induced depression-like behavior, concomitant with increases in dendritic spine density and the expression of GluA1 and SYN1 in hippocampal regions. Conclusion: Our findings indicate that hippocampal BAIAP2 can prevent stress-induced depression-like behavior and may be a promising target for the treatment of depression or other stress-related diseases.

CircSYNDIG1 ameliorates stress-induced abnormal behaviors by suppressing miR-344-5p in mice.

Circular RNA (circRNA) plays an important role in diverse stress-related neuropsychiatric disorders like depression, anxiety and cognitive disorders. Here, using a circRNA microarray, we found that circSYNDIG1, an unreported circRNA, was significantly downregulated in the hippocampus of chronic unpredictable mild stress (CUMS) mice and further validated this finding in corticosterone (CORT) and lipopolysaccharide (LPS) mice by qRT-PCR, and it was negatively correlated with depressive- and anxiety-like behaviors of these three stressed mice. Furthermore, the interaction of miR-344-5p and circSYNDIG1 was confirmed by in situ hybridization (FISH) assay in hippocampus and dual luciferase reporter assay in 293 T cells. And miR-344-5p mimics could simulate the dendritic spine density reduction, depressive- and anxiety-like behaviors and memory impairment induced by CUMS. Overexpression of circSYNDIG1 in hippocampus significantly ameliorated these abnormal changes induced by CUMS or miR-344-5p. It indicated that circSYNDIG1 functions as an miR-344-5p sponge to inhibit miR-344-5p impact, resulting in the increase of dendritic spine density and the subsequent amelioration of the abnormal behaviors. Therefore, the downregulation of circSYNDIG1 in hippocampus participates in CUMS-induced depressive and anxiety-like behavior of mice though miR-344-5p. These findings represent the first evidence for the involvement of circSYNDIG1 and its coupling mechanism in depression and anxiety, suggesting that circSYNDIG1 and miR-344-5p might be new targets for the treatment of stress-related disorder.

Maternal exposure to triclosan during lactation alters social behaviors and the hippocampal ultrastructure in adult mouse offspring.

We recently reported that exposure to triclosan (TCS), a broad-spectrum antibacterial agent, affects social behaviors in adult mice, however, the long-lasting effects of TCS exposure during early life on social behaviors are still elusive. The present study aimed to investigate the long-lasting impacts of adding TCS to the maternal drinking water during lactation on the social behaviors of adult mouse offspring and to explore the potential mechanism underlying these effects. The behavioral results showed that TCS exposure decreased body weight, increased depression-like behavior and decreased social dominance in both male and female offspring, as well as increased anxiety-like behavior and bedding preference in female offspring. In addition, enzyme-linked immunosorbent assay (ELISA) indicated that TCS exposure increased peripheral proinflammatory cytokine levels, altered serum oxytocin (OT) levels, and downregulated the expression of postsynaptic density protein 95 (PSD-95) in the hippocampus. Morphological analysis by transmission electron microscopy (TEM) demonstrated that exposure to TCS induced morphological changes to synapses and neurons in the hippocampus of offspring. These findings suggested that TCS exposure during lactation contributed to abnormal social behaviors accompanied by increased peripheral inflammation and altered hippocampal neuroplasticity, which provides a deeper understanding of the effects of TCS exposure during early life on brain function and behavioral phenotypes.

Long-lasting effects of postweaning sleep deprivation on cognitive function and social behaviors in adult mice.

Sleep deprivation (SD) has adverse effects on physical and mental health. Recently increasing attention has been given to SD in the early-life stage. However, the effects and mechanisms of postweaning SD on cognitive function and social behaviors are still unclear. In this study, SD was conducted in mice from postnatal Day 21 (PND21) to PND42, 6 h a day. Meanwhile, changes in body weight, food and water intake were continuously monitored. Behavioral tests were carried out in adulthood of mice. The levels of serum corticosterone, the proinflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), and the anti-inflammatory cytokines interleukin-10 (IL-10), vasopressin (VP) and oxytocin (OT) were measured by ELISA. Golgi staining was used to calculate neural dendritic spine density in the dorsal hippocampus (dHPC) CA1 region and medial prefrontal cortex (mPFC). We found that postweaning SD increased the food intake and the weight of female mice. Behavioral results showed that postweaning SD caused cognitive impairment and lowered social dominance in adult male mice but not in female mice. ELISA results showed that SD increased the levels of serum corticosterone, VP and OT in male mice and serum OT in female mice. Golgi staining analysis showed that SD decreased neural dendritic spine density in the dHPC in male mice. These results suggest that postweaning SD has a long-term effect on social dominance and cognitive function in male mice, which may provide a new insight into the role of SD in regulating cognitive function and social behaviors.

Elevation of N-acetyltransferase 10 in hippocampal neurons mediates depression- and anxiety-like behaviors.

Major depressive disorder (MDD) is one of the most debilitating and severe mental diseases globally. Increasing evidence has shown that epigenetics is critical for understanding brain function and brain disorders, including MDD. N-acetyltransferase 10 (NAT10), acting on histones, mRNA and other substrates, has been reported to be involved in epigenetic events, including histone acetylation and mRNA modifications. NAT10 is highly expressed in the brain. However, the potential effects of NAT10 on MDD are still unknown. Here, we exploited chronic mild stress (CMS) to induce anxiety- and depression-like behaviors in mice and found that the expression of NAT10 in the mouse hippocampus was upregulated after CMS treatment. Inhibition of NAT10 by pharmacological methods produced anxiolytic- and antidepressant-like effects. Neuron-specific overexpression of NAT10 in the hippocampus resulted in anxiety- and depression-like behaviors, accompanied by higher SIRT1 protein levels, and lower dendritic spine densities. Overall, it was found that elevation of NAT10 in hippocampal neurons is involved in the occurrence of anxiety- and depression-like behaviors, suggesting that NAT10 could be a potential new target for developing anxiolytics and antidepressants.

Sex-dependent and long-lasting effects of bisphenol AF exposure on emotional behaviors in mice.

We recently reported that maternal exposure to bisphenol AF (BPAF), an environmental endocrine disruptor (EED), induced significant alterations in emotional behaviors in offspring mice during adolescence in a sex-dependent manner. However, the effects of adult BPAF exposure and the potential long-lasting effects of maternal exposure to BPAF on offspring mice are still unknown. The present study aimed to investigate the neurobehavioral effects of adult and maternal exposure to BPAF, intragastrically (0.4, 4 mg•kg-1, i.g.), by using a series of classic emotional behavioral tests, mainly referring to depression, anxiety, and memory. The results showed that adult BPAF exposure significantly attenuated anxiety- and depression-like behaviors in adult male mice, while increasing anxiety-like behaviors, promoting novel object recognition memory formation, and impairing contextual fear conditioning memory formation in adult female mice. Maternal exposure to BPAF induced anxiety-like effects and anti-depression-like effects in male offspring mice during adulthood, while maternal BPAF exposure increased anxiety- and depression-like behaviors in female offspring mice during adulthood. Our present findings indicate that BPAF exposure significantly affects emotional behaviors in adult/offspring mice in a sex-dependent manner and that female adult mice are more likely to have adverse consequences to BPAF exposure during adulthood, even during early life stages.

Sulfur dioxide derivatives attenuates consolidation of contextual fear memory in mice.

Post-traumatic stress disorder (PTSD) is characterized by an enhancement of traumatic memory. Intervention strategies based on the different stages of memory have been shown to be effective in the prevention and control of PTSD. The endogenous gaseous molecule, sulfur dioxide (SO2), has been reported to significantly exert neuromodulatory effects; however, its regulation of learning and memory remains unestablished. This study aimed to investigate the effects of exogenous SO2 derivatives administration on the formation, consolidation, reconsolidation, retention, and expression of contextual fear memory. Behavioral results showed that both intraperitoneal injection (50 mg/kg, ip) and hippocampal infusion (5 µg/side) of SO2 derivatives (a mixture of sodium sulfite and sodium bisulfite, Na2SO3/NaHSO3, 3:1 M/M) significantly impaired consolidation but had no effect on reconsolidation and retention of contextual fear memory. These findings suggest that the attenuating effects of SO2 on the consolidation of fear memory involves, at least partially, the region of the hippocampus. The findings of this study provide direct evidence for the development of new strategies for PTSD prevention and treatment involving the use of gaseous SO2.

Purification and antioxidant properties of triterpenic acids from blackened jujube (Ziziphus jujuba Mill.) by macroporous resins.

In order to investigate the purification process and antioxidant activity of triterpenic acids from blackened jujube, the macroporous resin was applied to purify the crude extract from blackened jujube. The adsorption and desorption characterizations of five different macroporous adsorption resins (AB-8, D-101, X-5, HPD-100, S-8) for triterpenic acids of blackened jujube were compared, the optimum purification resins were screened, and the purification parameters were optimized. The antioxidant activity of crude extracts and purified products from blackened jujube was analyzed. The results showed that D-101 resin possessed the best effect on the purification of blackened jujube triterpenic acids. The optimum purification parameters were as follows: sample concentration 25.5 µg/ml, 130 ml of the sample volume was with a flow rate of 2.0 ml/min, eluted with 95% ethanol, and speed flow was 1.0 ml/min. The purity of triterpenic acids was increased by 2.49 times after purification with a recovery rate of (78.58 ± 0.67)%. Furthermore, the IC50 values of hydroxyl radical scavenging capacity from triterpenic acids crude extract and purified substances were 0.900 and 0.850 mg/ml, respectively, and the IC50 values of superoxide anion radical were 0.745 and 0.594 mg/ml, respectively, indicating that the antioxidative capacity of the purified product was stronger than the crude extract. The purified triterpenic acids (PTA) groups at different doses had excellent protective effects on H2O2-induced damage HUVEC cells. Results have revealed that triterpenic acids of blackened jujube have good antioxidant function and utilization and development prospects.

[Rhizoma Panacis majori reduces toxicity of chemotherapy in S180-bearing mice].

OBJECTIVE: To observe the attenuating effect of Rhizoma Panacis majoris (RPM) on toxicity of 5-fluorouracil (5-FU) chemotherapy in S180-bearing mice. METHODS: S180 cells were subcutaneously injected to the right armpit of the mice to establish the S180-bearing model, and thirty mice were randomly divided into untreated group, 5-FU group and 5-FU combined with RPM group (5-FU plus RPM group). The general condition of S180-bearing mice was observed. The white blood cells, red blood cells, and reticulocytes in the peripheral blood were counted, and the ratio of reticulocytes was measured too. The life-span of the S180-bearing mice was recorded. RESULTS: The white blood cell count and the ratio of reticulocytes in 5-FU plus RPM group were higher than those in 5-FU group (P<0.01). The average lifespan of 5-FU plus RPM group was 32.5 days and that of the 5-FU group was 23.5 days; there was a significant difference in the lifespan between the two groups (P<0.01). CONCLUSION: RPM can reduce the toxic effect of 5-FU and prolong the lifespan of S180-bearing mice.

Screening of QHF formula for effective ingredients from Chinese herbs and its anti-hepatic cell cancer effect in combination with chemotherapy.

BACKGROUND: Recent studies have shown that effective ingredients of Chinese herbs are used more and more widely in the treatment or co-treatment of cancers, however, they are usually used separately and there has been limited research about joint application of Chinese herbs in multi-modal treatment. The aim of this study was to screen a QHF (Q: Qingrejiedu, H: Huoxuehuayu and F: Fuzhengguben) formula for effective ingredients from Chinese medicines and assess its anti-hepatic cell cancer (HCC) effect in combination with chemotherapy. METHODS: Six effective ingredients from Chinese medicine were selected based on the previous literature and used in the study. The QHF formula and the best ratio of ingredients were evaluated in H(22) mouse (KM) models with solid tumors and ascites tumors by uniform design and monitoring inhibition of tumor growth and survival. We then observed the anti-hepatic cell cancer (HCC) effect of QHF when combined with cisplatin (DDP) in H(22) mouse (Balb/c) models with solid tumors and ascites tumors. Evaluating of the therapeutic effect included the general condition of the mice, inhibition of tumor growth, survival, changes in body weight, thymus index, spleen index and WBC counts. RESULTS: The optimal QHF dose ratio for anti-hepatic cell cancer treatment was: 800 mg/kg Cinobufotalin, 14 mg/kg Ginsenosides Rg3, 5.5 mg/kg PNS and 100 mg/kg Lentinan. Treatment was more efficient in inhibiting the growth of transplanted tumors in H(22) mice when using the QHF formula (55.91%) than using Cinobufotalin (33.25%), Ginsenosides Rg3 (35.11%), PNS (27.12%) or Lentinan (4.97%) separately. QHF also prolonged the life of H(22) ascites hepatic cancer mice more efficiently (38.13%) than Cinobufotalin (25.00%), Ginsenosides Rg3 (27.27%), PNS (23.30%) or Lentinan (24.43%). QHF combined with DDP could reduce DDP-induced leucopenia, spleen and thymus atrophy and other toxic reactions. Combining QHF with DDP the tumor growth inhibition reached 82.54% with a 66.83% increase in survival. CONCLUSIONS: QHF is more efficient in anti-hepatic cell cancer treatment than the single drugs that constitute the formula. QHF combined with DDP can attenuate tumor growth and suppresses the DDP-induced toxic reactions.