Objective To explore the inhibitory effect of guggulsterone(GS)on diethylnitrosamine(DEN)-induced liver fibrosis in rats and its mechanism.Methods DEN-induced liver fibrosis model was established in SD rats.The successful model rats were randomly divided into model group(n=6),GS group(n=6,50 mg/kg,intraperitoneal injection for 4 weeks),GS+SRI group(n=6,50 mg/kg+30 mg/kg,intraperitoneal injection for 4 weeks),and control group(n=6,without DEN-induced).Rats in the control group and the model group were injected with the same amount of normal saline.The pathological changes of the liver were detected by HE staining.Serum liver function indexes including alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB)and alkaline phosphatase(ALP)were detected by automatic biochemical analyzer.The serum levels of pro-collagen Ⅲ(PC-Ⅲ),collagen Ⅳ(Ⅳ-C),hyaluronidase(HA),laminin(LN),malondialdehyde(MDA),reduced glutathione(GSH),superoxide dismutase(SOD),and catalase(CAT)were detected by ELISA assay.The mRNA and protein expression of TGF-β1,Smad2,and p-Smad3/Smad3 were detected by Real-time PCR and Western blotting.Results Compared with the control group,the model group showed typical pathological changes of liver fibrosis;the serum ALB,GSH,SOD and CAT levels were significantly decreased(P＜0.05);the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA,LN and the mRNA expression of TGF-β1,Smad3 and protein expression of TGF-β1,p-Smad3 in liver tissues were significantly increased(P＜0.05).Compared with the model group,the pathological changes of liver fibrosis in the GS group were alleviated,and the serum levels of ALB,GSH,SOD and CAT were significantly increased(P＜0.05),the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN,the mRNA expression of TGF-β1 and Smad3,and protein expression of TGF-β1 and p-Smad3 in liver tissues were significantly decreased(P＜0.05).In addition,after the administration of SRI,TGF-β1 signaling pathway activator,compared with the GS group,the GS+SRI group showed significantly decreased serum ALB,GSH,SOD and CAT levels(P＜0.05),but significantly increased serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN as well as the mRNA expression of TGF-β1 and Smad3 and protein expression of TGF-β1 and p-Smad3 in liver tissues(P＜0.05).Therefore,SRI attenuated the anti-fibrotic effect of GS on rats with liver fibrosis.Conclusion GS has certain inhibitory effect on DEN-induced liver fibrosis in rats,and its mechanism may be related to the reduction of oxidative stress level and the inhibition of the activation of TGF-β1/Smad3 signaling pathway.

Purpose To investigate the value of intratumoral and peritumoral radiomics features based on multi-parametric MRI for preoperative prediction of lymphovascular invasion(LVI)in clinical lymph node-negative(cN0)breast cancer.Materials and Methods This retrospective study included 280 patients with pathologically confirmed breast cancer who underwent preoperative MRI at Henan Provincial People's Hospital from January 2017 to May 2021.Patients were randomly divided into a training cohort and a testing cohort.After Z-score normalization,feature selection was performed using Select K Best and least absolute shrinkage and selection operator regression.Random forest algorithms were used to construct intratumoral,peritumoral,and combined intratumoral-peritumoral radiomics models for LVI prediction.Model performance and clinical utility were evaluated using the area under the receiver operating characteristic curve(AUC),calibration curves and decision curve analysis.Results High Ki-67 expression(≥20%),axillary lymph node metastasis and positive diffusion weighted imaging(DWI)margin sign were more common in the LVI-positive group(χ2=5.959,18.316,20.554,all P<0.05).In the testing cohort,the AUC values of the dynamic contrast-enhanced(DCE)-Intra and DCE-Com models for predicting LVI status were higher than those of the DWI sequence,whereas the AUC value of the DWI-Peri model was higher than that of the DCE sequence.The DWI-DCE-Com model achieved AUCs of 0.836 and 0.818 in the training and testing cohorts,respectively,which surpassed the predictive performance of single-sequence intratumoral-peritumoral radiomics models(DWI-Com,DCE-Com).Decision curve analysis showed that the DWI-DCE-Com model provided greater net clinical benefit across a reasonable range of threshold probabilities.Conclusion Radiomics models based on multiparametric MRI features from intratumoral and peritumoral regions can effectively predict LVI status in cN0 breast cancer,offering valuable support for preoperative individualized treatment decision-making.

Objective To explore the inhibitory effect of guggulsterone(GS)on diethylnitrosamine(DEN)-induced liver fibrosis in rats and its mechanism.Methods DEN-induced liver fibrosis model was established in SD rats.The successful model rats were randomly divided into model group(n=6),GS group(n=6,50 mg/kg,intraperitoneal injection for 4 weeks),GS+SRI group(n=6,50 mg/kg+30 mg/kg,intraperitoneal injection for 4 weeks),and control group(n=6,without DEN-induced).Rats in the control group and the model group were injected with the same amount of normal saline.The pathological changes of the liver were detected by HE staining.Serum liver function indexes including alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB)and alkaline phosphatase(ALP)were detected by automatic biochemical analyzer.The serum levels of pro-collagen Ⅲ(PC-Ⅲ),collagen Ⅳ(Ⅳ-C),hyaluronidase(HA),laminin(LN),malondialdehyde(MDA),reduced glutathione(GSH),superoxide dismutase(SOD),and catalase(CAT)were detected by ELISA assay.The mRNA and protein expression of TGF-β1,Smad2,and p-Smad3/Smad3 were detected by Real-time PCR and Western blotting.Results Compared with the control group,the model group showed typical pathological changes of liver fibrosis;the serum ALB,GSH,SOD and CAT levels were significantly decreased(P＜0.05);the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA,LN and the mRNA expression of TGF-β1,Smad3 and protein expression of TGF-β1,p-Smad3 in liver tissues were significantly increased(P＜0.05).Compared with the model group,the pathological changes of liver fibrosis in the GS group were alleviated,and the serum levels of ALB,GSH,SOD and CAT were significantly increased(P＜0.05),the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN,the mRNA expression of TGF-β1 and Smad3,and protein expression of TGF-β1 and p-Smad3 in liver tissues were significantly decreased(P＜0.05).In addition,after the administration of SRI,TGF-β1 signaling pathway activator,compared with the GS group,the GS+SRI group showed significantly decreased serum ALB,GSH,SOD and CAT levels(P＜0.05),but significantly increased serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN as well as the mRNA expression of TGF-β1 and Smad3 and protein expression of TGF-β1 and p-Smad3 in liver tissues(P＜0.05).Therefore,SRI attenuated the anti-fibrotic effect of GS on rats with liver fibrosis.Conclusion GS has certain inhibitory effect on DEN-induced liver fibrosis in rats,and its mechanism may be related to the reduction of oxidative stress level and the inhibition of the activation of TGF-β1/Smad3 signaling pathway.

Purpose To investigate the value of intratumoral and peritumoral radiomics features based on multi-parametric MRI for preoperative prediction of lymphovascular invasion(LVI)in clinical lymph node-negative(cN0)breast cancer.Materials and Methods This retrospective study included 280 patients with pathologically confirmed breast cancer who underwent preoperative MRI at Henan Provincial People's Hospital from January 2017 to May 2021.Patients were randomly divided into a training cohort and a testing cohort.After Z-score normalization,feature selection was performed using Select K Best and least absolute shrinkage and selection operator regression.Random forest algorithms were used to construct intratumoral,peritumoral,and combined intratumoral-peritumoral radiomics models for LVI prediction.Model performance and clinical utility were evaluated using the area under the receiver operating characteristic curve(AUC),calibration curves and decision curve analysis.Results High Ki-67 expression(≥20%),axillary lymph node metastasis and positive diffusion weighted imaging(DWI)margin sign were more common in the LVI-positive group(χ2=5.959,18.316,20.554,all P<0.05).In the testing cohort,the AUC values of the dynamic contrast-enhanced(DCE)-Intra and DCE-Com models for predicting LVI status were higher than those of the DWI sequence,whereas the AUC value of the DWI-Peri model was higher than that of the DCE sequence.The DWI-DCE-Com model achieved AUCs of 0.836 and 0.818 in the training and testing cohorts,respectively,which surpassed the predictive performance of single-sequence intratumoral-peritumoral radiomics models(DWI-Com,DCE-Com).Decision curve analysis showed that the DWI-DCE-Com model provided greater net clinical benefit across a reasonable range of threshold probabilities.Conclusion Radiomics models based on multiparametric MRI features from intratumoral and peritumoral regions can effectively predict LVI status in cN0 breast cancer,offering valuable support for preoperative individualized treatment decision-making.

Lithium batteries are widely used in energy storage, power, and other fields due to their advantages such as high performance and low cost. With the rapid development of the lithium battery industry, its production is constantly growing. However, the identification of occupational hazards and assessment of their health risks in lithium battery industry has rarely been reported. The composition of lithium batteries is complex and involves large numbers of compounds. Besides the traditional occupational hazards, workers may be exposed to many emerging chemicals throughout the production of raw materials, assembly and disassembly of lithium batteries. Therefore, this paper introduced the process chain of lithium battery production, analyzed the underlying occupational hazards in the industry, reviewed the health impacts of typical occupational hazards, and proposed the future research needs according to the current status of research on occupational exposure and health hazards in the lithium battery industry.

Objective To observe the value of intratumoral and peritumoral radiomics based on diffusion weighted imaging(DWI)for predicting histological grade of breast cancer.Methods Preoperative DWI data of 700 patients with single breast cancer diagnosed by pathology were retrospectively analyzed.The patients were divided into training set(n= 560,including 381 of grade Ⅰ+Ⅱ and 179 of grade Ⅲ)and test set(n=140,including 95 of grade Ⅰ+Ⅱ and 45 of grade Ⅲ)at the ratio of 8∶2.Intratumoral ROI(ROIintra)was manually delineated on DWI,which was automatically expanded by 3 mm and 5 mm to decline peritumoral ROI(ROIperi,including ROI3 mm and ROI5 mm),then intratumoral-peritumoral ROI(ROIintra+3 mm,ROIintra+5 mm)were obtained.The optimal radiomics features were extracted and screened,and the radiomics model(RM)for predicting the histological grade of breast cancer were constructed.Receiver operating characteristic curves were drawn,and the areas under the curve(AUC)were calculated to evaluate the predictive efficacy of each model.Calibration curve method was used to evaluate the calibration degree,while decision curve analysis(DCA)was performed to explore the clinical practicability of each model.Results AUC of RMintra,RM+3 mm,RM+5mm,RMintra+3 mm and RMintra+5 mm was 0.750,0.724,0.749,0.833 and 0.807 in training set,while was 0.723,0.718,0.736,0.759 and 0.782 in test set,respectively.In training set,significant differences of AUC was found(all P＜0.01),while in test set,no significant difference of AUC was found among models(all P＞0.05).The calibrations of models were all high.DCA showed that taken 0.02-0.88 as the threshold,the clinical net benefit of RMintra+per were greater in training set,while taken 0.40-0.72 as the threshold,the clinical net benefit of RMintra+per was greater in test set.Conclusion Both DWI intratumoral and peritumoral radiomics could effectively predict histological grade of breast cancer.Combination of intratumoral and peritumoral radiomics was more effective.

A purified polysaccharide with a galactose backbone(SPR-1,Mw 3,622 Da)was isolated from processed Polygonati Rhizoma with black beans(PRWB)and characterized its chemical properties.The backbone of SPR-1 consisted of[(4)-β-D-Galp-(1]9→ 4,6)-β-D-Galp-(1 → 4)-α-D-GalpA-(1 → 4)-α-D-GalpA-(1 →4)-α-D-Glcp-(1 → 4,6)-α-D-Glcp-(1 → 4)-α/β-D-Glcp,with a branch chain of R1:β-D-Galp-(1 → 3)-β-D-Galp-(1 → connected to the →4,6)-β-D-Galp-(1 → via O-6,and a branch chain of R2:α-D-Glcp-(1 →6)-α-D-Glcp-(1 → connected to the →4,6)-α-D-Glcp-(1 → via O-6.Immunomodulatory assays showed that the SPR-1 significantly activated macrophages,and increased secretion of NO and cytokines(i.e.,IL-1β and TNF-α),as well as promoted the phagocytic activities of cells.Furthermore,isothermal titration calorimetry(ITC)analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant(KD)of 18.8 μM.It was suggested that SPR-1 activated the immune response through Toll-like receptor 4(TLR4)signaling and downstream responses.Our research demon-strated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response,and also provided an easily accessible way that can be used for PR deep processing.

Objective:To explore regulatory effects of short-chain fatty acids (SCFA) on hypoxia-induced oxidative stress and activation of pancreatic stellate cells (PSCs) .Methods:PSCs were cultured in normoxia or hypoxia conditions to establish normoxia or hypoxia group. PSCs were pre-treated with SCFA working solution (10 mmol/L sodium acetate, 0.5 mmol/L sodium propionate and 0.5 mmol/L sodium butyrate), and then cultured in hypoxia conditions to establish the hypoxia-SCFA group. PSCs pre-treated by normal saline was set as the hypoxia-control group. The relative growth viability of the cells was detected by the CCK-8 assay. Relative levels of reactive oxygen species (ROS) were detected by DCFH-DA fluorescence probe method. The mitochondrial membrane potential was detected by JC-1 fluorescence probe. Protein expression of cyclin-associated marker cyclin A and cyclin D, hypoxic marker HIF1α, activation marker α-SMA, and antioxidant marker NRF2 and HO-1 was detected by western blotting.Results:The relative viability of PSCs in hypoxia group was significantly higher than that in normoxia group at 48 h (1.23±0.05 vs 0.99±0.04), but the relative viability of hypoxia-SCFA group was significantly lower than that of the hypoxic-control group at both 36 h and 48 h (0.69±0.01 vs 0.86±0.03, 0.86±0.02 vs 1.25±0.05). The relative level of ROS was significantly higher in hypoxia group than normoxia group (1.74±0.11 vs 1.00±0.10). The relative level of ROS was significantly lower in the hypoxia-SCFA group than the hypoxia-control group (1.39±0.14 vs 1.66±0.11). The fluorescence signals of JC-1 polymer in hypoxia group were significantly higher than those in normoxia group (1.36±0.05 vs 1.00±0.11), whereas the fluorescence signals of JC-1 polymer were significantly lower in hypoxia-SCFA group than in hypoxia-control group (1.11±0.03 vs 1.32±0.06). The expression of cyclin A, cyclin D, HIF1α, α-SMA, NRF2, and HO-1 was significantly higher in hypoxia group than those in normoxia group (1.19±0.01 vs 0.63±0.02, 0.93±0.02 vs 0.83±0.03, 1.18±0.07 vs 0.41±0.02, 1.19±0.14 vs 0.66±0.04, 1.22±0.11 vs 0.61±0.04, 1.28±0.12 vs 0.68±0.02), but the expression of cyclin A, cyclin D, α-SMA, NRF2, and HO-1 in Hypoxia-SCFA group was significantly lower than those in hypoxia-control group (0.79±0.04 vs 1.15±0.03, 0.88±0.01 vs 0.95±0.03, 0.87±0.01 vs 1.18±0.05, 0.84±0.01 vs 1.22±0.04, and 0.92±0.02 vs 1.27±0.06). All these differences were statistically significant (all P values <0.05) . Conclusions:SCFA significantly improves the oxidative stress state of PSCs under hypoxic conditions, maintains the stability of mitochondrial membrane potential, and inhibites hypoxia-induced activation of PSCs.

Objective:To explore the neuroprotective effects and mechanisms of memantine on sepsis-associated encephalopathy (SAE) model mice.Methods:Totally 90 male C57BL/6J mice aged 8-12 weeks were randomly divided into 3 groups (with 30 mice in each group) : sham group, model group and memantine group. The SAE mouse model was established by cecum ligation and puncture while mouse in sham group received open and closed abdomen only. The mice in the memantine group were irrigation with memantine (15 mg · kg -1· d -1) 3 hours before surgery and 7 consecutive days after modeling. The mice in the model group and sham group were irrigation with an equal volume of 0.9% sodium chloride solution. The 7-day survival rate was observed, neurobehavioral and cognitive function scores of each group of mice after modeling were assessed.Blood-brain barrier permeability was measured by detecting the content of Evans blue. Immunofluorescence staining was used to detect the expression of astrocytes. Enzyme linked immunosorbent assay was conducted to detect cellular inflammatory factors and the glutamic acid content detection kit was used to detect the expression of glutamic acid. All data were analyzed by Graphpad Prism 8.3.0 software, survival rate was analyzed using Kaplan-Meier survival curve.Multigroup comparisons were conducted by one-way ANOVA or Kruskal-Wallis test. Results:(1) There was a statistically significant difference in the 7-day survival rate among the three groups of mice after modeling ( F=24.11, P<0.01), and the 7-day survival rate of the memantine group was higher than that of the model group (57% (17/30), 27% (8/30), P<0.01). (2)The behavioral results showed that after 7 days of modeling, there were statistically significant differences in the total distance of the open field test, central area stay time, four corner area stay time, neurobehavioral scores, pole climbing test, and preference index for new object recognition test among the three groups of mice ( F/ χ2=17.67, 17.30, 9.39, 14.06, 10.36, 14.81, all P<0.05).The neurobehavioral score, pole climbing test score, preference index for new object recognition test, total distance of open field test, and central area stay time of the model group were all lower than those of the sham group (all P<0.05), while four corner area stay time of the model group was higher than that of the sham group ( P<0.05).The total distance of open field test (1 564.07(1 363.24, 1 988.19) cm, 913.91 (574.32, 1 096.23) cm), central area stay time (5.21 (4.91, 8.76) s, 1.09 (0.25, 1.64) s), neurobehavioral scores (9.75±0.50, 8.25±0.50), pole climbing test scores (5.67±0.52, 4.56±0.53), and preference index for new object recognition test (56.50±10.59, 26.84±2.91) of the memantine group were all higher than those of the model group (all P<0.05). The four corner area stay time was lower than that of the model group ((480.30±50.64) s, (529.80±36.20) s, P<0.05).(3)The comparison of molecular indicators showed that there were statistically significant differences in the content of Evans blue in the brain, the number of astrocytes in the hippocampus and cerebral cortex, pro-inflammatory cytokines (TNF-α、IL-1β、IL-6), anti-inflammatory cytokines (IL-10), and glutamic acid among the three groups of mice ( F/ χ2=8.84, 6.43, 28.46, 23.63, 12.23, 16.04, 69.22, 6.65, all P<0.05).The content of Evans blue, the number of astrocytes in the hippocampus and cerebral cortex, the expression of TNF-α、IL-1β、IL-6, and glutamate in the model group were all lower than those in the sham group(all P<0.05). The levels of IL-10 in the model group was lower than that in the sham group ( P<0.05).The content of Evans blue ((5.67±1.38)μg/g, (11.08±2.79)μg/g), the number of astrocytes in the hippocampus (16.50 (13.75, 22.25)/μm 2), 80.00 (73.50, 83.50)/μm 2) and the cerebral cortex (40.00 (29.00, 48.00)/μm 2, 81.50 (72.25, 89.00)/μm 2) in the memantine group were lower than those in the model group (all P<0.05).The pro-inflammatory factor TNF-α, IL-1β, IL-6 and glutamic acid expression in the memantine group were lower than those in the model group (all P<0.05), and the anti-inflammatory cytokine IL-10 was higher than that in the model group ( P<0.05). Conclusions:Memantine can improve the neurobehaviors and cognitive functions of SAE mice through improving the integrity of the damaged blood-brain barrier, alleviating inflammation in the brain, as well as reducing glutamate levels in the brain.