ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside （Hyp） on lipopolysaccharide （LPS）-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L^-1 LPS or immersed in 1 g·L^-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25， 50， and 100 mg·L^-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate， malformation rate， body length， and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses， and macrophage migration was observed by fluorescence microscopy. Additionally， the mRNA levels of inflammation-related genes， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， chemokine C-C motif ligand 2 （CCL2）， chemokine C-X3-C motif receptor 1 （CX3CR1）， chemokine C-C motif receptor 2 （CCR2）， and genes associated with the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-kappa B （NF-κB） signaling pathway， were measured by Real-time quantitative polymerase chain reaction（Real-time PCR）. ResultsCompared with the pure water injection group， the model group exhibited increased mortality， malformation rates and yolk sac area ratio （P0.01）， reduced body length （P0.01）， increased total swimming distance and high-speed swimming duration （P0.01）， and up-regulated mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.01）. Hyp at low， medium and high doses， as well as aspirin， reduced the mortality and malformation rates （P0.05，P0.01）， increased the body length （P0.05，P0.01）， decreased the yolk sac area ratio （P0.01）， reduced the high-speed swimming duration （P0.01）， and down-regulated the mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.05，P0.01） compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish， thereby exerting the anti-inflammatory effect.

Objective To observe the value of conventional MRI and diffusion weighted imaging(DWI)for differentiating soft tissue lymphoma(STL)and soft tissue sarcoma(STS).Methods Conventional MRI and DWI data of 25 cases of STL(STL group)and 38 cases of STS(STS group)were retrospectively analyzed.MRI features being statistically different between groups were included in logistic regression analysis to screen the independent risk factors of STL and to evaluate the sensitivity,specificity and accuracy of their combination for predicting STL.Receiver operating characteristic curve was generated,the area under the curve(AUC)was calculated to assess the diagnostic efficacy of the mean apparent diffusion coefficient(ADCmean),the minimum apparent diffusion coefficient(ADCmin),the maximum apparent diffusion coefficient(ADCmax)values for distinguishing STL from STS.Results Slightly hyperintensity on T1WI,non-necrosis,involvement of multiple muscle groups and homogeneous enhancement were all independent risk factors of STL(all P＜0.05).The sensitivity,specificity and accuracy of their combination for predicting STL was 72.00％(18/25),89.47％(34/38)and 82.54％(52/63),respectively.ADCmean,ADCmin and ADCmax values of STL was(1.06±0.18)× 10-3,(0.77±0.14)×10-3 and(1.47±0.31)× 10-3mm2/s,respectively,all lower than those of STS([1.31±0.17]× 10-3,[1.02±0.23]× 10-3 and[1.64±0.16]× 10-3 mm2/s;t=-4.829--2.498,all P＜0.05).The AUC of ADCmean,ADCmin and ADCmax values and their combination for differential diagnosis of STL and STS was 0.845,0.844,0.683 and 0.877,respectively.Conclusion Conventional MRI features,including T1WI signal intensity,necrosis,involvement of multiple muscle groups and enhancement pattern,along with ADCmean and ADCmin values derived from DWI contributed to differentiating STL and STS.

Objective To investigate the effects of governor vessel pushing manipulation on behavioral outcomes in valproic acid(VPA)-induced autism spectrum disorder(ASD)rats and explore its underlying mechanisms using prefrontal RNA sequencing(RNA-Seq).Methods Nine Sprague-Dawley pregnant rats at gestational day 12.5 were divided into two groups,six received intraperitoneal VPA injection(600 mg/kg)for modeling,and three received saline.Male offspring at postnatal day 21 were evaluated using the three-chamber social test and open field test to validate the ASD model.VPA-induced male offspring were randomly assigned to the model group(n=5)or tuina group(n=5),while saline offspring formed the blank group(n=5).The blank group and model group received no intervention,while the tuina group underwent governor vessel pushing manipulation stimulation along the governor vessel using a custom device,twice a day for 14 days,totaling 28 times.Post-intervention,behavioral assessments included social index(SI)and social preference index(SPI)in the three-chamber test,total distance traveled and central zone time in the open field test,marble-burying test for stereotyped behaviors,and Nissl staining for prefrontal cortical neuron survival.RNA-Seq identified differentially expressed genes(DEGs)in the prefrontal cortex,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Real time fluorogenic quantitative PCR(RT-qPCR)validated DEGs,and Western blotting analyzed proteins in enriched pathways.Results Pre-intervention,both model and tuina groups showed reduced SI,SPI,total distance,and central zone time compared to the blank group(P<0.05),confirming successful modeling.Post-intervention,the model group exhibited lower SI,SPI,total distance,central zone time,increased marble-burying(P<0.05),and fewer Nissl bodies(P<0.01)versus the blank group.Compared to the model group,the tuina group displayed improved SI,SPI,total distance,central zone time(P<0.05),reduced marble-burying(P<0.05),and increased Nissl bodies(P<0.01).RNA-Seq revealed 213 prefrontal DEGs(181 upregulated,32 downregulated)in the tuina group.GO analysis highlighted cellular components,while KEGG identified 181 pathways,with 67 significantly enriched(P<0.05),notably the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway.RT-qPCR confirmed decreased collagen type Ⅰ alpha 2(Col1α2),transforming growth factor-α(TGF-α),epidermal growth factor receptor 3(ErbB3),and serum/glucocorticoid regulated kinase 2(Sgk2)(P<0.05),and increased hepatic growth factor(Hgf)(P<0.01)in the model group,reversed by governor vessel pushing manipulation.Western blotting showed reduced prefrontal NRG1,ErbB3,nNOS,PI3K,AKT,p-nNOS,p-PI3K,and p-AKT in the model group(P<0.05),which were upregulated by tuina.Conclusion Governor vessel pushing manipulation ameliorates social deficits,anxiety,stereotyped behaviors,and neuronal loss in ASD rats,potentially via activation of the PI3K/AKT signaling pathway.

Objective To observe the value of conventional MRI and diffusion weighted imaging(DWI)for differentiating soft tissue lymphoma(STL)and soft tissue sarcoma(STS).Methods Conventional MRI and DWI data of 25 cases of STL(STL group)and 38 cases of STS(STS group)were retrospectively analyzed.MRI features being statistically different between groups were included in logistic regression analysis to screen the independent risk factors of STL and to evaluate the sensitivity,specificity and accuracy of their combination for predicting STL.Receiver operating characteristic curve was generated,the area under the curve(AUC)was calculated to assess the diagnostic efficacy of the mean apparent diffusion coefficient(ADCmean),the minimum apparent diffusion coefficient(ADCmin),the maximum apparent diffusion coefficient(ADCmax)values for distinguishing STL from STS.Results Slightly hyperintensity on T1WI,non-necrosis,involvement of multiple muscle groups and homogeneous enhancement were all independent risk factors of STL(all P＜0.05).The sensitivity,specificity and accuracy of their combination for predicting STL was 72.00％(18/25),89.47％(34/38)and 82.54％(52/63),respectively.ADCmean,ADCmin and ADCmax values of STL was(1.06±0.18)× 10-3,(0.77±0.14)×10-3 and(1.47±0.31)× 10-3mm2/s,respectively,all lower than those of STS([1.31±0.17]× 10-3,[1.02±0.23]× 10-3 and[1.64±0.16]× 10-3 mm2/s;t=-4.829--2.498,all P＜0.05).The AUC of ADCmean,ADCmin and ADCmax values and their combination for differential diagnosis of STL and STS was 0.845,0.844,0.683 and 0.877,respectively.Conclusion Conventional MRI features,including T1WI signal intensity,necrosis,involvement of multiple muscle groups and enhancement pattern,along with ADCmean and ADCmin values derived from DWI contributed to differentiating STL and STS.

Objective To investigate the effects of governor vessel pushing manipulation on behavioral outcomes in valproic acid(VPA)-induced autism spectrum disorder(ASD)rats and explore its underlying mechanisms using prefrontal RNA sequencing(RNA-Seq).Methods Nine Sprague-Dawley pregnant rats at gestational day 12.5 were divided into two groups,six received intraperitoneal VPA injection(600 mg/kg)for modeling,and three received saline.Male offspring at postnatal day 21 were evaluated using the three-chamber social test and open field test to validate the ASD model.VPA-induced male offspring were randomly assigned to the model group(n=5)or tuina group(n=5),while saline offspring formed the blank group(n=5).The blank group and model group received no intervention,while the tuina group underwent governor vessel pushing manipulation stimulation along the governor vessel using a custom device,twice a day for 14 days,totaling 28 times.Post-intervention,behavioral assessments included social index(SI)and social preference index(SPI)in the three-chamber test,total distance traveled and central zone time in the open field test,marble-burying test for stereotyped behaviors,and Nissl staining for prefrontal cortical neuron survival.RNA-Seq identified differentially expressed genes(DEGs)in the prefrontal cortex,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Real time fluorogenic quantitative PCR(RT-qPCR)validated DEGs,and Western blotting analyzed proteins in enriched pathways.Results Pre-intervention,both model and tuina groups showed reduced SI,SPI,total distance,and central zone time compared to the blank group(P<0.05),confirming successful modeling.Post-intervention,the model group exhibited lower SI,SPI,total distance,central zone time,increased marble-burying(P<0.05),and fewer Nissl bodies(P<0.01)versus the blank group.Compared to the model group,the tuina group displayed improved SI,SPI,total distance,central zone time(P<0.05),reduced marble-burying(P<0.05),and increased Nissl bodies(P<0.01).RNA-Seq revealed 213 prefrontal DEGs(181 upregulated,32 downregulated)in the tuina group.GO analysis highlighted cellular components,while KEGG identified 181 pathways,with 67 significantly enriched(P<0.05),notably the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway.RT-qPCR confirmed decreased collagen type Ⅰ alpha 2(Col1α2),transforming growth factor-α(TGF-α),epidermal growth factor receptor 3(ErbB3),and serum/glucocorticoid regulated kinase 2(Sgk2)(P<0.05),and increased hepatic growth factor(Hgf)(P<0.01)in the model group,reversed by governor vessel pushing manipulation.Western blotting showed reduced prefrontal NRG1,ErbB3,nNOS,PI3K,AKT,p-nNOS,p-PI3K,and p-AKT in the model group(P<0.05),which were upregulated by tuina.Conclusion Governor vessel pushing manipulation ameliorates social deficits,anxiety,stereotyped behaviors,and neuronal loss in ASD rats,potentially via activation of the PI3K/AKT signaling pathway.

Objective:To evaluate the therapeutic effects of Yufu ointment for acute radiation-induced skin injury. Methods:We enrolled a total of 104 patients with malignant tumors who developed acute skin injury of grade 2-3 during or after the first course of radiotherapy from June 2019 to February 2023. The observation group ( n=53) and control group ( n=51) received external application of Yufu ointment and Shirun Shaoshang ointment, respectively. We recorded the changes in the grade of skin injury and associated symptoms (such as pain, itching, and burning sensation) and healing speed and time for the two groups. Results:A total of 102 patients completed the study, with 53 cases in the observation group and 49 cases in the control group. The incidence rate of moisture skin lesions in the observation group was significantly lower than that in the control group (62.26% vs. 83.67%, P<0.05). The healing speed of moisture skin ulcerations was significantly faster in the observation group than in the control group (1.67 cm 2/d vs. 0.55 cm 2/d, P<0.05). The observation group had a significantly shorter time to skin injury healing than the control group (10.40 d vs. 14.41 d, P<0.05), significantly different for skin injury of grade 2 (10.21 d vs. 17.57 d, P<0.05) but not for skin injury of grades 2.5 and 3 ( P>0.05). Regarding clinical symptoms, both groups experienced significant reductions in pain and burning sensation scores after treatment ( P<0.05); the grade of itching was significantly decreased for the observation group ( P<0.05), but had no significant change for the control group after treatment ( P>0.05). Conclusions:Yufu ointment can significantly alleviate secondary damage for patients with acute radiation-induced skin injury, by accelerating the healing process and relieving symptoms such as pain, itching, and burning sensation with good tolerability, which deserves further promotion.

Objective:To evaluate the value of 18F-FDG PET metabolic parameters in predicting histopathological grade of soft tissue sarcoma (STS). Methods:From December 2012 to December 2021, 51 patients (26 males, 25 females, age range: 32-84 years) who underwent 18F-FDG PET/CT imaging before treatment and confirmed STS pathologically in the First Affiliated Hospital of Dalian Medical University were retrospectively collected. 18F-FDG PET metabolic parameters SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG) and intertumoral FDG uptake heterogeneity (IFH) were measured. Kruskal-Wallis rank sum test was used to analyze the differences in metabolic parameters among different groups and Spearman rank correlation analysis was used to analyze the correlation of each metabolic parameter and histological grade. Logistic regression was used to screen and construct the prediction model for high-grade STS. ROC curve was plotted and Delong test was used to analyze the differences among AUCs. Results:The metabolic parameters SUV max, MTV, TLG and IFH were significantly different among French Federation of Cancer Centers Sarcoma Group (FNCLCC)Ⅰ( n=8), Ⅱ( n=10) and Ⅲ ( n=33) grade groups ( H values: 16.24, 10.52, 19.29 and 16.99, all P<0.05), and each metabolic parameter was positively correlated with histological grade ( rs values: 0.58, 0.45, 0.52, and 0.62, all P<0.05). Multivariate logistic regression analysis showed that SUV max(odds ratio ( OR)=1.27, 95% CI: 1.06-1.51, P=0.009) and IFH ( OR=6.83, 95% CI: 1.44-32.27, P=0.015) were independent risk indicators for high-grade STS. The prediction model constructed by combining SUV max and IFH had better diagnostic efficacy for differentiating high-grade STS with the AUC of 0.93, and the sensitivity of 93.9%(31/33) and the specificity of 16/18, respectively. The AUC of prediction model was significant different from SUV max, MTV, TLG and IFH (AUCs: 0.81, 0.78, 0.86 and 0.85; z values: 2.69, 2.53, 1.94 and 1.97, all P<0.05). Conclusions:The metabolic parameters SUV max, MTV, TLG and IFH are valuable predictors for histological grade of STS. The combination of SUV max and IFH may be a more meaningful method than using each of the above metabolic parameters alone.

Objective To investigate the correlations of serum eukaryotic translation promoter 2α (eIF2α) and activated transcription factor 4 (ATF4) levels with the degree of renal tissue injury and renal function in patients with diabetic nephropathy (DN). Methods A total of 102 patients with DN (DN group) and 102 patients with simple diabetes (control group) were selected. According to the severe degree of renal tissue damage, the patients with DN were divided into microalbuminuria group (MG group, 35 cases) and dominant albuminuria group (PG group, 41 cases) and renal dysfunction group (RIG group, 26 cases). Serum levels of eIF2α, ATF4, urea nitrogen (BUN), creatinine (Scr), cystatin C (CysC) and estimated glomerular filtration rate (eGFR) were measured. Pearson correlation analysis was used to explore the correlations of eIF2α and ATF4 with BUN, Scr, CysC and eGFR; multivariate Logistic regression analysis was used to explore the risk factors of DN; receiver operating characteristic (ROC) curve was used to analyze the value of eIF2α and ATF4 in diagnostic of DN. Results Serum levels of eIF2α, ATF4, BUN, Scr and CysC in the DN group were higher than those in control group, eGFR was lower than that in control group (P < 0.05). Serum eIF2α and ATF4levels in the RIG group were higher than those in PG and MG groups (P < 0.05). Serum eIF2α and ATF4 levels in DN patients were positively correlated with BUN, Scr and CysC, and negatively correlated with eGFR (P < 0.05). Long duration of diabetes, higher body mass index, high level of eIF2α and high level of ATF4 were risk factors for DN (P < 0.05). The area under the curve of eIF2α and ATF4 in diagnosis DN was 0.770 and 0.799, respectively, and the area under the curve of their combined diagnosis was 0.879, which was higher than that of single diagnosis (P < 0.05). Conclusion Serum levels of eIF2α and ATF4 are increased in patients with DN, which is related to the severity of renal injury and renal dysfunction in DN. The combination of eIF2α and ATF4 is of high value in the diagnosis of DN.

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

Objective:To compare the effect and safety of continuous veno-venous hemofiltration (CVVH)+double plasma molecular absorption (DPMA)+hemoperfusion (HP), CVVH+HP, and CVVH+plasma exchange (PE) in treatment of patient with severe wasp stings injury.Methods:Multicenter, historical cohort study and superiority test were used. From July 2020 to October 2022, patients with wasp sting injury and multiple organ damage admitted to the intensive care units (ICU) of five hospitals were consecutively screened and recruited into the CVVH+DPMA+HP group (intervention group). Propensity score matching was used to establish historical cohorts. Patients with severe wasp sting injury who hospitalized from January 2016 to June 2020 in each ICU were collected and matched 1∶1 with the intervention group, and divided into CVVH+HP group and CVVH+PE group according to their actual hemopurification protocols (historical control groups). The primary outcome was the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score on days 3 and 7 after initiation of treatment. Secondary outcomes included complications, length of ICU and hospital stays, and all-cause mortality. Multivariate Cox proportional risk regression was used to analyze the prognosis of patients.Results:After propensity score matching, 56 patients in intervention group and each of the two historical control groups were matched successfully. There were no significant differences in age, gender, comorbidities, biochemical test indices and critical illness scores among the groups. After treatment, APACHE Ⅱ score markedly declined in all groups, and the decrease was faster in the intervention group; treatment with DPMA [hazard ratio ( HR) = 1.04, 95% confidence interval (95% CI) was 1.02-1.08, P = 0.00], the decreased levels of body temperature ( HR = 1.02, 95% CI was 1.00-1.03, P = 0.02), serum creatine kinase (CK; HR = 0.98, 95% CI was 0.96-1.00, P = 0.05) and myoglobin (MYO; HR = 2.88, 95% CI was 1.24-6.69, P = 0.01) were independent risk factors for APACHE Ⅱ score decline to the target value (15 scores). There were no significant differences in the incidence of bleeding complications, filter or perfusion thrombosis, blood pressure reduction, catheter-related infection and anaphylaxis among the groups. Conclusion:CVVH+DPMA+HP regimen can significantly reduce the APACHE Ⅱ score of patients with severe wasp sting injury, and the efficacy is superior to CVVH+HP and CVVH+PE regimens, with safety.