OBJECTIVE To explore the effect and mechanism of Zexie tang （ZXT） on reducing lipid accumulation through network pharmacology， and compare the difference of traditional decoction versus formula granules. METHODS The active components and targets of ZXT were identified using TCMSP and SwissTargetPrediction databases. GeneCards， OMIM， DisGeNET and TTD databases were used to analyze the related targets of non-alcoholic fatty liver disease （NAFLD）； protein-protein interaction network model was constructed by String database；“ ZXT-NAFLD target-pathway” network diagram was constructed by using CytoScape software； target enrichment analysis was performed by using Metascape platform. Fat accumulation model of human hepatocellular carcinoma HepG2 cells was established to observe the effects of traditional decoction and formula granules of ZXT on lipid accumulation of cells. RESULTS Alisol B， alisol C， 1-monolinolein and alisol B monoacetate were the key active components of ZXT in the treatment of NAFLD. The core targets included MDM2， MAPK1， PIK3CB， PRKCQ and MAPK14， etc. The core signaling pathways included endocrine resistance， insulin resistance and Th17 cell differentiation. Compared with model group， except for the Zexie formula granules group and Baizhu formula granules group， the absorbance values in all other administration groups were significantly decreased （P＜0.01）； the absorbance value of Baizhu traditional decoction group was significantly higher than that of ZXT traditional decoction group （P＜0.01）； the absorbance values of Zexie formula granule group and Baizhu formula granule group were significantly higher than that of ZXT formula granule group （P＜0.01）； the absorbance value of Zexie formula granule group was significantly higher than that of Zexie traditional decoction group （P＜0.01）； the absorbance value of Baizhu formula granule group was significantly higher than that of Baizhu traditional decoction group （P＜0.01）. CONCLUSIONS ZXT reduces lipid accumulation of human hepatocellular carcinoma cells through multiple components， multiple target and multiple pathways， and its traditional decoction and formula granules exhibit slightly different lipid-lowering effects.

Cuproptosis, a recently identified form of regulated cell death triggered by excess intracellular copper, has emerged as a promising cytotoxic strategy for cancer therapy. However, the therapeutic efficacy of copper ionophores such as elesclomol (ES) is often hindered by cellular copper homeostasis mechanisms that limit copper influx and cuproptosis induction. To address this challenge, we developed a nanoagent utilizing outer membrane vesicle (OMV) derived from Akkermansia muciniphila (Akk) for co-delivery of antioxidant 1 copper chaperone (Atox1)-targeting siRNA and ES (siAtox1/ES@OMV) to tumors. In vitro, we demonstrated that Atox1 knockdown via siRNA significantly disrupted copper export mechanisms, resulting in elevated intracellular copper levels. Simultaneously, ES facilitated efficient copper influx and mitochondrial transport, leading to Fe-S cluster depletion, increased proteotoxic stress, and robust cuproptosis. In vivo, siAtox1/ES@OMV achieved targeted tumor delivery and induced pronounced cuproptosis. Furthermore, leveraging the immunomodulatory properties of OMVs, siAtox1/ES@OMV promoted T-cell infiltration and the activation of tumor-reactive cytotoxic T cells, enhancing tumor immune responses. The combination of siAtox1/ES-induced cuproptosis and immunogenic cell death synergistically suppressed tumor growth in both subcutaneous breast cancer and orthotopic rectal cancer mouse models. This study highlights the potential of integrating copper homeostasis disruption with a copper ionophore using an immunomodulatory OMV-based vector, offering a promising combinatorial strategy for cancer therapy.

OBJECTIVES: To explore the therapeutic mechanism of puerarin for alleviating synovitis in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of puerarin at low, moderate and high doses (10, 30, and 100 mg/kg, respectively) for 3 weeks, with tripterygium glycosides (GTW, 10 mg/kg) as the positive control, on swelling in the hind limb joints regions evaluated by arthritis index scoring. Mass fraction of the liver of the rats was calculated, and pathologies in joint synovial membrane were observed with HE staining. The expressions of transforming growth factor β‑activated kinase-1 (TAK1), Toll-like receptor 4 (TLR4), and nuclear factor kappa-Bp65 (NF‑κB p65) at the mRNA and protein levels in the synovial tissues were detected using Real-time PCR and Western blotting. RESULTS: Compared with those in the model group, the rats in GTW group and high-dose puerarin group showed significantly reduced mass fraction of the liver. Treatment with GTW and puerarin at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, and improved synovitis in CIA rats (P<0.05), and the effects of puerarin showed an obvious dose dependence. Both GTW and puerarin treatments significantly lowered TAK1, TLR4, and NF‑κB p65 mRNA and protein expressions in the synovium of CIA rats. CONCLUSIONS Puerarin alleviates synovium damages in CIA rats possibly by suppressing the TLR4/NF‑κB signaling pathway via downregulating TAK1 expression.
Animals ; Toll-Like Receptor 4/metabolism* ; Rats, Sprague-Dawley ; Rats ; MAP Kinase Kinase Kinases/metabolism* ; Signal Transduction/drug effects* ; Arthritis, Rheumatoid/drug therapy* ; NF-kappa B/metabolism* ; Isoflavones/therapeutic use* ; Male ; Arthritis, Experimental/drug therapy* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/metabolism*

Objective:To evaluate the diagnostic performance of radiomics model based on contrast-enhanced ultrasound(CEUS) in predicting pathological complete response(pCR) after neoadjuvant chemoradiotherapy(nCRT) in patients with locally advanced rectal cancer(LARC).Methods:One hundred and six patients with LARC who underwent total mesorectal excision after nCRT between April 2018 and April 2023 in the First Affiliated Hospital of Guangxi Medical University were retrospectively included, the patients were randomly divided into a training set of 63(14 pCR patients) and a validation set of 43(12 pCR patients) in a 6∶4 ratios. Radiomics features were extracted from the tumors′ region of interest of CEUS images based on PyRadiomics. Intra-class correlation coefficient(ICC), Mann-Whitney U test, and least absolute shrinkage and selection operator(LASSO) algorithms were used to reduce features dimension. Finally, 7 radiomics features relevanted to pCR were selected to construct an ultrasomics model using elastic network regression, based on the R language. A combined model was constructed by jointing clinical feature. The performance of the models was assessed with the area under the ROC curve(AUC). Results:The AUC of the ultrasomics model and the combined model was 0.695(95% CI=0.532-0.859) and 0.726(95% CI=0.584-0.868) respectively in the training set. The AUC of the ultrasomics model and the combined model was 0.763(95% CI=0.625-0.902) and 0.790(95% CI=0.653-0.928) respectively in the validation set. Both univariate and multivariate Logistic regression analyses showed that CA199( P<0.05) and ultrasomics score( P<0.001) could be an independent predictor of pCR after nCRT in patients with LARC. Conclusions:The CEUS-based radiomics scores has certain predictive value for whether LARC patients achieve pCR after nCRT, and may provide a non-invasive imaging biomarker for predicting LARC patients achieve pCR after nCRT.

ObjectiveTo explore the efficacy and predictive indicators of stellate ganglion block （SGB） as an adjunctive intervention for chronic subjective tinnitus and accumulate experience for the application of SGB in the clinical treatment of tinnitus. MethodsA retrospective review was conducted on the data of chronic subjective tinnitus patients who received SGB intervention， with unsatisfactory outcomes otherwise. Pure tone audiometry （PTA）， tinnitus loudness evaluation and Pittsburgh sleep quality index （PSQI） were used. The tinnitus handicap inventory （THI） scores were compared before and after SGB intervention. Correlation analysis and linear regression equations were employed to identify the potential indicators predicting the effectiveness of SGB intervention. Statistical analysis was performed by SPSS 24.0 software. ResultsBy April 2023， a total of 107 patients with chronic subjective tinnitus had undergone SGB intervention， including 67 male and 40 female， with a mean age of （45.32±11.40） years old and an average tinnitus history of （20.32±24.64） months ［16 （12~20）］. Only 7 patients （6.54%） quitted the intervention for personal reasons， which demonstrated good compliance with the intervention. No patients experienced adverse reactions such as infection at the injection site， hematoma， nerve injury， local anesthetic intoxication and so on， which revealed good safety. After SGB intervention， THI scores decreased to below 36 points in 77 patients and decrease by 10 points or more in 12 of the remaining patients， with a total effective rate of 89%. A paired sample t-test showed a significant difference in THI scores before and after SGB intervention （t=15.575， P<0.001）， indicating good improvement. Pearson correlation analysis suggested that pre-intervention THI scores and subjective tinnitus loudness were significantly positively correlated with the improvement level of THI scores （P<0.05）. Further stepwise linear regression analysis found that "pre-intervention THI scores" had statistical significance （P<0.001）， with a regression coefficient of 0.308， predicting a 17.4% improvement level in THI scores. ConclusionsDue to its good and safe short-term effects， SGB intervention can be used as a supplementary option for chronic subjective tinnitus when other interventions are not ideal， especially for patients with higher THI scores. However， further research is needed to clarify the long-term efficacy and underlying mechanisms， in order to establish a more solid theoretical basis for SGB intervention in the treatment of subjective tinnitus.

Objective To analyze the correlation between inflammation,nutritional indicators and hy-poproteinemia in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Meth-ods The clinical data of patients with AECOPD admitted to the Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Xiamen University from January 2020 to September 2022 were ret-rospectively analyzed,and the patients were divided into the hypoproteinemia group(n=73)and the non-hy-poproteinemia group(n=141)according to whether the serum albumin(ALB)was lower than 35 g/L.The clinical data,inflammatory indicators and nutritional indicators of the two groups were compared,Spearman correlation analysis was performed,and binary logistic regression analysis was performed to analyze the influ-encing factors of patients with AECOPD complicated with hypoproteinemia.Results There were statistically significant differences in age,length of hospital stay,and body weight between the two groups(P＜0.05).There were no significant differences in gender,number of hospitalizations in the past 1 year,height,diabetes,hypertension and proportion of coronary heart disease(P＞0.05).Compared with the non-hypoproteinemia group,the hypoproteinemia group had longer hospital stays and higher levels of C-reactive protein,neutrophil/albumin ratio(NAR),neutrophil to lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),and systemic immunoinflammatory index(SII).The prognostic nutritional index(PNI),body mass index(BMI),hemoglo-bin and total protein levels were lower,and the difference was statistically significant(P＜0.05).Body weight,BMI,hemoglobin,total protein,PNI and AECOPD patients with hypoproteinemia were negatively cor-related(P＜0.05),while age,length of hospital stay,C-reactive protein,NAR,NLR,PLR,SII and AECOPD patients with hypoproteinemia were positively correlated(P＜0.05).Binary logistic regression analysis showed that PNI,SII and NLR were the influencing factors of hypoproteinemia in AECOPD patients.Conclusion In clinical practice,attention should be paid to and timely correction of hypoproteinemia in pa-tients with AECOPD,improvement of inflammatory indicators and nutritional status of patients,and preven-tion of acute exacerbation.

Objective:To assess the effectiveness and safety of beat chemotherapy in treating non-small cell lung cancer, and to investigate its anti-tumor molecular mechanism.Methods:In this study, we developed a subcutaneous tumor model of lung cancer in mice.The mice were subsequently divided into two groups: the beat chemotherapy group and the placebo group(negative control group).Throughout the treatment period, we monitored the changes in body weight and tumor size of the mice.At the conclusion of the treatment, we collected blood samples from the mice to conduct blood routine and biochemical examinations.Furthermore, we obtained tumor tissues from the mice to perform immunohistochemical staining and sequencing of the transcriptome.Results:The study found that beat chemotherapy could effectively delay the growth of lung cancer.The tumor tissues in the beat chemotherapy group were significantly smaller compared to the placebo group.The results of routine blood and blood biochemistry tests showed that the levels of red blood cells(RBCs), white blood cells(WBCs), alanine aminotransferase(ALT), aspartate aminotransferase(AST)and blood creatinine(Scr)were similar between the placebo group and the beat chemotherapy group.The values for RBCs, WBCs, ALT, AST and Scr in the placebo group were(6.97 ± 0.41)× 10 12/L, (13.26 ± 0.29)× 10 9/L, (33.33 ± 2.51)U/L, (235.33 ± 57.62)U/L and(20.67 ± 2.08)μmol/L, respectively.The corresponding values in the beat chemotherapy group were(6.87 ± 0.66)× 10 12/L, (12.59 ± 2.27)× 10 9/L, (38.67 ± 3.79)U/L, (225.33 ± 6.81)U/L and(20.33 ± 3.79)μmol/L.Statistical analysis showed no significant differences between the two groups( t=0.509, 0.209, 2.032, 0.299, 0.134, P=0.638, 0.845, 0.112, 0.780, 0.900).Furthermore, there were no signs of inflammatory infiltration or pathological changes in the liver, kidney, spleen, and lung tissues of the mice.Transcriptome analysis identified 68 differentially expressed genes, which were mainly associated with signal transduction and immunity.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis revealed the involvement of several signaling pathways, including the transforming growth factor β(TGF-β)signaling pathway, the interleukin-17(IL-17)signaling pathway, and the tumor necrosis factor(TNF)signaling pathway. Conclusions:The use of chemotherapy has been proven to be safe and effective in treating non-small cell lung cancer.It primarily functions by regulating tumor growth through various signaling pathways, including the TGF-β signaling pathway, IL-17 signaling pathway, and TNF.

Objective:To evaluate the efficacy of cerebral-placental-uterine ratio(CPUR)in predicting late-on-set fetal growth restriction(FGR).Methods:From May 2020 to May 2021,1255 women with singleton pregnancy who underwent prenatal examinations at the University of Hong Kong Shenzhen Hospital were selected for fetal growth and Doppler measurements at 35-37 +6 weeks of gestation.Pregnant women with birth weight of newbo-rns＜the 10th percentile were the FGR group.The pulsatility index(PI)of uterine artery(UtA),umbilical artery(UA)and fetal middle cerebral artery(MCA)were analyzed separately and in combination.ROC curve was used to analyze the cerebral-placental-uterine ratio(CPUR),cerebral-placental ratio(CPR),cerebral-uterine ratio(C-UtA)for predicting late-onset FGR;and to evaluate the sensitivity,positive and negative predictive value and of CPUR in the prediction of late-onset FGR.Results:The area under the curve(AUC)of CPUR,CPR,C-UtA and mean UtA-PI for FGR grope were 0.88,0.86,0.84 and 0.72.Under certain cut-off values and 87% specificity,the specificity of CPUR,CPR,C-UtA and mean UtA-Pifor predicting FGR group was 43.2%,46.6%,39.8% and 23.9%,respectively.The positive predictive values of CPUR,CPR,C-UtA and mean UtA-PI,UA-PI for predicting FGR group were 90.5%,71.9%,83.3%,63.6%and 5.2%,respectively.Conclusions:CPUR is more effective in predicting late onset FGR than CPR,C-UtA and mean UtA-PI.It can effectively increase the detection rate of fetal growth restrictionand reduce the FGR risk.

BACKGROUND:Clinical studies have found good analgesic effects of silver needle-thermal conduction therapy in patients with myofascial pain syndrome,but the exact mechanism remains unclear. OBJECTIVE:To observe the effect of silver needle-thermal conduction therapy on silent information regulator homolog 3(SIRT3)changes and mitochondrial ultrastructure in a rat model of myofascial pain syndrome. METHODS:Twenty rats were randomly selected from 26 Sprague-Dawley rats and were subjected to percussion combined with motor fatigue for replicating the rat model of myofascial pain syndrome.Sixteen rats that were successfully modeled were randomly divided into model group and silver needle-thermal conduction therapy group(treatment group),with eight rats in each group.The remaining rats were used as controls(normal group).The treatment group was treated with silver needle-thermal conduction therapy.Mechanical withdrawal threshold and thermal withdrawal latency of rats were measured at 1 day before modeling,1 day after modeling and 14 days after treatment.Electromyographic activities of the right medial femoral muscle were measured at 14 days after treatment.The right medial femoral muscle tissue was taken for hematoxylin-eosin staining to observe the local morphology and for transmission electron microscopy to observe the mitochondrial ultrastructure.Western blot assay was performed to detect SIRT3 expression. RESULTS AND CONCLUSION:Pain threshold:The mechanical withdrawal threshold and thermal withdrawal latency of the model and treatment groups were significantly decreased compared with those in the normal group and before modeling(P＜0.01).After treatment,the mechanical withdrawal threshold and thermal withdrawal latency of rats were significantly higher in the treatment group compared with the model group(P＜0.01).Electromyography:The rats in the model group showed spontaneous electrical activity in the right medial femur,while the rats in the treatment group showed reduced spontaneous electrical activity,longer time frame(P＜0.01)and lower wave amplitude(P＜0.05)compared with the model group.Hematoxylin-eosin staining:In the normal group,rat muscle fibers arranged closely and regularly.In the model group,the muscle fibers of rats were atrophied,degenerated,and disordered in arrangement.In the treatment group,rat muscle structure disorder improved.Mitochondrial microstructure:Under the transmission electron microscope,mitochondrial structure in the normal group was normal;mitochondrial swelling with broken or disappeared cristae appeared in the model group;mitochondrial swelling in the treatment group was obviously relieved or tended to be normal.SIRT3 expression:SIRT3 expression was significantly downregulated in the model group compared with the normal group,but was significantly upregulated in the treatment group compared with the model group(P＜0.05).To conclude,abnormalities in local muscle mitochondria and downregulation of SIRT3 expression suggest the presence of impaired energy metabolism in the rat model of myofascial pain syndrome.Mitochondrial changes recover and are close to normal after the silver needle-thermal conduction therapy,and the expression of SIRT3 is also upregulated close to the normal group,indicating the silver needle-thermal conduction therapy may play a therapeutic role by promoting mitochondrial repair and improving energy metabolism disorder.

Objective:To understand the current status of gastroscopy in diagnosing gastric lesions in general population, and to recommend the optimal age for the first gastroscopy and intervals for repeated gastroscopy.Methods:The gastroscopy records of residents aged 18-80 years in Yinzhou District of Ningbo, Zhejiang Province, between April 2010 and December 2021 were analyzed retrospectively. The detections of gastric lesions across different years, age and genders were described. Goodness of fit tests were applied to compare the differences in detection rates of different lesions in first-time endoscopy in different age groups and different populations. Generalized additive models were used to fit the trend of age specific gastric lesion detection rate explore the optimal age for gastroscopy. The appropriate gastroscopy intervals were determined according to the progress of the gastric lesions detected in repeated gastroscopy.Results:A total of 237 751 participants with 344 398 gastroscopy records were included in analyses. A total of 5 597 cases of chronic atrophic gastritis (CAG), 9 796 cases of intestinal metaplasia (IM), 165 cases of low-grade intraepithelial neoplasia (LGIN), 52 cases of high-grade intraepithelial neoplasia (HGIN) and 435 cases of gastric cancer were detected by the first gastroscopy. The overall detection rate of gastric lesions increased significantly in age group 45-70 years, and remained stable after 70 years old, with LGIN and HGIN showing notable increases at 50 and 55 years old, respectively. Repeated gastroscopy detected CAG, IM, LGIN, and HGIN at a higher rate compared with the first gastroscopy. Normal/superficial gastritis progressed in 3-5 years, whereas CAG or more severe lesions progressed in 1-6 years.Conclusion:Gastroscopy is recommended for general population aged 45 years and above. Furthermore, gastroscopy can be performed every 3-5 years for individuals with normal endoscopy results and once a year for patients with CAG or more severe gastric lesions.