This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Mice ; Network Pharmacology ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Chromatography, High Pressure Liquid ; Liver/metabolism* ; Mice, Inbred C57BL ; Humans ; Mass Spectrometry ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation

Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

Objective:To experimentally validate clinical samples, analyze the mRNA expression of the FYVE domain containing phosphatidylinositol 3-phosphate 5 kinase ( PIKFYVE) gene, and its clinical significance based on the Cancer Genome Atlas (TCGA) database in hepatocellular carcinoma (HCC). Methods:Data information on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of non-tumorous liver tissues) were collected based on the TCGA database. Cox regression analysis and the Kaplan-Meier method were used to analyze the relationship between mRNA expression of the PIKFYVE gene and the clinical characteristics as well as survival prognosis in patients with HCC. The relationship between the PIKFYVE gene and immune cell infiltration was examined by correlation analysis with 24 kinds of immune cells. In addition, the mRNA expression level of the PIKFYVE gene and RAC-alpha serine/threonine-protein kinase ( AKT1), phosphatase and tensin homolog ( PTEN), protein kinase C alpha ( PRKCA), inositol polyphosphate-5-phosphatase ( INPP5D), phosphoinositide-3-kinase regulatory subunit 1 ( PIK3R1), inositol polyphosphate 4-phosphatase type II ( INPP4B) and phospholipase C beta 4 ( PLCB4) gene correlations were analyzed in HCC tissues. At the same time, paraffin sections of highly differentiated, moderately differentiated, poorly differentiated, and non-tumor liver tissues from patients with HCC were collected from the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University. The histopathological observation was performed by HE staining. Immunohistochemistry was used to verify the expression levels of the PIKFYVE and Ki67 proteins in each clinical sample. The t-test was used for intergroup comparison of continuous data. The χ2 test and Wilcoxon rank sum test were used for intergroup comparison of enumeration data. The Kaplan-Meier method was used for survival analysis. Results:The expression level of the PIKFYVE gene was higher in the HCC tumor than that in normal liver tissue ( P<0.01). The overall survival time of patients was significantly longer in the low expression group than that in the high expression group ( HR=1.57, 95% CI: 1.10～2.25, P=0.014). The results of univariate Cox regression analysis showed that tumor stage, pathological grade, tumor status, residual tumor, and PIKFYVE expression level all had an effect on OS ( P<0.05). The PIKFYVE prognostic risk model had a proportionate score of HR=1.533 (95% CI: 1.077～2.181, P=0.018). Multivariate Cox risk regression analysis showed that the PIKFYVE prognostic risk model had a proportionate score of HR=1.481 (95% CI: 0.886～2.476, P=0.134) and an area under the receiver operating characteristic curve of 0.559, indicating that it had predictive value for survival prediction. The results of the correlation analysis showed that the expression level of PIKFYVE was strongly correlated with immune cell infiltration and TP53 ( P<0.01). The results of immunohistochemical staining showed that the expression level of PIKFYVE was significantly higher in HCC tissue samples than that in non-tumor liver tissues ( P<0.01), and was negatively correlated with the degree of differentiation. Conclusion:PIKFYVE, as an independent risk factor, is expected to be developed into a biomarker for clinical diagnosis, offering a reference for novel therapeutic agents in HCC.

Objective:To explore the effect of kidney-strengthening and blood stasis-eliminating formula on nutritional status and quality of life in patients with osteoporosis combined with hemodialysis.Methods:From January 2024 to January 2025,60 patients with liver and kidney yin deficiency and blood stasis obstruction were selected from the Pizhou City Traditional Chinese Medicine Hospital's Hemodialysis Center.60 patients were randomly divided into two groups,30 in each group.The matched group received general treatment plus paricalcitol,while the treatment group received the same treatment plus Yishen Zhuyu Fang(a traditional Chinese medicine formula for kidney and blood stasis).The treatment course lasted 12 weeks.Changes in TCM syndrome scores,the Modified Subjective Global Assessment(MQSGA),the Kidney and Life Quality(KDQOLTM-36)scale,lipid levels,and nutritional indicators were compared before and after treatment.Results:After treatment,the TCM syndrome scores in both groups decreased(P＜0.05),with a more pronounced decrease in the treatment group(P＜0.05).The KDQOLTM-36 score in the treatment group increased(P＜0.05),while the increase was not significant in the matched group(P＞0.05),indicating that the treatment group performed better than the matched group(P＜0.05).Both groups experienced a decrease in the MQSGA score(P＜0.05),although the difference was not statistically significant(P＞0.05),the treatment group showed a more noticeable decline.The TC,TG,LDL,and TG/HDL levels in the treatment group all decreased significantly,while HDL levels increased(P＜0.05).In contrast,the TC and HDL levels in the matched group did not change(P＞0.05),while the TG,LDL,and TG/HDL levels increased(P＜0.05).The treatment group performed significantly better than the matched group(P＜0.05).The TRF,Hb,and ALB levels in the treatment group increased(P＜0.05),while the increase was not significant in the matched group(P＞0.05).The total effective rate of the treatment group was 90％,higher than the matched group(23.3％)(P＜0.05).Conclusion:The formula of tonifying the kidney and removing stasis can improve the nutritional status and quality of life of patients with liver and kidney yin deficiency and blood stasis obstruction in hemodialysis combined with osteoporosis.

Objective:To explore the effect of kidney-strengthening and blood stasis-eliminating formula on nutritional status and quality of life in patients with osteoporosis combined with hemodialysis.Methods:From January 2024 to January 2025,60 patients with liver and kidney yin deficiency and blood stasis obstruction were selected from the Pizhou City Traditional Chinese Medicine Hospital's Hemodialysis Center.60 patients were randomly divided into two groups,30 in each group.The matched group received general treatment plus paricalcitol,while the treatment group received the same treatment plus Yishen Zhuyu Fang(a traditional Chinese medicine formula for kidney and blood stasis).The treatment course lasted 12 weeks.Changes in TCM syndrome scores,the Modified Subjective Global Assessment(MQSGA),the Kidney and Life Quality(KDQOLTM-36)scale,lipid levels,and nutritional indicators were compared before and after treatment.Results:After treatment,the TCM syndrome scores in both groups decreased(P＜0.05),with a more pronounced decrease in the treatment group(P＜0.05).The KDQOLTM-36 score in the treatment group increased(P＜0.05),while the increase was not significant in the matched group(P＞0.05),indicating that the treatment group performed better than the matched group(P＜0.05).Both groups experienced a decrease in the MQSGA score(P＜0.05),although the difference was not statistically significant(P＞0.05),the treatment group showed a more noticeable decline.The TC,TG,LDL,and TG/HDL levels in the treatment group all decreased significantly,while HDL levels increased(P＜0.05).In contrast,the TC and HDL levels in the matched group did not change(P＞0.05),while the TG,LDL,and TG/HDL levels increased(P＜0.05).The treatment group performed significantly better than the matched group(P＜0.05).The TRF,Hb,and ALB levels in the treatment group increased(P＜0.05),while the increase was not significant in the matched group(P＞0.05).The total effective rate of the treatment group was 90％,higher than the matched group(23.3％)(P＜0.05).Conclusion:The formula of tonifying the kidney and removing stasis can improve the nutritional status and quality of life of patients with liver and kidney yin deficiency and blood stasis obstruction in hemodialysis combined with osteoporosis.

Objective:To experimentally validate clinical samples, analyze the mRNA expression of the FYVE domain containing phosphatidylinositol 3-phosphate 5 kinase ( PIKFYVE) gene, and its clinical significance based on the Cancer Genome Atlas (TCGA) database in hepatocellular carcinoma (HCC). Methods:Data information on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of non-tumorous liver tissues) were collected based on the TCGA database. Cox regression analysis and the Kaplan-Meier method were used to analyze the relationship between mRNA expression of the PIKFYVE gene and the clinical characteristics as well as survival prognosis in patients with HCC. The relationship between the PIKFYVE gene and immune cell infiltration was examined by correlation analysis with 24 kinds of immune cells. In addition, the mRNA expression level of the PIKFYVE gene and RAC-alpha serine/threonine-protein kinase ( AKT1), phosphatase and tensin homolog ( PTEN), protein kinase C alpha ( PRKCA), inositol polyphosphate-5-phosphatase ( INPP5D), phosphoinositide-3-kinase regulatory subunit 1 ( PIK3R1), inositol polyphosphate 4-phosphatase type II ( INPP4B) and phospholipase C beta 4 ( PLCB4) gene correlations were analyzed in HCC tissues. At the same time, paraffin sections of highly differentiated, moderately differentiated, poorly differentiated, and non-tumor liver tissues from patients with HCC were collected from the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University. The histopathological observation was performed by HE staining. Immunohistochemistry was used to verify the expression levels of the PIKFYVE and Ki67 proteins in each clinical sample. The t-test was used for intergroup comparison of continuous data. The χ2 test and Wilcoxon rank sum test were used for intergroup comparison of enumeration data. The Kaplan-Meier method was used for survival analysis. Results:The expression level of the PIKFYVE gene was higher in the HCC tumor than that in normal liver tissue ( P<0.01). The overall survival time of patients was significantly longer in the low expression group than that in the high expression group ( HR=1.57, 95% CI: 1.10～2.25, P=0.014). The results of univariate Cox regression analysis showed that tumor stage, pathological grade, tumor status, residual tumor, and PIKFYVE expression level all had an effect on OS ( P<0.05). The PIKFYVE prognostic risk model had a proportionate score of HR=1.533 (95% CI: 1.077～2.181, P=0.018). Multivariate Cox risk regression analysis showed that the PIKFYVE prognostic risk model had a proportionate score of HR=1.481 (95% CI: 0.886～2.476, P=0.134) and an area under the receiver operating characteristic curve of 0.559, indicating that it had predictive value for survival prediction. The results of the correlation analysis showed that the expression level of PIKFYVE was strongly correlated with immune cell infiltration and TP53 ( P<0.01). The results of immunohistochemical staining showed that the expression level of PIKFYVE was significantly higher in HCC tissue samples than that in non-tumor liver tissues ( P<0.01), and was negatively correlated with the degree of differentiation. Conclusion:PIKFYVE, as an independent risk factor, is expected to be developed into a biomarker for clinical diagnosis, offering a reference for novel therapeutic agents in HCC.

Objective To investigate the effect of parent-child alienation on depression in surface ship officers and soldiers based on the theory of"diathesis-stress",and the mediating role of resilience between parent-child alienation and depression in them.Methods A cross-sectional study was conducted on 599 officers and soldiers from a surface ship unit.The participants were surveyed with inventory of alienation toward parents,connor-davidson resilience scale and patient health questionnaire-9 to obtain and analyze their demographic-military characteristics of their depression scores.The participants with depression scores ≥5 were recruited as the subjects,and Spearman correlation analysis was used to explore the correlation among parent-child alienation,resilience and depression.On the basis of hierarchical regression analysis,AMOS software was used to establish a structural equation modelling of intermediary effects.Results The depression score was 1(0,4)in the participants,and the depression scores of those with service length ≥11 years were comparatively higher than those with shorter length.Our results indicated that parent-child alienation was positive correlated with depression(r=0.451,P＜0.001),while resilience was negatively correlated with depression and parent-child alienation(r=-0.412,-0.407,P＜0.001).Regression analysis revealed that parent-child alienation had a direct positive predictive value for depression(β=0.574,P＜0.001),and resilience showed a negative predictive value for depression(β=-0.211,P＜0.01).Model analysis displayed that resilience had a significant mediating role in the effect of parent-child alienation on depression among these surface ship officers and soldiers,with an effect value of 0.088,and accounting for 15.86％of the total effect.Conclusion Parent-child alienation has a significant influence on depression among surface ship officers and soldiers,with resilience playing a partial mediating role.

Lithium(Li)salts are commonly used as psychotropic medications for the treatment of major depressive disorders.However,long-term use of Li salts poses a high risk of toxicity,necessitating continuous monitoring of Li concentration in patient blood to ensure medication safety,which is crucial for clinical treatment.Laser-induced breakdown spectroscopy(LIBS),as a rapid analytical technique,has been widely applied in the elemental analysis of complex matrices in various practical scenarios.In this study,LIBS technology combined with partial least squares(PLS)was employed for quantitative analysis of Li elements in blood matrix.A total of 45 clinical blood samples were utilized,and the quantitative models for plasma and whole blood matrices were separately investigated.The number of latent variables in the PLS algorithm was optimized using a five-fold cross-validation method.Results revealed that the PLS quantitative model constructed on the basis of plasma matrix achieved a predictive determination coefficient(R2)of 0.992,a predictive root mean square error(RMSEP)of 0.204 μg/mL,and a relative standard error(RSD)of 2.14%.In contrast,for the PLS quantitative model constructed on the basis of whole blood matrix,the R2 was 0.984,the RMSEP was 0.728 μg/mL,and the RSD was 3.45%Consequently,the LIBS model constructed on the basis of plasma calibration values demonstrated superior performance in quantitative analysis of Li element in whole blood,and LIBS technology provided a new possibility for rapid assessment of blood Li levels in clinical practice,with promising prospects for application.

Elemental imaging analysis based on laser induced-breakdown spectroscopy(LIBS)can provide significant reference value for oil and gas exploration activities.Improving the scanning speed and spatial resolution of LIBS elemental imaging analysis instruments contributes to enhancing the efficiency of mineral surface elemental analysis,which is crucial for achieving in-situ,real-time,and rapid LIBS analysis.In this study,a high-speed scanning LIBS elemental imaging analysis instrument was developed based on a scanning mirror device,achieving a scanning speed of 100 Hz and a spatial resolution of 50 μm.The stability of spectral data collected by this instrument was validated using aluminum alloy standard samples with uniform elemental distribution.The experimental results showed that the relative standard deviations(RSD)of the spectral data collected at different locations were 2.76％,2.79％,2.35％and 2.55％,respectively,demonstrating that the instrument's performance met analysis requirements.Analysis of spectral acquisition channels led to the selection of the 337-595 nm spectral range.Imaging analysis of major elements on the surface of meteorite mineral samples with complex matrices was conducted using this instrument,coupled with a multi-element imaging algorithm enabling visualization analysis of four major elements on the same image.The results revealed a higher level of detail and complexity in element distribution.The study demonstrated that this instrument,combined with multi-element imaging analysis algorithms,could provide crucial technical support for rapid imaging of element distribution in minerals at a microscopic scale during geological research.

Objective To study the rules of acupoint selection and prescription in clinical acupuncture and moxibustion treatment of acute renal colic.Methods The clinical literature on the treatment of acute renal colic by acupuncture and moxibustion has been published and included in CNKI,Wanfang,VIP and PubMed databases.Through strict screening,Microsoft Excel,SPSS 26.0,IBM SPSS Modeler 15.0 software and Apriori algorithm were used to conduct in-depth information mining and analysis of the included literature.Results A total of 110 acupuncture prescriptions were included in the clinical literature on the treatment of acute renal colic,involving the use of a total of 59 acupoints,of which Shenshu(BL23),Ashi and Sanyinjiao(SP6)were the most frequently used;the commonly used meridians were the foot taiyang bladder meridian,the foot taiyin spleen meridian,and the foot yangming stomach meridian;the acupoints were mainly located in the lower limbs and the lumbar back;in terms of the type of points,the Wushu(BL67),back-shu point,lower confluent point are the first choice;in the combination of two acupoints,the combination of Shenshu and Ashi points had the highest support;among the three-point combinations,the combination of Shenshu,Sanyinjiao and Ashi points had the highest support;and the core acupoint combination was the combination of Shenshu and Ashi points.Conclusion The selection of acupoints and the combination of prescriptions for acupuncture and moxibustion treatment of acute renal colic has a retrospective law to follow,which can provide important reference value for clinical treatment and scientific research.