Objective To investigate the predictive value of triglyceride glucose-body mass index(TyG-BMI),serum triglyceride-to-high-density lipoprotein cholesterol ratio(TG/HDL-C),and metabolic score for insulin resistance(METS-IR)for fatty pancreatic disease(FPD).Methods A total of 240 patients with FPD treated in The First Affiliated Hospital of Zhengzhou University from January 2020 to November 2023 were included as the case group,while 480 healthy subjects who underwent healthy checks in the same period were randomly selected as the control group.General clinical data and laboratory indicators were collected.The Mann-Whitney U test and chi-square test were used to compare non-normally distributed continuous variables,and categorical variables between groups,respectively.A binary logistic regression model was used to assess the relationship between TyG-BMI,TG/HDL-C,and METS-IR and FPD.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate the predictive diagnostic value of those simplified insulin resistance indicators for FPD in the general population and different sex populations.Results Age,BMI,systolic blood pressure,diastolic blood pressure,fasting plasma glucose,uric acid,alanine aminotransferase,aspartate aminotransferase,gamma-glutamyl transferase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,TyG-BMI,TG/HDL-C,and METS-IR in the case group were significantly higher than those in the control group(all P<0.05).The case group had significantly higher proportions of individuals with hypertension,diabetes,and fatty liver disease than the control group(all P<0.05).The high-density lipoprotein cholesterol level was significantly lower in the case group than in the control group(P<0.05).The multivariable Logistic regression analysis showed that after adjusting for various influencing factors,TyG-BMI,TG/HDL-C,and METS-IR remained as independent risk factors for the development of FPD,with the odds ratios(95%confidence intervals)being 1.027(1.018-1.037),6.964(2.022-23.989),and 1.184(1.123-1.248),respectively.In the ROC curve analysis,the AUCs of METS-IR and TyG-BMI were 0.823 and 0.803,respectively,with their sensitivities being 76.3%and 75.8%,specificities being 74.6%and 71.7%,and optimal cut-off values being 34.86 and 196.70,respectively;the next were BMI(AUC=0.758)and TG/HDL-C(AUC=0.734);in the sex-stratified analysis,the AUC values of METS-IR were highest in both the male and female subgroups,which were 0.834 and 0.810,respectively.Conclusion TyG-BMI,TG/HDL-C,and METS-IR show good predictive value for the development of FPD,in which METS-IR is more excellent.

As a hot spot in clinical research today, immune checkpoint inhibitor has been recommended by guidelines in the first- and second-line treatments of advanced cervical cancer as immune monotherapy or combination therapy. It has also achieved good efficacy in clinical practice. In locally advanced cervical cancer, immune checkpoint inhibitors have been included in the guidelines for adjuvant therapy, and good tumor regression effects have been achieved in clinical practice. Based on the results of existing trials, immune checkpoint inhibitors have also shown good clinical potential as neoadjuvant therapy. Furthermore, the issue of immunotherapy rechallenge has increasingly captured clinicians’ attention, offering a potential new therapeutic strategy for cervical cancer patients with prior immunotherapy exposure. In this article, the clinical application and research progress of immune checkpoint inhibitors in the treatment of cervical cancer in recent years are summarized to provide valuable ideas and directions for clinical treatment.

Objective:To investigate differentially expressed lipid molecules and their associated metabolic pathways in lung tissue using lipidomic analysis in a rat model of acute lung injury (ALI).Methods:An ALI rat model was established via intratracheal instillation of lipopolysaccharide (LPS). Twenty rats were randomly allocated into an ALI group and a control group ( n = 10 per group). The left lung was subjected to histopathological evaluation, while the right lung underwent untargeted lipidomics analysis. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed for lipid profiling. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were performed to assess intergroup differences and determine variable importance in projection (VIP) scores. Differential lipids were screened based on VIP and fold change.Lipid identification and metabolic pathway analysis were conducted using MetaboAnalyst 5.0 and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results:Among 1 022 detected lipid molecules, 47 were differentially expressed (VIP > 1, FC > 2.0 or < 0.5, P< 0.05). Subsequent analysis identified 12 structurally annotated lipids ( P < 0.05), predominantly enriched in glycerophospholipid metabolism, linoleic acid metabolism, and α-linolenic acid metabolism pathways. Notably, phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs) exhibited significant alterations in the ALI group. Conclusions:The ALI model demonstrated substantial dysregulation of lipid metabolism, particularly involving PCs and LPCs, with prominent perturbations in glycerophospholipid metabolism. This provides a scienctific basis for indepth research on the pathogenesis mechanism of ALI/acute respiratory distress syndrome (ARDS) .

Objective To analyze the changes in optical coherence tomography angiography (OCTA) parameters in patients with essential hypertension，and to explore the effect of blood pressure on OCTA parameters. Methods A total of 164 patients with essential hypertension were selected and divided into controlled blood pressure group (n=92) and uncontrolled blood pressure group (n=72). OCTA examination was performed on the optic disc and macula of all patients, and the right eyes were selected for analysis. Results There were no significant differences in retinal nerve fiber layer (RNFL) thickness, radial peripapillary capillary (RPC) total vascular density, RPC total small vessel density, perifovea superficial capillary plexus (SCP) vascular density, and perifovea deep capillary plexus (DCP) vascular density between the two groups of patients. There were no significant differences in foveal avascular zone (FAZ) area, FAZ diameter, and fovea retinal thickness between the two groups of patients. The density of the parafovea SCP, parafovea DCP, and fractal dimension (FD) in the uncontrolled blood pressure group were significantly lower than those in the controlled blood pressure group (P＜0.05). Multiple linear regression analysis showed that elevation of blood pressure was a independently related factor of reduced parafovea DCP density (P＝0.026), while there was no correlation between the uncontrolled blood pressure and parafovea SCP density and FD level. Conclusions The blood pressure level is correlated with the parafovea DCP density, while has no correlation with other OCTA parameters in hypertension patients.

Objective To explore the roles of transcription factor E26 transformation-specific 1(ETS1)and F-box protein 45(FBXO45)in invasion and metastasis in hepatocellular carcinoma cells and the potential molecular mechanism.Methods Jaspar,hTFtarget and Cistrome transcription factor database prediction websites were used to predict the transcription factors of FBXO45.According to the intersection of the predicted results of each database,the expression of FBXO45 was detected after the candidate transcription factors were knockdown in HCCLM3 and Huh7 liver cancer cells,respectively.The most significant influence on FBXO45 expression was selected for further analysis,and chromatin immunoprecipitation assay(ChIP)was used to verify the binding to the FBXO45 promoter.Finally,the potential transcription factor of FBXO45 was identified.The effect of ETS1 overexpression on invasion and migration in HCCLM3 and Huh7 cells was detected by Transwell assay,and the expression levels of epithelial-mesenchymal transition(EMT)pathway proteins were detected by Western blot assay.The effects of FBXO45 knockdown on the invasion and migration under the condition of overexpression of ETS1 were also studied.Results Intersection of FBXO45 transcription factors identified 3 candidate transcription factors,ETS1,SPI1 and YY1.When the 3 transcription factors were knocked down in HCCLM3 and Huh7 cells,respectively,ETS1 knockdown significantly reduced the expression of FBXO45.According to the analysis of The Cancer Genome Atlas(TCGA)data and the Gene Expression Omnibus(GEO)data,the expression levels of ETS1 and FBXO45 were significantly positively correlated(R=0.31,P<0.000 1;R=0.40,P=0.021 9).ChIP suggested that ETS1 could specifically bind to FBXO45 promoter sequence to regulate its expression,confirming that ETS1 was a potential transcription factor of FBXO45.After overexpression of ETS1 in HCCLM3 and Huh7 cells,the invasion and migration abilities of cells were significantly enhanced,and the expression of N-cadherin and Snail was up-regulated(P<0.01).In addition,in the case of ETS1 overexpression,FBXO45 knockdown significantly inhibited the invasion and migration(P<0.01).Conclusion ETS1 activates the transcription of FBXO45 and leads its high expression,which enhances the invasion and migration of HCC cells via EMT pathway and promotes the progression of hepatocellular carcinoma.

Objective To investigate the predictive value of triglyceride glucose-body mass index(TyG-BMI),serum triglyceride-to-high-density lipoprotein cholesterol ratio(TG/HDL-C),and metabolic score for insulin resistance(METS-IR)for fatty pancreatic disease(FPD).Methods A total of 240 patients with FPD treated in The First Affiliated Hospital of Zhengzhou University from January 2020 to November 2023 were included as the case group,while 480 healthy subjects who underwent healthy checks in the same period were randomly selected as the control group.General clinical data and laboratory indicators were collected.The Mann-Whitney U test and chi-square test were used to compare non-normally distributed continuous variables,and categorical variables between groups,respectively.A binary logistic regression model was used to assess the relationship between TyG-BMI,TG/HDL-C,and METS-IR and FPD.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate the predictive diagnostic value of those simplified insulin resistance indicators for FPD in the general population and different sex populations.Results Age,BMI,systolic blood pressure,diastolic blood pressure,fasting plasma glucose,uric acid,alanine aminotransferase,aspartate aminotransferase,gamma-glutamyl transferase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,TyG-BMI,TG/HDL-C,and METS-IR in the case group were significantly higher than those in the control group(all P<0.05).The case group had significantly higher proportions of individuals with hypertension,diabetes,and fatty liver disease than the control group(all P<0.05).The high-density lipoprotein cholesterol level was significantly lower in the case group than in the control group(P<0.05).The multivariable Logistic regression analysis showed that after adjusting for various influencing factors,TyG-BMI,TG/HDL-C,and METS-IR remained as independent risk factors for the development of FPD,with the odds ratios(95%confidence intervals)being 1.027(1.018-1.037),6.964(2.022-23.989),and 1.184(1.123-1.248),respectively.In the ROC curve analysis,the AUCs of METS-IR and TyG-BMI were 0.823 and 0.803,respectively,with their sensitivities being 76.3%and 75.8%,specificities being 74.6%and 71.7%,and optimal cut-off values being 34.86 and 196.70,respectively;the next were BMI(AUC=0.758)and TG/HDL-C(AUC=0.734);in the sex-stratified analysis,the AUC values of METS-IR were highest in both the male and female subgroups,which were 0.834 and 0.810,respectively.Conclusion TyG-BMI,TG/HDL-C,and METS-IR show good predictive value for the development of FPD,in which METS-IR is more excellent.

Objective:To explore the predictive value of myocardial work echocardiography on short-term mortality of patients with sepsis and septic shock(SSS).Methods:Patients who hospitalized in the ICU department of the Affiliated Lianyungang Hospital of Xuzhou Medical University from September 2022 to December 2023 were selected through prospective research.These patients,who need use vasopressor drugs,appeared clinical symptoms of sepsis and occurred septic shock.A total of 33 adult patients were continuously enrolled.According to whether patients with SSS died or survived within 28 days,they were divided into a survival group(23 cases)and a non-survival group(10 cases).The changes of myocardial function,serum lactic acid level,white blood cell(WBC)count,c-reactive protein(CRP)and other indexes were compared and assessed between the two groups after admission,and the predictive value of these parameters on short-term mortality in patients with sepsis and septic shock was investigated.Results:On the 3rd day after admission of patients with sepsis and septic shock,the heart rate,serum lactic acid level,white blood cell(WBC)count,global wasted work(GWW),and high-sensitivity cardiac troponin Ⅰ(hs-cTnⅠ)of non-survival group significantly higher than those of survival group(Z=-2.668,-2.550,-2.338,-2.175,-2.998,P＜0.05),and the global work efficiency(GWE)of non-survival group significantly decreased(Z=-2.311,P＜0.05).On the 5th day after admission,the heart rate,serum lactic acid level,WBC count,c-reactive protein(CRP)level of non-survival group significantly increased(Z=-3.073,-2.494,-3.408,-2.999,P＜0.05),and the pH value and global work index(GWI)of that significantly decreased(Z=-1.997,-2.546,P＜0.05).Serum lactic acid on the 3rd day and global work index on the 5th day were respectively independent risk factors for 28-day mortality in SSS patients after admission(OR=5.120,0.997,P＜0.05).On the 5rd GwI and serum lactic acid on the 3rd have similar values in predicting 28-day mortality in SSS patients[area under curve(AUC)value of receiver operating characteristics(ROC)curve of them were respectively 0.784 and 0.801,P＞0.05].Conclusion:Myocardial work echocardiography is helpful to identify the high risk of short-term death of SSS patients.Serum lactic acid of the 3rd day and global work index of the 5th day after admission are respectively independent risk factors for 28-day death in SSS patients.

Objective To investigate the expression of hepatoma-derived growth factor(HDGF)in hepatocellular carcinoma(HCC)and its effects on DNA damage,proliferation,migration,epithelial mesenchymal transition(EMT),and expression of osteoprotegerin(OPG)in HCC cells.Methods GEO database was analyzed to obtain the expression features of differential expressed mRNAs in liver tumors between HCC patients with bone metastasis and those without,and then HDGF was found as the most significantly differentially expressed gene.The mRNA expression of HDGF was verified in the HCC cells with varying metastatic capabilities by qRT-PCR.DNA damage levels in different groups of liver cancer cells were analyzed through y-H2AX immunofluorescence assay.The effects of HDGF on cell proliferation and migration were detected with CCK-8 assay,colony formation assay,and Transwell migration assay.Western blotting was employed to measure the expression of EMT-related proteins Vimentin and E-cadherin in HCC cells with various capacities of bone metastasis.Then qRT-PCR and Western blotting were performed to determine the differential expression of OPG in various groups of liver cancer cells.Results HDGF was highly expressed in HCC tissues with bone metastasis and in high-metastatic HCC cell lines.High expression of HDGF inhibited DNA damage repair.HDGF promoted the proliferation and migration of HCC cell lines.HDGF up-regulated the protein expression level of Vimentin while down-regulated that of E-cadherin(both P＜0.05),and overexpression of HDGF down-regulated the expression of OPG.Conclusion HDGF is highly expressed in bone metastatic hepatocellular tumors and may promote bone metastasis by facilitating EMT,migration,and proliferation.

Objective To investigate the mechanism of Gentianopsis paludosa xanthone(GPX)combined with probiotics in the intervention of colon inflammation-tumor transformation in rats by regulating TGF-β1/Smads pathway and inflammatory factors.Methods Ninety rats were divided into the normal group,the model group[drinking sodium dextran sulfate(DSS)for 3 days]and the intervention group by random number table method.The model group was subdivided into the inflammatory stage group,the pre-inflammatory cancer group(DMH injection for 4 weeks),the intermediate inflammatory cancer group(DMH injection for 13 weeks)and the advanced inflammatory cancer group(DMH injection for 21 weeks).The administration group was subdivided into the groups(after the first day of drinking DSS,drugs for each group were given by gavage once a day for 8 weeks)on the basis of the advanced inflammatory cancer group,including the GPX group(GPX 69.3 mg/kg),the probiotic group,the combined group(GPX+probiotics 400 mg/kg)and the thalidomide group(thalidomide 13.5 mg/kg).The disease activity index(DAI),colon length and wet mass index were compared between all groups.Characteristics of colon tumors were observed,and pathological changes of colon were observed by HE staining.The expression levels of transforming growth factor(TGF)-β1,Smad4,Smad7,interleukin(IL)-6 and tumor necrosis factor(TNF)-α were detected by Western blot assay and enzyme-linked immunosorbent assay,respectively.Results Compared with the advanced inflammatory cancer group,the administration groups showed an increase in colon length,the expression levels of TGF-β1 and Smad4 protein,a decrease in colon wall thickness,wet mass index,maximum tumor diameter,the levels of Smad7,IL-6,TNF-α,and DAI score decreased in the GPX group and the combined group(P＜0.05).The structure and morphology of intestinal mucosa were improved in the GPX group,the probiotic group and the combination group,and the structure of colonic crypt and goblet cell number were increased.Compared with the probiotic group and the GPX group,the colon wall thickness,colon wet mass index and tumor number were decreased,the protein expression levels of TGF-β1 and Smad4 were increased,and levels of IL-6 and TNF-α were decreased in the combination group(P＜0.05).Conclusion GPX combined with probiotics could inhibit the transformation of colon inflammation-tumor,and the mechanism may be related to the regulation of TGF-β1/Smads pathway and the inhibition of pro-inflammatory factors of IL-6 and TNF-α.

Objective:To investigate the expression of nucleoporin 43 (NUP43) in hepato-cellular carcinoma tissues and its impact on prognosis of patients and proliferation and migration of hepatocellular carcinoma cells.Methods:The retrospective cohort study and experi-mental study were conducted. The clinicopathological data of 102 hepatocellular carcinoma patients who were admitted to The First Affiliated Hospital of Army Medical University from January 2008 to December 2012 were collected. There were 83 males and 19 females, aged 56(range, 19-87)years. The expression of NUP43 in hepatocellular carcinoma tissues was analyzed by immunohistochemical staining. HepG2 and SK-HEP-1 hepatocellular carcinoma cells were cultured in vitro. The Western blot was used to verify the effects of Flag-NUP43 overexpression plasmid in transfected cells. The CCK-8 and cell migration experiments were used to analyze the effect of NUP43 overexpression on HepG2 and SK-HEP-1 hepa-tocellular carcinoma cells. Measurement data of normal distribution were expressed as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data of skewed distribution were represented as M(range). Count data were expressed as absolute numbers, and comparisons between groups was conducted using the paired chi-square test. The Kaplan-Meier method was used to calculate survival time, and Log-rank test was used for survival analysis. The R 4.2.1 software was used to draw survival curves. The COX proportional hazards regre-ssion model was used for univariate and multivariate analyses. Results:(1) Expression of NUP43 in hepatocellular carcinoma and adjacent tissues, and analysis of clinicopathological characteristics of patients with high and low expression of NUP43. Results of immunohistochemical staining showed that NUP43 was mainly expressed in the cytoplasm and nuclear membrane of cells. Of 102 hepatocellular carcinoma tissue samples, there were 49 samples with low expression of NUP43 and 53 samples with high expression of NUP43. Of 102 hepatocellular carcinoma adjacent tissue samples, there were 80 samples with low expression of NUP43 and 22 samples with high expression of NUP43. There was a significant difference in the expression of NUP43 between hepatocellular carcinoma and adjacent tissues ( χ2=16.505, P<0.05). Of 102 hepatocellular carcinoma tissue samples, there were significant differences in tumor diameter, pathological grading, and intrahepatic metastasis between the patients with low expression of NUP43 and the patients with high expression of NUP43 ( χ2=5.104, 23.217, 4.169, P<0.05). (2) Survival of hepatocellular carcinoma patients and prognostic factors analysis. The follow-up time of 102 hepatocellular carcinoma patients was 17.9(range, 0.1-107.9)months. The postoperative 1-, 3-, and 5-year overall survival rates were 79.59%, 53.06% and 34.69% for the patients with low expression of NUP43, versus 52.83%, 18.87%, and 9.43% for the patients with high expre-ssion of NUP43, showing a significant difference between them ( χ2=27.071, P<0.05). Results of multi-variate analysis showed that gender, NUP43 expression, TNM staging, and pathological grading were independent influencing factors for postoperative survival in patients with hepatocellular carcinoma ( hazard ratio=1.846, 2.206, 2.040, 2.177, 95% confidence interval as 1.231-2.768, 1.419-3.429, 1.322-3.148, 1.377-3.254, P<0.05). (3) Effects of NUP43 overexpression on the proliferation and migration of HepG2 and SK-HEP-1 hepatocellular carcinoma cells. Western blot analysis showed that transfection of Flag-NUP43 overexpression plasmid significantly increased the expression of NUP43 in HepG2 and SK-HEP-1 cells. Results of CCK-8 experiment showed that after transfection with the control plasmid and Flag-NUP43 overexpression plasmid, the cell proliferation indices of HepG2 were 0.79±0.07 and 1.47±0.05, respectively, showing a significant difference between them ( t=19.402, P<0.05). After transfection with the control plasmid and Flag-NUP43 overexpression plasmid, the cell proliferation indices of SK-HEP-1 cells were 0.59±0.05 and 0.95±0.05, respectively, showing a significant difference between them ( t=15.753, P<0.05). Results of cell migration experiments showed that after transfection with the control plasmid and Flag-NUP43 overexpression plasmid, the number of cell migrations in HepG2 was 188±8 and 595±13, respectively, showing a significant difference between them ( t=46.192, P<0.05). After transfection with the control plasmid and Flag-NUP43 overexpre-ssion plasmid, the number of cell migrations in SK-HEP-1 cells were 136±10 and 447±20, respectively, showing a significant difference between them ( t=24.721, P<0.05). Conclusions:The expression of NUP43 in hepatocellular carcinoma tissues is significantly higher than that in adjacent tissues. Gender, NUP43 expression, TNM staging, and pathological grading are independent influen-cing factors for postoperative survival of hepatocellular carcinoma patients. Overexpression of NUP43 can significantly promote the proliferation and migration of HepG2 and SK-HEP-1 hepatocellular carcinoma cells.