Gastroesophageal varices （GOV） bleeding is a severe complication of portal hypertension with a high mortality rate. Animal models are indispensable tools for investigating its pathogenesis and developing novel therapeutic strategies. This article systematically reviews the methods for establishing various GOV models， with a particular focus on their efficacy in simulating the key pathological processes such as an increase in hepatic venous pressure gradient and the risk of bleeding， and it also proposes targeted strategies for model selection. Finally， this article discusses the application prospects of emerging techniques in the era of precision medicine， such as organoids and gene editing， in order to provide model selection and a theoretical reference for exploring the mechanism and clinical translation of GOV.

Objective:To investigate the clinical value of laparoscopic evaluation of anato-mical position of inferior mesenteric artery (IMA), inferior mesenteric vein (IMV) and left colic artery (LCA).Methods:The prospective one-arm study was conducted. The clinical data of 229 pati-ents who underwent laparoscopic left hemicolectomy for left colon or laparoscopic radical resection of rectal cancer in The Second Affiliated Hospital of Air Force Medical University from December 2022 to December 2023 were selected. The distance between the origin point of IMA and the origin point of the first branch (L1) as well as the distance from the origin point of LCA root to the junction of LCA and IMV (L2) were measured during the operation. IMA classification, the location relation-ship of LCA and IMV junction were recorded. Observation indicators: (1) situations of enrolled patients; (2) difference analysis between L1, L2 and clinical features; (3) distribution characteristics of the location relationship between LCA and IMV in different types of IMA. Mann-Whitney U test was used for comparison of measurement data with skewed distribution between groups, Kruskal-Wallis H test was used for comparison between multiple groups, and Dunn-Bonferroni test was used for pairwise comparison. Comparison of count data between groups was performed by chi-square test. Pearson or Spearman correlation analysis was conducted for correlation of continuous variables. Results:(1) Situations of enrolled patients. A total of 229 eligible patients were screened out, including 146 males and 83 females, aged 64(range, 55-71)years. The height of 229 patients was 168(range, 160-172)cm, the weight was 65.0(55.5,71.5)kg, the body surface area was (1.68±0.17)m 2, the tumor maximum diameter was 3.0(2.5,4.0)cm. The total number of lymph nodes dissected was 19(17,21), and the number of No.253 lymph node dissected was 4(3,5). The L1 was 3.50(1.20,8.00)cm, and the L2 was 2.20(0.50,7.30)cm. There were 58, 31, 32, 71, 22, 90, 26 and 212 patients with smoking, alcohol drinking, diabetes, hypertension, coronary heart disease, neoadjuvant chemo-therapy, neoadjuvant radiotherapy and preservation of the LCA, respectively. Among 229 patients, cases with BMI <18.5 kg/m 2, 18.5-23.9 kg/m 2 and >23.9 kg/m 2 were 11, 133 and 85, respectively. There were 153 cases in pathological stage Ⅰ-Ⅱ and 76 cases in stage Ⅲ. There were 168 cases of Dixon operation, 6 cases of Miles operation and 55 cases of sigmoid colon resection. There were 135 cases of IMA type 1, 44 cases of IMA type 2, 23 cases of IMA type 3, 2 cases of IMA type 4, and 25 cases of IMA type unable to judge. (2) Difference analysis between L1, L2 and clinical features.Correlation analysis showed negative correlation between the height, body surface area and L1 ( r=-0.17, -0.15, P<0.05). The L1 was 3.20(2.68,4.00)cm for male patients and 3.60(3.00,4.20)cm for female patients, respectively, showing a significant difference between the two groups ( Z=-2.37, P<0.05). The L1 of patients with IMA type 1, 2, and 3 was 3.20(2.80,4.00)cm, 3.85(3.00,4.48)cm, and 3.20(2.50,4.30)cm, respectively, showing a significant difference among them ( H=7.54, P<0.05). Further pairwise com-parison showed that there was a significant difference in L1 between patients with IMA type 2 and those with IMA type 1 ( P<0.05). The L2 of smokers and non-smokers were 2.50(1.95,3.20)cm and 2.20(1.60,2.80)cm, respectively, showing a significant difference between the two groups ( Z=-2.24, P<0.05). (3)Distribution characteristics of the location relationship between LCA and IMV in different types of IMA. There was no significant difference in LCA distribution between the anterior and posterior positions of IMV among the three IMA types (type 1, 2, 3) ( χ2=1.63, P>0.05). Conclusions:Patients with greater height have larger body surface area and shorter L1. L1 is significantly longer in female patients than in male patients. L1 is significantly longer in patients with IMA type 2 than in those with type 1. L2 is significantly longer in smokers than in non-smokers. There was no significant difference in the distribution location between LCA and IMV among patients of IMA type 1, 2 and 3.

AIM:The study aims to investigate the effects of Huayu-Qutan formula(HYQT)-medicated serum on oleic acid-induced lipid damage and endoplasmic reticulum stress(ERS)in HepG2 cells,and to explore the mecha-nism underlying the prevention and treatment of lipid metabolism disorders by HYQT.METHODS:The HepG2 cells were treated with various concentrations of oleic acid,and CCK8 assay,oil red O staining and ELISA were used to identify the optimal treatment concentration and time of oleic acid and HYQT-medicated serum.Moreover,the cells were divided into control,model,thapsigargin(Tg),and Tg+HYQT groups.Cellular lipid deposition was measured using oil red O staining,while triglyceride(TG)and free fatty acid(FFA)levels were assessed by ELISA.Transmission electron micros-copy was used to examine endoplasmic reticulum structures,and RT-qPCR and Wes fully automated protein quantification analysis system were used to measure the mRNA and protein expression of glucose-regulated protein 78(GRP78),sterol regulatory element binding protein 1c(SREBP1c),acetyl coenzyme A carboxylase(ACC1),fatty acid synthase(FAS)and stearoyl coenzyme A desaturase 1(SCD1)in different groups.RESULTS:Significant lipid deposition was induced in HepG2 cells after treatment with 1 000 μmol/L oleic acid,while treatment with serum containing 10%HYQT for 48 h was found to be optimal.Compared with control group,the cells in model group showed significant deposition of oil red O-stained lipid droplets in the cytoplasm,associated with endoplasmic reticulum expansion,ERS,and nuclear condensa-tion.The TG and FFA levels,and the mRNA and protein expression levels of GRP78,SREBP1c,ACC1,FAS and SCD1 were increased significantly(P<0.01).Compared with model group,the cells treated with HYQT-mediated serum showed marked decrease in the number of lipid droplets in the cytoplasm,with restored endoplasmic reticulum morphology.The TG and FFA levels were significantly reduced(P<0.01),and the mRNA and protein levels of factors related to ERS and de novo fatty acid synthesis were markedly decreased(P<0.01).Treatment with Tg,an ERS agonist,led to greater accu-mulation of cytoplasmic lipid droplets and increased endoplasmic reticulum expansion.Marked variations in the morpholo-gy and size of the endoplasmic reticulum were observed,with fusion and clustering of vacuoles.The TG and FFA levels,and the expression of ERS-and fatty acid synthesis-related factors were increased(P<0.01).Compared with Tg group,the cells treated with Tg+HYQT showed reduced number of cytoplasmic lipid droplets,attenuated endoplasmic reticulum dilation,and decreased number and volume of vacuoles,while the TG and FFA levels and the expression of ERS-and fatty acid synthesis-associated factors were significantly decreased(P<0.01).CONCLUSION:Serum containing HYQT alle-viates oleic acid-induced lipid damage in HepG2 cells by inhibiting ERS-induced de novo synthesis of fatty acids.

Objective To explore the relationship between the levels of serum death-associated protein kinase 1(DAPK1)and total tau(T-tau)protein and cognitive dysfunction in patients with type 2 diabetes mellitus(T2DM).Methods A total of 178 patients with T2DM who were diagnosed and treated at the Affiliated Hospital of Xuzhou Medical University from May 2024 to January 2025 were selected.According to whether the patients had cognitive dysfunction,they were divided into cognitive dysfunction group(88 cases)and control group(90 cases).Based on Montreal cognitive assessment(MoCA)score,patients with cognitive dysfunction were further divided into severe group(MoCA score＜10 points,24 cases);moderate group(10 points ≤MoCA score ≤17 points,31 cases),and mild group(18 points ≤MoCA score＜26 points,33 cases).The levels of serum DAPK1 and T-tau proteins were detected by enzyme-linked immunosorbent assay,and the risk factors were analyzed by Logistic regression.Spearman correlation analysis was used to evaluate the correlation between T-tau protein,DAPK1 and the severity of cognitive dysfunction.Results The age,duration of diabetes mellitus,proportion of hyperlipidemia,fasting blood glucose,2-hour postprandial blood glucose,glycated hemoglobin,T-tau protein,and DAPK1 of patients in cognitive dysfunction group were significantly higher than those in control group,while the educational level was significantly lower than that in control group(P＜0.05).Logistic regression analysis showed that the duration of diabetes mellitus,T-tau protein,DAPK1,and glycated hemoglobin were all independent risk factors for cognitive dysfunction in patients with T2DM(P＜0.05).The T-tau protein and DAPK1 of patients in severe group were significantly higher than those in mild group and moderate group(P＜0.001).Spearman correlation analysis showed that DAPK1 and T-tau proteins were positively correlated with severity of cognitive dysfunction(P＜0.05).Conclusion The duration of diabetes mellitus,glycated hemoglobin,DAPK1 and T-tau protein are all independent risk factors for cognitive dysfunction in patients with T2DM.The levels of DAPK1 and T-tau protein are related to the severity of cognitive dysfunction and can be used as potential markers for risk assessment.

AIM:The study aims to investigate the effects of Huayu-Qutan formula(HYQT)-medicated serum on oleic acid-induced lipid damage and endoplasmic reticulum stress(ERS)in HepG2 cells,and to explore the mecha-nism underlying the prevention and treatment of lipid metabolism disorders by HYQT.METHODS:The HepG2 cells were treated with various concentrations of oleic acid,and CCK8 assay,oil red O staining and ELISA were used to identify the optimal treatment concentration and time of oleic acid and HYQT-medicated serum.Moreover,the cells were divided into control,model,thapsigargin(Tg),and Tg+HYQT groups.Cellular lipid deposition was measured using oil red O staining,while triglyceride(TG)and free fatty acid(FFA)levels were assessed by ELISA.Transmission electron micros-copy was used to examine endoplasmic reticulum structures,and RT-qPCR and Wes fully automated protein quantification analysis system were used to measure the mRNA and protein expression of glucose-regulated protein 78(GRP78),sterol regulatory element binding protein 1c(SREBP1c),acetyl coenzyme A carboxylase(ACC1),fatty acid synthase(FAS)and stearoyl coenzyme A desaturase 1(SCD1)in different groups.RESULTS:Significant lipid deposition was induced in HepG2 cells after treatment with 1 000 μmol/L oleic acid,while treatment with serum containing 10%HYQT for 48 h was found to be optimal.Compared with control group,the cells in model group showed significant deposition of oil red O-stained lipid droplets in the cytoplasm,associated with endoplasmic reticulum expansion,ERS,and nuclear condensa-tion.The TG and FFA levels,and the mRNA and protein expression levels of GRP78,SREBP1c,ACC1,FAS and SCD1 were increased significantly(P<0.01).Compared with model group,the cells treated with HYQT-mediated serum showed marked decrease in the number of lipid droplets in the cytoplasm,with restored endoplasmic reticulum morphology.The TG and FFA levels were significantly reduced(P<0.01),and the mRNA and protein levels of factors related to ERS and de novo fatty acid synthesis were markedly decreased(P<0.01).Treatment with Tg,an ERS agonist,led to greater accu-mulation of cytoplasmic lipid droplets and increased endoplasmic reticulum expansion.Marked variations in the morpholo-gy and size of the endoplasmic reticulum were observed,with fusion and clustering of vacuoles.The TG and FFA levels,and the expression of ERS-and fatty acid synthesis-related factors were increased(P<0.01).Compared with Tg group,the cells treated with Tg+HYQT showed reduced number of cytoplasmic lipid droplets,attenuated endoplasmic reticulum dilation,and decreased number and volume of vacuoles,while the TG and FFA levels and the expression of ERS-and fatty acid synthesis-associated factors were significantly decreased(P<0.01).CONCLUSION:Serum containing HYQT alle-viates oleic acid-induced lipid damage in HepG2 cells by inhibiting ERS-induced de novo synthesis of fatty acids.

OBJECTIVE To analyze the levels of NOD like receptor thermal protein domain associated protein 3(NLRP3),nuclear factor κB(NF-κB)and Caspase-1 in peripheral blood mononuclear cells in patients with recur-rent spontaneous abortion(RSA)and reproductive tract infection(RTI),and the relationship between above inde-xes and pregnancy outcome.METHODS A total of 136 patients with RSA and RTI who were admitted to Nanyang First People's Hospital from Mar.2021 to Apr.2024 were selected as the study group,70 patients with RSA but without RTI during the same period were selected as the control group,and those patients with RSA and RTI who were pregnant again were divided into the continued pregnancy group and the abortion group based on their preg-nancy outcomes.The levels of NLRP,NF-κB and caspase-1 in peripheral blood mononuclear cells were compared between the study group and the control group,Multivariate logistic regression analysis was used to identify risk factors for adverse pregnancy outcomes in patients with RSA and RTI.Receiver's operating characteristic(ROC)curves were used to evaluate the value of NLRP,NF-κB,and Caspase-1 in peripheral blood mononuclear cells in predicting pregnancy outcomes of patients with RSA and RTI.RESULTS The levels of NLRP,NF-κB and caspase-1 in the study group were(1.93±0.49),(1.82±0.41)and(2.23±0.41)respectively,which were higher than those in the control group(P＜0.05).The proportion of abortion in the study group was 39.79％,which was higher than that in the control group(P=0.036).Pre-pregnancy body mass index(BMI)and the levels of glycated hemoglobin,triacylglycerol,NLRP,NF-κB and Caspase-1 in the abortion group were higher than those in the continued pregnancy group.Multivariate logistic regression analysis showed that NLRP3(OR=4.721,95％CI:1.336-16.680,P=0.016),NF-κB(OR=4.669,95％CI:1.495-14.58,P=0.008),caspase-1(OR=4.358,95％CI:1.260-15.070,P=0.023)and pre-pregnancy BMI(OR=2.927,95％CI:1.280-6.693,P=0.011)were risk factors affecting pregnancy outcomes of patients with RSA and RTI(P＜0.05).ROC curves indicated that the area under the curve(AUC)of NLRP,NF-κB and Caspase-1 for pregnancy outcome in patients with RSA combined with RTI was 0.846,0.885 and 0.938.CONCLUSION The NLRP,NF-κB and Caspase-1 in peripheral blood mononuclear cells is highly expressed in patients with RSA and RTI,and the high expression of the above indicators is closely related to the adverse pregnancy of patients,which can be used as a predictor of pregnancy outcomes in patients with RSA and RTI.

Objective:To observe the early efficacy of intense pulsed light(IPL)combined with non-ablative fractional laser(NAFL)in preventing postoperative pathological scar formation and intervention of inflammatory factors.Methods:93 patients with postoperative pathological scar formation who were admitted to our hospital from March 2022 to September 2024 were selected,they were divided into control group A(silicone gel treatment,n=31),control group B(NAFL on the basis of control group A,n=31)and study group(IPL on the basis of control group B,n=31)using the random number table method.The clinical efficacy,simple quality of life scale(SF-36),vancouver scar scale(VSS),inflammatory factors[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)],and adverse reactions among three groups were compared.Results:The clinical total effective rate in the study group were higher than those in the control group A and control group B(P＜0.05).SF-36 increased sequentially and VSS decreased sequentially in control group A,control group B,and study group after treatment(P＜0.05).CRP,IL-6,and TNF-α decreased sequentially in control group A,control group B,and study group after treatment(P＜0.05).There was no significant difference in the incidence of adverse reactions among the three groups(P＞0.05).Conclusion:IPL combined with NAFL in preventing postoperative pathological scar formation,can effectively reduce scar formation,reduce inflammatory factors levels,improve patients' quality of life,and be safe and reliable.

Objective To investigate the predictive value of pre-transfer serum fibroblast growth factor 21(FGF-21),anti-Müllerian hormone(AMH),and neuropilin-1(NRP-1)for early pregnancy loss at 6 weeks following in vitro fertilization-embryo transfer(IVF-ET),and to establish an early predictive model based on serum biochemical markers.Methods This prospective study consecutively enrolled 322 women who achieved clinical pregnancy after IVF-ET at our center between September 2022 and September 2024.Participants were randomly divided into a modeling cohort(n=225)and a validation cohort(n=97)at a 7:3 ratio.According to ultrasound findings at 6 weeks of gestation,patients in the modeling cohort were classified into an early pregnancy loss group(n=59)and an ongoing pregnancy group(n=166).Baseline clinical characteristics and pre-transfer serum levels of FGF-21,AMH,and NRP-1 were collected.Multivariate logistic regression was applied to identify inde-pendent risk factors for early pregnancy loss and to construct a predictive model.Model discrimination,calibra-tion,and stability were evaluated using receiver operating characteristic(ROC)curves,the Hosmer-Lemeshow goodness-of-fit test,and bootstrap resampling in both cohorts.Results Univariate analysis revealed that the FSH/LH ratio,antral follicle count,and number of retrieved oocytes were significantly associated with early pregnancy loss(P<0.001).Compared with the ongoing pregnancy group,women with early loss showed significantly elevated pre-transfer serum FGF-21 levels,whereas AMH and NRP-1 levels were markedly reduced(P<0.001).Multivariate logistic regression demonstrated that an FSH/LH ratio<1.8(OR=1.629,P=0.002)and higher FGF-21 levels(OR=1.338,P=0.002)were independent risk factors,while higher AMH(OR=0.741,P=0.010)and NRP-1 levels(OR=0.874,P=0.007)were protective.Stratified analysis indicated that among patients with FSH/LH≥1.8,FGF-21 levels were significantly higher and AMH and NRP-1 levels significantly lower(all P<0.001).Interaction analysis further suggested that the FSH/LH ratio significantly modified the associations between these biomarkers and pregnancy loss risk(P for interaction<0.05).Specifically,in the higher FSH/LH subgroup,the risk effect of FGF-21 was amplified,while the protective effects of AMH and NRP-1 were more pronounced.The combined predictive model achieved C-indices of 0.869(95%CI:0.826～0.926)in the modeling cohort and 0.835(95%CI:0.811～0.907)in the validation cohort.Its AUC for predicting early pregnancy loss was 0.934 in the modeling co-hort and 0.909 in the validation cohort,both significantly outperforming individual markers(AUCs:FGF-21=0.867,AMH=0.881,NRP-1=0.853;Z=2.024,1.831;P<0.001).Decision curve analysis showed that the model provided consistent net clinical benefit across threshold probabilities of 0.1～0.4,underscoring its clinical utility.Conclusions Elevated pre-transfer serum FGF-21 and reduced AMH and NRP-1 levels are strongly associ-ated with early pregnancy loss at 6 weeks after IVF-ET.The predictive model developed in this study demonstrates robust accuracy and stability,offering substantial clinical application value for early risk stratification.

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C

This study aims to investigate the scientificity and efficacy of the compatibility of Jinlingzi San from pharmacokinetics. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was utilized to determine the plasma concentrations of the active components: toosendanin, tetrahydropalmatine A, and tetrahydropalmatine B at various time points following the gavage of Jinlingzi San and its single medicines in rats. Subsequently, WinNonlin was employed to calculate pertinent pharmacokinetic parameters. The pharmacokinetic parameters in rat plasma were compared between the single medicines and the compound formula of Jinlingzi San. It was discovered that the area under the curve(AUC_(all)) and peak concentrations(C_(max)) of tetrahydropalmatine A, and tetrahydropalmatine B were significantly elevated in the compound formula group compared with the single medicine groups. Conversely, the AUC_(all )and C_(max) of toosendanin notably decreased. Furthermore, the compound formula group had longer mean residence time(MRT) and lower apparent clearance(CL/F) of all three active ingredients than the single medicine groups(P<0.05). These findings indicated that Jinlingzi San enhanced the absorption of tetrahydropalmatine A and tetrahydropalmatine B in vivo, facilitating their pharmacological actions. Concurrently, it inhibited the absorption of toosendanin, thereby preventing potential toxic reactions. Moreover, the compatibility prolonged the residence time of the active ingredients in the body. This study provides a reference for exploring the compatibility rationality of Jinlingzi San.
Animals ; Rats ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Chromatography, Liquid/methods* ; Berberine Alkaloids/blood* ; Liquid Chromatography-Mass Spectrometry