ObjectiveTo construct and validate a predictive model for hepatic encephalopathy （HE） in patients with end-stage liver disease （ESLD） by combining key indicators such as cytokines and Model for End-Stage Liver Disease （MELD） score， and to provide evidence-based support for the early identification of high-risk populations and the optimization of intervention strategies in clinical practice. MethodsA retrospective analysis was performed for 2 167 patients with ESLD who were admitted to The Third People’s Hospital of Kunming from January 2022 to December 2024， the patients were divided into a training set with 1 517 patients and a validation set with 650 patients at a ratio of 7∶3 using the stratified random sampling method. A univariate analysis and a least absolute shrinkage and selection operator （LASSO） regression analysis were performed for the training set to identify potential influencing variables， and then a binary Logistic regression model was constructed to investigate the independent influencing factors for HE in ESLD patients. A nomogram prediction model was established based on this regression model， and the Hosmer-Lemeshow goodness-of-fit test was performed. The receiver operating characteristic （ROC） curve， calibration curves， decision curve analysis， and clinical impact curve were used to comprehensively evaluate the degree of fit， accuracy， consistency， and clinical practicability of the predictive model derived from the training set. The Mann-Whitney U test was used for comparison of non-normally distributed quantitative data between two groups. The chi-square test or Fisher exact test was used for comparison of categorical data between two groups. ResultsThe univariate analysis showed that there were significant differences between the study group and the control group in age， sex， blood ammonia， lymphocytes， hemoglobin， platelet count， prothrombin time， fibrinogen， international normalized ratio， total bilirubin， aspartate aminotransferase， total protein， albumin， prealbumin， alkaline phosphatase， cholinesterase， total bile acid， triglyceride， total cholesterol， high-density lipoprotein， low-density lipoprotein， blood glucose， CD3⁺ T cells， CD4⁺ T cells， CD8⁺ T cells， high-sensitivity C-reactive protein， carcinoembryonic antigen， triiodothyronine， thyroxine， free triiodothyronine， free thyroxine， interleukin-1β， interleukin-5， interleukin-6， interleukin-8， interleukin-12p70， interleukin-17， interferon-γ， and MELD score （all P<0.05）. The LASSO regression analysis identified nine variables of age， blood ammonia， albumin， prealbumin， cholinesterase， total cholesterol， thyroxine， interleukin-17， and MELD score， and the binary Logistic regression analysis showed that blood ammonia， interleukin-17， and MELD score were independent risk factors for HE in ESLD patients， while age and thyroxine were independent protective factors （all P<0.05）. A nomogram model was constructed based on these five variables. The Hosmer-Lemeshow goodness-of-fit test in the training set showed a good degree of fit （P=0.207）， with a McFadden’s pseudo-R² of 0.184， suggesting that the model had acceptable explanatory power； the Hosmer-Lemeshow goodness-of-fit test in the internal validation set further confirmed the calibration stability of the model （P=0.067）， suggesting that the model had a good degree of fit in independent data. The model had an area under the ROC curve of 0.784 in the validation set， with a sensitivity of 0.710 and a specificity of 0.752. The mean absolute error of the calibration curve was 0.067， and decision curve analysis and clinical impact curve showed that the nomogram model had positive net benefit and good clinical practicability. ConclusionThe nomogram model constructed based on age， blood ammonia， thyroxine， interleukin-17， and MELD score for predicting HE in patients with ESLD has a good degree of fit， high accuracy and consistency， and excellent clinical practicability.

The C 2-C 7 sagittal vertical axis (SVA) is an essential biomechanical parameter for evaluating cervical spine alignment, and it is integral to the pathogenesis, progression, and prognosis of cervical spine disorders. This parameter is widely used in evaluating cervical sagittal balance and functional status. Internationally, a C 2-C 7 SVA of less than 25 mm is considered within the cervical range for sagittal balance, while values exceeding 40 mm indicate cervical sagittal imbalance or deformity. An increased C 2-C 7 SVA disrupts cervical spine biomechanics, leading to heightened static and dynamic loads on the cervical musculature. This, in turn, results in muscle fatigue and discomfort. In the short term, patients may experience axial neck symptoms, while a sustained elevation in SVA over time significantly raises the risk of cervical disc degeneration, radiculopathy, and myelopathy. Additionally, a higher C 2-C 7 SVA postoperatively places excessive stress on adjacent spinal segments, which can accelerate degeneration of intervertebral discs and facet joints, contributing to adjacent segment degeneration. Both short-term and long-term postoperative evaluations have shown that an increase in C 2-C 7 SVA is typically associated with poorer surgical outcomes, whereas effective control of SVA values is closely linked to better functional recovery. Therefore, in clinical practice, maintaining C 2-C 7 SVA within the normal range (<25 mm) is critical not only for optimizing treatment results but also for significantly reducing postoperative complications and improving overall patient quality of life.

The C 2-C 7 sagittal vertical axis (SVA) is an essential biomechanical parameter for evaluating cervical spine alignment, and it is integral to the pathogenesis, progression, and prognosis of cervical spine disorders. This parameter is widely used in evaluating cervical sagittal balance and functional status. Internationally, a C 2-C 7 SVA of less than 25 mm is considered within the cervical range for sagittal balance, while values exceeding 40 mm indicate cervical sagittal imbalance or deformity. An increased C 2-C 7 SVA disrupts cervical spine biomechanics, leading to heightened static and dynamic loads on the cervical musculature. This, in turn, results in muscle fatigue and discomfort. In the short term, patients may experience axial neck symptoms, while a sustained elevation in SVA over time significantly raises the risk of cervical disc degeneration, radiculopathy, and myelopathy. Additionally, a higher C 2-C 7 SVA postoperatively places excessive stress on adjacent spinal segments, which can accelerate degeneration of intervertebral discs and facet joints, contributing to adjacent segment degeneration. Both short-term and long-term postoperative evaluations have shown that an increase in C 2-C 7 SVA is typically associated with poorer surgical outcomes, whereas effective control of SVA values is closely linked to better functional recovery. Therefore, in clinical practice, maintaining C 2-C 7 SVA within the normal range (<25 mm) is critical not only for optimizing treatment results but also for significantly reducing postoperative complications and improving overall patient quality of life.

Objective The equilibrium solubility and oil-water partition coefficient of caffeic acid in different pH environments were determined,and its biopharmaceutical classification system(BCS)classification was speculated.The dissolution curve of caffeic acid tablets was determined,and the above parameters were substituted into the rat PBPK model for modeling.Gastroplus software was used to predict the in vitro and in vivo correlation of caffeic acid tablets.Methods Quantitative analysis of caffeic acid was performed by a high-performance liquid chromatography in this research,the chromatographic column was Agilent Eclipse Plus C18(4.6 mm×250 mm,5 &mu;m),the mobile phase was 0.32%glacial acetic acid solution-methanol(70∶30),the flow rate was 1.0 mL·min-1,the detection wavelength was 323 nm,the column temperature was 25℃,the injection volume was 10 &mu;L.The equilibrium solubility,solubility volume(DSV)and oil-water partition coefficient(P)of caffeic acid in different pH buffers were measured by the shake flask method and n-octanol-water system,and its BCS classification was speculated.The dissolution curves of caffeic acid tablets in water,pH1.2,pH4.5 and pH6.8 were determined.The Z-Factor values of these dissolution curves were analyzed using Gastroplus software.The relevant parameters were substituted into the physiological pharmacokinetic(PBPK)model of rats to simulate the in vivo pharmacokinetic(PK)curve of rats.Compared with the measured PK curve that was reported previously,the correlation between in vivo and in vitro was speculated.Results The equilibrium solubility of caffeic acid in pH1.2,pH4.5 and pH6.8 were 0.676,1.266 and 4.624 mg·L-1,and the DSV were 443 787,236 967 and 64 879 mL,which showed that caffeic acid was an insoluble drug which had a strong pH dependence in dissolution;The oil-water partition coefficients(P)of caffeic acid in water,pH1.2 buffer,pH4.5 buffer and pH6.8 buffer were 4.33(logP=0.64),28.87(logP=1.46),19.77(logP=1.30)and 0.28(logP=-0.56),which indicated that caffeic acid was a BCS Ⅱ drug with high permeability.The results of the Cmax,tmax and AUC of caffeic acid in rats obtained by a software simulation was 0.358 &mu;g·mL-1,0.39 h and 0.320 &mu;g·h-1·mL-1,which was basically matched with the results[Cmax∶(0.250±0.037)&mu;g·mL-1、tmax∶(0.33±0.12)h、AUC∶(0.303±0.024)&mu;g·h-1·mL-1]that reported previously,so was the PK curves.Conclusion Caffeic acid is a drug with low solubility and high permeability.It is speculated that caffeic acid is a BCS Ⅱ drug,and its tablets show a high correlation in vivo and in vitro in rats.

Objective:To investigate the dose-effect relationship of Xianfu ointment and its decomposed recipes the 1-chloro-2,4-dini-trochlorobenzene(DNCB) induced chronic eczema in mice, and confirm the median effective dose (ED50) of each formula and the synergetic effect by compatibility. Methods:DNCB was used to induce chronic eczema in C57 mice. The mice were treated with gradient dosages of the Xianfu ointment (11.71-11 662.50 mg?kg-1?d-1,k = 0.316), Anemone flaccid (0.53-530.12 mg?kg-1?d-1,k = 0.316), Xianfu ointment without Anemone flaccid (11.18-11 132.40 mg?kg-1?d-1,k =0.316),respectively. The pathological features were observed after hematoxylin-eosin staining. The volume ratio of epidermides and the number of lymphocyte infiltrated in dermis were analyzed with morphometry. The serum levels of IL-2,IFN-γ,IL-4,and IL-13 were detected by ELISA assay. The ED50was calculated by non-linear regression with various slope using Prism-5.0 software.Results:The effects of Xianfu ointment and its decomposed recipes on chronic eczema showed a dose-dependent tendency. The dose-response curves showed"S"shape. The efficacy of Xianfu ointment on chronic eczema was the most significant among the three formulas, which was demonstrated by decreased epidemical thicknes (ED50= 377.90 mg?kg-1?d-1), reduced infiltrated lymphocyte number(ED50= 153.20 mg?kg-1?d-1), increased serum IL-2(ED50=608.90 mg?kg-1?d-1) and IFN-γ (ED50= 205.50 mg?kg-1?d-1) levels, and decreased serum IL-4(ED50= 198.70 mg?kg-1?d-1) and IL-13 levels (ED50= 117.60 mg?kg-1?d-1). And the dose-effect curves of Anemone flaccid and Xianfu ointment without Anemone flaccid groups were both right shift when compared with that of Xianfu ointment. Conclusion:Xianfu ointment and its decomposed recipes can effectively treat chronic eczema. Anemone flaccid has obvious compatibility synergy in the whole formula. The effects of Xianfu ointment is most significant.

Objective: To study the dose-effect relationship of Yuning ointment and its decomposed recipes in the treatment of oleic acid induced acne in mice. Methods: Oleic acid was administrated to the back (2 cm ×2 cm) of the mice (once a day) for 21 days to induce acne. At d22, the gradient dosage of Anemone flaccida crude drug (1. 06-1 060. 23 mg?kg-1?d-1,k=3. 16), Yuning oint-ment without Anemone flaccida crude drug (4. 73-1 767. 75 mg?kg-1?d-1, k=3. 16) and Yuning ointment (2. 84-2 827. 28 mg?kg-1?d-1, k=3. 16) was respectively administrated to the back of mice for 14 days. The pathological changes of skin were observed by hematoxylin-eosin (HE) staining. The diameter of sebaceous glands and the ratio of follicular keratinization area were morphomet-rically analyzed. The serum levels of IL-1, IL-6 and TNF-α were detected by ELISA assay. The median effective dosages (ED50) of A-nemone flaccida in the three prescriptions were regressed by Prism 5. 01 software to determine the prescription dose-effect. Results: All the therapy groups were with significantly relieved pathological changes of sebaceous glands hypertrophy and follicular keratinization, and decreased serum levels of IL-1, IL-6 and TNF-α in a dose-dependent manner. The dose-response curves showed an "S" shape. A-mong the three therapy groups, the effect of Yuning ointment was the best. The ED50of Yuning ointment regressed by Anemone flaccida dose was 0. 28-fold for improving sebaceous glands hypertrophy, 0. 14-fold for inhibiting follicular keratinization, and 0. 15-, 0. 49-and 0. 24-fold for decreasing serum levels of IL-1, IL-6 and TNF-α. . Regressed by Yuning ointment without Anemone flaccida, the ED50of Yuning ointment was lower than Yuning ointment without Anemone flaccid in terms of improving pathological changes and inhibiting the secretion of cytokines. Conclusion: Yuning ointment can prevent and treat acne through regulating immune function. And the prescrip-tion compatibility can enhance the effects of Anemone flaccida.

Objective: To study the relaxant effect and underlying mechanisms of evodiamine on isolated myometrium of rats. Methods:Prostaglandin F2α( PGF2α) was used to induce isolated myometrium contraction. The relaxant effect of evodiamine and the influence of capsazepine (an antagonist of transient receptor potential cation channel, subfamily V, member 1, TRPV1), U73122 (an antagonist of phospholipase Cβ,PLCβ) and W-7 ( an antagonist of camodulin, CaM) on the relaxant effect of evodiamine on myometri-um were observed respectively by biological function experiments. The median effective concentration ( EC50 ) was analyzed by non-line-ar various slope regressions using Prism-5. 01 software. Results:Evodiamine showed concentration-dependent relaxant effect on PGF2α-induced myometrium contraction with the EC50of 9.56 ×10 -9mol·L-1. Incubation with capsazepine (6.30 ×10 -11 mol·L-1), U73122 (2. 57 × 10 -11 mol·L-1 ) and W-7 (5. 65 × 10 -13 mol·L-1 ) markedly increased the relaxant effect of evodiamine, the EC50 of evodiamine decreased and dose-effect curves left shifted. The order of EC50 was as follows: W-7- evodiamine (8. 88 × 10 -15 mol· L-1) < capsazepine-evodiamine (7.35 ×10 -13 mol·L-1) < U73122-evodiamine (1.95 ×10 -12mol·L-1). Conclusion: Evodia-mine can inhibit myometrium contraction induced by PGF2αobviously, and the mechanisms are probably related to TRPV1, PLCβand CaM.

Objective: To study the relaxant effect and underlying mechanisms of evodiamine on isolated myometrium of rats. Methods:Prostaglandin F2α( PGF2α) was used to induce isolated myometrium contraction. The relaxant effect of evodiamine and the influence of capsazepine (an antagonist of transient receptor potential cation channel, subfamily V, member 1, TRPV1), U73122 (an antagonist of phospholipase Cβ,PLCβ) and W-7 ( an antagonist of camodulin, CaM) on the relaxant effect of evodiamine on myometri-um were observed respectively by biological function experiments. The median effective concentration ( EC50 ) was analyzed by non-line-ar various slope regressions using Prism-5. 01 software. Results:Evodiamine showed concentration-dependent relaxant effect on PGF2α-induced myometrium contraction with the EC50of 9.56 ×10 -9mol·L-1. Incubation with capsazepine (6.30 ×10 -11 mol·L-1), U73122 (2. 57 × 10 -11 mol·L-1 ) and W-7 (5. 65 × 10 -13 mol·L-1 ) markedly increased the relaxant effect of evodiamine, the EC50 of evodiamine decreased and dose-effect curves left shifted. The order of EC50 was as follows: W-7- evodiamine (8. 88 × 10 -15 mol· L-1) < capsazepine-evodiamine (7.35 ×10 -13 mol·L-1) < U73122-evodiamine (1.95 ×10 -12mol·L-1). Conclusion: Evodia-mine can inhibit myometrium contraction induced by PGF2αobviously, and the mechanisms are probably related to TRPV1, PLCβand CaM.