ObjectiveThis study aims to compare the modeling effects of submaxillary gland antigen and salivary gland antigen in the establishment of Sjögren syndrome (SS) mouse models, and to characterize the phenotypic and immunological features of these models in comparison with spontaneous SS-prone non-obese diabetic (NOD)/LtJ mice. MethodsAdult C57BL/6J mice (equal numbers of males and females) were immunized with submaxillary gland antigen or salivary gland antigen, respectively, combined with Freund's adjuvant to induce SS models. Mice immunized with phosphate-buffered saline (PBS) combined with Freund's adjuvant served as the control group. Immunization was induced via multiple subcutaneous injections in the back with antigen combined with Freund's complete adjuvant (FCA) on Days 1 and 7. A booster immunization was administered via multiple subcutaneous injections in the back with antigen combined with Freund's incomplete adjuvant (FIA) on Day 14. Female NOD/LtJ mice were used as the spontaneous SS model group, with ICR mice as the corresponding control strain for comparative analysis. Body weight, water intake, and salivary flow rate of mice were dynamically monitored for 4 weeks. At the end of the experiment, tissue and serum samples were collected, the weights of submaxillary glands, thymus, and spleen were measured, and organ indices (organ-to-body weight ratios) were calculated. Pathological morphological analysis of the submaxillary gland and spleen was performed with hematoxylin and eosin (HE) staining. Serum interleukin-17 (IL-17) level was detected using enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction was used to detect the mRNA expression levels of SS type A (SSA) and SS type B (SSB) in submaxillary gland tissues. ResultsFemale mice in the submaxillary gland antigen group exhibited significantly increased water intake (P<0.05) and reduced salivary flow rate (P<0.05) compared with the female control group. No statistically significant differences were observed in the submaxillary gland index, thymus index and spleen index (P>0.05). Focal lymphocytic infiltration was observed in the submaxillary glands, and the splenic marginal zone was enlarged. Serum IL-17 levels were significantly increased (P<0.05). There was no significant difference in submaxillary gland SSA/SSB expression levels (P>0.05). Compared with the female control group, female mice in the salivary gland antigen group showed no statistically significant differences in water intake, salivary flow rate, submaxillary gland index, and spleen index (P>0.05), whereas the thymus index was significantly reduced (P<0.01). Mild inflammatory cell infiltration and glandular atrophy were observed in the submaxillary glands, and the splenic white pulp and marginal zone were slightly enlarged. Serum IL-17 levels and submaxillary gland SSB mRNA expression levels were significantly increased (P<0.01), whereas no significant change was observed in submaxillary gland SSA expression levels (P>0.05). Compared with the male control group, mild submaxillary gland atrophy was observed in male mice in the submaxillary gland antigen group, whereas no obvious changes were found in other modeling-related indicators (P>0.05). Compared with the ICR control group, NOD/LtJ model mice exhibited elevated water intake (P<0.05), significantly reduced salivary flow rate (P<0.01), no significant differences in the submaxillary gland index or spleen index (P>0.05), but a significantly increased thymus index (P<0.05). Marked focal infiltration was observed in the submaxillary glands, the splenic marginal zone was obviously enlarged, and serum IL-17 concentrations as well as submaxillary gland SSA/SSB expression levels were significantly increased (P<0.05). ConclusionSubmaxillary gland antigen and salivary gland antigen can induce SS-related features in female C57BL/6J mice. The SS-related phenotype is more pronounced in the submaxillary gland antigen group than in the salivary gland antigen group, but weaker than that in spontaneously SS-prone female NOD/LtJ mice. Immunization of male C57BL/6J mice with submaxillary or salivary gland antigens fails to induce an obvious SS phenotype.

The interleukin-10 （IL-10） family is expressed in various types of cells and has a wide range of biological functions， and it plays an important role in the development and progression of hepatic fibrosis. Hepatic fibrosis is a chronic liver disease characterized by abnormal repair of hepatic tissues after injury， activation of hepatic stellate cells， and excessive accumulation of extracellular matrix. The IL-10 family members include IL-10， IL-19， IL-20， IL-22， IL-24， IL-26， IL-28， IL-29， and IL-35， with similarities in structure and function， and changes in their expression levels are closely associated with the progression of hepatic fibrosis. Moderate upregulation of the expression of IL-10 family members can help maintain the quiescent state of hepatic stellate cells， promote the transformation of macrophages to anti-inflammatory phenotype， and regulate the activity of natural killer cells， thereby inhibiting inflammatory response， regulating cell apoptosis and autophagy， and finally reversing the progression of hepatic fibrosis. This article discusses the mechanism of action of IL-10 family members and their application in traditional Chinese medicine and Western medicine therapies， in order to provide new thoughts for the treatment of hepatic fibrosis.

Objective To evaluate the predictive efficacy of individualized dosage support software-Smart Dose,PharmVan and JPKD-on vancomycin plasma concentration in patients undergoing infective endocarditis(IE)surgery,and to analyze the influencing factors.Methods A retrospective analysis was conducted in IE patients who received intravenous vancomycin in our hospital from January 2019 to December 2022.The above softwares were used to predict the steady-state trough concentration of vancomycin,and the relative prediction error and absolute weight deviation(AWE)between the predicted and measured values were compared.According to the AWE value,the results were divided into accurate prediction group(AWE＜30％)and the inaccurate prediction group(AWE≥30％).Univariate analysis and Logistic regression analysis were used to explore the influencing factors,and to evaluate the predictive value through the receiver operating characteristic curve(ROC).Results A total of 27 patients were enrolled,with 27 concentrations of initial regimen and 35 of adjustment regimen.When PharmVan predicted the adjusted concentration,the AWE was 24.84(11.54,39.78)％,with higher accuracy than other predicted results.The Univariate analysis of factors influencing the performance of PharmVan in predicting the adjusted concentration showed that patients in the accurate prediction group was significantly younger than that in the inaccurate prediction group(P＜0.05).Multivariate analysis showed that advanced age was an independent risk factor for the inaccurate prediction of PharmVan for adjustment concentration[OR=0.856,95％CI was(0.757,0.969),P=0.014].ROC curve analysis indicated that when patients were older than 48.5 years old,the risk of inaccurate prediction was increased with a sensitivity of 78.9％and a specificity of 93.7％.Conclusions Only the PharmVan software has a higher accuracy in predicting the adjusted concentration among the three softwares,but it is still need to be cautious in combination with the analysis results of ROC curve.Therefore,when using vancomycin in IE patients,attention should be paid to renal function and plasma concentration should be actively monitored.

Objective:To explore the predictive value of atherogenic index of plasma(AIP)combined with neutro-phil/HDL-C ratio(NHR),lymphocyte/HDL-C ratio(LHR)and monocyte/HDL-C ratio(MHR)for major adverse cardiovascular events(MACE)in patients with acute coronary syndrome(ACS).Methods:This retrospec-tive study enrolled 320 patients underwent coronary angiography in Department of Cardiovascular Medicine,Harri-son International Peace Hospital between January 2021 and December 2022,including 215 ACS patients and 105 pa-tients without ACS;according to Gensini score,ACS patients were divided into low risk group(n=50),medium risk group(n=70)and high risk group(n=95).According to the presence of MACE within 1 year,patients were divided into MACE group(n=55)and no MACE group(n=160).After admission,blood routine,blood lipids,C-reactive protein(CRP)and endothelin-1(ET-1)levels were measured,then NHR,LHR,MHR and AIP were calculated.Spearman method was used to analyze the association of above-mentioned indexes with Gensini score;stepwise Logistic regression was used to analyze the influencing factors of MACE within 1 year in ACS patients;and ROC curve was used to analyze the predictive value of single and combined detection of above indexes for MACE within 1 year in ACS patients.Results:Compared to patients in no ACS group,those in ACS group had significantly higher BMI[(23.59±0.85)kg/m2 vs.(21.57±1.16)kg/m2],proportions of hypertension(57.67％vs.13.33％),diabetes(23.26％vs.8.57％),NHR[(12.09±3.46)vs.(3.81±1.29)],MHR[(0.70±0.18)vs.(0.33±0.10)],LHR[(0.79±0.21)vs.(0.40±0.09)],AIP[(0.21±0.06)vs.(0.11±0.02)],CRP[(9.82±3.09)mg/L vs.(2.20±0.58)mg/L],ET-1[(31.25±10.34)μg/L vs.(10.60±1.96)μg/L](P＜0.001 all).Compared to those in no MACE group,patients in MACE group had significantly higher NHR[(17.33±3.87)vs.(10.12±2.68)],MHR[(0.93±0.24)vs.(0.61±0.13)],LHR[(1.05±0.27)vs.(0.71±0.16)],AIP[(0.28±0.04)vs.(0.17±0.02)],CRP[(15.52±3.83)mg/L vs.(7.69±2.40)mg/L],ET-1[(46.68±9.51)μg/L vs.(25.47±4.66)μg/L]levels(P＜0.001 all).Spearman correlation analysis showed that NHR,MHR,LHR and AIP were significant positively correlated with Gensini score(r=0.837～0.868,P＜0.001 all).Stepwise Logistic regression analysis showed that NHR(OR=1.225,95％CI 1.016～1.550,P=0.035),AIP(OR=2.632,95％CI 1.055～6.566,P=0.038)were independent risk factors for MACE within 1 year in ACS patients.ROC curve shows that AUC of AIP combined with NHR,MHR and LHR predicting MACE within 1 year in ACS patients was 0.786(95％CI 0.725～0.839),which was significantly higher than those of NHR(AUC 0.768,95％CI 0.706～0.823),LHR(AUC 0.749,95％CI 0.686～0.806)and AIP(AUC 0.764,95％CI 0.701～0.819)alone(Z=2.597,2.687,1.965,P＜0.05 or＜0.01).Conclusion:AIP combined with NHR,MHR and LHR have certain predictive value for MACE within 1 year in ACS patients.

Objective To evaluate the clinical efficacy and safety of vericiguat combined with the new"Quadruple Therapy"for treating heart failure with reduced ejection fraction(HFrEF)and to explore its impact on left ventricular reverse remodeling(LVRR)in patients with different baseline characteristics.Methods A total of 87 patients with chronic heart failure treated with vericiguat at the Department of Cardiology,Nanjing Drum Tower Hospital from June 2022 to March 2024,were consecutively enrolled as the observation group.These patients were matched at 1:1 by age,sex,and left ventricular ejection fraction(LVEF)with 87 patients who received the standard quadruple therapy without vericiguat as the control group.Propensity score matching was used to further balance confounding factors,resulting in 64 patients in each group for final analysis.Changes in echocardiographic parameters,liver and kidney function,electrolyte levels,and blood pressure were analyzed at baseline and during the 6-month follow-up to assess the efficacy and safety of vericiguat.The primary efficacy endpoint was the occurrence of LVRR.Subgroup analyses were conducted based on baseline characteristics such as age and sex.Interaction analysis was utilized to evaluate the heterogeneity of vericiguat's efficacy.Results After 6 months of treatment,the vericiguat group showed significant improvements in cardiac structure and function compared to the control group.The left ventricular end-diastolic diameter was significantly reduced[-0.43(-1.00,-0.10)mm vs.-0.22(-0.53,0.02)mm,P=0.002],and the LVEF was significantly increased[8.45％(1.40％,16.50％)vs.2.75％(0,11.00％),P=0.002].The percentage of patients in the vericiguat group who achieved LVRR was significantly larger than in the control group(46.4％vs.27.4％,P=0.011).Multivariate logistic regression revealed that the combination of vericiguat was an independent predictor of LVRR(Model 2:OR=2.54,95％CI:1.29～5.01,P=0.007).The reverse remodeling effect remained consistent across different subgroups and was not significantly influenced by specific baseline characteristics(Pinteraction>0.05).Vericiguat did not affect blood pressure,liver and kidney function,or electrolyte levels,achieving satisfactory safety,despite its significantly higher incidence of gastrointestinal reactions(16.1％vs.5.7％,P<0.001).Conclusion The addition of vericiguat to the quadruple therapy significantly improves cardiac function and promotes left ventricular reverse remodeling in HFrEF patients while maintaining a favorable safety profile.

Objective:To construct a mindfulness based cancer rehabilitation training program for patients with malignant hematologic diseases based on the Liverpool mindfulness model, providing practical guidance for improving their physical and mental symptoms.Methods:The system searched for relevant literature on the application of mindfulness intervention in patients with malignant hematological diseases retrieved from Cochrane Library, PubMed, CINAHL, PsycInfo, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. The search period was from January 1, 1982 to December 26, 2023. Using the Liverpool mindfulness model as the theoretical framework, based on the literature review, group meetings and semi-structured interviews, a preliminary draft of a mindfulness cancer rehabilitation training program for patients with malignant hematologic diseases was developed. After 2 rounds of Delphi expert consultation, the final version of the intervention plan was determined.Results:Among the 19 experts, there were 4 males and 15 females, aged 30-61 (47.11 ± 7.64) years old. The effective recovery rates of the two rounds of expert inquiry questionnaires were both 19/19, and the expert authority coefficients were both 0.88. The Kendall coordination coefficients for the two rounds of inquiry were 0.214 and 0.220, respectively ( χ2=77.37, 108.66, both P<0.01).A mindfulness based cancer rehabilitation training program for patients with malignant hematologic diseases was ultimately developed, including intervention subjects, intervention personnel, intervention sites and forms, intervention timing, intervention intensity, intervention process and training theme content. Conclusions:The mindfulness based cancer rehabilitation training program for patients with malignant hematologic diseases constructed based on the Liverpool mindfulness model is necessary, scientific, and clinically suitable, and can provide a basis for clinical psychological nursing practice for patients with malignant hematologic diseases.

Objective To analyze the target,signal pathway and potential mechanism of Banxia Baizhu Tianma Decoction in the treatment of epilepsy based on network pharmacology,and to verify it by molecular docking technology and animal experiments.Methods The active ingredients and drug targets of Banxia Baizhu Tianma Decoction were screened by BATMAN and other databases.The targets of epilepsy-related diseases were obtained by GeneCards and other databases,and the intersection targets were taken.Constructing'drug-ingredient-target-disease'network and PPI network to screen the core targets.The core active ingredients were screened according to GO,KEGG functional enrichment analysis and'pathway-target-active ingredient'network.Molecular docking was used to verify the core targets and core active ingredients.In the animal experiment,the rat model of epilepsy was induced by lithium chloride-pilocarpine,and 40 Wistar rats were divided into normal control group,model control group,carbamazepine group and Banxia Baizhu Tianma Decoction group.The seizures were observed by behavior.Nissl staining was used to observe neuronal damage in hippocampus.Immunohistochemistry was used to detect the expression of BAX,BCL-2 and Caspase-3 protein.Results A total of 1072 targets of Banxia Baizhu Tianma Decoction were screened,1046 disease targets of epilepsy were screened,and 220 intersection targets of Banxia Baizhu Tianma Decoction in the treatment of epilepsy were screened.The core targets AKT1,ALB,ACTB,INS and TNF of PPI network were obtained.KEGG pathway mainly involves TNF signaling pathway,IL-17 signaling pathway,cAMP signaling pathway,pathways of neurodegeneration-multiple diseases,serotonergic synapse and Dopaminergic synapse.The core active ingredients with the highest correlation in the'pathway-target-active component'network were Betulin,Ephedrine,Ergotamine and Thymol.Results of molecular docking indicated that the core target had satisfactory affinity with those active ingredients.Animal experiments showed that Banxia Baizhu Tianma Decoction could effectively reduce epileptic seizures in rats,improve hippocampal neuronal damage in rats,significantly reduce the percentage of neuronal apoptosis,significantly down-regulate the expression of pro-apoptotic proteins BAX and Caspase-3,and up-regulate the expression of anti-apoptotic protein BCL-2.Conclusion Banxia Baizhu Tianma Decoction has the characteristics of multi-component,multi-target and multi-pathway in the treatment of epilepsy.Inhibiting neuronal apoptosis and reducing hippocampal neuronal damage may be one of the important mechanisms for its treatment of epilepsy.

A 58-year-old female patient presented with red papules, plaques, and scabs on her right foot accompanied by pain and itching for 14 years. Dermatological examination revealed extensive red plaques on her right foot and ankle, with scattered red papules in between; some of the plaques were covered with a moderate amount of yellow-brown crusts, and a small amount of yellow exudate was observed at the junction of the toes and the dorsum of the foot. Histopathological examination of the skin lesions showed hyperkeratosis, parakeratosis, pseudoepitheliomatous hyperplasia, neutrophil aggregation in the epidermis, and mixed inflammatory cell infiltration in the dermis. Three different types of colonies were cultured from the skin lesion tissues: light brown granular colonies, black granular colonies, and white-brown filamentous colonies. Under the microscope, the filamentous colonies appeared as long chains of brown conidia with short cylindrical beaks, while the black and light brown granular colonies appeared as clusters of spores, with single or multiple septa inside, and some budding spores were observed. Electron microscopy further confirmed the above structures. Molecular biological analysis revealed that the three types of colonies were all identified as Alternaria alternata. The patient was diagnosed with cutaneous alternariosis caused by Alternaria alternata with special morphology. After 7 months of treatment with oral itraconazole, the skin lesions healed, and no recurrence was observed during a 3-year follow-up.

Objective:To identify independent risk factors for early recurrence following curative resection of resectable pancreatic cancer and establish a nomogram prediction model.Methods:Clinical data from 405 patients with resectable pancreatic cancer treated at Renji Hospital, Shanghai Jiao Tong University School of Medicine from February 2010 to December 2020 were retrospectively reviewed. Patients were stratified into a training cohort (265 patients form February 2010 to December 2018) and a validation cohort (140 patients from January 2019 to December 2020) based on surgery dates. Optimal cutoff values for clinical variables were determined using X-tile software. Independent risk factors were identified through univariate and multivariate Cox proportional hazards regression analyses. Kaplan-Meier curves for recurrence-free survival (RFS) were generated across subgroups, and a nomogram was developed to predict early recurrence (within 1 year post-surgery). Time-dependent receiver operating characteristic (tROC) curves was drawn and area under the curve (AUC) metrics were utilized to evaluate predictive accuracy, while model reliability was assessed by calibration curves. Individualized risk scores derived from the nomogram were stratified into high- and low-risk groups using X-tile-derived cutoff values. Survival differences between groups were analyzed via log-rank tests. The clinical application value was judged by decision curve analysis (DCA) compared to TNM staging. Results:In the training cohort, 139 patients (52.45%) experienced early recurrence, with a median RFS of 11.1 months [interquartile range ( IQR): 6.0-26.0]. The validation cohort reported 70 early recurrences (50.00%) and a median RFS of 11.8 months ( IQR: 4.9-21.4). Univariate analysis revealed significant associations between early recurrence and tumor diameter, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), systemic immune-inflammation index (SⅡ), and prognostic nutritional index (PNI). Multivariate analysis identified tumor diameter ≥3.75 cm ( HR=1.718, 95% CI 1.223-2.412, P=0.002), CA19-9≥218 U/ml ( HR=1.567, 95% CI 1.107-2.220, P=0.011), CA125≥20.98 U/ml ( HR=2.501, 95% CI 1.768-3.539, P<0.001), SⅡ≥388.28 ( HR=1.708, 95% CI 1.096-2.662, P=0.018), and PNI<53.18 ( HR=0.596, 95% CI 0.404-0.879, P=0.009) as independent risk factors for early recurrence. The nomogram achieved AUC values of 0.771 and 0.708 in the training and validation cohorts, respectively. Calibration curves demonstrated strong agreement between predicted and observed survival probabilities. Kaplan-Meier analysis revealed significantly lower 1-year RFS rates in high-risk versus low-risk groups for both cohorts (training: HR=3.65, 95% CI 2.45-5.44, P<0.001; validation: HR=2.37, 95% CI 1.39-4.06, P=0.001). DCA indicated superior net benefit of the nomogram over TNM staging across threshold probabilities of 0.2-0.9. Conclusions:The proposed nomogram effectively integrates clinical and serological biomarkers to preoperatively assess early recurrence risk in resectable pancreatic cancer patients, offering enhanced precision for clinical decision-making.

Objective To explore the clinical significance of pulse pressure variability(PPV)in early prevention and diagnosis of prostate resection syndrome by observing the changes in PPV during transurethral resection of the prostate.Methods Eighty patients undergoing transurethral resection of the prostate(TURP)under general anesthesia from March to April 2023 were randomly divided into a control group and an observation group,with 40 patients in each group.The control group underwent routine monitoring of invasive blood pressure,while the observation group continued to monitor PPV in addition to invasive blood pressure monitoring.Observe and record the hemodynamic parameters,electrolyte Na+,K+,CL-,Changes in hemoglobin(Hb)and hematocrit(Hct),recording surgical time,intraoperative lavage fluid dosage,and occurrence of dilutive hyponatremia(TURS).Results One patient in the observation group experienced two unexplained drops in blood pressure and heart rate during surgery,and was diagnosed with TURS based on blood gas analysis.Among them,the observation group showed a decreasing trend in PPV with the prolongation of surgery time.PPV gradually decreased at 45～60 minutes after surgery,and at 90 minutes after surgery,PPV decreased significantly compared to preoperative levels.Among them,6 patients had a 50%decrease in PPV compared to preoperative levels.For patients with significantly reduced PPV,immediate treatment was given 10～20 mg of furosemide and 10 mg of dexamethasone.By the end of surgery,PPV had basically recovered to preoperative levels.Both groups of patients showed varying degrees of decrease in Na+,K+,Hct,and Hb levels.Conclusions PPV can reflect the volume status of patients.When PPV decreases by more than 50%compared to preoperative levels and there are unexplained hemodynamic changes and abnormal clinical manifestations during surgery,it is necessary to be vigilant and handle them promptly to reduce and prevent the occurrence of TURS.