ObjectiveTo investigate the mechanism of topical treatment of allergic contact dermatitis （ACD） mice with Portulacae Herba based on the nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/nuclear factor-κB （NF-κB） signaling pathway. MethodsA total of 70 6-week-old specific pathogen free （SPF） female Kunming mice were adaptively fed for 1 week and randomly divided into blank group， model group， compound dexamethasone acetate cream group （2.075×10^-2 g·g^-1）， blank matrix cream group， low-dose Portulacae Herba cream group （0.1 g·g^-1）， high-dose Portulacae Herba cream group （0.2 g·g^-1）， and Portulacae Herba + inhibitor group （0.2 g·g^-1 + 30 mg·kg^-1 ML385）， with 10 mice in each group. One day before the experiment， the mice were shaved on the neck and back. Except for the blank group， the mice in the other groups were treated with 2，4-dinitrochlorobenzene （DNCB） to establish an ACD model. After respective administration， the skin lesion of the mice was scored， and the histopathological changes of the skin were stained with hematoxylin-eosin （HE）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， reactive oxygen species （ROS）， superoxide dismutase （SOD） activity， and malondialdehyde （MDA） in serum of mice. The expression of Nrf2/HO-1/NF-κB signaling pathway-related proteins in mouse skin tissue was detected by immunohistochemistry （IHC）， Western blot， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， the mice in the model group had an increased skin lesion score （P<0.01）， severe pathological damage to skin tissue， increased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and decreased content of SOD （P<0.01）. In addition， the mRNA and protein expression levels of Nrf2， HO-1， and nuclear factor-κB inhibitor α （IκBα） in skin tissue were up-regulated （P<0.01）， while the protein expression levels of phosphorylated （p）-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.01）. Compared with the model group and the blank matrix cream group， the mice treated with Portulacae Herba had a decreased skin lesion score （P<0.01）， reduced pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and increased content of SOD （P<0.01）. Additionally， the mRNA and protein expression levels of Nrf2， HO-1， and IκBα in skin tissue were down-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were up-regulated （P<0.05，P<0.01）. Compared with the Portulacae Herba + inhibitor group， the high-dose Portulacae Herba cream group had a decreased skin lesion score （P<0.01）， alleviated pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in the serum of mice （P<0.05，P<0.01）， and increased content of SOD （P<0.01）. The protein expression levels of Nrf2， HO-1， and IκBα and the mRNA expression of Nrf2 and HO-1 in skin tissue were up-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.05）. ConclusionPortulacae Herba can improve DNCB-induced ACD skin damage in mice by regulating the Nrf2/HO-1/NF-κB signaling pathway.

Objective To analyze the effect of graded exercise rehabilitation in patients with acute exacerbation of chronic obstructive pulmonary disease,and to provide references for clinical nursing practice.Methods A total of 70 patients with acute exacerbation of chronic obstructive pulmonary disease who met the criteria in the Department of Respiratory Medicine of a tertiary hospital in Zunyi City from September to December 2023 were randomly divided into an experimental group and a control group(with 35 cases in each group).The experimental group implemented graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines,and the control group implemented routine exercise rehabilitation.After intervention,the lung function,blood gas analysis,oxygenation index,6 min walking test and the incidence of complications related to non-invasive mechanical ventilation were compared between the 2 groups.Results Finally,34 cases were included in the experimental group and 35 cases in the control group.After intervention,the forced expiratory volume in the first second of the experimental group was improved compared with the control group(P＜0.05).The 6-minute walking test of the experimental group was higher than that of the control group(P＜0.05).The total incidence of non-invasive mechanical ventilation-related complications in the experimental group was lower than that in the control group(P＜0.05).There was no significant difference in blood gas analysis and oxygenation index between the 2 groups(P＜0.05).Conclusion The implementation of graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines can help patients with acute exacerbation of chronic obstructive pulmonary disease improve their respiratory function,improve their exercise endurance,and reduce non-invasive mechanical ventilation-related complications.

Objective:To assess the safety and efficacy of thiotepa, busulfan, and etoposide (TBE) conditioning followed by autologous hematopoietic stem-cell transplantation (TBE auto-HSCT) in primary central nervous system lymphoma (PCNSL) patients.Methods:Clinical data from 27 PCNSL patients who received TBE auto-HSCT at the Fifth Medical Center of PLA General Hospital between November 1, 2021, and April 30, 2024, were retrospectively analyzed.Results:Twenty-seven patients [16 males, 11 females; median age 57 (23–72) years] were included, with 12 (44.4%, 12/27) over 60. Twenty-five had newly diagnosed PCNSL and 2 were relapsed. Median time from diagnosis to transplantation was 6.9 (5.0–10.0) months. TBE auto-HSCT increased complete remission (CR) rate from 63.0 to 96.3% ( P= 0.005), and 9 of 10 patients in partial remission achieving CR post-transplant. Median follow-up was 24.5 months (range 2.0–36.0). Two-year progress-free and OS rates were (87.2±6.9) % and (88.6±6.2) %, respectively. Common grade 3 nonhematologic adverse events were diarrhea (18.5%, 5/27) and bacterial infections (14.8%, 4/27). One patient (64 years old) died from carbapenem-resistant Enterobacteriaceae infection within 2 months post-transplant, yielding a 100-day treatment-related mortality of 3.7% (1/27) . Conclusion:TBE-conditioned high-dose chemotherapy with auto-HSCT is effective, safe, and well-tolerated in PCNSL patients, including the elderly.

Objective:To identify and validate secreted effector proteins of Chlamydia psittaci ( C. psittaci) through bioinformatic prediction and experimental verification, and to characterize their subcellular localization in host cells. Methods:Potential effector proteins were predicted using bioinformatics tools. Candidate effectors were fused to β-lactamase through the constructed expression vectors, and these vectors were transformed into C. psittaci. The secretion of these candidate effectors was evaluated by β-lactamase translocation assays. Eukaryotic expression vectors of confirmed effectors were transfected into host cells to determine their intracellular localization patterns. Results:Bioinformatic analysis identified 29 candidate effector proteins. Experimental validation confirmed the secretion of five effectors, with four exhibiting cytoplasmic localization and one displaying nuclear localization in host cells.Conclusion:This study characterizes five novel C. psittaci secreted effector proteins, providing critical insights for investigating the molecular pathogenesis of psittacosis.

This study aims to explore protective effects of Lycium barbarum polysaccharides(LBP)on intestinal damage caused by lipopolysaccharide(LPS)-induced inflammatory bowel disease(IBD)in chicks.Network pharmacology was initially employed to determine the target proteins of wolfberry in the prevention and treatment of IBD.Following this,protein-protein interaction analy-sis,GO and KEGG pathway enrichment analysis,and molecular docking studies were conducted.Subsequently,an animal study was conducted:a total of 100 one-day-old male Hy-line brown lay-ing hens were randomly divided into five groups:a blank control group(CON),an LPS treatment group(LPS),a low-dose LBP group(LPS+LBP 0.25 g/L,L-LBP),a medium-dose LBP group(LPS+LBP 0.5 g/L,M-LBP),and a high-dose LBP group(LPS+LBP 1 g/L,H-LBP).Upon reac-hing 21 days old,duodenal,jejunal,ileal,and cecal tissues were collected to determine SOD and GSH-Px levels.Furthermore,the mRNA expression levels of TNF-α,AKT1,IL-6,IL-1β and TP53 in the intestinal tissues were measured using quantitative real-time PCR.The results demonstrated that network pharmacology identified 45 active ingredients in wolfberry that target 116 key protein sites,including TNF,AKT1 and IL6.The primary objectives focus on signaling pathways including AGE-RAGE,IL-17,TNF,HIF-1,and NF-κB.Molecular docking showed excellent ligand-receptor docking scores,with stable binding facilitated by hydrogen bonds and hydrophobic interactions.Compared to the LPS group,the 0.5 g/L LBP exhibited notably higher levels of SOD and T-AOC.In comparison with the LPS group,the medium and high-dose LBP experimental groups showed notably decreased the mRNA expressions of TNF-α,AKT1,IL-6,and IL-1β,while TP53 mRNA expression was significantly upregulated(P＜0.01).In summary,wolfberry exerts preventive and therapeutic effects on IBD through a multi-component,multi-target,and multi-pathway mecha-nism.

Objective The mechanism of Huazhuo xingxue decoction(HZXXD)in the treatment of ischemic stroke was explored through network pharmacology,molecular docking and cell validation.Methods TCMSP,TCMID,BATMAN-TCM database and literature search were used to get the chemical components and related target proteins of Huazhuo Xingxue Decoction,and the targets of dementia,stroke and amnesia were obtained from Genecards database and OMIM database.The traditional Chinese medicine-active components-target-network and protein interaction map were constructed by using Cytoscape,and the target was enriched by KEGG pathway by David database.Western blot was used to investigate the effect of HZXXD on inflammation-related core targets expression using oxygen and glucose deprivation/reoxygenation cell model.Finally,Autodock was used for molecular docking of key active ingredients and important targets to evaluate their binding activity.Results 76 active molecules and 33 common targets of herb-disease were screened out.KEGG bioaccumulation results involve multiple inflammatory signal pathways such as TNF,chemical carcinogenesis-reactive oxygen species and HIF-1.TNF-α was found to be the core target of HZXXD by oxygen glucose deprivation/reoxygenation cell experiments.Five compounds with the strongest binding ability to TNF-α,kaempferol,apigenin,aloe-emodin,baicalein and stigasterol,were screened by traditional Chinese medicine-active ingredient-target network map and molecular docking.Conclusion Huazhuo Xingxue Decoction may down regulate the expression of core target TNF-α,kaempferol,apigenin,aloe emodin,baicalein and stigasterol may be the main active substances for TNF-α binding.

Objective:To analyze the clinical characteristics of warfarin-related nephropathy (WRN).Methods:Medical records of patients with WRN admitted to Linyi People′s Hospital Affiliated to Shandong Second Medical University from January 1, 2020 to December 31, 2024 were collected. The patients′ basic information (gender, age), warfarin medication details (indications, dosage, frequency, etc.), comorbidities, concomitant medication usage, international normalized ratio (INR) and serum creatinine (Scr) test results before and after the occurrence of WRN, as well as the clinical manifestations, interventions, and outcomes of WRN were extracted. The causal relationship between warfarin and renal dysfunction was evaluated according to the Adverse Drug Reaction Reporting and Monitoring Manual. The clinical data of patients were descriptively and statistically analyzed. Results:A total of 11 patients were entered in the analysis, including 7 males and 4 females; the age ranged from 49 to 85 years, with a median age of 70 years, and 9 cases were older than 60 years. The causality evaluation showed that 3 patients were definite and 8 patients were probable. All the 11 patients had at least one comorbidity, including 6 cases of heart failure, 6 cases of hypoproteinemia, 4 cases of chronic kidney disease, 3 cases of hypertension, 3 cases of pulmonary infection, and 1 case of diabetes. Seven patients were treated with warfarin combined with broad-spectrum antibiotics, 6 combined with diuretics, and 3 combined with renin angiotensin system blockers. The time from the highest INR to the highest Scr level was 0-6 days, with a median time of 2 days, and it was ≤2 days in 9 patients. Six patients had bleeding manifestations such as microscopic hematuria, melena, epistaxis, hematochezia, and skin ecchymosis. Among the 11 patients, 10 stopped warfarin immediately and 1 reduced dosage. All patients received different doses of vitamin K 1 according to the INR level. Among the 6 patients of bleeding, 4 received symptomatic treatments such as omeprazole, tranexamic acid, somatostatin, thrombin powder and octreotide, and 2 patients received hemodialysis due to high Scr level. One patient with severe anemia received blood transfusion. After 1-5 days of treatments (with a median time of 2 days), the INR in all patients decreased to <3.00, of which 5 patients continued to take warfarin, 1 changed warfarin to rivaroxaban, and 5 did not continue anticoagulation therapy. After 2 to 14 days of treatments, Scr in 8 patients recovered to the reference value range, and Scr in 3 patients was still at a high level, of which 1 patient died of unexplained cardiac arrest. Conclusions:WRN is a common adverse reaction of warfarin, with or without bleeding. After the occurrence of WRN, the drug should be stopped as soon as possible and symptomatic treatment should be given. The prognosis is generally good, but it may also lead to chronic kidney disease.

Objective:To explore the relationship between early fecal calprotectin (FC) level and the long-term efficacy of infliximab (IFX) in the treatment of Crohn′s disease (CD) and predictive the value.Methods:From January 2018 to December 2023, at the First Affiliated Hospital with Nanjing Medical University, the clinical data of patients with moderate-to-severe CD who received IFX as first-line therapy were retrospectively collected. The main outcomes were clinical and endoscopic remission at week 52 after IFX treatment, and the secondary outcome was clinical response at week 14 after IFX treatment. The predictive value of FC levels at week 0 (at baseline when first administered) and week 14 of treatment was evaluated for the clinical and endoscopic remission at week 52 after IFX treatment. Multivariate logistic regression was performed to investigate the factors predicting endoscopic remission. The optimal cutoff value was calculated, model was established, the data was divided into training set and validation set at a ratio of 7∶3 using the random number table method and the corresponding column chart was drawn. Receiver operating characteristic curve (ROC) and calibration curve were used to evaluate the discrimination and calibration of the model, respectively. Mann-Whitney U test was used for statistical comparison. Results:A total of 165 patients with CD were enrolled, of whom 150 cases (90.9%) achieved clinical response after induction therapy, and 15 cases (9.1%) were primary non-response. Among the 150 patients with clinical response, 112 cases (74.7%) achieved clinical remission at week 52 after treatment, while 38 cases (25.3%) did not achieve clinical remission. Endoscopic evaluation was performed at week 52 after treatment in 139 patients, of whom 54 cases (38.8%) achieved endoscopic remission and 85 cases (61.2%) did not. At week 14 of treatment, there was no statistically significant difference in FC level between the patients achieved and did not achieve clinical response (263.24 (93.96, 675.28) μg/g vs. 556.35 (245.77, 953.56) μg/g, P>0.05). At week 52 after treatment, the FC level of patients who achieved clinical remission was lower than that of patients did not achieve(103.20(44.11, 456.57) μg/g vs. 531.26(222.06, 998.40) μg/g) and the decreased value of FC at week 52 and week 0 after treatment of patients achieved clinical remission was more than that of patients did not achieve clinical remission (443.34 (82.25, 788.95) μg/g vs. 269.91 (-79.20, 522.54) μg/g), and the differences were statistically significant ( U=1 078.00, 2 677.00; P<0.001, =0.018). At week 52 after treatment, the FC level of patients achieved endoscopic remission was lower than that of patients did not achieve endoscopic remission (52.80(31.93, 83.47) μg/g vs. 506.18(217.44, 778.02) μg/g), and the decreased value of FC at week 52 and week 0 after treatment of patients achieved endoscopic remission was more than that of patients did not achieve endoscopic remission (428.85(140.20, 863.60) μg/g vs. 309.61(-62.37, 683.82) μg/g), and the differences were statistically significant ( U=500.00, 2 812.00; P<0.001, =0.025). The FC level at week 14 of treatment could predict the clinical and endoscopic remission at week 52 after treatment (area under the curve (AUC) =0.663, 0.773; 95% confidence interval (95% CI): 0.566 to 0.760, 0.694 to 0.852; P=0.006, <0.001). The optimal cutoff value of FC at week 14 of treatment for predicting endoscopic remission at week 52 after treatment was 246.13 μg/g, with a sensitivity of 0.741 and a specificity of 0.671. The results of multivariate logistic regression analysis revealed that FC ≤ 246.13 μg/g at week 14 of treatment ( OR=4.576, 95% CI: 2.021 to 10.363, P<0.001), baseline albumin ( OR=1.093, 95% CI: 1.006 to 1.188, P=0.035), and baseline platelet-to-lymphocyte ratio (PLR) ( OR=0.995, 95% CI: 0.990 to 1.000, P=0.046) were independent influencing factors of endoscopic remission at week 52 after treatment. A predictive model for endoscopic remission at week 52 after IFX treatment was established based on FC ≤ 246.13 μg/g at week 14 of treatment, baseline albumin and PLR. The results of ROC analysis showed that this model had good discriminative ability, with an AUC of 0.780 (95% CI: 0.700 to 0.878) in the validation set, with a sensitivity of 0.812 and a specificity of 0.760. The results of calibration curve analysis demonstrated that the average absolute error of the prediction model in the validation set was 0.038, and the consistency between the predicted probability and the actual probability was good. Conclusion:FC ≤ 246.13 g/g at week 14 of IFX treatment has good predictive value for endoscopic remission at week 52 after treatment in CD patients.

Objective Traditional methods for sample size estimation in clinical trial do not consider the patient size applicable to the results during the estimation process,and use point estimation for unknown true values of parameters,which has certain limitations in rare disease clinical trials.This article introduces a sample size estimation method based on Bayesian decision theory.Methods This article proposes a Tripartite Balanced Benefit Function(TBBF)and constructs a benefit function model based on the characteristics of acute and chronic diseases.The sample size in clinical trial is determined by maximizing expected benefits.Results The case analysis of hemophilia B demonstrated the application process of the model,and the sample size obtained by maximizing expected benefits is feasible in practical situations.This method has the advantage of being suitable for estimating sample sizes in small sample clinical trials.Conclusion TBBF fully utilizes prior information,incorporates patient size into the estimation process,and makes the quantitative form of different stakeholders'interests clearer,making the decision-making process more scientific and interpretable.

Objective:To investigate the outcomes of natural cycle (NC) and modified natural cycle (MNC) assisted reproductive technology (ART) in patients with diminished ovarian reserve (DOR), and to provide a scientific basis for individualized treatment strategies for DOR patients.Methods:A retrospective cohort analysis was performed on the clinical data of DOR patients who underwent ART at the Center for Reproductive Medicine of the Department of Obstetrics and Gynecology, Peking University Third Hospital from January 1, 2015 to December 31, 2023. Patients were divided into the NC group ( n=801) and the MNC group ( n=385) based on their treatment protocol. The primary outcomes were cycle cancellation rate and oocyte retrieval rate. Secondary outcomes included clinical pregnancy rate and live birth rate per fresh embryo transfer cycle and frozen-thawed embryo transfer cycle, cumulative pregnancy rate and cumulative live birth rate per started cycle and per transfer cycle, as well as laboratory parameters such as the number of retrieved oocytes, the number of two pronuclei (2PN) fertilized oocytes, the number of transferable embryos, and transferable embryo formation rate. Further, multivariate logistic regression was used to analyze the impact of the treatment protocol on pregnancy and live birth outcomes. Results:There were no statistically significant differences between the NC and MNC groups in terms of general characteristics such as age, body mass index, and baseline hormone levels (all P>0.05). The cycle cancellation rate was significantly higher in the NC group [19.10% (153/801)] than in the MNC group [10.65% (41/385), P<0.001], and the oocyte retrieval rate was significantly lower in the NC group [66.31% (431/650)] than in the MNC group [74.86% (259/346), P=0.005]. The number of retrieved oocytes [1 (0,1)], the number of 2PN fertilized oocytes [1 (0,1)], and the number of transferable embryos [0 (0, 1)] were also significantly lower in the NC group than in the MNC group [1 (1, 2), P<0.001; 1 (1, 1), P<0.001; 0 (0, 1), P<0.001]. However, there were no statistically significant differences in 2PN fertilization rate and transferable embryo formation rate between the NC and MNC groups (all P>0.05). In both fresh embryo transfer cycles and frozen-thawed embryo transfer cycles, there were no statistically significant differences in clinical pregnancy rate and live birth rate between the NC and MNC groups (all P>0.05). The cumulative pregnancy rate per started cycle and transfer cycle, the cumulative live birth rate per started cycle and per transfer cycle were also not significantly different between the NC and MNC groups (all P>0.05). Multivariate logistic analysis showed no significant association between NC and clinical pregnancy or live birth compared with MNC. Conclusion:While MNC to some extent reduced the cycle cancellation rate and improved oocyte retrieval rates compared with NC, it did not ultimately improve pregnancy outcomes in DOR patients.