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 evaluate the stability of tick-borne encephalitis inactivated vaccine(0. 5 mL/dose) with pre-pottingsyringe in order to ensure the effectiveness and safety of the product. Methods The optimized stock solution of tick-borneencephalitis inactivated vaccine(0. 5 mL/dose, pre-potting syringe) was stored at(5 ± 3) ℃ for 120 days. The indicators ofsterility, antigen content, protein content, bovine serum albumin residue and hamster kidney cell protein residue weredetected and compared with those of vaccine before optimization(0. 1 mL/dose, vial). The long-term stability(0-33 monthsat 2-8 ℃), accelerated stability [0, 3, 6 months at(25 ± 2) ℃] and accelerated destruction stability [0, 7, 14 days at(37 ±1) ℃] of the optimized tick-borne encephalitis inactivated vaccine were investigated according to the relevant requirements ofTechnical Guidelines for Stability Research of Biological Products, including appearance, titer, aluminum content, osmoticmolar concentration and other indicators. Results Before and after optimization, all indicators of the stock solution of tick-borne encephalitis inactivated vaccine were qualified. There was no statistically significant difference in bovine serumalbumin residue and hamster kidney cell protein residue(F = 3. 33 and 0. 61, P = 0. 077 and 0. 627, respectively), but theF P differenceofproteincontentwasstatisticallysignificant(=38.07,<0.05),whileallofthemwerewithinthestandard rangeof ≤ 80 μg/mL. After optimization, the indicators of long-term stability, accelerated stability and accelerated destructionstability of the finished product of tick-borne encephalitis inactivated vaccine were all qualified. In the tests of long-termstability, respectively the vaccine titer after optimization was significantly higher than that before optimization(F = 62. 32,P < 0. 05); the differences of osmotic pressure molar concentration were statistically significant(F = 40. 47 and 12. 50 respec-tively, each P < 0. 05), but the fluctuation was controlled within the standard range of 240-320 mOsmol/kg. Conclusion Tick-borne encephalitis inactivated vaccine(0. 5 mL/dose) with pre-potting syringe has good stability under the conditions of long-term storage, transportation and short-term overtemperature, and its quality meets the standard.

OBJECTIVE To study the effects and mechanism of Portulaca oleracea cream on skin pruritus and barrier function in allergic contact dermatitis （ACD） mice. METHODS Low-concentration and high-concentration P. oleracea creams were prepared， with the P. oleracea extract solution （1 g/mL， calculated by crude drug） concentrations of 10% and 20%. Sixty BALB/c mice were randomly allocated into blank group， model group， Mometasone furoate cream group （positive control）， blank matrix cream group， P. oleracea low-concentration and high-concentration cream groups. Except for blank group， ACD model was induced in each group using 2，4-dinitrochlorobenzene solution. The blank group and model groups received normal saline， while the remaining groups were treated with their respective creams， once a day， at a dose of approximately 0.5 g per application， continuously for 14 days. At 24 h post-final administration， skin lesions of mice were observed and scored； pathological changes of skin tissue were observed； serum levels of immunoglobulin E（IgE） and tumor necrosis factor-α （TNF-α） were quantified. mRNA expression of MAS-related G protein-coupled receptors （including MrgprA3， MrgprC11， and MrgprD） in dorsal root ganglion （DRG） was assessed； while protein expressions of skin barrier function-related proteins Claudin-1 and Occludin in skin tissues were determined. RESULTS Compared with blank group， mice in the model group exhibited severe skin damage， characterized by loss of epidermal architecture， hyperkeratosis of the skin tissue， and the infiltration of a large number of inflammatory cells. The skin injury scores， as well as the serum levels of IgE and TNF-α， and the mRNA expression levels of MrgprA3， MrgprC11， and MrgprD in DRG， were all significantly elevated compared to the blank group （P＜0.05 or P＜0.01）； in contrast， the protein expression levels of Claudin-1 and Occludin in the skin tissue were markedly reduced （P＜0.05）. Compared with model group， mice in P. oleracea low-concentration and high- concentration cream groups demonstrated significant alleviation of skin damage， as evidenced by reduced epidermal hyperplasia， mitigated spongiosis in the dermis， and decreased infiltration of inflammatory cells； these quantitative indicators were almost significantly reversed （P＜0.05 or P＜0.01）. No significant differences were observed in the aforementioned skin injuries， pathological alterations， or quantitative indicators between the blank matrix cream group and the model group. CONCLUSIONS P. oleracea may ameliorate skin lesions and restore skin barrier function of ACD mice， the mechanism of which may be associated with downregulating mRNA expressions of MrgprA3， MrgprC11 and MrgprD in DRG， and up-regulating the protein expressions of Claudin-1 and Occludin in skin tissue.

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.

Polygonatum sibiricum polysaccharide(PSP)is a polysaccharide with multiple pharma-cological activities that has been widely studied and used in the human body.However,there is cur-rently a lack of research investigating the potential advantages of PSP in poultry farming.This study investigated the effects of adding PSP to drinking water on the growth performance,antioxi-dant status,serum biochemical indicators,ileal tissue morphology,immune organs,and intestinal function of chicks.88 Hailan brown laying hens were randomly divided into 4 groups,with 22 hens in each group,namely the blank control group(CON),and fed with basic feed;The low-dose PSP group(250 mg/L),the medium dose PSP group(500 mg/L),and the high-dose PSP group(1 000 mg/L)were fed with corresponding doses of PSP through drinking water on the basis of basic feed,and the experimental period was 21 d.The initial and final body weight and immune or-gan relative quality of chicks,serum biochemical indicators,the activities of SOD,CAT,and GSH-Px,as well as the contents of T-AOC and MDA in the serum of chicks were measured;HE stai-ning method was used to observe the pathological changes of intestinal tissue slices in the ileum;Real time fluorescence quantitative PCR technology was used to detect the mRNA expression lev-els of cytokines ZO-1,Claudin-1,Occludin,Mucin-2,IL-1β,TNF-a,IFN-γ,IL-4,IL-8,and IL-10 in the ileum.The results showed that compared with the blank control group,the addition of medium dose PSP significantly increased the final relative quality(P＜0.01),the final body weight and ADG of PSP500 group chicks significantly increased(P＜0.01),and the F/G of PSP250 and PSP500 groups significantly decreased(P＜0.05 or P＜0.01).The villus height of the jejunum in the 200,500,and 1 000 mg/L PSP groups of chicks significantly increased(P＜0.05).The SOD ac-tivity significantly increased(P＜0.01),and the CAT activity in the PSP1000 group significantly increased(P＜0.01).The PSP500 and PSP1000 groups significantly reduced the mRNA expression of cytokines IL-1β,IL-4,and IFN-γ in the ileum(P＞0.05);PSP did not show significant changes in serum total protein(TP),albumin(ALB),glucose(GLU),cholesterol(T-CHO)content,and immune organ index(P＜0.05).In summary,PSP can improve growth performance,enhance an-tioxidant capacity,improve ileal morphology and epithelial barrier function,and regulate mucosal immune status.Considering the overall economic benefits,the recommended level of PSP addition is 500 mg/L.

OBJECTIVE: To compare the effects of different chest compression rates (60-140 times/min) on hemodynamic parameters, return of spontaneous circulation (ROSC), resuscitation success, and survival in a porcine model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). METHODS: Forty healthy male domestic pigs were randomly divided into five groups based on chest compression rate: 60, 80, 100, 120, and 140 times/min (n = 8). All animals underwent standard anesthesia and tracheal intubation. A catheter was inserted via the left femoral artery into the thoracic aorta to monitor aortic pressure (AOP), and another via the right external jugular vein into the right atrium to monitor right atrial pressure (RAP). In each group, animals were implanted with a stimulating electrode via the right external jugular vein to the endocardium, and ventricular fibrillation (VF) was induced by delivering alternating current stimulation, resulting in CA. After a 1-minute, manual chest compressions were performed at the assigned rate with a compression depth of 5 cm. The first defibrillation was delivered after 2 minutes of CPR. No epinephrine or other pharmacologic agents were administered during the entire resuscitation process. From 1 minute before VF induction to 10 minutes after ROSC, dynamic monitoring of AOP, coronary perfusion pressure (CPP), and partial pressure of end-tidal carbon dioxide (P_ETCO₂). Cortical ultrastructure was examined 24 hours post-ROSC using transmission electron microscopy. RESULTS: With increasing compression rates, both the total number of defibrillations and cumulative defibrillation energy significantly decreased, reaching their lowest levels in the 120 times/min group. The number of defibrillations decreased from (4.88±0.83) times in the 60 times/min group to (2.25±0.71) times in the 120 compressions/min group, and energy from (975.00±166.90)J to (450.00±141.42)J. However, both parameters increased again in the 140 times/min group [(4.75±1.04)times, (950.00±207.02)J], the differences among the groups were statistically significant (both P < 0.01). As compression frequency increased, P_ETCO₂, pre-defibrillation AOP and CPP significantly improved, peaking in the 120 times/min group [compared with the 60 times/min group, P_ETCO₂ (mmHg, 1 mmHg≈0.133 kPa): 18.69±1.98 vs. 8.67±1.30, AOP (mmHg): 95.13±7.06 vs. 71.00±6.41, CPP (mmHg): 14.88±6.92 vs. 8.57±3.42]. However, in the 140 times/min group, these values declined significantly again [P_ETCO₂, AOP, and CPP were (10.59±1.40), (72.38±11.49), and (10.36±4.57) mmHg, respectively], the differences among the groups were statistically significant (all P < 0.01). The number of animals achieving ROSC, successful resuscitation, and 24-hour survival increased with higher compression rates, reaching a peak in the 120 times/min group (compared with the 60 times/min group, ROSC: 7 vs. 2, successful resuscitation: 7 vs. 2, 24-hour survival: 7 vs.1), then decreased again in the 140 times/min group (the animals that ROSC, successfully recovered and survived for 24 hours were 3, 3, and 2, respectively). Transmission electron microscopy revealed that in the 60, 80, and 140 times/min groups, nuclear membranes in cerebral tissue were irregular and incomplete, nucleoli were indistinct, and mitochondria were swollen with reduced cristae and abnormal morphology. In contrast, the 100 times/min and 120 times/min groups exhibited significantly attenuated ultrastructural damage. CONCLUSIONS Among the tested chest compression rates of 60-140 times/min, a chest compressions frequency of 120 times/min is the most favorable hemodynamic profile and outcomes during CPR in a porcine CA model. However, due to the wide spacing between groups, further investigation is needed to determine the optimal compression rate range more precisely.
Animals ; Cardiopulmonary Resuscitation/methods* ; Swine ; Male ; Heart Arrest/therapy* ; Heart Massage/methods* ; Hemodynamics

Objective To develop a machine learning model integrating preoperative chest CT radiomic features with clinical data for predicting 5-year postoperative recurrence risk in stage Ⅰ non-small cell lung cancer(NSCLC)patients undergoing surgical resection.Methods A total of 217 patients with pathologically confirmed stage Ⅰ NSCLC(selected from 778 initially screened cases based on our inclusion and exclusion criteria)treated in Army Medical Center of PLA between January 2014 and December 2019 were retrospectively enrolled,including 53 recurrence cases and 164 non-recurrence cases within 5-year follow-up.They were randomly divided into a training set(n=173)and a validation set(n=44)in a ratio of 8:2.Radiomic models were established based on extracted features from tumor-dominant regions of interest(ROI)on CT images,while clinical models were developed using demographic characteristics and preoperative laboratory examinations.A combined model was further constructed by integrating both feature sets,and model performance was compared to identify the optimal predictive model.Results This study screened the features from non-contrast CT images and ultimately selected 7 radiomic features for constructing radiomic model.Among 6 machine learning algorithms,the adaptive boosting(Adaboost)model demonstrated the best overall predictive performance,with an area under the curve(AUC)of 0.866(95%CI:0.808～0.923;accuracy:0.832,specificity:0.884)in the training set and of 0.806(95%CI:0.630～0.983;accuracy:0.795,specificity:0.971)in the validation set.Univariate and multivariate logistic regression analyses identified 4 clinical features for clinical model construction.The clinical model achieved an AUC value of 0.874(95%CI:0.821～0.928;accuracy:0.827,specificity:0.891)in the training set and 0.813(95%CI:0.677～0.948;accuracy:0.636,specificity:0.600)in the validation set.By integrating the 7 radiomic features and 4 clinical features using a feature-level fusion strategy,the combined model exhibited further improved predictive performance,with an AUC value of 0.953(95%CI:0.924～0.983;accuracy:0.884,specificity:0.860)and 0.852(95%CI:0.729～0.976;accuracy:0.682,specificity:0.629),respectively in the training set and the validation set.Conclusion The combined model integrating preoperative CT radiomic features with clinical risk factors may provide an evidence-based framework for evaluating 5-year postoperative recurrence risk in stage Ⅰ NSCLC patients.

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 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.