ObjectiveTo explore the mechanism of Shaoyaotang in the prevention and treatment of colitis-associated carcinogenesis （CAC） based on myeloid-derived suppressor cells （MDSCs）-related immunosuppressive microenvironment. MethodsA total of 140 six-week-old SPF FVB male mice were randomly divided into seven groups： Blank group， Shaoyaotang without model group （7.12 g·kg^-1）， model group， sulfasalazine group （0.52 g·kg^-1）， Shaoyaotang low-dose group （3.56 g·kg^-1）， Shaoyaotang medium-dose group （7.12 g·kg^-1） and Shaoyaotang high-dose group （14.24 g·kg^-1）， with 20 mice in each group. The blank control group and the Shaoyaotang without model group received a single intraperitoneal injection of physiological saline （10 mg·kg^-1）， while the other five groups were given a single intraperitoneal injection of azoxymethane （AOM） （10 mg·kg^-1）. After 1 week， the mice were given drinking water containing 2% dextran sulfate sodium （DSS） for 1 week， followed by normal drinking water for 2 weeks. This cycle was repeated three times over a total period of 14 weeks to establish the CAC mouse model. Each group was administered gavage once daily for 2 weeks starting on the 14^th day of the experiment， followed by three times a week until the end of the experiment. The body weight of the mice was recorded weekly. Mice were sacrificed on the 28^th and 98^th days of the experiment. After dissection， the colon length， colon weight， spleen weight， tumor size， and tumor number were measured. Hematoxylin and eosin （HE） staining was used to assess the pathological morphology of colon tumor tissue. Flow cytometry was used to detect MDSCs， regulatory T cells （Tregs）， CD4⁺ T cells， CD8⁺ T cells， and the CD4⁺/CD8⁺ T cell ratio in the spleen. Immunohistochemistry was used to detect the expression levels of programmed cell death protein-1 （PD-1）， programmed cell death ligand 1 （PD-L1）， phosphorylated AMP-activated protein kinase （p-AMPK）， phosphorylated nuclear factor-κB （p-NF-κB）， and hypoxia-inducible factor 1α （HIF-1α） in the colon tissue. ResultsOn day 14， compared with the blank group， the body weight of the model group was significantly reduced （P<0.01）， reaching its lowest point on day 28 （23.39 ± 0.95 ） g. On days 28 and 98， compared with the blank group， the colon length in the model group was significantly shortened （P<0.01）， the colon index significantly increased （P<0.01）， the spleen index significantly increased （P<0.01）， and the tumor load significantly increased （P<0.01）. HE staining showed that in the model group， tumor cells， a large number of inflammatory cell infiltrates， goblet cell disappearance， and crypt loss were observed. In each dose group of Shaoyaotang， the damage to the colonic mucosa， inflammatory cell infiltration， and crypt structure destruction were alleviated. Compared with the model group， the body weight of mice in each dose group of Shaoyaotang increased. On day 98， the colon length was significantly increased （P<0.01）， the colon index significantly decreased （P<0.01）， the spleen index significantly decreased （P<0.01）， and the tumor burden significantly decreased （P<0.01） in each Shaoyaotang dose group. On days 28 and 98， MDSCs and Tregs in the spleen of the medium- and high-dose Shaoyaotang groups were significantly reduced （P<0.01）， while CD4⁺ T cells and the CD4⁺/CD8⁺ T cell ratio were significantly increased （P<0.01）. The proportion of CD8⁺ T cells in the spleen and the expression levels of PD-1 and PD-L1 in the colon tissues of mice in each Shaoyaotang dose group were significantly increased to varying degrees （P<0.05， P<0.01）. On days 28 and 98， the expression of p-AMPK-positive cells in the colon tissue of the medium- and high-dose Shaoyaotang groups was significantly increased （P<0.01）， while the expression of p-NF-κB and HIF-1α was significantly reduced （P<0.01）. ConclusionShaoyaotang can regulate MDSC recruitment and modulate the immune function of T lymphocyte subsets to inhibit the occurrence and development of AOM/DSS-induced CAC in mice. The mechanism may be related to the activation of the AMPK/NF-κB/HIF-1α pathway.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P＞0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P＜0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.

The aim of this study is to explore the immunogenicity of African swine fever virus p37 recombinant protein in mice.C57BL/6J mice were immunized subcutaneously in the abdomen using p37 recombinant protein as antigen.The second immunization was performed 21 d after the first immunization.Serum-specific antibody levels were detected by ELISA;serum cytokine levels were detected using a multifactor assay technique;mice splenic lymphocytes were isolated 7 d after sec-ondary immunization,and the number of splenic lymphocytes secreting IFN-γ after recombinant protein stimulation was detected by ELISpot;and the ratio of CD4+T cells to CD8+T cells was detected by flow cytometry.The results of indirect ELISA showed that p37 recombinant protein could stimulate mice to produce high levels of specific antibodies;ELISpot showed that p37 recom-binant protein could significantly stimulate splenic lymphocytes to produce IFN-γ(P＜0.001)and activate cellular immune responses;the results of flow cytometry showed that it could signifi-cantly stimulate the differentiation of T-lymphocytes to CD4+T-lymphocytes(P＜0.001).In ad-dition,serum levels of IL-2,IL-4,IFN-γ,and TNF-α immune-related cytokines were significantly higher after the second immunization.Immunization of mice with p37 recombinant protein induced strong humoral and cellular immune responses with good immunogenicity,providing reference for the subsequent epitope identification and functional study of p37 protein and the antigen screening of ASF mRNA vaccine.

Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P＞0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P＜0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.

Objective:To explore differences in dose-adjusted plasma concentrations of valproic acid between different valproate formulations in patients with mental disorders based on therapeutic drug monitoring data.Methods:A retrospective analysis was performed; clinical data, including demographic characteristics, therapeutic drug monitoring results, comorbidities, medication details (daily valproic acid dose, concomitant medications), and liver and kidney function indicators, were collected from 633 patients with bipolar disorder or schizophrenia who were hospitalized at Xi'an Mental Health Center and received different valproates from January 2024 to June 2024 (98 patients receiving sodium valproate and 535 receiving magnesium valproate). Clinical data between a sodium valproate group and a magnesium valproate group were compared. Multivariate linear regression was used to identify independent influencing factors for dose-adjusted plasma concentration of valproic acid. Valproic acid daily doses, and plasma concentrations and dose-adjusted plasma concentrations of valproic acid were compared between the two groups, with subgroup analyses conducted by gender and age categories.Results:A total of 658 measurements of plasma valproic acid concentration were obtained in 633 patients, including 104 measurements in the sodium valproate group and 554 in the magnesium valproate group. Significant differences in proportions of comorbidities and concomitant use of olanzapine, quetiapine and clozapine were observed between the sodium valproate group and magnesium valproate group ( P<0.05). After adjusting for age, gender, body mass index, comorbidities, concomitant medications, and liver and kidney function indicators, the type of valproates remained an independent influencing factor for dose-adjusted plasma concentration of valproic acid (adjusted unstandardized B coefficient=13.814, 95% CI: 8.090-19.540, P<0.001). Daily dose in the sodium valproate group (1.0[1.0, 1.0] g/d) was significantly higher than that in the magnesium valproate group (0.5[0.5, 1.0] g/d), and dose-adjusted plasma concentration of valproic acid in the magnesium valproate group (93.00 [75.60, 117.40] [μg/mL]/[g·d]) was statistically higher than that in the sodium valproate group (78.55 [57.90, 90.00][μg/mL]/[g·d], P<0.05). Subgroup analysis revealed that, among patients stratified by genders and ages (<40 years vs. ≥40 years), the daily dose in the sodium valproate group was significantly higher than that in the magnesium valproate group, while the dose-adjusted plasma concentration of valproic acid in the magnesium valproate group was significantly higher than that in the sodium valproate group ( P<0.05). Conclusion:Significant differences in dose-adjusted plasma concentrations of valproic acid are observed among different valproate formulations for the treatment of mental disorders; therefore, therapeutic drug monitoring should be performed in patients when switching valproates to facilitate precise individualized dosage adjustment.

Sennoside A(SA),a typical prodrug,exerts its laxative effect only after its transformation into rhei-nanthrone catalyzed by gut microbial hydrolases and reductases.Hydrolases have been identified,but reductases remain unknown.By linking a photoreactive group to the SA scaffold,we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling(ABPP).From lysates of an active strain,Bifidobacterium pseudocatenulatum(B.pseu-docatenulatum),397 proteins were enriched and subsequently identified using mass spectrometry(MS).Among these proteins,chromate reductase/nicotinamide adenine dinucleotide(NADH)phosphate(NADPH)-dependent flavin mononucleotide(FMN)reductase/oxygen-insensitive NADPH nitroreductase(nfrA)was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource(UniProt)database screening.We also determined that recombinant nfrA could reduce SA.Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Objective Low-dose CT(LDCT)images significantly affect clinical diagnosis due to the substantial presence of noise and artifacts.To address the challenges such as over-smoothing of images,loss of texture details,and the presence of residual noise artifacts,a deconvolution-convolution residual network integrating multi-scale dilated convolution(MDC-DCRN)is proposed for LDCT denoising.Methods The network employed deconvolution-convolution architecture to better preserve image details and integrated an MDC module to enhance the feature extraction capabilities at different scales.Moreover,the issue of excessive image smoothing was effectively mitigated by the composite loss function combining L1 loss and perceptual loss.Results The experimental results on the Mayo dataset demonstrated that MDC-DCRN outperformed 4 classic denoising methods,namely RED-CNN,EDCNN,WGAN-RAM,and CTformer.MDC-DCRN effectively eliminated noise and artifacts while recovering more texture detail information.Compared with LDCT images,the images processed by MDC-DCRN had an average increase of 13.64%in peak signal-to-noise ratio,an average increase of 4.57%in structural similarity index,and an average decrease of 37.40%in root mean square error.Conclusion The proposed MDC-DCRN model can effectively preserve details while reducing noise from low-dose scanning,offering a novel approach to clinical LDCT image denoising.

Objective:To develop and validate machine learning models for predicting the cumulative live birth rate (CLBR) following in vitro fertilization (IVF) and to analyze key predictive features using SHAP values. Methods:This retrospective study included data from patients who underwent IVF-embryo transfer at the Department of Reproductive Medicine, Baoding Maternal and Child Health Hospital, between January 2017 and December 2022. Patients were categorized into two groups based on live birth outcome: the live birth group ( n=1 036) and the non-live birth group ( n=756). The dataset was randomly divided into a training set and a validation set in a ratio of 7∶3. Five algorithms were utilized for model development: logistic regression, random forest, extreme gradient boosting (XGBoost), support vector machine, and neural networks. Model performance was assessed using the area under the receiver operating characteristic (AUC) curve, F1 score, and calibration curves. Clinical decision curve analysis (DCA) was employed to evaluate the clinical utility of the models. SHAP values were used to interpret feature importance in the XGBoost model and enhance its explainability. Results:The XGBoost model demonstrated the best performance in predicting CLBR,with accuracy of 72.44%, AUC of 0.775, and F1 score of 0.654, accuracy and F1 score outperforming logistic regression (accuracy was 70.02%, F1 score was 0.585), random forest (accuracy was 71.69%, F1 score was 0.606), support vector machine (accuracy was 70.20%, F1 score was 0.607), and neural network (accuracy was 68.72%, F1 score was 0.560). The calibration curve of XGBoost closely aligned with the diagonal line, indicating that the predicted probabilities were very close to the actual outcomes, demonstrating good calibration. DCA indicated that the XGBoost model provided higher net benefits across a wide range of clinical decision thresholds. SHAP value analysis identified number of previous IVF failures, antral follicle count, anti-Müllerian hormone level, percentage of normal sperm morphology, and sperm DNA fragmentation index as key predictors of CLBR.Conclusion:The XGBoost model exhibits excellent predictive performance and calibration for CLBR, with SHAP values providing important insights into feature importance. This model has the potential to support the development of personalized treatment strategies in clinical practice. However, its generalizability needs to be validated using external datasets to ensure its applicability to diverse populations.

Objective: To investigate the efficacy, safety, and traditional Chinese medicine (TCM) medication patterns of rituximab (RTX) combined with TCM on treating children with steroid-dependent nephrotic syndrome (SDNS). Methods: One hundred and forty-three children with SDNS who visited the Pediatric Nephrology Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 2018 to December 2022 were enrolled. A cohort study design was adopted, with " RTX treatment" as the exposure factor. Children who met this exposure factor were assigned to the RTX cohort (RTX, glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment), whereas those who did not were assigned to the basic treatment cohort (glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment ), and followed up for 6 months. The frequency of urinary protein recurrences, urinary protein remission duration, proportion and duration of steroid reduction and cessation, cumulative usage of steroids, proportion of recurrence, recurrence amount of steroid used, efficacy of TCM syndrome, and laboratory and safety indicators after treatment, and height and CD19+ B cell count before and after treatment were compared between the two cohorts. The medication patterns of TCM in the two cohorts were analyzed using frequency statistics, association rule analysis, and systematic clustering analysis. Results: Compared with the basic treatment cohort, the RTX cohort showed a decrease in the frequency of urinary protein recurrence, extended sustained remission of urinary protein, an increase in the proportion of steroid reduction and cessation, a shorter duration of steroid reduction and cessation, a decrease in cumulative steroid dosage, a lower recurrence rate, a decrease in CD19+ B cell count, and a decrease in 24-h urinary total protein quantification and the level of cholesterol (P<0.05). No significant difference in the recurrence amount of steroid used, height, TCM syndrome efficacy, albumin, aspartate transaminase, blood urea nitrogen, platelet count, and safety indicators between the two cohorts. Children with SDNS were mostly characterized by qi and yin deficiency syndrome, followed by spleen and kidney yang deficiency syndrome. A total of 175 TCMs were included, including 28 high-frequency drugs such as Huangqi, Fuling, Gancao, Baizhu, Dangshen, and Jiuyurou. The primary use of medication is to nourish the qi and spleen, nourish the kidney, and warm yang. The analysis of association rules yielded eight binary associations and ten three-phase associations, with Huangqi, Baizhu, Fuling, and Dangshen, being the most closely related. Cluster analysis identified four TCM combinations, primarily focusing on tonifying kidney and replenishing essence, benefiting qi and nourishing yin, and removing blood stasis. Conclusion RTX combined with TCM syndrome differentiation treatment can reduce the recurrence frequency of SDNS, prolong the remission period, reduce the glucocorticoid dosage, and have no marked effect on height growth. No apparent adverse reactions were observed. TCM should focus on nourishing qi and yin while removing blood stasis.