ObjectiveThis paper aims to investigate the differential mechanisms underlying the staged therapeutic effects of Qijia Rougan formula on liver fibrosis using proteomic technology. MethodsThe staged rat model of liver fibrosis was established by subcutaneous injection of carbon tetrachloride （CCl₄） and olive oil. One hundred and four SD rats were randomized into thirteen groups：a normal group，a two-week model group，a four-week model group，a six-week model group，an eight-week model group，a two-week Qijia Rougan formula group，a four-week Qijia Rougan formula group，a six-week Qijia Rougan formula group，an eight-week Qijia Rougan formula group，a two-week compound Biejia Ruangan tablet group，a four-week Compound Biejia Ruangan Tablet group，a six-week Compound Biejia Ruangan Tablet group，and an eight-week compound Biejia Ruangan tablet group. After two weeks of drug intervention，liver tissue and abdominal aortic blood samples were collected from the rats for testing. Hematoxylin-eosin （HE） staining，Masson staining，and Picro Sirius red staining were used to observe pathological damage and collagen fiber deposition in liver tissues. Immunohistochemistry （IHC） was employed to detect the contents of fibrosis markers in liver tissues. The contents of liver function indicators in the serum were measured using a fully automated biochemical analyzer，and the levels of liver fibrosis indicators in the serum were assessed by enzyme-linked immunosorbent assay （ELISA）. Liver tissues from the normal group，each model group，and each Qijia Rougan formula group were subjected to label-free quantitative proteomic analysis to identify differential proteins among the groups，with key proteins validated by Western blot. Finally，bioinformatics analysis was performed on the differential proteins. Results（1） The staged rat model of liver fibrosis constructed with CCl₄ and olive oil showed pathological results at the 2^nd，4^th，6^th，and 8^th weeks of modeling that were consistent with the Metavir standards for the F1，F2，F3，and F4 stages. Compared with those in the normal control group，the protein expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were significantly increased in each stage （P<0.05）. The levels of liver function indicators in the serum，including alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），direct bilirubin （DBIL），and total bilirubin （TBil） in each model group，were significantly elevated in each stage （P<0.01）. The levels of liver fibrosis indicators in the serum，including procollagen Ⅲ peptide （PⅢP），type Ⅳ collagen（Ⅳ-C），hyaluronic acid （HA），and laminin （LN） in each model group，were significantly increased in each stage （P<0.05，P<0.01）. This study successfully established a staged rat model of liver fibrosis. （2） Compared with the model groups at each stage，the administration groups showed a reduction in hepatocyte ballooning degeneration，a more orderly arrangement of hepatocytes，and a decrease of inflammatory cell infiltration. The blue-stained collagen fibers became significantly thinner and finer，with reduced and narrowed fibrous septa. The areas of collagen fibers and Picro Sirius red staining were reduced （P<0.05）. The positive areas of α-SMA and Collagen Ⅰ expression were significantly decreased （P<0.05）. The levels of ALT，AST，ALP，DBIL，and TBil in the rats of the model groups at each stage were significantly reduced （P<0.05，P<0.01）. The levels of PⅢP，Ⅳ-C，HA，and LN in the rats of the model groups at each stage were significantly decreased （P<0.05）. Among these，the improvements in all indicators were most significant in the F3 stage （P<0.01）.（3） The proteomic results show that a total of 165 differential proteins exhibit a callback trend when comparing the model groups at four stages with the normal group，and when comparing the Qijia Rougan formula group with the model group. Western blot analysis reveals that the levels of NAD（P）H：quinone oxidoreductase 1 （NQO1），mitogen-activated protein kinase 1 （MAPK1），arginase 1 （Arg1），and glutathione S-transferase α1 （GSTA1） were consistent with the proteomic results. Bioinformatics results reveal that 165 differentially expressed proteins are enriched in multiple signaling pathways. Notably，signaling pathways such as drug metabolism-cytochrome P450，arginine biosynthesis，and the peroxisome proliferator-activated receptor （PPAR） signaling pathway were found to be closely associated with liver fibrosis，suggesting that the Qijia Rougan formula may exert its staged regulatory effects on liver fibrosis by regulating these pathways. ConclusionThe Qijia Rougan formula may achieve staged regulation of liver fibrosis by regulating drug metabolism-cytochrome P450，arginine biosynthesis，and the PPAR signaling pathway.

Objective To develop and validate a machine learning model integrating serum tumor markers with multiparametric magnetic resonance imaging(mpMRI)-derived scores for discriminating prostate cancer(PCa)from benign prostatic hyperplasia(BPH)in men with a total prostate-specific antigen(tPSA)of 4-10 ng/mL, so as to optimize prostate biopsy decisions. Methods A retrospective analysis was conducted on the clinical data of 85 PCa patients and 204 BPH patients treated in our hospital during Jan. 2022 and May 2025. All patients underwent prostate biopsy to obtain the pathological results. The data collected were analyzed using univariate and multivariate logistic regression to determine the independent risk factors for PCa. Model performance was assessed in terms of discrimination, calibration, and clinical utility using receiver operating characteristic(ROC)curves, calibration plots, and decision curve analysis(DCA). A classification and regression tree(CART)algorithm was further developed to derive biopsy decision rules. The area under the ROC curve(AUC)of the logistic and CART models were compared to select the optimal predictive model, which was subsequently visualized using SHAP values. Results Age, free prostate-specific antigen(fPSA), fPSA/tPSA(f/tPSA)ratio, and Prostate Imaging-Reporting and Data System(PI-RADS)scores differed significantly between the PCa and BPH groups(P＜0.05). Univariate and multivariate logistic regression identified age, f/tPSA ratio, and PI-RADS scores as independent influencing factors(P＜0.05). A logistic model incorporating these variables achieved an AUC of 0.785(95%CI:0.724-0.846, P＜0.05), with a sensitivity of 70.6% and specificity of 77.9%. The model showed excellent calibration. DCA indicated a positive net benefit when the risk threshold exceeded 7%. The CART model yielded an AUC of 0.769(95%CI:0.717-0.821), with the sensitivity of 63.5% and specificity of 79.9%. Within threshold probabilities of 5%-56%, the CART model provided higher net benefit. When the risk threshold reached 55%, the number of diagnosed cases of PCa began to converge with the actual number. Conclusion Compared with the CART model, the logistic model based on f/tPSA, PI-RADS score and age has a higher diagnostic efficacy for PCa and is the optimal model.

Objective To develop an erythrocyte-based delivery system for butyrylcholinesterase(BChE)that is capable of prophylaxis against organophosphorus nerve agents.Methods Recombinant BChE was produced and analyzed for oligomerization via polyacrylamide gel electrophoresis(PAGE)and Western blotting.A modified hypotonic preswelling method was employed to prepare BChE-loaded erythrocytes.The drug loading capacity and encapsulation efficiency were quantified using enzyme-linked immunosorbent assay(ELISA).Catalytic activity was assessed in vitro with an activity detection kit.The system was characterized via scanning electron microscopy(SEM),flow cytometry and a hematology analyzer.Results Recombinant BChE predominantly existed as dimers(85％dimer,15％monomer).The optimized volume ratio of erythrocytes to hypotonic solution was determined as 1:7.Compared with native and empty erythrocytes,BChE-loaded erythrocytes exhibited significantly higher catalytic activity(P＜0.001).The mean corpuscular volume of BChE-loaded erythrocytes increased(P＜0.001),while the mean content of corpuscular hemoglobin and hemoglobin in erythrocytes per 100 mL decreased(P＜0.001).SEM revealed no morphological differences(biconcave disc shape).Hypotonic preswelling moderately increased erythrocyte apoptosis(P＜0.001),but no statistical difference was observed between BChE-loaded and hypotonic-treated erythrocytes(P＞0.05).CD47 expression remained unchanged compared to native erythrocytes(P＞0.05).Conclusion The modified hypotonic preswelling method can generate BChE-loaded erythrocytes that retain the characteristics of native erythrocytes while conferring catalytic activity,offering a novel strategy for clinical intervention against organophosphorus poisoning.

OBJECTIVES: To evaluate the osteogenic efficacy of three-dimensional printing individualized titanium mesh (3D-PITM) as a scaffold material in guided bone regeneration (GBR). METHODS: 1) Patients undergoing GBR for alveolar bone defects were enrolled as study subjects, and postoperative healing complications were recorded. 2) Postoperative cone beam computed tomography (CBCT) scans acquired at least 6 months post-surgery were used to calculate the percentage of actual bone formation volume. 3) Alveolar bone specimens were collected during the first-stage implant surgery for histomorphometric analysis. This analysis quantitatively measured the proportions of newly formed bone and newly formed unmineralized bone within the specimens. Specimens were categorized into three groups based on healing complications (good healing group, wound dehiscence group, 3D-PITM exposure group) to compare differences in the proportions of newly formed bone and newly formed unmineralized bone. RESULTS: 1) Twelve patients were included. Guided bone regeneration failed in one patient, and 3D-PITM exposure occurred in three patients (exposure rate: 25%). 2) The mean percentage of actual bone formation volume in the 11 successful guided bone regeneration cases was 95.23%±28.85%. 3) Histomorphometric analysis revealed that newly formed bone constituted 40.35% of the alveolar bone specimens, with newly formed unmineralized bone accounting for 13.84% of the newly formed bone. Intergroup comparisons showed no statistically significant differences (P>0.05) in the proportions of newly formed bone or newly formed unmineralized bone between the good healing group and the wound dehiscence group or the 3D-PITM exposure group. CONCLUSIONS 3D-PITM enables effective bone augmentation. Radiographic assessment demonstrated favorable bone formation volume, while histological analysis confirmed substantial formation of newly formed mineralized bone within the surgical site.
Humans ; Printing, Three-Dimensional ; Titanium ; Cone-Beam Computed Tomography ; Bone Regeneration ; Osteogenesis ; Surgical Mesh ; Tissue Scaffolds ; Alveolar Process/surgery* ; Adult ; Male ; Middle Aged ; Female ; Wound Healing ; Guided Tissue Regeneration, Periodontal/methods* ; Alveolar Bone Loss/surgery*

Objective To compare the clinical efficacy of high-dose tigecycline(TGC)and polymyxin B(PMB)in the treatment of pulmonary infection due to carbapenem-resistant organism(CRO).Methods Clinical data of pa-tients with CRO pulmonary infection and received PMB or high-dose TGC combined with other antimicrobial treat-ment regimens in Department of Critical Care Medicine of Xiangya Hospital,Central South University from January 2019 to March 2022 were analyzed retrospectively,including basic information,pathogen detection results,antimi-crobial use regimen,clinical efficacy,30-day mortality,bacterial clearance rate,etc.Results A total of 173 pa-tients were included in analysis,with 103 in the TGC group and 70 in the PMB group.Compared with TGC group,PMB group had a higher score of acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)(25.0 vs 20.0,P＜0.001),but clinical efficacy rates were not statistically different(67.1％vs 52.4％,P=0.054).Stratified analysis revealed that when the APACHE Ⅱ score was ≥15 points,compared with TGC group(n=78),PMB group(n=66)had a higher APACHE Ⅱ score(27.0 vs 22.0,P=0.005)and a higher clinical efficacy rate(66.7％vs 47.4％,P=0.020).After adjusting confounding factors through logistic regression analysis,it was found that PMB treatment was a protective factor for clinical efficacy rate compared with TGC treatment.Conclusion For treating pulmonary infection caused by CRO in patients,PMB-based treatment regimen has a significant protec-tive effect on the clinical efficacy rate compared with the high-dose TGC-based treatment regimen.

Objective:To investigate the feasibility and safety of laparoscopic purse- string suture clamps combined with multi-functional seal caps for esophagojejunal Roux-en-Y anastomosis during total laparoscopic radical total gastrectomy (TLTG).Methods:This was a retrospective descriptive study of 42 patients with primary gastric malignancies who underwent TLTG at the First Affiliated Hospital of Nanjing Medical University that utilized laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis between May, 2024 and January, 2025. The cohort included 33 males and 9 females, with a mean age of (67.7 ±9.5) years and a mean body mass index (BMI) of (23.9±2.9) kg/m 2. The American Society of Anesthesiologists (ASA) physical status classifications were I - II in 40 patients and III in 2 patients, and all patients were definitively diagnosed preoperatively via gastroscopy, dual-energy CT, and/or MRI. Tumor locations included the gastroesophageal junction (GEJ) in 28 cases (Siewert type II - III), the upper third of the stomach in 12 cases, and the middle third in 2 cases. The median distance of esophageal invasion was 1.3 cm, though in 10 cases this was ≥2 cm. Preoperative TNM staging was I-II in 17 patients and III in 25 patients. Surgical outcomes including operative time, anastomosis time, intraoperative blood loss, pathological results, and postoperative recovery were retrospectively analyzed. Results:All 42 operations were successful. The mean operative time was(212.5±26.4) minutes, and the average time from multi-functional seal cap placement to completion of the esophagojejunal anastomosis was (54.2±7.5) minutes. Mean intraoperative blood loss was (79.9±21.3) ml. Postoperative pathology confirmed R0 resection in all specimens, with a mean proximal esophageal margin distance of (2.1±1.6) cm. Furthermore, (51.9±15.1) lymph nodes on average were harvested from each patient; the mean time to oral intake was (149.5±41.4) hours; and the mean hospital stay was (11.3±5.4) days. Postoperative complications occurred in 6 patients: anastomotic leakage ( n=2), residual intra-abdominal infection ( n=1), pulmonary infection ( n=3), and Clavien-Dindo grade III or higher complications occurred in 2 patients. No recurrence, mortality, or anastomosis-related complications were observed within a median follow-up of 5.8 months (range 3.5-11.2). Conclusion:We find the application of the laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis in TLTG to be safe and feasible, with satisfactory short-term outcomes.

OBJECTIVE: To observe the effects of antagonistic needling therapy on lower limb spasticity and the muscle morphology of the tibialis anterior and gastrocnemius in patients with stroke. METHODS: A total of 100 patients with post-stroke lower limb spasticity were randomly divided into an antagonistic needling group (50 cases, 1 case dropped out) and a routine acupuncture group (50 cases, 1 case dropped out). Both groups received basic treatment and rehabilitation training. The routine acupuncture group was treated with scalp acupuncture at anterior oblique line of vertex-temporal and vertex lateral line 1, combined with body acupuncture at Jianyu (LI15), Hegu (LI4), Zusanli (ST36), Taichong (LR3), etc. on the affected side, with Quchi (LI11) and Hegu (LI4), Zusanli (ST36) and Fenglong (ST40), Yanglingquan (GB34) and Taichong (LR3) connected to an electroacupuncture device, using disperse wave at 2 Hz of frequency. The antagonistic needling group used the same scalp and upper limb acupoints as the routine acupuncture group, with additional antagonistic needling on the lower limb at Yanglingquan (GB34), Qiuxu (GB40), Jiexi (ST41), and Xuanzhong (GB39) on the affected side, with Quchi (LI11) and Hegu (LI4), Yanglingquan (GB34) and Qiuxu (GB40), Jiexi (ST41), and Xuanzhong (GB39) connected to an electroacupuncture device, using disperse wave at 2 Hz of frequency. Both groups received treatment once daily for 6 consecutive days per course, with a total of 4 courses. The modified Ashworth scale (MAS), Holden functional ambulation classification (FAC), lower limb Fugl-Meyer assessment (FMA), composite spasticity scale (CSS), and musculoskeletal ultrasound parameters (thickness and fiber length of the tibialis anterior and gastrocnemius, and pennation angle of the gastrocnemius on both sides) were evaluated before and after treatment. Clinical efficacy was compared between the two groups. RESULTS: Compared before treatment, the MAS grades and CSS scores were decreased in both groups after treatment (P<0.01), with greater reductions in the antagonistic needling group (P<0.05, P<0.01). FAC grades and FMA scores were increased in both groups after treatment (P<0.01, P<0.05), with greater improvements in the antagonistic needling group (P<0.05). The muscle thickness, fiber length of the tibialis anterior, the muscle thickness, fiber length and pennation angle of the gastrocnemius on the affected side were improved in both groups after treatment (P<0.01), with greater improvements in the antagonistic needling group (P<0.01, P<0.05). On the unaffected side, these parameters were also increased after treatment in both groups (P<0.01, P<0.05), but the antagonistic needling group showed smaller increases than the routine acupuncture group (P<0.01, P<0.05). The total effective rate in the antagonistic needling group was 91.8% (45/49), higher than 81.6% (40/49) in the routine acupuncture group (P<0.05). CONCLUSION Antagonistic needling could effectively reduce spasticity, improve motor function, and enhance muscle structure in patients with post-stroke lower limb spasticity.
Humans ; Male ; Female ; Acupuncture Therapy ; Middle Aged ; Muscle Spasticity/pathology* ; Aged ; Stroke/physiopathology* ; Lower Extremity/physiopathology* ; Acupuncture Points ; Adult ; Muscle, Skeletal/pathology* ; Treatment Outcome

Objective:To investigate the short-term efficacy of robotic versus laparoscopic-assisted right hemicolectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 99 patients of right colon cancer who were admitted to Tianjin Medical University General Hospital from January 2020 to December 2023 were collected. There were 50 males and 49 females, aged 69(range, 26?89)years. Of the 99 patients, 41 patients undergoing robotic-assisted right hemicolectomy were divided into the robotic group, and 58 patients undergoing laparoscopic-assisted right hemicolectomy were divided into the lapa-roscopic group. Patients received robotic-assisted or laparoscopic-assisted right hemicolectomy operated by the same major surgeon. Observation indicators:(1) propensity score matching status and com-parison of clinical data of patients between the two groups after matching; (2) intraoperative and postoperative conditions.Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶1 nearest neighbor matching method. The caliper value was set as 0.1. Results:(1) Propensity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 99 patients, 82 patients were successfully matched, with 41 cases in each of the robotic group and the laparoscopic group. After propensity score matching, the elimination of history of abdominal operation confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After propensity score matching, the operation time of the robotic group was 215(range, 130?340)minutes, the volume of intraoperative blood loss was 50(range, 10?400)mL, the number of lymph node dissected was 21(range, 5?55), the number of intensive care unit stay was 15, time to postoperative first flatus was 3(range, 1?12)days, time to postoperative first food intake was 4(range, 2?14)days, duration of postoperative hospital stay was 8(range, 5?25)days. The above indicators of the laparoscopic group were 210(range, 140?370)minutes, 50(range, 5?150)mL, 19(range, 5?34),20, 3(range, 0?9)days, 5(range, 2?10)days, 8(range, 6?17)days, respectively. There was no significant difference in the above indicators between patients of the two groups ( Z=?0.94, ?1.87, ?1.32, χ2=1.25, Z=0.13, ?0.83, ?0.65, P>0.05). There was no patient converted to open operation in the robotic group, versus 1 patient converted to open operation in the laparoscopic group, showing no significant difference between patients of the two groups ( P>0.05). There were 6 cases in the robotic group and 4 cases in the laparoscopic group with complications, showing no significant difference between the two groups ( χ2=0.46, P>0.05). Both groups of patients achieved R 0 resection and had no readmission 30 days after surgery. The hospital expense was (11.0±1.8)×10 4 yuan of the robotic group, versus (9.0±1.7)×10 4 yuan of the laparoscopic group, showing a significant difference between the two groups ( t=?5.27, P<0.05). Conclusion:Robot-assisted right hemicolectomy is non inferior to laparoscopic-assisted right hemicolectomy in safety and efficacy, but with higher hospitalization costs.

Objective To explore the characteristic changes in white matter microstructure in Parkinson's disease(PD)patients via automated fiber quantification(AFQ)technology,providing a basis for the identification and diagnosis of PD,and to analyze the feasibility of combining the AFQ method with support vector machine(SVM)in the diagnosis of PD.Methods Forty patients with primary PD(PD group)and 20 healthy controls(HC)(HC group)were prospectively selected.The AFQ technology was applied for white matter fiber tract analysis.Statistical analyses were performed using FSL(v6.0)software and SPSS 27.0 software.Independent-sample t-tests were conducted for comparisons between groups in AFQ analysis.The AFQ method was used to analyze the relationship between diffusion tensor imaging(DTI)parameters and Montreal Cognitive Assessment(MoCA)scores.Results(1)The results of AFQ analysis revealed that compared with the HC group,the PD group exhibited significantly lower fractional anisotropy(FA)values in the right cingulum bundle,left cingulum bundle hippocampus,and left uncinate fasciculus,with no differences in the FA values of the remaining 17 fiber tracts.Moreover,PD group demonstrated higher mean diffusivity(MD)values in the left cingulum bundle,left cingulum bundle hippocampus,left inferior frontal occipital fasciculus,left inferior longitudinal fasciculus,left superior longitudinal fasciculus,and left uncinate fasciculus.These differences were statistically significant(P<0.05),while no significant differences were found in the MD values of the remaining 14 fiber tracts.Furthermore,the MD values of the left inferior frontal occipital fasciculus,and left inferior longitudinal fasciculus were negatively correlated with the MoCA scores.(2)The classification results of SVM showed that the best results were achieved when combining the differential nodes of FA and MD as classification features,with an area under the curve(AUC)of 0.922,an accuracy of 84.81%,a sensitivity of 87.50%,and a specificity of 82.05%.Conclusion The DTI parameters in PD patients can serve as potential biomarkers for diagnosis.The AFQ methods provides an effective approach for detecting alterations white matter tract integrity,offering important insights for the identification and diagnosis of PD.The best results are achieved when combining the differential nodes of FA and MD as classification features.

Objective To investigate the effect of tritiated water on the immune system of zebrafish and its potential molecular mechanism. Methods Zebrafish embryos (2.5 to 3 hours post-fertilization [hpf]) were exposed to 3.7 × 10⁴ Bq/mL tritiated water (tritiated water group), and those exposed to E3 culture medium were used as the control group. The mortality rate, hatching rate, deformity rate, heart rate, body length, yolk sac area, neutrophil count in the tail, immune-related gene expression, and immune-related protein expression of zebrafish in the two groups were determined. Then transcriptome technology was used to further analyze the possible mechanism of tritiated water affecting the immune system of zebrafish. Results Compared with the control group, zebrafish at 72 hpf in the tritiated water group had no significant changes in the mortality rate, hatching rate, deformity rate, body length, and yolk sac area((t = 0.9045, 0.5000, 1.0000, 0.7238, 0.0337, P = 0.4169, 0.6433, 0.3739, 0.4785, 0.9735), but had significantly increased heart rate(t = 4.575，P = 0.002). At 4 days post-fertilization (dpf), the neutrophil count in the tail of zebrafish in the tritiated water group was significantly increased(t = 2.563，P = 0.0196), the mRNA expression of TNF-α was significantly decreased(t = 2.891, P = 0.045), the protein expression of nuclear factor-kappa B (NF-κB) was significantly increased(t = 3.848, P = 0.018), and the protein expression of NLRP3 was significantly decreased(t = 14.98, P = 0.001). At 7 dpf, the neutrophil count in the tail and the protein expression levels of NF-κB, NLRP3, and interleukin-1β were significantly decreased(t = 3.772, 7.048, 15.620, 4.423, P = 0.014, 0.002, 0.0001, 0.012). Transcriptome sequencing revealed that differentially expressed genes were mainly enriched in the “neutrophil activation” and “platelet activation pathways” at 4 dpf and in the “neutrophil apoptosis”, “ferroptosis”, and “necroptosis” pathways at 7 dpf. Conclusion Tritiated water exposure induces a temporally dynamic immune response in zebrafish, potentially affecting immune homeostasis by regulating neutrophil activation and apoptosis, as well as the expression of NF-κB and NLRP3.