ObjectiveTo investigate the effects of targeted silencing of Runt-related Transcription Factor 3 （RUNX3） on the proliferation and migration of Mouse Hepatic Stellate Cells （HSCs）， as well as subsequent collagen deposition. MethodsMouse hepatic stellate cell line （JS-1） was selected and then morphologically observed and identified under a microscope. After the cells had fully adhered， they were treated with 5 ng/mL of transforming growth factor beta 1 （TGF-β₁） for 24 hours to induce hepatic stellate cell activation. Furthermore， a RUNX3 silencing model was established using RUNX3 lentiviral infection. The experiment was divided into four groups： Control group， TGF-β₁ group， TGF-β₁+siRNA-NC group， and TGF-β₁+siRNA-RUNX3 group. Protein expression changes of RUNX3， alpha-smooth muscle actin （α-SMA）， and Alpha 1 type I collagen （Collagen I） were detected using Western blot method. Cellular immunofluorescence assays were employed to investigate the deposition changes of α-SMA and RUNX3 in hepatic stellate cells. RT-qPCR was utilized to examine the mRNA expression changes of RUNX3， α-SMA， and Collagen I. The proliferative capacity of hepatic stellate cells was assessed using Edu staining. The migratory ability of hepatic stellate cells was evaluated through wound healing assays and Transwell migration experiments. ResultsCompared with Control group， a significant elevation in RUNX3 was observed in the TGF-β₁-induced activated HSCs （P<0.01）. Meanwhile， the protein and mRNA levels of fibrosis-related markers and α-SMA and Collagen I were significantly upregulated （P<0.001）. Additionally， the proliferation and migration capabilities of HSCs were significantly enhanced （P<0.001）. In contrast， when compared to TGF-β₁+siRNA-NC group， TGF-β₁+siRNA-RUNX3 group exhibited a notable decrease in RUNX3 and other related indicators， such as the protein and mRNA levels of α-SMA and Collagen I （P<0.05）. Concurrently， the proliferation and migration capabilities of HSCs were significantly inhibited in TGF-β₁+siRNA-RUNX3 group （P<0.01）. ConclusionSilencing RUNX3 can inhibit the deposition of collagen and the proliferation and migration of hepatic stellate cells. Conversely， RUNX3 promotes the proliferation and migration capabilities of HSCs， thereby facilitating the activation of HSC.

Background/Aims: Spinal cord injury (SCI) frequently impairs defecation, severely affecting the quality of life. This study examines compensatory neural remodeling after SCI, focusing on basal colonic contractility, neural responses to electrical field stimulation, and alterations in excitatory cholinergic and inhibitory nitrergic pathways. Methods: Female Sprague–Dawley rats underwent either sham surgery or T10 spinal cord transection and were categorized into 3 groups: sham, 1-week post-SCI (acute), and 4-week post-SCI (chronic). Colonic contractility was assessed in an organ bath using electrical field stimulation in the presence of a nitric oxide synthase inhibitor. Neural protein expression was analyzed by immunofluorescence and Western blotting. Results: SCI produced region- and time-dependent impairments in colonic contractility, with distinct alterations in the proximal circular and longitudinal muscles across acute and chronic phases. Neural excitability shifted dynamically, showing enhanced excitatory activity in the proximal longitudinal muscle at 1-week and the distal circular muscle at 4-week post-SCI. Protein analysis revealed increased neuronal nitric oxide synthase in the proximal colon, decreasedsoluble guanylyl cyclase in the distal colon, upregulated muscarinic M3 receptor in the proximal colon, and reduced vaso-active intestinal peptide receptor 1 in both proximal and distal regions. Conclusion SCI induces spatiotemporal remodeling of excitatory and inhibitory neural pathways, contributing to colonic dysmotility and revealing potential targets for therapeutic intervention.

Objective: To evaluate the diagnostic performance of the “probable hepatocellular carcinoma (HCC)” category in the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) v2022 guidelines. Materials and Methods: This multicenter retrospective study included patients at risk of HCC who underwent gadoxetic acid-enhanced MRI between January 2015 and June 2018; a subgroup of these patients also underwent liver CT. Eligible patients had at least one non-cystic lesion (≥10 mm) with a reference standard. Four radiologists interpreted the images independently and the results were pooled. The performance of “definite HCC” and “probable HCC” together and “probable HCC” alone were compared between v2018 and v2022. Results: A total of 2,237 patients (1,666 men; mean age, 59 ± 11 years) with 2,445 lesions were included. In v2022, 1.5% (143/9,780) of the lesions were additionally categorized as “probable HCC” by four reviewers on MRI; among these, 104 lesions were not HCCs. Focal nodular hyperplasia (FNH) or FNH-like nodules constituted 90.4% (94/104) of the false positives. When “definite HCC” and “probable HCC” were combined, v2022 showed higher sensitivity (83.7% [5,670/6,776] vs. 83.1% [5,631/6,776]) but lower specificity (77.1% [2,316/3,004] vs. 80.6% [2,420/3,004]) than v2018 (P < 0.001). For “probable HCC” alone, v2022 showed a lower positive predictive value (PPV) than v2018 (64.1% [373/582] vs. 76.1% [334/439], P < 0.001). In v2022, lesions with non-rim arterial-phase hyperenhancement (APHE) showed a lower PPV than those without APHE (42.3% [91/215] vs. 76.8% [282/367], P < 0.001). In the CT subgroup (n = 1,590), 1.6% (99/6,360) of the lesions were reassessed as “probable HCC,” and its PPV was 83.8% (83/99) in v2022 whereas no lesions were classified as “probable HCC” under v2018. Conclusion The revised “probable HCC” category in the KLCA-NCC v2022 aligns with updates in the diagnostic flow, demonstrating acceptable performance on MRI and CT. Notably, FNH or FNH-like nodules can be misclassified as “probable HCC” when MRI is used.

With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.

Introduction: Hypertension is common in obesity and increases cardiovascular risk. Bariatric surgery improves metabolic health, but subgroup differences in blood pressure response remain unclear. This study examined 1-year changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after bariatric surgery across sex, age group, and diabetes status. Methodology: This study included 32 obese adults undergoing bariatric surgery, with blood pressure measured at baseline, 6 and 12 months. Generalized estimating equation models were used to evaluate changes in SBP and DBP over time, adjusting for age, sex, surgery type, diabetes category, baseline body mass index, antihypertensive medication use, and baseline blood pressure. Interaction terms were tested to assess differences in blood pressure trajectories across subgroups. Results: Participants were predominantly female (67.4%), with a mean age of 36.9 ± 6.2 years and a mean body mass index of 40.7 ± 8.8 kg/m². Hypertension and diabetes were present in 40.6 and 31.3% of participants, respectively. There was a significant time effect for both SBP (p <0.001) and DBP (p = 0.004). At 12 months post-surgery, mean SBP decreased by 15 mmHg and DBP by 7.9 mmHg compared with baseline (both p <0.001). No significant interactions were observed between time and sex, diabetes category, or age category, indicating that blood pressure improvements were comparable across subgroups. Conclusion Bariatric surgery was associated with clinically meaningful reductions in both SBP and DBP, with similar improvement patterns observed across demographic and metabolic subgroups. These findings support the effectiveness of bariatric surgery as a strategy for blood pressure reduction and cardiovascular risk management in patients with obesity.
Blood Pressure ; Bariatric Surgery

ObjectiveTo investigate the efficacy and safety of Shuganning injection in the treatment of liver injury by observing the clinical outcome of patients with liver injury after treatment with Shuganning injection and comparing it with reduced glutathione （GSH）. MethodsThis study was conducted among 175 patients with liver injury who attended 6 hospitals in China （Beijing YouAn Hospital， Capital Medical University； Nanyang First People’s Hospital； The Second Affiliated Hospital of Xi’an Jiaotong University； The Fifth Medical Center of Chinese PLA General Hospital； The Third Hospital of Hebei Medical University； The Affiliated Hospital of Guizhou Medical University） from April 25， 2019 to February 28， 2022. The patients were divided into experimental group （89 patients treated with Shuganning injection） and control group （86 patients treated with GSH）， and the course of treatment was 4 weeks for both groups. Related indicators were recorded before treatment， after treatment， and after drug withdrawal for 8 weeks， including liver function parameters， blood biochemical parameters， blood lipids， coagulation profiles， liver fibrosis markers， traditional Chinese medicine （TCM） syndrome score， and ultrasound findings， as well as adverse events during treatment. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The Wilcoxon signed-rank test was used for comparison of observation indicators before treatment， at week 4 of treatment， and after drug withdrawal for 8 weeks. When the efficacy evaluation of TCM syndromes was used as the outcome， a pooled analysis was performed for the effective cases and the markedly effective cases， and a Logistic regression model was used to calculate the odds ratio （OR） and its 95%CI. ResultsAfter 4 weeks of treatment with Shuganning injection， the patients showed significant reductions in TCM syndrome score （P<0.001） and the levels of aspartate aminotransferase， alanine aminotransferase， total bilirubin， and direct bilirubin （all P<0.001） and a significant increase in the level of albumin （P=0.002）， and these significant improvements persisted after drug withdrawal for 8 weeks. Furthermore， compared with the control group， the experimental group had a significantly higher proportion of patients assessed as effective or markedly effective cases （48.31% vs 32.56%， P=0.033）. Compared with the control group， the experimental group had a significantly greater change in TCM syndrome score at weeks 1-4 of treatment and after drug withdrawal for 8 weeks （P<0.05）. At week 4 of treatment， the experimental group had a significantly greater reduction in alanine aminotransferase than the control group （P<0.05）， and at week 8 after drug withdrawal， the experimental group had a significantly greater reduction in alanine aminotransferase and aspartate aminotransferase than the control group （all P<0.05）. One patient in the experimental group （1.12%） experienced an adverse event， which was determined to be associated with the progression of viral hepatitis. ConclusionShuganning injection can effectively improve liver injury， with good long-term efficacy and a low incidence rate of adverse reactions.

Objective: To examine the association between parent-child relationships and bullying behaviors among junior high school students, and to explore the moderating effect of community cohesion, so as to provide evidences for bullying intervention strategies. Methods: From November to December 2017, a cluster sampling method was used to survey 1 589 students in grades 6- 8 from three junior high schools in Jing an District,Shanghai. Anonymous electronic questionnaires collected data on parent-child relationships, community cohesion, and bullying behaviors. Multivariate Logistic regression analyzed the associations and moderation effects. Results: The prevalence of bullying behaviors among junior high school students was 7.80%. Spearman correlation analysis revealed negative associations between both parent-child relationships ( r =-0.13) and community cohesion ( r =-0.10) with bullying behaviors, while parent-child relationships positively correlated with community cohesion ( r =0.29) (all P <0.01). Junior high school students with positive parent-child relationships and higher perceived community cohesion showed lower risks of bullying behaviors ( OR=0.51, 95%CI =0.36-0.72; OR=0.58, 95%CI =0.45-0.76), with a significant interaction effect between the two factors (all P <0.05). Conclusions Positive parent-child relationships and community cohesion are negatively associated with bullying behaviors in middle school students. Supportive family relationships help reduce bullying, while stronger community cohesion enhances the protective effect of positive parent-child relationships against bullying.

T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.

Objective To explore the influencing factors on foot function recovery after distraction device-assisted repositioning of small incisions treatment for Sanders Ⅱ and Ⅲ calcaneal fractures,and to provide guidance for timely clinical interventions.Methods A retrospective analysis was conducted on 80 patients with Sanders type Ⅱ and Ⅲ calcaneal fractures admitted to the People's Hospital of Bozhou from January 2021 to June 2023.Data were collected using a general information questionnaire,the hospital's electronic medical record system,the visual analog scale(VAS),the Marland foot function scale(MFS),the perceived social support scale(PSSS),and the perceived stress scale(PSS).The influencing factors of postoperative foot function recovery were analyzed using univariate factor analysis,multivariate linear regression,and structural equation modeling.Results The MFS scores of 80 patients at 6 months post-operation were significantly higher than preoperative scores(P＜0.001).The rates of excellent,good,fair,and poor foot function at 6 months post-operation were 56.3％,31.3％,10.0％,and 2.5％,respectively.Univariate analysis revealed significant differences in MFS scores based on different ages,time to start full weight-bearing exercise,bone mineral density,surgical timing,body mass index(BMI),postoperative VAS score,PSSS score,PSS score,and the presence of postoperative peroneal muscle spasm and peroneal muscle tendon adhesion(P＜0.05).Multivariate linear regression identified age,time to start full weight-bearing exercise,surgical timing,BMI,postoperative fibular muscle spasm,postoperative fibular muscle tendon adhesion,postoperative VAS score,PSSS score,and PSS score as significant factors affecting foot function recovery(P＜0.05).Structural equation modeling indicated that age,time to start full weight-bearing exercise,bone density,operative timing,BMI,postoperative peroneal muscle spasm,postoperative peroneal tendon adhesion,and pain severity directly influenced postoperative foot functional recovery.Additionally,psychological stress not only directly affected postoperative foot functional recovery but also indirectly influenced it through the mediating effect of social support.Conclusions Foot function recovery after surgery for Sanders type Ⅱ and Ⅲ calcaneal fractures is influenced by multiple factors.Psychological stress not only directly affects the recovery of foot function after surgery,but also mitigates the harm to foot function through social support.