ObjectiveTo investigate the protective effect of genistein （Gen） on etoposide-induced chondrocyte senescence and its underlying mechanism. MethodsThe C28/I2 cell line was treated with different concentrations of Gen and etoposide， and the cell viability was detected by the CCK-8 assay. The senescence model of C28/I2 chondrocytes was induced by etoposide， with Gen intervention. Senescence-associated β-galactosidase （SA-β-gal） staining was performed to detect the senescence-positive rate and staining characteristics of chondrocytes. The expressions of peroxiredoxin 6 （Prdx6）， cyclin-dependent kinaseto clarify the functional necessity of Prdx6. ResultsCompared with the etoposide group， the C28/I2 chondrocyte viability significantly increased （P<0.01）， the expression ofsenescence-associated proteins p21 and p16 decreased （P<0.01， P<0.05）， the expression of senescence-associated genes p21 and p16 reduced （both P<0.01）， the fluorescence intensity of senescence-associated proteins p21 and p16 was diminished （P<0.05， P<0.01）， and the proportion of SA-β-gal-positive cells decreased （P<0.01） in the Gen+etoposide group. Compared with the Control group， the expression of Prdx6 was downregulated in the etoposide group （P<0.05）. Compared with the etoposide group， the expression of Prdx6 was upregulated in the Gen+etoposide group （P<0.01）. Compared with the Control group， the GPx activity significantly decreased in the si-Prdx6 group （P<0.01）. Furthermore， compared with the si-Prdx6 group， the GPx activity increased in the si-Prdx6+Gen group （P<0.05）. Molecular docking results revealed that Gen formed hydrogen bond interactions with the active site of Prdx6. After Prdx6 knockdown， the expression of senescence-associated genes p21 and p16 and the fluorescence intensity of senescence-associated proteins p21 and p16 both increased in the Gen+etoposide+si-Prdx6 group （both P<0.01）. ConclusionGen can inhibit etoposide-induced senescence of C28/I2 chondrocytes by upregulating the expression of Prdx6. This study provides potential drug targets and experimental basis for the prevention and treatment of chondrocyte senescence-related diseases.

ObjectiveTo investigate the effects and mechanisms of pulchinenoside A （PSA） on tumor necrosis factor-α （TNF-α） -induced abnormal proliferation， migration， and invasion of synovial fibroblasts. MethodsA synovitis model was established by stimulating SW982 synovial cells with TNF-α. The low-density lipoprotein receptor-related protein 1 （LRP1） was knocked down using LRP1-specific siRNA or inhibited by the receptor-associated protein （RAP）. Cells were treated with various concentrations of PSA， and cell viability was assessed by CCK-8 assay. Protein levels of LRP1， matrix metalloproteinase-3 （MMP3）， and N-cadherin were measured by Western blotting. Proliferation was evaluated using an EdU incorporation assay. Migration and invasion capacities were examined by Transwell and wound-healing assays. mRNA expression of LRP1， MMP3， N-cadherin， IL-1β， IL-6， and TNF-α was detected by reverse transcription quantitative real-time PCR （RT-qPCR）. Immunofluorescence staining was used to visualize the expression of MMP3 and N-cadherin. The involvement of LRP1 was further verified with the inhibitor RAP. ResultsCompared with the TNF-α-treated model group， PSA treatment significantly reduced SW982 cell viability （P<0.05）， downregulated MMP3 and N-cadherin expression （both P<0.01）， and decreased the proportion of EdU-positive cells （P<0.05）. Moreover， TNF-α stimulation upregulated LRP1 expression compared with normal controls （P<0.01）， whereas PSA treatment reversed this increase （P<0.05）. LRP1 knockdown or inhibition markedly decreased MMP3 and N-cadherin levels compared with the model group （both P<0.01）. Similarly， the combination of PSA and RAP led to significant reductions in MMP3 and N-cadherin expression compared with the model group （both P<0.01）. ConclusionPSA inhibits TNF-α-induced abnormal proliferation， migration， and invasion of synovial， at least in part， by downregulating LRP1 expression.

Objective : To explore the effects and mechanisms of Kobophenol A ( KPA) on lipopolysaccharide ( LPS) -induced M1 macrophage polarization，and to provide a theoretical basis for the treatment of inflammatory immune diseases and the development of new drugs． Methods: The M1 macrophage polarization model of RAW264. 7 was established by LPS induction，and the peroxiredoxin 6 ( Prdx6) knockdown model was constructed using the Prdx6 inhibitor MJ33 and Prdx6-siRNA．RAW264. 7 cells，a mouse macrophage cell line，were treated with various concentrations of KPA． Cell viability was assessed using the CCK-8 assay．The expression levels of Prdx6 and M1 macrophage polarization-related proteins，including inducible nitric oxide synthase ( iNOS) and cyclooxygenase-2 ( COX-2) ，were detected by Western blot and immunofluorescence staining．The expression levels of Prdx6 and M1 macrophage polarization-related genes iNOS，interleukin-6 ( IL-6) ，and tumor necrosis factor α ( TNF-α) ，were measured by RT-qPCR. Flow cytometry was employed to detect the expression of cluster of differentiation 86 ( CD86) ，a marker of M1 macrophages． Results: Compared with the LPS-induced M1 macrophage polarization model ， KPA significantly reversed the morphological changes of M1 macrophage polarization in RAW264. 7 macrophages and decreased the expression of M1 macrophage polarization-related proteins iNOS，COX- 2，CD86 and related genes iNOS，IL-6，TNF-α ( all P＜0. 05) ．In addition，LPS significantly downregulated the expression of Prdx6 in RAW264. 7 macrophages，while KPA upregulated the expression of Prdx6．Moreover，treatment with the Prdx6 inhibitor MJ33 significantly upregulated the expression of iNOS，a marker of M1 macrophage polarization，in RAW264. 7 macrophages，whereas treatment with KPA significantly downregulated the expression of iNOS ( all P＜0. 05) ． Conclusion KPA inhibits LPS-induced M1 polarization of RAW264. 7 macrophages by upregulating the expression of Prdx6．

Objective:To evaluate the relationship between the mechanism of buprenorphine in attenuating neuroinflammation in microglia and the MAM domain-containing glycosylphosphatidylinositol anchor gene 1 ( MDGA1). Methods:The human microglial cell line HMC-3 was cultured in vitro and divided into 4 groups ( n=6 each) using a table of random numbers: control group (Con group), lipopolysaccharide(LPS)group, buprenorphine + LPS group (Bup+ LPS group) and buprenorphine + LPS + MDGA1 knockdown group (Bup+ LPS+ shMDGA1 group). LPS group was incubated with LPS at a final concentration of 1 μg/ml for 4 h. Bup+ LPS group was incubated with buprenorphine at a final concentration of 100 ng/ml for 1 h, followed by incubation with LPS at a final concentration of 1 μg/ml for 4 h. Bup+ LPS+ shMDGA1 group was transfected with MDGA1-specific shorthairpin RNA for knockdown, and the remaining treatment was similar to those previously described in Bup+ LPS group. The expression of MDGA1 in microglia was detected using real-time quantitative polymerase chain reaction, and the concentrations of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) in the supernatant were measured using enzyme-linked immunosorbent assay. Results:Compared with Con group, the concentrations of IL-6, IL-1β, TNF-α and iNOS in the supernatant were significantly increased, and the expression of MDGA1 in microglia was down-regulated in LPS group ( P<0.05). Compared with LPS group, the concentrations of IL-6, IL-1β, TNF-α and iNOS in the supernatant were significantly decreased, and the expression of MDGA1 in microglia was up-regulated in Bup+ LPS group ( P<0.05). Compared with Bup+ LPS group, the concentrations of IL-6, IL-1β, TNF-α and iNOS in the supernatant were significantly increased, and the expression of MDGA1 in microglia was down-regulated in Bup+ LPS+ sh MDGA1 group ( P<0.05). Conclusions:The mechanism by which buprenorphine alleviates neuroinflammation in microglia may be related to the up-regulation of the expression of MDGA1.

The esophagogastric junction serves as a natural anti-reflux barrier and possesses a complex anatomical configuration composed of several key components, including the lower esophageal sphincter, diaphragmatic crura, His angle, and phrenoesophageal ligament. Alterations in these anatomical structures or dysfunction thereof may predispose individuals to gastroesophageal reflux disease (GERD). In response to such structural and functional impairments, various therapeutic strategies have been developed. Surgical intervention is currently regarded as an effective approach for fundamentally addressing GERD, with commonly employed techniques including laparoscopic fundoplication, magnetic sphincter augmentation, and endoscopic radiofrequency ablation. The author classifies the anti-reflux mechanisms at the esophagogastric junction into intramural and extramural components, and based on this classification, systematically reviews and evaluates the indications and clinical applications of major surgical interventions for GERD, aiming to provide clinicians with evidence-based guidance for selecting appropriate therapeutic modalities.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Currently, the performance of D2 lymphadenectomy for locally advanced gastric cancer (LAGC) has become an established therapeutic consensus. The accumulating evidence supporting the application of laparoscopic techniques in such procedures signifies the transition of laparoscopic radical gastrectomy from an exploratory phase into mature clinical practice, with the surgical volume showing a yearly increasing trend. Alongside advancements in imaging equipment, innovations in surgical instrument, and updates in therapeutic concepts, surgeons are placing increasing emphasis on the radicality of the operation, the quality of lymph node dissection, and perioperative safety. Lymph node dissection in the supra-pancreatic area along the celiac arterial system constitutes a critical step in radical gastrectomy for gastric cancer. Supra-pancreatic area serves not only as a major lymphatic drainage hub for the stomach but also presents significant surgical challenges due to its complex anatomy, difficult exposure, high risk of bleeding, and injury to vital structures traversing the area. Therefore, how to effectively reduce the difficulty for the assistant to expose, optimize the surgeon's control over the anatomical planes in this region, achieve more refined maneuvers, and consequently reduce bleeding, lower complication rates, and shorten operative time are core issues currently concerning surgeons. This article, based on author's clinical experience, aims to provide an in-depth discussion on the strategies for supra-pancreatic lymph node dissection in laparoscopic gastric cancer surgery.

Objective:To investigate the efficacy of lightroom therapy on depressive mood and sleep problems in patients with depression, and the potential effects on physiological indices related to circadian rhythms.Methods:From October 2021 to July 2023, 54 patients with acute-phase depression hospitalized in the Mental Health Center of the First Hospital of Hebei Medical University were recruited. The participants were randomly assigned to either medication combined with the bright light therapy group (bright light group, n=36) or medication combined with the dim light therapy group (dim light group, n=18). Both groups received light therapy for 2 weeks, at 10 000 lx in the bright light group and 300 lx in the dim light group. Both groups received 30 minutes of light therapy from 7:30-8:00 a.m daily over two weeks, followed up for 1 week post-treatment. The Hamilton Depression Rating Scale (HAMD 17) was used to assess patients′ depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess patients′ sleep quality at baseline, at the end of every week. The 32-Item Hypomania Checklist (HCL-32) was used at the end of week 2 to assess the risk of manic switching after treatment. Daily measurements of body temperature, heart rate, and blood pressure were taken before and after light therapy, along with recording adverse events related to the therapy. Paired t- tests were used to compare changes in physiological indicators before and after treatment, and repeated measures ANOVA was applied to compare clinical symptom changes between the two groups. Results:Thirty-one and fifteen patients completed this study in the bright light and dim light groups, respectively, with no statistically significant difference in dropout rates( P>0.05). There were significant interaction effects between the time and group for HAMD 17 and PSQI score( F=5.51,4.11, both P<0.05). Both groups showed significant reductions in HAMD 17 and PSQI scores at baseline, week 1, week 2, and week 3 ( P<0.001). In the bright light group, body temperature increased significantly post-treatment on days 1-4, day 7, and day 12 (all P<0.05). Heart rate elevated on day 5 ( P<0.05).Systolic blood pressure decreased on days 4, 5, 11, and 12 compared to the pre-treatment baseline(all P<0.05). In the dim light group, systolic blood pressure increased on day 11 ( P<0.05). Diastolic blood pressure in the bright light group decreased on days 1, 5, and 6( P<0.05). No serious adverse events, vision loss, ocular structural changes occurred in either group. No hypomania or mania episodes were observed. The incidence of adverse events did not differ significantly ( P>0.05). Conclusion:Medication combined with indoor bright light is more effective than the combination of dim light for depressive symptoms and sleep problems in patients with depression. Patients receiving bright light also may exhibit a higher body temperature, accelerated heart rate, and reduced blood pressure.

Objective:To explore the effects of childhood trauma on resting blood pressure, heart rate, and heart rate variability in patients with depression.Methods:A cross-sectional study was designed to prospectively collect clinical data on a total of 163 patients with depression, including 47 males and 116 females, aged 18-50 years,with mean[ M( Q1, Q3)] [29.0, (21.0, 37.0)]years, who were either the outpatients or the inpatients in the Mental Health Center of the First Hospital of Hebei Medical University from September 2022 to June 2024. The Childhood Trauma Questionnaire-Short form (CTQ-SF) was used to assess the experience of abuse and neglect during childhood. According to the CTQ-SF score, the subjects were divided into a trauma group ( n=80) and a non-trauma group ( n=83). The 17-item Hamilton Depression Scale (HAMD 17) and Hamilton Anxiety Scale (HAMA) were used to assess depressive and anxiety symptoms in the participants, respectively. A digital blood pressure monitor and an autonomic nervous system response detector were employed to measure resting blood pressure, heart rate, and heart rate variability (HRV). Spearman correlation analysis was used to examine the relationships between childhood trauma and resting blood pressure, heart rate, and HRV. Multiple linear regression analysis was performed to analyze factors influencing these parameters. The Bootstrap method was employed to test the potential mediating role of parasympathetic nervous system activity in the relationships between childhood trauma and resting blood pressure, and heart rate. Results:No significant difference was observed in resting heart rate between the trauma and non-trauma groups ( P>0.05). However, the trauma group exhibited higher resting systolic and diastolic blood pressure [(123.3±9.1) mmHg (1 mmHg=0.133 kPa) vs(116.9±10.8) mmHg, (80.0±8.6) mmHg vs (77.0±8.0) mmHg; Z=4.08, 2.24, all P<0.05]. HRV indices, including the standard deviation of normal to normal interval (SDNN), root mean square of successive differences (RMSSD), total power (TP), low frequency (LF), and high frequency (HF), were significantly lower in the trauma group [25.3 (19.4, 30.4) me vs 36.3 (27.4, 49.0) ms, 18.3 (12.9, 27.2) me vs 26.2 (19.0, 38.5) ms, 6.0(5.4, 6.5)ms 2vs 7.0(6.3, 7.4)ms 2,4.4(3.7,5.3)ms 2vs 5.8(4.9,6.3)ms 2, 4.2(3.4, 5.2)ms 2vs 5.2(4.6, 6.1)ms 2, respectively; all P<0.001]. Spearman correlation analysis showed that childhood trauma experiences in patients with depression were positively correlated with resting systolic blood pressure and diastolic blood pressure ( r=0.309, 0.236; P<0.01), childhood trauma was negatively correlated with HRV (SDNN, RMSSD, TP, LF, HF) ( r=-0.264, -0.274, -0.271, -0.235, -0.279; all P<0.01). Multiple linear regression analysis showed that childhood trauma was positively correlated with resting-state systolic blood pressure and resting-state diastolic blood pressure ( β=0.305, 0.291; all P<0.001). Childhood trauma was negatively correlated with RMSSD, TP, LF, and HF( β=-0.244, -0.249, -0.233, -0.263; all P<0.01). Mediation effect analysis showed that parasympathetic activity partially mediated the relationship between childhood trauma and resting systolic blood pressure (effect size 0.04, standard error 0.02, 95% CI=0.01-0.09), accounting for 14.29% (0.04/0.28) of the total effect. Conclusion:Childhood trauma experiences are associated with elevated resting blood pressure and reduced HRV in patients with depression. Decreased parasympathetic activity partially mediates the relationship between childhood trauma and elevated resting systolic blood pressure in these patients.

Objective:To analyze the efficacy and prognosis of surgical patients with traumatic epidural hematoma straddling the transverse sinus (TEHSTS).Methods:Clinical data of 4 360 patients with epidural hematoma admitted to the First Affiliated Hospital of Henan University of Science and Technology from January 2010 to April 2024 were collected. Among them, 109 cases (2.5%) were diagnosed with TEHSTS. Based on the rapid progression criteria for posterior fossa epidural hematoma [sudden deterioration of Glasgow Coma Scale (GCS) score within hours (a decrease of ≥1 point in the best motor response and/or a decrease of ≥2 points in GCS score), and progressive enlargement of TEHSTS on repeat CT scan], the timing and method of surgery were determined. Two surgical approaches were compared: combined supratentorial and infratentorial craniotomy (craniotomy group) and modified supratentorial burr-hole drainage (burr-hole group). Clinical data, surgical timing, surgical outcomes, and prognosis were compared between the two groups.Results:There were 57 cases (52.3%) in the craniotomy group and 52 cases (47.7%) in the modified burr-hole group. The proportion of patients presenting with vomiting upon admission was higher in the craniotomy group than in the burr-hole group [77.2%(44/57) vs 59.6%(31/52), P=0.048], and the proportion of patients with linear occipital fractures on CT was also higher in the craniotomy group [91.2%(52/57) vs 75.0%(39/52), P=0.023]. No significant differences were observed in other admission symptoms or CT findings between the two groups (all P>0.05). The GCS score upon admission was significantly lower in the craniotomy group [(11.0±1.0)points] than in the modified burr-hole group [(13.0±1.0)points] ( P<0.05). Four cases in the burr-hole group developed delayed hematomas, including two cases of bilateral delayed epidural hematomas. The preoperative GCS score in the craniotomy group [(9.0±0.5)points] was significantly lower than upon admission [(11.0±1.0)points] ( P<0.05), and the surgical timing was (6.5±1.5)hours after injury. The preoperative GCS score in the burr-hole group [(11.5±0.5)points] was also significantly lower than upon admission [(13.0±1.0)points] ( P<0.05), with surgical timing at (19.5±5.5)hours after injury. Preoperative CT scans showed no significant difference in hematoma volume between the burr-hole group [(35.5±7.5)ml] and the craniotomy group [(36.5±9.5)ml] ( P>0.05). The preoperative GCS score was significantly lower in the craniotomy group than in the burr-hole group ( P<0.05). The GCS scores at 24 hours postoperatively were significantly improved compared to preoperative scores in both groups (all P<0.05). The burr-hole group had significantly shorter operative time, less intraoperative blood loss, shorter intensive care unit (ICU) stay, and shorter hospital stay than the craniotomy group (all P<0.01). The incidence of postoperative pulmonary infection was lower in the burr-hole group than in the craniotomy group ( P<0.05). At 3-month follow-up, the rate of good recovery [Glasgow Outcome Scale (GOS) score≥4 points] was significantly higher in the burr-hole group (98.1%) than in the craniotomy group (93.0%) ( P<0.01). Conclusions:TEHSTS should be managed with different surgical approaches based on admission symptoms, GCS score, and the speed of disease progression. The modified burr-hole drainage procedure is convenient, safe, and associated with better prognosis.