Third Hospital of Hebei Medical University

The poor prognosis and high mortality rate of non‑small cell lung cancer are largely driven by its aggressive migratory and invasive behavior. Epithelial‑mesenchymal transition (EMT) is a central mechanism conferring these malignant traits. The present study examined the expression profile of the sodium channel β4 subunit (SCN4B) in lung adenocarcinoma (LUAD) and explored its regulatory role in EMT. Transcriptomic data from The Cancer Genome Atlas were analyzed to compare SCN4B expression between LUAD and normal tissues, and to assess its relationship with TNM clinical stage (I‑IV), overall survival and diagnostic performance using non‑parametric tests, Kaplan‑Meier analysis and receiver operating characteristic curves, respectively. Functional enrichment analysis, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and immune cell infiltration profiling were performed on SCN4B‑associated differentially expressed genes. In vitro, the A549 and H1299 LUAD cell lines were engineered to overexpress SCN4B. Viability, migration, invasion and apoptosis were evaluated using Cell Counting Kit‑8 assays, wound healing assays, Transwell assays and flow cytometry. In addition, western blotting was conducted to assess EMT markers, including E‑cadherin, N‑cadherin, Vimentin and Snail. The results demonstrated that SCN4B expression was markedly reduced in LUAD tissues and low SCN4B expression was associated with unfavorable clinical outcomes. KEGG analysis revealed enrichment of SCN4B‑related genes in the 'cell adhesion molecules' pathway, and SCN4B expression levels differed markedly between TNM tumor (T) pathologic stages T1 and T2. Furthermore, SCN4B overexpression suppressed viability, migration and invasion of A549 and H1299 cells, while promoting apoptosis. Western blotting demonstrated upregulation of E‑cadherin, and downregulation of N‑cadherin, Vimentin and Snail in the SCN4B overexpression group compared with the empty vector group, indicating inhibition of EMT. In conclusion, low SCN4B expression was associated with poor prognosis in LUAD. Notably, restoring SCN4B levels suppressed LUAD cell viability, migration and invasion in vitro, accompanied by inhibition of EMT. These findings highlighted SCN4B as a potential tumor suppressor and a promising therapeutic target for LUAD.

This study aims to explore the relationship between postoperative bone loss and cage subsidence (CS), as well as paraspinal muscle state and CS. The difference in vertebral Hounsfield Units (HU) between preoperative and postoperative CT scans was used to assess bone loss. Baseline characteristics of CS and non-CS groups were compared, followed by propensity score matching (PSM) and inverse probability treatment weighting (IPTW) for balance. Potential predictors from univariate analysis were adjusted for sex, age, and BMI in multivariate analysis to identify independent risk factors for CS. A total of 129 participants were included in the final analysis. The subsidence rate was 34.9%. The CS group had lower HU values. PSM successfully matched 36 pairs of patients, and the CS group exhibited more pronounced bone loss (CS 12.04 (11.07) vs. non-CS 5.64 (11.50), p = 0.016). IPTW analysis confirmed the robustness of the results. Univariate analysis indicated association between age, paraspinal muscle density, cage height, HU, bone loss, and CS. In multivariate analysis, only bone loss (OR: 1.96, 95% CI: 1.20–3.18, p = 0.01), and low HU (OR: 0.43, 95% CI: 0.22–0.84, p = 0.01) were identified as independent risk factors. Sensitivity analysis results were consistent with the main analysis. Preoperative vertebral HU, and postoperative bone loss were identified as independent risk factors for CS. Our study suggested that spine surgeons should pay attention to the preoperative bone status of lumbar fusion patients and emphasize postoperative anti-bone loss treatments to avoid implant complications.

Stress promotes the progression from borderline hypertension to sustained hypertension, but the mechanism remains unclear. We investigated the role of corticotropin-releasing factor (CRF)-expressing neurons in the central nucleus of amygdala (CeA) on arterial blood pressure (ABP) and sympathetic activity of borderline hypertensive rats (BHRs) subjected to chronic unpredictable mild stress (CUMS). CUMS induced sustained hypertension, and led to increased delta-FosB expression as well as enhanced spontaneous and evoked firing of CeA CRF-expressing neurons in BHRs. Furthermore, optogenetic activation of CeA CRF-expressing neurons significantly increased the sympathetic outflow and ABP in BHRs. Impaired GABAergic inhibition, a depolarizing shift of GABA reversal potential (EGABA), disrupted chloride homeostasis and increased NKCC1 expression were observed in CeA CRF-expressing neurons in BHRs subjected to CUMS. NKCC1 inhibition with bumetanide restored GABAergic inhibition and chloride homeostasis, normalized neuronal excitability, leading to reduced sympathetic vasomotor tone in CUMS BHRs. These results indicate that NKCC1-mediated disruption of chloride homeostasis in CeA CRF-expressing neurons contributes to elevated sympathetic activity and hypertension under chronic stress. These findings enhance our understanding of the neuronal and molecular mechanisms underlying stress-induced hypertension and reveal potential targets for its prevention and treatment.

Intervertebral disc degeneration (IVDD) is characterized by the senescence and apoptosis of nucleus pulposus cells (NPCs), metabolic imbalance of the extracellular matrix (ECM), and local chronic inflammation, presenting a long-standing challenge in clinical treatment. Recent studies have confirmed that transplanted stem cells are prone to apoptosis in vivo, and the apoptotic extracellular vesicles (ApoEVs) they produce are key mediators of tissue repair. Given that both the physiological state of mesenchymal stem cells (MSCs) and the IVDD microenvironment exhibit hypoxic and inflammatory features, this study investigated the therapeutic effect and mechanism of MSCs-derived apoptotic bodies (I-ApoEVs) pretreated with a hypoxic-inflammatory composite microenvironment on IVDD. The results showed that compared with ApoEVs under conventional hypoxic conditions, I-ApoEVs more significantly inhibited NPCs senescence and promoted ECM synthesis. More importantly, they could target and regulate the STAT6 signaling pathway, induce macrophages to polarize towards the M2 anti-inflammatory phenotype, thereby remodeling the local inflammatory microenvironment of the intervertebral disc and alleviating inflammation-mediated degenerative damage. In conclusion, pretreatment with a hypoxic-inflammatory composite microenvironment enhances the therapeutic function of ApoEVs by regulating macrophage polarization, providing a novel and highly translatable therapeutic strategy for IVDD.

To review the research progress related to pain in knee osteoarthritis (KOA). A systematic review of relevant research literature at home and abroad in recent years was conducted to analyze the roles played by multi-dimensional factors such as demographics, imaging, serology, bone metabolism, biomechanics, neurological factors, and macrophages in the occurrence and development of KOA pain. The mechanisms of pain induction were expounded and the research directions were prospectively proposed. The occurrence of KOA pain is a complex process interwoven with multiple factors. Demographic factors such as gender, age, and body weight are closely related to its occurrence and pain degree. Structural changes shown by imaging examinations (such as MRI, ultrasound, and X-ray films) can be used to assess the level of pain. A variety of inflammatory factors released by intra-articular inflammation directly participate in the initiation of pain. Bone metabolic factors can also induce pain by influencing changes in bone density. Biomechanical factors are involved in the pain process by altering the concentrated distribution of joint stress. The various mediators released by the local inflammatory response of the joint trigger hyperalgesia and peripheral nerve sensitization through damage receptors, promoting the conduction and amplification of pain signals. The bidirectional interaction between nerves and joints further intensifies the pain. In addition, the expression of certain ion channels, the mediation and release of pain signals by macrophages and osteoclasts, provide a theoretical direction for in-depth exploration of the microscopic mechanism of KOA pain. Future research needs to integrate multiple regulatory mechanisms such as biomechanics, inflammation and neural regulation, systematically explore key intervention targets, in order to deepen the understanding of the pain mechanism of KOA and promote the formation of more comprehensive and precise pain diagnosis and treatment plans.

To analyze the clinical and hepatic pathological characteristics of patients with chronic hepatitis B (CHB) alone or with non-alcoholic fatty liver disease (NAFLD), who have normal alanine aminotransferase (ALT) levels. The patients with normal ALT levels and pathologically diagnosed CHB alone or in combination with NAFLD were enrolled, the demographic, laboratory, and pathological data were collected and analyzed. Among 391 enrolled CHB patients with normal ALT levels, 107 individuals combined with NAFLD. The incidence of significant liver injury (G and/or S ≥ 2) in patients with CHB alone was lower significantly than that of patients with CHB and NAFLD (64.08% vs. 78.50%, P < 0.05), especially by the subgroup analyses in HBeAg positive, male, age > 30 years (P < 0.05). In all patients, who with negative HBcAg expression had lower HBV DNA levels than those with positive HBcAg expression (P < 0.001). Patients with G and/or S ≥ 2 had a higher proportion of HBcAg cytoplasm/cytoplasmic nucleus expression type compared to patients with liver tissue G and S < 2 (32.42% vs. 16.67% in CHB alone, 36.91% vs. 21.74% in CHB + NAFLD, all P < 0.001). Aspartate aminotransferase to ALT ratio index (AAR) demonstrated relatively superior efficacy in diagnosing significant liver fibrosis among patients with CHB and NAFLD, while fibrosis-4 (FIB-4) exhibited superior performance in patients with CHB alone. Patients with normal ALT can still demonstrate significant liver tissue damage. The combination of NAFLD will significantly increase the incidence of significant liver injury in patients with CHB, especially in those who are HBeAg positive, male, over 30 years old.

Hyaluronic acid (HA) is a cornerstone of aesthetic skin treatments due to its vital role in skin hydration and combating aging signs. This trial evaluated the efficacy and safety of a novel non-cross-linked HA gel for improving skin quality in a Chinese population. In this multicenter, randomized, controlled trial, 420 subjects were enrolled (2:1, treatment: control). The treatment group received three full-face intradermal injections of the HA gel at 3-week intervals, whereas the control group received no intervention. Primary end points were blinded evaluations of the Global Aesthetic Improvement Scale and a composite improvement rate for skin dryness/dullness. The treatment group showed significantly higher Global Aesthetic Improvement Scale improvement (90.63% vs 3.65%) and composite improvement rates (83.20% vs 3.65%) than control group (p < .0001), with effects sustained for 6 months. Skin hydration and elasticity significantly increased from baseline (p < .05). Peak efficacy rates for fine lines and roughness reached 51.59% and 50.00%, respectively. Adverse events were mild and transient, with decreasing incidence. This non-cross-linked HA gel effectively enhances skin hydration, elasticity, and texture with sustained 6-month benefits and a favorable safety profile, supporting its use for facial rejuvenation.