Southwest Hospital

This study investigated the association of BMI, weight change patterns, and absolute weight change with mortality in adults (≥ 50 years) with diabetes or prediabetes. A longitudinal cohort analysis of 11,518 NHANES (2005-2018) participants assessed BMI categories, weight change patterns (stable normal weight, persistent overweight, obesity transitions, persistent obesity), and absolute weight change (loss, stable, gain). Cox models and restricted cubic splines evaluated mortality risks, adjusting for covariates. BMI showed a U-shaped mortality relationship, with obesity increasing all-cause (HR: 1.60, 95% CI: 1.20-2.13) and diabetes-related mortality (HR: 2.53, 95% CI: 1.35-4.75). Persistent obesity from young adulthood raised mortality risks (all-cause: +60%; diabetes-related: +153%), while later-life persistent overweight reduced risk. Weight loss (≥ 2.5kg) increased mortality, whereas moderate gain (2.5-20kg) was protective. Results remained robust in sensitivity analyses. For person with diabetes or prediabetes prevention, maintaining normal weight in early adulthood and modest weight gain with aging is beneficial. Older adults may benefit from mild overweight to lower mortality risk. Age-specific weight management strategies should guide clinical and public health recommendations. The online version contains supplementary material available at 10.1007/s40200-026-01896-6.

Current frozen shoulder (FS) therapies present a clinical dilemma: although intra-articular corticosteroids with home exercise provide proven medium-term (3-month) benefits, they lack short-term (<4-week) efficacy for rapid recovery; conversely, manipulative treatments achieve faster outcomes but carry invasiveness risks. These limitations highlight the urgent need for developing and validating novel noninvasive approaches with prompt therapeutic effects. To compare the efficacy and safety of ultrasound-guided tendon surface (UGTS) injection versus manipulation under local anesthesia (MULA) and blind tender point (BTP) injection, all combined with intra-articular injection and home exercise. Randomized controlled trial; Level of evidence, 1. The authors first developed a novel ultrasound-based strategy, which they named "ultrasound-guided tendon surface." Then they conducted a multicenter randomized controlled trial (2019-2022). The primary outcome was 4-week shoulder function assessed by the Beijing Friendship Hospital Scale (BFHS), a modified version of the Constant-Murley Score adapted for Chinese populations with demonstrated validity. Secondary outcomes included (1) short-term (1-month) pain (visual analog scale [VAS]) score, active range of motion (ROM), Evaluation Scale of the Shoulder under Ultrasound (ESSU) score, pain relief, treatment sessions, and cartilage thickness; and (2) long-term (2-year) complete remission rates (tele-follow-up). Among 365 screened patients, 139 were enrolled and randomized to receive UGTS (n = 49), MULA (n = 43), and BTP (n = 47). At the 1-week follow-up visit, the UGTS group showed rapid improvement in BFHS scores compared to both the MULA and BTP groups. These early functional advantages were also indicated by the VAS score, ROM, ESSU score, and pain relief. UGTS achieved faster complete remission (1 month: 59.2% vs 31.0% and 34.9% for BTP and MULA, respectively; 3-month: 79.6% vs 53.2% and 69.8% for BTP and MULA, respectively; P < .05), with remission rates converging by 24 months (P = .216), yet retained early rapid response as its key clinical advantage. UGTS showed no significant impact on articular cartilage thickness. Serial ultrasound monitoring demonstrated no rotator cuff injuries attributable to either the UGTS procedure or prescribed exercises. UGTS combined with intra-articular injection and exercise promotes faster recovery without safety concerns, representing an effective noninvasive first-line option for rapid relief in FS. ChiCTR1900025874 (Chinese Clinical Trial Registry number).

Peripheral nerve regeneration and functional recovery hold immense clinical significance, as they are critical for reinnervating the motor and sensory functions of organs. In this study, piezoelectric nerve guidance conduits (NGCs) with multidimensional oriented structures and zinc oxide (ZnO) nanoparticles were developed for this purpose, fabricated via a combination of digital light processing (DLP) 3D printing and directional freezing technologies. The therapeutic efficacy of the NGCs was evaluated in a rat model of sciatic nerve defect, with continuous monitoring of neuromorphological and functional recovery metrics. Results indicated that the oriented structure of the NGCs and the piezoelectrically generated electric field significantly promoted both morphological regeneration and functional restoration of peripheral nerves, achieving repair effects comparable to the gold-standard autologous nerve transplantation. This work presents a promising strategy for the clinical treatment of peripheral nerve defects.

Neointimal hyperplasia, driven by abnormal proliferation and survival of vascular smooth muscle cells (VSMCs), underlies atherosclerotic stenosis and restenosis after angioplasty or stenting. Edelfosine (ET-18-OCH₃) is an alkylphospholipid with pro-apoptotic activity. We tested whether edelfosine limits pathological VSMC growth and neointimal lesion formation by enforcing cell-cycle arrest and apoptosis. Primary VSMCs from mouse and rat aortas were exposed to edelfosine (0–15 µM). Viability (MTT) and DNA synthesis (BrdU) were quantified. DNA content and binucleation were assessed by laser scanning cytometry and immunofluorescence. Apoptosis was measured by TUNEL and by cleavage of caspase-9, -7, and -3, with the pan-caspase inhibitor Z-VAD-FMK to test caspase dependence. Apoptosis in live cells was also analyzed using Annexin V and propidium iodide staining. Intracellular Ca²⁺ was imaged and measured in fluorescent Ca²⁺ indicator-loaded cells. In vivo, carotid artery ligation in mice induced neointimal hyperplasia; edelfosine or vehicle was delivered locally, and lesion size was measured morphometrically. Vascular apoptosis was further evaluated by TUNEL. Edelfosine reduced VSMC viability and proliferation in a dose- and time-dependent manner; at 5–10 µM it suppressed BrdU incorporation by > 90% and triggered extensive cell death. Cells accumulated with 4 N DNA content and showed increased binucleation, consistent with G₂/M arrest and failed cytokinesis. Approximately 40% of edelfosine-treated VSMCs were TUNEL-positive versus ~ 5% with vehicle (p < 0.001), coincident with activation of caspase-9, -7, and -3; Z-VAD-FMK prevented caspase-3 cleavage and reduced TUNEL positivity. Mechanistically, edelfosine induced endoplasmic reticulum (ER) stress (increased phospho-eIF2α), upregulated Bax, and evoked a rapid rise in intracellular Ca²⁺ in the presence of extracellular Ca²⁺. Edelfosine-induced Ca²⁺ elevation was reduced by extracellular Ca²⁺ chelation with EGTA, blockade of VGCCs with nifedipine, and perturbation of IP₃ receptor-linked Ca²⁺ pathways with 2-APB. In vivo, edelfosine significantly reduced neointimal lesion size after carotid ligation, lowering the intima-to-lumen ratio (p < 0.05) and increasing TUNEL positivity within the vessel wall. Edelfosine enforces G₂/M cell-cycle arrest and caspase-dependent apoptosis in VSMCs, linked to ER stress and Ca²⁺ influx, thereby limiting neointimal hyperplasia after blood flow cessation. Local edelfosine delivery may offer a dual anti-proliferative and pro-apoptotic strategy to prevent restenosis.

Context Ginkgolic acid (GAC), one of the major active constituents of Ginkgo biloba L. (Ginkgoaceae) extract, has been reported as a potential anticancer agent. Objective To investigate the effect of GAC on the viability of human hepatocellular carcinoma (HCC) cells and to identify its primary target and underlying mechanism. Materials and methods Human HCC cell lines and an orthotopic HCC mouse model were employed. The mechanism of GAC was elucidated through integrated analyses of cell viability, RNA sequencing, and biomarkers. The primary target of GAC was identified by drug affinity responsive target stability (DARTS) coupled with LC-MS/MS and further validated using molecular docking (MD), cellular thermal shift assay (CETSA), and microscale thermophoresis (MST) assay. Mechanistic roles were confirmed using genetic approaches, including gene knockdown and the construction of mutant plasmids. A KFERQ reporter system was used to detect the activity of chaperone-mediated autophagy (CMA). Results GAC effectively inhibits the viability of HCC by triggering ferroptosis. HSPA8 was identified as the direct target of GAC. The binding of GAC with HSPA8 enhances its interaction with glutathione peroxidase 4 (GPX4), which leads to the degradation of GPX4 via CMA. This process depleted glutathione (GSH) and caused lipid peroxidation, finally inducing ferroptosis in HCC cells. Furthermore, GAC suppressed tumor growth in an orthotopic HCC model, increased lipid peroxidation, and GPX4 degradation in tumor tissues. Discussion and conclusions Our results revealed a novel mechanism by which GAC induces ferroptosis in HCC cells through direct targeting of HSPA8 and promoting CMA-dependent GPX4 degradation. These findings suggest GAC-mediated ferroptosis as a potential therapeutic strategy against HCC and expand the pharmacological application of CMA-targeted cancer therapies.

This study aimed to compare the outcomes of no-touch radiofrequency ablation (NT-RFA) and conventional RFA (C-RFA) in the treatment of solitary recurrent hepatocellular carcinoma (rHCC) ≤ 3 cm. 255 patients with rHCC treated with RFA in our center from January 2017 to December 2023 were retrospectively analyzed (NT-RFA: 63, C-RFA: 192 patients). Short- and long-term outcomes were compared, and survival rates were calculated. The ablation range and safety margin differed significantly between the two groups (both p < 0.01). The 1-, 3-, and 5- years overall survival (OS) rates were 96.83%, 75.51% and 45.61% respectively in the NT-RFA group, while 97.39%, 77.48% and 48.56% in the C-RFA group, with no significant difference between the two groups (P = 0.510). The 1-, 3-, and 5-year recurrence-free survival (RFS) rates in the NT-RFA group were 73.02%, 46.22% and 36.77%, respectively, while 69.70%, 38.95% and 27.78% in the C-RFA group, with no significant difference between the two groups (P = 0.338). The 1-, 3-, 5-year local tumor progression (LTP) free survival rates in the NT-RFA and C-RFA group were 84.13%, 67.04%, 67.04% and 78.02%, 53.70%, 48.80% respectively, with significant difference between the two groups (P = 0.047). However, there was no significant difference in intrahepatic distant recurrence free survival rates between the two groups (P = 0.068). NT-RFA treatment for rHCC ≤ 3 cm is as safe as C-RFA, but it achieves a larger ablation range and safety margin. Although NT-RFA does not significantly improve RFS or OS in rHCC ≤ 3 cm, it significantly reduces the LTP.