The rapid advancement of cell therapies underscores the importance of understanding fundamental cellular attributes. Among these, cell fitness—how transplanted cells adapt to new microenvironments and maintain functional stability in vivo—is crucial. This study identifies a chemical compound, FPH2, that enhances the fitness of human chondrocytes and the repair of articular cartilage, which is typically nonregenerative. Through drug screening, FPH2 was shown to broadly improve cell performance, especially in maintaining chondrocyte phenotype and enhancing migration. Single-cell transcriptomics indicated that FPH2 induced a super-fit cell state. The mechanism primarily involves the inhibition of carnitine palmitoyl transferase I and the optimization of metabolic homeostasis. In animal models, FPH2-treated human chondrocytes substantially improved cartilage regeneration, demonstrating well-integrated tissue interfaces in rats. In addition, an acellular FPH2-loaded hydrogel proved effective in preventing the onset of osteoarthritis. This research provides a viable and safe method to enhance chondrocyte fitness, offering insights into the self-regulatory mechanisms of cell fitness.

The present study aimed to explore whether high-salt diet (HSD) could cause cardiac damage independent of blood pressure, and whether nitric oxide (NO) could alleviate high-salt–induced cardiomyocyte apoptosis and autophagy in rats. The rats received 8% HSD in vivo. H9C2 cells or primary neonatal rat cardiomyocytes (NRCM) were treated with sodium chloride (NaCl) in vitro. The levels of cleaved-caspase 3/caspase 3, cleaved-caspase 8/caspase 8, Bax/Bcl2, LC3 II/LC3 I, Beclin-1 and autophagy related 7 (ATG7) were increased in the heart of HSD rats with hypertension (HTN), and in hypertension-prone (HP) and hypertension-resistant (HR) rats. Middle and high doses (50 and 100 mM) of NaCl increased the level of cleaved-caspase 3/caspase 3, cleaved-caspase 8/caspase 8, Bax/Bcl2, LC3 II/LC3 I, Beclin-1, and ATG7 in H9C2 cells and NRCM. The endothelial NO synthase (eNOS) level was increased, but p-eNOS level was reduced in the heart of HSD rats and H9C2 cells treated with 100 mM NaCl. The level of NO was reduced in the serum and heart of HSD rats. NO donor sodium nitroprusside (SNP) reversed the increases of cleaved-caspase 3/caspase 3, cleaved-caspase 8/caspase 8, Bax/Bcl2 induced by NaCl (100 mM) in H9C2 cells and NRCM. SNP treatment attenuated the increases of cleaved-caspase 3/caspase 3, Bax/Bcl2, LC3 II/LC3 I, Beclin-1, and ATG7 in the heart, but had no effect on the blood pressure of HSD rats with HR. These results demonstrated that HSD enhanced cardiac damage independently of blood pressure. Exogenous NO supplementarity could alleviate the high salt–induced apoptosis and autophagy in cardiomyocytes.

Purpose: Osteoarthritis (OA) is a widespread joint disease characterized by the gradual loss of cartilage. Intra-articular injections, including platelet-rich plasma (PRP), are commonly used for treatment, but the optimal PRP preparation method remains debated. This study aims to perform a network meta-analysis of randomized controlled trials to compare the efficacy of different PRP preparation methods and determine the most effective protocols. Methods: The literature search was conducted based on PRISMA guidelines. Randomized controlled trials (RCTs) evaluating intra-articular injectables in osteoarthritic knees were included. Data were extracted, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were analyzed at 3, 6, and 12–18 months. Clinical outcomes were compared using a frequentist network meta-analysis, and treatment options were ranked using the P-Score. Statistical analysis was performed using R 4.3.2. Results: Twenty-three RCTs with 1752 patients were included. Treatments included PRP, plasma rich in growth factor (PRGF), leukocyte-poor PRP (LP-PRP), leukocyte-rich PRP (LR-PRP), hyaluronic acid (HA), and saline placebo. Leukocyte-rich PRP with low platelet concentration increase, using both anticoagulant and activator showed the best effects on WOMAC pain and stiffness scores within 6 months (WMD = 26.02; 95% CrI, 0.92–52.46). Leukocyte-poor PRP with high platelet concentration increase, using anticoagulant without activator was most effective for WOMAC function and stiffness at 12–18 months (WMD = 18.94; 95% CrI, 8.34–28.12). Long-term results indicated Leukocyte-poor PRP with low platelet concentration increase, using anticoagulant without activator yielded the best outcomes for cartilage repair and function (WMD = 17.09; 95% CrI, -8.4 to 42.78). Conclusions: Optimizing OA treatment involves tailoring PRP protocols to disease stage, with low platelet, high leukocyte PRP (RPRP_LPC_Y_Y) recommended for early OA due to its anti-inflammatory effects and high platelet, low leukocyte PRP (PPRP-HPC) preferred for advanced OA to promote tissue repair and regeneration.

Objective: To investigate the clinical value of percutaneous radiofrequency ablation (RFA) for liver metastasis from lung cancer (LCLM). Materials and Methods: We retrospectively enrolled 58 patients who underwent RFA for LCLM between January 2014 and December 2019. Primary lung cancer histology included 38 adenocarcinomas, 15 squamous carcinomas, and 5 small cell carcinomas. For 83 metastatic lesions (mean tumor diameter 3.3 ± 1.1 cm, range 0.9–5.0 cm), 65 RFA sessions were performed. Before RFA, 17 and 41 patients presented no and stable extrahepatic metastasis, respectively, whereas 18 and 40 patients had synchronous and metachronous liver metastasis, respectively. Survival was analyzed using the Kaplan-Meier method. Cox proportional hazards model was used for multivariable analysis. Results: The technical success rate was 96.3% (80/83 lesions). Local tumor progression was observed in 8 (9.8%, 8/82) lesions of 57 (14.0%, 8/57) patients at 4–12 months after RFA. New liver metastases occurred in 27 (46.6%) patients. The overall survival (OS) rates at 1, 2, 3, and 5 years after RFA were 55.2%, 26.0%, 22.0%, and 14.4%, respectively. The median OS after RFA and after liver metastasis were 14.0 ± 1.6 and 20.0 ± 1.5 months, respectively. Based on the univariable analysis, tumor size (p=0.017), histological type (p=0.015), and timing of liver metastasis (p=0.046) were related to OS. In further multivariable analyses, squamous carcinoma (hazard ratio= 2.269, 95% confidence interval: 1.186-4.339, p=0.013) was an independent unfavorable prognostic factor for OS. Based on the univariable analysis, histological type (p=0.010) was identified as parameters significantly related to local tumor progression (LTP)-free survival. Further multivariable analyses revealed that squamous carcinoma (hazard ratio=2.394, 95% confidence interval: 1.260–4.550, p=0.008) was an independent unfavorable prognostic factor for LTP-free survival. Conclusion: RFA is a safe therapeutic option for LCLM with acceptable local tumor control, especially in patients with a tumor size ≤3 cm, adenocarcinoma/small cell carcinoma, and metachronous liver metastases.

Background: Intravaginal electrical stimulation (IVES) has been explored as a potential treatment for pelvic floor disorders (PFDs), although its efficacy remains a subject of debate. We aim to conducted a comprehensive meta-analysis of relevant trials.Methods: This meta-analysis was performed under the PRISMA 2020 guideline. We meticulously searched for randomized controlled trial (RCT) studies in various databases, including PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov, spanning from inception to March 6, 2023. All studies included one treatment group of intravaginal electrical stimulation and the diseases spectrum of the studies involved different kinds of PFDs, including urinary incontinence, overactive bladder, etc. Risk of bias charts were used to assess the risk of bias in the studies and forest plots were used the demonstrate the overall effects.Results: Our analysis encompassed a total of 13 RCT studies. In most of the assessed PFD cure outcomes, the results demonstrated positive effects of IVES therapy, as indicated by the following findings: daily voiding frequency (MD = −1.57, 95% CI = −3.08 to −0.06, I² = 68%,), nocturia (MD = −1.07, 95% CI = −2.01 to −0.13, I² = 71%), Pad test, and Urinary incontinence. Nevertheless, the data concerning the impact of IVES therapy on the quality of life of individuals with PFDs did not confirm these positive results.Discussion: In light of the insufficiency in both the quality and quantity of the included studies, it is premature to draw a definitive conclusion regarding the efficacy of IVES therapy for treating PFDs. Nonetheless, our study does provide several pieces of evidence in support of the potential therapeutic effects of electrical stimulation therapy in this context. We recommend that further research in this area be conducted to provide more conclusive insights into the efficacy of IVES therapy for PFDs.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023442171.

SUMMARY: The human uterus is a highly dynamic tissue that undergoes repeated damage repair and regeneration during the menstrual cycle, which make it ideal model to study tissue regeneration and pathological process. Stem/progenitors were speculated to be involved in the regeneration of endometrial epithelial and pathogenesis of endometriosis. But the identity, microenvironment and regulatory mechanisms of the uterus epithelial stem/progenitors in vivo remain unclear. Here, we dissected the cell heterogeneities of the full-thickness human uterus epithelial cells (11 clusters), stroma cells (6 clusters), endothelial cells (5 clusters), smooth muscle cells (2 clusters), myofibroblasts (2 clusters) and immune cells (6 clusters) from 2735 single cell by single cell RNA-seq. Further analysis identified a unique ciliated epithelial cell cluster showing characteristics of stem/progenitors with properties of epithelial-mesenchymal transition (EMT) that mainly localized in the upper functionalis of the endometrium. Ordering the cell subpopulations along the pseudo-space revealed cell clusters possess cellular states of stress, inflammation and apoptosis in the upper functionalis cellular ecosystem of the endometrium. Connectivity map between the human uterus subpopulations revealed potential inflammatory (cytokines and chemokines) and developmental (WNT, FGF, VEGF) signals within the upper functionalis cellular ecosystem of the endometrium, especially from other epithelial clusters, regulating cell plasticity of the EMT-epithelial clusters. This study reconstructed the heterogeneities, space-specific distribution and connectivity map of human uterus atlas, which would provide insight in the regeneration of uterus endometria and reference for the pathogenesis of uterus.