Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine

ObjectiveTo elucidate the molecular mechanisms underlying thrombin-induced suppression of osteoblast differentiation, and to identify the MEK inhibitor PD0325901 (PD03) as a potential therapeutic candidate.MethodsFollowing treatment of primary rat osteoblasts with thrombin (20 U/mL) and PD03 (0.1 μM) during osteogenic induction, the cells were harvested and subjected to RNA sequencing to identify differentially expressed genes (DEGs). The combination of network pharmacology and RNA sequencing was used to predict the targets of PD03 in thrombin-induced osteoblasts. Alkaline phosphatase (ALP) activity was assessed through staining and quantitative analysis; the expression of osteogenic genes was measured by quantitative PCR (qPCR) and western blot; mineralized nodule formation was evaluated by Alizarin Red S staining; the expression of signaling pathway-related proteins (p-Erk1/2, p-Stat3, p-p65, MMP-9, COX-2) and proliferation-related proteins (PCNA and MCM2) were examined by western blot; nuclear localization of NF-κB was observed by immunofluorescence (IF); intracellular calcium levels were quantified using a calcium assay and probe labeling; osteoblast proliferation was evaluated by EdU staining; IL-1β secretion in cell supernatants was detected by ELISA; the expression of IL-1RA was measured by western blot; the effects of MMP-9 knockdown and COX-2 overexpression on osteogenic differentiation were investigated.ResultsThrombin promoted osteoblast proliferation and inhibited osteogenic differentiation by upregulating inflammatory factors and activating inflammatory signaling pathways, including MEK-Erk1/2 and NF-κB, which in turn reduced ALP activity, calcium ion influx, expression of osteogenic markers (e.g., Col1α1, Runx2, OCN), and mineralized nodule formation. PD03 reverses these effects by suppressing thrombin-induced activation of IL-1β-dependent signaling pathway, in which the downstream gene MMP-9 plays a critical role.ConclusionPD03 inhibits thrombin-induced activation of the IL-1β-mediated feedback loop between the MEK-Erk1/2 and NF-κB pathways, thereby restoring bone formation and offering a promising therapeutic approach for mitigating bone loss in patients with elevated thrombin levels.

Allergic rhinitis is a common chronic non-infectious inflammatory disease. Research indicates that the gut microbiota, as a core human microecosystem, may play a pivotal role in the pathogenesis and progression of AR through the “gut-nose axis.” Tradi

Inflammatory factors are closely related to the recurrence of atrial fibrillation (AF) after cryoablation. The objective of this study was to assess the potential of the serum uric acid (UA) to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) for post-cryoablation AF recurrence. Among 519 patients diagnosed with nonvalvular AF who received cryoablation at the Shanghai Tenth People’s Hospital, individuals were categorized into four groups according to their UHR quartiles. Multivariate logistic regression was employed to identify the independent factors predicting AF recurrence post-cryoablation. Subgroup analyses were conducted according to AF type. Kaplan–Meier analysis was used to evaluate the AF-free survival of patients during follow-up. ROC curves were employed to determine the predictive value of the UHR index for AF recurrence post-cryoablation. As UHR quartiles increased from lowest to highest, patients showed progressively decreasing HDL-C levels ([Formula: see text] [Formula: see text]mmol/L versus [Formula: see text] [Formula: see text]mmol/L versus [Formula: see text] [Formula: see text]mmol/L versus [Formula: see text] [Formula: see text]mmol/L, [Formula: see text]), increasing UA values ([Formula: see text]mol/L versus [Formula: see text]mol/L versus [Formula: see text]mol/L versus [Formula: see text]mol/L, [Formula: see text]), and a higher incidence of AF recurrence (3.88% versus 9.92% versus 17.69% versus 61.24%, [Formula: see text]). Persistent AF ([Formula: see text], 95% CI: 1.394–6.426, [Formula: see text]) and UHR ([Formula: see text], 95% CI: 1.012–1.019, [Formula: see text]) were identified as independent predictors of AF recurrence post-cryoablation. A clear trend across increasing UHR quartiles was observed for AF recurrence (P for [Formula: see text]). ROC analysis revealed a UHR cutoff point of 413.46, which exhibited a sensitivity of 60.0% and specificity of 95.7% in predicting AF recurrence. The ROC curve for UHR had an area under the curve (AUC) of 0.880 (95% CI: 0.820–0.940, [Formula: see text]) for late AF recurrence and 0.803 (95% CI: 0.745–0.860, [Formula: see text]) for extremely late AF recurrence. Decision curve analysis (DCA) showed a wide threshold range (0.02–0.95) with significant net clinical benefits for practical application. Our findings suggest UHR as a novel and reliable predictor of AF recurrence after cryoablation, including both late and extremely late recurrence, thereby offering valuable insights for clinical practice.

To explore the effectiveness of mini external fixators combined with bone cement spacers in the treatment of gouty hallux rigidus with bone defects. A retrospective analysis was conducted on the clinical data of 21 male patients diagnosed with gouty hallux rigidus and bone defects, treated with mini external fixators combined with bone cement spacers between January 2017 and December 2024. The age ranged from 35 to 72 years, with an average age of 61.1 years. The disease duration was 12-35 years, with an average of 18.2 years. The American College of Rheumatology (ACR) gout score ranged from 16 to 23, with an average of 18.6. All 21 cases of hallux rigidus were classified as grade 3 according to the Coughlin classification. Clinical efficacy was evaluated preoperatively and at 6 months postoperatively using the visual analogue scale (VAS) score for pain, the dorsiflexion angle of first metatarsophalangeal joint in a weight-bearing state, and the American Orthopaedic Foot & Ankle Society (AOFAS) score. Radiological evaluation was performed by measuring the hallux valgus angle (HVA) using weight-bearing X-ray films and the tophi volume using dual-energy CT. The operation time ranged from 30 to 56 minutes, with an average of 42.05 minutes. The intraoperative blood loss varied between 10 and 30 mL, averaging 20 mL. All 21 patients were followed up 6-15 months, averaging 9.3 months. One patient experienced delayed wound healing due to the liquefaction of residual tophus; no other patients exhibited complications such as wound or pin tract infections, skin necrosis, fractures, or metastatic metatarsalgia. Six patients experienced acute gout attacks 4-7 days postoperatively, which were effectively alleviated through symptomatic treatment. At 6 months after operation, patients showed significant improvements in HVA, tophus volume, VAS scores, AOFAS scores, and the dorsiflexion angle of first metatarsophalangeal joint compared to preoperative values, with significant differences ( P<0.05). Mini external fixator combined with a cement spacer is an effective treatment for gouty hallux rigidus with bone defects.

Bacterial infection can cause severe pneumonia which leads to high morbidity and mortality. The pathophysiology of pneumonia is characterized by epithelial damage. Our lab recently reported on miRNA-302 (miR-302) family that plays an important role in epithelial regeneration by promoting proliferation of alveolar epithelial progenitor cells to regenerate alveolar epithelial cells (AECs). The existing dilemma on miRNA therapeutics in clinical applications is characterized by effectiveness of cellular uptake and endosomal escape. Here, we describe an optimized lipid nanoparticle (LNP) strategy for the delivery of miRNA mimics to AECs for respiratory tract infection. In this study, we developed miR-302-LNP mimics delivered by nasal administration for lung therapy. Optimized treatment of Klebsiella pneumoniae (Kp)-infected mice with miR-302 mimics improved pulmonary function, host recovery, and survival. To understand the mechanisms of protection against pneumonia, we examined AECs damage and regeneration in Kp-infected mouse lungs. Our results showed that Kp-infected murine pneumonia model with lethal dosage, resulting in severe damage to AECs. We found an increase of miR-302 in AECs, which coincided with AECs regeneration in the miR-302–treated mice. These results demonstrate a promising miRNA-based therapy to enhance host recovery from bacterial pneumonia, which can be used as a novel application of regenerative medicine for the treatment of lung injury.

Background Muscle atrophy—the decline of skeletal muscle volume and function—is pervasive in chronic disease, aging, and inactivity. As the primary driver of human mobility and metabolic health, skeletal muscle loss diminishes quality of life and increases healthcare burden. Atrophy impairs recovery and prognosis by reducing metabolic capacity, accelerating systemic protein catabolism, and compromising the biomechanical support necessary for movement and respiration. Although core molecular pathways and cellular changes are well characterized, the role of mechanical cues in modulating these mechanisms remains underexplored. Main Findings Our review reveals five convergent atrophy drivers—mechanical unloading, ECM alterations, mitochondrial dysfunction/oxidative stress, inflammation, and endocrine imbalance—that converge on inhibited mTORC1 signaling, activated FoxO/UPS/autophagy, and impaired satellite‐cell function. Quantitative data show that axial stretch preserves PI3K/Akt/mTOR activity, with phosphorylated Akt levels increasing by two‐ to three‐fold and fiber cross‐sectional area expanding by 10%–20%; low‐intensity compression activates AMPK and autophagy, with AMPK phosphorylation rising by 1.5‐fold without triggering excessive protein breakdown; and shear stress enhances VEGF and Nrf2‐mediated angiogenesis and antioxidant defenses, doubling VEGF expression and reducing ROS levels by 25% to mitigate neurogenic atrophy. Moreover, stem‐cell myogenic differentiation is optimized on 3D biomimetic substrates with stiffness from 11 to 17 kPa under physiological loading, and advances in biomaterials and tissue engineering enable more accurate muscle‐tissue models. Future Directions Translating these biomechanical insights into tailored clinical interventions—combining stretch, compression, and shear modalities with biomaterials, stem-cell technologies, and personalized exercise programs— holds promise for preventing and reversing muscle atrophy across diverse patient populations.

ABSTRACTIntroductionInflammation has been implicated in both reproduction and sleep; however, the relationships remain unclear, and conclusive evidence for genetic associations is lacking.MethodsThis study utilized the 2013–2020 National Health and Nutrition Examination Survey (NHANES) data and conducted a Mendelian randomization (MR) analysis to investigate the associations among inflammation, sleep, and female infertility. A cross‐sectional study was performed on 370 infertile women aged 20–44 years. Multiple linear regression was applied to evaluate the associations between sleep and the inflammatory markers. Subgroup and interaction analyses were conducted to assess the robustness of the findings. MR analysis was performed on 91 circulating inflammatory proteins, 11 sleep traits, and infertility to examine potential genetic associations.ResultsA total of 370 infertile participants aged 20–44 years were included. The logarithmic platelet–lymphocyte ratio (PLR) was significantly higher in the sleep disorder group (p < 0.05). After adjusting for potential confounders, sleep disorders remained associated with a reduction in PLR (β = −0.145, 95% CI: −0.267 to −0.023, p < 0.05). MR analysis using the inverse variance weighted (IVW) method indicated that insomnia, subjective long sleep duration, and high sleep efficiency were associated with increased levels of oncostatin‐M, artemisinin, and adenosine deaminase, all of which are implicated in infertility. Additionally, the morning type was associated with increased levels of C‐X‐C motif chemokine 5, which reduced the risk of infertility.ConclusionSleep is associated with various inflammatory factors in the body and may contribute to infertility. Inflammation appears to play a key role in mediating the complex interplay between sleep and reproduction. These findings highlight the potential value of screening and managing specific inflammatory markers in infertile patients with sleep disorders to improve reproductive outcomes. However, further clinical studies and mechanistic experiments are needed to validate the genetic associations identified in this study.

Thalidomide, once discovered and used to treat pregnancy sickness, fell out of favor with teratogenicity scandals, and then re-entered the public eye with its amazing efficacy against leprosy and multiple myeloma, and its anti-tumor and anti-inflammatory effects were gradually discovered. In recent years, thalidomide has also begun to gain prominence for its role in digestive disorders, particularly for its anti-angiogenic effects, which are effective in the treatment of dysplastic gastrointestinal hemorrhage. The therapeutic effects of thalidomide in other digestive disorders, including radiation proctitis, inflammatory bowel disease, and malignant tumors of the digestive tract, such as liver, colorectal, gastric, esophageal, and pancreatic cancers, have been proposed in several clinical trials and case reports. Due to its potential adverse effects and controversial clinical utility, it has not been put into clinical use for digestive diseases in large numbers, but its unique therapeutic effects still warrant further study, so this paper analyses and summarizes the use, mechanism of action, and potential therapeutic uses of thalidomide in digestive diseases.

To compare the early clinical outcomes of posterior cruciate ligament-retaining (CR) and posterior stabilized (PS) knee prostheses in total knee arthroplasty for patients with rheumatoid arthritis. A retrospective analysis was conducted on 74 patients with rheumatoid arthritis (RA) who underwent unilateral total knee arthroplasty (TKA) from January 2021 to December 2022. Among these, 39 patients received CR prostheses (CR group), while 35 received PS prostheses (PS group). Data on operation time, intraoperative blood loss, hospital stay, preoperative and postoperative Visual Analogue Scale (VAS) scores, American Knee Society Score (AKSS), Functional Joint Score-12 (FJS-12) scores, Health Assessment Questionnaire scores (HAQ) and postoperative complications were recorded and compared between the two groups. All 74 patients successfully completed the surgery without complications. The average operation time for the CR group was shorter than that of the PS group, with no statistically significant differences in intraoperative blood loss or hospital stay. Both groups showed improved postoperative AKSS scores, VAS scores, and HAQ Scores compared to preoperative levels. Between-group comparisons showed no statistical differences in postoperative AKSS, VAS, HAQ scores. However, the CR group had significantly higher FJS-12 scores at 6 and 12 months postoperatively compared to the PS group. Both CR and PS prostheses can achieve good clinical outcomes in TKA for RA patients. Compared to PS prostheses, CR prostheses may provide better knee proprioception postoperatively, as indicated by higher FJS-12 scores at 6 and 12 months postoperatively.