AIM:To evaluate visual outcomes and visual function in nonamblyopic adults with myopic anisometropia treated with small incision lenticule extraction(SMILE).METHODS:Prospective comparative cohort study. The consecutive patients who underwent SMILE for the treatment of myopia or myopic astigmatism at Zhongshan Ophthalmic Center(Guangzhou, China)between October 2015 and January 2016 were included. They were divided into two groups based on the bilateral difference of a spherical equivalent(SE)refraction ≥1.50 D: the anisometropic myopia group(interocular SE difference ≥1.50 D)and non-anisometropic myopia group(interocular SE difference<1.50 D). Refractive status, uncorrected and corrected distance visual acuity(UDVA and CDVA), and visual function parameters including fusional vergence amplitude, stereoacuity and horizontal phoria were measured preoperatively and at 1 wk,1,3 and 6 mo after surgery.RESULTS:A total of 49 cases(98 eyes)were included in the study, and 19 cases(38 eyes)in the anisometropic group, including 11 males and 8 females, with a mean age of 25.4±6.2 y, and 30 cases(60 eyes)in the non-anisometropic myopia group, including 19 males and 11 females, with a mean age of 26.8±4.6 y. The CDVA of the non-anisometropia group was significantly better than that of the anisometropia group 6 mo postoperatively(P=0.036). However, the safety and efficacy indexes of the two groups did not show significant differences. The fusional vergence(break point and recovery point)of the anisometropia group decreased(P=0.005 and P=0.03)and was significantly lower than that in the non-anisometropia group at 6 mo post operatively(P=0.029 and P=0.046). Both groups showed a significant improvement in distance and near stereopsis at 1, 3 and 6 mo in comparison with the preoperative baseline and 1 wk postoperatively(all P<0.05). No clinically significant change in the amount of ocular alignment in terms of distance and near deviation postoperatively in either groups.CONCLUSION: SMILE is a predictable, effective, and safe method for correcting myopic anisometropia in adults without amblyopia. Although the fusional vergence amplitudes changed, stereopsis can be improved after surgery.

Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

Objective To investigate the post-discharge exercise behavior and factors influencing moderate to vigorous intensity physical activity (MVPA) in patients undergoing lung surgery. Methods A total of 2874 patients from the large prospective, observational perioperative lung symptom study cohort (CN-PRO-Lung 3) in the Department of Thoracic Surgery at Sichuan Cancer Hospital between April 7, 2021, and January 31, 2024, were selected as the survey subjects. A survey was conducted using the Investigation of Exercise Behavior after Lung Surgery questionnaire and the International Physical Activity Questionnaire-Short Form (IPAQ-SF) among patients who underwent lung surgery. Binary logistic regression was used to analyze the factors influencing patients’ engagement in MVPA. Results A total of 702 patients were surveyed, including 252 males and 450 females, with an average age of (52.4±10.2) years. Patients with lung cancer accounted for 85.9%. Only 36.0% of the patients had regular exercise habits, while 42.3% did not engage in any physical activity. The three main barriers for postoperative exercise were physical discomfort (pain, coughing, shortness of breath, etc, 54.7%), lack of professional guidance (41.7%), and concerns about the surgical wound (28.9%). The proportions of patients engaging in vigorous, moderate, and low-intensity physical activity were 5.7%, 28.2%, and 66.1%, respectively. Multivariate analysis showed that patients with a personal annual income ≥50000 yuan (OR=1.52, 95%CI 1.01-2.29, P=0.044), high school education or above (OR=1.92, 95%CI 1.33-2.76, P<0.001), and lobectomy (OR=1.44, 95%CI 1.02-2.03, P=0.037) engaged in more MVPA. Conclusion Patients undergoing lung surgery have inadequate physical activity after discharge, particularly lacking in MVPA. Patients with higher income, higher educational levels, and lobectomy are more frequently engaged in MVPA. Measures such as symptom control, providing exercise guidance, and enhancing education on wound care may potentially improve the inadequate physical activity in lung surgery patients after discharge.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVE: To evaluate the clinical efficacy of modified high tibial osteotomy combined with platelet-rich plasma in the treatment of moderate to severe knee osteoarthritis. METHODS: From January 2021 to March 2022, the clinical data of 60 patients with moderate to severe knee osteoarthritis admitted to the Third Affiliated Hospital of Beijing University of Chinese Medicine were analyzed. Among them, 30 patients were treated with modified tibia high osteotomy combined with platelet-rich plasma as the observation group, including 12 males and 18 females, aged from 51 to 74 years old, with an average age of (64.37±5.72) years old. The course of disease ranged from 1 to 7 years with an average of(3.43±1.41) years. Thirty patients were treated with modified high tibial osteotomy combined with sodium hyaluronate as control group, including 10 males and 20 females, aged from 50 to 78 years, with an average age of (64.33±8.18) years. The course of disease was 1 to 7 years with an average of(3.30±1.39) years. Knee X-rays were taken before surgery and at the last follow-up, and the changes of lower limb bearing-line ratio (WBLR), proximal medial tibial Angle (MPTA), femoro-tibial angle (FTA) and posterior tibial slope (PTS) were compared between the two times. Visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Lysholm score were used to evaluate knee pain and functional changes before surgery and at 1, 3, and 6 months after surgery. RESULTS: The wounds of all patients healed in stage I after surgery. All 60 patients completed treatment and follow-up, with an average follow-up duration of (8.08±1.75) months, ranged from 6 to 12 months. No serious adverse events or complications occurred. At the last follow-up, WBLR, MPTA and FTA were significantly improved in both groups (P<0.05). At the last follow-up, there was no significant difference in PTS between the two groups compared with pre-operation(P>0.05). At the last follow-up, there were no significant differences in WBLR, MPTA, FTA and PTS between the observation group and the control group (P>0.05). The VAS scores, WOMAC scores and Lysholm scores of both groups were significantly Modified with time after operation (P<0.05). At 1, 3 and 6 months after operation, VAS score, WOMAC score and Lysholm score of the observation group were significantly better than those of the control group, with statistical significance (P<0.05). CONCLUSION For patients with moderate and severe knee osteoarthritis, modified high tibial osteotomy can significantly correct lower limb alignment, and combined with platelet-rich plasma therapy can further significantly relieve knee pain and improve knee function, the effect is better than combined with sodium hyaluronate.
Humans ; Male ; Female ; Osteoarthritis, Knee/physiopathology* ; Middle Aged ; Osteotomy/methods* ; Platelet-Rich Plasma ; Aged ; Tibia/surgery*

The healing of the tendon-bone interface is a complex dynamic process involving the interaction of multiple cellular and molecular signaling pathways. Bone mesenchymal stem cells (BMSCs) have the potential to differentiate into various types of cells, including osteoblasts, chondrocytes and adipocytes, etc., and have the potential to regenerate damaged tissues. They are potential seed cells for promoting tendon-bone healing. How to precisely regulate the proliferation and differentiation of BMSCs to accelerate the process of tendon-bone healing is a current research hotspot. Monomers of traditional Chinese medicine can promote tendon-bone healing by regulating signaling pathways such as Wnt/β-catenin and BMP/Smad to induce osteogenic and chondrogenic differentiation of BMSCs. This article reviews from several aspects such as the regulatory role of related signaling pathways on tendine-bone healing, traditional Chinese medicine monomers and their mechanism of regulating BMSCs to promote tendine-bone healing in order to providing new ideas for promoting tendine-bone healing.
Mesenchymal Stem Cells/cytology* ; Humans ; Animals ; Bone Marrow Cells/cytology* ; Bone and Bones/drug effects* ; Wound Healing/drug effects* ; Medicine, Chinese Traditional ; Tendons/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Cell Differentiation/drug effects*