Objective:To prepare heparin (Hep)-modified gelatin methacryloyl (GelMA) microspheres and to investigate their application in liver-targeted delivery of adipose-derived mesenchymal stem cells (ADSCs).Methods:GelMA microspheres were modified with Hep to obtain GelMA-Hep microspheres. The surface morphology of the GelMA-Hep microspheres was observed by scanning electron microscopy. The changes of carbon atoms, nitrogen atoms and sulfur atoms on the surface of the GelMA-Hep microspheres were detected by X-ray photoelectron spectroscopy. The surface chemical group composition of the GelMA-Hep microspheres was analyzed by Fourier transform infrared spectrometer. The swelling properties of the GelMA-Hep microspheres were detected by water absorption swelling experiment. Human liver HL-7702 cells transfected with lentivirus were co-cultured with GelMA, GelMA-dopamine (GelMA-dop) and GelMA-Hep microspheres. The effects of microspheres on cell proliferation activity were evaluated by cell counting kit-8 method and live/dead cell staining experiment. The adhesion of microspheres to cells was observed by confocal microscopy. The GelMA-Hep microspheres loaded with ADSCs were injected into C57BL/6 mice through the tail vein, and its efficiency of liver-targeted delivery of ADSCs was observed by a small animal in vivo imaging system. The data were compared by independent sample t test or one-way analysis of variance. Results:The GelMA-Hep microspheres were prepared by modifying the GelMA microspheres with Hep. Compared with the GelMA microspheres, the size of the GelMA-Hep microspheres did not change significantly, and the surface did not collapse and showed some crystalline particles. The binding energy of sulfur atoms on the surface of the GelMA-Hep microspheres increased from 166 eV to 168 eV. On the surface of the GelMA-Hep microspheres, the characteristic peaks of sulfonic acid and sulfate groups of Hep were detected at 1 490 cm ?1 and from 1 135 cm ?1 to 1 050 cm ?1, respectively. The swelling rate of the GelMA-dop microspheres was uniform, while the swelling rate of the GelMA microspheres and the GelMA-Hep microsphere was quite different, but the final swelling mass of the three microspheres tended to be consistent at 5 min. After 12, 24, 36 and 48 h of culture, the relative proliferation of cells in the GelMA-Hep group (1.61±0.29, 1.78±0.05, 2.27±0.08, 2.26±0.33) were higher than those in the negative control group (1.00±0.00, 1.28±0.06, 1.39±0.02, 1.41±0.04) (all P<0.05). After 36 h of culture, the relative proliferation of cells in the GelMA-Hep group was higher than that in the GelMA-dop group (1.63±0.21), with significant difference ( P<0.05). Live/dead cell staining experiment showed that after 12 h of cell culture in the GelMA-Hep group, only a few microspheres had cell adhesion; at 24 h, the cells were densely distributed on the surface of the microspheres. After 36 h, the number of cells increased further. At 48 h, live cells were distributed throughout the microspheres. Confocal microscopy showed that after 24 h of culture, cells adhered to the surface of the microspheres in the GelMA-Hep group and showed a stretched morphology. The liver of the GelMA-Hep+ADSCs group showed strong fluorescence at 0.5 h, and the fluorescence brightness continued to 48.0 h. The number of ADSCs reaching the liver was more than that of ADSCs group and GelMA+ADSCs group. Conclusions:GelMA-Hep microspheres were successfully prepared, which can improve the efficiency of liver-targeted delivery of ADSCs.

Left atrial appendage closure(LAAC)is an important intervention method for preventing thromboembolic events in patients with non-valvular atrial fibrillation(NVAF).However,incomplete endothelialization following the procedure can impact its long-term efficacy and safety.This article proposes the view of qi flourishment promoting tissue regeneration based on the traditional Chinese medicine(TCM)theory of qi and blood,and explores diagnostic and therapeutic strategies for post-LAAC incomplete endothelialization by examining the theoretical connotation of qi flourishment promoting tissue regeneration and the relationship between qi and vascular endothelial cells.It is proposed that the primary pathogenesis in patients after LAAC is due to qi deficiency.Guided by the view of qi flourishment promoting tissue regeneration,therapeutic approaches such as tonifying qi to promote granulation,supplementing qi to activate blood circulation,and harmonizing the viscera can be employed to address incomplete endothelialization in NVAF patients following LAAC.Clinically,the qi-supplementing and blood-activating classic formula Neituo Shengji San,mainly composed of Astragali Radix,Glycyrrhizae Radix et Rhizoma,Olibanum,Myrrha,Paeoniae Radix Alb,Trichosanthis Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.,is usually utilized for modified use.Depending on the specific symptom patterns or pathogenesis characteristics of patients with incomplete endothelialization,this basic formula may be used by combining with Shengmai San or augmented with qi-supplementing and blood-activating herbs such as Chuanxiong Rhizoma,Fici Simplicissimae Radix,and Notoginseng Radix et Rhizoma to promote endothelialization.Diagnosing and treating post-LAAC incomplete endothelialization in NVAF patients following the view of qi flourishment promoting tissue regeneration,it is expected to offer a novel TCM perspective and therapeutic strategy to enhance post-LAAC outcomes and address the challenge of incomplete endothelialization.This approach can further serve as a reference for TCM clinicians to manage endothelialization issues following implantation procedures.

OBJECTIVE: To explore the effectiveness of the modified Lemaire procedure in anterior cruciate ligament reconstruction (ACLR) in patients with a highly positive pivot shift test. METHODS: The clinical data of 18 patients with anterior cruciate ligament (ACL) rupture and highly positive pivot shift test between April 2020 and September 2022 were retrospectively analyzed. There were 13 males and 5 females with an average age of 28.3 years (range, 17-41 years). Causes of injury included 11 cases of direct violence injury, including 6 cases of traffic accident injury, 4 cases of sports injury, 1 case of falling injury; 7 cases of indirect violence injury, all sports injury. All patients had complete ACL rupture, including 15 acute injuries and 3 old injuries. The preoperative pivot shift test was grade Ⅱ in 9 cases and grade Ⅲ in 9 cases. All patients were treated with ACLR combined with modified Lemaire procedure. The International Knee Documentation Committee (IKDC) score and Lysholm score were used to evaluate the effectiveness before operation and at 3, 6, 12 months after operation. KT-2000 arthrometer was used to measure the anterior stability of the knee joint, and the difference between the healthy and affected sides was recorded. Pivot shift test was used to evaluate the rotational stability of the knee joint. During the follow-up, X-ray films were taken to observe the bone tunnel and internal fixation, and MRI was used to examine the healing of ACL, anterolateral collateral ligament and fibular collateral ligament grafts. RESULTS: All patients completed the operation successfully without complications such as knee joint infection, vascular and nerve injury. All patients were followed up 12-19 months (mean, 13.2 months). After operation, the rotational stability of the knee joint recovered satisfactorily, and there was no adverse symptom such as knee instability and locking at last follow-up. X-ray film and MRI showed that the bone tunnel was anatomically located and healed well, the internal fixation was in good position, and the reconstructed ACL and iliotibial band were continuous and in good tension. The IKDC score, Lysholm score, and the difference of KT-2000 between the healthy and the affected sides significantly improved at 3, 6, and 12 months after operation ( P<0.05). All the indicators further improved with time after operation, except that there was no significant difference in IKDC score between 3 and 6 months after operation and in the difference of KT-2000 between 3 months and 6, 12 months after operation ( P>0.05), and there were significant differences in other indicators between different time points ( P<0.05). Pivot shift test was negative immediately after operation and at last follow-up. CONCLUSION In ACL injuries with a highly positive pivot shift test, ACLR combined with the modified Lemaire procedure can effectively restore anterolateral knee stability, leading to satisfactory knee stability and function in the early postoperative period.
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Male ; Female ; Anterior Cruciate Ligament Injuries/physiopathology* ; Adult ; Adolescent ; Retrospective Studies ; Young Adult ; Anterior Cruciate Ligament/surgery* ; Treatment Outcome ; Joint Instability/surgery* ; Knee Joint/physiopathology* ; Range of Motion, Articular

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective:By comparing the relevant image manifestations and diagnostic results of high resolution CT (HRCT) and digital radio graphy (DR), to deeply explore the clinical application value of HRCT in the diagnosis and staging of occupational pneumoconiosis.Methods:A total of 180 pneumoconiosis patients with different stages diagnosed in Guangzhou Twelfth People's Hospital from January 2022 to May 2023 were selected as the research objects by systematic sampling method, and their HRCT and DR examinations were performed. The display of lung imaging features of patients with pneumoconiosis by the two examination methods was analyzed, and the chi-square test and rank sum test were used to compare the differences in diagnostic staging results and the detection of pulmonary complications.Results:Among the patients with pneumoconiosis, there were 174 males and 6 females, with an age of (53.11±12.22) years old and a working age of (14.94±11.43) years. The number of lung areas with category 0 small opacity profusion in the HRCT images of patients was less than that in the DR images, and the number of lung areas with category 1 small opacity profusion was more than that in the DR images ( P<0.05). There was no statistically significant difference in the number of lung areas with category 2 and category 3 small opacity profusion detected by the two images ( P>0.05). The distribution of diagnostic differences between HRCT and DR images for the staging of pneumoconiosis was statistically significant ( P<0.05), and the detection rates of HRCT for pneumoconiosis complicated with pulmonary tuberculosis, pneumonia, atelectasis, lymph node tumefaction, and pleural thickening were all higher than those of DR ( P<0.05) . Conclusion:In the diagnosis of pneumoconiosis, HRCT has advantages over DR images in showing the fine structure of the lungs, determining the degree and extent of lesions. It is of great significance for discovering and differentiating complications of pneumoconiosis, and providing an important basis for clinical staging.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

AIM:To investigate the regulatory effects of proanthocyanidins on autophagy and apoptosis in the retinas of guinea pigs with form-deprivation myopia via the AMPK/Wnt/β-catenin pathway.METHODS:Fifty guinea pigs were randomly divided into a normal control group, a myopia model group, and low-dose, medium-dose, and high-dose proanthocyanidins groups(25, 50 and 100 mg/kg). Refractive power and axial length of right eye were measured using a retinoscope and A-scan ultrasound. Retinal pathological changes were observed via HE staining. Immunohistochemistry assessed p-AMPK and p-mTOR expression in the retina. Immunofluorescence detected p62 and LC3 expression. TUNEL staining evaluated retinal cell apoptosis. Western blot examined expression of proteins related to the AMPK/Wnt/β-catenin pathway and autophagy(p62, Beclin1, LC3-II/LC3-I), and apoptosis-related proteins(Bax, Bcl-2, Cleaved-Caspase3, Caspase3)in the retina.RESULTS:Compared with the control group, the myopia model group showed significantly reduced refractive power and significantly increased axial length(both P<0.05); retinal cell arrangement became sparse and retinal thickness thinned. The p-AMPK levels in the retina were significantly reduced, while p-mTOR levels were significantly increased(both P<0.05), indicating suppression of the AMPK-Wnt/β-catenin pathway. The p62 levels were significantly elevated and LC3 levels were significantly reduced(both P<0.05), suggesting inhibition of autophagy. Bax and Cleaved-Caspase3 were significantly increased, while Bcl-2 was significantly decreased, indicating significantly increased apoptosis(both P<0.05). Compared with the myopia model group, all proanthocyanidins dose groups significantly inhibited refractive error reduction and axial length growth(both P<0.05), restored retinal cell alignment and thickness, activated the AMPK/Wnt/β-catenin pathway, significantly increased p-AMPK expression, and suppressed p-mTOR expression(all P<0.05); significantly suppressed p62 expression, increased Beclin1 and LC3-II/LC3-I expression(both P<0.05), and activated retinal autophagy; significantly suppressed Bax and Cleaved-Caspase3 expression, increased Bcl-2 expression(both P<0.05), and inhibited retinal cell apoptosis.CONCLUSION:Proanthocyanidins enhance retinal autophagy by activating the AMPK/Wnt/β-catenin pathway, thereby inhibiting retinal apoptosis and preventing or alleviating the onset of myopia.

Objective:By comparing the relevant image manifestations and diagnostic results of high resolution CT (HRCT) and digital radio graphy (DR), to deeply explore the clinical application value of HRCT in the diagnosis and staging of occupational pneumoconiosis.Methods:A total of 180 pneumoconiosis patients with different stages diagnosed in Guangzhou Twelfth People's Hospital from January 2022 to May 2023 were selected as the research objects by systematic sampling method, and their HRCT and DR examinations were performed. The display of lung imaging features of patients with pneumoconiosis by the two examination methods was analyzed, and the chi-square test and rank sum test were used to compare the differences in diagnostic staging results and the detection of pulmonary complications.Results:Among the patients with pneumoconiosis, there were 174 males and 6 females, with an age of (53.11±12.22) years old and a working age of (14.94±11.43) years. The number of lung areas with category 0 small opacity profusion in the HRCT images of patients was less than that in the DR images, and the number of lung areas with category 1 small opacity profusion was more than that in the DR images ( P<0.05). There was no statistically significant difference in the number of lung areas with category 2 and category 3 small opacity profusion detected by the two images ( P>0.05). The distribution of diagnostic differences between HRCT and DR images for the staging of pneumoconiosis was statistically significant ( P<0.05), and the detection rates of HRCT for pneumoconiosis complicated with pulmonary tuberculosis, pneumonia, atelectasis, lymph node tumefaction, and pleural thickening were all higher than those of DR ( P<0.05) . Conclusion:In the diagnosis of pneumoconiosis, HRCT has advantages over DR images in showing the fine structure of the lungs, determining the degree and extent of lesions. It is of great significance for discovering and differentiating complications of pneumoconiosis, and providing an important basis for clinical staging.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.