Regenerating periodontal bone defect surrounding periodontal tissue is crucial for orthodontic or dental implant treatment. The declined osteogenic ability of periodontal ligament stem cells (PDLSCs) induced by inflammation stimulus contributes to reduced capacity to regenerate periodontal bone, which brings about a huge challenge for treating periodontitis. Here, inspired by the adhesive property of mussels, we have created adhesive and mineralized hydrogel microspheres loaded with traditional compound cordycepin (MMS-CY). MMS-CY could adhere to the surface of alveolar bone, then promote the migration capacity of PDLSCs and thus recruit them to inflammatory periodontal tissues. Furthermore, MMS-CY rescued the impaired osteogenesis and ligament-forming capacity of PDLSCs, which were suppressed by the inflammation stimulus. Moreover, MMS-CY also displayed the excellent inhibitory effect on the osteoclastic activity. Mechanistically, MMS-CY inhibited the premature senescence induced by the inflammation stimulus through the nuclear factor erythroid 2-related factor (NRF2) pathway and reducing the DNA injury. Utilizing in vivo rat periodontitis model, MMS-CY was demonstrated to enhance the periodontal bone regeneration by improving osteogenesis and inhibiting the osteoclastic activity. Altogether, our study indicated that the multi-pronged approach is promising to promote the periodontal bone regeneration in periodontitis condition by reducing the inflammation-induced stem cell senescence and maintaining bone homeostasis.
Animals ; Bone Regeneration/drug effects* ; Rats ; Periodontal Ligament/cytology* ; Microspheres ; NF-E2-Related Factor 2 ; Hydrogels ; Periodontitis/therapy* ; Osteogenesis/drug effects* ; Disease Models, Animal ; Stem Cells ; Male ; Rats, Sprague-Dawley ; Humans

Chronic wounds, defined as persistent failure to heal due to specific etiological factors, remain a major clinical challenge. Current standard interventions such as negative pressure wound therapy are limited by complications like hypergranulation and poor patient compliance, while emerging stem cell-based therapies carry potential tumorigenic risks. Consequently, identifying strategies to safely and effectively accelerate wound healing continues to be a critical focus in contemporary clinical research. Platelet-rich plasma derived extracellular vesicles (PRP-EVs) are extracellular vesicles released by platelets after activation. They have the characteristics of autologous origin, higher safety, and more mild and convenient clinical application. Studies have shown that PRP-EVs are rich in bioactive molecules such as lipids, proteins and RNA, which have outstanding performance in regulating wound inflammation, promoting angiogenesis, enhancing cell migration and proliferation, and are expected to become an effective tool for the treatment of chronic wounds. This review discusses the methods, mechanisms of action, and challenges associated with the use of PRP-EVs in chronic wound management, providing a foundation for future research and clinical applications in this field.

Chronic wounds, defined as persistent failure to heal due to specific etiological factors, remain a major clinical challenge. Current standard interventions such as negative pressure wound therapy are limited by complications like hypergranulation and poor patient compliance, while emerging stem cell-based therapies carry potential tumorigenic risks. Consequently, identifying strategies to safely and effectively accelerate wound healing continues to be a critical focus in contemporary clinical research. Platelet-rich plasma derived extracellular vesicles (PRP-EVs) are extracellular vesicles released by platelets after activation. They have the characteristics of autologous origin, higher safety, and more mild and convenient clinical application. Studies have shown that PRP-EVs are rich in bioactive molecules such as lipids, proteins and RNA, which have outstanding performance in regulating wound inflammation, promoting angiogenesis, enhancing cell migration and proliferation, and are expected to become an effective tool for the treatment of chronic wounds. This review discusses the methods, mechanisms of action, and challenges associated with the use of PRP-EVs in chronic wound management, providing a foundation for future research and clinical applications in this field.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective To explore the risk factors for acute thrombosis of arteriovenous fistulae(AF)in maintenance hemodialysis(MHD)patients and the construction of a Nomogram prediction model.Methods A total of 418 patients who underwent MHD treatment in the outpatient clinic of the Third Affiliated Hospital of Xinxiang Medical University from December 2020 to December 2022 were selected for the study.The patients were divided into the acute thrombosis group(n=32)and non-acute thrombosis group(n=386)according to whether acute thrombosis of AF was formed or not.The influencing factors affecting acute thrombosis of AF in MHD patients were analyzed using univariate and multivariate analysis.A Nomogram predic-tion model was established based on their independent risk factors,and Bootstrap was used to validate the efficacy of the Nomo-gram model.Results The complicated diabetes,complicated hypotension,puncture failure on dialysis,calcium-phosphorus product,hypersensitive C-reactive protein(hs-CRP),total cholesterol(TC),and low density lipoprotein-cholesterol(LDL-C)levels in patients in the acute thrombosis group were significantly higher than those in the non-acute thrombosis group(P＜0.05);logistic regression analysis showed that diabetes,hypotension,puncture failure on dialysis,calcium-phosphorus product elevation,high hs-CRP and high LDL-C level were the independent risk factors affecting acute thrombosis of AF in patients undergoing MHD(P＜0.05);the Nomogram model was constructed based on the 6 independent risk factors,and the consistency index(C-index)of the model was 0.893(95％confidence interval:0.833-0.928);in addition,its calibration curve and the standard curve were well fitted,the area under the curve was 0.918.Conclusion Diabetes,hypotension,puncture failure during dialysis,calcium-phosphorus product elevation,and high levels of hs-CRP and LDL-C are the risk factors for acute thrombosis of AF in patients undergoing MHD,and the Nomogram model constructed based on the independent risk factors has excellent predictive ability in predicting the occurrence of acute thrombosis of AF in patients undergoing MHD,which can help in the early screening of patients with high risk of clinical acute thrombosis.

Objective To prepare 4-sulfonylcalix[6]arene-modified cotton fibers for adsorption and removal of uranium based on the specific complexation of calix[6]arene with uranium (VI). Methods Chemical grafting was used for the modification of cotton, which reacted with α-bromoisobutyryl bromide, glycidyl methacrylate, and 4-sulfonylcalix[6]arene. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FTIR) were used to characterize the structure of 4-sulfonylcalix[6]arene-modified cotton (Cotton S-C[6]a). A Franz diffusion cell was used to simulate uranium-contaminated skin. Laser fluorimetry was used to determine the uranium content. Results SEM, XPS, and FTIR showed that cotton fibers were successfully grafted with 4-sulfonylcalix[6]arene. The optimal conditions of Cotton S-C[6]a for the adsorption of uranium (VI) was pH 4.0, duration of 20 min, and 20 mg of adsorbent. The adsorption process fitted well with pseudo-secondary-order kinetics. The uranium removal efficiency of Cotton S-C[6]a was up to 78.46% in aqueous solution and 81.72% on skin. Conclusion The synthesized Cotton S-C[6]a is highly efficient in the removal of uranium (VI) in solution and on contaminated skin.

BACKGROUND: Dabrafenib+Trametinib/Dabrafenib targeted therapy has been approved for V-RAF murine sarcoma viral oncogene homolog B1 with amino acid substitution for valine at position 600 (BRAF V600E) in lung cancer patients, however, the targeted therapy strategy for lung cancer patients with BRAF non-V600E mutations has not been determined yet. This study intends to explore the efficacy of targeted therapy for BRAF non-V600E mutant lung cancer, and provide a reference for clinical treatment. METHODS: Computer search of PubMed, Cochrane Library, Embase, Web of Science, Clinicaltrials.gov, CBM, CNKI, Wanfang database. Collect the relevant literature relevant on the targeted therapy of BRAF non-V600E mutant lung cancer, and conduct a descriptive analysis of the included literature. RESULTS: There were 10 articles that met the inclusion criteria, including 3 cohort studies and 7 case reports. 18 patients with BRAF non-V600E mutant lung cancer were ineffective to vermurafenib; 1 patient obtained partial response (PR) after applying vermurafenib, 5 patients did not respond to BRAF inhibitors; 9 patients showed a potential clinical benefit rate of 34% after monotherapy with trametinib; 7 patients have different degrees of benefit from dabrafenib and trametinib on progression-free survival (PFS); 1 patient is effective to sorafenib. CONCLUSIONS At present, there is no standard treatment specification for BRAF non-V600E mutation targeted therapy. The challenge lies in the heterogeneous mutation of BRAF gene. Different mutation types respond differently to targeted therapy. In addtion, real-world research evidence is scarce, so it is necessary to carry out further large-sample high-quality research to provide reference for clinical practice.
Animals ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/genetics* ; Mice ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins B-raf/genetics*

Objective To explore dendritic cells (DCs)-mediated antigen presentation for radiation-injured cells by using the in vitro cell co-culture technology to simulate the in vivo microenvironment of the lung tissue. Methods ⁶⁰Co γ-irradiated mouse lung epithelial cells (MLE-12) were cultured with bone marrow-derived DCs and/or splenic T lymphocytes for 48 hours. Flow cytometry was used to measure the expression levels of costimulatory molecules (CD80/86) and antigenic peptide recognition complexes (the major histocompatibility complex [MHC] class Ⅰ/Ⅱ) on DCs and T cell activation markers (CD69/28/152) as well as the numbers of CD4⁺ and CD8⁺ T cells. Results ⁶⁰Co γ irradiation significantly increased the apoptosis rate of MLE-12 cells in a dose-dependent manner, and significantly stimulated the expression of CD80/86 and MHC Ⅱ on DCs, without direct activation of T cells. After γ (6 Gy)-irradiated MLE-12 cells were co-cultured with DCs and T lymphocytes for 48 h, there were significant increases in the expression of CD69 and CD28 on T cells, the numbers of CD4⁺ and CD8⁺ T cells, and the expression of CD86 and MHC I on DCs, as compared with the control groups. Conclusion Radiation-injured cells can stimulate antigen presentation by DCs and activate T cells.

Objective To investigate the role of complement in radiation-induced lung injury in mice after chest irradiation with ⁶⁰Co γ-rays at a single dose of 20 Gy. Methods C57BL/6 mice underwent chest irradiation with ⁶⁰Co γ-rays at a single dose of 20 Gy, followed by observation for the inflammatory reaction of the lung tissue in the early stage (within 15 d) and pulmonary fibrosis in the later stage (30 and 180 d). Enzyme-linked immunosorbent assay was used to measure the levels of C2, C3a, C4, and C5b-9 in the lung tissues at 1, 3, 7, 15, 30, and 180 d after irradiation. The expression of complement mRNA in BEAS-2B cells after irradiation was determined using RT-PCR. Results Radiation-induced lung injury in micepresented as inflammatory response in the early stage and fibrosis in the late stage. Complement C2, C4, and C5b-9 complexes were increased in the early period (3 or 7 d) after irradiation (P < 0.05), which might be associated with the inflammatory response induced by irradiation. During 3 to 180 d, complement C3a was significantly higher in the irradiated mice than in the control mice, suggesting a close relationship between C3a and radiation-induced lung injury. The irradiated cells showed increased mRNA expression of C2 and C3, with no changes in the mRNA levels of C4 and C5. Conclusion Different complement proteins have varying responses to radiation-induced lung injury, among which C3a is closely related to radiation-induced lung injury, suggesting that regulating C3a and its receptors may be a new way to prevent and treat radiation-induced lung injury.

OBJECTIVE：To study the effects of Modified liuwei dihuang decoction on kidney/bone injury of chronic kidney disease-mineral and bone disorder（CKD-MBD）model rats. METHODS ：The male SD rats were randomly divided into normal group（n＝10），high phosphorus group （n＝30），model group （n＝30），calcitriol group （positive control ，0.09 μg/kg，n＝30）， Modified liuwei dihuang decoction group （10 g/kg by crude drug ，n＝30）. CKD-MBD model was established by high phosphorus and adenine diet for 6 weeks. After modeling ，normal group and model group were given normal diet/high phosphorus diet and intragastric administration of water. Administration groups were fed with normal diet and given corresponding solution intragastrically（water as solvent ），0.1 mL/kg，once a day ，for consecutive 6 weeks. Blood sample of rats in the normal group were collected ，and they were sacrificed after the last administration. Blood sample of 10 rats in each other group were collected ， and they were sacrificed at 2，4 and 6 weeks after administration. The contents of blood urea nitrogen （BUN），serum creatinine （Scr），calcium，phosphorus，iPTH，FGF-23，RANKL and osteocalcin in serum were detected in each group. The bone mineral density（BMD）of femoral was measured ，the morphological changes of renal tissue and bone tissue were observed ，and the percentage of renal tubular injury and the score of renal interstitial fibrosis were calculated. RESULTS ：Compared with normal group，above indexes in high phosphorus group had no significant change at different time points （P＞0.05）. There was no abnormal change in renal/bone tissue. Compared with high phosphorus group at the same time point ，the contents of BUN ，Scr， phosphorus，iPTH，FGF-23，RANKL and osteocalcin in serum ，the percentage of renal tubular injury and the score of renal interstitial fibrosis in the model group were significantly increased ，while the contents of calcium in serum and the BMD of femoral were significantly decreased （P＜0.05 or P＜0.01）. The renal tissue showed diffuse fibrosis. The width of trabecular bone was increased and the number of osteoblasts was decreased. Compared with the model group at the same time point ，the contents of BUN（except for Modified liuwei dihuang decoction group after 2 weeks of administration ），Scr，serum phosphorus ，iPTH， FGF-23，RANKL and osteocalcin ，the percentage of renal tubular injury and the score of renal interstitial fibrosis in Modified liuwei dihuang decoction group and calcitriol group were decreased significantly at each time point ；serum calcium content and BMD（except for 2 weeks of administration ）were significantly increased （P＜0.05 or P＜0.01），and the pathological changes of renal/bone tissue were significantly improved ；there was no statistical significance in above indexes between Modified liuwei dihuang decoction group and calcitriol group （P＞0.05）. CONCLUSIONS ：Modified liuwei dihuang decoction can improve kidney/ bone injury of CKD-MBD model rats ，and improve BMD and regulate disorder of calcium and phosphorus metabolism.