BACKGROUND:Hydrogels have become a research hotspot due to their unique advantages in the biomedical field due to their superior mechanical and biological properties.At present,related research involves tissue engineering,wound dressing and so on. OBJECTIVE:To review the advantages and properties of hydrogels and the research progress of their application in the repair of oral and maxillofacial defects,discuss the current limitations and challenges of hydrogels in application and promotion,and provide new ideas for future research directions. METHODS:Relevant literature was searched in PubMed,CNKI,and WanFang database by computer.The search terms were"hydrogel,oral and maxillofacial defects,mechanical properties,tissue engineering,wound dressing"in Chinese and"hydrogel,oral and maxillofacial defects,mechanical properties,guided tissue regeneration,wound dressing"in English.Preliminary screening was carried out by reading titles and abstracts,and articles not related to the topic of the article were excluded.According to the inclusion and exclusion criteria,108 articles were finally included for the result analysis. RESULTS AND CONCLUSION:(1)The hydrogel has good biological activity,mechanical controllability,and stimulation response.(2)Polymer,metal,and ceramic hydrogel composites have appropriate mechanical properties,biodegradability,and controlled release rate,which are suitable for maxillofacial bone tissue engineering.(3)Fibrin-based hydrogel could fill the hollow nerve conduit through the nerve defect area and promote the regeneration and growth of axons to restore the function of maxillofacial nerve.(4)Controlling the interaction between nanomaterials and hydrogels can improve the formation of muscle fiber oriented structure to promote maxillofacial muscle tissue regeneration.(5)Polysaccharide hydrogel has gradually become the first choice for repairing irregular periodontal defects due to its ability to control drug delivery,carry bioactive molecules,and combine with other materials to produce the best scaffold matching the extracellular matrix.(6)Calcium phosphate or calcium carbonate-based hydrogels can be used to fill irregular or fine tissue defects and remineralize hard tissues.The self-assembled hydrogels are simple to prepare and have good biological activity.(7)Salivary gland-derived extracellular matrix-like gel is expected to participate in the treatment of many salivary gland diseases.(8)Hydrogels can be used as wound dressings in combination with biological adhesives,acellular biomaterials,antimicrobials,antioxidants,or stem cells to treat various wounds.(9)Fibrin-based hydrogel has the most potential in the repair of oral and maxillofacial defects.It has excellent biocompatibility,flexibility,and plasticity.It can combine with cells,extracellular matrix proteins,and various growth factors,and promote the osteogenic differentiation of mesenchymal stem cells,axon regeneration and growth,angiogenesis,myotube differentiation,salivary gland tissue regeneration,and periodontal tissue regeneration.It has a broad prospect in the repair of oral and maxillofacial defects.However,its therapeutic effect depends on the function of the substance carried.The complex preparation process,its safety and long-term efficacy,and the special anatomical oral and maxillofacial structure is the problem that hinders its promotion,which also provides directions for future research.

ObjectiveTo study the regulatory effect of the partial sequence within the 3’ untranslated region （3’UTR） of slit guidance ligand 1 （Slit1） （Slit1-3’UTR） on the fibrotic phenotypes of cardiac fibroblasts （CFs） and its potential mechanism. MethodsThe adenovirus vector was used to overexpress the 1526nt sequence of Slit1-3’UTR in ICR neonatal mouse CFs （mCFs）. The expression of fibrosis-related genes in mCFs， such as collagen type 1 alpha1（COL1A1）， collagen type 3 alpha3 （COL3A1） and alpha smooth muscle actin （α-SMA） were detected by Western blot assay. The effect of Slit1-3’UTR 1526nt on the proliferation and migration of mCFs was assessed by EdU staining and Trans-well assays. Angiotensin Ⅱ （Ang Ⅱ） was used to treat mCFs， and the impact of Slit1-3’UTR 1526nt on the fibrotic phenotypes of Ang Ⅱ-induced mCFs was evaluated. After overexpression of Slit1-3’UTR 1526nt， miR-34a-5p mimic was transfected into mCFs， followed by actinomycin D treatment to detect the mRNA stability of Slit1-3’UTR 1526nt， and the levels of miR-34a-5p and its target gene SIRT1（si-SIRT1） in mCFs were determined. The effects of miR-34a-5p and small interfering RNA targeting SIRT1 on the Slit1-3’UTR 1526nt-mediated regulation of fibrotic phenotypes were also determined. ResultsAdenovirus-mediated overexpression of Slit 1-3’UTR 1526nt was achieved in mCFs. Overexpression of Slit 1-3’UTR 1526nt markedly inhibited the expression of the fibrosis-related genes， proliferation and migration of mCFs and fibrotic phenotypes of Ang Ⅱ. The results of actinomycin D assay showed that miR-34a-5p inhibited the stability of Slit1-3’UTR 1526nt in mCFs， while the level of miR-34a-5p was reduced in mCFs with overexpression of Slit1-3’UTR 1526nt. Transfection of miR-34a-5p promoted the fibrotic phenotypes， and reversed the inhibitory effect of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. Overexpression of Slit1-3’UTR 1526nt significantly increased the level of miR-34a-5p target gene SIRT1 in mCFs. Transfection of miR-34a-5p and si-SIRT1 consistently reversed the inhibitory effects of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. ConclusionSlit1-3’UTR1526nt inhibits the fibrotic phenotypes of mCFs by binding to miR-34a-5p and increasing the expression of its target gene of SIRT1.

ObjectiveTo investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A （IDH3A） on cardiomyocyte hypertrophy. MethodsThe expression of IDH3A in the myocardium of healthy volunteers （n=10） and patients with heart failure （HF） （n=10）， and in the myocardium of mice subjected to transverse aortic constriction （TAC） surgery and sham operation， as well as in phenylephrine （PE）-induced neonatal rat ventricular cardiomyocytes （NRVCs）， was assessed by real-time quantitative polymerase chain reaction （RT-qPCR） and Western blot assay. The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated. The effect of IDH3A on NRVCs area was examined by phalloidin staining assay. A mutant of IDH3A with abolished enzymatic activity， IDH3A_D208A， was generated through site-directed mutagenesis. The impact of this IDH3A mutant on the hypertrophic phenotype， ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity. The effect of exogenous α-ketoglutaric acid （AKG） on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay， respectively. ResultsIDH3A was significantly decreased in the myocardium of HF patients， in the myocardium of TAC-operated mice， and in PE-induced NRVCs （P = 0.005 2，P = 0.026 6，P = 0.041 3 and P = 0.006 6， respectively）. Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs （P < 0.000 1， P = 0.000 1 and P = 0.000 2， respectively）. The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs （P = 0.001 2 and P<0.000 1， respectively）， whereas the enzymatically inactive IDH3A mutant lacked this effect. Exogenous AKG provision could， but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy. ConclusionIDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level， providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.

ObjectiveTo evaluate the clinical efficacy and safety of acupuncture combined with levodopa in the treatment of Parkinson's disease（PD）. MethodsA total of 60 patients with PD were enrolled and randomly assigned to test group or control group， with 30 patients in each group. The control group received levodopa only， starting at 100 mg per dose， three times daily， with gradual increases not exceeding a maximum daily dose of 800 mg. The test group received acupuncture three times per week in addition to levodopa. Both groups were treated for 12 weeks. Assessments were conducted before treatment， after 6 and 12 weeks treatment， using the Unified Parkinson's Disease Rating Scale（UPDRS）， Wearing-Off Questionnaire-9（WOQ-9）， Montreal Cognitive Assessment（MoCA）， Mini-Mental State Examination（MMSE）， Depression Rating Scale（DRS）， Hamilton Depression Scale（HAMD）， Hamilton Anxiety Scale（HAMA）， PD Questionnaire-39（PDQ-39）， and Pittsburgh Sleep Quality Index（PSQI）. Repeated measures ANOVA was utilized to evaluate the effects of time， group， and their interaction on each index. Spearman correlation analysis was conducted to examine the relationships between combined treatment and outcome scores. Adverse events in both groups were recorded throughout the study. ResultsBoth groups showed significant improvements after 6 and 12 weeks treatment， with decreases in UPDRS total score， WOQ-9 total score， DRS score， HAMD score， HAMA score， PDQ-39 score， and PSQI score， and increases in MoCA and MMSE scores（P＜0.05）. Compared with the control group， the test group demonstrated significantly greater improvements in all the above indicators after 6 and 12 weeks （P＜0.05）. Repeated measures ANOVA showed significant time main effects， group main effects， and their interaction across all outcome measures（P＜0.01）. Spearman correlation analysis revealed that combined therapy was significantly negatively correlated with UPDRS， WOQ-9， DRS， HAMD， HAMA， PDQ-39， and PSQI scores， while positively correlated with MoCA and MMSE scores after 12 weeks of treatment（P＜0.05）. Both groups did not experience any serious adverse events and did not affect treatment. ConclusionAcupuncture combined with levodopa is more effective than levodopa alone in improving motor function， non-motor symptoms， cognitive function， depression and anxiety， quality of life， and sleep quality in patients with PD， with good safety.

OBJECTIVE: To compare the clinical efficacy of electroacupuncture (EA) at neuro-arterial stimulation points with topical western medication in treating post-stroke shoulder-hand syndrome (SHS). METHODS: A total of 72 patients with post-stroke SHS were randomly assigned to an observation group (n=36, 2 cases dropped out) and a control group (n=36, 3 cases dropped out). Both groups received standard neurological treatment, comprehensive rehabilitation, and physical therapy. The observation group received EA at neuro-arterial stimulation points, including the ipsilateral stellate ganglion point, vagus nerve trunk and auricular branch (left side), and stimulation points of the radial and ulnar arteries, radial nerve, ulnar nerve, and median nerve, once daily for 4 weeks. The control group was treated with topical diclofenac diethylamine emulgel, and mucopolysaccharide polysulfate cream was added for patients with pronounced early-stage edema, twice a day for 4 weeks. The VAS pain score and hand edema volume were recorded before treatment, at 2 and 4 weeks during treatment, and 2 weeks after treatment completion (follow-up). Musculoskeletal ultrasound was used to measure the thickness of the dorsal hand and middle finger skin on the affected side before and after 4 weeks of treatment. RESULTS: Compared before treatment, the VAS pain scores and edema volume of the affected hand in both groups were decreased at week 2, week 4, and follow-up (P<0.05). At week 4, both groups showed lower VAS pain scores and edema volume than those at week 2 (P<0.05); during follow-up, both VAS pain scores and edema volume were further reduced compared to those at week 4 (P<0.05). At week 2, week 4, and follow-up, the VAS scores and edema volume of the affected hand in the observation group were lower than those in the control group (P<0.05). Compared before treatment, the dorsal hand skin thickness and middle finger skin thickness on the affected side were decreased in both groups after 4 weeks of treatment (P<0.05). Compared with the control group, the observation group showed thinner dorsal hand and middle finger skin thickness after 4 weeks of treatment (P<0.05). CONCLUSION EA at neuro-arterial stimulation points effectively alleviates pain and edema in patients with post-stroke SHS, and demonstrates superior efficacy compared to topical western medication.
Humans ; Male ; Female ; Middle Aged ; Electroacupuncture ; Aged ; Stroke/complications* ; Acupuncture Points ; Adult ; Reflex Sympathetic Dystrophy/physiopathology* ; Treatment Outcome ; Hand

Clinical trials have demonstrated that kilohertz-frequency transcutaneous spinal cord stimulation (TSCS) can be used to facilitate the recovery of sensory-motor function for patients with spinal cord injury, whereas the neural mechanism of TSCS is still undetermined so that the choice of stimulation parameters is largely dependent on the clinical experience. In this paper, a finite element model of transcutaneous spinal cord stimulation was used to calculate the electric field distribution of human spinal cord segments T ₁₂ to L ₂, whereas the activation thresholds of spinal fibers were determined by using a double-cable neuron model. Then the variation of activation thresholds was obtained by varying the carrier waveform, the interphase delay, the modulating frequency, and the modulating pulse width. Compared with the sinusoidal carrier, the usage of square carrier could significantly reduce the activation threshold of dorsal root (DR) fibers. Moreover, the variation of activation thresholds was no more than 1 V due to the varied modulating frequency and decreases with the increased modulating pulse width. For a square carrier at 10 kHz modulated by rectangular pulse with the frequency of 50 Hz and the pulse width of 1 ms, the lowest activation thresholds of DR fibers and dorsal column fibers were 27.6 V and 55.8 V, respectively. An interphase delay of 5 μs was able to reduce the activation thresholds of the DR fibers to 20.1 V. The simulation results can lay a theoretical foundation on the selection of TSCS parameters in clinical trials.
Humans ; Spinal Cord Stimulation/methods* ; Nerve Fibers/physiology* ; Finite Element Analysis ; Spinal Cord/physiology* ; Computer Simulation ; Spinal Cord Injuries/physiopathology* ; Lumbosacral Region ; Lumbar Vertebrae ; Transcutaneous Electric Nerve Stimulation/methods* ; Models, Neurological

Objective To investigate the common molecular features of immunothrombosis, thus enhancing the comprehension of thrombosis triggered by immune and inflammatory responses and offering crucial insights for identifying potential diagnostic and therapeutic targets. Methods Differential gene expression analysis and functional enrichment analysis were conducted on datasets of systemic lupus erythematosus (SLE) and venous thromboembolism (VTE). The intersection of differentially expressed genes in SLE and VTE with those of neutrophil extracellular traps (NET) yielded cross-talk genes (CG) for SLE-NET and VTE-NET interaction. Further analysis included functional enrichment and protein-protein interaction (PPI) network assessments of these CG to identify hub genes. Venn diagrams and receiver operating characteristic (ROC) curve analysis were employed to pinpoint the most effective shared diagnostic CG, which were validated using a graft-versus-host disease (GVHD) dataset. Results Differential expression genes in SLE and VTE were associated with distinct biological processes, whereas SLE-NET-CG and VTE-NET-CG were implicated in pathways related to leukocyte migration, inflammatory response, and immune response. Through PPI network analysis, several hub genes were identified, with matrix metalloproteinase 9 (MMP9) and S100 calcium-binding protein A12 (S100A12) emerging as the best shared diagnostic CG for SLE (AUC: 0.936 and 0.832) and VTE (AUC: 0.719 and 0.759). Notably, MMP9 exhibited good diagnostic performance in the GVHD dataset (AUC: 0.696). Conclusion This study unveils the common molecular features of SLE, VTE, and NET, emphasizing MMP9 and S100A12 as the optimal shared diagnostic CG, thus providing valuable evidence for the diagnosis and therapeutic strategies related to immunothrombosis. Additionally, the expression of MMP9 in GVHD highlights its critical role in the risk of VTE associated with immune system disorders.
Humans ; Computational Biology/methods* ; Lupus Erythematosus, Systemic/immunology* ; Protein Interaction Maps/genetics* ; Venous Thromboembolism/therapy* ; Matrix Metalloproteinase 9/genetics* ; Extracellular Traps/metabolism* ; Gene Regulatory Networks ; Thrombosis/immunology* ; Graft vs Host Disease/genetics* ; Gene Expression Profiling

Objective To establish a weightlessness simulation animal model using miniature pigs, leveraging the characteristic of multiple systems’ tissue structures and functions similar to those of humans, and to observe pathophysiological changes, providing a new method for aerospace research. Methods Nine standard-grade miniature pigs were selected and randomly divided into an experimental group (n=7) and a control group (n=2). The experimental group was fixed using customized metal cages, with canvas slings suspending their hind limbs off the ground, and the body positioned at a -20° angle relative to the ground to simulate unloading for 30 days (24 hours a day). Data on body weight, blood volume, and blood biochemistry indicators were collected at different time points for statistical analysis of basic physiological changes. After the experiment, the miniature pigs were euthanized and tissue samples were collected for histopathological observation of the cardiovascular, skeletal and muscle systems HE and Masson staining. Statistical analysis was also conducted on the thickness of arterial vessels and the diameter of skeletal muscle fibers. Additionally, western blotting was employed to detect the expression levels of skeletal muscle atrophy-related proteins, including muscle-specific RING finger protein 1 (MuRf-1) and muscle atrophy F-box (MAFbx, as known as Atrogin-1), while immunohistochemistry was used to detect the expression of glial fibrillary acidic protein (GFAP), an indicator of astrocyte activation in the brain, reflecting the pathophysiological functional changes across systems. Results After hindlimb unloading, the experimental group showed significant decreases in body weight (P<0.001) and blood volume (P<0.01). During the experiment, hemoglobin, hematocrit, and red blood cell count levels significantly decreased (P<0.05) but gradually recovered. The expression levels of alanine aminotransferase and γ-glutamyltransferase initially decreased (P<0.05) before rebounding, while albumin significantly decreased (P<0.001) and globulin significantly increased (P<0.01). Creatinine significantly decreased (P<0.05). The average diameter of gastrocnemius muscle fibers in the experimental group significantly shortened (P<0.05), with a leftward shift in the distribution of muscle fiber diameters and an increase in small-diameter muscle fibers. Simultaneously, Atrogin-1 expression in the gastrocnemius and paravertebral muscles significantly increased (P<0.05). These changes are generally consistent with the effects of weightlessness on humans and animals in space. Furthermore, degenerative changes were observed in some neurons of the cortical parietal lobe, frontal lobe, and hippocampal regions of the experimental group, with a slight reduction in the number of Purkinje cells in the cerebellar region, and a significant enhancement of GFAP-positive signals in the hippocampal area (P<0.05). Conclusion Miniature pigs subjected to a -20° angle hind limb unloading for 30 days maybe serve as a new animal model for simulating weightlessness, applicable to related aerospace research.

Objective: To investigate the rifampicin resistance status and its influencing factors among elderly patients with pulmonary tuberculosis in Changzhou City, Jiangsu Province, so as to provide the basis for improving drug-resistant pulmonary tuberculosis prevention and control strategies. Methods: Patients aged over 60 years with pulmonary tuberculosis treated in tuberculosis designated hospital was selected. Demographic information, history of previous disease, history of diagnosis and treatment and drug sensitivity test were collected. Rifampicin resistance among elderly patients with pulmonary tuberculosis and its influencing factors was analyzed. Results: Totally 249 elderly patients with pulmonary tuberculosis were included, with an average of (69.75±4.36) years. There were 147 males and 102 females, with a gender ratio of 1.44∶1. There were 183 treatment-naïve patients (73.49%) and 66 retreated patients (26.51%). Rifampicin resistance was found in 21 cases, with a drug resistance rate of 8.43%. Among them, there were 7 treatment-naïve patients (3.83%), and 14 retreated patients (21.21%). Multivariable logistic regression analysis showed that retreated elderly patients with pulmonary tuberculosis had a higher risk of rifampicin resistance (OR=10.551, 95%CI: 1.344-82.857). Conclusion The rifampicin resistance rate of 249 elderly patients with pulmonary tuberculosis was 8.43% and was associated with the type of treatment.

ObjectiveTo investigate the regulatory effect of circular RNA circ_0120051 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe expression of circ_0120051 and its host gene of solute carrier family 8 member A1（SLC8A1） mRNA in the myocardium of healthy organ donors （n=24） and heart failure （HF） patients （n=21） were assessed by real-time quantitative polymerase chain reaction （RT-qPCR） assay. RNA stability of circ_0120051 was identified by RNase R exonuclease digestion assay. The cytoplasmic and nuclear distribution of circ_0120051 in human cardiomyocyte AC16 was detected by RT-qPCR assay. The expression of fibrosis-related genes in mouse cardiac fibroblasts （mCFs） with adenovirus-mediated overexpression of circ_0120051 was detected by RT-qPCR and Western blot assay， respectively. The effect of overexpression of circ_0120051 on the migration activity of mCFs was evaluated by wound-healing assay. RNA co-immunoprecipitation （RIP） was conducted to detect the interaction between circ_0120051 and miR-144-3p. The binding site of miR-144-3p in the 3'-UTR of isocitrate dehydrogenase 2 （Idh2） mRNA was identified by the dual luciferase reporter gene assay. ResultsCirc_0120051 was significantly up-regulated in the myocardium of HF patients， while the mRNA expression of its host gene SLC8A1 was not changed. Circ_0120051 was mainly located in the cytoplasm of human AC16 cells. Results of RNase R exonuclease digestion revealed that circ_0120051 possesses the characteristic stability of circular RNA compared to the linear SLC8A1 mRNA. Overexpression of circ_0120051 could inhibit the expression of fibrosis-related gene in mCFs and mCFs migration. RIP assay confirmed the specific interaction between circ_0120051 and miR-144-3p. Transfection of miR-144-3p mimic could efficiently promote the expression of fibrosis-related genes in mCFs and reverse the inhibitory effect of circ_0120051 on the fibrotic phenotype of mCFs. Results of the dual luciferase reporter gene assay confirmed the interaction between miR-144-3p and the 3'-UTR of Idh2. Transfection of miR-144-3p transcriptionally inhibited Idh2 expression， and overexpression of circ_0120051 enhanced IDH2 expression in mCFs. MiR-144-3p mimic and Idh2 small interfering RNA （siRNA） could consistently reverse the inhibitory effects of circ_0120051 on fibrosis-related genes expression in mCFs and mCFs migration. ConclusionsCirc_0120051 inhibits the fibrotic phenotype of cardiac fibroblasts via sponging miR-144-3p to enhance the target gene of IDH2 expression.