The application of mechanics in clinical wound healing has a long history;however,the systematic underlying mechanisms remain unclear.With recent advancements in biomechanics and mechanobiology,the principles regarding how mechanical factors influence the formation,progression,and healing of wounds have gradually been elucidated.Herein,based on progress in theories,technologies,and clinical practices concerning the interplay between mechanics and wound healing,this study introduces the concept of wound-repairing mechanomedicine.Relevant research is systematically reviewed from the perspectives of biomechanics,mechanobiology,and mechanotherapy.Additionally,potential future development directions are prospectively analyzed to provide novel insights into wound care and strategies for preventing scar formation.

The application of mechanics in clinical wound healing has a long history;however,the systematic underlying mechanisms remain unclear.With recent advancements in biomechanics and mechanobiology,the principles regarding how mechanical factors influence the formation,progression,and healing of wounds have gradually been elucidated.Herein,based on progress in theories,technologies,and clinical practices concerning the interplay between mechanics and wound healing,this study introduces the concept of wound-repairing mechanomedicine.Relevant research is systematically reviewed from the perspectives of biomechanics,mechanobiology,and mechanotherapy.Additionally,potential future development directions are prospectively analyzed to provide novel insights into wound care and strategies for preventing scar formation.

ObjectiveTo investigate the mechanism of anti-pulmonary fibrosis of cannabidiol by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）. MethodSD rats were randomly divided into blank group， model group， prednisone group（3.15 mg·kg^-1） and cannabidiol low， medium and high dose groups（12， 36， 108 mg·kg^-1）， with 8 rats in each group. The rat model of pulmonary fibrosis was established by intratracheal injection of bleomycin（5 mg·kg^-1）， which was administered continuously for 28 days after successful modeling. The pathological changes of rat lung tissue were observed， and enzyme-linked immunosorbent assay（ELISA） was used to detect the expression levels of matrix metalloproteinase-7（MMP-7）， type Ⅱ alveolar cell surface antigen（KL-6）， pulmonary surfactant-associated protein A（SP-A） and SP-D in serum. The expression levels of type Ⅰ collagen（Col-Ⅰ） and fibronectin（FN） in lung tissues were detected by immunohistochemistry， and the expression of mucin 5 subtype AC（MUC5AC） was detected by immunofluorescence. UPLC-Q-TOF-MS was used to search for potential biomarkers and related metabolic pathways of cannabidiol in treating pulmonary fibrosis. ResultCompared with the blank group， there were a large number of inflammatory cell infiltration and continuous fibrosis lesions in the lung tissue of rats in the model group. Compared with the model group， the inflammatory infiltration and blue collagen deposition in the lung tissue of rats in the prednisone and cannabidiol groups were reduced. Compared with the blank group， the expressions of MMP-7， KL-6， SP-A and SP-D in serum of the model group were significantly increased（P<0.01）， while the expressions of MMP-7， KL-6， SP-A and SP-D in the prednisone and cannabidiol high dose groups were significantly decreased by comparing with the model group（P<0.05， P<0.01）. Compared with the blank group， the expression levels of Col-Ⅰ and FN in the lung tissues of the model group were significantly increased， and the fluorescence intensity of MUC5AC was significantly increased（P<0.01）. Compared with the model group， the expression levels of Col-Ⅰ and FN in the lung tissues of the prednisone and cannabidiol high dose groups were significantly decreased（P<0.05， P<0.01）， and the expression of MUC5AC was significantly decreased（P<0.01）. Compared with the blank group， a total of 18 differential compounds were screened out in the model group， which could be used as potential biomarkers， and cannabidiol could call back 16 of them， mainly involving 4 metabolic pathways（linoleic acid metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， arachidonic acid metabolism， and niacin and niacinamide metabolism）. Compared with the blank group， the relative contents of potential biomarkers arachidonic acid and linoleic acid were significantly increased in the model group（P<0.05， P<0.01）， while the relative contents of 5，6-EET， L-tyrosine and niacinamide were significantly decreased（P<0.01）. Compared with the model group， cannabidiol could significantly reduce the relative contents of arachidonic acid and linoleic acid， and significantly increase the relative contents of 5，6-EET， L-tyrosine and niacinamide（P<0.01）. ConclusionCannabidiol has an intervention and remission effect on pulmonary fibrosis， and its mechanism may be related to linoleic acid metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， arachidonic acid metabolism， niacin and niacinamide metabolism.

The clinical data of a child with congenital ectopic gastric mucosa and infections admitted to Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology in May 2020 were analyzed retrospectively.The child was a female who presented to the doctor with " phlegm in the throat with mild cough for more than 1 month" at the age of 1 month and 27 days.The pleural biopsy showed that the gastrointestinal mucosa tissue submitted for examination resembled the gastric mucosa under the microscope.The patient was diagnosed with pleural ectopic gastric mucosa.The child was discharged after her conditions improved.Twenty four days after the discharge, she returned to the hospital due to hemoptysis once.Closed thoracic drainage, partial lobectomy, thoracoscopic resection of mediastinal lesions and thoracoscopic conversion were then performed.In chest exploration, gastric mucosa-like tissue was seen on the top of the left pleura.The first case of pediatric pleural ectopic gastric mucosa in China was analyzed in this study.The results suggested that chest exploration should be performed on children with cough and hemoptysis if necessary to confirm the diagnosis as soon as possible.

Objective:To observe the effect of transplanting neural stem cells (NSCs) and nerve growth factor (NGF) nanoparticles on hippocampal synaptophysin (SYN) levels in APP/PS1 double-transgenic mice and on their behavior.Methods:NSCs from the brains of transgenic mouse fetuses were cultured in vitro. Twenty-four 12-month-old male APP/PS1 mice with Alzhaimer′s disease (AD ) were randomly divided into an NSC combined with NGF transplantation group (NSCs+ NGF-NP group), an NSC transplantation group (NSCs group) and an AD control group (AD group), each of 8. Another 8 healthy male counterparts formed a normal control group (WT group). The rats in the NSCs+ NGF-NP and NSCs groups had NSCs combined with NGF nanoparticles or NSCs alone injected into their brains, while the bilateral hippocampi of the other two groups were injected with the same volume of phosphate buffer. Four weeks later the Morris water maze test was used to quantify the rats′ learning and memory functioning. The migration and differentiation of the transplanted cells were measured using fluorescence immunohistochemistry, while the level of synaptophysin protein in the hippocampus was detected using western blotting.Results:Neurospheres cultured in vitro showed positive expression of enhanced green fluorescent protein(EGFP) and nestin, which are specific markers of neural stem cells. Four weeks after the transplantation, cells traced using EGFP had survived and migrated to the corpus callosum and deep into the hippocampus and dentate gyrus. Transplanted cells had differentiated into DCX-positive neurons and GFAP-positive glial cells. The samples from the NSCs+ NGF-NP group showed a larger number of viable cells with longer protrusions, and some had crossed the hippocampal granular layer. The average synaptophysin levels in the WT, NSCs and NSCs+ NGF-NP groups were significantly higher than that of the AD group. The average synaptophysin level of the NSCs+ NGF-NP group was significantly higher than in the NSCs group but not significantly different from the WT group′s average. The Morris water maze results showed that compared with the AD group the time in the platform quadrant and the platform crossing times increased significantly in the WT, NSCs and NSCs+ NGF-NP groups. The average platform crossing time of the NSCs+ NGF-NP group was greater than that of the NSCs group but not significantly different from the WT group′s average.Conclusion:Injecting NSCs combined with NGF nanoparticles can promote the survival and maturation of the transplanted cells in vivo, increase hippocampal synapses, and thus improve learning and memory, at least in AD mice.

Hyaluronic acid (HA) is a natural ligand of tumor-targeted drug delivery systems (DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors (HARE and LYVE-1) are also overexpressing in the reticuloendothelial system (RES). Therefore, polyethylene glycol (PEG) modification of HA-based DDS is necessary to reduce RES capture. Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement, significantly compromising the antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform (Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage. The and investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and nonspecific biodistribution.

Objective To investigate the protective effect of Honokiol on the airway inflammation induced by particulate matter 2.5(PM2.5)in the asthmatic mice and its mechanism.Methods Fifty male specific pathogen free (SPF)Balb/c mice were randomly divided into 5 groups.Group A:normal control group;group B:asthmatic model group;group C:PM2.5 exposure asthmatic group;group D:TAK -242 group;group E:Honokiol group. Asthmatic mouse models were established by ovalbumin(OVA)sensitization and challenge.On days 0 and 7,the mice in B-E groups were injected intraperitoneally with injection 100 mg/L OVA and aluminum hydroxide for sensitization;on days 14 to 21,10 g/L OVA solution was given 30 min per day to challenge.During challenge phrase,the mice in C -E groups received intratracheal injection of PM2.5,every other day,4 times totally.On this basis,the mice in group D re-ceived TAK-242 intraperitoneal injection,and the mice in group E received honokiol intragastric administration.Group A was given saline instead of OVA.Animals were sacrificed 24 h after the final inhalation challenge,and the bronchoal-veolar lavage fluid(BALF)of the left lung was used for differential inflammatory cell counts.The expressions of Toll-like receptors 4(TLR4)and nuclear factor(NF)-κB at mRNA level were detected by real-time quantitative PCR. Flow cytometry analysis was performed to measure the levels of Th17 and Treg cells.Results Compared with group A,mice in group B and group C expressed more serious disorders of bronchial epithelial cells,alveolar wall congestion and edema,increased mucus secretion in the airway and infiltration of inflammatory cells in the lung,and those in group C were more obvious than those of group B and group E significantly reduced respiratory inflammation;compared with group A[(4.15 ± 1.35)×108/L,0.012 0 ± 0.002 3],the total number of inflammatory cell counts[(16.79 ± 5.62)×108/L and(24.58 ± 13.46)×108/L],eosinophils proportions(0.113 8 ± 0.022 3 and 0.197 8 ± 0.084 9)in group B and group C,were significantly higher,and the differences were statistically significant(all P<0.05);The total number of inflammatory cell counts and eosinophils proportion in group E(8.56 ± 3.28)×108/L and 0.041 5 ± 0.013 5)were significantly lower than those in group C,and the differences were statistically significant(all P <0.05);The expressions of TLR4 mRNA and NF-κB mRNA in group B and C(1.85 ± 0.56,1.82 ± 0.28 and 2.97 ± 0.41,2.83 ± 0.32)were significantly higher,and the differences were statistically significant(all P <0.05);The expressions of TLR4 mRNA and NF-κB mRNA in group E(1.60 ± 0.28,1.54 ± 0.25)was significantly lower than those in group C,and the differences were statistically significant(all P<0.05);the expressions of Th17 in group B and C[(2.89 ± 0.61)% and(4.96 ± 0.27)%]were significantly higher than those of group A[(1.03 ± 0.35)%] (all P<0.05);The expression of Th17 in group E[(1.83 ± 0.23)%]was significantly lower than that of group C,and the differences were statistically significant(P<0.05);the expressions of Treg in group B and C[(4.96 ± 0.35)%and(2.27 ± 0.41)%]were significantly lower than those of group A[(7.37 ± 0.56)%],and the differences were sta-tistically significant(all P<0.05);The expression of Treg in group E was significantly increased[(6.45 ± 0.38)%] compared with that in group C,and the difference were statistically significant(P<0.05);and those of group D and E were improved remarkably.Conclusions Honokiol can relieve PM2.5 exposure of asthmatic airway inflammation through down-regulating the expression of TLR4 and NF-κB and Th17 and regulating the balance of Th17 and Treg cells.

Objective To investigate the anti-inflammatory and immunosuppressive effects of honokiol in a mouse model of particulate matter ( PM ) 2.5-induced asthma .Methods Female SPF BALB/c mice were randomly divided into five groups:normal saline group (group A), ovalbumin (OVA)-sensitized group ( group B), PM2.5-exposed+OVA-sensitized group ( group C), dexamethasone-treated group (group D) and honokiol-treated group (group E).All mice except those in group A were sensitized and challenged with OVA, and the mice in groups C, D and E were exposed to PM2.5 every two days since the first challenge.Samples of lung sections were stained with hematoxylin and eosin (HE) to observe in-flammatory infiltration.Bronchoalveolar lavage fluid (BALF) and PBMCs were collected from each mouse . Expression of RORγt and Foxp3 at mRNA level was detected by quantitative real-time PCR.Flow cytometry analysis was performed to measure the percentages of Th 17 and Treg cells.ELISA was performed to measure the levels of IFN-γ, IL-10 and IL-17 in the supernatants of cell culture .Results Compared with group B , group C showed an enhanced expression of RORγt at mRNA level, increased IL-17 level and up-regulated percentage of Th17 cells (all P<0.05), but a suppressed expression of Foxp3 at mRNA level, decreased IL-10 level and down-regulated percentage of Th17 cells (all P<0.05).No significant difference in the per-centage of Th1 cells or in the expression of Th 1-related cytokines was observed .The expression of RORγt at mRNA level, IL-17 level and the percentage of Th 17 cells were decreased in PM2.5-exposed mice upon honokiol intervention (all P<0.05), while the expression of Foxp3 at mRNA level, IL-10 level and the per-centage of Treg cells were increased after honokiol intervention (all P<0.05).Honokiol had similar efficacy to dexamethasone in the treatment of asthma .Conclusion Honokiol can alleviate airway inflammation in mice with PM2.5 exposure-induced asthma through regulating the percentages of Th 17 and Treg cells.