BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.

Objective To investigate the effects of anti-HLA donor-specific antibodies(DSA)and desensitization for DSA+patients on engraftment of haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods The patients who underwent haplo-HSCT and examinations for HLA antibodies and DSA in our department from March 2017 to July 2023 were recruited in this study.The effects of desensitization measure on engraftment in the DSA+patients after haplo-HSCT were analyzed.Results Among the 70 patients who underwent haplo-HSCT and test for HLA antibodies,15(21.4％)patients were DSA positive,including 7(46.7％)cases of strong positive,3(20.0％)cases of moderate positive,and 5(33.3％)cases of weak positive.The median duration for neutrophil implantation was significantly extended in the DSA+patients than the negative patients(P=0.027).For the 6 patients developed graft failure(GF),4 were DSA+which was statistically higher than the DSA-patients(P=0.025).Multivariate regression analysis showed that DSA was an independent factor affecting GF(HR=9.273,95％CI:1.505～57.124,P=0.016).Among the 10 patients(7 strong positive and 3 moderate positive DSA)received desensitization therapy,4 patients received combination desensitization,with a 100％rate of successful transplantation,and 6 received single desensitization,with 4(66.7％)experiencing GF,so the GF rate was obviously lower in the combination than the single desensitization(P=0.008).Conclusion In haplo-HSCT patients,DSA is an important factor leading to implantation delay and GF.While,single desensitization treatment has limited efficacy.In combined DSA desensitization therapy,the decrease of antibody titer should be dynamically monitored to ensure the successful implantation of stem cells and reduce GF rate.

The overall health condition of patients significantly affects the diagnosis,treatment,and prognosis of endodontic diseases.A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy,as well as selecting appropriate therapeutic approaches.This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures,improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

A 72-year-old female patient was admitted to the emergency department of Qintang District People′s Hospital of Guigang City in August 2023 due to chills and fever, abdominal distension and pain, diarrhea, cough and shortness of breath for 1 day. She had a history of chronic obstructive and pulmonary heart disease, stage Ⅲ hypertension, and ceftazidime allergy. Clinical diagnosis of acute bacterial infection of chronic obstructive pneumonia was made and levofloxacin combined with piperacillin/tazobactam were given as symptomatic treatment. The blood culture reported Campylobacter fetus after four days, and the patient was cured and discharged after seven days with negative blood culture. The morphology and mass spectrometry identification of the strain were consistent with the definition of Campylobacter fetus. Whole genome sequencing predicted the multi-site sequence type as Campylobacter fetus subsp. fetus( Cff) ST20, carrying the tetracycline resistance gene tet (O/M/O), 18 flagella genes (including rpoN gene from Campylobacter jejuni. these genes were not found in the other two Campylobacter fetus subspecies), and six virulence genes (including like-typhoidal toxin and typhoid toxin genes). The pathogen has the ecological characteristics of parasitic farmed animal colonization and the biological characteristics of high mobility and virulence. These attributes facilitated its entry into the bloodstream via the fecal-oral route, leading to invasive infections.

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Objective To explore the relationship between non-high density lipoprotein cholesterol(non-HDL-C)level and leptomeningeal collateral circulation in patients with acute middle cerebral artery occlusion.Methods A total of 85 patients with first-onset acute cerebral infarction with middle cerebral artery M1 segment occlusion were enrolled.According to the results of DSA,LMC circulation was assessed by American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology Collateral Circulation Assess-ment System.All patients were assigned to better LMC circulation group(score 2～4,n = 30)and worse LMC circulation group(score 0～1,n = 55),and the levels of non-HDL-C were compared between the two groups.Results The levels of LDL-C and non-HDL-C in worse LMC circulation group were significantly higher than those of the better LMC circulation group(P = 0.026,P = 0.010).non-HDL-C was an independent risk factor for the worse LMC circulation(OR = 3.019,95%CI:1.053～8.658,P = 0.04).LMC circulatory score of patients was negatively correlated with the levels of non-HDL-C level(r =-0.228,P = 0.036).The AUC of non-HDL-C predicted for the worse LMC circulation was 0.638(95%CI:0.521～0.755,P = 0.036).Conclusions non-HDL-C in patients with acute cerebral infarction was significantly related to worse LMC circulation,and was a risk factor for worse LMC circulation.It is suggested that the higher expression of non-HDL-C could be used to predict worse LMC circulation as a serological indicator.

Ischemic stroke is an acute and serious cerebrovascular accident.Neurodegenerative disorders are characterized by progressive degeneration of neu-rons in the central nervous system(CNS),resulting in severe disability and death.Myelin is essential for the health and function of neuronal axons.Oligodendrocytes,the myelinating cells of CNS,are vulnerable to ischemia and neurodegenerative disorders.G protein-coupled receptor 17(GPR17)is a dual receptor activated by uracil nucleotides/cysteinyl leukotrienes(CysLTs).Abnormal GPR17 activation contributes to oligodendrocyte dysfunc-tion and axonal damage.Gelosa et al.reported that CysLT1 receptor antagonist montelukast increased the recruitment and proliferation of oligodendrocyte precursor cells(OPCs)at the acute phase after ischemic stroke.Similarly,a study showed that montelukast stimulated neural progenitor proliferation and hippocampal neuro-genesis of aged rats through inhibition of GPR17.These results were supported by several studies on neurode-generative diseases.The authors showed that pharmaco-logical blockade of GPR17 with CysLT1 or CysLT2 recep-tor antagonists(montelukast or HAMI3379)improved oli-godendrocyte function and fiber connectivity,highlighting GPR17 as a potential therapeutic target in oligodendro-cyte protection and remyelination.Recently,growing evi-dence has revealed a significant interaction between mi-croglia and oligodendrocytes in CNS injury and disease.It was reported that M2 microglia promoted,while M1 microglia inhibited oligodendrogenesis,OPCs maturation and remyelination.Microglia-mediated neuroinflamma-tion,considered as an important pathological event,neg-atively affected OPCs fate and function in experimental neurological disorders.This was further corroborated by later studies.It was recently reported that montelukast enhanced OPCs differentiation and maturation by upreg-ulating the number of M2 microglia at chronic phase of brain ischemia.In line with the above results,inhibition of microglial inflammation by montelukast was shown to be responsible for neurite outgrowth.Although the exact mechanisms were not fully clarified,these results indi-cate that montelukast may indirectly promote OPCs dif-ferentiation and remyelination by a microglia-dependent manner.It has been widely accepted that CysLT1,CysLT2 and GPR17 receptors are localized in various cell types and their expression are upregulated after brain damage.Therefore,it is likely that CysLT receptor antagonists confer neuroprotection by targeting different receptors and multiple cell functions.Many studies have reported that CysLT receptor antagonists promote protec-tion of oligodendrocytes by inhibiting GPR17.Moreover,they may improve OPCs differentiation and neuronal sur-vival by regulating CysLTs-mediated microglial activation.Altogether,these data open novel perspectives in the treatment of cerebral ischemia and neurodegenerative diseases.

OBJECTIVES: Currently, it is difficult to assess the expression status of hormone receptor (HR) in breast malignant tumors with human epidermal growth factor receptor 2 (HER-2)-positive in the early preoperative stage, and it is difficult to predict whether it is non-invasively. This study aims to explore the value of MRI on the different HR expression status (HR⁺/HR^-) in HER-2 positive breast cancer. METHODS: Thirty patients with HR+ HER-2-positive breast cancer (HR+ group) and 23 patients with HR-HER-2-positive breast cancer (HR- group) from the First Hospital of Hunan University of Traditional Chinese Medicine between January 7, 2015 and November 26, 2021 were selected as subjects, and all the patients were examined by MRI and all were confirmed by surgery or pathological biopsy puncture. The immunohistochemical staining results were used as the gold standard to analyze the basic clinical conditions, peri-lesion conditions and MRI sign characteristics in the 2 groups. RESULTS: There were all significant differences in terms of mass margins, internal reinforcement features, and apparent diffusion coefficient (ADC) values between the HR+ group and the HR- group (all P<0.05). The logistic multivariate regression model showed that: when the lesion presented as a mass-type breast cancer on MRI, the internal enhancement features of the lesion were an independent predictor for differentiation in the 2 types of breast cancer [odds ratio (OR)=5.95, 95% CI: 1.223 to 28.951, P<0.05], and the mass margin (OR=0.386, 95% CI: 0.137 to 1.082, P>0.05) and ADC value (OR=0.234, 95% CI: 0.001 to 105.293, P>0.05) were not the independent predictors in distinguishing the 2 types of breast cancer. CONCLUSIONS Multiparametric MRI has good diagnostic value for HR expression status in HER-2-positive breast cancer. Combined logistic regression analysis to construct a predictive model may be helpful to the identical diagnosis.
Humans ; Female ; Breast Neoplasms/surgery* ; Magnetic Resonance Imaging/methods* ; Diffusion Magnetic Resonance Imaging/methods* ; Breast ; Magnetic Resonance Spectroscopy ; Retrospective Studies

Objective:To explore the application value of tidal lung function combined with fractional exhaled nitric oxide (FeNO) in children with respiratory syncytial virus (RSV) pneumonia.Methods:The clinical data of 65 children with RSV pneumonia in Shanghai Pudong New Area Gongli Hospital from April 2019 to October 2020 were retrospectively collected. According to the pneumonia severity index (PSI), they were divided into severe group (PSI score>130 points, 19 cases), mild to moderate group (PSI score ≤130 points, 46 cases), and 72 healthy children in the same period were selected as the normal control group. The levels of interleukin (IL)-8, IL-6, tumor necrosis factor-α(TNF-α), high-sensitivity C-reactive protein (hs-CRP) and tidal lung function parameters and FeNO were compared among the three groups and analyzed their correlation and evaluated the value in disease severity.Results:The level of FeNO in the severe group was higher than that in the mild to moderate group and the normal control group: (23.04 ± 5.49) ppb vs. (15.75 ± 8.24), (9.28 ± 3.51) ppb; the levels of tidal volume per kilogram of body mass (VT/kg), peak time ratio (TPEF/TE), peak volume ratio (VPEF/VE) in the severe group were lower than those in the mild to moderate group and the normal control group: (6.21 ± 1.89) ml/kg vs. (8.40 ± 1.27), ( 9.39 ± 3.04) ml/kg; (16.39 ± 6.61)% vs. (21.72 ± 5.39)%, (38.65 ± 7.20)%; (22.81 ± 6.39)% vs. (25.62 ± 5.30)%, (39.67 ± 4.04)% , there were statistical differences ( P<0.05). The correlation analysis results showed that the VT/kg, TPEF/TE, VPEF/VE were negatively correlated with IL-6 ( r = - 0.584, - 0.519, - 0.528; P<0.01), IL-8 ( r = - 0.521, - 0.542, - 0.567; P<0.01), TNF-α ( r = - 0.559, - 0.534, - 0.572; P<0.01) and hs-CRP ( r = - 0.528, - 0.567, - 0.533; P<0.01); the level of FeNO was positively correlated with IL-6, IL-8, TNF-α, hs-CRP ( r = 0.672, 0.639, 0.641, 0.672; P<0.01); the levels of VT/kg, TPEF/TE, VPEF/VE were negatively correlated with PSI scores in children with RSV pneumonia ( r = - 0.842, - 0.713, - 0.741; P<0.05); the level of FeNO was positively correlated with PSI scores in children with RSV pneumonia ( r = 0.809, P<0.05). The area under the curve of VT/kg, TPEF/TE, VPEF/VE combined with FeNO to assess the severity of RSV pneumonia in children with RSV pneumonia was 0.888, and the sensitivity and specificity were 73.68% and 91.30%, respectively. Conclusions:Tidal lung function parameters and FeNO are closely related to the severity of RSV pneumonia. The combined detection can be used as an objective basis for assessing the severity of RSV pneumonia.

Objective:To investigate the effect of hsa-miR-199a-5p on keloid fibroblasts (KFs) fibrosis and its relationship with TGF-β/Smad signaling pathway in vitro. Methods:KFs were infected with the lentiviral vector carrying hsa-miR-199a-5p (hsa-miR-199a-5p group) or the blank vector (rLv-NC group), and a blank control group was set. The proliferation status of KFs were detected by CCK-8 assay. At 48 hours after infection, the expression of hsa-miR-199a-5p in KFs were detected by quantitative real-time PCR (qRT-PCR); cell apoptosis was detected by flow cytometry analysis; cell invasion ability was detected by Transwell; The mRNA and protein levels of collagen Ⅰ, collagen Ⅲ, α-smooth muscle actin(α-SMA), Smad3 and TGF-β1 were detected by qRT-PCR and Western blotting, respectively.Results:At 48 hours after infection with RLV-hsa-miR-199a-5p lentiviral vector, the mRNA expression level of hsa-miR-199a-5p in hsa-miR-199a-5p group KFs was significantly higher than that in rLv-NC group and blank control group, and the difference was statistically significant ( P<0.01). Compared with the rLv-NC and blank control groups, the proliferation rate and invasiveness of the hsa-miR-199a-5p group decreased, the apoptosis rate increased, with statistical significance ( P<0.01); the mRNA and protein expression levels of collagen Ⅰ, collagen Ⅲ, α-SMA, Smad3 and TGF-β1 in hsa-miR-199a-5p group were significantly lower than those in rLv-NC group and blank control group, with statistical significance ( P<0.01). Conclusions:hsa-miR-199a-5p may inhibit the proliferation and invasion of KFs by inhibiting TGF-β/Smad pathway, and promote the apoptosis of KFs, thus inhibiting keloid fibrosis.