In recent years, mesenchymal stem cell-derived exosomes (MSC-EXO) have garnered increasing attention in the field of stomatology and have become an established research area in biomedical research. This article reviews the engineering of exosomes derived from mesenchymal stem cells and their application in the field of stomatology, in order to provide new ideas for the development of stomatology. Exosomes are nanoscale membrane vesicles secreted by cells and contain a variety of proteins, RNAs, lipids, and other biomolecules. They are transported through the circulatory system and can interact with other cells to regulate their biological behavior and participate in a variety of physiological and pathological processes. In the treatment of oral diseases, exosomes have shown great potential due to their natural biological activity and versatility. However, studies have found that relying solely on the function of natural exosomes may not fully meet the complex clinical requirements. Therefore, the concept of engineered exosomes has emerged. Engineered exosomes can be modified by bioengineering technology to enhance their targeting, allowing them to reach the lesion site more accurately. At the same time, engineered exosomes can also be surface modified or loaded internally to carry specific therapeutic molecules, such as drugs, gene editing tools or signaling molecules to improve the therapeutic effect. In addition, this engineered treatment can also confer greater stability to exosomes, making them better able to resist clearance by the immune system when circulating in the body, extending their half-life, and improving the effectiveness of treatment. Although engineered exosomes have attracted extensive attention in the fields of stomatology and other fields, their application is still mainly in the stage of basic research. To promote the clinical application of engineered exosomes, it is necessary to provide more sufficient evidence of biocompatibility and clarify their therapeutic effect and mechanism.

Heart and spleen deficiency syndrome is the most common syndrome type in patients with insomnia. Based on the theory of disease syndrome-combined animal model， this paper used multiple databases to search for the keywords "heart and spleen deficiency"， "insomnia"， "sleepless"， "disease syndrome-combined animal model"， "model evaluation"， etc. It selected the literature related to the animal model of insomnia with heart and spleen deficiency in the past 20 years to evaluate from the aspects of model establishment， modeling factors， syndrome model， disease model， macro characterization & macro characterization evaluation scale， micro indicators， etc. It is found that the existing animal model of insomnia with heart and spleen deficiency is not completely constructed by the method of disease syndrome combination of disease modeling factors and syndrome modeling factors. In the model using this method， the single establishment factor of heart and spleen deficiency does not conform to the clinical reality of disease， and the selection of the factors for the insomnia model is not closely related to or even separated from the syndrome performance. There is a problem of insufficient quantification of macro representation when the macro representation of the model replaces the symptoms related to heart and spleen deficiency syndrome and insomnia in an equivalent manner for macro representation evaluation， which can be improved according to the quantitative ideas and examples of the existing macro representation and macro representation evaluation scale. There are few specific indicators of heart and spleen deficiency syndrome in micro indicators. The micro research of heart and spleen deficiency syndrome and the essence of other traditional Chinese medicine （TCM） syndromes can be carried out by metabonomics and other technologies combined with the theory of corresponding prescription and syndrome， along the specific related ideas of "prescription and syndrome， treatment principle and selection of prescription， treatment principle and selection of acupoints， as well as therapeutic mechanism and syndrome essence". The future users and researchers of animal models of insomnia with heart and spleen deficiency can get improved methods and ideas through the shortcomings of animal models of heart and spleen deficiency listed in this paper and construct animal models of insomnia with heart and spleen deficiency that are more suitable for clinical practice， so as to establish a more perfect modeling method and evaluation system of disease syndrome-combined animal model.

Heart and spleen deficiency syndrome is the most common syndrome type in patients with insomnia. Based on the theory of disease syndrome-combined animal model， this paper used multiple databases to search for the keywords "heart and spleen deficiency"， "insomnia"， "sleepless"， "disease syndrome-combined animal model"， "model evaluation"， etc. It selected the literature related to the animal model of insomnia with heart and spleen deficiency in the past 20 years to evaluate from the aspects of model establishment， modeling factors， syndrome model， disease model， macro characterization & macro characterization evaluation scale， micro indicators， etc. It is found that the existing animal model of insomnia with heart and spleen deficiency is not completely constructed by the method of disease syndrome combination of disease modeling factors and syndrome modeling factors. In the model using this method， the single establishment factor of heart and spleen deficiency does not conform to the clinical reality of disease， and the selection of the factors for the insomnia model is not closely related to or even separated from the syndrome performance. There is a problem of insufficient quantification of macro representation when the macro representation of the model replaces the symptoms related to heart and spleen deficiency syndrome and insomnia in an equivalent manner for macro representation evaluation， which can be improved according to the quantitative ideas and examples of the existing macro representation and macro representation evaluation scale. There are few specific indicators of heart and spleen deficiency syndrome in micro indicators. The micro research of heart and spleen deficiency syndrome and the essence of other traditional Chinese medicine （TCM） syndromes can be carried out by metabonomics and other technologies combined with the theory of corresponding prescription and syndrome， along the specific related ideas of "prescription and syndrome， treatment principle and selection of prescription， treatment principle and selection of acupoints， as well as therapeutic mechanism and syndrome essence". The future users and researchers of animal models of insomnia with heart and spleen deficiency can get improved methods and ideas through the shortcomings of animal models of heart and spleen deficiency listed in this paper and construct animal models of insomnia with heart and spleen deficiency that are more suitable for clinical practice， so as to establish a more perfect modeling method and evaluation system of disease syndrome-combined animal model.

OBJECTIVE: To precise classify sacral meningeal cysts, effective guide minimally invasive neurosurgery and postoperative personalized rehabilitation by multiple dimensions radiographic reconstruction MRI. METHODS: From March to December 2021, based on the original 3D-fast imaging employing steadystate acquisition (FIESTA) scanning sequence, 92 patients with sacral meningeal cysts were pre-operatively evaluated by multiple dimensional reconstruction MRI. The shape of nerve root and the leakage of cyst were reconstructed according to the direction of nerve root or leakage track showed on original MRI scans. Sacral canal cysts were accurately classified as including nerve root and without nerve root, so as to accurately design the incision of skin and formulate corresponding open range of the posterior wall of the sacral canal. Under the microscope intraoperation, the shape of the nerve roots inside cysts or leakage track of the cysts without nerve roots were verified and explored. After the reinforcement and shaping operation, several reexaminations of multiple dimensional reconstruction MRI were performed to understand the deformation of the nerve root and hydrops in the operation cavity, so as to formulate a persona-lized rehabilitation plan for the patients. RESULTS: Among the 92 patients with sacral mengingeal cyst, 58 (63.0%) cysts with nerve root cyst, 29 (31.5%) cysts without nerve root cyst, and 5 (5.4%) cysts with mixed sacral canal cyst. In 58 patients with nerve root cysts, the accuracy of preoperative clinical classification on MRI image reached 96.6% (56/58) through confirmation by operating microscope. Only 2 cases of large single cyst with nerve root on the head of cyst were mistaken for without nerve root type. In 29 patients with sacral cyst without nerve root, the accuracy of preoperative image reached 100% through confirmation by operating microscope. The accuracy of judging the internal nerve root and leakage of 12 cases with recurrent sacral cyst was also 100%. Two cases of delayed postoperative hydrops were found one month after operation. After rehabilitation treatment by moxibustion and bathing, the hydrops disappeared 4-6 months after operation. CONCLUSION Multiple dimensional reconstruction MRI can precisely make clinical classification of sacral meningeal cysts before operation, guide minimally invasive neurosurgery effectively, and improve the rehabilitation effect.
Humans ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Sacrum/surgery* ; Adult ; Middle Aged ; Imaging, Three-Dimensional/methods* ; Cysts/rehabilitation* ; Aged ; Adolescent ; Young Adult ; Spinal Nerve Roots/diagnostic imaging* ; Minimally Invasive Surgical Procedures ; Neurosurgical Procedures/methods*

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

Objective To establish a method for determining hydrogen sulfide(H2S)in blood and apply it to practical cases.Methods A delute solution was achieved by adding 0.8 mL saturated borax solution into 0.2 mL blood sample was diluted with.1 mL acetonitrile solution containing 0.1％formic acid was then taken in a test tube,followed by adding 0.1 mL dilute solution and 0.1 mL thiozine aqueous solution(1％).After thorough mixing,the mixture was left to stand for 30 minutes.Subsequently,the sample was subjected to liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis after centrifugation and membrane filtration.Results The results showed that H2S exhibited good linearity within the concentration range of 10～2 000 ng/mL,with the R2 value of 0.998 5.The detection limit was 5 ng/mL,and the quantification limit was 10 ng/mL.In three cases of H2S poisoning,sulfur ions were detected in the blood of the deceased individuals,with concentrations ranging from 0.17 to 0.56 μg/mL.Conclusion For the first time,this study established a LC-MS/MS method for determining H2S in blood,which can meet the detection needs of H2S poisoning cases.

Objective To investigate the risk factors of short-term adverse prognosis and the predictive value of Charlson comorbidities index(CCI)in patients with central pulmonary embolism(PE).Methods 115 cases of central PE patients were retrospectively analyzed.According to the adverse prognosis during hospitalization,the subjects were divided into adverse event group and no adverse event group.The clinical characteristics of the ad-verse event group were analyzed.Multivariate Logistic regression analysis was performed for statistically significant indicators.Results The most common clinical symptoms of central PE patients were chest distress or dyspnea(77.4％ ),followed by cough(35.7％ ),chest pain(28.7％ ),syncope(9.6％ )and hemoptysis(7.8％ ).There were no statistically significant differences in gender,smoking history,drinking history,symptoms and signs between the two groups.In univariate analysis,CCI,grouping score of thrombus location,white blood cell count,neutrophil count and urea nitrogen were associated with adverse events in central PE patients,with statistical signif-icance(P＜0.05).After Logistic regression multivariate analysis,increased neutrophil count(OR=1.494,95％ CI:1.073-2.080,P=0.017)was an independent risk factor(P＜0.05).The CCI in the group with adverse e-vents was higher than that in the group without adverse events(P=0.004).Multivariate analysis showed that in-creased CCI(Oβ=1.342,95％ CI:1.022-1.763,P=0.034)was an independent risk factor,and the risk of adverse events increased by 34.2％ for every one-point increase in CCI.The thrombus location score of the group with adverse events was significantly higher than that of the group without adverse events(OR=2.586,95％ CI:1.366-4.896,P=0.004),and the risk of adverse events increased 1.586 times with each increase of thrombus location score.Conclusion Increased neutrophil count,CCI,and thrombus location score are associated with poor short-term prognosis in central PE patients.

Objective To evaluate the clinical outcome of kidney transplantation from donation after brain death(DBD)donors complicated with acute kidney injury(AKI).Methods Clinical data of 216 DBD donors were retrospectively analyzed,and they were divided into the AKI group(n=69)and control group(n=147)according to the Kidney Disease:Improving Global Outcomes(KDIGO)guidelines.Donors in the AKI group were further divided into the KDIGO stage 1 and stage 2-3 subgroups.One hundred and thirty-five recipients were assigned into the AKI group and 288 recipients in the control group.Postoperative recovery of renal function and clinical outcomes of the recipients were recorded.The risk factors of delayed graft function(DGF)were identified.Results The highest serum creatinine(Scr)level,Scr level before procurement,the highest blood sodium level and blood sodium level before procurement in the AKI group were higher than those in the control group.The application duration of vasopressors in the AKI group was longer than that in the control group.In the AKI group,the amount of fluid resuscitation within 48 h was higher,the HCO3-level at admission was lower,and the incidence of diabetes insipidus and hypotension was higher than those in the control group.The highest Scr level and the Scr level before procurement in KDIGO stage 2-3 donors were significantly higher than those in KDIGO stage 1 counterparts(all P＜0.05).Compared with the control group,the incidence of DGF and acute rejection was higher,the proportion of continuous renal replacement therapy was higher,the Scr level within postoperative 90 d was higher,and the urine amount within postoperative 3 d was less than those of recipients in the AKI group.Compared with KDIGO stage 1 recipients,KDIGO stage 2-3 recipients had higher Scr levels at postoperative 3,4,5 and 15 d,and less urine amount at postoperative 2 d(all P＜0.05).Univariate analysis showed that donor age,the highest Scr level,the highest blood sodium level and the amount of fluid resuscitation within 48 h were the risk factors for DGF in recipients after kidney transplantation.Multivariate analysis showed that donor age was the independent risk factor for DGF in recipients after kidney transplantation(all P＜0.05).Conclusions For the application of DBD donors complicated with AKI,active organ maintenance should be performed to alleviate AKI.It exerts no effect upon graft function and survival rate at postoperative 6 months,which may achieve equivalent efficacy as non-AKI donors and may be used as a source of extended criteria donor kidneys.