BACKGROUND:A large number of studies have confirmed that the therapeutic effectiveness of mesenchymal stem cell secretome is comparable to that of mesenchymal stem cells,but the mechanism of its action is still unclear. OBJECTIVE:To summarize the research progress of mesenchymal stem cell secretome in recent years,to investigate the molecular mechanism of its therapeutic effect,to analyze the current problems and to look forward to the future development. METHODS:The terms"exosomes,mesenchymal stem cells secrete,extracellular vesicles,mesenchymal stem cells,mechanism"were used as English search terms in the PubMed database.Articles that were not related to the research purpose of the article and duplicated articles were excluded.At the same time,we combined the method of literature tracking.Finally,109 articles that met the criteria were incuded for the review. RESULTS AND CONCLUSION:(1)The mesenchymal stem cell secretome promotes tissue repair and regeneration through delivering genetic material,immunomodulatory factors,growth factors,etc.to target cells,by activating anti-apoptotic,regulating angiogenesis,modulating fibrosis and pro-survival pathways in target cells.(2)The potential of mesenchymal stem cell secretome in disease therapy has also been confirmed.Numerous research results have shown that mesenchymal stem cell secretome can be used as a new cell-free treatment for inflammatory and degenerative diseases.(3)Mesenchymal stem cell secretome has been engineered to have more efficient therapeutic effects in recent years.However,due to the heterogeneity of the mesenchymal stem cell secretome and the complexity of its components,the exact mechanism of its therapeutic effect is still unclear.(4)At present,further research is needed to identify the key targets of mesenchymal stem cell secretome,and innovative specific and enhanced mesenchymal stem cell secretome should be developed by combining with engineering and genetic engineering technologies in the future.

ObjectiveTo explore the distribution pattern of tongue image characteristics in patients with glucolipid metabolic disorders and its main syndromes. MethodsA total of 841 patients with glucolipid metabolic disorders （disease group）， and 380 healthy subjects （control group） were included. The disease group was classified into three syndrome types： 283 cases of liver depression and spleen deficiency syndrome， 311 cases of phlegm-dampness obstruction syndrome， and 247 cases of qi stagnation and blood stasis syndrome. Tongue image data were collected using the TFDA-1 Tongue Diagnosis Instrument， and the TDAS V3.0 software was used to analyze the color， texture， and morphological features of the tongue body （TB） and tongue coating （TC） in patents with different syndromes of disease group （including lightness （L）， red-green axis （a）， yellow-blue axis （b）， luminance （Y）， difference between red signal and brightness （Cr）， difference between blue signal and brightness （Cb）， contrast （CON）， angular second moment （ASM）， entropy （ENT）， mean value （MEAN）， tongue coating area/tongue surface area （perAll）， and tongue coating area/non-coated area （perPart））. Logistic regression analysis was conducted to identify influencing factors for different syndrome types of glucolipid metabolic disorders. ResultsThe tongue body indicators TB-L， TB-Y， and TB-Cb in the disease group were significantly higher than those in the control group， while TB-a， TB-b， and TB-Cr were significantly lower. The tongue coating indicators TC-L， TC-Y， TC-Cb， perAll， and perPart in the disease group were significantly higher than those in the control group， while TC-a， TC-b， and TC-Cr were significantly lower （P＜0.05）. Comparing with the different syndromes in disease group， the TB-L and TB-Y of the liver depression and spleen deficiency syndrome， and the phlegm-damp obstruction syndrome were higher than those of the qi stagnation and blood stasis syndrome； the TB-a and TB-Cr of the phlegm-damp obstruction syndrome were lower than those of the qi stagnation and blood stasis syndrome； the perAll of the phlegm-damp obstruction syndrome was higher than that of the qi stagnation and blood stasis syndrome （P＜0.05）. In the analysis of the morphological characteristics of tongue signs， more spotted tongue in disease group compared with control group， more teeth-marked tongue in liver depression and spleen deficiency syndrome than the other two syndromes， more greasy coating in phlegm-damp obstruction syndrome， and more stasis spots of tongue in qi stagnation and blood stasis syndrome （P＜0.05）. Logistic regression analysis identified that greasy coating， spotted tongue， stasis spots of tongue， tooth-marked tongue， perAll， and TB-Cb are the influencing factors of liver depression and spleen deficiency syndrome； greasy coating， tooth-marked tongue， TC-Cb， and TC-Cr are the influencing factors of phlegm-damp obstruction syndrome； cracked tongue， stasis spots of tongue， tooth-marked tongue， and TB-Y are the influencing factors of qi stagnation and blood stasis syndrome （P＜0.05）. ConclusionCompared to healthy individuals， patients with glycolipid metabolic disorder have darker tongue color and thicker， greasy tongue coating. Glycolipid metabolic disorder patients of liver depression and spleen deficiency syndrome exhibit a reddish tongue with finer textures and more tooth marks； patients of phlegm-damp obstruction syndrome have lighter tongue coating with a coarser texture and a higher prevalence of greasy coating； patients of qi stagnation and blood stasis syndrome display lower tongue brightness with a higher prevalence of blood stasis spots.

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Objective:To analyze the status quo of type D personality, intolerance of uncertainty and family support in first-episode stroke patients, and to explore the mediating role of family support between type D personality and intolerance of uncertainty in first-episode stroke patients, in order to provide reference for formulating relevant clinical intervention measures to promote the physical and mental health of first-episode stroke patients.Methods:This study was a cross-sectional investigation. A total of 300 patients with acute first-episode stroke who met the inclusion and exclusion criteria in the Department of Neurology of the General Hospital of Ningxia Medical University and the First People′s Hospital of Yinchuan from May 2023 to September 2023 were selected as the study objects by convenience sampling method. The general data questionnaire, Type D personality Scale-14, Family Caring Index Scale and the Intolerance of Uncertainty Scale were used to investigate them. Pearson correlation analysis was used to test the correlation between variables, and SPSS plug-in PROCESS 3.5 was used to test the mediation effect.Results:Finally, 300 questionnaires were effectively collected, including 228 males and 72 females. Patients aged ≥ 60 years old were the majority, accounting for 49.3% (148/300). The detection rate of type D personality in the first stroke patients was 37.3% (112/300), and the total score of Type D personality inventory, family support and intolerance of uncertainty of type D personality in the first stroke patients were (22.16 ± 9.95), (6.40 ± 2.23), (27.82 ± 7.93) points. The correlation analysis results showed that the intolerance of uncertainty of type D personality in the first stroke patients was positively correlated with type D personality scores ( r=0.675, P<0.001). There was a negative correlation with family support score ( r=-0.644, P<0.001). The results of mediating effect analysis showed that family support played a partial mediating role in the relationship between type D personality and intolerability of uncertainty in first-stroke patients, and the mediating effect accounted for 34.94% of the total effect. Conclusions:The mediating role of family support between type D personality and intolerability of uncertainty in first-stroke patients is established. In the future, the level of family support of patients can be continuously improved to reduce their intolerability of uncertainty, so as to promote the physical and mental health of patients and improve their quality of life.

BACKGROUND:Based on different algorithms of machine learning,how to carry out clinical research on lumbar disc herniation with the help of various algorithmic models has become a trend and hot spot in the development of intelligent medicine at present. OBJECTIVE:To review the characteristics of different algorithmic models of machine learning in the diagnosis and treatment of lumbar disc herniation,and summarize the respective advantages and application strategies of algorithmic models for the same purpose. METHODS:The computer searched PubMed,Web of Science,EMBASE,CNKI,WanFang,VIP and China Biomedical(CBM)databases to extract the relevant articles on machine learning in the diagnosis and treatment of lumbar disc herniation.Finally,96 articles were included for analysis. RESULTS AND CONCLUSION:(1)Different algorithm models of machine learning provide intelligent and accurate application strategies for clinical diagnosis and treatment of lumbar disc herniation.(2)Traditional statistical methods and decision trees in supervised learning are simple and efficient in exploring risk factors and establishing diagnostic and prognostic models.Support vector machine is suitable for small data sets with high-dimensional features.As a nonlinear classifier,it can be applied to the recognition,segmentation and classification of normal or degenerative intervertebral discs,and to establish diagnostic and prognostic models.Ensemble learning can make up for the shortcomings of a single model.It has the ability to deal with high-dimensional data and improve the precision and accuracy of clinical prediction models.Artificial neural network improves the learning ability of the model,and can be applied to intervertebral disc recognition,classification and making clinical prediction models.On the basis of the above uses,deep learning can also optimize images and assist surgical operations.It is the most widely used model with the best performance in the diagnosis and treatment of lumbar disc herniation.The clustering algorithm in unsupervised learning is mainly used for disc segmentation and classification of different herniated segments.However,the clinical application of semi-supervised learning is relatively less.(3)At present,machine learning has certain clinical advantages in the identification and segmentation of lumbar intervertebral discs,classification and grading of the degenerative intervertebral discs,automatic clinical diagnosis and classification,construction of the clinical predictive model and auxiliary operation.(4)In recent years,the research strategy of machine learning has changed to the neural network and deep learning,and the deep learning algorithm with stronger learning ability will be the key to realizing intelligent medical treatment in the future.

ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg^-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

ObjectiveTo investigate the mechanism of neferine（Nef） in promoting vascular regeneration against cerebral ischemia through modulation of mitochondrial calcium uniporter（MCU） ion channel. MethodTaking the area of subintestinal vessels in microvascular deficiency zebrafish as an index， the vascular regenerative efficacy of Nef was evaluated， and the median effective concentration（EC₅₀） was calculated. Rats were randomly divided into a sham operation group， a model group， a positive drug group（butylphthalide， 6 mg·kg^-1）， and Nef low， medium， and high dose groups（0.125， 0.625， 3.125 μg·kg^-1）. Except for the sham operation group， the middle cerebral artery occlusion（MCAO） model was established in other groups. After modeling， the groups were administered the corresponding dose of drugs by gavage， while the sham operation and model groups received equal volumes of saline， once a day for 7 consecutive days. Neurobehavioral scores were assessed for each group of rats， and the infarct rate of ischemic brain tissue was calculated by 2，3，5-triphenyltetrazolium chloride（TTC） staining. The regional cerebral blood flow（rCBF） of each group was measured using a speckle contrast imaging. Immunofluorescence and Western blot were conducted to detect the expression of vascular endothelial growth factor（VEGF）， platelet endothelial cell adhesion molecule-1（CD31）， and hypoxia-inducible factor-1α（HIF-1α） proteins in each group. Human umbilical vein endothelial cells（HUVECs） were divided into the normal group， model group， positive drug group（astragaloside Ⅳ， 10 μmol·L^-1）， and Nef group （32 nmol·L^-1）. In the verification of mitochondrial protection of Nef and its mechanism in promoting vascular regeneration， the spermine（MCU agonist） and Nef+spermine group were added. HUVECs model of oxygen-glucose deprivation（OGD） was established in all groups except the normal group， the cell viability was assessed using 3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide（MTT） assay， and cell migration ability was evaluated through scratch and tube formation assays. Fluorescent probes（Rhod-2 AM， Fluo-3 AM， JC-1， Calcein AM） and a cellular energy metabolism analyzer were used to analyze the mitochondrial protective effects of Nef. Molecular docking was performed to predict the binding ability of Nef with MCU and HIF-1α， and Western blot was used to detect the effects of Nef on the protein expressions of MCU， B-cell lymphoma-2 associated X protein（Bax）， Caspase-3 and HIF-1α in the OGD model HUVECs. ResultThe results of vascular regeneration in microvascular deficiency zebrafish showed that compared to the normal group， the area of subintestinal vessels in the model group significantly decreased（P<0.01）. Compared to the model group， different concentrations of Nef could significantly increase the area of subintestinal vessels（P<0.01）， with the maximum tolerated concentration of 10.24 μmol·L^-1 and the EC₅₀ of 0.23 μmol·L^-1. Anti-cerebral ischemia results on MCAO rats showed that compared to the sham operation group， the model group had a significant decrease in rCBF and a significant increase in infarct rate， while CD31 expression significantly decreased（P<0.01）， and VEGF and HIF-1α protein expressions significantly increased（P<0.05）. Compared to the model group， the treated groups showed significant increases in rCBF， significant reductions in infarct volume， and significant increases in CD31， VEGF， and HIF-1α protein expression（P<0.01）. Cell experiment results showed that compared to the normal group， the model group had decreased cell viability and migration ability， increased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， reduced mitochondrial permeability transition pore（MPTP） opening， and decreased mitochondrial energy metabolism capability， with increased expressions of MCU， Bax， Caspase-3 and HIF-1α proteins（P<0.05， P<0.01）. Compared to the model group， the Nef group showed increased cell viability and migration ability， decreased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， increased MPTP opening， enhanced mitochondrial energy metabolism capability， decreased expressions of MCU， Bax and Caspase-3 proteins， and increased HIF-1α protein expression（P<0.05， P<0.01）. ConclusionNef can stabilize mitochondrial membrane potential and inhibit mitochondrial apoptosis. By down-regulating the expression of MCU， it suppresses the activation of intracellular Bax and Caspase-3 while activating the HIF-1α signaling pathway， enhancing the expression of VEGF and CD31， thereby promoting vascular regeneration to treat ischemic brain injury.

Objective To explore the current status of posttraumatic growth (PTG) among nurses at psychiatric department and analyze its latent profiles and population characteristics. Methods A total of 357 nurses from psychiatric departments of five tertiary Grade A hospitals were selected as the research subjects using the convenience sampling method. The PTG and professional quality of life were studied using the Posttraumatic Growth Inventory and the Chinese version of the Compassion Fatigue Scale. Results The PTG score of the nurses was (56.6±23.2). The scores of compassion satisfaction, burnout, and secondary traumatic stress among nurses were (32.6±7.2), (26.9±5.9), and (26.0±5.4), respectively. The result of potential profile analysis showed that the nurses could be divided into three latent profiles based on PTG levels: low PTG group (34.4%), moderate PTG group (44.0%), and high PTG group (21.6%). The results of multinomial logistic regression analysis showed that the nurses who slept 7-8 hours per day were at higher risk of being in the high PTG group compared with those who slept more than eight hours per day (P<0.05). Psychiatric nurses who took regular exercise were at higher risk of being in the high PTG group compared with those who took irregular exercise (P<0.05). The nurses who had high job satisfaction scores were at higher risk of being in the high PTG group compared with those who had low job satisfaction scores (P<0.01). The nurses with higher compassion satisfaction scores increased the risk of being in the high PTG group compared with those with lower compassion satisfaction scores (P<0.01). The nurses with higher burnout scores increased the risk of being in the low PTG group compared with those with lower burnout scores (P<0.01). Conclusion The PTG characteristics of the nurses exhibit heterogeneity and can be categorized into three distinct profiles. Sleep duration, regular exercise, job satisfaction, compassion satisfaction, and burnout are influencing factors for the PTG latent profiles of nurses working at psychiatric department.

Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if past pulmonary tuberculosis(TB)affects ICIs'effectiveness and safety in lung cancer treatment.We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022.We compared outcomes and side effects between patients with and without prior TB.Of 116 patients(40 with TB history,76 without),prior TB didn't reduce treatment effectiveness but did increase severe side effects.Notably,older patients(≥65 years)faced a higher risk of severe side effects.Detailed cases of two patients with severe side effects underscored TB as a risk factor in lung cancer patients receiving ICIs,stressing the need for careful monitoring and personalized care.