The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

Objective:To investigate the clinical and genetic characteristics of a child with microcephaly-capillary malformation syndrome due to a STAMBP mutation. Methods:The clinical data of a case of microcephaly-capillary malformation syndrome caused by STAMBP gene mutation admitted to Anhui Children′s Hospital in August 2023 were collected. The genes of the child and his parents were detected by whole exome sequencing, and the risk was predicted by biological software. At the same time, the clinical characteristics of the child were analyzed and the literature was reviewed. Results:The patient is a male child aged 2 years and 7 months. The patient had special features, microcephaly, refractory epilepsy, severe comprehensive developmental delay, and capillary malformations. The results of genetic testing showed that the STAMBP gene in the child had complex heterozygous mutations NM_001353967: c.367delG[p.E123fs *27(p.Glu123fsTer27) and c.159A>C(p.Glu53Asp)], inherited from his mother and father respectively. The mutations have not been recorded in the HGMD, dbSNP and gnomAD databases,etc. The protein structure of the STAMBP gene was modeled that predicted c.367del(p.Glu123Lysfs *27) and c.159A>C (p.Glu53Asp) had a negative effect on the function of STAMBP protein. Conclusion:The STAMBP gene complex heterozygous mutations c.367delG(p.Glu123fsTer27) and c.159A>C(p.Glu53Asp) may be the pathogenic factor of this child, which further expands the variation spectrum of the STAMBP gene and the genotype of microcephaly-capillary malformation syndrome, and provides guidance for family genetic counseling.

Objective To investigate the effect of dihydroartemisinin(DHA)on the inflammatory response and skin wound healing in diabetic rats.Methods The ointment was prepared with Carbomer 980,Tween-80,glycerol,ultrapure water and sodium hydroxide as a base.DHA and ethyl nipagin were added and stirred evenly,resulting in DHA ointment.Fifty SPF-grade SD rats were used to create a diabetic rat model by intraperitoneal injection of streptozotocin,and 44 rats were successfully modelled.Whole skin defect wounds were created on the back of rats by using a 2.0 cm diameter circular punch.Thirty-six dorsal wounds were randomly divided into 4 groups(n=9)by the random number table.Then the wounds were applied respectively with 5%DHA,10%DHA,15%DHA and ointment base(control group)once a day for 14 consecutive days.On the 3th,7th and 14th days,the wound healing was observed,the specimens were cut from 0.2 cm of wound margin and would tissue,the histological changes were observed by HE staining.Collagen changes were observed by Masson staining,and the concentrations of interleukin 6(IL-6),interleukin 10(IL-10),and tumor necrosis factor-α(TNF-α)were detected by ELISA.The other eight rats were randomly divided into 10%DHA group and control group.The tissue was cut from the wound on the 7th day,and transcriptome sequencing was performed by high-throughput sequencing technology to screen the differentially expressed genes(DEGs)between the two groups.Gene ontology(GO)functional enrichment analysis as well as kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis were performed.Data were analyzed by one-way ANOVA using SPSS 27.0 statistical software.Results The different concentrations of DHA groups showed better wound healing rates than the control group.The 10%DHA group has the most significant effect(P＜0.05).Compared with the control group,each DHA group showed a decrease in inflammatory cell infiltration and an increase in collagen fibre area on the 7th and 14th days(P＜0.05).The expressions of IL-6 and TNF-α in each DHA group were significantly lower than those in the control group(P＜0.05),while the expression of IL-10 was significantly higher than that in the control group(P＜0.05).Differential gene volcano map showed that the 10%DHA group remarkably up-regulated anti-inflammatory and antibacterial genes such as hypoxia inducible factor 1α(Hif-1α),Smad homolog 12(Smad12)and β-defensin 4(Defb4).The GO functional enrichment analysis indicated that the 10%DHA group was significantly enriched in inflammatory response,immune response and defense response to bacterium.The KEGG enrichment analysis showed that the 10%DHA group was significantly enriched in chemokine signaling pathway,NOD-like receptor signaling pathway and so on.Conclusion DHA may inhibit excessive inflammatory responses by modulating inflammatory factors,anti-inflammatory and antimicrobial genes,chemokine signaling pathway and NOD-like receptor signaling pathway as well as reducing inflammatory cell infiltration,thereby enhancing wound healing.

OBJECTIVE To establish the fingerprint of Guiqi tongmai mixture and evaluate its quality in combination with chemical pattern recognition . METHODS Using narirutin as reference peak ，HPLC fingerprint of Guiqi tongmai mixture was established with Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition）. Common peaks identification and similarity evaluation were conducted . Hierarchical cluster analysis （HCA），principle component analysis （PCA）and orthogonal partial least square -discriminate analysis （OPLS-DA）were performed ，and the value of variable importance in the projection （VIP） greater than 1 was taken as the standard to screen the differential markers affecting the quality of Guiqi tongmai mixture . RESULTS Nineteen common peaks in the HPLC fingerprints of thirteen batches of Guiqi tongmai mixture were calibrated ，and the similarities of them were 0.928-0.990；eight common peaks were identified ，including the peak 7（hydroxysafflor yellow A ），peak 8（albiflorin），peak 9（paeoniflorin），peak 10（calycosin-7-O-glucoside），peak 12（liquiritin），peak 14（ammonium glycyrrhizinate ）， peak 16（narirutin）and peak 19（hesperidin）. According to the results of HCA ，thirteen batches of samples could be clustered into three categories ：S5，S9 and S 11-S13 were clustered into one category ；S4 and S 8 were clustered into one category ；S1-S3，S6- S7 and S 10 were clustered into one category . The results of PCA indicated that the accumulative variance contribution rate of the principle components 1-7 was 92.115%. The results of OPLS -DA showed that VIP values of narirutin ，paeoniflorin，liquiritin， ammonium glycyrrhizinate ，the components corresponding to peak 11 and peak 1 were greater than 1. CONCLUSIONS HPLC fingerprint of Guiqi tongmai mixture is established ，and it could be used for quality evaluation of Guiqi tongmai mixture by combining with chemical pattern recognition techniques . Six components such as narirutin are differential markers affecti ng the quality of Guiqi tongmai mixture .

Atherosclerosis (AS) is an invisible killer among cardiovascular diseases (CVD), which has seriously threatened the life of quality. The complex pathogenesis of AS involves multiple interrelated events and cell types, such as macrophages, endothelial cells, vascular smooth muscle cells and immune cells. Currently, the efficacy of recommended statin treatment is not satisfactory. Natural products (NPs) have attracted increasing attention with regard to their broad structural diversity and biodiversity, which makes them a promising library in the demand for lead compounds with cardiovascular protective bio-activity. NPs can preclude the development of AS by regulating lipid metabolism, ameliorating inflammation, stabilizing plaques, and remodeling the gut microbiota, which lays a foundation for the application of NPs in clinical therapeutics.
Humans ; Biological Products/metabolism* ; Endothelial Cells/metabolism* ; Atherosclerosis/metabolism* ; Macrophages/metabolism* ; Inflammation/metabolism*

Objective:To analyze the characteristics and prognosis of hearing loss in children with bacterial meningitis.Methods:This was a single-center retrospective cohort study. Patients diagnosed with bacterial meningitis who were hospitalized in Beijing Children′s Hospital between 2010 and 2016 and older than 28 days and younger than 18 years at symptom onset were included in this study ( n=573). All clinical information including hearing assessment results during hospitalization were reviewed. All patients with hearing loss were followed up to repeat their hearing test and assess their hearing condition with parents′ evaluation of aural and (or) oral performance of children (PEACH). Patients were grouped according to their hearing assessment results, and Logistic regression analysis was used to analyze the risk factors for hearing loss in patients with bacterial meningitis. Results:Five hundred and seventy-three patients were enrolled in this study, including 347 males and 226 females. The onset age ranged from 29 days to 15.8 years. Two hundred and forty-six patients had identified causative pathogens, among whom 92 cases (37.4%) were pneumococcal meningitis cases. Hearing loss was found in 160 cases (27.9%) during hospitalization, involving 240 ears. Permanent hearing loss was found in 20 cases (16.9%), involving 32 ears. In the patients with permanent hearing loss, 87.5% (28/32) of ears were identified as severe or profound hearing loss during hospitalization. Logistic regression analysis showed that dystonia, the protein concentration level in cerebrospinal fluid>1 g/L, glucose concentration level lower than 1 mmol/L and subdural effusion were independent risk factors for hearing loss ( OR=2.426 (1.450-4.059), 1.865 (1.186-2.932), 1.544 (1.002-2.381) and 1.904 (1.291-2.809)). Conclusions:Hearing loss is a common sequela of bacterial meningitis in children. Most patients have transient hearing loss, but patients with severe or profound hearing impairment have a higher risk of developing permanent hearing loss.

Objective:To investigate changes in long-term cognitive function of patients with prostate cancer treated by androgen deprivation therapy (ADT) and analyze its related factors.Methods:Using a prospective cohort study method, a total of 131 patients with non-metastatic prostate cancer who were admitted to the First Affiliated Hospital of Wenzhou Medical University from April 2016 to April 2018 were selected as the research objects. The patients who received ADT were set as the ADT group and the patients who did not use ADT were set as the non-ADT group. General Situation Questionnaire, Montreal Cognitive Assessment Basic Scale (MoCA-B) , Patient Health Questionnaire (PHQ-9) and Chinese version of Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) were used to investigate. Longitudinal comparisons of patients were made between the two groups on admission, 6 months later, 12 months later and 24 months later. Multivariate regression analysis was conducted to analyze factors associated with cognitive changes in prostate cancer patients receiving ADT.Results:At the end of the 24-month follow-up, a total of 123 patients had completed the investigation, including 55 in the ADT group and 68 in the non-ADT group. The FACT-Cog scores of patients in the ADT group were respectively (110.3±10.2) , (107.6±10.2) , (106.1±9.9) and (103.1±9.5) at the time of enrollment, 6 months, 12 months and 24 months. The FACT-Cog scores of patients in the non-ADT group were respectively (111.1±10.0) , (108.7±10.3) , (107.0±9.4) and (106.4±9.5) at the time of enrollment, 6 months, 12 months and 24 months. Multivariate analysis showed that treatment, age and PHQ-9 score were the influencing factors of cognitive decline in prostate cancer patients ( P<0.05) . Conclusions:The cognitive function of prostate cancer patients who have received ADT for a long time has declined over time. ADT, aging and depression are the main independent risk factors for cognitive decline, suggesting that nursing workers should pay attention to changes of cognitive function of patients at early stage and provide nursing intervention for risk factors to improve the cognitive status of patients.

The Wilderness Medical Society updated and published the Wilderness Medical Society practice guidelines for the prevention and treatment of frostbite in July 2019. The guidelines provide evidence-based recommendations for the prevention and treatment of frostbite, mainly including pathophysiology, classification, prevention, and treatment of frostbite. This paper focuses on the interpretation of the guidelines, aiming at making clinical medical staff understand the new progress of frostbite treatment and providing reference for clinical practice.

Objective:To explore the application of attributional training in postoperative emotion management of patients with non-small cell lung cancer (NSCLC) .Methods:Using the convenient sampling method, a total of 128 NSCLC patients after surgery who were admitted to the First Affiliated Hospital of Zhengzhou University from August 2017 to July 2019 were selected as research objects. A total of 64 NSCLC patients after surgery who were enrolled from August 2017 to July 2018 were set as the control group, and the other 64 NSCLC patients after surgery who were enrolled from August 2018 to July 2019 were set as the observation group. Patients in the control group were given routine nursing while patients in the observation group were given attribution training based on routine nursing. Attribution Style Questionnaire (ASQ) , Hospital Anxiety and Depression Scale (HADS) and Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L4) were used to evaluate the effect of intervention.Results:After intervention, the total ASQ score of the observation group was higher than that of the control group, and the difference was statistically significant ( P<0.01) . After intervention, the scores of anxiety and depression dimensions in HADS of the observation group were lower than those of the control group, and the differences were statistically significant ( P<0.01) . After intervention, the total score and scores of all dimensions of FACT-L4.0 of the observation group were all higher than those of the control group, and the differences were statistically significant ( P<0.01) . Conclusions:Attribution training can help postoperative NSCLC patients to establish positive attribution styles, effectively alleviate their negative emotions and improve their quality of life.

Objective To investigate the effect of maternal age,gestational weeks,numbers of previous spontaneous abortion and embryo gender on chromosomal abnormalities.Methods Bacs on Beads (BoBs) technology was used to detect the chromosome aneuploidy of 245 pregnant women with spontaneous abortion or stillbirth in Jinan Maternity and Child Care Hospital from January 2015 to December 2017 and to analyze the types of their chromosome abnormalities.Comparative analysis between different groups was carried out using Chi-square test.Results Karyotypes of all cases (n=245) were obtained using BoBs.Among them,113 had chromosome abnormalities (46.1％),including 66 autosomal aneuploidy (58.4％),26 sex chromosome aneuploidy (23.0％),seven autosomal partial trisomy (6.2％),five autosomal partial monomer (4.4％),seven triploid (6.2％),one complex triploid (0.9％) and one double trisomy (0.9％).Pregnant women aged over 35 had a higher incidence of chromosome abnormality than those under 35 [61.0％ (36/59) vs 41.4％ (77/186),x2=8.003,P＜0.05].The incidence of chromosome abnormality of women aborted in the first-trimester was also higher than those aborted in the second-trimester [48.5％ (99/204) vs 34.2％ (14/41),x2=4.634,P＜0.05].Moreover,male embryos were more likely to have chromosome abnormality than female ones [57.6％ (49/85) vs 40.0％(64/160),x2=6.483,P＜0.05)].However,there was no significant difference between gravidas with different times of spontaneous abortion (0,1 or ≥ 2,P＞0.05).Conclusions Chromosome abnormality is a major cause of spontaneous abortion,particularly in embryos with chromosome aneuploidy,partial trisomy,partial monomer and triploid.Advanced maternal age may increase the risk of chromosome abnormalities in pregnancies complicated with spontaneous abortion or stillbirth.