A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

ObjectiveTo investigate the effects of modified Buyang Huanwu Tang on cerebral ischemia-reperfusion injury （CI/RI） in mice via the PTEN-induced putative kinase 1/E3 ubiquitin ligase （PINK1/Parkin） signaling pathway-mediated mitophagy， and to explore the underlying mechanism by which modified Buyang Huanwu Tang improves CI/RI. MethodsSeventy-two male C57BL/6J mice were randomly divided into six groups （n = 12 per group）： Sham-operated group， middle cerebral artery occlusion/reperfusion （MCAO/R） model group， low-， medium-， and high-dose modified Buyang Huanwu Tang groups （8.84， 17.68， 35.36 g·kg^-1·d^-1）， and an aspirin group （13.00 mg·kg^-1·d^-1）. Neurological deficit scores were assessed using the Zea-Longa method. Cerebral infarct volume ratio was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Histopathological changes and neuronal injury in brain tissues were observed using hematoxylin-eosin （HE） staining and Nissl staining. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay. Mitochondrial ultrastructure in brain tissue was observed by transmission electron microscopy （TEM）. Serum levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of PINK1， Parkin， microtubule-associated protein 1 light chain 3B （LC3B， LC3Ⅱ/Ⅰ）， and p62 in brain tissues were detected by real-time quantitative reverse transcription PCR （Real-time PCR） and Western blot， respectively. ResultsCompared with the sham-operated group， the MCAO/R model group showed significantly increased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Severe cortical injury on the infarct side was observed， characterized by decreased neuronal density， cytoplasmic vacuolation， nuclear pyknosis， a marked reduction in Nissl bodies， dissolution of Nissl bodies in the cytoplasm of some pyramidal neurons， and blurred cellular boundaries. The number of TUNEL-positive cells increased significantly （P<0.01）. Mitochondria exhibited cristae membrane rupture and matrix vacuolation， with rupture of the outer mitochondrial membrane and formation of autophagosomes， the number of which increased significantly. Serum SOD activity decreased significantly （P<0.01）， while MDA content increased significantly （P<0.01）. In infarcted brain tissues of model mice， the relative mRNA expression and protein levels of PINK1， Parkin and LC3B were significantly increased （P<0.05， P<0.01）， whereas p62 mRNA and protein expression were significantly decreased （P<0.05， P<0.01）， showing statistical significance. Compared with the model group， all treatment groups showed significantly decreased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Neuronal density increased significantly， cytoplasmic vacuolation was alleviated， nuclear morphology tended to be more regular and clearer， Nissl body density increased significantly with reduced dissolution and improved contour clarity. The mitochondrial cristae structure was partially restored， with some mitochondria showing autophagosome encapsulation， and the degree of mitochondrial damage was alleviated. Serum SOD activity increased significantly （P<0.01）， while MDA content decreased significantly. The mRNA and protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ were significantly increased （P<0.05， P<0.01）， while p62 mRNA and protein expression in the low- and medium-dose modified Buyang Huanwu Tang groups were significantly decreased （P<0.05， P<0.01）， showing statistical significance. ConclusionModified Buyang Huanwu Tang can upregulate the protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ and downregulate p62 protein expression， suggesting that it may improve CI/RI by regulating the expression of proteins related to the PINK1/Parkin signaling pathway. Regulation of the mitophagy pathway may be one of the mechanisms by which modified Buyang Huanwu Tang alleviates CI/RI in mice.

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 analyze the influencing factors of mood state of common rheumatic (rheumatoid arthritis; systemic lupus erythematosus; ankylosing spondylitis) patients and find out the common characteristics of patients with negative emotions, so as to identify and treat rheumatic patients with anxiety and depression in clinical practice.Methods:A total of 205 patients with rheumatism (83 with rheumatoid arthritis, 74 with systemic lupus erythematosus, 48 with ankylosing spondylitis) admitted to the Shandong Provincial Hospital Affiliated to Shandong University from April to May 2023 were included. The general condition and POMS of patients were collected. All patients were divided into 3 groups of low-TMD/ middle-TMD/ high-TMD(TMD≤90 scores; 90 scores105 scores). The χ2 test was used for categorical variables, and the continuous variables were tested for normal distribution. If they followed a normal distribution, the independent sample t test (for homogeneous variance) or the Welch′s t test (for unequal variance) was used for comparison between the two groups, and one-way analysis of variance was used for comparison between multiple groups; if they did not follow a normal distribution, the Kruskal-Wallis H test was used for comparison between groups. Patients with TMD>90 scores were defined as the negative emotion group. Gender, age, education level, economic income status, and TMD were included in the two-step cluster analysis (TCA) to obtain three cluster groups and analyze the differences between the groups. Logistic regression was used to analyze the risk factors. Results:The study found that patients with rheumatic diseases with low serum albumin levels ( F=6.26, P=0.003), low education level ( χ2=8.36, P=0.015), low economic level ( χ2=15.59, P<0.001), short disease course ( H=28.01, P<0.001), and high disease activity ( χ2=56.93, P<0.001) had higher TMD scores, which was not related to the type of disease ( χ2=4.81, P=0.090). The negative mood group had a higher proportion of females (57.6% vs. 73.4%, χ2=5.16, P=0.023), a shorter course of disease [24(12, 48) months vs. 48(24, 93) months, Z=13.58, P<0.001], and a lower serum albumin [(42.2±4.0) g/L vs. (44.0±3.4)g/L, t=-14.09, P=0.002], low level of education ( χ2=9.04, P=0.029), low level of income ( χ2=10.29, P=0.036), high disease activity ( χ2=61.91, P<0.001). The results of cluster analysis indicated that the above factors were significantly different among the three cluster groups except the course of disease. It is noteworthy that age ( F=19.25, P<0.001) and serum albumin ( F=5.64, P=0.004) had the lowest value and the highest TMD score ( F=5.64, P<0.001). Regression analysis showed that gender, disease course and disease activity were related factors to the occurrence of negative emotions, and high disease activity was a risk factor [ OR(95% CI) =26.58(4.53, 156.09), P<0.001]. Men [ OR(95% CI)=0.20 (0.08, 0.50), P=0.001) and the course of [ OR(95% CI)=0.99 (0.98, 1.00), P=0.007) as the protective factors. Conclusion:Male, serum albumin level, education level, income level, disease course and disease activity were the main factors affecting the mood state of patients with rheumatism, in which high disease activity was the risk factor, male and long disease course were the protective factors.

OBJECTIVE To understand the drug resistance among the acquired immune deficiency syndrome(AIDS)population who failed in the antiviral therapy from 2022 to 2023 and analyze the molecular network.METHODS The plasma specimens were collected from the population with viral load no less than 1000 cps/ml who received antiviral therapy for more than 6 months in Aksu area from 2022 to 2023,which were delivered to Aksu Regional Center for Disease Control and Prevention for test.MEGA5 and the Stanford University drug resistance database were employed to determine the subtypes and drug resistance after the sequences of human immunodefi-ciency virus type Ⅰ polymerase gene region(HIV-1pol)were obtained,and the molecular network was established by HIV-trace.RESULTS Totally 648 sequences of HIV-1pol region were obtained,CRF07_BC(97.69％)was the major subtype,and the drug resistance rate was 58.33％;the drug resistance rates to non-nucleoside reverse transcriptase inhibitor(NNRTI),nucleoside reverse transcriptase inhibitor(NRTI)and protease inhibitor(PI)were 51.70％,19.75％and8.64％,respectively.The univariate analysis showed that year(x2=6.341),age(x2=18.455)and route of infection(x2=14.061)had remarkable effects on the drug resistance among the population with failed ART(P＜0.05).Multivariate regression analysis indicated that the drug resistance rate was higher in 2022 than in 2023(95％CI:1.132 to 2.191),and the drug resistance rate was higher among the population aged less than 60 years old than among the population more than 6 years old(95％CI:3.647 to 70.268,95％CI:1.435 to 8.235,95％CI:1.061 to 6.164,re-spectively).With 1.5％of the genetic distance set as the threshold,the molecular network was established,the network access rate was 49.07％,77.14％of the clusters had drug-resistant mutation sites,and the male population was at higher risk of network access than the female population.CONCLUSIONS The drug resistance rate is relatively high among the AIDS population with failed ART,and the drug-resistant strains appear in clusters in the molecular network.It is neces-sary to further strengthen the monitoring of drug resistance and improve the quality of the follow-up so as to reduce the occurrence of drug resistance and transmission of virulent strains.

OBJECTIVE To understand the drug resistance among the acquired immune deficiency syndrome(AIDS)population who failed in the antiviral therapy from 2022 to 2023 and analyze the molecular network.METHODS The plasma specimens were collected from the population with viral load no less than 1000 cps/ml who received antiviral therapy for more than 6 months in Aksu area from 2022 to 2023,which were delivered to Aksu Regional Center for Disease Control and Prevention for test.MEGA5 and the Stanford University drug resistance database were employed to determine the subtypes and drug resistance after the sequences of human immunodefi-ciency virus type Ⅰ polymerase gene region(HIV-1pol)were obtained,and the molecular network was established by HIV-trace.RESULTS Totally 648 sequences of HIV-1pol region were obtained,CRF07_BC(97.69％)was the major subtype,and the drug resistance rate was 58.33％;the drug resistance rates to non-nucleoside reverse transcriptase inhibitor(NNRTI),nucleoside reverse transcriptase inhibitor(NRTI)and protease inhibitor(PI)were 51.70％,19.75％and8.64％,respectively.The univariate analysis showed that year(x2=6.341),age(x2=18.455)and route of infection(x2=14.061)had remarkable effects on the drug resistance among the population with failed ART(P＜0.05).Multivariate regression analysis indicated that the drug resistance rate was higher in 2022 than in 2023(95％CI:1.132 to 2.191),and the drug resistance rate was higher among the population aged less than 60 years old than among the population more than 6 years old(95％CI:3.647 to 70.268,95％CI:1.435 to 8.235,95％CI:1.061 to 6.164,re-spectively).With 1.5％of the genetic distance set as the threshold,the molecular network was established,the network access rate was 49.07％,77.14％of the clusters had drug-resistant mutation sites,and the male population was at higher risk of network access than the female population.CONCLUSIONS The drug resistance rate is relatively high among the AIDS population with failed ART,and the drug-resistant strains appear in clusters in the molecular network.It is neces-sary to further strengthen the monitoring of drug resistance and improve the quality of the follow-up so as to reduce the occurrence of drug resistance and transmission of virulent strains.

Objective:To analyze the influencing factors of mood state of common rheumatic (rheumatoid arthritis; systemic lupus erythematosus; ankylosing spondylitis) patients and find out the common characteristics of patients with negative emotions, so as to identify and treat rheumatic patients with anxiety and depression in clinical practice.Methods:A total of 205 patients with rheumatism (83 with rheumatoid arthritis, 74 with systemic lupus erythematosus, 48 with ankylosing spondylitis) admitted to the Shandong Provincial Hospital Affiliated to Shandong University from April to May 2023 were included. The general condition and POMS of patients were collected. All patients were divided into 3 groups of low-TMD/ middle-TMD/ high-TMD(TMD≤90 scores; 90 scores105 scores). The χ2 test was used for categorical variables, and the continuous variables were tested for normal distribution. If they followed a normal distribution, the independent sample t test (for homogeneous variance) or the Welch′s t test (for unequal variance) was used for comparison between the two groups, and one-way analysis of variance was used for comparison between multiple groups; if they did not follow a normal distribution, the Kruskal-Wallis H test was used for comparison between groups. Patients with TMD>90 scores were defined as the negative emotion group. Gender, age, education level, economic income status, and TMD were included in the two-step cluster analysis (TCA) to obtain three cluster groups and analyze the differences between the groups. Logistic regression was used to analyze the risk factors. Results:The study found that patients with rheumatic diseases with low serum albumin levels ( F=6.26, P=0.003), low education level ( χ2=8.36, P=0.015), low economic level ( χ2=15.59, P<0.001), short disease course ( H=28.01, P<0.001), and high disease activity ( χ2=56.93, P<0.001) had higher TMD scores, which was not related to the type of disease ( χ2=4.81, P=0.090). The negative mood group had a higher proportion of females (57.6% vs. 73.4%, χ2=5.16, P=0.023), a shorter course of disease [24(12, 48) months vs. 48(24, 93) months, Z=13.58, P<0.001], and a lower serum albumin [(42.2±4.0) g/L vs. (44.0±3.4)g/L, t=-14.09, P=0.002], low level of education ( χ2=9.04, P=0.029), low level of income ( χ2=10.29, P=0.036), high disease activity ( χ2=61.91, P<0.001). The results of cluster analysis indicated that the above factors were significantly different among the three cluster groups except the course of disease. It is noteworthy that age ( F=19.25, P<0.001) and serum albumin ( F=5.64, P=0.004) had the lowest value and the highest TMD score ( F=5.64, P<0.001). Regression analysis showed that gender, disease course and disease activity were related factors to the occurrence of negative emotions, and high disease activity was a risk factor [ OR(95% CI) =26.58(4.53, 156.09), P<0.001]. Men [ OR(95% CI)=0.20 (0.08, 0.50), P=0.001) and the course of [ OR(95% CI)=0.99 (0.98, 1.00), P=0.007) as the protective factors. Conclusion:Male, serum albumin level, education level, income level, disease course and disease activity were the main factors affecting the mood state of patients with rheumatism, in which high disease activity was the risk factor, male and long disease course were the protective factors.

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.

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*