Objective: To investigate the effects of fine particulate matter (PM2.5) exposure on acute myocardial infarction (AMI) mortality and years of life lost (YLL). Methods: Mortality data in Haizhu District, Guangzhou City from 2020 to 2024 were collected by the China Population Death Information Registration Management System and Guangdong Death Certificate Management System. Air pollution and meteorological data of the same period were obtained from the national environmental monitoring sites on the National Real-time Air Quality Release Platform and the Guangzhou Observatory, respectively. The single-pollutant model and multi-pollutant model were established by distributed lag non-linear model to analyze the effects of PM2.5 on AMI mortality and YLL. Results: From 2020 to 2024, there were 2 466 AMI death cases in Haizhu District, including 949 males and 1 517 females. Among them, 530 cases were aged <65 years, 494 cases were aged 65-74 years, and 1 442 cases were aged >74 years. The median daily average number of deaths was 1.3 (interquartile range, 2.0) cases, and the median daily average YLL was 16.4 (interquartile range, 24.8) person years. The median daily average mass concentration of PM2.5 was 24.3 (interquartile range, 18.0) μg/m3. In single-pollutant models, the maximum effects of PM2.5 on AMI mortality and YLL were observed at a cumulative lag of 7 days. For per 10 μg/m3 increment in the daily average concentration of PM2.5, the excess risk of AMI mortality increased by 8.793% (95%CI: 4.201% to 13.588%), and YLL increased by 2.059 (95%CI: 1.081 to 3.037) person-years. Gender-stratified analyses showed that PM2.5 significantly affected AMI mortality in males and YLL in males and females (all P<0.05). Age-stratified analyses revealed that PM2.5 significantly affected AMI mortality and YLL among residents aged <65 years and 65-74 years (all P<0.05). However, the difference between genders or the two age groups was not statistically significant (both P>0.05). In multi-pollutant models, when NO2, SO2, or O3 were introduced respectively at a cumulative lag of 7 days, the effects of PM2.5 on AMI mortality and YLL were enhanced compared to the single-pollutant model (all P<0.05). When PM10 was introduced alone or in combination with PM10, SO2, NO2, and O3, the effects of PM2.5 on AMI mortality and YLL were not statistically significant (all P>0.05). Conclusion Exposure to PM2.5 may increase the risk of AMI mortality and YLL, with varying effects across populations of different genders and ages.

Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Objective:To explore the genotype-phenotype relationship in a child with Opitz G/BBB syndrome (OS) with mild clinical phenotype.Methods:A child with motor developmental delay as the initial symptom admitted to Xi ′an Children′s Hospital on June 10, 2021 was selected for this study. Clinical data were collected, and peripheral blood samples were obtained from the child and his mother. Whole exome sequencing (WES) was performed to identify genetic variant in the child. Candidate variant were verified by Sanger sequencing to assess inheritance patterns and pathogenicity. Real-time fluorescence quantitative PCR (RT-qPCR) and Western blot (WB) analyses were conducted to evaluate the effects of the variant on mRNA and protein expression, respectively, using recombinant expression plasmids generated in vitro. This study was approved by the Medical Ethics Committee of Xi′an Children′s Hospital (Ethics No. 20240045).Results:① The child, a 9-month-and-7-day-old boy, presented with a low nasal bridge, hypertelorism, and difficulty sitting independently. Echocardiography revealed an atrial septal defect. ② WES identified a homozygous variant in the MIDI gene, c. 1483C>T (p.R495X), which was confirmed by Sanger sequencing and found to be inherited from the mother.③ Recombinant expression plasmids were successfully constructed. RT-qPCR analysis showed that the variant significantly reduced MIDI gene mRNA expression, while WB results indicated that the variant led to the production of a truncated protein. Conclusion:The mild clinical phenotype of OS in this child may be attributed to the mRNA degradation escape mechanism induced by the nonsense variant c. 1483C>T(p.R495X) in the MIDI gene. These findings provide valuable diagnostic insights for this pedigree and contribute to the understanding of the genotype-phenotype correlation in OS.

OBJECTIVE: To investigate the effectiveness of Youngswick-Akin osteotomy in the treatment of moderate hallux valgus combined with mild to moderate hallux rigidus. METHODS: The clinical data of 43 patients with moderate hallux valgus combined with mild to moderate hallux rigidus who were admitted between August 2019 and August 2022 and met the selection criteria were retrospectively analyzed. There were 8 males and 35 females. The age ranged from 28 to 77 years, with an average age of 59.0 years. The disease duration ranged from 10 to 35 months, with an average of 20 months. The degree of hallux rigidus included 2 cases of CoughlinⅠ degree, 29 cases of Ⅱ degree, 12 cases of Ⅲ degree. The preoperative hallux valgus angle ranged from 25° to 40°, with an average of 32°. All patients were treated with Youngswick-Akin osteotomy. The first metatarsophalangeal joint space was compared before operation and at 6 months after operation. The American Orthopaedic Foot and Ankle Society (AOFAS) score and visual analogue scale (VAS) score were used to evaluate the functional recovery and pain relief of the patients before operation and at 6 and 24 months after operation. According to the severity of hallux rigidus, the patients were divided into mild group (Ⅰ, Ⅱ degree) and moderate group (Ⅲ degree) to compare the prognosis, including the changes of AOFAS score, VAS score, and the first metatarsophalangeal joint space. RESULTS: The operation time was 60-75 minutes (mean, 65 minutes). The intraoperative blood loss was 10-30 mL (mean, 20 mL). Two cases had superficial infection of the incision margin after operation, and healed well after dressing change and antibiotic treatment. The incisions of the other patients healed by first intention, and no medial cutaneous nerve injury of the great toe occurred. All patients were followed up 24-31 months, with an average of 25.8 months. The patient's hallux valgus deformity was corrected without recurrence; no complication such as osteomyelitis and hallux varus occurred. The AOFAS score, VAS score, and the first metatarsophalangeal joint space after operation significantly improved when compared with those before operation, the AOFAS score and VAS score at 24 months after operation further improved when compared with those at 6 months after operation, and the differences were significant ( P<0.05). The change of VAS score in mild group was significantly better than that in moderate group ( P<0.05); but there was no significant difference in the changes of AOFAS score and the first metatarsophalangeal joint space between the two groups ( P>0.05). CONCLUSION Youngswick-Akin osteotomy for moderate valgus deformity with mild to moderate hallux rigidus can achieve good functional recovery, pain relief, and joint space improvement.
Humans ; Osteotomy/methods* ; Hallux Valgus/diagnostic imaging* ; Male ; Female ; Middle Aged ; Hallux Rigidus/diagnostic imaging* ; Retrospective Studies ; Adult ; Aged ; Treatment Outcome ; Metatarsophalangeal Joint/surgery*

Objective To investigate the mechanisms through which Qinggan Yipi formula(QgYp)may alleviate liver fibrosis by integrating network pharmacology with experiments.Methods The active ingredients and gene targets of QgYp,associated with liver fibrosis,were sourced from several databases,including the Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),various professional chemical databases,the HERB database,the GeneCards database,and the Online Mendelian Inheritance in Man(OMIM)database.Protein-protein interaction(PPI)networks were developed using the STRING database and visualized through Cytoscape software.Furthermore,GO enrichment analysis and KEGG pathway analysis were conducted with the Metascape database,alongside molecular docking studies using the CB-DOCK 2 platform.HSC-T6 cells were used as the research model,and the MTT assay along with Western blotting were applied to evaluate cell proliferation and protein expression levels,and the expression of related proteins was also detected in the animal experiment.Results A total of 22 bioactive components and 124 gene targets were identified within the formula.Enrichment analyses revealed 896 GO entries and 123 signaling pathways,notably including the IL-7,TNF,Toll-like receptor,and NF-kappa B pathways.Molecular docking indicated that the key components of the formula exhibited a strong binding affinity with proteins involved in the TLR4/NF-κB signaling pathway.Additionally,experiments confirmed that QgYp effectively inhibited the proliferation of HSC-T6 cells induced by LPS,and the expression of α-SMA,COL-1,TLR4,IκB-α,and NF-κB p65 proteins in both HSC-T6 cells and rats with liver fibrosis decreased.Conclusion QgYp can effectively inhibit the TLR4/NF-κB signaling pathway and has a suppressive effect on the fibrosis process in hepatic stellate cells,offering a theoretical basis for its clinical application in treating liver fibrosis.

Aim Systematic evolution of ligands by exponential enrichment(SELEX)techniquewas employed to screen and identify nucleic acid aptamers that specifically bind to mouse atherosclerotic pathological tissues,aiming to pro-vide a research foundation for the development of molecular targets and diagnostic reagents for early atherosclerosis.Methods A single-stranded DNA(ssDNA)library with a capacity of 1015～1016 was constructed,which was then subjec-ted to binding-elution(negative selection)with normal mouse vascular tissue slices.The eluted library was subsequently bound to atherosclerotic tissue slices for binding-elution(positive selection).PCR was used to amplify the positive and negative screening products,and agarose gel electrophoresis was used to verify the amplified products.The ssDNA library after multiple rounds of selection was sequenced using T-A cloning and sequencing to obtain the primary structure of the nu-cleic acid aptamers,and the secondary structure was predicted using the Mfold online software.The selected nucleic acid aptamers were labeled with a FAM fluorescent group at the 5'-end and were bound to both positive and negative selection tissue slices,with fluorescence intensity observed under a fluorescence microscope.Image Pro Plus 6.0 was used to cal-culate the relative average fluorescence intensity to evaluate the binding specificity of nucleic acid aptamers.Results After 8 rounds of selection,agarose gel electrophoresis imaging showed PCR amplification products in the positive selection lanes,while no PCR amplification products were observed in the negative selection lanes,indicating the successful acquisi-tion of a nucleic acid aptamer library that specifically binds to atherosclerotic tissues.Five nucleic acid aptamers were i-dentified by T-A cloning and sequencing,and their predicted secondary structures all had stem-loop structures.Immuno-fluorescence staining verified that five nucleic acid aptamers had different degrees of binding with As blood vessels,and the quantitative results of the relative average fluorescence intensity showed that nucleic acid aptamer No.11 had the highest relative average fluorescence intensity value,which can be used as a candidate nucleic acid aptamer for subsequent re-search.Conclusion Specific nucleic acid aptamers that bind to atherosclerotic vesselswere successfully obtained,providing a research foundation for further screening of early molecular targets of Asand developing in vivo early diagnostic reagents.

Background and purpose:Breast cancer stem cells play an important role in the occurrence and development of cancer.The high mortality of breast cancer patients is closely related to the recurrence and metastasis of cancer.However,the self-renewal and differentiation ability of breast cancer stem cells can lead to chemotherapy resistance,thus affecting the recurrence and metastasis of cancer.This study aimed to explore the impact of miR-193a-3p on the migration and invasion of breast cancer stem cells by targeting the tripartite motif-containing protein 14(TRIM14).Methods:Human breast cancer cell T47D was randomly assigned into control group,NC mimics group(transfected with NC mimics),miR-193a-3p mimics group(transfected with miR-193a-3p mimics),miR-193a-3p mimics+pcDNA-NC group(transfected with miR-193a-3p mimics+pcDNA-NC)and miR-193a-3p mimics+pcDNA-TRIM14 group(transfected with miR-193a-3p mimics+pcDNA-TRIM14).Separation of stem cells using flow cytometry and detection of cell spheroidization ability were carried out.Cell counting kit-8(CCK-8)experiment was used to detect cell proliferation.Transwell experiment was used to measure cell migration and invasion.Flow cytometry was used to detect cell apoptotic rate.Western blot was used to detect the expressions of cyclin D1,matrix metalloproteinase-2(MMP-2),Bcl-2-associated X protein(Bax),and TRIM14 protein in cells.Dual luciferase assay was used to detect the interaction between miR-193a-3p and TRIM14.Results:T47D stem cells had the ability to form spheroids,and with increasing time,the spheroid volume of T47D stem cells gradually increased.Compared with the Control group and NC mimics group,the miR-193a-3p mimics group showed increased miR-193a-3p expression,apoptotic rate,and Bax protein expression(P＜0.05),and decreased TRIM14 mRNA and protein expression,survival rate,clone number,migration number,invasion number,cyclin D1 and MMP-2(P＜0.05).Compared with the miR-193a-3p mimics group and the miR-193a-3p mimics+pcDNA NC group,the miR-193a-3p mimics+pcDNA-TRIM14 group showed decreased cell apoptosis rate and Bax protein(P＜0.05),and increased TRIM14 mRNA and protein expression,survival rate,clone number,migration number,invasion number,cyclin D1 and MMP-2(P＜0.05).There were multiple binding sites between miR-193a-3p and TRIM14.Compared with the miR-NC+TRIM14-WT group,the miR-193a-3p mimics+TRIM14-WT group showed a prominent decrease in dual luciferase activity(P＜0.05).Conclusion:MiR-193a-3p may inhibit the migration and invasion of breast cancer stem cells through inhibiting TRIM14.

Objective To investigate the effects of transcutaneous electrical nerve stimulation(TENS)combined with mobilization with movement(MWM)on clinical efficacy,musculoskeletal ultrasound findings and bone metabolism indicators in patients with knee osteoarthritis(KOA).Methods Ninety KOA patients were collected and randomly divided into the control group(conventional rehabilitation+TENS,n=45)and the observation group(conventional rehabilitation+TENS+MWM,n=45)using a random number table.Clinical efficacy,knee joint function,musculoskeletal ultrasound indices and bone metabolism indices were compared between the two groups.Results The clinical efficacy of the observation group was superior to that of the control group(P＜0.05).At 2 and 6 months post-treatment,Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)were significantly lower in the observation group than those of the control group,and Lysholm Knee Scoring Scale scores were higher in the observation group than those of the control group(P＜0.05).Additionally,articular cartilage thickness,bone gla protein(BGP)and bone-specific alkaline phosphatase(BALP)were higher in the observation group than those of the control group,and synovial thickness,suprapatellar effusion and tartrate-resistant acid phosphatase 5b(TRACP-5b)were lower in the observation group than those of the control group(P＜0.05).Conclusion TENS combined with MWM in the treatment of KOA patients can not only improve knee joint function but also optimize musculoskeletal ultrasound indices and regulate bone metabolism indices.

Objective Investigating the correlation between fluctuations in proliferation-inducing ligand(APRIL),M-type phospholipase A2 receptor antibody(PLA2R Ab),and 25-hydroxyvitamin D3[25-(OH)D3]levels and their impact on the severity and prognosis of primary membranous nephropathy(PMN).Methods A prospective study design was employed,wherein 100 confirmed PMN patients from Xingtai People's Hospital were recruited as the PMN group,and 100 healthy volunteers served as the control group.The levels of APRIL,PLA2R Ab,and 25-(OH)D3 were compared between the two groups of participants,stratified by PMN disease stage and treatment outcomes.A simple linear correlation analysis was conducted to evaluate the correlation between APRIL,PLA2R Ab,and 25-(OH)D3 with renal function indicators.Additionally,a multiple regression model was utilized to analyze the associations between these indicators and patient treatment outcomes as well as prognosis.Results The levels of APRIL and PLA2R Ab in the MN group were significantly higher than those in the control group,whereas the levels of 25-(OH)D3 were significantly lower than those in the control group(P<0.05).Among 100 patients with PMN,there were 20 in stage I,42 in stage Ⅱ,34 in stage Ⅲ,and 4 in stage Ⅳ.The levels of APRIL and PLA2R Ab in stage Ⅲ+Ⅳ patients were significantly higher than those in stage Ⅰ+Ⅱ patients,while the level of 25-(OH)D3 was significantly lower in stage Ⅲ+Ⅳ patients compared to stage Ⅰ+Ⅱ patients(P<0.05).In PMN patients,serum APRIL and PLA2R-Ab levels were negatively correlated with urea nitrogen(BUN),creatinine(Scr),and 24-h urinary protein(P<0.05).Additionally,APRIL and PLA2R-Ab levels were positively correlated with total protein(TP)and albumin(ALB)(P<0.05),while serum 25-(OH)D3 levels were negatively correlated with BUN,Scr,and 24-h urinary protein(P<0.05).After treatment,42 patients achieved complete remission,while 58 patients did not meet the remission criteria.Serum APRIL and PLA2R-Ab levels in the remis-sion group were significantly lower than those in the non-remission group both before treatment and after 12 months of treatment.Furthermore,serum 25-(OH)D3 levels in the remission group were significantly higher than those in the non-remission group both before treatment and after 12 months of treatment(P<0.05).Conclusions Elevated levels of serum APRIL and PLA2R antibodies,which contribute to immune dysfunction,are closely asso-ciated with the onset and severity of PMN.Renal impairment leads to a substantial reduction in serum 25-(OH)D3 levels.Collectively,these three indicators serve as critical markers for the occurrence,progression,and prognosis of PMN.

Objective To investigate the changes in expression levels of Parkinson's disease protein 7(Park7)and P2X7R purinergic receptor(P2X7R)in the serum of patients with acute myocardial infarction(AMI)and their clinical significance.Methods A total of 145 AMI patients admitted to Chengde Veterans Hospital between February 2021 and May 2023 were recruited as the AMI group.According to the Gensini score for assessing the severity of coronary lesions,they were subdivided into a mild group(≤30 points,n=68),a moderate group(30-59 points,n=42),and a severe group(≥60 points,n=35).Additionally,120 healthy volunteers undergoing physical examinations at the same hospital were recruited as the control group.ELISA method was used to measure serum levels of Park7 and P2X7R.Correlation between serum Park7 and P2X7R levels and Gensini score in AMI patients was analysed by Spearman's method.ROC curves were used to evaluate the predictive value of serum Park7 and P2X7R for the occurrence of MACE.Plot Kaplan-Meier curves were plotted to analyze the cumulative MACE incidence rates in patients with different Park7 and P2X7R expression levels.Cox regression analysis was used to identify risk factors for MACE occurrence in AMI patients.Results Compared with the control group,the AMI group showed significantly increased levels of TC,TG,LDL-C,IL-6,CTnI,CK-MB,BNP,and serum P2X7R(P<0.05),and significantly decreased levels of serum HDL-C and Park7(P<0.05).Furthermore,statistically significant differences were observed in serum P2X7R and Park7 levels among patients with different severity levels(P<0.05).There was a negative correlation between serum Park7 and Gensini score in AMI patients(r=-0.497,P<0.05),while a positive correlation between P2X7R level and Gensini score(r=0.441,P<0.05).Serum Park7 level in the MACE group was significantly lower than that in the non MACE group(P<0.05),while the P2X7R level was significantly higher(P<0.05).The AUCs for serum Park7,P2X7R,and their combination in predicting MACE in AMI patients was 0.851,0.820,and 0.905,respectively,with the combined prediction demonstrating superior performance(Zcombination-Park7=2.324,Zcombination-P2X7R=2.538,P<0.05).The 6-month cumulative MACE incidence was lower in patients with low Park7 expression(51.22%)than in those with high Park7 expression(80.95%)(Log Rank χ2=12.178,P<0.001);conversely,the 6-month cumulative MACE incidence was higher in patients with low P2X7R expression(82.09%)than in those with high P2X7R expression(48.72%)(Log Rank χ2=20.233,P<0.001).CTnI,CK-MB,BNP,Park7,and P2X7R were identified as influencing factors for MACE in AMI patients(P<0.05).Conclusion Serum Park7 level is downregulated while P2X7Rlevel is upregulated in AMI patients,both closely related to the severity of the disease.The combination of the two has high predictive value for the occurrence of MACE in AMI patients.