BACKGROUND:Duhuo Jisheng Decoction is a classic prescription for the treatment of rheumatoid arthritis,but its specific mechanism is not clear.Extracellular vesicles have the powerful function of inter-cell communication and signal transmission,and may be the signal carrier for the Decoction.OBJECTIVE:To explore the effects of serum extracellular vesicles treated with Duhuo Jisheng Decoction on the proliferation,migration,invasion,and apoptosis of rheumatoid arthritis fibroblast-like synovial cells.METHODS:The rheumatoid arthritis fibroblast-like synovial cell model was established by co-culturing with tumor necrosis factor-α in vitro.The experiment was divided into five groups:normal group,model group,serum treated with Duhuo Jisheng Decoction group,extracellular vesicles treated with Duhuo Jisheng Decoction group,and extracellular vesicles treated with normal saline group.The optimal concentration and time of drug-containing serum and extracellular vesicles were screened by CCK-8 assay.Expression of inflammatory cytokines in the supernatants of cells in each group was detected by ELISA.The migration ability of rheumatoid arthritis fibroblast-like synovial cells was detected by scratch assay.The invasive ability of cells was measured by Transwell Invasion assay.Hoechst staining was adoped to detect cell apoptosis.The expression levels of apoptosis-related genes and proteins were detected by qRT-PCR and western blot assay.RESULTS AND CONCLUSION:(1)The optimal volume fraction of serum treated with Duhuo Jisheng Decoction was 10%and optimal mass concentration of extracellular vesicles treated with Duhuo Jisheng Decoction was 10 ng/mL;the optimal time for the interaction between the two was 24 hours.(2)Compared with the model group,serum treated with Duhuo Jisheng Decoction,extracellular vesicles treated with Duhuo Jisheng Decoction,and extracellular vesicles treated with normal saline could suppress the expression of inflammatory factors of rheumatoid arthritis fibroblast-like synovial cells(P<0.05),scratch healing(P<0.05),migration and invasion(P<0.05).Moreover,the inhibition of extracellular vesicles treated with Duhuo Jisheng Decoction was more significant(P<0.05).(3)Drug-containing serum and extracellular vesicles treated with Duhuo Jisheng Decoction promoted the apoptosis of rheumatoid arthritis fibroblast-like synovial cells.(4)Compared with the model group,serum treated with Duhuo Jisheng Decoction,extracellular vesicles treated with Duhuo Jisheng Decoction,and extracellular vesicles treated with normal saline could increase the expression of proapoptotic factors Caspase-3,Caspase-9,and Bax(P<0.05)and decrease the expression of antiapoptotic factor Bcl-2(P<0.05).Moreover,extracellular vesicles treated with Duhuo Jisheng Decoction had a more significant regulatory effect on apoptosis-related factors.Above findings indicate that extracellular vesicles treated with Duhuo Jisheng Decoction can inhibit the excessive proliferation,migration,and invasion of rheumatoid arthritis fibroblast-like synovial cells and promote their apoptosis.

Atherosclerosis(AS)is a multifactorial disease,in which mitochondrial dysfunction of macrophages plays a key role.Mitochondrial dysfunction of macrophages affects polarization direction of macrophages and leads to severe inflammatory reac-tions,is a potential therapeutic target for AS.This article mainly reviews the latest research progress on role of macrophage mitochon-drial dysfunction in occurrence and development of AS,as well as treatment methods for improving macrophage mitochondrial function.

Objective:To explore the association between the use of tetracyclines during pregnancy and congenital malformations, with the aim of providing evidence-based guidance for the rational use of antibiotics during pregnancy.Methods:Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database from January 2015 to September 2024 were collected. Five methods including Tree-based scan statistic (TreeScan), proportional reporting ratio (PRR), reporting odds ratio (ROR), the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard, and the Bayesian confidence propagation neural network (BCPNN) were used to detect signals of risk for congenital malformations in offspring following maternal use of tetracyclines during pregnancy. A signal that met the threshold criteria of all above 5 methods was considered as a risk signal. Based on population-based cohort of the drug exposures and adverse pregnancy outcomes (DEEP) data from January 2013 to December 2021 in Xiamen City, propensity score matching (PSM)-based Poisson regression was applied to evaluate the association between the first-trimester tetracyclines exposure and congenital malformations in offspring. Adjusted relative risk (a RR) and its 95% confidence interval ( CI) were calculated. Sensitivity analysis was conducted to validate the reliability of the results. Results:A total of 304 098 reports of adverse events during pregnancy were obtained from the FAERS and CVAR databases. Among them, 5 028 reports were related to tetracyclines, including 1 026 reports of congenital malformations in offspring, involving congenital malformations of musculoskeletal system, other digestive system, and other congenital malformations. Signal detection results suggested that tetracyclines may be a risk signal for above congenital malformations in offspring. The DEEP data included 411 936 pregnant women. After PSM, 240 pregnant women exposed to tetracyclines were included. The results showed no significant association between the first-trimester tetracyclines exposure and congenital malformations in offspring (a RR=0.75, 95% CI: 0.26-2.17), sensitivity analysis also showed no correlation. Conclusions:Data mining from the FAERS and CVAR databases suggests a potential association between tetracyclines use during pregnancy and congenital malformations in offspring. However, the DEEP data study shows no significant correlation.

Atherosclerosis(AS)is a multifactorial disease,in which mitochondrial dysfunction of macrophages plays a key role.Mitochondrial dysfunction of macrophages affects polarization direction of macrophages and leads to severe inflammatory reac-tions,is a potential therapeutic target for AS.This article mainly reviews the latest research progress on role of macrophage mitochon-drial dysfunction in occurrence and development of AS,as well as treatment methods for improving macrophage mitochondrial function.

BACKGROUND:Duhuo Jisheng Decoction is a classic prescription for the treatment of rheumatoid arthritis,but its specific mechanism is not clear.Extracellular vesicles have the powerful function of inter-cell communication and signal transmission,and may be the signal carrier for the Decoction.OBJECTIVE:To explore the effects of serum extracellular vesicles treated with Duhuo Jisheng Decoction on the proliferation,migration,invasion,and apoptosis of rheumatoid arthritis fibroblast-like synovial cells.METHODS:The rheumatoid arthritis fibroblast-like synovial cell model was established by co-culturing with tumor necrosis factor-α in vitro.The experiment was divided into five groups:normal group,model group,serum treated with Duhuo Jisheng Decoction group,extracellular vesicles treated with Duhuo Jisheng Decoction group,and extracellular vesicles treated with normal saline group.The optimal concentration and time of drug-containing serum and extracellular vesicles were screened by CCK-8 assay.Expression of inflammatory cytokines in the supernatants of cells in each group was detected by ELISA.The migration ability of rheumatoid arthritis fibroblast-like synovial cells was detected by scratch assay.The invasive ability of cells was measured by Transwell Invasion assay.Hoechst staining was adoped to detect cell apoptosis.The expression levels of apoptosis-related genes and proteins were detected by qRT-PCR and western blot assay.RESULTS AND CONCLUSION:(1)The optimal volume fraction of serum treated with Duhuo Jisheng Decoction was 10%and optimal mass concentration of extracellular vesicles treated with Duhuo Jisheng Decoction was 10 ng/mL;the optimal time for the interaction between the two was 24 hours.(2)Compared with the model group,serum treated with Duhuo Jisheng Decoction,extracellular vesicles treated with Duhuo Jisheng Decoction,and extracellular vesicles treated with normal saline could suppress the expression of inflammatory factors of rheumatoid arthritis fibroblast-like synovial cells(P<0.05),scratch healing(P<0.05),migration and invasion(P<0.05).Moreover,the inhibition of extracellular vesicles treated with Duhuo Jisheng Decoction was more significant(P<0.05).(3)Drug-containing serum and extracellular vesicles treated with Duhuo Jisheng Decoction promoted the apoptosis of rheumatoid arthritis fibroblast-like synovial cells.(4)Compared with the model group,serum treated with Duhuo Jisheng Decoction,extracellular vesicles treated with Duhuo Jisheng Decoction,and extracellular vesicles treated with normal saline could increase the expression of proapoptotic factors Caspase-3,Caspase-9,and Bax(P<0.05)and decrease the expression of antiapoptotic factor Bcl-2(P<0.05).Moreover,extracellular vesicles treated with Duhuo Jisheng Decoction had a more significant regulatory effect on apoptosis-related factors.Above findings indicate that extracellular vesicles treated with Duhuo Jisheng Decoction can inhibit the excessive proliferation,migration,and invasion of rheumatoid arthritis fibroblast-like synovial cells and promote their apoptosis.

Objective:To explore the association between the use of tetracyclines during pregnancy and congenital malformations, with the aim of providing evidence-based guidance for the rational use of antibiotics during pregnancy.Methods:Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database from January 2015 to September 2024 were collected. Five methods including Tree-based scan statistic (TreeScan), proportional reporting ratio (PRR), reporting odds ratio (ROR), the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard, and the Bayesian confidence propagation neural network (BCPNN) were used to detect signals of risk for congenital malformations in offspring following maternal use of tetracyclines during pregnancy. A signal that met the threshold criteria of all above 5 methods was considered as a risk signal. Based on population-based cohort of the drug exposures and adverse pregnancy outcomes (DEEP) data from January 2013 to December 2021 in Xiamen City, propensity score matching (PSM)-based Poisson regression was applied to evaluate the association between the first-trimester tetracyclines exposure and congenital malformations in offspring. Adjusted relative risk (a RR) and its 95% confidence interval ( CI) were calculated. Sensitivity analysis was conducted to validate the reliability of the results. Results:A total of 304 098 reports of adverse events during pregnancy were obtained from the FAERS and CVAR databases. Among them, 5 028 reports were related to tetracyclines, including 1 026 reports of congenital malformations in offspring, involving congenital malformations of musculoskeletal system, other digestive system, and other congenital malformations. Signal detection results suggested that tetracyclines may be a risk signal for above congenital malformations in offspring. The DEEP data included 411 936 pregnant women. After PSM, 240 pregnant women exposed to tetracyclines were included. The results showed no significant association between the first-trimester tetracyclines exposure and congenital malformations in offspring (a RR=0.75, 95% CI: 0.26-2.17), sensitivity analysis also showed no correlation. Conclusions:Data mining from the FAERS and CVAR databases suggests a potential association between tetracyclines use during pregnancy and congenital malformations in offspring. However, the DEEP data study shows no significant correlation.

Vitiligo is an immune memory skin disease. T-cell factor 1 (TCF1) is essential for maintaining the memory T-cell pool. There is an urgent need to investigate the characteristics of peripheral memory T-cell profile and TCF1⁺ T-cell frequencies in patients with vitiligo. In this study, 31 patients with active vitiligo (AV), 22 with stable vitiligo (SV), and 30 healthy controls (HCs) were included. We measured circulating memory and TCF1⁺ T-cell frequencies using flow cytometry. The Spearman's rank test was used to evaluate the correlation between cell frequencies and disease characteristics. Receiver operating characteristic curves (ROC) were constructed to investigate the discriminative power of the cell subpopulations. Circulating CD4⁺ and CD8⁺ terminally differentiated effector memory T-cell (T_EMRA) frequencies were significantly higher in the AV group than in HCs (P < 0.05). TCF1⁺ T-cell subpopulations were widespread increased in patients with vitiligo (P < 0.05). After adjusting for potential confounders, CD8⁺ and CD4⁺ central memory (T_CM) cells, and CD8⁺ T_EMRA were correlated with disease activity (P < 0.05). The combined diagnostic value of the four (naïve, effector memory, T_CM, and T_EMRA) CD8⁺TCF1⁺ T-cell subsets was relatively high (area under the ROC curve (AUC) = 0.804, sensitivity = 71.70%, specificity = 83.34%), and the CD8⁺ T-cell subsets combination performed well in discriminating disease activity (AUC = 0.849, sensitivity = 70.97%, specificity = 90.91%). We demonstrated an altered circulating memory T-cell profile and increased TCF1⁺ T-cell percentage in patients with vitiligo. T-cell subpopulations had a strong value for vitiligo diagnosis and activity evaluation. This evidence presents a potential new pharmacological target for inhibiting autoimmunity that leads to vitiligo.

Objective:To summarize the clinical features of 8 cases with intramycardial hematoma(IMH) following congenital cardiac surgery in children.Methods:We retrospectly searched 8 patients with intramycardial hematoma after congenital cardiac surgery in Guangzhou Women and Children’s Medical Center from 2008 to 2024.Results:Mean age and mean weight at surgery were(13±15) months and(7.8±3.5)kg respectively. 6 of 8 cases were interventricular septal hematoma. In the other 2 patients, intramycardial hematoma was located in left ventrical free wall. All IMH were postoperatively detected by transthoracic echocardiaography. Two patients were managed with ECMO intraoperatively. Finally, all patients were discharged successfully with good clinical results. Mean time to IMH resolution in six patients was(33.5±4.6) days and mean left ventricular ejection fraction(LVEF) was 0.60±0.09. Another patient was followed up for 3 months and the IMH was not absorbed. One patient was lost to follow-up.Conclusion:IMH is a rare complication after congenital heart disease. The absorption of hematoma is a dynamic process and mean time to IMH resolution is about 1month. In IMH patients with hemodynamic instability, ECMO can be a good treatment to create opportunities for hematoma absorbtion.

Objective To investigate the predictive value of serum 25-hydroxyvitamin D[25(OH)D]level in early renal transplantation for acute rejection(AR).Methods A total of 324 renal transplant recipients from January 2019 to August 2022 in the Second People's Hospital of Shanxi Province were selected.The clinical data of the recipients were collected.The levels of serum 25(OH)D,parathyroid hormone(PTH),and calcium,phosphorus in early(within 1 month)transplantation were detected by chemiluminescence immunoassay and colorimetry,respectively.The detection season was recorded,and the occurrence of AR within 1 year after renal transplantation was observed.The 25(OH)D level ≥ 20ng/ml was defined as normal,≥ 12 ng/ml～＜20 ng/ml as insufficient and＜12ng/ml as deficient,they were divided into of 25(OH)D normal group(n=106),insufficient group(n=112)and deficient group(n=106).According to the occurrence of AR,they were divided into AR group(n=51)and non-AR group(n=273).The basic situation of serum 25(OH)D level was analyzed.The differences in serum PTH,calcium,phosphorus levels and seasons as well as AR incidence among the three groups of 25(OH)D were compared.Multivariate logistic regression was used to analyze the influencing factors of AR,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum 25(OH)D level for AR.Results The incidence of serum 25(OH)D deficiency or insufficiency was 67.28％(218/324).In the 25(OH)D normal group,insufficient group and deficiency group,the serum PTH levels were 75.44(46.42,113.23)pg/ml,78.29(58.27,152.10)pg/ml and 86.84(54.64,127.3)pg/ml,and the incidences of AR were 2.47％(8/324),6.17％(20/324)and 7.10％(23/324),respectively.All of them were the highest in the deficiency group and the lowest in the normal group,and the differences were significant(H=6.784,x2=8.580,all P＜0.05).Additionally,25(OH)D deficiency(OR=3.340,95％CI:1.409～7.916),25(OH)D insufficiency(OR=2.442,95％CI:1.006～5.925)and human leucocyte antigen(HLA)mismatch(4～6)(OR=2.117,95％CI:1.027～4.363)were independent risk factors for AR(all P＜0.05).The area under the curve(AUC)of serum 25(OH)D level in predicting AR was 0.702(95％CI:0.625～0.779),the optimal cut-off value was 13.59 ng/ml,the specificity and the sensitivity were 66.7％and 65.6％,respectively.Conclusion In this study,25(OH)D deficiency(＜12ng/ml)or insufficiency(≥ 12～＜20ng/ml)was an independent risk factor for AR,and serum 25(OH)D level may have a certain predictive value for AR.

Vitiligo is an immune memory skin disease.T-cell factor 1(TCF1)is essential for maintaining the memory T-cell pool.There is an urgent need to investigate the characteristics of peripheral memory T-cell profile and TCF1+T-cell frequencies in patients with vitiligo.In this study,31 patients with active vitiligo(AV),22 with stable vitiligo(SV),and 30 healthy controls(HCs)were included.We measured circulating memory and TCF1+T-cell frequencies using flow cytometry.The Spearman's rank test was used to evaluate the correlation between cell frequencies and disease characteristics.Receiver operating characteristic curves(ROC)were constructed to investigate the discriminative power of the cell subpopulations.Circulating CD4+and CD8+terminally differentiated effector memory T-cell(TEMRA)frequencies were significantly higher in the AV group than in HCs(P＜0.05).TCF1+T-cell subpopulations were widespread increased in patients with vitiligo(P＜0.05).After adjusting for potential confounders,CD8+and CD4+central memory(TcM)cells,and CD8+TEMRA were correlated with disease activity(P＜0.05).The combined diagnostic value of the four(naive,effector memory,TcM,and TEMRA)CD8+TCF1+T-cell subsets was relatively high(area under the ROC curve(AUC)=0.804,sensitivity=71.70％,specificity=8334％),and the CD8+T-cell subsets combination per-formed well in discriminating disease activity(AUC=0.849,sensitivity=70.97％,specificity=90.91％).We demonstrated an altered circulating memory T-cell profile and increased TCF1+T-cell percentage in patients with vitiligo.T-cell subpopulations had a strong value for vitiligo diagnosis and activity evaluation.This evidence presents a potential new pharmacological target for inhibiting autoimmunity that leads to vitiligo.