OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVES: To summarize the clinical and genetic characteristics of epilepsy with intellectual disability caused by SETD1B gene variants in children. METHODS: A retrospective analysis was conducted on the clinical data of three children with SETD1B gene variants diagnosed and treated at the Department of Pediatric Neurology of Xiangya Hospital of Central South University. Relevant literature was reviewed to summarize the clinical characteristics of this condition. RESULTS: All three children presented with symptoms during infancy or early childhood, including mild intellectual disability and myoclonic seizures, with two cases exhibiting eyelid myoclonia. After treatment with three or more antiepileptic drugs, two cases achieved seizure control or partial control, while one case remained refractory. Each of the three children was found to have a heterozygous variant in the SETD1B gene (one deletion, one frameshift, and one missense variant). To date, 54 cases with SETD1B gene variants have been reported, involving a total of 56 variants, predominantly missense variants (64%, 36/56). The main clinical manifestations included varying degrees of developmental delay (96%, 52/54) and seizures (81%, 44/54). Among the 44 patients with seizures, myoclonic (20%, 9/44) and absence seizures (34%, 15/44) were common, with eyelid myoclonia reported in six cases. Approximately one-fifth of these patients had poorly controlled seizures. CONCLUSIONS The primary phenotypes associated with SETD1B gene variants are intellectual disability and seizures, and seizures exhibit distinct characteristics. Eyelid myoclonia is not uncommon.
Humans ; Intellectual Disability/complications* ; Epilepsy/complications* ; Male ; Female ; Histone-Lysine N-Methyltransferase/genetics* ; Child, Preschool ; Child ; Retrospective Studies

Objective To explore the efficacy and safety of dapagliflozin in patients with paroxysmal atrial fibrillation (PAF) combined with heart failure with preserved ejection fraction (HFpEF). Methods A total of 120 patients with PAF combined with HFpEF treated at Jinshan Hospital of Fudan University from July 2022 to July 2023 were selected and randomly divided into the dapagliflozin group (n＝60, standard treatment combined with dapagliflozin) and the control group (n＝60, standard treatment combined with placebo). After 12 months of follow-up, the Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS), PAF duration, recurrence rate and frequency of PAF, left atrial diameter, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular ejection fraction, P-wave dispersion, blood pressure, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), and glycated hemoglobin A_1C (HbA_1C) were compared between the two groups. Cardiovascular outcomes and adverse events were observed. Results A total of 10 patients lost to follow-up, and 110 patients were included in the analysis (55 in each group). After 12 months of treatment, the KCCQ-TSS in the dapagliflozin group was significantly higher than that in the control group ([61.68±2.65] points vs [44.98±4.76] points, P＜0.001). The PAF duration in the dapagliflozin group was significantly shorter than that in the control group ([144±18] min vs [270±24] min, P＝0.045). After treatment, frequency of PAF, NT-proBNP levels, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left atrial diameter, P-wave dispersion, and HbA_1C levels showed statistical differences between the two groups (P＜0.05). The heart failure readmission rate and PAF recurrence rate in the dapagliflozin group were significantly lower than those in the control group (P＜0.05). There was no significant difference in the incidence of adverse events between the two groups during treatment. Conclusions Dapagliflozin improves patients’ quality of life, reduces PAF duration and recurrence rate, decreases heart failure readmission rate, lowers NT-proBNP levels, reverses cardiac remodeling, and demonstrates favorable safety in patients with PAF combined with HFpEF.

Objective:To investigate the independent clinical factors of live birth rate of the first frozen-thawed embryo transfer (FET) cycle after transcervical resection of adhesion (TCRA).Methods:A retrospective case-control study was conducted to analyze the clinical data of patients with intrauterine adhesion (IUA) who received FET in Reproductive Center of Reproductive and Genetic Hospital of CITIC-XIANGYA from January 2019 to June 2022 ( n=6 154). According to the severity of intrauterine adhesions in patients, they were classified into mild adhesions ( n=172), moderate adhesions ( n=5 723), and severe adhesions ( n=259). Based on the FET outcome, the patients were divided into live birth group and non-live birth group. The risk factors and protective factors of live birth were analyzed by multivariate logistic regression. Results:1) No independent factor of live birth was found in the mild IUA group. 2) In the moderate IUA group, the protective factors of live birth included secondary infertility ( OR=1.39, 95% CI: 1.07-1.80, P=0.015), hysteroscopic polypectomy ( OR=1.38, 95% CI: 1.05-1.83, P=0.023), No. of high-quality embryos transferred (one embryo: OR=1.58, 95% CI: 1.37-1.82, P<0.001; two embryos: OR=2.55, 95% CI: 1.80-3.64, P<0.001), two embryos transferred ( OR=1.77, 95% CI: 1.48-2.12, P<0.001), embryo stage (blastocyst transferred, OR=4.93, 95% CI: 3.68-6.63, P<0.001; blastocyst+cleavage transferred OR=1.90, 95% CI: 1.11-3.21, P=0.021), preimplantation genetic testing embryo ( OR=1.42, 95% CI: 1.19-1.69, P<0.001), endometrial thickness before transplantation ( OR=1.11, 95% CI: 1.07-1.15, P<0.001). Risk factors of live birth included female age ( OR=0.94, 95% CI: 0.92-0.96, P<0.001), infertility due to male factor ( OR=0.83, 95% CI: 0.71-0.96, P=0.011), combined repeated implantation failure ( OR=0.60, 95% CI: 0.42-0.87, P=0.007), combined unicornuate uterus/uterus didelphys ( OR=0.25, 95% CI: 0.06-0.79, P=0.033), American Fertility Society score ( OR=0.94, 95% CI: 0.89-0.98, P=0.010), No. of TCRA ( OR=0.83, 95% CI: 0.77-0.90, P<0.001), gonadotropin-releasing hormone agonists down-regulation combined with artificial cycle ( OR=0.56, 95% CI: 0.45-0.69, P<0.001), artificial cycle ( OR=0.62, 95% CI: 0.51-0.76, P<0.001). 3) In the severe IUA group, the risk factor of live birth was artificial cycle ( OR=0.25, 95% CI: 0.07-0.80, P=0.027). Conclusion:The clinical factors that affect the live birth outcome of the first FET cycle after TCRA have different results in patients with different degrees of adhesion. In patients with moderate adhesions, there are 17 clinical indicators that affect the live birth rate. In patients with severe adhesions, the artificial cycle is an independent factor affecting the live birth rate.

Objective To analyze the relationship between the expression of ferroptosis markers in the tumor microenvironment(TME)and the prognosis of transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC).Methods This prospective observational study included 100 HCC patients who received TACE treatment at Langfang Hospital of Traditional Chinese Medicine from March 2019 to June 2021 as the study subjects.The levels of 8-isoprostaglandin F2α(8-iso-PGF2α),4-hydroxy-2-nonenal(4-HNE),8-hydroxy-2'deoxyguanosine(8-OH-dG)and hepcidin in plasma were evaluated by ELISA kit at baseline(1 day before TACE),1 day after TACE and 4～8 weeks.The changes of ferroptosis related markers during TACE treatment were compared.The difference between the level of 8-iso-PGF2α,4-HNE and the baseline 1 day after TACE treatment was recorded as △8-iso-PGF2α,△4-HNE.Results Compared with the baseline,the levels of 8-iso-PGF2α and 4-HNE increased significantly and the level of hepcidin decreased significantly one day after TACE treatment,and the differences were statistically significant(t=8.03,16.29,2.92,all P<0.05).Compared with 1 day after treatment,the levels of 8-iso-PGF2α,4-HNE decreased and the level of 8-OH-dG increased at 4～8 weeks after TACE treatment,and the differences were statistically significant(t=9.12,17.17,2.63,all P<0.05).Multivariate COX analysis showed that △8-iso-PGF2α,△4-HNE and 8-iso-PGF2α 1 day after TACE treatment were independent factors affecting the overall survival after TACE(Wald χ2=5.205,13.801,6.054,all P<0.05).The survival time of patients with △4-HNE>2.01 μg/ml was significantly longer than that of patients with △4-HNE≤2.01 μg/ml(Log-rank=5.718,P=0.017),and that of patients with△8-iso-PGF2α>1.75ng/ml was sig-nificantly longer than that of patients with△8-iso-PGF2≤1.75ng/ml(Log-rank=4.163,P=0.041).Conclusion The prognosis of HCC patients who are in a state of high ferroptosis(4-HNE and 8-iso-PGF2 increased)at 1 day after TACE treatment is better,which indicate that ferroptosis mediated HCC death induced by TACE treatment.

Objective:To investigate the independent clinical factors of live birth rate of the first frozen-thawed embryo transfer (FET) cycle after transcervical resection of adhesion (TCRA).Methods:A retrospective case-control study was conducted to analyze the clinical data of patients with intrauterine adhesion (IUA) who received FET in Reproductive Center of Reproductive and Genetic Hospital of CITIC-XIANGYA from January 2019 to June 2022 ( n=6 154). According to the severity of intrauterine adhesions in patients, they were classified into mild adhesions ( n=172), moderate adhesions ( n=5 723), and severe adhesions ( n=259). Based on the FET outcome, the patients were divided into live birth group and non-live birth group. The risk factors and protective factors of live birth were analyzed by multivariate logistic regression. Results:1) No independent factor of live birth was found in the mild IUA group. 2) In the moderate IUA group, the protective factors of live birth included secondary infertility ( OR=1.39, 95% CI: 1.07-1.80, P=0.015), hysteroscopic polypectomy ( OR=1.38, 95% CI: 1.05-1.83, P=0.023), No. of high-quality embryos transferred (one embryo: OR=1.58, 95% CI: 1.37-1.82, P<0.001; two embryos: OR=2.55, 95% CI: 1.80-3.64, P<0.001), two embryos transferred ( OR=1.77, 95% CI: 1.48-2.12, P<0.001), embryo stage (blastocyst transferred, OR=4.93, 95% CI: 3.68-6.63, P<0.001; blastocyst+cleavage transferred OR=1.90, 95% CI: 1.11-3.21, P=0.021), preimplantation genetic testing embryo ( OR=1.42, 95% CI: 1.19-1.69, P<0.001), endometrial thickness before transplantation ( OR=1.11, 95% CI: 1.07-1.15, P<0.001). Risk factors of live birth included female age ( OR=0.94, 95% CI: 0.92-0.96, P<0.001), infertility due to male factor ( OR=0.83, 95% CI: 0.71-0.96, P=0.011), combined repeated implantation failure ( OR=0.60, 95% CI: 0.42-0.87, P=0.007), combined unicornuate uterus/uterus didelphys ( OR=0.25, 95% CI: 0.06-0.79, P=0.033), American Fertility Society score ( OR=0.94, 95% CI: 0.89-0.98, P=0.010), No. of TCRA ( OR=0.83, 95% CI: 0.77-0.90, P<0.001), gonadotropin-releasing hormone agonists down-regulation combined with artificial cycle ( OR=0.56, 95% CI: 0.45-0.69, P<0.001), artificial cycle ( OR=0.62, 95% CI: 0.51-0.76, P<0.001). 3) In the severe IUA group, the risk factor of live birth was artificial cycle ( OR=0.25, 95% CI: 0.07-0.80, P=0.027). Conclusion:The clinical factors that affect the live birth outcome of the first FET cycle after TCRA have different results in patients with different degrees of adhesion. In patients with moderate adhesions, there are 17 clinical indicators that affect the live birth rate. In patients with severe adhesions, the artificial cycle is an independent factor affecting the live birth rate.

Objective To analyze the relationship between the expression of ferroptosis markers in the tumor microenvironment(TME)and the prognosis of transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC).Methods This prospective observational study included 100 HCC patients who received TACE treatment at Langfang Hospital of Traditional Chinese Medicine from March 2019 to June 2021 as the study subjects.The levels of 8-isoprostaglandin F2α(8-iso-PGF2α),4-hydroxy-2-nonenal(4-HNE),8-hydroxy-2'deoxyguanosine(8-OH-dG)and hepcidin in plasma were evaluated by ELISA kit at baseline(1 day before TACE),1 day after TACE and 4～8 weeks.The changes of ferroptosis related markers during TACE treatment were compared.The difference between the level of 8-iso-PGF2α,4-HNE and the baseline 1 day after TACE treatment was recorded as △8-iso-PGF2α,△4-HNE.Results Compared with the baseline,the levels of 8-iso-PGF2α and 4-HNE increased significantly and the level of hepcidin decreased significantly one day after TACE treatment,and the differences were statistically significant(t=8.03,16.29,2.92,all P<0.05).Compared with 1 day after treatment,the levels of 8-iso-PGF2α,4-HNE decreased and the level of 8-OH-dG increased at 4～8 weeks after TACE treatment,and the differences were statistically significant(t=9.12,17.17,2.63,all P<0.05).Multivariate COX analysis showed that △8-iso-PGF2α,△4-HNE and 8-iso-PGF2α 1 day after TACE treatment were independent factors affecting the overall survival after TACE(Wald χ2=5.205,13.801,6.054,all P<0.05).The survival time of patients with △4-HNE>2.01 μg/ml was significantly longer than that of patients with △4-HNE≤2.01 μg/ml(Log-rank=5.718,P=0.017),and that of patients with△8-iso-PGF2α>1.75ng/ml was sig-nificantly longer than that of patients with△8-iso-PGF2≤1.75ng/ml(Log-rank=4.163,P=0.041).Conclusion The prognosis of HCC patients who are in a state of high ferroptosis(4-HNE and 8-iso-PGF2 increased)at 1 day after TACE treatment is better,which indicate that ferroptosis mediated HCC death induced by TACE treatment.

This study utilized a chiral liquid chromatography-mass spectrometry (LC-MS)-guided isolation strategy to accurately capture angular-type pyranocoumarins (APs) in Peucedani Radix (Chinese name: Qianhu). Sixteen APs were successfully purified from the ethyl acetate extract of Peucedani Radix through deploying various techniques such as silica gel, ODS, Sephadex LH-20, and achiral (chiral) semi-preparative liquid chromatography. After extensive structural measurements, such as ¹H and ¹³C NMR spectroscopy, their structures were identified as (3′S)-3′-(2-methyl-butyroyl)-4′-oxo-3′,4′-dihydroseselin (1A), (3′R)-3′-(2-methyl-butyroyl)-4′-oxo-3′,4′-dihydroseselin (1B), (3′S)-3′-isovaleryl-4′-oxo-lomatin (2A), (3′R)-3′-isovaleryl-4′-oxo-lomatin (2B), (3′S)-3′-angeloyloxy-4′-oxo-3′,4′-dihydroseselin (3A), (3′R)-3′-angeloyloxy-4′-oxo-3′,4′-dihydroseselin (3B), (3′S,4′S)-praeruptorin B (4A), (3′R,4′R)-praeruptorin B (4B), (3′S,4′S)-praeruptorin E (5A), (3′R,4′R)-praeruptorin E (5B), 3′-isovaleryl-4′-angeloyl-cis-khellactone (6), 3′-angeloyl-4′-(2-methyl-butyroyl)-cis-khellactone (7), (3′S,4′S)-praeruptorin A (8A), (3′R,4′R)-praeruptorin A (8B), (3′S,4′S)-khellactone (9A), and (3′R,4′R)-khellactone (9B), respectively. Thereof, compounds 1A and 1B were new compounds, while compound 2A represents a new configuration for a known planar structure. Compounds 2A and 2B were isolated for the first time from Peucedani Radix. Above all, chiral LC-MS-guided isolation strategy is advantageous at rapid capturing new compounds from herbal medicines, providing an effective means for the separation of novel structures, especially new enantiomers.

Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P＜0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P＜0.01);the proportion of CD3+T cells apparently increased(P＜0.05);the level of p16 protein signifi-cantly decreased(P＜0.05);the level of Bcl-2 pro-tein significantly increased(P＜0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P＜0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P＜0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.