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

Metabolic diseases have seen a steady increase in incidence in recent years, becoming one of the main causes of sub-health status globally. Neutrophil extracellular traps(NETs) are reticular complexes containing DNA, which trap foreign microorganisms or induce an immune response. Current research indicates that NETs are widely active in various metabolic diseases and can cause severe damage to the body through multiple mechanisms, including promoting blood glucose elevation, damaging vascular endothelial cells, forming vascular embolisms, triggering intense inflammation, and promoting lipid accumulation. Therefore, intervening in NETs is an important approach to treating metabolic diseases. Research has shown a close relationship between the theory of spleen heat-turbid toxin theory and metabolic diseases-NETs mechanism. The basic pathogenesis include the internal accumulation of phlegm-dampness, qi stagnation and blood stasis, internal accumulation of dampness-heat, phlegm and blood stasis, and flourishing toxic heat. Various Chinese herbal medicines with the functions of dispelling dampness, resolving phlegm, promoting blood circulation to remove blood stasis, and clearing heat and toxins, along with their extracts and compound prescriptions, can treat metabolic diseases by regulating NETs and delaying disease progression. This paper systematically outlined the formation mechanisms of NETs, their connection to metabolic diseases, the theoretical basis in TCM, their roles in numerous metabolic diseases, and the current research status of TCM in regulating NETs to prevent and control metabolic diseases, aiming to provide effective reference ideas for developing therapeutic strategies for metabolic diseases.
Humans ; Extracellular Traps/metabolism* ; Metabolic Diseases/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Neutrophils/metabolism* ; Medicine, Chinese Traditional

Objective:To explore the gene mutations of Langerhans cell histiocytosis in children,and to analyze the correlation of BRAF V600E mutation with clinical features and prognosis of LCH,so as to provide reference for clinical diagnosis and treatment. Methods:Fluorescence PCR was used to detect gene mutations in paraffin-embedded tissue samples from 78 children with LCH,and the correlation of BRAF V600E mutation with clinical characteristics and prognosis of LCH in children was analyzed. Results:Among the 78 children,41 cases (52.6％) had BRAF V600E mutation,8 cases (10.3％) had MAP2K1 mutation,1 case (1.3％) had BRAF Exon 12 mutation,1 case (1.3％) had ARAF mutation,and 1 case (1.3％) had PIK3CA mutation. BRAF V600E mutation was not significantly correlated with sex,age,multisystem involvement,risk-organ involvement,CNS-risk lesions,and early treatment response in children with LCH (P>0.05),and it was also not significantly correlated with the recurrence and event-free survival (EFS) of children with LCH (P>0.05). Conclusion:LCH is an inflammatory myeloid tumor. BRAF V600E mutation is not correlated with clinical features,early treatment response,recurrence and prognosis of LCH.

Objective To explore the effect of Shexiang Baoxin pill on cardiac tissue angiogenesis in spontaneously hypertensive rats(SHR).Method Twenty 12 week old male SHR were randomly divided into experimental group and model group,with 12 week old male SD rats as the normal control group.The experimental group rats were orally administered with Shexiang Baoxin pill(45 mg·kg-1)daily,and their blood pressure was monitored using a non-invasive tail artery blood pressure gauge every four weeks.Eight weeks later,cardiac tissue was taken for platelet endothelial cell adhesion molecule-1(PECAM-1/CD31)immunofluorescence staining to observe CD31 expression level.Use protein blotting to detect the expression levels of myocardial endothelial growth factor(VEGF),myocardial endothelial growth factor receptor 2(VEGF-R2),basic fibroblast growth factor(bFGF)and phosphorylated protein kinase B(p-Akt)/protein kinase B(Akt)proteins.Result There was significant increase in blood pressure between the experimental group,model group and normal group at the same time point(all P＜0.01),but there was no statistically significant difference in blood pressure changes between the experimental group and model group at the same time point(all P＞0.05).The CD31 expression rates of the normal group,model group and experimental group were(3.79±0.84)％,(2.54±0.42)％and(3.56±0.49)％;VEGF levels were 0.95±0.10,0.73±0.08 and 0.94±0.15;VEGF-R2 levels were 0.85±0.10,0.61±0.14 and 0.80±0.10;bFGF levels were 0.84±0.04,0.51±0.21 and 0.74±0.14;p-Akt/Akt levels were 0.85±0.15,0.57±0.13 and 0.80±0.20,respectively.The differences between the normal group and the model group,as well as the experimental group and the model group,were statistically significant(all P＜0.05).Conclusion Shexiang Baoxin pill can promote the neovascularization of microvessels in the heart tissue of spontaneously hypertensive rats,and its mechanism may be related to the activation of PI3K/Akt phosphorylation,upregulation of bFGF,VEGF and their receptor VEGF-R2 in myocardial tissue.

Objective To summarize and analyze the epidemiological and clinical characteristics of COVID-19 Omicron variant cases in makeshift hospital, and the influence of age, sex and vaccination status on the disease duration, so as to provide reference for the prevention and control of the COVID-19 epidemic. Methods The epidemiological and clinical characteristics of COVID-19 cases admitted to makeshift hospital of National Convention and Exhibition Center (Shanghai) from April 9 to May 31, 2022 were retrospectively described and analyzed, and further cohort analysis was conducted to determine the influence of age, sex and vaccination status on the disease duration of COVID-19 cases in the author's branch hospital. Results Among the 174 466 COVID-19 cases in makeshift hospital, most of them were male, accounting for 59.38%. The infected cases were mainly young and middle-aged people aged 18-59 years old, accounting for 83.50%, followed by 12.30% of the elderly group over 60 years old; the average hospital stay was 7.40 days; the proportion of patients with fever was less than 27.79%; 15.37% (26 817/174 466) of the patients complicated with underlying diseases, and the top three were hypertension, diabetes and coronary heart disease. The proportion of people who received COVID-19 vaccine accounted for 79.56% (13 799/17 956), of which the highest proportion of three doses was 44.09%. The disease duration of 17 956 COVID-19 cases in the author's branch of makeshift hospital was 10.18 (7.34, 13.05) days. The disease duration in the elderly group was the longest with 11.34 (8.35, 14.37) days, followed by 11.17 (9.07, 14.33) days in the preschool group, 10.37 (8.14, 13.34)· days in the middle-aged group, 10.07 (7.37, 12.37) days in the school-age group, and 9.34 (7.05, 12.16) days in the young group. There was significant difference in the overall distribution of disease duration among the five groups (H=550.479 P<0.01). The disease duration in each age group basically showed a V-shaped distribution. The disease duration was 10.27 (7.34, 12.57) days in males and 10.10 (7.25, 13.09) days in females, and there was no significant difference (Z=-1.505 P>0.05). The disease duration of vaccinated patients was 10.24 (7.35, 13.05) days, and that of unvaccinated patients was 9.47 (7.09, 12.47) days. There was significant difference between the two groups (Z=-4.338 P<0.01). Conclusions COVID-19 Omicron variant cases have a high proportion of males, mainly young and middle-aged, and the proportion of fever patients is less than 30%. The disease duration is significantly lower than that of the original strain in Wuhan, and shows "V" distribution with each age group. Sex had no effect on the disease duration. COVID-19 vaccination did not have a clinical effect on the disease duration.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: This study was to investigate the main characteristics and related factors of wideband absorbance (WBA) in children with normal hearing and to obtain age-specific reference range of WBA. Methods: 384 children between 0-12 years old (615 ears) who visited the Beijing Children's Hospital, Capital Medical University from October 2019 to February 2021 were enrolled, including 230 males (376 ears) and 154 females (239 ears), with totally 306 left ears and 309 right ears. Wideband tympanometry (WBT) was performed and normative WBA data were analyzed by SPSS 24.0 statistical software. Repeated measures and multivariate analysis of variance were applied to the data from 16 points at 1/3-octave frequencies (226, 324, 408, 500, 667, 841, 1 000, 1 297, 1 682, 2 000, 2 670, 3 364, 4 000, 5 339, 6 727 and 8 000 Hz) to evaluate the effects of frequency, age, external auditory canal pressures, gender and ear on WBA. Results: According to the WBT frequency-absorbance curve, the subjects were divided into seven groups: 1-month old group, 2-month old group, 3-month old group, 4-5 month old group, 6-24 month old group,>2-6 year old group and>6-12 year old group. The WBA of normal-hearing children underwent a series of developmental changes with age at both ambient pressure and tympanometric peak pressures. WBA results for 1-month group and 2-month old group exhibited a multipeaked pattern, with the peaks occurring around 2 000 and 4 897 Hz, and a notch around 3 886 Hz. WBA results for 3-month group and 4-5 month old group exhibited a single broad-peaked pattern, with the peak occurring between 2 000-4 757 Hz. The WBA of 1-month old group to 4-5 month old group decreased gradually at low frequency (226-408 Hz) and 6 727 Hz, and increased at middle to high frequency (2 670-4 000 Hz). The WBA of 6-24 month old group were significantly lower than that of 2-month old group to 4-5 month old group at all frequencies except 3 364 and 4 000 Hz. WBA results for 6-24 month old group,>2-6 year old group and>6-12 year old group exhibited a single-peaked pattern, and the peak frequency of WBA moved to the lower frequency successively. From 6-24 month old group to>6-12 year old group, the WBA gradually increased at low to middle frequencies (667-2 670 Hz) and 8 000 Hz, and decreased at middle to high frequencies (3 364-5 339 Hz). Among the 16 frequencies of all age groups, the difference between WBA under ambient pressure and tympanometric peak pressure were -0.09-0.06, and 43.75%-81.25% frequency points had statistically significant difference, which was mainly manifested in that WBA under ambient pressure were lower than that under tympanometric peak pressure at 226-1 682 Hz. There was no significant ear effect on all of the age groups. Similarly, there was no significant gender effect except for 3-month old group and 4-5 month old group. Conclusions: The WBA of normal-hearing children measured at ambient pressure and tympanometric peak pressure varied across the frequencies with age from 1 month to 12 years old, and different frequencies followed different change patterns (increase vs. decrease) in WBA. There was also significant external auditory canal pressures effect on all of the age groups. The establishment of age-specific reference range of WBA for 0-12 years old normal-hearing children in this study would be useful for clinical practice of determining normative data regarding WBT.
Male ; Female ; Humans ; Child ; Infant, Newborn ; Infant ; Child, Preschool ; Cross-Sectional Studies ; Acoustic Impedance Tests/methods* ; Ear ; Reference Values ; Ear Canal

Humans ; Fibrous Dysplasia, Polyostotic/complications* ; Hemangioma

Objective: To investigate the clinicopathological features, immunophenotypes and molecular genetics of EWSR1-SMAD3 positive fibroblastic tumor (ESFT) with an emphasis on differential diagnosis. Methods: The clinicopathological data, immunohistochemical profiles and molecular profiles of 3 ESFT cases diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center from 2018 to 2021were analyzed. The related literature was also reviewed. Results: There were two males and one female. The patients were 24, 12 and 36 years old, respectively. All three tumors occurred in the subcutis of the foot with the disease duration of 6 months to 2 years. The tumors were presented with a slowly growing mass or nodule, accompanied with pain in 1 patient. The tumors ranged in size from 0.1 to 1.6 cm (mean, 1.0 cm). Microscopically, the tumors were located in the subcutaneous tissue with a nodular or plexiform growth pattern. They were composed of cellular fascicles of bland spindle cells with elongated nuclei and fine chromatin. One of the tumors infiltrated into adjacent adipose tissue. There was no nuclear atypia or mitotic activities. All three tumors showed prominent stromal hyalinization with zonal pattern present in one case. Focal punctate calcification was noted in two cases. The immunohistochemical studies showed that tumor cells were diffusely positive for ERG and negative for CD31 and CD34, with Ki-67 index less than 2%. Fluorescence in situ hybridization on the two tested cases identified EWSR1 gene rearrangement. The next generation sequencing analysis demonstrated EWSR1-SMAD3 fusion in all three cases. During the follow up, one patient developed local recurrence 24 months after the surgery. Conclusions: ESFT is a benign fibroblastic neoplasm and has a predilection for the foot, characterized by ERG immunoreactivity and EWSR1-SMAD3 fusion. Local recurrence might occur when incompletely excised. Familiarity with its clinicopathological features is helpful in distinguishing it from other spindle cell neoplasms that tend to occur at acral sites.
Adult ; Child ; Female ; Humans ; Male ; Biomarkers, Tumor/analysis* ; China ; In Situ Hybridization, Fluorescence ; Neoplasms, Fibrous Tissue/pathology* ; RNA-Binding Protein EWS/genetics* ; Smad3 Protein/genetics* ; Soft Tissue Neoplasms/surgery*

This paper compared the differences between two kinds of Bufonis Venenum produced by Bufo gargarizans gargarizans and B. gararizans andrewsi, and verified the rationality of the market value orientation of Bufonis Venenum based on the zebrafish mo-del. Twenty batches of Bufonis Venenum from Jiangsu province, Hebei province, Liaoning province, Jilin province, and Liangshan, Sichuan province, including B. gargarizans gargarizans and B. gararizans andrewsi, were collected. The UHPLC-LTQ-Orbitrap-MS combined with principal component analysis was used to compare the differences between two kinds of Bufonis Venenum. According to the limiting conditions of VIP>1, FC<0.5 or FC>2.0, and peak total area ratio>1%, 9 differential markers were determined, which were cinobufagin, cinobufotalin, arenobufagin, resibufogenin, scillaredin A, resibufagin, 3-(N-suberoylargininyl)-arenobufagin, 3-(N-suberoylargininyl)-marinobufagin, and 3-(N-suberoylargininyl)-resibufogenin. The content of 20 batches of Bufonis Venenum was determined according to the Chinese Pharmacopoeia(2020 edition) by high-performance liquid chromatography, and the 2 batches of Bufonis Venenum, CS7(8.99% of total content) and CS9(5.03% of total content), with the largest difference in the total content of the three quality control indexes of the Chinese Pharmacopoeia(bufalin, cinobufagin, and resibufogenin) were selected to evaluate their anti-liver tumor activity based on the zebrafish model. The tumor inhibition rates of the 2 batches were 38.06% and 45.29%, respectively, proving that only using the quality control indexes of the Chinese Pharmacopoeia as the value orientation of Bufonis Venenum market circulation was unreasonable. This research provides data support for the effective utilization of Bufonis Venenum resources and the establishment of a rational quality evaluation system of Bufonis Venenum.
Animals ; Zebrafish ; Bufanolides/analysis* ; Bufonidae ; Chromatography, High Pressure Liquid ; Quality Control ; Cell Line, Tumor