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

Brasilicardin A, a diterpene glycoside isolated from pathogenic actinomycete Nocardia brasiliensis IFM 0406, has become a novel immunosuppressant candidate due to its significant immunosuppressive activity, low toxicity and unique mechanism of action. However, brasilicardin A and its analogues have become a research hotspot to the development of this promising immunosuppressant because of the low-yield production in the natural pathogenic producer and the synthetically challenging skeleton. According to the reported biosynthetic pathway of brasilicardin A, the function of involved diterpene synthase was analyzed by bioinformatics. Then the genes bra1-5 that synthesize the brasilicardin A skeleton were directionally amplified from the pathogenic strain N. brasiliensis IFM 0406, and heterologous expression was achieved successfully in Streptomyces albus R1. The compounds were isolated and purified by using various column chromatographies including silica gel column chromatography and semi-preparative HPLC. Six new brasilicardins were established and named brasilicardin H-M. The activity of brasilicardins was screened using lipopolysaccharide (LPS)-activated mouse primary macrophage inflammation model. Brasilicardin H-M exhibited good inhibitory activity on nitric oxide (NO) release with IC₅₀ values of 28.24 ± 3.70, 37.44 ± 2.00, 39.85 ± 4.02, 26.77 ± 4.40, 65.25 ± 1.48 and 15.24 ± 2.72 μmol·L^-1, respectively (indomethacin as the positive control with IC₅₀ value of 34.28 ± 4.10 μmol·L^-1). The results indicated that six compounds had potential anti-inflammatory activity. This study laid a foundation for the elucidation of the brasilicardin A biosynthetic pathway and evaluation of the structure-activity relationship as well as new drug developments.

Objective: The study investigated cognitive performance and brain function between treatment-resistant depression (TRD) and non- TRD patients to find potential neurobiological markers associated with refractoriness in depression patients. Methods: Fourteen TRD patients, 26 non-TRD patients and 23 healthy controls (HC) were included in the present study. The neural function of prefrontal cortex (PFC) and cognitive performance among the three group were examined using near-infrared spectroscopy (NIRS) during verbal fluency task (VFT). Results: Both TRD and non-TRD groups exhibited significantly worse VFT performance and lower activation of oxygenated hemoglobin (oxy-Hb) changes in the bilateral dorsolateral PFC (DLPFC) compared to the HC group. Within the TRD and non-TRD groups, VFT performance was no significant difference, but activation of oxy-Hb changes in dorsomedial PFC (DMPFC) in TRD patients was significantly lower than non-TRD patients. In addition, activation of oxy-Hb changes in right DLPFC were negatively correlated with the severity of depressive symptoms in depression patients. Conclusion Both TRD patients and non-TRD patients exhibited lower oxy-Hb activation in DLPFC. TRD patients exhibit lower oxy- Hb activation in DMPFC than non-TRD patients. fNIRS maybe a useful tool for predict depressive patients with or without treatment resistant.

BACKGROUNDSpine surgery using computer-assisted navigation (CAN) has been proven to result in low screw misplacement rates, low incidence of radiation exposure and excellent operative field viewing versus the conventional intraoperative image intensifier (CIII). However, as we know, few previous studies have described the learning curve of CAN in spine surgery.

METHODSWe performed two consecutive case cohort studies on pedicel screw accuracy and operative time of two spine surgeons with different experience backgrounds, A and B, in one institution during the same period. Lumbar pedicel screw cortical perforation rate and operative time of the same kind of operation using CAN were analyzed and compared using CIII for the two surgeons at initial, 6 months and 12 months of CAN usage.

RESULTSCAN spine surgery had an overall lower cortical perforation rate and less mean operative time compared with CIII for both surgeon A and B cohorts when total cases of four years were included. It missed being statistically significant, with 3.3% versus 4.7% (P = 0.191) and 125.7 versus 132.3 minutes (P = 0.428) for surgeon A and 3.6% versus 6.4% (P = 0.058), and 183.2 versus 213.2 minutes (P = 0.070) for surgeon B. In an attempt to demonstrate the learning curve, the cases after 6 months of the CAN system in each surgeon's cohort were compared. The perforation rate decreased by 2.4% (P = 0.039) and 4.3% (P = 0.003) and the operative time was reduced by 31.8 minutes (P = 0.002) and 14.4 minutes (P = 0.026) for the CAN groups of surgeons A and B, respectively. When only the cases performed after 12 months using the CAN system were considered, the perforation rate decreased by 3.9% (P = 0.006) and 5.6% (P < 0.001) and the operative time was reduced by 20.9 minutes (P < 0.001) and 40.3 minutes (P < 0.001) for the CAN groups of surgeon A and B, respectively.

CONCLUSIONSIn the long run, CAN spine surgery decreased the lumbar screw cortical perforation rate and operative time. The learning curve showed a sharp drop after 6 months of using CAN that plateaued after 12 months; which was demonstrated by both perforation rate and operative time data. Careful analysis of the data showed CAN is especially useful for less experienced surgeon to reduce perforation rate and intraoperative time, although further comparative studies are anticipated.

Cohort Studies ; Humans ; Spine ; surgery ; Surgery, Computer-Assisted ; methods

OBJECTIVETo identify polymorphisms of the serotonin transporter(5-HTT) gene and to find out whether there was relationship between any such polymorphisms and sleep apnea syndrome (SAS).

METHODSFor two polymorphisms of 5-HTT target DNA gene was amplified using polymerase chain reaction (PCR) and 6% non-denaturing polyacrylamide gels electrophoresis. The frequencies of the different forms of the genotypes and alleles of 5-HTT gene were analyzed in 104 patients with SAS and 150 healthy controls.

RESULTSThe frequencies of the S or L alleles and the S/S, S/L or L/L genotypes in promoter region of 5-HTT gene in SAS group were not significantly different to those in healthy controls (P > 0.05). However, the frequencies of 10/10, 12/10 genotypes of 5-HTT-VNTR in SAS patients were significantly higher than those in healthy control subjects (P < 0.05). Moreover, the frequency of the allele 10 of 5-HTT-VNTR in SAS patients was significantly higher than that in healthy controls (P<0.01).

CONCLUSIONThe allele 10 of 5-HTT-VNTR might be a susceptible factor in the pathogenesis of SAS.

Adult ; Aged ; Alleles ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Male ; Middle Aged ; Minisatellite Repeats ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Promoter Regions, Genetic ; genetics ; Serotonin Plasma Membrane Transport Proteins ; genetics ; Sleep Apnea Syndromes ; genetics ; Young Adult

Objective:To explore the quality of life in patients with primary insomnia.Methods:Comprising 85 patients diagnosed as primary insomnia and 57 healthy controls,the study analyzed and compared the differences in quality of life between the two groups.Results:(1)Compared with healthy controls,the patients with primary in- somnia decreased in quality of life.total score,Physical functions,psychological function and social function in pri- mary insomnia group were significantly lower than those in control group in score of generic quality of life inventory (score:254.9?26.4/287.1?30.4,t=-5.15,P