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

Objective:To explore the efficacy of a bleeding risk graded management program in patients with lower extremity deep vein thrombosis (DVT) undergoing catheter-directed thrombosis (CDT) .Methods:Convenience sampling was used to select 100 DVT patients who underwent CDT from October 2021 to December 2023 in the Nanjing First Hospital as study subjects. According to the propensity matching score ratio of 1: 1, patients were divided into control group and observation group, with 50 cases in each group. Control group implemented CDT routine nursing and rehabilitation exercises, and observation group implemented a bleeding risk graded management program based on control group by dynamically monitoring changes in plasma fibrinogen and blood pressure. Differences in the rates of swelling reduction in the limbs, venous patency, bleeding events and hospitalization satisfaction were compared between the two groups.Results:After the intervention, the swelling reduction rate of the limbs of DVT patients in observation group was (85.07±11.96) %, and the rate of venous patency was (89.00±25.33) %, and that of control group was (70.85±21.73) %, (75.00±35.36) %, and the differences were statistically significant (all P<0.05). The rate of bleeding events was lower in the observation group than in the control group, and the difference was statistically significant ( P<0.05). The difference in hospitalization satisfaction between the two groups was not statistically significant ( P>0.05) . Conclusions:The bleeding risk graded management program developed after comprehensive assessment can realize the balance between the therapeutic benefit and bleeding risk of CDT for DVT patients, and can improve the safety and effectiveness of CDT.

Objective:To explore the efficacy of a bleeding risk graded management program in patients with lower extremity deep vein thrombosis (DVT) undergoing catheter-directed thrombosis (CDT) .Methods:Convenience sampling was used to select 100 DVT patients who underwent CDT from October 2021 to December 2023 in the Nanjing First Hospital as study subjects. According to the propensity matching score ratio of 1: 1, patients were divided into control group and observation group, with 50 cases in each group. Control group implemented CDT routine nursing and rehabilitation exercises, and observation group implemented a bleeding risk graded management program based on control group by dynamically monitoring changes in plasma fibrinogen and blood pressure. Differences in the rates of swelling reduction in the limbs, venous patency, bleeding events and hospitalization satisfaction were compared between the two groups.Results:After the intervention, the swelling reduction rate of the limbs of DVT patients in observation group was (85.07±11.96) %, and the rate of venous patency was (89.00±25.33) %, and that of control group was (70.85±21.73) %, (75.00±35.36) %, and the differences were statistically significant (all P<0.05). The rate of bleeding events was lower in the observation group than in the control group, and the difference was statistically significant ( P<0.05). The difference in hospitalization satisfaction between the two groups was not statistically significant ( P>0.05) . Conclusions:The bleeding risk graded management program developed after comprehensive assessment can realize the balance between the therapeutic benefit and bleeding risk of CDT for DVT patients, and can improve the safety and effectiveness of CDT.

A 3-year-old boy presented with bluish patch and scattered blue spots on the left side of his face. After several sessions of laser treatment, the azury patch in the periorbital area became even darker. Histopathology showed many bipolar, pigment-laden dendritic cells scattered in the papillary and upper reticular dermis. Immunohistochemically, these cells were positive for S100, SOX-10, melan-A, P16, and HMB-45. The positive rate of Ki-67 was less than 5%. Finally, the lesion was diagnosed with nevus of Ota concurrent with common blue nevus. Therefore, for cases of the nevus of Ota with poor response to laser treatment, the possible coexisting diseases should be suspected.
Male ; Humans ; Child, Preschool ; Nevus, Blue/pathology* ; Nevus of Ota/therapy* ; Skin/pathology* ; Face ; Skin Neoplasms/pathology*

Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.

Humans ; Child ; Neurofibromatosis 1/drug therapy* ; Benzimidazoles/therapeutic use*

Deep venous thrombosis (DVT) poses a major challenge to public health worldwide. Endothelial cell injury evokes inflammatory and oxidative responses that contribute to thrombus formation. Tea polyphenol (TP) in the form of epigallocatechin-3-gallate (EGCG) has anti-inflammatory and oxidative effect that may ameliorate DVT. However, the precise mechanism remains incompletely understood. The current study was designed to investigate the anti-DVT mechanism of EGCG in combination with warfarin (an oral anticoagulant). Rabbits were randomly divided into five groups. A DVT model of rats was established through ligation of the inferior vena cava (IVC) and left common iliac vein, and the animals were orally administered with EGCG, warfarin, or vehicle for seven days. In vitro studies included pretreatment of human umbilical vein endothelial cells (HUVECs) with different concentrations of EGCG for 2 h before exposure to hydrogen peroxide. Thrombus weight and length were examined. Histopathological changes were observed by hematoxylin-eosin staining. Blood samples were collected for detecting coagulation function, including thrombin and prothrombin times, activated partial thromboplastin time, and fibrinogen levels. Protein expression in thrombosed IVCs and HUVECs was evaluated by Western blot, immunohistochemical analysis, and/or immunofluorescence staining. RT-qPCR was used to determine the levels of AGTR-1 and VEGF mRNA in IVCs and HUVECs. The viability of HUVECs was examined by CCK-8 assay. Flow cytometry was performed to detect cell apoptosis and ROS generation was assessed by 2',7'-dichlorofluorescein diacetate reagent. In vitro and invivo studies showed that EGCG combined with warfarin significantly reduced thrombus weight and length, and apoptosis in HUVECs. Our findings indicated that the combination of EGCG and warfarin protects HUVECs from oxidative stress and prevents apoptosis. However, HIF-1α silencing weakened these effects, which indicated that HIF-1α may participate in DVT. Furthermore, HIF-1α silencing significantly up-regulated cell apoptosis and ROS generation, and enhanced VEGF expression and the activation of the PI3K/AKT and ERK1/2 signaling pathways. In conclusion, our results indicate that EGCG combined with warfarin modifies HIF-1α and VEGF to prevent DVT in rabbits through anti-inflammation via the PI3K/AKT and ERK1/2 signaling pathways.
Animals ; Anticoagulants/pharmacology* ; Catechin/analogs & derivatives* ; Eosine Yellowish-(YS)/pharmacology* ; Fibrinogen/pharmacology* ; Hematoxylin/pharmacology* ; Human Umbilical Vein Endothelial Cells ; Humans ; Hydrogen Peroxide/pharmacology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; MAP Kinase Signaling System ; Phosphatidylinositol 3-Kinases/metabolism* ; Polyphenols/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; RNA, Messenger ; Rabbits ; Rats ; Reactive Oxygen Species/metabolism* ; Signal Transduction ; Sincalide/pharmacology* ; Tea ; Thrombin/pharmacology* ; Vascular Endothelial Growth Factor A/metabolism* ; Venous Thrombosis/pathology* ; Warfarin/pharmacology*

Clinical genomics mainly studies the clinical application of genomics in diagnosis,treatment decision,and prognosis prediction.Artificial intelligence enables the processing of complex and massive data in genomics which are difficult to be dealt with traditional algorithms and techniques.At present,artificial intelligence is involved in many tasks of clinical genomics,such as variant calling and classification,imaging and genetic diagnosis,electronic health record-based genetic diagnosis,and prediction of drug effect and adverse reaction.This review elaborates the application of artificial intelligence in different aspects of clinical genomics.
Algorithms ; Artificial Intelligence ; Diagnostic Imaging ; Genomics ; Prognosis

Hyperuricemia is a chronic metabolic disease caused by the accumulation of uric acid in the body caused by purine metabolism disorder. In recent years, the incidence of hyperuricemia has increased and the age of onset is showing a younger trend. Finding effective therapeutic targets and treatment methods is a hot spot of current research. The urate transporter ATP-binding cassette subfamily G member 2 (ABCG2) is mainly expressed in the kidney and promotes uric acid excretion. In this study, ABCG2 mRNA was synthesized in vitro and transfected into hyperuricemia model mice to observe its effect on mouse uric acid levels. Firstly, the DNA template of ABCG2 mRNA was chemically synthesized, and then transcribed into mRNA in vitro, followed by modification and transfection into mouse TCMK-1 renal tubular epithelial cells. Finally, the protein expression in the cells was detected by Western blot. The results showed that the amount of protein expression in TCMK-1 cells was positively correlated with the amount of transfected mRNA (P < 0. 01), indicating a successful transfection. In animal experiments, twenty-four SPF mice were randomly divided into four groups (n = 6): control group, hyperuricemia model group, benzbromarone group [20 mg/(kg•d)] and mRNA group [2 mg/(kg•3d)]. The mice have been modeled and treated for 28 days. During this period, the body weight and growth status of the mice were monitored daily. After the treatment, the levels of serum uric acid, urine uric acid, serum creatinine, blood urea nitrogen and liver xanthine oxidase were analyzed. The results showed that compared with the model group of mice, mRNA treatment can significantly reduce the levels of serum uric acid (100. 38 ± 10. 94), blood urea nitrogen (6. 30 ± 1. 10), and serum creatinine (30. 86 ± 5. 78, P<0. 05 or P<0. 01). It can also increase the level of urine uric acid (617. 48 ± 50. 34, P<0. 05) in mice and promote the excretion of uric acid. But it has no significant effect on the activity of xanthine oxidase (26. 19 ± 2. 58) in the liver. The pathological changes of mice kidney were observed by HE staining. The results showed that compared with mice in the model group, pathological damages such as renal tubular cell edema and inflammatory cell infiltration in the mRNA treatment group were significantly improved. The relative expression of mRNA in mice kidney was detected by qRT-PCR, and the protein expression of ABCG2 in mice kidney was detected by immunohistochemistry and Western blot. The results showed that the relative expression of ABCG2 mRNA and its protein were significantly up-regulated in the kidney tissues of mice in the mRNA group (P < 0. 01), indicating that the transfection was successful in vivo. In conclusion, ABCG2 mRNA synthetized and modified in vitro can be successfully expressed in hyperuricemia mice and promote excretion of uric acid and other organic ions, as well as improvement of renal injury in mice. These results provide experimental basis for the clinical application of ABCG2 as a target for the treatment of hyperuricemia related diseases.