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

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.
China ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Prescriptions ; Public Health

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in

ObjectiveTo compare the efficiency of paramagnetic relaxation enhancement of five gadolinium-based contrast agents （GBCAs） at the same dilution ratio and molar concentration.MethodsFive commonly used GBCAs， including 2 linear and 3 macrocyclic GBCAs， were employed and prepared to phantoms with the same molar concentration and dilution rate using distilled water. The phantoms were scanned in a 3.0 T MRI scanner under the same sequences and parameters. The regions of interest （ROIs） were drawn on the T₁WI SE and T₁ mapping images to quantitatively measure the T₁WI signal intensity and T₁ value from phantoms， calf muscles and surrounding air. The T₁ relaxation rate （R₁）， signal to noise ratio （SNR） and contrast noise ratio（CNR） were then calculated based on the T₁WI signal intensity and T₁ value. The relationship from signal intensity （Sp）， RSI， T₁ value，R₁， SNR， CNR and molar concentration were analyzed. The differences from Sp， RSI， T₁ value， R₁， SNR， CNR in 5 GBCAs were compared.ResultsIn the process of phantoms’s preparation， the total used dose of Gd-DO3A-butrol was lowest. Sp and RSI were curvilinearly correlated with the molar concentration of GBCAs（r_s=0）. While T₁p and SNR were negatively correlated with the molar concentration of GBCAs（r_s<0）， R₁ and CNR were positively correlated with the molar concentration of GBCAs. The Sp， T₁ values， RSI， SNR and CNR from these five GBCAs were detected to be similar to each other， even between linear and macrocyclic GBCAs.ConclusionsUnder the same molar concentration， there are no significant difference of T₁WI signal intensity and T₁ value between linear and macrocyclic GBCAs phantoms found from Magnetic resonance imaging. What’s more， both high and low molar concentration of gadolinium-based contrast agents can decrease the T₁WI signal intensity of phantom， but the T₁ value will continue to decrease with the increase of the molar concentration.

ObjectiveTo compare the efficiency of paramagnetic relaxation enhancement of five gadolinium-based contrast agents （GBCAs） at the same dilution ratio and molar concentration.MethodsFive commonly used GBCAs， including 2 linear and 3 macrocyclic GBCAs， were employed and prepared to phantoms with the same molar concentration and dilution rate using distilled water. The phantoms were scanned in a 3.0 T MRI scanner under the same sequences and parameters. The regions of interest （ROIs） were drawn on the T₁WI SE and T₁ mapping images to quantitatively measure the T₁WI signal intensity and T₁ value from phantoms， calf muscles and surrounding air. The T₁ relaxation rate （R₁）， signal to noise ratio （SNR） and contrast noise ratio（CNR） were then calculated based on the T₁WI signal intensity and T₁ value. The relationship from signal intensity （Sp）， RSI， T₁ value，R₁， SNR， CNR and molar concentration were analyzed. The differences from Sp， RSI， T₁ value， R₁， SNR， CNR in 5 GBCAs were compared.ResultsIn the process of phantoms’s preparation， the total used dose of Gd-DO3A-butrol was lowest. Sp and RSI were curvilinearly correlated with the molar concentration of GBCAs（r_s=0）. While T₁p and SNR were negatively correlated with the molar concentration of GBCAs（r_s<0）， R₁ and CNR were positively correlated with the molar concentration of GBCAs. The Sp， T₁ values， RSI， SNR and CNR from these five GBCAs were detected to be similar to each other， even between linear and macrocyclic GBCAs.ConclusionsUnder the same molar concentration， there are no significant difference of T₁WI signal intensity and T₁ value between linear and macrocyclic GBCAs phantoms found from Magnetic resonance imaging. What’s more， both high and low molar concentration of gadolinium-based contrast agents can decrease the T₁WI signal intensity of phantom， but the T₁ value will continue to decrease with the increase of the molar concentration.

OBJECTIVETo explore the intrinsic connection between activation of classical nuclear factor-κB (NF-κB) pathway and gefitinib resistance in human lung adenocarcinoma H1650 cells.

METHODSHuman lung adenocarcinoma H1650 cells were exposed to gefitinib continuously for 60 days to obtain resistant H1650 cells. The expressions of P-IκBα, P-p50 and P-p65 in the cytoplasm or nuclei were detected using Western blotting in human lung adenocarcinoma HCC827 cells, parental H1650 cells and gefitinib-resistant H1650 cells. The effects of gefitinib alone or in combination with PDTC on the survival rate and expressions of NF-κB P-p50 and P-p65 were compared among the 3 cell lines.

RESULTSGefitinib-resistant H1650 cells showed increased cytoplasmic and nuclear P-IκBα expressions. The expressions of P-p50 and P-p65 differed significantly among the 3 cell line, decreasing in the order of resistant H1650 cells, parental H1650 cells, and gefitinib sensitive HCC827 cell lines (P<0.05 or 0.01). Treatment with gefitinib alone resulted in a significantly lower cell inhibition rate in resistant H1650 cells than in the parental H1650 cells (P<0.05) and HCC827 cells (P<0.01). The resistant H1650 cells had a significantly higher expression of P-p50 and P-p65 than other two cell lines (P<0.05). In both the resistant and parental H1650 cells, gefitinib significantly lowered P-p50 and P-p65 expressions (P<0.05 or 0.01), and the combined treatment with gefitinib and PDTC significantly decreased the cell survival rate and further lowered the cytoplasmic and nuclear expressions of P-p50 and P-p65 (P<0.01 or 0.01).

CONCLUSIONThe activation of classical NF-κB pathway is a key factor contributing to transformation of the parental H1650 cells into gefitinib-resistant cells. Gefitinib combined with PDTC can inhibit P-IκBα production and NF-κB P-p50 and P-p65 activation to suppress the survival of residual H1650 cells and the generation of gefitinib-resistant cells.

Objective: To investigate the safety and efficacy of pulmonary vein deployment technique for percutaneous closure of atrial septal defects (ASD) solely under echocardiography guidance. Methods: A total of 38 ASD patients received pulmonary vein deployment in our hospital from 2012-10 to 2016-09 since the conventional method could not deliver the occluder to correct place. The patients were with the mean age at (16.0±15.6) years, body weight at (37.2±22.9) kg and ASD diameter at (17.1±4.2) mm. Operative effect was assessed by echocardiography. Follow-up study was conducted at 1, 3, 6, 12 months post-operation and at each year thereafter. Results: 37 patients were successfully finished pulmonary vein deployment for percutaneous closure of ASD solely under echocardiography guidance. One patient was successfully treated by a controlled steerable sheath. The mean operative time was (25.2±5.1) min and mean diameter of ASD occluder was (22.9±5.6) mm. 2 patients had trivial residual shunt at the early post-operative stage. No peripheral vascular injury, pulmonary vein and cardiac perforation occurred. All 38 patients were recovered and discharged. The average in-hospital time was (2.9±0.7) days. The patients were followed-up for (23.9±15.4) months, without complications of residual shunt, pericardial effusion, aortic regurgitation and pulmonary vein stenosis. Conclusion: Pulmonary vein deployment technique for percutaneous closure of ASD solely under echocardiography guidance was safe and effective; it can avoid radiation damage and provided a simple and practical method for ASD patients who failed to conventional method under echocardiography guidance.

Objectives: The present first-in-human study aimed to assess the feasibility of percutaneous balloon mitral valvuloplasty (PBMV) for the treatment of isolated mitral stenosis (MS) under echocardiography guidance only. Methods: Data were obtained from 24 consecutive patients with severe MS, who underwent PBMV from October 2016 to October 2017 under the guidance of echocardiography only. Outpatient follow-up including chest radiography, electrocardiography, and transthoracic echocardiography was conducted at 1, 3, 6 and 12 months post procedure. Results: PBMV was successful in all 24 patients under echocardiography guidance without radiation and contrast agent. Mitral transvalvular pressure gradient derived invasive catheterization measurement dropped from(15.0±5.1) mmHg to (6.7±2.9) mmHg (P<0.01). Mitral valve area increased from (0.8±0.1) cm2at pre-PBMV to (1.7±0.1) cm2post-PBMV (P<0.01). Mean balloon diameter was (26.7±1.2) mm. Mild mitral regurgitation developed in 8 patients. Mean follow-up duration was (7.4±3.1) months. At the last follow-up, mitral valve area remained high (1.6±0.1) cm2and mean transmitral pressure gradient remained low (9.0±4.3) mmHg. No pericardial effusion or peripheral vascular complications occurred. Conclusions: In this patient cohort, PBMV could be successfully performed with echocardiography as the single imaging guidance modality, this procedure is safe and effective and avoids the radiation exposure and contrast agent use.

Clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for sepsis is strictly in accordance with the latest diagnostic criteria for sepsis (sepsis-3) for the treatment of septic patients at different stages through syndrome differentiation. At present, the abuse of antibiotics and the prevalence of drug-resistant bacteria are very serious, without effective solutions. Thus, this is the first time to focus on traditional Chinese medicine combined with antibiotics to treat sepsis, in order to minimize the incidence of drug-resistant bacteria. This Guideline tends to systematically analyze the sepsis period, septic shock period as well as different clinical symptoms and traditional Chinese medicine measures for organ dysfunction in the sepsis process. By analyzing and interpreting the Guideline systematically, the clinicians could understand its purpose, significance and core ideas more thoroughly, and grasp the recommended specific interventions as well as their advantages and disadvantages, hoping to better implement the Guideline, provide guidance to clinicians and standardize the treatment of sepsis by traditional Chinese medicine.
Anti-Bacterial Agents ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Sepsis ; drug therapy

To investigate the clinical application of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for sepsis, in order to promote the follow-up revision and further promotion of the Guidelines. Copies of 500 application evaluation questionnaire and 500 copies of applicability evaluation questionnaire were given to the clinicians who had used this Guideline in China, both in a form of registered questionnaire, and a database was established by Excel 2016 for descriptive statistical analysis. Copies of 211 application evaluation questionnaire and 211 copies of applicability evaluation questionnaire were collected. We can conclude from the survey that we should adjust the whole content and structure on the basis of better evaluation of the present recommendation scheme, update the prescription selection and clinical evidence of the recommendation scheme, and put forward the improvement measures for the hindrance factors in the application of the Guideline. Furthermore, in order to promote the Guideline more clearly, we should strengthen the doctor-patient education, improve guidance quality and increase the publicity, providing basis for the implementation and promotion strategies of the Guideline.
Anti-Bacterial Agents ; therapeutic use ; China ; Humans ; Medicine, Chinese Traditional ; Sepsis ; drug therapy ; Surveys and Questionnaires