ObjectiveTo identify and validate the optimal compatibility dosage of astragaloside Ⅰ （ASⅠ） and calycosin （CY） in the treatment of cholestatic liver fibrosis. MethodsA 3，5-diethoxycarbonyl-1，4-dihydrocollidine （DDC） diet was used to establish a mouse model of liver fibrosis， and the uniform design method was used to identify the optimal combination ratio of the saponin component ASⅠ and the flavonoid component CY in Astragalus membranaceus. In the uniform design experiment， 80 male C57/BL6J mice were divided into normal group， model group， total astragalosides （TAS） group， groups A — F with a uniform design， and obeticholic acid （OCA） group using a random number table， with 8 mice in each group. The multiple regression analysis was used to establish the optimal regression equation and obtain the potential optimal combination ratio. The in vivo efficacy of the empirically optimal combination identified in the uniform design and the optimal dose combination predicted by the regression equation were compared for validation. A one-way analysis of variance was used for comparison of continuous data between multiple groups； the Levene test was used to determine the homogeneity of variance， and the least significant difference t-test was used for comparison of data with homogeneity of variance between two groups， while the Dunnett T3 test was used for comparison of data with heterogeneity of variance. ResultsIn the uniform design regimen， the JYB combination （3.125 mg/kg ASI+50 mg/kg CY） significantly reduced the serum levels of alanine aminotransferase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， total bile acid （TBA）， total bilirubin （TBil）， and indirect bilirubin （IBil） in mice with DDC-induced cholestatic liver fibrosis （all P<0.05）， and it also reduced hepatic Hyp content （P<0.01）， semi-quantified collagen deposition area （P<0.001）， and the mRNA expression levels of Acta2， Col1a1， Ck7， Ck19， Adgre1， TLR4， TNF-α， and CCL5 in liver tissue （all P<0.05）. The regression equation showed that 50 mg/kg ASⅠ+50 mg/kg CY was the potential optimal combination， which was named as P1 combination. However， subsequent validation experiments showed that P1 combination only significantly improved the serum levels of AST and IBil and hepatic Hyp content in DDC mice （all P<0.05）， with no significant impact on hepatic collagen deposition and the mRNA expression levels of Acta2， Ck7， Ck19， Adgre1， and CCL5 （all P>0.05）. In contrast， the JYB combination significantly improved the serum levels of ALP， ALT， AST， TBA， TBil， and IBil， hepatic collagen deposition， hepatic Hyp content， and the mRNA expression levels of Acta2， Col1a1， Ck7， Ck19， Adgre1， TLR4， TNF-α， and CCL5 （all P<0.05）. ConclusionThis study shows that the JYB combination （3.125 mg/kg ASⅠ+50 mg/kg CY） can significantly alleviate DDC-induced liver fibrosis， with comparable efficacy to total saponins from Astragalus membranaceus， and compared with ASⅠ or CY administered alone， the JYB combination has a significantly better regulatory effect on the serum levels of ALP and TBA.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

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

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

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OBJECTIVE: To investigate the clinical efficacy and safety of single Kirschner wire assisted poking and closed reduction in the treatment of Gartland type Ⅲ supracondylar humeral fractures in children. METHODS: A retrospective analysis was performed on patients diagnosed with Gravland type Ⅲ supracondylar humeral fractures between January 2022 and June 2023. A total of 46 patients were treated with closed reduction assisted by Kirschner wires and percutaneous Kirschner wire internal fixation.There were 25 males and 21 females. The age ranged from 5 to 10 years old, with an average of (5.8±1.8) years old. The left side was involved in 28 patients and the right side in 18 patients. Record the operative duration for patients, the number of fluoroscopic exposures, fracture healing time, postoperative carrying angle, Baumann angle, elbow joint function score at three months post-operation, and any associated complications. RESULTS: All 46 patients were followed up for a period of 12 to 16 weeks, with an average of (13.74±1.44 )weeks. The operation duration was (30.7±5.1) minutes, the fluoroscopy count was (10.2±2.7) times, the postoperative carrying angle of the elbow joint was (8.7±2.2) degrees, and the Baumann angle was (71.5±2.9) degrees. All fractures achieved successful union in all patients, with a mean healing time of (25.5±1.7) days.At the final follow-up, elbow joint function was assessed using the Flynn criteria, with 43 patients rated as excellent and 3 patients rated as good. No complications were observed, including cubitus varus, nerve injury, or local infection. CONCLUSION The use of a single Kirschner wire assisted prying reduction for treating Gartland type Ⅲ supracondylar humeral fractures in children demonstrates excellent clinical efficacy and safety.
Humans ; Male ; Female ; Child ; Bone Wires ; Child, Preschool ; Humeral Fractures/physiopathology* ; Retrospective Studies ; Fracture Fixation, Internal/instrumentation* ; Treatment Outcome ; Fracture Healing

OBJECTIVES: To construct a Z-score regression model for coronary artery diameter based on echocardiographic data from children in Sichuan Province and to establish a Z-score calculation formula. METHODS: A total of 744 healthy children who underwent physical examinations at Sichuan Provincial People's Hospital from January 2020 to December 2022 were selected as the modeling group, while 251 children diagnosed with Kawasaki disease at the same hospital from January 2018 to December 2022 were selected as the validation group. Pearson correlation analysis was conducted to analyze the relationships between coronary artery diameter values and age, height, weight, and body surface area. A regression model was constructed using function transformation to identify the optimal regression model and establish the Z-score calculation formula, which was then validated. RESULTS: The Pearson correlation analysis showed that the correlation coefficients for the diameters of the left main coronary artery, left anterior descending artery, left circumflex artery, and right coronary artery with body surface area were 0.815, 0.793, 0.704, and 0.802, respectively (P<0.05). Among the constructed regression models, the power function regression model demonstrated the best performance and was therefore chosen as the optimal model for establishing the Z-score calculation formula. Based on this Z-score calculation formula, the detection rate of coronary artery lesions was found to be 21.5% (54/251), which was higher than the detection rate based on absolute values of coronary artery diameter. Notably, in the left anterior descending and left circumflex arteries, the detection rate of coronary artery lesions using this Z-score calculation formula was higher than that of previous classic Z-score calculation formulas. CONCLUSIONS The Z-score calculation formula established based on the power function regression model has a higher detection rate for coronary artery lesions, providing a strong reference for clinicians, particularly in assessing coronary artery lesions in children with Kawasaki disease.
Humans ; Male ; Female ; Child, Preschool ; Child ; Coronary Artery Disease/diagnostic imaging* ; Infant ; Mucocutaneous Lymph Node Syndrome ; Regression Analysis ; Coronary Vessels/diagnostic imaging* ; Echocardiography ; Adolescent

OBJECTIVES: To compare the efficacy of transcatheter tricuspid valve replacement (TTVR) using Lux-Valve and Lux-Valve Plus in patients with severe tricuspid regurgitation. METHODS: A total of 28 consecutive patients with severe tricuspid regurgitation who underwent TTVR with Lux-Valve (n=14) or Lux-Valve Plus (n=14) in the First Affiliated Hospital of the Air Force Medical University from August 2019 to November 2023 were enrolled. Transthoracic echocardiography was performed in all patients before and 6 months after the TTVR. The ultrasound indexes were compared before and 6 months after the TTVR in all patients and between Lux-Valve and Lux-Valve Plus groups. RESULTS: Compared with the Lux-Valve group, the Lux-Valve Plus group showed significantly reduced intraoperative bleeding and shorter postoperative hospital stays (both P<0.05). Six months after the TTVR, none of the patients exhibited more than a mild tricuspid valve regurgitation, and none of the patients had moderate or above perivalvular leakage except for one patient in the Lux-Valve Plus group who had a separation of the clamping member from the anterior tricuspid leaflet. The incidence of perivalvular leakage was significantly lower in the Lux-Valve Plus group (14.29%, 2/14) than in the Lux-Valve group (64.29%, 9/14, P<0.05). At 6 months after operation, the right chamber volume and right ventricle middle transverse diameter were reduced (both P<0.05); the peak blood flow velocity across the tricuspid valve, peak pressure gradient across the tricuspid valve, mean blood flow velocity of tricuspid valve, mean pressure gradient across the tricuspid valve and velocity time integral were increased in both groups (all P<0.05).Compared with the Lux-Valve group, the Lux-Valve Plus group showed higher left ventricular ejection fraction at 6 months postoperatively (P<0.05), while the rest of the indicators were not statistically different (all P>0.05). CONCLUSIONS The efficacy of using Lux-Valve and Lux-Valve Plus for TTVR in patients with severe tricuspid regurgitation is comparable. Six months after the TTVR, the right side of the heart has undergone reverse remodeling.While Lux-Valve Plus offers greater minimally invasive benefits, valve selection should consider device-specific characteristics and differences in individual patients.
Humans ; Tricuspid Valve Insufficiency/surgery* ; Male ; Female ; Heart Valve Prosthesis Implantation/methods* ; Middle Aged ; Aged ; Tricuspid Valve/surgery* ; Heart Valve Prosthesis ; Treatment Outcome ; Echocardiography ; Adult ; Cardiac Catheterization/methods*

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*