Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Objective:To investigate the application value of exercise rehabilitation mode based on cardiopulmonary exercise testing(CPET)in the treatment and rehabilitation of coronary heart disease(CHD).Methods:This ran-domized controlled study enrolled 260 CHD patients admitted in Hai'an People's Hospital between January 2021 and June 2022.They were divided into control group(n=130,routine nursing)and intervention group(n=130,addi-tional exercise rehabilitation training nursing).After 6-month intervention,scores of Heart Health-Self-Effica-cy and Self-Management(HH-SESM)scale,Chinese Quality of Life Questionnaire for Cardiovascular Patients(CQQC),peak oxygen uptake(VO2peak),percentage of peak oxygen uptake in predicted maximum(VO2peak％Pred),peak metabolic equivalent(peak Mets),cardiac function indexes,and incidence of adverse events were com-pared between two groups.Results:After intervention,compared with patients in control group,those in interven-tion group had significant higher scores of HH-SESM[(76.57±5.88)points vs.(64.51±5.16)points]and CQQC[(111.66±7.93)points vs.(84.16±6.96)points],VO2peak[(1.41±0.11)L/min vs.(1.19±0.26)L/min],VO2peak％Pred[(59.32±3.51)％vs.(51.27±3.11)％],peak Mets[(7.89±1.86)vs.(5.22±1.16)],6MWD[(473.53±18.12)m vs.(354.27±23.11)m],and significant lower serum N-terminal pro brain natri-uretic peptide(NT-proBNP)[(5.13±2.17)pg/ml vs.(13.81±2.22)pg/ml],cardiac troponin Ⅰ(cTnⅠ)[(2.90±0.51)ng/ml vs.(4.76±1.32)ng/ml](P＜0.001 all).Intervention group had significant lower incidence of adverse events comparing to control group(3.85％vs.13.85％,P=0.005).Conclusion:Exercise rehabilitation treatment based on cardiopulmonary exercise test could effectively improve self-efficacy and self-management,quality of life,cardiopulmonary function and reduce risk of adverse events in patients with coronary heart disease.

ObjectiveTo investigate the effect of icariin （ICA） on steroid-induced ferroptosis in bone microvascular endothelial cells （BMECs）. MethodsRat BMECs were selected and treated with 500 mg·L^-1 hydrocortisone for 1.5 h to establish a ferroptosis model of BMECs. The experimental cells were divided into a blank group， hormone group （500 mg·L^-1 hydrocortisone）， ICA group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA）， and ferroptosis agonist group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA + 2.7 mg·L^-1 erastin）. Cell viability was detected by CCK-8. The levels of ferrous ion， glutathione （GSH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and reactive oxygen species （ROS） were detected by related kit species. The ferroptosis-related proteins， such as glutathione peroxidase 4（GPX4）， ferritin light chain （FTL）， and transferrin receptor protein1 （sTfR） were detected by Western blot， as well as autophagy-related proteins including microtubule-associated protein 1 light chain 3B （LC3B）， Beclin1， B-cell lymphoma-2 （Bcl-2）， and Caspase-3. Results500 mg·L^-1 hydrocortisone intervention for 1.5 h could effectively induce ferroptosis in BMECs， and ferroptosis levels could reach a peak as the intervention continued. In terms of cellular antioxidant capacity， compared with those in the blank group， the cell vitality， GSH in the hormone group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions were significantly increased （P<0.01）. Compared with those in the hormone group， the cell viability， GSH were significantly increased， and the levels of ROS， SOD， MDA， and ferrous ions were decreased in the ICA group （P<0.01）. Compared with those in the ICA group， the cell vitality， GSH in the ferroptosis agonist group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions increased significantly （P<0.01）. In terms of the relationship between ferroptosis and autophagy， compared with the blank group， the hormone group had significantly increased expression levels of LC3B， sTfR， Beclin1， and FTL and significantly decreased expression levels of GPX4 （P<0.01）. Compared with the hormone group， The ICA group had significantly decreased expression levels of LC3B， sTfR， and FTL and significantly increased expression levels of Beclin 1 and GPX4 （P<0.01）. Compared with those in the ICA group， the expression levels of LC3B， sTfR， and FTL increased in the rapamycin group， and those of Beclin 1 and GPX4 decreased （P<0.01）. In terms of cell ferroptosis and apoptosis，compared with the blank group， the hormone group had significantly increased expression levels of FTL， sTfR and Caspase-3 and significantly decreased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with the hormone group， the ICA group had significantly decreased expression levels of FTL， sTfR and Caspase-3 and significantly increased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with those in the ICA group， the expression levels of FTL， sTfR and Caspase-3 in the ferroptosis agonist group were increased， and the expression levels of GPX4， and Bcl-2 were decreased （P<0.01）. In terms of cell function，compared with that in the blank group， the ability of cell migration and tube formation was significantly decreased in the hormone group （P<0.01）. Compared with that in the hormone group， the cell migration and tube formation ability in the ICA group were significantly increased （P<0.01）. ConclusionFerroptosis is involved in steroid-induced damage in BMECs. ICA can inhibit steroid-induced ferroptosis in BMECs， and the mechanism may be associated with the inhibition of ferroptosis by regulating autophagy.

Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

OBJECTIVE: This cross-sectional study assessed the methodological quality of systematic reviews (SRs) of Chinese herbal medicine (CHM) published in Chinese between Jan 2021 and Sep 2022. METHODS: Chinese language CHM SRs were identified through literature searches across 3 international and 4 Chinese databases. Methodological quality was appraised using A MeaSurement Tool to Assess systematic Reviews 2. Logistic regressions were used to explore associations between bibliographical characteristics and quality. RESULTS: Analyses of methodological quality found that among the 213 sampled SRs, 69.5% were of critically low quality, 30.5% were of low quality, and none achieved high or moderate quality. Common shortcomings included the failure to identify the studies excluded from the analysis, failure to disclose funding sources, and limited evaluation of the potential impact of bias on conclusions. Logistic regressions revealed that SRs led by corresponding authors affiliated with universities or academic institutions tended to be of lower quality than SRs led by authors affiliated with hospitals or clinical facilities. CONCLUSION Recent Chinese language CHM SRs exhibited limited methodological quality, making them unlikely to support the development of clinical practice guidelines. Urgent initiatives are needed to enhance training for researchers, peer-reviewers and editors involved in the preparation and publication of SRs. Adoption of Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines in Chinese language journals is crucial to improve the relevance of SRs for Chinese medicine development. Addressing deficiencies in methodology and reporting is essential for promoting evidence-based practices and informed clinical decisions in Chinese medicine. Please cite this article as: Jiang Y, Zhong CC, Wang BH, Xu SS, Ho FF, Kwong MH, Ho L, Zhou JHS, Lam KC, Liu JP, Zhang BT, Chung VCH. Methodological quality of systematic reviews on orally administered Chinese herbal medicine published in Chinese between 2021 and 2022: A cross-sectional study. J Integr Med. 2025; 23(5):492-501.
Cross-Sectional Studies ; Drugs, Chinese Herbal/administration & dosage* ; Systematic Reviews as Topic/standards* ; Humans ; China ; Administration, Oral ; Medicine, Chinese Traditional

Objective:To explore the changes of the Curative Care Expenditure(CCE)of outpatient and inpatient among local cancer patients and foreign cancer patients before and after the comprehensive reform of medical-pharmaceutical Separation and linkage of medical consumption in Beijing.Methods:According to A System of Health Accounts 2011(SHA 2011),multi-stage stratified sampling and multi-stage stratified sampling were used to analyze the CCE of cancer patients in Beijing from 2016 to 2019.Results:Compared with 2016,the proportion of drugs in the CCE of local residents in secondary hospitals and tertiary hospitals in 2019 decreased by 8.62 and 9.26 percentage points,respectively,and the proportion of drugs in the CCE of foreign patients in secondary hospitals and tertiary hospitals decreased by 5.60 and 5.66 percentage points,respectively.The consumption of local and nonlocal patients in tertiary hospitals decreased by 6.89 and 8.86 percentage points.In Beijing,the proportion of outpatient services in local secondary hospitals for patients increased from 30.32%to 35.09%,and the proportion of inpatient services increased from 43.25%to 52.27%.The proportion of in-patient services in tertiary hospitals for patients with external medical treatment increased to 91.91%after the comprehensive reform of linkage of medical consumption.Conclusion:The comprehensive reform on drug standard and consumption proportion are remarkable,and the flow of patients from different sources of cancer was optimized by comprehensive medical reform,but it is necessary to strengthen the role of primary medical institutions in cancer prevention and treatment and focus on the medical burden of non-local patients in Beijing.

OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate

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

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional