The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified SmIAA7 which is potentially associated with Salvia miltiorrhiza leaf development through comparatively analyzed the transcriptome data from different pinnate leaves. SmIAA7 was successfully isolated from S. miltiorrhiza using the specific primers. Then subsequent bioinformatic analysis, prokaryotic expression and purification, subcellular localization, and induction expression analysis under auxin and abiotic stress were performed. The full-length of SmIAA7 contained an ORF of 684 bp encoding a protein of 227 amino acid with a molecular weight of 25.3 kD. Conserved domain analysis showed that SmIAA7 contains the conserved Aux_IAA domain (pfam02309). Sequence analysis and phylogenetic tree analysis results indicated SmIAA7 was phylogenetically close to IAA7 and IAA14 from other plants, suggesting SmIAA7 involved in plant growth and development as well as response to environmental stresses. The prokaryotic expression vector pET28a-SmIAA7 was constructed and SmIAA7 recombinant protein was successfully expressed in E. coli Rosetta (DE3) strain. Subcellular localization experiment demonstrated that SmIAA7 localized in the nucleus of plant cells. Real-time fluorescence quantitative PCR results showed that the expression level of SmIAA7 was upregulated in response to auxin. Drought, low temperature, and salt stress significantly increased the transcript level of SmIAA7 gene. This study lays a foundation for further elucidating the role of SmIAA7 in leaf development, signal transduction, and stress defense in S. miltiorrhiza.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

OBJECTIVE: To evaluate the safety and clinical therapeutic effect of in-line mechanical in-exsufflation to assist sputum clearance in patients with invasive mechanical ventilation. METHODS: A prospective observational study was conducted at the department of critical care medicine, the First Affiliated Hospital of Sun Yat-sen University from April 2022 to May 2023. Patients who were invasively ventilated and treated with in-line mechanical in-exsufflation to assist sputum clearance were enrolled. Baseline data were collected. Sputum viscosity, oxygenation index, parameters of ventilatory function and respiratory mechanics, clinical pulmonary infection score (CPIS) and vital signs before and after day 1, 2, 3, 5, 7 of use of the in-line mechanical in-exsufflation were assessed and recorded. Statistical analyses were performed by using generalized estimating equation (GEE). RESULTS: A total of 13 invasively ventilated patients using in-line mechanical in-exsufflation were included, all of whom were male and had respiratory failure, with the main cause being cervical spinal cord injury/high-level paraplegia (38.46%). Before the use of the in-line mechanical in-exsufflation, the proportion of patients with sputum viscosity of grade III was 38.46% (5/13) and decreased to 22.22% (2/9) 7 days after treatment with in-line mechanical in-exsufflation. With the prolonged use of the in-line mechanical in-exsufflation, the patients' CPIS scores tended to decrease significantly, with a mean decrease of 0.5 points per day (P < 0.01). Oxygenation improved significantly, with the oxygenation index (PaO₂/FiO₂) increasing by a mean of 23.3 mmHg (1 mmHg ≈ 0.133 kPa) per day and the arterial partial pressure of oxygen increasing by a mean of 12.6 mmHg per day (both P < 0.01). Compared to baseline, the respiratory mechanics of the patients improved significantly 7 days after in-line mechanical in-exsufflation use, with a significant increase in the compliance of respiratory system (Cst) [mL/cmH₂O (1 cmH₂O ≈ 0.098 kPa): 55.6 (50.0, 58.0) vs. 40.9 (37.5, 50.0), P < 0.01], and both the airway resistance and driving pressure (DP) were significantly decreased [airway resistance (cmH₂O×L^-1×s^-1): 9.6 (6.9, 10.5) vs. 12.0 (10.0, 13.0), DP (cmH₂O): 9.0 (9.0, 12.0) vs. 11.0 (10.0, 15.0), both P < 0.01]. At the same time, no new lung collapse was observed during the treatment period. No significant discomfort was reported by patients, and there were no substantial changes in heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure before and after the in-line mechanical in-exsufflation treatment. CONCLUSIONS The combined use of the in-line mechanical in-exsufflation to assist sputum clearance in patients on invasive mechanical ventilation can effectively improve sputum characteristics, oxygenation and respiratory mechanics. The in-line mechanical in-exsufflation was well tolerated by the patients, with no treatment-related adverse events, which demonstrated its effectiveness and safety.
Humans ; Prospective Studies ; Respiration, Artificial/methods* ; Respiratory Insufficiency/therapy* ; Sputum

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective:To discuss the effect of acupuncture on the differentiation and apoptosis of quadriceps muscle satellite cells in model rats with knee osteoarthritis(KOA),and to clarify its related mechanism.Methods:A total of 40 SPF-grade rats were selected and randomly divided into control group,model group,celecoxib group,and acupuncture group,with 10 rats in each group.The rats in control group only underwent joint cavity incision followed by suturing,while the rats in model group,celecoxib group,and acupuncture group were used to replicate the KOA models.The maximum circumference of the femoral segment of the affected limb,rat body mass,and quadriceps wet weight of the rats in various groups were measured;the quadriceps wet weight maintenance rate and quadriceps wet weight/body mass ratio of the rats in various groups were calculated.HE staining was used to observe the pathomorphology of articular cartilage and quadriceps muscle tissue of the rats in various groups;terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL)method was used to detect the apoptosis indexes in articular cartilage and quadriceps muscle tissue of the rats in various groups;immunofluorescence method was used to detect the protein expression levels of interleukin-6(IL-6),Janus kinase(JAK),and signal transducer and activator of transcription 3(STAT3)in quadriceps muscle tissue of the rats in various groups;Western blotting method was used to detect the expression levels of IL-6/JAK/STAT3 signaling pathway proteins,and muscle satellite cells,and apoptosis-related proteins in quadriceps muscle tissue of the rats in various groups.Results:Compared with control group,the affected hind limb circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight/body mass ratio of the rats in model group were significantly decreased(P<0.05);compared with model group,the affected hind limb circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight/body mass ratio of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05);compared with celecoxib group,the affected hind limb circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight/body mass ratio of the rats in acupuncture group were significantly increased(P<0.05).The HE staining results showed that the knee articular cartilage of the rats in control group remained intact,chondrocytes were aggregated and horizontally arranged with smooth edges,and quadriceps muscle cells were long cylindrical,orderly arranged,and regular in shape;in model group,the knee articular cartilage was thinner with rough edges,reduced number of cartilage layers,and disordered arrangement,and the quadriceps muscle fibers were disorganized,with some muscle fiber dissolution and muscle cell membrane damage,accompanied by muscle fiber fragments and a large amount of inflammatory exudate;in celecoxib group,the morphology of knee articular cartilage was generally normal,occasionally with irregular cartilage arrangement and reduced thickness,sporadically visible necrotic chondrocytes,quadriceps muscle fibers and sarcolemma were relatively intact,new muscle fibers appeared,some muscle fiber edges were blurred,accompanied by a small amount of cell debris and mild inflammatory infiltration;in acupuncture group,the knee articular cartilage structure remained intact with smooth edges,occasionally rough edges,and chondrocytes were aggregated and orderly arranged.The TUNEL assay results showed that compared with control group,the apoptosis indexes in articular cartilage and quadriceps muscle tissue of the rats in model group were significantly increased(P<0.05);compared with model group,the apoptosis indexes in articular cartilage and quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly decreased(P<0.05);compared with celecoxib group,the apoptosis index in articular cartilage and quadriceps muscle tissue of the rats in acupuncture group were significantly decreased(P<0.05).The immunofluorescence assay results showed that compared with control group,the expression levels of IL-6,JAK,and STAT3 proteins in quadriceps muscle tissue of the rats in model group were significantly decreased(P<0.05);compared with model group,the expression levels of IL-6,JAK,and STAT3 proteins in quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05);compared with celecoxib group,the expression levels of IL-6,JAK,and STAT3 proteins in quadriceps muscle tissue of the rats in acupuncture group were significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of IL-6,JAK,STAT3,paired box transcription factor 7(Pax7),Desmin,Myosin,and Myogenin proteins in quadriceps muscle tissue of the rats in model group were significantly decreased(P<0.05);compared with model group,the expression levels of IL-6,JAK,STAT3,Pax7,Desmin,Myosin,and Myogenin proteins in quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05);compared with celecoxib group,the expression levels of IL-6,JAK,STAT3,Pax7,Desmin,Myosin,and Myogenin proteins in quadriceps muscle tissue of the rats in acupuncture group were significantly increased(P<0.05).Compared with control group,the expression levels of B-cell lymphoma 2(Bcl-2),B-cell lymphoma-xl(Bcl-xl),and myeloid cell leukemia 1(MCL1)proteins in quadriceps muscle tissue in model group were significantly decreased(P<0.05),and the expression levels of Bcl-2-associated X protein(Bax)and cysteinyl aspartate specific proteinase-3(Caspase-3)proteins were significantly increased(P<0.05);compared with model group,the expression levels of Bcl-2,Bcl-xl,and MCL1 proteins in quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05),and the expression levels of Bax and Caspase-3 proteins were significantly decreased(P<0.05);compared with celecoxib group,the expression levels of Bcl-2,Bcl-xl,and MCL1 proteins in quadriceps muscle tissue of the rats in acupuncture group were significantly increased(P<0.05),and the expression levels of Bax and Caspase-3 proteins were significantly decreased(P<0.05).Conclusion:Acupuncture can promote the differentiation of quadriceps muscle satellite cells and inhibit muscle cell apoptosis in the model rats with KOA,and the mechanism may be related to the up-regulation of expressions of IL-6,JAK,and STAT3 proteins in the quadriceps muscle tissue.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

The uniqueness of the location of large general hospitals in urban areas determines that the contradiction between space constraints and medical expansion has become a problem of management bottleneck.The situation that expert visits are too concentrated on a certain working day morning has been significantly improved by carrying out peak load shifting in the visiting arrangements and visiting units of large general hospitals through the Total Quality Management theory and continuous improvement of work mode,greatly alleviating public transportation congestion around the hospital.Through the internal construction of the quality of outpatient clinics,it can effectively improve the patients'sense of access to health care.

The uniqueness of the location of large general hospitals in urban areas determines that the contradiction between space constraints and medical expansion has become a problem of management bottleneck.The situation that expert visits are too concentrated on a certain working day morning has been significantly improved by carrying out peak load shifting in the visiting arrangements and visiting units of large general hospitals through the Total Quality Management theory and continuous improvement of work mode,greatly alleviating public transportation congestion around the hospital.Through the internal construction of the quality of outpatient clinics,it can effectively improve the patients'sense of access to health care.