ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

Plant-derived exosome-like nanovesicles (PELNs), characterized by a natural lipid bilayer membrane, have rapidly emerged as a prominent research frontier in medicine owing to their unique biological properties and robust therapeutic potential. This review comprehensively examines the biological profiles, mechanistic functions, and recent engineering advancements of PELNs. In terms of composition, PELNs are uniquely enriched in plant-specific glycolipids, phosphatidylserine, secondary metabolites, and highly stable 2'-O-methylated miRNAs. This distinct molecular makeup endows them with exceptional biocompatibility, negligible immunogenicity, and the capacity for cross-species molecular communication. Mechanistically, PELNs demonstrate profound anti-inflammatory efficacy by suppressing the NF-κB and NLRP3 inflammasome pathways. They also serve as potent immune modulators, driving macrophage M1/M2 polarization and regulating T cell activity. Additionally, PELNs exhibit promising antitumor capabilities, targeting malignancies via reactive oxygen species (ROS) induction, TRAIL pathway activation, and tumor microenvironment remodeling. Crucially, the plant miRNAs encapsulated within PELNs remain highly stable in the gastrointestinal tract, allowing them to selectively alter gene expression in specific gut microbiota communities. This interaction deeply influences host immunity and metabolism, highlighting the vital role in cross-species regulation. Advancements in bioengineering have further expanded the clinical utility of PELNs. Targeted delivery efficiency can be significantly amplified via surface functionalization (e.g., folate and RGD sequences) and state-of-the-art drug loading technologies such as sonication and electroporation. Consequently, engineered PELNs surpass traditional synthetic nanocarriers in penetrating natural physiological barriers, particularly for oral and transdermal drug administration. Despite these advantages, clinical translation is currently hindered by the lack of standardized isolation protocols, challenges in scalable manufacturing, and the need for robust quality control frameworks. Looking forward, the integration of multi-omics approaches and AI-driven “molecular fingerprinting”—coupled with the design of synthetic biomimetic vesicles—will be instrumental in overcoming these bottlenecks, ultimately establishing PELNs as a next-generation platform for precision medicine and targeted nanotherapeutic delivery.

ObjectiveThe frequency difference limen (FDL) serves as a fundamental metric utilized for effectively quantifying the precise perceptual capabilities of the central auditory system. However, traditional measurement methods rely heavily on the active behavioral responses of subjects and are consequently highly susceptible to the negative influence of confounding subjective factors. Furthermore, existing research paradigms frequently employ uniform stimulus configurations that overlook critical individual perceptual differences. Based on brain-computer interface (BCI) technology, this comprehensive study aims to establish an objective and quantitative evaluation method for auditory frequency discrimination by systematically analyzing and decoding the specific neural responses elicited at the exact threshold state. MethodsWe designed a personalized rapid serial auditory presentation (RSAP) paradigm customized based on each individual’s precise FDL. A cohort of eleven healthy participants was recruited to evaluate the paradigm using pure-tone sequences at a baseline frequency of 4 000 Hz. This experimental paradigm simulates a realistic auditory perception environment through the continuous presentation of acoustic stimuli, thereby allowing for an in-depth investigation into the specific neural representations evoked by weak frequency deviations at the threshold state. Given that auditory stimulus-evoked response features exhibit complex and differentiated spatiotemporal distribution patterns across multiple frequency domains, this study further deeply integrates the cross-scale feature interaction module with the dynamic spatiotemporal attention allocation strategy, innovatively proposing the Multi-Scale Spatial-Temporal Dual Attention Network (MS-STAMNet). Specifically, the network constructs parallel processing branches with multiple receptive fields and introduces a dynamic adaptive weighting strategy to precisely localize core neural activity signals, further deeply integrating multi-scale information through cross-branch feature information interaction to achieve robust single-trial decoding of weak auditory evoked responses. ResultsThe comprehensive electrophysiological data analysis demonstrated that subtle auditory frequency deviation stimuli presented at the threshold level successfully elicited pronounced N2 and P3 event-related potential features, reflecting pre-attentive mismatch detection and subsequent cognitive evaluation, which were prominently distributed over the frontal, central, and temporal regions of the scalp. In the complex time-frequency domain, the extracted neural response characteristics exhibited distinct, statistically significant event-related synchronization within both the low-frequency δ and θ frequency bands, which was simultaneously accompanied by a widespread, prominent event-related desynchronization within the higher α band. A comparative analysis of model performance demonstrated that MS-STAMNet achieved an average unweighted average recall (UAR) of (69.67±6.12)% and area under the curve (AUC) of 0.761 8±0.07, significantly outperforming the established baseline models such as EEGNet and PLNet. Furthermore, a distinct dissociation phenomenon was verified between neural decoding and behavioral performance through regression analysis (R²=0.016, P=0.709), indicating that this model can effectively capture the implicit features of subtle frequency deviations, even when they fail to trigger explicit conscious responses. Additionally, attention weight visualization analysis further reveals the highly accurate focus of the network on key features concentrated over the bilateral temporal and fronto-parietal regions. ConclusionThis study systematically and comprehensively uncovers the multi-dimensional spatiotemporal evolutionary patterns of complex neural responses processing subtle acoustic variations under long-sequence threshold auditory stimulation. Concurrently, it verifies the efficacy and robustness of the proposed MS-STAMNet architecture in accurately deciphering weak, single-trial electroencephalogram signals amidst complex background noise. Ultimately, these neurophysiological and algorithmic findings lay a solid theoretical and methodological foundation for the objective and quantitative evaluation of individual auditory cognitive capabilities in clinical applications, transcending the fundamental limitations of traditional behavioral paradigms and providing robust technical support for future auditory research and related clinical assessments.

This study established a droplet digital PCR(ddPCR)EvaGreen assay and probe methods for Schistosoma japonicum detection,and evaluated their application in detecting early infections in the S.japonicum host oncomelania and mice.Primers and corresponding probes for both ddPCR methods were designed and synthesized,and plasmids containing target sequences were constructed.The sensitivity of the two methods was tested through detection of the corresponding plasmids,and infectious and mixed oncomelania genomic DNA.Their specificity was evaluated by the detection of genomic DNA of negative oncomelania,Schistosoma mansoni,Clonorchis sinensis,Spirometra mansoni,and S.japonicum(as a positive control).The ddPCR probe method was evaluated by detection of early infection of oncomelania exposed tomiracidium with various ratios and incubation times,and the early migration and distribution of cercaria or schistosomula in mouse hosts infected with 200 cercaria via abdominal skin contact.According to standard curves constructed through the detection of plasmid serial dilutions,the regression equation for the EvaGreen assay was y=-0.839 9x+7.050 9,with a correlation coefficient R2=0.988 1,and the regression equation for the probe method was y=-1.047 5x+7.255 1,with a correlation coefficient R2=0.999 8.The lowest limit of plasmid detection with the probe method was between 38.94 cp/μL and 194.74 cp/μL.Both methods successfully detected positive reactions in the genomic DNA samples of infectious oncomelania at concentrations above 0.002 ng/μL and in the genomic DNA of each group of oncomelania mixtures.No significant differences between probe methods were observed in the detection values in the control group and the genomic DNA of negative oncomelania,S.mansoni,C.sinensis,and S.mansoni.However,the detection value of genomic DNA of negative oncomelania(291 ng/μL)with the EvaGreen assay was(20.3±4.39)cp/μL,a value significantly higher than the(1.5±0.1)cp/μL observed in the control group.For detection of early infection in oncomelania,the probe method detected Schistosoma japonicum DNA after 30 s incubation at room temperature with a≥5∶1 ratio of miracidium to oncomelania;the detection value peaked after a short time(5 min),and the peak value showed a fold increase similar to the increase in the miracidium to oncomelania ratio.Detection of early stage infection in mice with the probe method revealed that the schistosomula entered the lungs on day 2 and the liver on day 4,and continually migrated within the organs with abundant blood supply(spleen,kidney,and brain)in the first 9 days;moreover,a tendency toward ectopic parasitism was observed in the heart and pancreas on day 9,and a constantly negative control level was observed in the testes.The ddPCR probe method was more accurate and specific than the EvaGreen assay in the detection of plasmids,and infectious and mixed oncomelania,and the latter showed non-specific reactions in negative oncomelania detection.In a practical application,the probe method was demonstrated to be sensitive,to effectively reflect the early infection of oncomelania,and to reveal schistosomula migration and distribution in multiple organs of infected mice.

Objective Radial artery occlusion(RAO)is one of the common complications following coronary intervention via the traditional radial artery approach.This study aims to evaluate the clinical effectiveness of retrograde recanalization of occluded radial arteries through the distal transradial approach(dTRA)approach.Methods A total of 35 patients with RAO admitted to the cardiovascular department of the Anhui Chest hospital between December 2022 and April 2024,who were scheduled to undergo coronary intervention and had attempted recanalization of RAO via dTRA approach were selected.The primary result was the success rate of recanalizing RAO via dTRA.The secondary results included factors influencing the failure of recanalization via dTRA,postoperative puncture complications,and the patency rate at the 3-month follow-up.Results This study divided the patients into a successful group(29 cases,82.9％)and a failed group(6 cases,17.1％)based on whether the distal radial artery was successfully opened and occluded.The proportion of smoking(100.00％vs.17.24％,P=0.040),history of diabetes(100.00％vs.10.34％,P=0.025),and chronic total occlusion of coronary artery(83.33％vs.17.24％,P=0.030)in the failure group were higher than those in the success group,and the difference was statistically significant.The application rate of balloon tracking assisted technology in the failed group(16.67％vs.58.62％,P=0.045),and the diameter of the radial artery at 3 days after surgery[(1.63±0.13)mm vs.(2.13±0.32)mm,P=0.021]and the peak radial artery blood flow velocity at 3 days postoperatively[(0.10±0.78)m/s vs.(0.50±0.13)m/s,P＜0.001]were all lower in the successful group,and the differences were statistically significant.Logistic regression analysis 3 days after surgery showed that chronic complete occlusion of the coronary artery was an independent risk factor for surgical opening failure(OR 0.042,95％CI 0.004-0.438,P=0.008).After 3 months of follow-up,the patency rate of the successful group was 55.2％.Conclusions Retrograde recanalization of RAO via dTRA is safe and feasible,but its long-term patency rate is not high.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

To investigate the anti-atherosclerotic effects of dietary hesperidin and naringin on ather-osclerosis in rabbits.Twenty-four adult healthy male New Zealand Large White rabbits were ran-domly assigned to four groups based on one factor:control(Con),model(Mod),hesperidin(HP),and naringenin(NG),each containing six rabbits and housed in solitary cages.During the experi-mental period,the control group received normal feed;the model group was fed high-fat for 30 d to establish the atherosclerosis,(AS)model and continued to be fed high-fat feed;the hesperidin and naringenin groups were fed high-fat for 30 d and then underwent AS modeling,and at a later stage,150 mg of hesperidin(or naringenin)was added to the diets at a rate of 1.5 mg per kg of di-et,respectively,for 30 d.Relative body quality,blood lipids,oxidation,and inflammatory factor lev-els were all assessed.At the end of the test period,the test rabbits were sacrificed to obtain the common carotid artery for histopathological section HE staining,Oil red O staining,and Sirius red staining in order to observe vascular tissue structure,lipid and inflammatory cell infiltration,and e-lastic plate and elastic fiber damage.The results indicated that the relative body quality of the mod-el,HP and NG groups increased rapidly,and the difference with the control group within the same period was highly significant(P＜0.01);The HP and NG interventions significantly decreased to-tal cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C)levels(P＜0.01),while also leading to a significant increase in high-density lipoprotein cholesterol(HDL-C)levels(P＜0.01);MDA levels exhibited a significant decrease(P＜0.01),while SOD levels showed a notable in-crease(P＜0.01)following the HP and NG interventions;After HP and NG interventions,TNF-α and IL-1 were regressed(P＜0.01)and IL-10 was significantly elevated(P＜0.01);Compared with the control group,the model group showed approximately 41.8 and 2.5 fold thickening of the maximal endo-medial membrane,respectively,and the HP and NG interventions showed approxi-mately 13 and 15 fold thickening of the maximal endo-medial membrane,and both of the maximal medial membranes thickened by approximately 1.4 fold;Staining of pathological sections showed that HP and NG intervened to significantly reduce inflammatory cell infiltration,deposition of lipid components,slight thickening of the endothelium,and intact fibroblastic components.The results showed that the addition of HP and NG to diets could regulate blood lipids and exert anti-inflam-matory and antioxidant effects by inhibiting the expression of inflammatory factors and oxidizing factors,showing significant anti-AS effects,and the two effects were comparable.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

This study established a droplet digital PCR(ddPCR)EvaGreen assay and probe methods for Schistosoma japonicum detection,and evaluated their application in detecting early infections in the S.japonicum host oncomelania and mice.Primers and corresponding probes for both ddPCR methods were designed and synthesized,and plasmids containing target sequences were constructed.The sensitivity of the two methods was tested through detection of the corresponding plasmids,and infectious and mixed oncomelania genomic DNA.Their specificity was evaluated by the detection of genomic DNA of negative oncomelania,Schistosoma mansoni,Clonorchis sinensis,Spirometra mansoni,and S.japonicum(as a positive control).The ddPCR probe method was evaluated by detection of early infection of oncomelania exposed tomiracidium with various ratios and incubation times,and the early migration and distribution of cercaria or schistosomula in mouse hosts infected with 200 cercaria via abdominal skin contact.According to standard curves constructed through the detection of plasmid serial dilutions,the regression equation for the EvaGreen assay was y=-0.839 9x+7.050 9,with a correlation coefficient R2=0.988 1,and the regression equation for the probe method was y=-1.047 5x+7.255 1,with a correlation coefficient R2=0.999 8.The lowest limit of plasmid detection with the probe method was between 38.94 cp/μL and 194.74 cp/μL.Both methods successfully detected positive reactions in the genomic DNA samples of infectious oncomelania at concentrations above 0.002 ng/μL and in the genomic DNA of each group of oncomelania mixtures.No significant differences between probe methods were observed in the detection values in the control group and the genomic DNA of negative oncomelania,S.mansoni,C.sinensis,and S.mansoni.However,the detection value of genomic DNA of negative oncomelania(291 ng/μL)with the EvaGreen assay was(20.3±4.39)cp/μL,a value significantly higher than the(1.5±0.1)cp/μL observed in the control group.For detection of early infection in oncomelania,the probe method detected Schistosoma japonicum DNA after 30 s incubation at room temperature with a≥5∶1 ratio of miracidium to oncomelania;the detection value peaked after a short time(5 min),and the peak value showed a fold increase similar to the increase in the miracidium to oncomelania ratio.Detection of early stage infection in mice with the probe method revealed that the schistosomula entered the lungs on day 2 and the liver on day 4,and continually migrated within the organs with abundant blood supply(spleen,kidney,and brain)in the first 9 days;moreover,a tendency toward ectopic parasitism was observed in the heart and pancreas on day 9,and a constantly negative control level was observed in the testes.The ddPCR probe method was more accurate and specific than the EvaGreen assay in the detection of plasmids,and infectious and mixed oncomelania,and the latter showed non-specific reactions in negative oncomelania detection.In a practical application,the probe method was demonstrated to be sensitive,to effectively reflect the early infection of oncomelania,and to reveal schistosomula migration and distribution in multiple organs of infected mice.