ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P0.01）， significantly decreased fractional shortening （FS） （P0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P0.05， P0.01）， significantly increased FS （P0.05， P0.01）， significantly decreased LVDD and LVDS （P0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P0.01）， and significantly decreased BV at high， medium， and low shear rates （P0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P0.05， P0.01）， while HDL levels were significantly decreased （P0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P0.05， P0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P0.05， P0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P0.05， P0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P<0.01）， significantly decreased fractional shortening （FS） （P<0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P<0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P<0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P<0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P<0.05， P<0.01）， significantly increased FS （P<0.05， P<0.01）， significantly decreased LVDD and LVDS （P<0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P<0.01）， and significantly decreased BV at high， medium， and low shear rates （P<0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P<0.05， P<0.01）， while HDL levels were significantly decreased （P<0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P<0.05， P<0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P<0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P<0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P<0.05， P<0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P<0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P<0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P<0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P<0.05， P<0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

Objective Magnetic resonance angiography(MRA)offers a non-invasive and radiation-free advantage in detecting and diagnosing intracranial artery stenosis;however,it is associated with high equipment costs.Transcranial color-coded Duplex ultrasound(TCCD)combined with contrast-enhanced ultrasound(CEUS)presents advantages such as non-invasiveness,real-time dynamic monitoring,and low cost.Nevertheless,there were no reports comparing the sensitivity,specificity,diagnostic agreement with MRA,or health economic evaluation of TCCD combined with CEUS for detecting major intracranial artery stenosis.Methods From April 2023 to August 2024,a total of 55 patients suspected of having intracranial artery stenosis or occlusion were recruited at Beijing Tiantan Hospital,Capital Medical University.Both TCCD combined with CEUS and MRA were performed to evaluate the degree of stenosis in the terminal segment of the internal carotid artery,M1 and M2 segments of the middle cerebral artery,A1 and A2 segments of the anterior cerebral artery,P1 and P2 segments of the posterior cerebral artery,and the V4 segment of the vertebral artery.Intracranial artery stenosis was categorized into three groups:normal/mild,moderate,and severe/occlusion.Sensitivity,specificity,and consistency between the two methods were calculated.The Wilcoxon signed-rank test was used to compare the differences in examination costs and diagnostic time.Results Fifty-five high-risk patients(110 cerebral hemispheres in total)with suspected cerebrovascular stenosis were included(median age:46 years;69.0%male).TCCD combined with CEUS and MRA were performed simultaneously.TCCD combined with CEUS showed high sensitivity and specificity in diagnosing intracranial artery stenosis,with good consistency compared to MRA.The highest diagnostic consistency was observed in the M2 segment(Kappa=0.704)and A2 segment(Kappa=0.650),while the M1 segment showed moderate consistency(Kappa=0.569).The average cost of TCCD combined with CEUS was 240 CNY with a diagnostic duration of 21 min,compared to 722 CNY and 287 min for MRA(P<0.001,effect sizer=0.89-0.91).Conclusion Compared to MRA,TCCD combined with CEUS demonstrates higher consistency in screening for stenosis in the M2 segment of the middle cerebral artery and the A2 segment of the anterior cerebral artery.It is also more cost-effective.However,MRA has advantages in assessing deep intracranial vessels.A synergistic use of both methods can optimize the allocation of diagnostic resources for intracranial artery stenosis.It is recommended that primary healthcare institutions adopt TCCD as the initial screening tool,and,with standardized training and technical upgrades,combine it with CEUS.Complex cases should be referred for detailed evaluation by using MRA.

Objective To identify potential drug target genes associated with idiopathic pulmonary fibrosis(IPF)and predict therapeutic candidates using a two-sample Mendelian randomization(MR)approach across the druggable genome.Methods Druggable genome data from the DGIdb database and Finan were integrated to identify overlapping genes.A two-sample MR analysis was performed to infer causal relationships between genes and IPF.Functional enrichment analyses,including Gene Ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG),were conducted to explore biological pathways.Drug-target interactions were predicted via DSigDB database screening,followed by molecular docking simulations to evaluate binding affinities.Results Among the 2588 overlapping druggable genes,thirty exhibited significant causal associations with IPF(P＜0.05).Four hub genes(NOD2,LATS2,LTA,and TCF7L2)were enriched in IPF-related pathways,notably Hippo and TNF signaling.Six potential therapeutics were identified:oxyphenbutazone,moexipril,α-galactosylceramide,GSK429286A,CGP74514A,and JW-7-24-1.Molecular docking confirmed strong binding affinities between these drugs and their targets.Conclusion This study has identified thirty druggable gene targets and six candidate drugs for IPF.The enrichment of hub genes in key pathways and validated drug-target interactions provide insights into IPF therapies.

Objective Magnetic resonance angiography(MRA)offers a non-invasive and radiation-free advantage in detecting and diagnosing intracranial artery stenosis;however,it is associated with high equipment costs.Transcranial color-coded Duplex ultrasound(TCCD)combined with contrast-enhanced ultrasound(CEUS)presents advantages such as non-invasiveness,real-time dynamic monitoring,and low cost.Nevertheless,there were no reports comparing the sensitivity,specificity,diagnostic agreement with MRA,or health economic evaluation of TCCD combined with CEUS for detecting major intracranial artery stenosis.Methods From April 2023 to August 2024,a total of 55 patients suspected of having intracranial artery stenosis or occlusion were recruited at Beijing Tiantan Hospital,Capital Medical University.Both TCCD combined with CEUS and MRA were performed to evaluate the degree of stenosis in the terminal segment of the internal carotid artery,M1 and M2 segments of the middle cerebral artery,A1 and A2 segments of the anterior cerebral artery,P1 and P2 segments of the posterior cerebral artery,and the V4 segment of the vertebral artery.Intracranial artery stenosis was categorized into three groups:normal/mild,moderate,and severe/occlusion.Sensitivity,specificity,and consistency between the two methods were calculated.The Wilcoxon signed-rank test was used to compare the differences in examination costs and diagnostic time.Results Fifty-five high-risk patients(110 cerebral hemispheres in total)with suspected cerebrovascular stenosis were included(median age:46 years;69.0%male).TCCD combined with CEUS and MRA were performed simultaneously.TCCD combined with CEUS showed high sensitivity and specificity in diagnosing intracranial artery stenosis,with good consistency compared to MRA.The highest diagnostic consistency was observed in the M2 segment(Kappa=0.704)and A2 segment(Kappa=0.650),while the M1 segment showed moderate consistency(Kappa=0.569).The average cost of TCCD combined with CEUS was 240 CNY with a diagnostic duration of 21 min,compared to 722 CNY and 287 min for MRA(P<0.001,effect sizer=0.89-0.91).Conclusion Compared to MRA,TCCD combined with CEUS demonstrates higher consistency in screening for stenosis in the M2 segment of the middle cerebral artery and the A2 segment of the anterior cerebral artery.It is also more cost-effective.However,MRA has advantages in assessing deep intracranial vessels.A synergistic use of both methods can optimize the allocation of diagnostic resources for intracranial artery stenosis.It is recommended that primary healthcare institutions adopt TCCD as the initial screening tool,and,with standardized training and technical upgrades,combine it with CEUS.Complex cases should be referred for detailed evaluation by using MRA.

Objective To investigate extended high-frequency hearing in young adults and to analyse its char-acteristics.Methods A total of 230 freshmen(101 males and 129 females,aged 17-19 years old)from the class of 2023 at the Air Force Medical University underwent audiometric tests,including acoustic impedance,conventional frequency and extended high-frequency audiometry,and distortion product otoacoustic emissions(DPOAE).Ac-cording to the results of extended high-frequency audiometry,the students were divided into normal and abnormal groups,and the hearing thresholds at conventional frequencies were compared between the two groups.Results Of the 230 students,47.83％(110/230)showed abnormal extended high-frequency hearing.The hearing thresholds of the right ear were 1 to 3 dB higher than those of the left ear at most frequencies.The hearing thresholds of the ab-normal group were higher than those of the normal group in the conventional frequencies(P＜0.05).The difference in extended high-frequency thresholds between the two groups increased with higher frequency.Conclusion Ex-tended high-frequency hearing loss occurs earlier,and has a higher prevalence in young adults,and right ear hearing is worse than that of left ear.Extended high-frequency audiometry can be used as a predictive tool for detecting con-ventional frequency hearing loss.

Clinical chemotherapy for prostate cancer is still compromised by high treatment thresholds and severe off-target toxicity of drugs. Given the limited progress in improving therapeutic outcomes and reducing toxicity with the existing toolbox, efforts to broaden the chemotherapeutic window are highly desired. Here, we discover that gossypol (GSP, a natural compound) dramatically enhances the chemosensitivity of cabazitaxel (CTX), even at previously ineffective concentrations. Based on this interesting finding, we exploit a carrier-free chemotherapeutic nano-booster for prostate cancer treatment, which is molecularly co-assembled by GSP and cabazitaxel (CTX). GSP not only readily forms nanoassembly with CTX, but also functions as a chemotherapeutic enhancer that unlocks an ultra-low-dose chemotherapeutic window. Not only that, precise dual-drug nanoassembly confers CTX a significantly larger maximum tolerable dose. As expected, the nano-booster exerts striking therapeutic benefits in mouse prostate tumor xenograft models. This study advances chemotherapeutic window expansion and self-sensitized chemotherapy toward clinical applicability.

Objective To evaluate the clinical efficacy of Shenshi Jiangzhuo Formula(composed of Poria,Atractylodis Rhizoma,Magnoliae Officinalis Cortex,Pinelliae Rhizoma Praeparatum,Aurantii Fructus Immaturus,Arecae Semen,Talcum,Tetrapanacis Medulla,Notoginseng Radix et Rhizoma,Paeoniae Radix Rubra,Rubiae Radix et Rhizoma,Broussonetiae Fructus,etc.)in treating non-alcoholic fatty liver disease(NAFLD)with phlegm blended with stasis syndrome.Methods A total of 76 NAFLD patients with phlegm blended with stasis syndrome from the Seventh School of Clinical Medicine,Guangzhou University of Chinese Medicine(Shenzhen Bao'an Traditional Chinese Medicine Hospital)were enrolled between February 2024 and December 2024.The patients were randomly assigned(via random number table)to either the trial group(n=38,treated with Silibinin Meglumine Tablets plus Shenshi Jiangzhuo Formula)or the control group(n=38,treated with Silibinin Meglumine Tablets alone)for 8 weeks.The changes in liver controlled attenuation parameter(CAP),liver function markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT)],lipid profiles[triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)],and traditional Chinese medicine(TCM)syndrome scores were observed before and after treatment.Clinical efficacy and safety were evaluated.Results(1)One case dropped out from each group during the study and 37 cases in each group were included for final statistics.(2)After 8 weeks of treatment,the overall response rate in the trial group was 94.59％(35/37),compared with 62.16％(23/37)in the control group.Intergroup comparison revealed that the trial group demonstrated significantly superior overall therapeutic efficacy(by rank-sum test)and overall response rate(by chi-square test)compared with the control group(P＜0.01).(3)Both groups showed improved CAP values after treatment,and the trial group demonstrated significantly greater improvement compared to the control group(P＜0.01).(4)Post-treatment improvements in alanine aminotransferase(ALT),aspartate aminotransferase(AST),and gamma-glutamyl transferase(GGT)were improved in both groups(P＜0.01),with the trial group showing significantly superior improvements(P＜0.05 or P＜0.01).(5)Triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)were improved in both groups after treatment,and the trial group exhibited significantly better outcomes(P＜0.01).(6)Both groups presented reduced TCM syndrome scores after treatment,and the trial group showed greater reduction(P＜0.01).(7)No significant adverse recations were observed in both groups,showing high safety.Conclusion Integrative therapy with Shenshi Jiangzhuo Formula exerts certain effects in improving CAP values,liver function,lipid metabolism,and TCM symptoms in NAFLD patients with phlegm blended with stasis syndrome,demonstrating robust clinical value.

Objective To investigate the early dynamic changes of biomarkers associated with capillary leak syndrome(CLS)in patients with severe acute pancreatitis(SAP)and their correlation with multiple organ failure(MOF).Methods A total of 171 SAP patients admitted to the West China Centre of Excellence for Pancreatitis,West China Hospital,Sichuan University between September 1,2019 and December 31,2020 were enrolled for this study.The patients were divided into MOF and non-MOF groups based on the occurrence of MOF in the first 5 days of hospitalization,and were further divided into subgroups based on the presence of moderate-to-severe intra-abdominal hypertension(IAH).We performed dynamic monitoring of the blood biomarkers(hematocrit[HCT].blood urea nitrogen[BUN].and creatinine[Cr]),plasma proteins(albumin[Alb].total protein[TP].and non-albumin plasma proteins[NAPP]),and intra-abdominal pressure.Trends in these indicators across groups were analyzed comprehensively.Results No significant differences in baseline data between the two groups were observed.The baseline data of the 2 groups were comparable.The MOF group had significantly higher rates of persistent systemic inflammatory response syndrome(SIRS)lasting 48 hours(91.3％vs.71.8％),ICU admission(70.4％vs.17.6％),and length-of-stay([32±17.7]days vs.[19.0±12.2]days)compared to those of the non-MOF group(P＜0.05).The incidences of respiratory,circulatory,and renal failures were higher in the MOF group than those in the non-MOF group,showing significant differences in circulatory failure(69％vs.3.5％)and renal failure(65.5％vs.3.5％)(P＜0.05).In the first 5 days of hospitalization,the MOF group showed significantly elevated BUN and Cr levels,while Alb and TP levels dropped rapidly upon admission and then gradually recovered.The NAPP level of the MOF group continued to decrease after admission,and on the third day after admission,the NAPP level was lower than that of the Non-MOF group,showing statistically significant difference(P＜0.001).The Alb/NAPP ratio of the MOF group decreased significantly on day 1 and then rapidly increased,showing significant differences between the groups on days 3 and 4(P=0.001).Subgroup analysis of MOF patients with moderate-to-severe IAH revealed similar trends in the dynamic changes and the overall changes in the indicators,and the difference was even more pronounced.The mixed linear model showed that the average levels of HCT,BUN,Alb/NAPP,and Alb/TP were higher and increased over time in the MOF combined with IAP subgroup(P＜0.001).Conclusion The CLS model of SAP patients is validated,confirming that CLS is a key factor in the progression from SIRS to MOF.The loss of NAPP is an early and important indicator of CLS persistence and progression to MOF.Additionally,moderate-to-severe IAH accelerates the deterioration of MOF.These findings provide valuable insights into the potential mechanisms of MOF and warrant further validation through large-scale prospective studies.

Objective To evaluate the clinical efficacy of stellate ganglion block(SGB)combined with intranasal dexmedetomidine for the treatment of insomnia.Methods A total of 64 patients aged 18 to 75 with insom-nia were randomly assigned to either the experimental group(DS group)or the control group(S group).The S group received SGB treatment for 14 consecutive days,whereas the DS group received an additional intranasal dexmedeto-midine spray at a dose of 100 μg,administered 30 minutes before bedtime on days 1 through 6,in conjunction with SGB.We measured and recorded the Pittsburgh Sleep Quality Index(PSQI),Self-Rating Depression Scale(SDS),Self-Rating Anxiety Scale(SAS)scores,and Psychomotor Vigilance Test(PVT)results for both groups at three time points:baseline(T1),the day after treatment(T2),and one month after treatment(T3).Results Intra-group Com-parison:In both the DS and S groups,PSQI scores and dimensionspecific scores at T2 and T3 were significantly lower compared to T1(P<0.05).SAS and SDS scores in both groups showed a significant reduction at T3 compared to T1 and T2(P<0.05),while PVT results exhibited no significant changes(P>0.05).Inter-group Comparison:The PSQI scores and dimensionspecific scores in the DS group at T2(8.44±2.99)and T3(8.22±2.60)were significantly lower than those in the S group at T2(10.88±2.56)and T3(10.88±2.84)(P<0.05).However,no significant differences were observed in SDS and SAS scores between the DS and S groups at T2 and T3(P>0.05).Conclusion Compared to standalone SGB,the combination of SGB with intranasal dexmedetomidine significantly enhances sleep quality in patients with insomnia,while not impacting their levels of anxiety,depression,or alertness.