ObjectiveTo investigate the mechanisms of Tongmai Yangxin pills （TMYX） and Tongxinluo capsules （TXL） in treating no-reflow （NR） after myocardial ischemia and reperfusion following the concept of treating the same disease with different methods， based on integrative pharmacology and experimental validation. MethodsEighty 8-week-old SPF-grade SD rats were randomly assigned into four groups （n=20）： sham operation， NR， TMYX （4 g·kg^-1）， and TXL （2 mg·kg^-1）. A rat model of myocardial ischemia-reperfusion no-reflow was established by in-situ ligation of the left anterior descending coronary artery. Gastric gavage was first performed 4 h after the operation， and samples were collected on day 7. Thioflavin S staining was used to observe the NR area in rat myocardium. Echocardiography was performed to examine the cardiac function. Hematoxylin-eosin （HE） staining was conducted to observe the pathological changes of the myocardial tissue. An automatic biochemical analyzer was adopted to measure myocardial enzyme activity. Then， integrated pharmacology was applied for Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Finally， Western blot was employed to quantify the protein levels of key targets in the myocardial tissue， including soluble guanylyl cyclase （sGC）， cyclic guanosine monophosphate （cGMP）/dependent protein kinase （PKG）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， and hypoxia-inducible factor-1α （HIF-1α）. ResultsCompared with the sham operation group， the NR group showed increased NR area of myocardium， decreased left ventricular ejection fraction （EF）， left ventricular fractional shortening （FS）， left ventricular outflow tract peak velocity （LVOT Peak）， and left ventricular stroke volume （LVSV） （P<0.01）， fractured and disordered myocardial fibers as well as inflammatory cell infiltration in the myocardial tissue， enhanced activities of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in the myocardial tissue （P<0.01）， and downregulated protein levels of sGC， PKG， phosphorylated （p）-PI3K （Tyr458）， and p-Akt （Tyr315） in the myocardial tissue （P<0.05， P<0.01）. The expression level of HIF-1α protein showed a downward trend. Compared with the NR group， the TMYX group and TXL group exhibited a decreasing trend in myocardial NR area， EF， FS， and LVOT Peak significantly increased （P<0.05， P<0.01）， LVSV showed an upward trend， ameliorated myocardial pathological morphology and inflammatory infiltration， reductions in CK， CK-MB， and LDH activities （P<0.05， P<0.01）， and upregulated protein levels of sGC， PKG， p-PI3K （Tyr458） in myocardial tissue （P<0.05， P<0.01）， the protein expressions of p-Akt （Tyr315） and HIF-1α showed an upward trend. A comparison of the therapeutic effects between the two compound prescriptions showed that TMYX tended to exert a better effect in restoring cardiac function and protecting cardiac structure in NR rats， whereas TXL was more effective in reducing myocardial NR area and lowering myocardial enzyme activities in NR rats. Integrative pharmacology analysis combined with experimental verification demonstrated that both TMYX and TXL could alleviate NR through the following mechanisms： activating the cyclic cGMP/PKG signaling pathway to regulate vascular tone， activating the PI3K/Akt signaling pathway to dilate blood vessels， and activating the HIF-1 signaling pathway to inhibit oxidative stress. However， TMYX had an advantage in activating the cGMP/PKG pathway， while TXL was superior in activating the PI3K/Akt pathway. The two compound prescriptions exerted comparable effects on the HIF-1 signaling pathway， which might serve as their common therapeutic pathway. ConclusionBoth TMYX and TXL could alleviate NR damage. TMYX exerts its protective effect against NR mainly by activating the cGMP/PKG signaling pathway， while TXL exerts its effect mainly through the PI3K/Akt pathway. The HIF-1α signaling pathway may be a common pathway for the two compound prescriptions to exert their protective effects against NR. This study reveals the similarities and differences between TMYX and TXL in the treatment effect and mechanism for NR， providing an experimental basis and a theoretical basis for better clinical application of the two compound prescriptions.

Objective To explore the mechanism of the intervention effect of Qizhu Xiaozheng Fang(QZXZF),a representative prescription of Yiqi Jianpi Jiedu(replenishing qi,strengthening spleen,and removing toxicity),in treating HBx-mediated liver cancer stem cells(LCSCs).Methods The Kaplan-Meier survival analysis was used to investigate the effects of Yiqi Jianpi Jiedu on the prognosis of patients with HBV-HCC.The network pharmacology method was utilized to predict the targets and pathways of QZXZF in treating HBx-related LCSCs(HBx-LCSCs).HBx-LCSCs cells were screened by stably transfecting HBx and serum-free culture.The therapeutic effect of QZXZF on HBx-LCSCs was tested in vitro,and its effect on stemness markers and PI3K/Akt pathway was verified by qRT-PCR and Western blot.Results Yiqi Jianpi Jiedu could improve the overall survival time of HBV-HCC patients.Combined with the results of network pharmacology,the mechanism of action of QZXZF against HBx-LCSCs was explored from the PI3K/Akt pathway.Compared with the blank vector group,HBx can promote the expression of stemness markers in HBx-LCSCs cells;compared with the HBx-LCSCs control group,QZXZF could significantly inhibit the proliferation and colony formation of HBx-LCSCs cells(in a concentration-dependent manner),and could reduce the expression of stemness markers(EpCAM,NANOG,SOX2,and OCT4),phosphorylated PI3K(p-PI3K)and phosphorylated AKT(p-AKT)proteins.Conclusion QZXZF may regulate HBx-mediated LCSCs through PI3K/AKT pathways,providing a reference for the mechanism of TCM intervention in LCSCs.

Objective To explore the mechanism of the intervention effect of Qizhu Xiaozheng Fang(QZXZF),a representative prescription of Yiqi Jianpi Jiedu(replenishing qi,strengthening spleen,and removing toxicity),in treating HBx-mediated liver cancer stem cells(LCSCs).Methods The Kaplan-Meier survival analysis was used to investigate the effects of Yiqi Jianpi Jiedu on the prognosis of patients with HBV-HCC.The network pharmacology method was utilized to predict the targets and pathways of QZXZF in treating HBx-related LCSCs(HBx-LCSCs).HBx-LCSCs cells were screened by stably transfecting HBx and serum-free culture.The therapeutic effect of QZXZF on HBx-LCSCs was tested in vitro,and its effect on stemness markers and PI3K/Akt pathway was verified by qRT-PCR and Western blot.Results Yiqi Jianpi Jiedu could improve the overall survival time of HBV-HCC patients.Combined with the results of network pharmacology,the mechanism of action of QZXZF against HBx-LCSCs was explored from the PI3K/Akt pathway.Compared with the blank vector group,HBx can promote the expression of stemness markers in HBx-LCSCs cells;compared with the HBx-LCSCs control group,QZXZF could significantly inhibit the proliferation and colony formation of HBx-LCSCs cells(in a concentration-dependent manner),and could reduce the expression of stemness markers(EpCAM,NANOG,SOX2,and OCT4),phosphorylated PI3K(p-PI3K)and phosphorylated AKT(p-AKT)proteins.Conclusion QZXZF may regulate HBx-mediated LCSCs through PI3K/AKT pathways,providing a reference for the mechanism of TCM intervention in LCSCs.

Hashimoto's thyroiditis(HT)is an autoimmune thyroid disease characterized by diffuse enlargement of thyroid gland and elevated thyroid autoantibodies.HT is closely related to emotional factors,conveyance and dispersion function of the liver,and the qi movement of the five zang organs.This paper explores the approach to the differentiation and treatment of HT based on Professor Yang Shuyu's view of regulation of both mind and body.In the view of regulation of both mind and body,the regulation of mind is to harmonize emotions,and the regulation of body refers to the conveyance and dispersion function of zang-fu organs.Based on the view of regulation of both mind and body,the pathological changes of HT are characterized by the disordered conveyance and dispersion of qi movement,and the stable phase,hyperthyroid phase,and hypothyroid phase of HT correspond to obstructed conveyance and dispersion,excessive conveyance and dispersion,and insufficient conveyance and dispersion,respectively.The emotional disorders caused by the failure of mind regulation exist throughout the disease course.Therefore,the treatment of HT can be conducted by using the therapies of unblocking,suppressing,and tonifying separately for stable phase,hyperthyroid phase,and hypothyroid phase to address the root cause,and then the conveyance and dispersion of visceral qi movement are restored.Besides,the therapeutic method of resolution is used to alleviate symptoms by removing goiter and dissipating nodules.Simultaneously,emotional regulation therapy is incorporated to achieve a comprehensive efficacy for harmonizing physique-spirit and mind-body through the regulation of emotions,conveyance and dispersion of qi movement,and visceral functions.The view of regulation of both mind and body provides new methods and approaches for traditional Chinese medicine management of HT.

Objective:To detect the expression levels of long non-coding RNAs(lncRNA)in elderly patients with pulmonary tuberculosis(PTB)and those with non-tuberculous lung diseases(non-TB), and to assess the performance of these lncRNA in the differential diagnosis of PTB.Methods:A total of 300 elderly patients with suspected PTB were recruited from Beijing Chest Hospital between January 2024 and September 2024, and were further divided into the PTB group and the non-TB lung disease group based on the results of mycobacterium tuberculosis(MTB)pathogenicity testing.Peripheral blood mononuclear cells were isolated using a lymphocyte separation solution, and RNA was extracted using the TRIzol method.Nine lncRNAs, previously identified as differentially expressed in PTB through our group's microarray analysis, were selected and detected by real-time fluorescence quantitative polymerase chain reaction to evaluate the expression levels of these lncRNAs between the PTB and non-TB lung disease groups.The overall patients were randomly divided into training and validation sets in a 7∶3 ratio.Lasso regression was employed to select the characteristic variables, and a random forest algorithm was then used to construct the lncRNA diagnostic portfolio.Receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic performance of individual lncRNAs and the combined panel in differentiating elderly patients with PTB from those with other non-TB lung diseases.Results:A total of 201 cases were included, with 105 confirmed elderly patients diagnosed with PTB(52.2%)and 96 elderly patients suffering from non-TB lung disease(47.8%).Compared to the elderly patients with non-TB lung disease, the expression levels of ENST00000417346.1, ENST00000620744.1, lncRNA PWP1, ENST00000583184.1, lncRNA ABHD17B, ENST00000607464.1, ENST00000516057.1, and NR_003000 were significantly downregulated in the PTB patients, whereas the expression level of lncRNA BCL2L10 was significantly upregulated in the PTB patients.ROC analysis revealed that the area under the curve(AUC)for each lncRNA ranged from 0.659 to 0.848.The diagnostic panel, which included NR_003000, ENST00000607464.1, ENST00000583184.1, and ENST00000620744.1 as determined by Lasso analysis, exhibited AUC values of 0.917 and 0.906 in the training and validation sets, respectively.The performance of this panel was superior to that of each individual lncRNA.Conclusions:The random forest model, which incorporates NR_003000, ENST00000607464.1, ENST00000583184.1, and ENST00000620744.1, demonstrates potential in differentiating between PTB and non-TB lung diseases.

Objective:To detect the expression levels of long non-coding RNAs(lncRNA)in elderly patients with pulmonary tuberculosis(PTB)and those with non-tuberculous lung diseases(non-TB), and to assess the performance of these lncRNA in the differential diagnosis of PTB.Methods:A total of 300 elderly patients with suspected PTB were recruited from Beijing Chest Hospital between January 2024 and September 2024, and were further divided into the PTB group and the non-TB lung disease group based on the results of mycobacterium tuberculosis(MTB)pathogenicity testing.Peripheral blood mononuclear cells were isolated using a lymphocyte separation solution, and RNA was extracted using the TRIzol method.Nine lncRNAs, previously identified as differentially expressed in PTB through our group's microarray analysis, were selected and detected by real-time fluorescence quantitative polymerase chain reaction to evaluate the expression levels of these lncRNAs between the PTB and non-TB lung disease groups.The overall patients were randomly divided into training and validation sets in a 7∶3 ratio.Lasso regression was employed to select the characteristic variables, and a random forest algorithm was then used to construct the lncRNA diagnostic portfolio.Receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic performance of individual lncRNAs and the combined panel in differentiating elderly patients with PTB from those with other non-TB lung diseases.Results:A total of 201 cases were included, with 105 confirmed elderly patients diagnosed with PTB(52.2%)and 96 elderly patients suffering from non-TB lung disease(47.8%).Compared to the elderly patients with non-TB lung disease, the expression levels of ENST00000417346.1, ENST00000620744.1, lncRNA PWP1, ENST00000583184.1, lncRNA ABHD17B, ENST00000607464.1, ENST00000516057.1, and NR_003000 were significantly downregulated in the PTB patients, whereas the expression level of lncRNA BCL2L10 was significantly upregulated in the PTB patients.ROC analysis revealed that the area under the curve(AUC)for each lncRNA ranged from 0.659 to 0.848.The diagnostic panel, which included NR_003000, ENST00000607464.1, ENST00000583184.1, and ENST00000620744.1 as determined by Lasso analysis, exhibited AUC values of 0.917 and 0.906 in the training and validation sets, respectively.The performance of this panel was superior to that of each individual lncRNA.Conclusions:The random forest model, which incorporates NR_003000, ENST00000607464.1, ENST00000583184.1, and ENST00000620744.1, demonstrates potential in differentiating between PTB and non-TB lung diseases.

The presence of physiological barriers in the eye(both external and internal)makes conventional ophthalmic medications(eye drops,ointments,gels,etc.)less bioavailable and difficult to reach the posterior segment of the eye.Although intravitreal injection can deliver drugs to the posterior segment of the eye,it has disadvantages such as infection,injury,and poor tolerance.Ophthalmic microneedle breaks through the intra-and extra-ocular barriers,enabling the drug to reach the target site accurately and to be released continuously greatly avoiding intraocular infections and injuries,and improving the bioavailability of the drug,which has obvious advantages as an ophthalmic drug delivery tool.Ophthalmic microneedle can be classified into hollow microneedle,dissolving microneedle,and coated microneedle according to the usage methods.Each type of microneedle has its own advantages and has shown satisfactory performance in the treatment of diseases such as bacterial and fungal keratitis,glaucoma,exudative age-related macular degeneration,diabetic macular edema,non-infectious uveitis,corneal neovascularization,and even choroidal melanoma.

OBJECTIVE To observe the changes of static functional connectivity(sFC) and dynamic functional connectivity(dFC) of amygdala subregions in patients with bilateral idiopathic tinnitus and hearing loss(TINHL). METHODS The resting-state functional magnetic resonance imaging(fMRI) data of 30 patients with bilateral tinnitus and hearing loss and 37 normal controls(NCs) were collected to analyze the intensity changes of sFC and dFC in 8 subregions of amygdala and the whole brain in TINHL patients. RESULTS There were no significant differences in age,sex and education between the two groups. Compared with the NCs group,the sFC intensity of the right basolateral subregion and right cerebellar peduncle 1 region,the left basolateral subregion and left orbital medial frontal gyrus and left angular gyrus in TINHL group was significantly decreased. The dFC intensity of left amygdalostriatal subregion and left precuneus in TINHL group was increased,but the dFC intensity was reduced in the left basolateral subregion and right angular gyrus as well as between the right superficial subregion and right medial orbital of superior frontal gyrus. CONCLUSION Among the 8 subregions of amygdala,the bilateral basolateral subregions,the left amygdalostriatal subregion and the right superficial region shown abnormal functional connectivity with other regions of the brain,which are the important parts of emotional abnormalities in TINHL.

To provide basis for prevention and treatment by analyzing the clinical features, emotional and cognitive states and their correlations of idiopathic tinnitus. Cross-sectional study was used. Thirty-six right, 44 left, and 46 bilateral idiopathic tinnitus patients diagnosed in Beijing Tongren Hospital were prospectively enrolled from October, 2020 to February, 2022. The clinical data was recorded and the THI, DBI, STAI, and MoCA were evaluated. The clinical features and the incidence of severe tinnitus, hearing lose, anxiety, and cognitive impairment were compared by one-way ANOVA, Kruskal-Wallis H, and chi-square test. The correlation between tinnitus or hearing and emotional and cognitive states were evaluated by multivariable correlation analysis. There was no significant difference in age, BMI, years of education, tinnitus duration, and the incidence of hearing loss among groups ( F=0.730, P=0.484; F=1.535, P=0.219; F=1.506, P=0.226;χ2=4.242, P=0.120;χ2=6.672, P=0.083). In right, left, and bilateral tinnitus patients, the number of severe tinnitus was 12, 7, and 20 cases and the incidence was 33.3%, 15.9%, and 43.5%; the number of depression was 13, 14, and 26 cases and incidence was 36.1%, 31.8%, and 53.5%; the number of trait anxiety was 3, 2, and 10 cases and the incidence was 8.3%, 4.5%, and 21.7%. Compared with left tinnitus patients, the incidence of severe tinnitus, depression, and trait anxiety was higher in bilateral tinnitus patients (χ2=8.139, P=0.004;χ2=5.558, P=0.018;χ2=5.753, P=0.007). The incidence of state anxiety and cognitive impairment were no significant difference among groups (χ2=0.142, P=0.931;χ2=1.338, P=0.512). The overall incidence of state anxiety and cognitive impairment were 16.7%(21/126) and 37.3%(47/126) respectively. There was positive correlation between THI score and BDI, S-AI, and T-AI scores ( r=0.529, P=0.001; r=0.649, P<0.001; r=0.483, P=0.003) and negative correlation between THI and MoCA scores ( r=-0.364, P=0.029) in right tinnitus group. The positive correlation was found between THI score and BDI, S-AI, and T-AI scores in left tinnitus group ( r=0.508, P<0.001; r=0.506, P<0.001; r=0.357, P=0.017). The positive correlation between THI score and BDI, S-AI, and T-AI scores ( r=0.753, P<0.001; r=0.527, P<0.001; r=0.536, P<0.001) and the positive correlation between tinnitus duration and MoCA score( r=0.334, P=0.023) were also found in bilateral tinnitus group.

To provide basis for prevention and treatment by analyzing the clinical features, emotional and cognitive states and their correlations of idiopathic tinnitus. Cross-sectional study was used. Thirty-six right, 44 left, and 46 bilateral idiopathic tinnitus patients diagnosed in Beijing Tongren Hospital were prospectively enrolled from October, 2020 to February, 2022. The clinical data was recorded and the THI, DBI, STAI, and MoCA were evaluated. The clinical features and the incidence of severe tinnitus, hearing lose, anxiety, and cognitive impairment were compared by one-way ANOVA, Kruskal-Wallis H, and chi-square test. The correlation between tinnitus or hearing and emotional and cognitive states were evaluated by multivariable correlation analysis. There was no significant difference in age, BMI, years of education, tinnitus duration, and the incidence of hearing loss among groups ( F=0.730, P=0.484; F=1.535, P=0.219; F=1.506, P=0.226;χ2=4.242, P=0.120;χ2=6.672, P=0.083). In right, left, and bilateral tinnitus patients, the number of severe tinnitus was 12, 7, and 20 cases and the incidence was 33.3%, 15.9%, and 43.5%; the number of depression was 13, 14, and 26 cases and incidence was 36.1%, 31.8%, and 53.5%; the number of trait anxiety was 3, 2, and 10 cases and the incidence was 8.3%, 4.5%, and 21.7%. Compared with left tinnitus patients, the incidence of severe tinnitus, depression, and trait anxiety was higher in bilateral tinnitus patients (χ2=8.139, P=0.004;χ2=5.558, P=0.018;χ2=5.753, P=0.007). The incidence of state anxiety and cognitive impairment were no significant difference among groups (χ2=0.142, P=0.931;χ2=1.338, P=0.512). The overall incidence of state anxiety and cognitive impairment were 16.7%(21/126) and 37.3%(47/126) respectively. There was positive correlation between THI score and BDI, S-AI, and T-AI scores ( r=0.529, P=0.001; r=0.649, P<0.001; r=0.483, P=0.003) and negative correlation between THI and MoCA scores ( r=-0.364, P=0.029) in right tinnitus group. The positive correlation was found between THI score and BDI, S-AI, and T-AI scores in left tinnitus group ( r=0.508, P<0.001; r=0.506, P<0.001; r=0.357, P=0.017). The positive correlation between THI score and BDI, S-AI, and T-AI scores ( r=0.753, P<0.001; r=0.527, P<0.001; r=0.536, P<0.001) and the positive correlation between tinnitus duration and MoCA score( r=0.334, P=0.023) were also found in bilateral tinnitus group.