ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

ObjectiveTo study the chemical constituents of Bidens pilosa and the in vitro antiproliferative activity of some compounds against gastric cancer cells. MethodsThe chemical constituents were isolated and purified by methods such as silica gel column chromatography， preparative thin layer chromatography， medium pressure preparation chromatography， semi-preparative high performance liquid chromatography（HPLC） and recrystallization， their structures were identified on the basis of physicochemical properties， spectral data and circular dichroism spectra. Thiazole blue（MTT） assay was used to determine the in vitro inhibitory activityies of some isolated compounds against human gastric cancer SGC-7901 cells， and molecular docking was used to predict their potential targets. ResultsTwenty-five compounds were isolated from the petroleum ether fraction of B. pilosa and identified as bidpillignan A（1）， 5α， 8α-epidioxy-（22E， 24R）-ergosta-6， 22-diene-3β-ol（2）， 3β-hydroxysitost-5-en-7-one（3）， （20R）-6β-hydroxystigmasta-4， 22-dien-3-one（4）， 3β-hydroxylstigmasta-5， 22-dien-7-one（5）， （22E， 24S）-24-methyl-5α-choleata-7， 22-diene-3β， 5α， 6β-triol（6）， stigamast-5-ene-3β， 7α-diol（7）， stigmast-5， 22-diene-3β， 7α-diol（8）， 7β-hydroxysitosterol（9）， stigmasterol（10）， artabotrol（11）， cosmosoic acid（12）， ent-4（15）-eudesmene-1β， 6α-diol（13）， clovandiol（14）， 1H-indole-3-carboxaldehyde（15）， 6， 7-dimethoxycoumarin（16）， 3'， 4'-dimethoxyquercetin（17）， 8， 8'-bis-（dihydroconiferyl）-diferuloylate（18）， hydroxydihydrobovolide（19）， 2-deacetyl-11β， 13-dihydroxyxanthinin（20）， loliolide（21）， pubescone（22）， （+）-dehydrovomifoliol（23）， 2， 3-dihydroxypropyl palmitate（24） and n-hexadecane acid（25）. Among them， compound 1 was a new compound， compounds 3-9， 11-12， 18-20， 22-23 were first isolated from Bidens genus plants， and compounds 13 and 14 were isolated from this plant for the first time. Compounds 17 and 18 showed good in vitro proliferation inhibitory activities against SGC-7901 cells with the half inhibitory concentrations（IC₅₀） of 3.11， 7.22 μmol·L^-1， respectively. Molecular docking results showed that the potential targets of the two exerting anti-gastric cancer activity might be vascular endothelial growth factor receptor 2（VEGFR2） and poly（adenosine diphosphate-ribose） polymerase 7（PARP7）. ConclusionOne new compound， 14 genus first compounds， and 2 species first compounds were isolated from B. pilosa， among which compounds 17 and 18 processed anti-gastric cancer cell proliferation activity in vitro， and the targets may be VEGFR2 and PARP7.

ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions， so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values（L^*） of the surface， cross-section and powder of the samples， texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography（HPLC） was used to determine the contents of seven nucleoside components（uracil， hypoxanthine， uridine， inosine， guanosine， β-thymidine and adenosine） in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis（PCA） was used to comprehensively rank the data of various indicators， and partial least squares-discriminant analysis（PLS-DA） was used to screen differential components with variable importance in the projection（VIP） value>1. Furthermore， the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature， the color of the intermittently dried samples gradually deepened， while their hardness gradually decreased. Concurrently， the contents of extract， total starch， uridine and adenosine exhibited an upward trend， whereas the contents of uracil， hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group， the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose， the hardness and the total content of nucleoside components in the samples showed a downward trend， while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L^* was negatively correlated with the contents of uracil， hypoxanthine and inosine， and positively correlated with the contents of uridine， guanosine and adenosine. Hardness was negatively correlated with adenosine content， and positively correlated with the contents of inosine， uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components， the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract， the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition， while uridine， uracil， guanosine， adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination， which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.

AIM: To investigate the effects of Conbercept on various optical coherence tomography(OCT)biomarkers in patients with retinal vein occlusion-related macular edema(RVO-ME), and to analyze the correlation of these biomarker changes with visual prognosis.METHODS: Retrospective study. A total of 57 patients(57 eyes)with RVO-ME, including 25 patients(25 eyes)with central retinal vein occlusion(CRVO)and 32 patients(32 eyes)with branch retinal vein occlusion(BRVO), were enrolled in this study. All the patients received intravitreal injection of conbercept once a month, three times in total. The preoperative and postoperative best-corrected visual acuity(BCVA), and changes in OCT biomarkers, including central macular thickness(CMT), the length of disorganization of the retinal inner layers(DRIL), the number of hyperreflective dots(HRD), the area of intraretinal fluid(IRF), the area of subretinal fluid(SRF), and the length of ellipsoid zone(EZ)disruption were compared. Furthermore, the relationship of these changes with BCVA was analyzed.RESULTS:Compared with the baseline, at 3 mo post-treatment, BCVA(LogMAR)was improved, CMT was decreased, the length of DRIL was shortened, the number of HRD was reduced, the area of IRF was decreased, the area of SRF was reduced, and the length of EZ disruption was shortened(all P<0.05). Spearman correlation analysis showed that there was no correlation between the changes in CMT, the length of DRIL, the number of HRD, the area of IRF, the area of SRF and the change in BCVA before and after treatment(P>0.05). However, the change in the length of EZ disruption was positively correlated with the change in BCVA(rs=0.34, P=0.011), and the R2 value of the fitting curve between the change in the length of EZ disruption and the change in BCVA was 0.113(P=0.011). When comparing the pre- and post-treatment changes in BCVA, the length of DRIL, the number of HRD, the area of IRF, the area of SRF, and the length of EZ disruption between patients in the CRVO group and BRVO group, no significant differences were observed(all P>0.05). In contrast, a significant difference was found in the change in CMT between the two groups(P=0.002).CONCLUSION:Conbercept effectively improves multiple OCT biomarkers in patients with RVO-ME. Repair of EZ disruption is a key driver of visual recovery, and its stability may serve as a novel indicator for personalized decision-making in anti-vascular endothelial growth factor therapy.

Objective To compare the results obtained from an artificial intelligence (AI)-based chromosome image scanning and processing system, the Metafer 4 chromosome scanning and analysis system, and manual analysis of dicentric chromosomes, and to explore the feasibility of applying AI technology for dicentric chromosome detection and biological dose estimation. Methods Healthy human elbow vein blood was collected and subjected to ⁶⁰Co in vitro irradiation. Chromosome samples were prepared using conventional methods. The slides were scanned and automatically analyzed using the AI-based system and the Metafer 4 system. The results were manually analyzed and confirmed. Results The number of cells was comparable between the AI-based system and the Metafer 4 system. However, the scanning speed of the AI-based system was 4.5 seconds per image, which was significantly faster than the 7.3 seconds per image of the Metafer 4 system (t = −6.19, P < 0.05). At a confidence level of 0.7, the AI-based system demonstrated a true positive rate of 96.7% and a false positive rate of 6.5%, which were significantly better than the true positive rate (45.4%-54.5%) and false positive rate (22.2%-29.2%) of the Metafer 4 system (all P < 0.05). In the biological dose estimation, the deviation of the dose-response curve was ≤ ± 10% in the automatic analysis using the Metafer 4 system. Due to the use of the manual dose-response curve, the deviation of the AI-based System was ≤ ± 15%. However, there were no significant differences in the estimated doses when the two systems were compared with the manual analysis (P > 0.05). Conclusion Both the AI-based chromosome image scanning and processing system and the Metafer 4 chromosome scanning and analysis system greatly improved the analysis speed of chromosome aberrations. However, the scanning speed, true positive rate, and false positive rate of the AI-based system were superior to those of the Metafer 4 system. Therefore, the AI-based system is more suitable for rapid and high-throughput biological dose estimation in large-scale radiation accidents.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.