Objective: To enhance the ability of nanoparticles to target and bind tumor cells by constructing a neutrophil hitchhiking system based on hyaluronic acid (HA)-modified dual-drug loaded lipid nanoparticles. Methods: Lipid nanoparticles (LNPs) were prepared using microfluidic technology, and the nitrogen/phosphate (N/P) ratio, flow rate ratio, and drug-to-lipid ratio were optimized. HA-modified LNPs (HA-LNPs) were prepared and characterized. The interaction between the nanoparticles and tumor cells was evaluated through in vitro cell experiments. Results: The optimal preparation conditions for LNPs are N/P=8, flow rate ratio=5, and drug-to-lipid ratio=1∶30 (w∶w). HA-LNPs has a particle size of (177.28±2.41) nm, a polydispersity index (PDI) of 0.198±0.10, and an siRNA encapsulation efficiency of (91.37±0.47)%. The optimal binding rate with neutrophils was (98.64±2.34)%. Conclusion: An HA-modified dual-drug loaded lipid nanoparticle-neutrophil hitchhiking system was successfully constructed, enhancing the synergistic anti-tumor activity of the nanomedicine and the uptake of nanoparticles by tumor cells, providing a novel delivery strategy for targeted therapy of bone marrow tumors.

Asarum forbesii is a perennial herb born in a shaded and humid environment, which is warm in nature. With the efficacy of warming lung, resolving fluid retention, and relieving coughs, it can be used to treat the syndrome of cold fluid accumulating in lung. To investigate the effects of different shading conditions on the composition and efficacy of A. forbesii, this study planted A. forbesii under 20% natural light(NL20), 40% natural light(NL40), 60% natural light(NL60), and 80% natural light(NL80) and utilized ultra performance liquid chromatography(UPLC) and micro broth 2-fold dilution method to detect the volatile chemical compounds and the minimum inhibitory concentration. At the same time, the study investigated the effects of A. forbesii grown under different shading conditions on the signs, pathological changes of lung tissues, serum cytokine levels, activities of mitochondrial respiratory chain complexes Ⅰ-Ⅴ in lung tissues, and relative expression of related genes of mice with syndrome of cold fluid accumulating in lung. The results indicated that with the increase of shading, the content of kakuol, methyl eugenol, and asarinin in A. forbesii and the antibacterial effect showed a tendency of increasing first and then decreasing, and the NL40 group was significantly better than the other groups. Under the conditions of NL20 and NL40, A. forbesii significantly alleviated the pathological damage to lung tissues, restored the homeostasis of the lung, and enhanced the energy metabolism level of mice with syndrome of cold fluid accumulating in lung. In addition, A. forbesii planted under the two conditions reduced the content of interleukin-8(IL-8), interleukin-13(IL-13), tumor necrosis factor-α(TNF-α), and mucin 5AC(MUC5AC), increased the levels of interleukin-10(IL-10) and aquaporin 1(AQP1), lowered the expression of MMP9, VEGF, TGF-β, and MAPK3. In conclusion, the therapeutic effect of A. forbesii on the syndrome of cold fluid accumulating in lung was positively correlated with the degree of shading, and the chemical composition and efficacy of warming lung and resolving fluid retention were optimal under the conditions of NL20-NL40. This study can provide reference for the pharmacological research and cultivation of A. forbesii.
Animals ; Mice ; Lung/pathology* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Light ; Cytokines/genetics* ; Humans

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.

Objective To explore the prognostic value of hyperdense artery sign(HAS)in elderly patients with acute anterior LVO in anterior circulation undergoing mechanical thrombectomy.Methods A single-center retrospective analysis was conducted on 109 patients with acute LVO of anterior circulation admitted in our department from January 2019 to December 2022.According to their preoperative plain CT scans,they were divided into HAS positive(39 patients)and HAS negative(70 patients)groups.Baseline features,surgical indicators,complications and outcomes were compared between the two groups.Results The patients with HAS had significantly larger proportions of atrial fibrillation and symptomatic intracranial hemorrhage than those without the sign(53.8％vs 31.4％,20.5％vs 5.7％,P＜0.05).The rate of 90-day good prognosis was a little higher in the HAS positive group than the negative group,though no statistical difference(48.7％vs 38.6％,P＞0.05).Male,stroke history,SBP,NIHSS at admission,HAS positivity,revasculiza-tion,and symptomatic intracranial hemorrhage were independent influencing factors for favorable prognosis in the patients(P＜0.05,P＜0.01).Conclusion The presence of HAS is a prognostic marker for patients with acute LVO in anterior circulation undergoing mechanical thrombectomy,and it is associated with a higher risk of symptomatic intracranial hemorrhage.

[Objective]To evaluate the utility of left atrial(LA)volume and strain measured by 4D auto left atrial quantification(4D auto LAQ)in differentiating pre-capillary from post-capillary pulmonary hypertension(PH),and to compare its discriminative performance with echocardiographic pulmonary to left atrial global strain ratio(ePLAGS).[Methods]A total of ninety-eight subjects with intermediate to high probability of PH were prospectively enrolled.Clinical history and laboratory data were collected.All patients underwent comprehensive transthoracic echocardiography,and LA volume and strain parameters were measured by dedicated commercial software for LA 4D analysis.[Results]Based on pulmonary arterial wedge pressure,patients were divided into pre-capillary PH group[n=39;mean age(53±24)years]and post-capillary PH group[n=59;mean age(57±18)years].Compared to the pre-capillary PH group,the post-capillary PH group showed significantly higher LAVImax,LAVImin and LAVIpreA but markedly lower LASr and LAScd.Multivariate logistic regression identified LAVImax[OR:1.40;95%CI:(1.052,1.872);P=0.021]and LAScd[OR:1.76;95%CI:(1.183,2.489);P=0.004]as independent predictors of post-capillary PH.ROC analysis demonstrated that LAVImax(AUC=0.82,P＜0.001)and LAScd(AUC=0.78,P＜0.001)had strong discriminating power for predicting post-capillary PH group,with optimal cutoff values of 35.69 mL/m2(sensitivity 86%,specificity 74%)and-9%(sensitivity 80%,specificity70%).[Conclusion]LAVImax and LAScd measured with 4D auto LAQ are robust parameters for distinguishing pre-capillary PH from post-capillary PH.

Objective:To explore the efficacy and safety of orelabrutinib combined with R-CHOP in patients with high-risk nongerminal center B-cell (non-GCB) diffuse large B-cell lymphoma (DLBCL) with extranodal involvement.Methods:This retrospective study was conducted on 35 patients who were seen at Guangxi Medical University Cancer Hospital and were immunohistochemically confirmed to have non-GCB DLBCL, had an International Prognostic Index score of 3 - 5, and confirmed to have ≥2 extranodal involvement on PET/CT. The treatment comprised the standard R-CHOP regimen combined with oral orelabrutinib (150 mg/day) for six cycles. In patients who developed neutropenia or grade 3 neutropenia with fever during treatment, administration of prophylactic pegylated granulocyte colony-stimulating factor 48 h after the end of chemotherapy was started on the next cycle. The endpoints included overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS) time, overall survival (OS) time, and safety assessment.Results:The 35 eligible patients enrolled had a median age of 53 years (21 - 72 years) and a median follow-up time of 28 months (12 - 36 months) ; 19 patients had double-expressor (DE) status. The ORR was 88.6%, and the CR rate was 68.6%. The 2-year PFS and OS rates were 68.6% (95% CI 54.0% - 7.2%) and 87.5% (95% CI 76.7% - 100%), respectively. The 2-year PFS rate was significantly lower in patients with DE status than in those without DE status [54.4% (95% CI 35.4% - 84.2%) vs. 85.2% (95% CI 68.3% - 100%), P=0.048]. Serious adverse events included febrile neutropenia, pneumonia, and atrial flutter, but no treatment-related deaths. Conclusion:In patients with high-risk non-GCB DLBCL and extranodal involvement, the combination of orelabrutinib with R-CHOP regimen had good efficacy and manageable toxicity.

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

OBJECTIVE: To determine the carrier rate for thalassemia mutations in the ethnic Miao population of Qianxinan Prefecture. METHODS: Ethnic Miao people suspected for thalassemia trait at the People's Hospital of Qianxinan Prefecture, Guizhou Province between November 2020 to September 2024 were selected as the study subjects. Gap-PCR technology combined with high-throughput sequencing was used to screen a total of 666 individuals. ArcMap v10.8.2 was used to create a spatial distribution map of thalassemia based on the screening results. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2016-01). RESULTS: In total 254 positive cases were detected, with an overall positive rate of 38.14%. Among these, 173 cases were α-thalassemia (25.98%), 77 cases were β-thalassemia (11.56%), and 4 cases were αβ compound thalassemia (0.60%). The most common genotypes for α-thalassemia were αα/--^SEA (positive rate = 10.06%, accounting for 38.73%), αα/-α^3.7 (positive rate = 8.86%, accounting for 34.10%), and α^CSα/αα (positive rate = 4.95%, accounting for 19.08%). The most common genotypes for β-thalassemia were β^41/42(-TTCT)/β^A (positive rate = 5.11%, accounting for 44.16%) and β^{17 (A>T)}/β^A(positive rate = 4.20%, accounting for 36.36%), with these two genotypes accounting for as much as 80.52%. The spatial distribution map indicated that the highest overall detection rate of thalassemia and α-thalassemia in the Miao population of Qianxinan Prefecture was in Xingyi City. The highest detection rate of β-thalassemia was in Zhenfeng County, and the highest detection rate of αβ compound thalassemia was in Wangmo County. CONCLUSION The detection rate of thalassemia among the ethnic Miaos from Qianxinan Prefecture is relatively high, which primarily consisted of α-thalassemia. Regular monitoring and educational outreach should be conducted.
Humans ; China/ethnology* ; Female ; Male ; Genetic Testing ; Adult ; alpha-Thalassemia/genetics* ; Thalassemia/ethnology* ; Ethnicity/genetics* ; Genotype ; beta-Thalassemia/ethnology* ; Adolescent ; Mutation ; Middle Aged ; Child ; Asian People/genetics* ; Young Adult