Xuefu zhuyu decoction is a classic formula for promoting blood circulation and resolving blood stasis， characterised by its remarkable ability to treat different diseases with the same approach. Qi stagnation and blood stasis， the primary syndrome for which this formula is indicated， has been found through modern medical research to be intrinsically linked to a wide range of pathophysiological processes， including microcirculatory disorders， abnormalities in hemorheology， inflammatory responses and endothelial dysfunction； which opens up vast scope for the innovative application of traditional formulas. In terms of pharmacological effect and mechanism， the formula exerts a synergistic regulatory effect across multiple key pathological pathways， including the regulation of coagulation function， the maintenance of vascular structure and function， anti-inflammatory and immunomodulatory actions， the mitigation of oxidative stress， and the modulation of programmed cell death （such as pyroptosis and ferroptosis）. This systematically demonstrates its scientific rationale， which is based on integrated regulation through multiple constituents， multiple targets and multiple pathways. In terms of clinical application， the formula has expanded from cardiovascular diseases to multiple disciplines， including gastroenterology， respiratory medicine， urology， neurology， endocrinology， gynaecology and andrology， with evidence-based medical evidence continuing to accumulate. Current research still faces bottlenecks such as a relatively low level of clinical evidence， insufficient systems biology analysis of the mechanisms underlying the compound’s formulation， and a weak correlation between quality control indicators and therapeutic efficacy. Future efforts should focus on conducting multicentre randomised controlled trials for conditions where the formula demonstrates particular efficacy， deepening research into the relationship between integrated pharmacology and spectrum-efficacy relationship， and promoting the precise application and formulation innovation of classical herbal formulas.

Xuefu zhuyu decoction is a classic formula for promoting blood circulation and resolving blood stasis， characterised by its remarkable ability to treat different diseases with the same approach. Qi stagnation and blood stasis， the primary syndrome for which this formula is indicated， has been found through modern medical research to be intrinsically linked to a wide range of pathophysiological processes， including microcirculatory disorders， abnormalities in hemorheology， inflammatory responses and endothelial dysfunction； which opens up vast scope for the innovative application of traditional formulas. In terms of pharmacological effect and mechanism， the formula exerts a synergistic regulatory effect across multiple key pathological pathways， including the regulation of coagulation function， the maintenance of vascular structure and function， anti-inflammatory and immunomodulatory actions， the mitigation of oxidative stress， and the modulation of programmed cell death （such as pyroptosis and ferroptosis）. This systematically demonstrates its scientific rationale， which is based on integrated regulation through multiple constituents， multiple targets and multiple pathways. In terms of clinical application， the formula has expanded from cardiovascular diseases to multiple disciplines， including gastroenterology， respiratory medicine， urology， neurology， endocrinology， gynaecology and andrology， with evidence-based medical evidence continuing to accumulate. Current research still faces bottlenecks such as a relatively low level of clinical evidence， insufficient systems biology analysis of the mechanisms underlying the compound’s formulation， and a weak correlation between quality control indicators and therapeutic efficacy. Future efforts should focus on conducting multicentre randomised controlled trials for conditions where the formula demonstrates particular efficacy， deepening research into the relationship between integrated pharmacology and spectrum-efficacy relationship， and promoting the precise application and formulation innovation of classical herbal formulas.

OBJECTIVE: To explore the effect and mechanism of DNA methyltransferase 1 (DNMT1) knockout on the inhibition of acute myeloid leukemia (AML) by natural killer (NK) cells. METHODS: The peripheral blood NK cells of AML patients and controls were collected, and the mRNA and protein level of DNMT1 were measured by PCR and Western blot, respectively. The DNMT1 knockout mice were constructed to obtain NK^DNMT1-/- cells. The NK cells were stimulated with interleukin (IL)-12, IL-15, and IL-18 to construct memory NK cells, and then the interferon-γ (IFN-γ) levels were measured by ELISA. After co-culturing with memory NK cells and HL60 cells, the killing effect of NK^DNMT1-/- cells on HL60 cells was detected by LDH assay. Then, the HL60 cell apoptosis and NK cell NKG2D level were measured by flow cytometry. The perforin and granzyme B protein levels of NK cells were measured by Western blot. The AML model mice were constructed by injecting HL60 cells into the tail vein, meanwhile, memory NK cells were also injected, and then the mouse weights, CD33 positive rates, and survival time were detected. RESULTS: The mRNA and protein levels of DNMT1 in NK cells of AML patients were significantly higher than those in the control group (both P < 0.01), while the IFN-γ level induced by interleukin was significantly lower than that in the control group (P < 0.05). Compared with NK^DNMT1+/+ cells, the ability of NK^DNMT1-/- cells to secrete IFN-γ after interleukin stimulation was significantly increased (P < 0.05). The killing and apoptosis-inducing effects of NK^DNMT1-/- cells on HL60 cells were significantly stronger than those of NK^DNMT1+/+ cells (both P < 0.05). The NKG2D level and expression of perforin and granzyme B of NK^DNMT1-/- cells were significantly increased compared with NK^DNMT1+/+ cells (all P < 0.05). Compared with AML mice injected with NK^DNMT1+/+ cells, AML mice injected with NK^DNMT1-/- cells showed significantly increased body weight, decreased CD33 positive rate, and prolonged survival time (all P < 0.05). CONCLUSION Knocking out DNMT1 can enhance the inhibitory effect of NK cells on AML, which may be related to enhancing NK cell memory function.
Killer Cells, Natural/metabolism* ; Animals ; Leukemia, Myeloid, Acute ; Humans ; DNA (Cytosine-5-)-Methyltransferase 1 ; Mice ; Mice, Knockout ; HL-60 Cells ; Apoptosis ; Interferon-gamma/metabolism* ; Granzymes/metabolism* ; Perforin/metabolism* ; NK Cell Lectin-Like Receptor Subfamily K/metabolism*

OBJECTIVE: To analyze the laboratory detection results of hemolytic disease of the fetus and newborn(HDFN). METHODS: Related test results of 283 newborns and their mothers' blood samples from Kunming Maternal and Child Health Hospital from August 2023 to May 2024 were collected, including mother and child ABO blood group, RhD blood group, as well as 3 tests of HDFN, total bilirubin (TBil) and indirect bilirubin (IBil). RESULTS: 283 were ABO incompatibility, among which 187 were HDFN positive, with a positive rate of 66.08%; the positive rate of HDFN in neonates with antigen-A incompatibility was 74.12%(126/170), the positive rate of HDFN in neonates with antigen-B incompatibility was 53.57%(60/112), which was the highest in neonates with O/A incompatibility ［75.45%(126/167)］, followed by O/B incompatibility［54.55%(60/110)］. Group by age, the positive rates of HDFN in the ≤1 d group, 2 d group, 3 d group, 4 d group, 5 d group and ≥6 d group were 76.03%(111/146), 67.86%(38/56), 57.14%(24/42), 38.46%(5/13), 46.15%(6/13) and 23.08%(3/13), respectively. With the increase of age, the positive rates of HDFN gradually decreased, there was a statistically significant difference between the ≤3 day age group and >3 day age group ( P <0.05). There was no statistically significant difference in TBil and IBil levels between the "direct antibody+indirect antibody+release+" group and the HDFN negative group in newborns. HDFN infants exhibited a rapid increase in bilirubin levels within the first day after birth, with significantly higher TBil and IBil values compared to Non ABO-HDFN infants in the ≤1 day group ( P <0.01). However, the difference of bilirubin levels between the two groups gradually narrowed from 2-6 days after birth, and the difference was not statistically significant (P >0.05). The peak value of TBil and IBil occurred on the 4th day after birth in HDFN infants. CONCLUSION ABO-HDFN is most commonly seen in newborns whose mothers are type-O, and the positive rate was the highest in newborns with O/A incompatibility. The detection rate of HDFN is affected by the age of the newborns, and the two were correlated inversely. ABO-HDFN group developed more rapidly with a higher peak. Therefore, HDFN tests should be carried out as soon as possible for mothers and newborns with incompatible blood types, and appropriate treatment should be provided to prevent complications.
Humans ; Infant, Newborn ; ABO Blood-Group System ; Erythroblastosis, Fetal/epidemiology* ; Female ; China/epidemiology* ; Blood Group Incompatibility ; Male ; Bilirubin/blood*

In recent years, gastrointestinal stromal tumors (GIST) have increased incidence and mortality, and most GIST is caused by the activation mutation of the c-KIT gene. Therefore, c-KIT has become a promising therapeutic target of GIST. At present, the drugs approved for the treatment of GIST including imatinib, sunitinib, regorafenib and ripretinib, are mostly prone to developing resistance and accompanied by various degrees of adverse reactions. Therefore, there is an urgent need to develop new c-KIT inhibitors to solve the problem of resistance. In this study, we investigated the anti-tumor effect of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells in vitro. We found that PN17-1 significantly inhibited the proliferation, colony formation and migration ability of GIST-882 cells, and significantly downregulated the protein expression levels of p-c-KIT and its downstream signals p-AKT, p-STAT5 and p-ERK in GIST-882 cells. In addition, PN17-1 induced apoptosis in GIST-882 cells, and the apoptosis may be mainly related to the mitochondrial-dependent endogenous pathway. In conclusion, the novel c-KIT inhibitor PN17-1 is a promising anti-GIST drug, and this study provides new ideas for further development of c-KIT inhibitors in the future.

The plants of the genus Caragana Fabr. are desert plants of the Leguminosae family, which are widely used in traditional ethnomedicine, with the effects of nourishing Yin and nourishing blood, dispelling wind and removing dampness, clearing heat and detoxifying toxins. The anti-inflammatory effect of Caragana Fabr. has attracted much attention, the research on the related mechanism has made some progress, but it lacks systematic collation. By summarising the anti-inflammatory effects of the active ingredients of Caragana Fabr., the authors found that they have good anti-inflammatory activities on different inflammatory cell models in vitro, and have good improvement effects on rheumatoid arthritis, colitis, complex nephritis, and acute lung injury and other disease models. The anti-inflammatory effects of the active components of this genus mainly include the reduction of the levels of a variety of pro-inflammatory factors, and the signalling pathways involved mainly include TLR4/NF-κB, TLR4/MAPK, TLR4/NF-κB/IRF3, JAK/STAT-1, ERK/STAT-1 and so on. Therefore, the paper mainly reviews the research progress on the anti-inflammatory effects and mechanisms of the Caragana Fabr. plants and their active components according to disease types, with a view to providing reference for the in-depth study of their anti-inflammatory activities and the development of new products with related functions.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Objective:To explore the improvement of the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection and conduct safety tests including abnormal toxicity test,allergic reaction test,hemolysis and coagulation test.Methods:Ginkgo Leaf Extract and Dipyridamole Injection from 3 different manufactures(A,B and C)were tested respectively through abnormal toxicity test and acute toxicity test in mice,active systemic anaphylaxis test in guinea pigs and hemolysis test in vitro.Five mice were used in each batch for abnormal toxicity test according to the abnormal toxicity test method in general notice of the Chinese Pharmacopoeia 2020 Volume Ⅳ(1141),and 50 mice were selected in each batch for acute toxicity test to determine the median lethal dose(LD50)or maximum tol-erable dose(MTD)of Ginkgo Leaf Extract and Dipyridamole Injection,which were used to establish the method of abnormal toxicity experiment.The anaphylaxis of Ginkgo Leaf Extract and Dipyridamole Injection was evaluated by active systemic anaphylaxis test in guinea pigs,which was used to establish the method of allergic test.The hemoly-sis test of Ginkgo Leaf Extract and Dipyridamole Injection was studied by conventional tube method in vitro(macro-scopic observation)and improved hemolysis method in vitro(spectrophotometric method),which were used to establish the method of hemolysis and coagulation test.Results:① In manufacture A,the results of abnormal toxicity test were showed that LD50 was20.8 mL·kg-1and MTD was 16.5 mL·kg-1.No death or abnormal reac-tions were observed in mice tested for abnormal toxicity of 2 manufactures(B and C),and MTD was 50 and 40 mL·kg-1,respectively.②The no-observed-adverse-effect dose of Ginkgo Leaf Extract and Dipyridamole Injec-tion from 3 manufactures to guinea pig intravenous was 0.83 mL·kg-1,and no allergic reaction symptoms were observed when Ginkgo Leaf Extract and Dipyridamole Injection was diluted 4 times to challenge the sensitized guinea pigs(equivalent to human clinical dosage).③Differences were observed in the hemolytic effects of Ginkgo Leaf Extract and Dipyridamole Injection from 3 manufactures,but no obvious hemolytic reaction occurred when it was diluted 1.2 times(equivalent to 5%of the maximum clinical concentration).Conclusion:It is recommended to add abnormal toxicity test,allergic reaction test,hemolysis and coagulation test in the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection as safety test items to control the risk.The proposed method is diluting Ginkgo Leaf Extract and Dipyridamole Injection by 5 times,4 times and 1.2 times to perform abnormal toxicity test,allergic reaction test,hemolysis test and coagulation test respectively.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent cause of chronic liver disease worldwide, and its intricate pathogenesis presents challenges in the development of new drugs. As a common way of post-translational modification, acetylation regulates protein stability, enzyme activity, and subcellular localization, occurring extensively in MASLD-associated processes such as lipid metabolism, inflammatory response, and oxidative stress. In this paper, we comprehensively review the mechanism of acetylation in MASLD, analyze the expression levels of acetylases in liver tissues of MASLD patients from the gene expression omnibus (GEO), discuss the changes in relevant enzyme expression and mechanisms in animal models, and further explore the feasibility of targeting acetylation for MASLD treatment, in the hope of offering a new perspective for advancing drug discovery in the field of MASLD.

Aim To evaluate the in vitro anti-chronic obstructive pulmonary disease(COPD)effects of six batches of Rhizoma Pinelliae(RP)ethanol extracts by the technique for order preference by similarity to an i-deal solution(TOPSIS),so as to establish a new method for comprehensive quality evaluation of RP.Methods Cigarette smoke extract(CSE)and lipopo-lysaccharide(LPS)were utilized to establish an airway inflammation model of Beas-2b human normal lung cells.MTT assay was employed to determine the toxici-ty and pharmacological concentrations of Pinellia Ter-nata(PT)and six different batches RP of their ethanol extracts.EC50 and IC50 values were calculated accord-ingly.Additionally,relevant markers were assessed u-sing qRT-PCR and the superoxide dismutase(SOD)assay kit.Finally,a comprehensive evaluation invol-ving multiple indices was performed using the TOPSIS method for both PT and the six batches of RP extracts.Results According to the IC50 values of seven differ-ent Pinellia ternata,the toxicity ranking was as fol-lows:PT＞RP④＞RP①＞RP⑤＞RP③＞RP⑥＞RP ②.On the other hand,the expressions of TNF-α,IL-6 and IL-8 were down-regulated in the treatment group compared with those of the model group by qRT-PCR.In addition,the levels of SOD de-creased in all groups after treatment.All the data were normalized and the comprehensive ranking results were obtained through TOPSIS analysis as follows:RP⑥＞RP⑤＞RP②＞RP①＞RP③＞RP④＞PT.Con-clusions The ethanol extracts of different Rhizoma Pinelliae varieties all demonstrate the capacity to sup-press inflammation and oxidative stress induced by LPS and CSE.The comprehensive evaluation indicates that the quality of the ⑥ batch of RP shows the highest quality.Moreover,the TOPSIS method can serve as an assessment approach for medicinal materials,offering a pathway for controling the varying quality of herbal ma-terials available in the market.