OBJECTIVE To study the extraction process of Hongqijin granules with the standard decoction of Hongqijin formula as the reference. METHODS Fifteen batches of Hongqijin formula standard decoction were prepared. The reference characteristic chromatogram was established， and the chromatographic similarity was calculated. The average extraction yield and average transfer rates of calycosin-7-glucoside， salidroside， curcumin， and emodin of the 15 batches of standard decoction were determined. Taking soaking time， water addition amount， and decoction time as influencing factors， and extraction yield， transfer rates of marker components， as well as chromatographic similarity with the reference characteristic chromatogram as evaluation indexes， orthogonal test combined with principal component analysis was adopted to optimize the extraction process of Hongqijin granules， followed by process verification. RESULTS The average extraction yield of 15 batches of Hongqijin formula standard decoction was 32.55%. The average transfer rates of calycosin-7-glucoside， salidroside， curcumin， and emodin were 70.68%， 74.35%， 2.16%， and 4.62%， respectively. The optimal extraction process of Hongqijin granules was confirmed as follows： extraction was carried out twice； the first extraction used 8-fold water for 60 min， and the second extraction adopted 6.5-fold water for 45 min. In three validation tests， the average extraction yield was 33.01%. The average transfer rates of the four marker components were 79.51%， 75.54%， 1.84%， and 4.30%， with all RSD values less than 2%. The chromatographic similarities between the extracting solution and reference characteristic chromatogram were all higher than 0.990. CONCLUSIONS The optimized extraction process of Hongqijin granules exhibits good stability， and the material basis of the extracting solution is consistent with that of Hongqijin formula standard decoction.

In this work,near infrared carbon quantum dots(NIR-CDs)were synthesized by hydrothermal method using biomass material Clausena lansium leaves.The synthesized NIR-CDs emitted maximum fluorescence signal at 677 nm,which was independent of excitation wavelength.The characterization results showed that there were abundant groups on the surface of NIR-CDs.Pd2+could form non-fluorescent compounds with the surface groups of NIR-CDs,resulting in fluorescence quenching(Fluorescence signal was denoted as F0).Because chlorpromazine hydrochloride(CPZ)parent nucleus contained unoxidized S atom,CPZ could form stable colored complex with Pd2+under acidic conditions.In the presence of CPZ,Pd2+dissociated from the surface of NIR-CDs and bonded with CPZ,so that the fluorescence signal could be restored(Fluorescence signal was denoted as F).An"on-off-on"fluorescence sensor was thus constructed.The fluorescence signal recovery value of NIR-CDs(△F=F-F0)showed a good linear relationship with the concentration of CPZ in the range of 5.68-28.43 μg/mL,and the detection limit(3σ)was 0.078 μg/mL.The sensor was applied to determination of CPZ in pharmaceutical preparations,and the recoveries were 94％-106％.The developed fluorescence sensor was expected to be used in quality control of actual pharmaceutical preparations.

INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

Objectives: Osteoblast is known to regulate hematopoiesis according to preclinical studies but the causal rela tionship in human remains uncertain. We aimed to evaluate causal relationships of bone mineral density (BMD) with blood cell traits using genetic data. Methods: Summary statistics from the largest available genome-wide association study were retrieved for total body BMD (TBBMD), lumbar spine BMD (LSBMD), femoral neck BMD (FNBMD) and 29 blood cell traits including red blood cell, white blood cell and platelet-related traits. Using two-sample Mendelian randomization (MR) approach, inverse-variance weighted method was adopted as main univariable MR analysis. Multivariable MR (MVMR) analysis was conducted to evaluate whether the casual effect is independent of confounders. Results: BMD was positively associated with reticulocyte-related traits, including high light scatter reticulocyte count and percentage, immature reticulocyte fraction, reticulocyte count and percentage, with causal effect estimate (beta) ranging from 0.023 to 0.064. Conversely, inverse association of BMD with hematocrit, hemo globin, and red blood cell count was observed, with beta ranging from − 0.038 to − 0.019. The association remained significant in MVMR analysis after adjustment for confounders. For white blood cells, BMD was inversely associated with neutrophil count (beta: 0.029 to − 0.019) and white blood cell count (beta: 0.024 to − 0.02). Results across TBBMD, LSBMD, and FNBMD were consistent. Conclusions This study suggested bone metabolism had a causal effect on hematopoietic system in humans. Its causal effect on red blood cell traits was independent of confounders. Further studies on how improving bone health can reduce risk of hematological disorders are warranted.

Objectives: Osteoblast is known to regulate hematopoiesis according to preclinical studies but the causal rela tionship in human remains uncertain. We aimed to evaluate causal relationships of bone mineral density (BMD) with blood cell traits using genetic data. Methods: Summary statistics from the largest available genome-wide association study were retrieved for total body BMD (TBBMD), lumbar spine BMD (LSBMD), femoral neck BMD (FNBMD) and 29 blood cell traits including red blood cell, white blood cell and platelet-related traits. Using two-sample Mendelian randomization (MR) approach, inverse-variance weighted method was adopted as main univariable MR analysis. Multivariable MR (MVMR) analysis was conducted to evaluate whether the casual effect is independent of confounders. Results: BMD was positively associated with reticulocyte-related traits, including high light scatter reticulocyte count and percentage, immature reticulocyte fraction, reticulocyte count and percentage, with causal effect estimate (beta) ranging from 0.023 to 0.064. Conversely, inverse association of BMD with hematocrit, hemo globin, and red blood cell count was observed, with beta ranging from − 0.038 to − 0.019. The association remained significant in MVMR analysis after adjustment for confounders. For white blood cells, BMD was inversely associated with neutrophil count (beta: 0.029 to − 0.019) and white blood cell count (beta: 0.024 to − 0.02). Results across TBBMD, LSBMD, and FNBMD were consistent. Conclusions This study suggested bone metabolism had a causal effect on hematopoietic system in humans. Its causal effect on red blood cell traits was independent of confounders. Further studies on how improving bone health can reduce risk of hematological disorders are warranted.

Objective:To investigate the changes of left ventricular systolic function in patients after pacing in differ-ent sites of right ventricle.Methods:The clinical data of 95 patients requiring right ventricular pacing who were ad-mitted to our hospital from February 2018 to May 2020 were collected.According to pacing site,they were divided into right ventricular apex pacing(RVAP)group(n=47)and right ventricular outflow tract septal pacing(RVSP)group(n=48).The pacing threshold,perception threshold,electrode impedance,left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),stroke volume(SV),left ventricular ejection fraction(LVEF)were compared between the two groups.According to incidence of cardiac insufficiency on one year after pacing,patients were divided into cardiac insufficiency group(n=18)and normal cardiac function group(n=77).Influencing factors of cardiac insufficiency in patients requiring right ventricular pacing were analyzed.Results:Compared with one week after pacing,on one year after pacing,perception threshold[(11.51±1.21)mV vs.(12.11±0.81)mV]significantly increased in RVAP group,P=0.004.Compared with RVAP group on one year after pacing,there were significant rise in LVESV[(25.32±7.63)ml vs.(29.77±12.36)ml],LVEDV[(58.30±15.71)ml vs.(68.33±25.31)ml],SV[(31.36±10.73)ml vs.(41.29±16.15)ml],and significant reductions in LVEF[(60.55±8.76)％vs.(54.10±6.44)％]and proportion of cardiac insufficiency(27.66％vs.10.42％)in RVSP group,P＜0.05 or＜0.01.Non-conditional multivariate Logistic regression model analysis indicated that LVEF was inde-pendent protective factor for cardiac insufficiency in patients requiring right ventricular pacing(OR=0.854,P=0.003),while RVAP and age ≥60 years were its independent risk factors(OR=9.041,4.145,P=0.003,0.024).Conclusion:Compared with right ventricular apex pacing,right ventricular outflow tract septal pacing can significantly improve stroke volume,and incidence rate of cardiac insufficiency significantly reduces.

Objectives: Osteoblast is known to regulate hematopoiesis according to preclinical studies but the causal rela tionship in human remains uncertain. We aimed to evaluate causal relationships of bone mineral density (BMD) with blood cell traits using genetic data. Methods: Summary statistics from the largest available genome-wide association study were retrieved for total body BMD (TBBMD), lumbar spine BMD (LSBMD), femoral neck BMD (FNBMD) and 29 blood cell traits including red blood cell, white blood cell and platelet-related traits. Using two-sample Mendelian randomization (MR) approach, inverse-variance weighted method was adopted as main univariable MR analysis. Multivariable MR (MVMR) analysis was conducted to evaluate whether the casual effect is independent of confounders. Results: BMD was positively associated with reticulocyte-related traits, including high light scatter reticulocyte count and percentage, immature reticulocyte fraction, reticulocyte count and percentage, with causal effect estimate (beta) ranging from 0.023 to 0.064. Conversely, inverse association of BMD with hematocrit, hemo globin, and red blood cell count was observed, with beta ranging from − 0.038 to − 0.019. The association remained significant in MVMR analysis after adjustment for confounders. For white blood cells, BMD was inversely associated with neutrophil count (beta: 0.029 to − 0.019) and white blood cell count (beta: 0.024 to − 0.02). Results across TBBMD, LSBMD, and FNBMD were consistent. Conclusions This study suggested bone metabolism had a causal effect on hematopoietic system in humans. Its causal effect on red blood cell traits was independent of confounders. Further studies on how improving bone health can reduce risk of hematological disorders are warranted.

Objectives: Osteoblast is known to regulate hematopoiesis according to preclinical studies but the causal rela tionship in human remains uncertain. We aimed to evaluate causal relationships of bone mineral density (BMD) with blood cell traits using genetic data. Methods: Summary statistics from the largest available genome-wide association study were retrieved for total body BMD (TBBMD), lumbar spine BMD (LSBMD), femoral neck BMD (FNBMD) and 29 blood cell traits including red blood cell, white blood cell and platelet-related traits. Using two-sample Mendelian randomization (MR) approach, inverse-variance weighted method was adopted as main univariable MR analysis. Multivariable MR (MVMR) analysis was conducted to evaluate whether the casual effect is independent of confounders. Results: BMD was positively associated with reticulocyte-related traits, including high light scatter reticulocyte count and percentage, immature reticulocyte fraction, reticulocyte count and percentage, with causal effect estimate (beta) ranging from 0.023 to 0.064. Conversely, inverse association of BMD with hematocrit, hemo globin, and red blood cell count was observed, with beta ranging from − 0.038 to − 0.019. The association remained significant in MVMR analysis after adjustment for confounders. For white blood cells, BMD was inversely associated with neutrophil count (beta: 0.029 to − 0.019) and white blood cell count (beta: 0.024 to − 0.02). Results across TBBMD, LSBMD, and FNBMD were consistent. Conclusions This study suggested bone metabolism had a causal effect on hematopoietic system in humans. Its causal effect on red blood cell traits was independent of confounders. Further studies on how improving bone health can reduce risk of hematological disorders are warranted.

Objectives: Osteoblast is known to regulate hematopoiesis according to preclinical studies but the causal rela tionship in human remains uncertain. We aimed to evaluate causal relationships of bone mineral density (BMD) with blood cell traits using genetic data. Methods: Summary statistics from the largest available genome-wide association study were retrieved for total body BMD (TBBMD), lumbar spine BMD (LSBMD), femoral neck BMD (FNBMD) and 29 blood cell traits including red blood cell, white blood cell and platelet-related traits. Using two-sample Mendelian randomization (MR) approach, inverse-variance weighted method was adopted as main univariable MR analysis. Multivariable MR (MVMR) analysis was conducted to evaluate whether the casual effect is independent of confounders. Results: BMD was positively associated with reticulocyte-related traits, including high light scatter reticulocyte count and percentage, immature reticulocyte fraction, reticulocyte count and percentage, with causal effect estimate (beta) ranging from 0.023 to 0.064. Conversely, inverse association of BMD with hematocrit, hemo globin, and red blood cell count was observed, with beta ranging from − 0.038 to − 0.019. The association remained significant in MVMR analysis after adjustment for confounders. For white blood cells, BMD was inversely associated with neutrophil count (beta: 0.029 to − 0.019) and white blood cell count (beta: 0.024 to − 0.02). Results across TBBMD, LSBMD, and FNBMD were consistent. Conclusions This study suggested bone metabolism had a causal effect on hematopoietic system in humans. Its causal effect on red blood cell traits was independent of confounders. Further studies on how improving bone health can reduce risk of hematological disorders are warranted.

ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma （HCC） and its relationship with prognosis， clinical stage and immune infiltration. MethodsIn this study， TCGA， GTEx， TIMER2.0， HPA database and qRT-PCR， western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages； Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC； the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC； the STRING database was used to detect the protein binding with FANCI； the TCGA and GTEx databases were used for GO and KEGG enrichment analysis； Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues， the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated （P<0.001）； and HCC patients with high expression of FANCI had poor prognosis （P<0.001）； the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4⁺ T cells， the number of Th2 cells and the expression of immune checkpoints， and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group （P<0.01）； GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity； Cell experiments showed that knockdown of FANCI could inhibit the proliferation， invasion and migration of HCC （P<0.05）. ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues， which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport， and is associated with poor prognosis. The proliferation， invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.