ObjectiveTo investigate the therapeutic mechanism of Xuefu Zhuyutang （XFZYT） for metabolic-associated fatty liver disease （MAFLD） through integrated network pharmacology and animal experiments. MethodsNetwork pharmacology was utilized to predict the core components， key therapeutic targets， and signaling pathways of XFZYT in the treatment of MAFLD. For animal experiments， a rat model of MAFLD was established by feeding a high-cholesterol diet for 4 weeks. Intervention was then administered with low-dose （2 g·kg^-1） and high-dose （4 g·kg^-1） XFZYT for 2 weeks. Biochemical assays were performed to measure the serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. In addition， the activities of superoxide dismutase （SOD） and catalase （CAT） and levels of malondialdehyde （MDA） and glutathione （GSH） in the serum were measured. The same way was adopted to measure the levels of TC and TG in the liver tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the serum levels of interleukin （IL）-6， IL-1β， and tumor necrosis factor-alpha （TNF-α）. Histopathological evaluations included hematoxylin and eosin （HE） staining for liver tissue morphology， Oil Red O staining for lipid deposition， and dihydroethidium （DHE） probe staining for reactive oxygen species （ROS） levels. Western blot analysis was conducted to assess the protein levels of AMP-activated protein kinase （AMPK）， phosphorylated （p）-AMPK， nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， nuclear factor-kappa B （NF-κB）， and p-NF-κB in the liver tissue. Untargeted metabolomics analysis of the serum was performed by liquid chromatography-tandem mass spectrometry （LC-MS/MS）. ResultsNetwork pharmacology analysis predicted 155 potential targets of XFZYT for MAFLD treatment， with core targets including signal transducer and activator of transcription 3 （STAT3）， protein kinase B1 （Akt1）， TNF， and IL-6. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment primarily implicated the AMPK signaling pathway. Animal experiments demonstrated that compared with the normal group， the model group exhibited dyslipidemia， hepatic function impairment， pronounced hepatic lipid deposition， and inflammatory manifestations， with elevated serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， reduced HDL and GSH levels plus decreased SOD and CAT activities （P<0.05）， downregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and upregulated protein level of p-NF-κB （P<0.05） in the liver tissue. Compared with the model group， XFZYT intervention groups showed significant amelioration of dyslipidemia and hepatic function impairment， markedly reduced hepatic lipid deposition and inflammatory cell infiltration， decreased serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， increased HDL and GSH levels plus enhanced SOD and CAT activities （P<0.05）， upregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and downregulated protein level of p-NF-κB （P<0.05）. Serum metabolomics revealed 511 differentially expressed metabolites （231 upregulated and 280 downregulated） between normal and model groups， while XFZYT groups versus model group showed 94 differential metabolites （51 upregulated and 43 downregulated）. Among them， 11 metabolites displayed the most significant alterations， with enriched pathways including glycerolipid metabolism， cholesterol metabolism， and insulin resistance， multiple of which demonstrated AMPK association. ConclusionXFZYT alleviates MAFLD by regulating the AMPK signaling pathway and associated metabolic networks.

Nuclear radiation exposure events and tumor radiotherapy are highly susceptible to a range of psychological, physiological and other health problems, which can seriously affect patients' quality of life. It has been shown that 87.5 % of tumor patients are exposed to varying degrees of radiation injury during radiotherapy. The treatment of radiation injury (RI) in modern medicine is limited to drug therapy, cell therapy, etc. Among them, the most chemical drugs cause many adverse reactions including fatigue, nausea, vomiting, etc., and there are very few drugs dedicated to the treatment of RI. Traditional Chinese medicine (TCM) is a rich natural medicinal resource, which has a wide range of pharmacological activities, multiple targets of action and minimal toxic side effects. Many studies have demonstrated that TCM and its compound preparations have enormous potential in the treatment of radiation induced comprehensive diseases. However, TCM is limited in clinical application due to its slow onset of action, complex active ingredients, and low bioavailability. Therefore, the article reviews the application, molecular mechanisms, and new dosage forms of TCM in the prevention and treatment of RI. On this basis, we will focus on discussing the development advantages and application prospects of the combination of traditional Chinese and Western medicine to achieve highly efficient treatment of RI. This review aims to provide scientific and effective drug delivery strategies and basic theoretical support for the clinical effective treatment of RI with TCM, and further promote the innovative development of TCM.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Objective:To investigate the effect of circular RNA (circRNA)_005987 on contrast-associated acute kidney injury (CA-AKI) and its mechanism, and provide new ideas for the prevention and treatment of CA-AKI.Methods:CA-AKI rat models and HK-2 cell injury models were established using iopromide, and CA-AKI-related circRNA_005987 was screened based on circRNA expression chip and real-time quantitative PCR (RT-qPCR). Knockdown and overexpression of circRNA_005987 were performed in HK-2 cell model, respectively. Cell counting kit-8 (CCK-8) and Edu staining assays were used to evaluate cell proliferation. Western blotting was used to detect the protein expression of autophagy-related protein microtubule-associated protein 1 light chain 3B (LC3B), P62, beclin-1 and autophagy-related gene 14 (ATG14). Immunofluorescence staining was used to detect protein expression of LC3B. Electron microscope was used to observe the autophagosome formation. Autophagy activator rapamycin and autophagy inhibitor 3-methyladenine were used for in vitro rescue experiments to observe the changes of the above indicators. Mechanistically, bioinformatics analysis was applied to analyze the binding site among circRNA_005987, miR-129-5p and ATG14, and dual luciferase reporter assay was used to verify their interactions. CircRNA_005987 was knocked down and overexpressed in HK-2 cell model, and RT-qPCR was used to detect the expression of miR-129-5p. HK-2 cells were treated with miR-129-5p inhibitor and mimic, Western blotting was used to detect the protein expression of ATG14, and CCK8 and Edu staining assays were used to evaluate cell proliferation. Results:CircRNA_005987 expression was up-regulated in vitro and vivo CA-AKI models (both P<0.05). Overexpression of circRNA_005987 inhibited cell proliferation and promoted cell autophagy, while knockdown of circRNA_005987 had opposite effects (all P<0.05). In vitro rescue experiments confirmed that circRNA_005987 inhibited cell proliferation by activating autophagy ( P<0.05). The dual luciferase reporter assay suggested that there was an interaction between circRNA_005987, miR-129-5p and ATG14. Knockdown of circRNA_005987 increased miR-129-5p expression, while overexpression of circRNA_005987 inhibited miR-129-5p expression (both P<0.05). Knockdown of miR-129-5p inhibited cell proliferation, while overexpression of miR-129-5p reversed the effect (both P<0.05). Conclusion:CircRNA_005987 promotes CA-AKI through activating autophagy via sponging miR-129-5p, suggesting that circRNA_005987 plays an important role in the pathological process of CA-AKI.

Objective:To analyze the serological and molecular characteristics of rare A el and B el subtypes in the ABO blood group system, and to explore their genotype-phenotype correlation and the potential clinical significance. Methods:From January 1st, 2021, to January 1st, 2025, 289, 815 samples subjected to ABO blood grouping in Henan Provincial People′s Hospital were selected. Samples demonstrating discrepancies between forward and reverse typing, or consistent typing but with abnormal agglutination degree were included. Those affected by underlying diseases, transplantation, age-related and other interferences were excluded. A total of 169 suspected ABO subgroup samples were identified. Sanger sequencing of exons 1-7 and relevant regulatory regions of the ABO gene was performed. Protein structure modeling and mutation effect analysis for two'el′ subtype glycosyltransferases (GTs) were conducted using SWISS-MODEL and PyMOL.Results:A total of 12 Ael, 6 B el, and 2 AB el subtypes were identified. Serological analysis revealed that all 18 A el/B el samples exhibited O phenotype in forward typing. Among them, A el subtypes showed weaker agglutination in reverse typing with A 1c than with Bc (>2+), while the opposite pattern was observed in B el subtypes. The two AB el samples were typed as A in forward typing, with agglutination ranging from 0-1+with Bc in reverse typing. Genetic analysis indicated that AEL.02 (c.646T>A, p.Phe216Ile) was the predominant allele in A el samples accounting for 7 cases. Also, we found an AEL.02-like variant (lacking c.681G>A), AEL.10 (c.963insC), and carrying a compound variant of c.322C>T (p.Gln108Ter) and c.296C>T (p.Thr99Ile). Among B el samples, BEL.03 (c.502C>T, p.Arg168Trp) accounted for 4 cases, one of which lacked the c.297A>G mutation, and novel mutations such as c.145_146dupCG were detected. Structural simulation demonstrated that AEL.02 and BEL.03 disrupted the hydrogen-bonding network within the active centers of GTA and GTB, respectively, and these mutations probably significantly impaired the structural stability of the corresponding GTs. Additionally, the c.296C>T mutation also markedly affected GTA structural stability. Conclusion:A el/B el subtypes are prone to mis-identify routine blood types. Their molecular mechanisms involved a variety of functional variantions, and integrating molecular detection is crucial for achieving accurate sub-typing and transfusion safety.

OBJECTIVE: To analyze the clinical data and results of prenatal diagnosis for fetuses with high-risk for trisomy/monosomy 13 by non-invasive prenatal testing (NIPT). METHODS: Clinical data of pregnant women with fetus at a high risk for trisomy/monosomy 13 by NIPT at the First Affiliated Hospital of Zhengzhou University from May 2016 to May 2024 were reviewed, and relevant data such as Z-score, positive predictive value (PPV) and fetal fraction (FF) were analyzed to assess the correlation between them. This study was approved by the Ethics Committee of the Hospital (No. 2018-YB-08). RESULTS: 71 fetuses were found to have a high risk by NIPT, including 58 cases for trisomy 13 (T13) and 13 cases for monosomy 13 (M13). 52 women had opted invasive prenatal diagnosis and 13 cases were confirmed, which yielded a positive prediction value (PPV) of 25%. 12 fetuses were confirmed as T13 (PPV = 29.3%; 12/41), 1 was confirmed as M13 (PPV = 9.1%; 1/11). The PPV had increased along with the Z-score. Fetal faction (FF) was not correlated with the age of woman but gestational age, and was negatively correlated with the body mass index. No statistical difference was found in FF and Z-score between true- and false-positive fetuses, and there was a weak correlation between the Z-score and FF. The PPV of the NIPT could be improved by combining the results of ultrasonography. CONCLUSION The high false positive rate for T13 may be related to confined placental mosaicism, PPV is related to the Z-score, which in turn is related to FF. High-risk women are strongly recommended to undergo genetic counseling and prenatal diagnosis. Clinicians should consider relevant information such as the age of women, gestational age, indication for prenatal screening, Z-score, PPV, and FF in order to accurately interpret the result of NIPT, reduce anxiety, and avoid direct termination of the pregnancy.
Humans ; Female ; Pregnancy ; Trisomy 13 Syndrome/genetics* ; Adult ; Prenatal Diagnosis/methods* ; Noninvasive Prenatal Testing/methods*

Objective:To analyze the clinical data and results of prenatal diagnosis for fetuses with high-risk for trisomy/monosomy 13 by non-invasive prenatal testing (NIPT).Methods:Clinical data of pregnant women with fetus at a high risk for trisomy/monosomy 13 by NIPT at the First Affiliated Hospital of Zhengzhou University from May 2016 to May 2024 were reviewed, and relevant data such as Z-score, positive predictive value (PPV) and fetal fraction (FF) were analyzed to assess the correlation between them. This study was approved by the Ethics Committee of the Hospital (No. 2018-YB-08). Results:71 fetuses were found to have a high risk by NIPT, including 58 cases for trisomy 13 (T13) and 13 cases for monosomy 13 (M13). 52 women had opted invasive prenatal diagnosis and 13 cases were confirmed, which yielded a positive prediction value (PPV) of 25%. 12 fetuses were confirmed as T13 (PPV = 29.3%; 12/41), 1 was confirmed as M13 (PPV = 9.1%; 1/11). The PPV had increased along with the Z-score. Fetal faction (FF) was not correlated with the age of woman but gestational age, and was negatively correlated with the body mass index. No statistical difference was found in FF and Z-score between true- and false-positive fetuses, and there was a weak correlation between the Z-score and FF. The PPV of the NIPT could be improved by combining the results of ultrasonography. Conclusion:The high false positive rate for T13 may be related to confined placental mosaicism, PPV is related to the Z-score, which in turn is related to FF. High-risk women are strongly recommended to undergo genetic counseling and prenatal diagnosis. Clinicians should consider relevant information such as the age of women, gestational age, indication for prenatal screening, Z-score, PPV, and FF in order to accurately interpret the result of NIPT, reduce anxiety, and avoid direct termination of the pregnancy.

BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.