NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Chronic myelomonocytic leukemia(CMML)complicated with immune thrombocytopenia(ITP)is rare.This article reports the clinical data of a patient with CMML complicated with ITP treated with a combination of venetoclax,ripertamab(an anti-CD20 monoclonal antibody),and hetrombopag.The coexistence mechanism of CMML and ITP needs to be further clarified.Venetoclax combined with anti-CD20 monoclonal antibody and thrombopoietin receptor agonist may be an effective strategy for the treatment of this complication.

Objective:To explore the application of list nursing management combined with different artificial liver treatment modes in patients with liver failure.Methods:Fifty-three patients with liver failure hospitalized in Bethune Hospital of Shanxi Province from July 2020 to July 2021 were selected as the control group, 63 patients with liver failure hospitalized in Bethune Hospital of Shanxi Province from July 2021 to July 2022 were selected as the intervention group. According to the different treatment modes of artificial liver for patients, plasma exchange (PE), double plasma molecular adsorption system (DPMAS) and PE + DPMAS treatment were set up in the two groups. The control group received routine nursing care, while the intervention group received checklist nursing care in addition. The changes of albumin (ALB) and prothrombin time (PT) indexes before and after the different treatment modes were compared, together with the occurrence of complications between the two groups after the intervention.Results:The baseline data between the two groups was balanced, the difference had no statistical significant ( P>0.05). After the therapy, the level of ALB of patients who had accepted DPMAS and PE + DPMAS in the intervention group were 25.3(24.0, 27.9) and 23.2(22.4, 26.3) g/L, which were lower than the 28.2(26.3, 29.7) and 29.4(27.2, 30.0) g/L in the control group, the differences were significant ( Z = 2.47, 3.55, both P<0.05). After the therapy, the level of PT of patients in the intervention group under all three treatment modes were 15.8(14.8, 16.8), 22.7(19.2, 26.2) and 6.0(14.6, 20.0) s, which were lower than the 17.4(15.9, 20.9), 26.3(21.4, 36.4) and 21.2(16.9, 23.4) s in the control group, the differences were significant ( Z = 2.10, 2.07, 2.21, all P<0.05). In the intervention group, there were 6 cases of hypotension, anaphylaxis, bleeding, coagulation and infection under the DPMAS treatment mode, which was significant lower than the 11 cases in the control group ( χ2 = 4.97, P<0.05). There were 4 cases in the intervention group with the PE + DPMAS treatment mode occurred complications in above, which were significant lower than the 11 cases in the control group ( χ2 = 6.87, P<0.01). Conclusions:Artificial liver treatment can improve patients′ liver function and coagulation, and list nursing management may help to improve the effect of artificial liver treatment. It can improve nurses′ awareness of risk prejudgement, reduce various risks in the treatment process, reduce the incidence of adverse reactions, and enhance health care and patient satisfaction.

Objective:To explore the association between the intraperitoneal pressure (IPP) and clinical symptoms in peritoneal dialysis (PD) patients.Methods:It was a cross-sectional study. PD patients of Peking University First Hospital from January 1, to October 31, 2021, were enrolled according to the inclusion and exclusion criterion. The gold standard—Durand method was used to measure the IPP of PD patients for 2 L intraperitoneal volume, and clinical and laboratory data were collected. According to whether the IPP ≥ 18 cmH 2O or not, the participants were divided into elevated IPP group and normal IPP group. A self-designed semi-quantitative questionnaire was used to investigate the frequency and degree of five clinical symptoms, including abdominal distension, bloating, acid reflux, hiccup and chest tightness or suffrage, as well as the degree of symptom relief after emptying peritoneal dialysate. Pearson or Spearman correlation analysis was used to analyze the correlation between each variable and intraperitoneal pressure. Results:A total of 194 PD patients were enrolled, with age of (51.6±12.9) years old. Of them, there were 123 males (63.4%), 71 females (36.6%) and 60 patients (30.9%) with diabetes. The median dialysis vintage was 24.0 (10.0, 54.0) months. The IPP was (16.2±4.3) cmH 2O, and 70 (36.1%) patients had elevated IPP. Correlation analysis results showed that IPP was positively correlated with body weight ( r=0.23, P<0.001), body mass index ( r=0.41, P<0.001), body surface area ( r=0.15, P=0.030), triglyceride ( r=0.22, P=0.001), high-sensitivity C-reactive protein ( r=0.20, P<0.001), and negatively correlated with diabetes ( r=-0.14, P=0.034) and serum calcium ( r=-0.15, P=0.034). There was no significant correlation between IPP and the total frequency score of five clinical symptoms ( r=0.122, P=0.092). The frequency of stomach distension in elevated IPP group was significantly higher than that in normal IPP group ( P=0.002), and there were no significant differences in the degree and relief degree of stomach distension between the two groups (all P>0.05). There were no statistically significant differences in the extent, frequency and degree of relief of other four clinical symptoms between the two groups (all P>0.05). Conclusion:The increased IPP has little correlation with clinical symptoms, suggesting that it may be unreliable to adjust the infusion volume only by the subjective feeling of patients. It is necessary to monitor IPP as an objective variable.

Objective:To automatically synthesize Al 18F-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04, perform PET/CT imaging in vivo, and evaluate its diagnostic efficacy on tumors. Methods:Al 18F-NOTA-FAPI-04 was produced in All-in-one automatic synthesis module and its quality control was conducted by high performance liquid chromatography (HPLC) equipped with a radioactive detector. Al 18F-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice ( n=3) and 4T1 breast cancer models ( n=3) to determine its biodistribution. Then Al 18F-NOTA-FAPI-04 and 18F-FDG PET/CT imaging were performed in a hepatocellular carcinoma patient (male, 51 years old). Results:The synthesis time of Al 18F-NOTA-FAPI-04 was about 35 min, and the radiochemical yield was (25.2±1.9)% (attenuation correction, n=3). The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (46.11±3.07) GBq/μmol (attenuation correction, n=3). The radiochemical purity was above 99.0% and was still above 98.0% at room temperature after 6 h. PET/CT imaging in mice showed that physiological uptake of Al 18F-NOTA-FAPI-04 was mainly in biliary system and bladder, and Al 18F-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that Al 18F-NOTA-FAPI-04 obtained high tumor background ratio (TBR) values of 4.1, 8.9, 5.4, 4.8, 2.2 in parasternal lymph nodes, anterior diaphragmatic lymph nodes, hilar lymph nodes, pancreaticoduodenal ligament lymph nodes, abdominal aortic lymph nodes, respectively, while TBR values were 1.0, 2.8, 5.0, 2.1, 1.1 by 18F-FDG. Conclusions:Al 18F-NOTA-FAPI-04 can be synthesized with short time, high radiochemical yield and good stability using All-in-one module. Al 18F-NOTA-FAPI-04 PET/CT imaging has high contrast and excellent diagnostic efficacy on tumors.

Glycyrrizae Radix et Rhizoma has high medicinal value and is widely used in compatibility. It is used most frequently in the compatibility of Chinese medicine prescriptions，and is known as ''Guolao''（national medicine） and "master of all medicines". The characteristic active ingredients are mainly liquitin，glycyrrizic acid，glycyrrizin，and licochalcone. In different compatibilities，based on traditional and modern pharmacological theories，the corresponding effect of Glycyrrizae Radix et Rhizoma are brought into play through different mechanisms. Based on the traditional pharmacology of Glycyrrizae Radix et Rhizoma for tonifying spleen，replenishing Qi，clearing heat，removing toxin，dispelling phlegm，relieving cough and pain，and harmonizing various medicines，this paper used herbal authentication to analyze its compatibility application and mechanism. It was found that Glycyrrizae Radix et Rhizoma played corresponding effect in compatibilities through "tonification"，"harmonization"，and "regulation". For example，Glycyrrizae Radix et Rhizoma was combined with tonics including Ginseng Radix et Rhizoma and Atractylodis Macrocephalae Rhizoma to tonify the five Zang-organs through its strong tonifying effect，combined with Paeoniae Radix Alba and Aconiti Lateralis Radix Praeparata to relieve emergencies and pains through harmonizing medicine power and properties，and combined with Rhei Radix et Rhizoma and Natrii Sulfas to reduce medicine intensity through regulating medicine properties and body characteristics. The application law and mechanism of the modern pharmacological compatibility of Glycyrrizae Radix et Rhizoma were analyzed by data mining and network pharmacology. It was found that the modern clinical formula was often compatible with Glycyrrizae Radix et Rhizoma for anti-inflammation，cardiovascular and cerebrovascular protection，anti-virus，and anti-tumor，Ephedrae Herba and Scutellariae Radix for anti-inflammation，Bambusae Caulis in Taenias，Salviae Miltiorrhizae Radix et Rhizoma，and Aurantii Fructus Immaturus for cardiovascular and cerebrovascular protection，and Ophiopogonis Radix and Chuanxiong Rhizoma for nerves protection. Meanwhile，the important targets of the characteristic ingredients were protein kinase B1 （Akt1），interleukin-6 （IL-6），tumor necrosis factor （TNF），and epidermal growth factor receptor （EGFR）. The important characteristic pathways such as tyrosine kinase inhibitor resistance pathway and cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG） signal pathway played the role of cardiovascular and cerebrovascular protection，and proteoglycan pathway in cancer played a neuroprotective role. This study is expected to provide references for the rational compatibility and application of Glycyrrizae Radix et Rhizoma，as well as the compatibility application of Chinese medicine prescriptions.

【Objective】 To learn the production efficient of platelet components among prefecture-level blood stations in China, to provide supporting data for those blood stations to optimize the production mode of platelet components and continuously improve production efficiency and supply capacity. 【Methods】 The data from 2017 to 2020 was obtained from 24 prefecture-level blood stations who were the members of the practice comparison network for blood institutes in China. The collection units of apheresis platelets, the number of dual-collections of apheresis platelets and plasma, the average apheresis units of one platelet apheresis procedure, the discarded rate of apheresis platelets, the amount of expired apheresis platelets and the amount of apheresis platelets issued were collected. For concentrated platelets, the prepared amount of platelet concentrates and the amount of expired platelet concentrates were collected; both the quantity of qualified and issued concentrated platelets were submitted for statistical analysis.The total output and efficiency of platelet components were calculated based on the collected data. 【Results】 The average annual growth rate of apheresis platelets collection in 24 prefecture-level blood stations was 12.23%, accounting for 99.80% of the total platelet output; the average collection unit of one platelets apheresis procedure was 1.75; from 2019 to 2020, only 5 blood stations performed dual-collection of platelet and plasma during one apheresis procedure; the discarded rate of apheresis platelets was 0.28%, of which 0.007% was due to expiration. A total of 1 621.2 therapeutic units of concentrated platelets were prepared, and 13.03% of them was discarded due to the expiration. The production efficiency of platelet components was 97.56%, of which the production efficiency of apheresis platelets was 97.61% and the production efficiency of concentrated platelets was 74.43%. 【Conclusion】 There are large regional differences in the supply capacity of platelet components in prefecture-level blood stations. Apheresis platelets are the main resource of platelet components product, and the collection capacity is increasing over the years with the characteristics of high production efficiency and low expiration scrapping rate. However, the preparation of concentrated platelets are still limited with relatively low production and high expiration discarded rate.

Objective:To explore the effect of empowerment education in patients with coronary heart disease after percutaneous coronary intervention (PCI) .Methods:From June 2020 to July 2021, convenience sampling was used to select 90 patients with coronary heart disease who received PCI in the Department of Cardiology of Qinhuai Medical District, Eastern Theater Command General Hospital as the research object. The 45 patients admitted from June to December 2020 were set as the control group, and the 45 patients admitted from January to July 2021 were set as the observation group. The control group received routine health education, and the observation group was given empowerment education on this basis. The physical activity level and aerobic exercise endurance of the two groups of patients were compared.Results:Repeated measures analysis of variance showed that there were between-group, time and interaction effects in the 6-minute walking distance between the two groups before intervention, one month and three months after intervention, and the differences were statistically significant ( P<0.05) . The physical activity levels of patients in the observation group were higher than those in the control group after one and three months of intervention, and the differences were statistically significant ( P<0.05) . Conclusions:Empowerment education can improve physical activity level and aerobic exercise endurance in patients with coronary heart disease after PCI.

Objective:To provide epidemiological data and clinical evidence for cosmetic adverse reactions.Methods:A retrospective clinical analysis was carried out on a total 820 outpatients (23 males and 797 females) suspected to be with cosmetic adverse reactions from January 2014 - October 2017, and average age of these patients was 7~75 (32.66±8.09) years. Suspicious cosmetics patch tests were performed in some patients. Suspicious cosmetics patch tests were performed in 687 patients.Results:Among 820 patients with cosmetic adverse reactions, women accounted for 97.20% and men accounted for 2.80%. Age distribution was most common among young people aged 21-40 years, accounting for 71.34%. The highest level of education was higher education, accounting for 59.69%. Occupational distribution was most commonly concentrated in employees and unemployed persons, accounting for 28.54% and 18.66%, respectively. A history of cosmetics allergies accounted for 17.28%. Cosmetic contact dermatitis was the most common clinical type of cosmetic adverse reactions, accounting for 92.70%. A total of 1682 suspected pathogenic cosmetics were involved. The positive rate of the cosmetic original patch test was 42.39%. Among the cosmetics with a positive patch test, moisturizing, anti-wrinkle and whitening freckle cosmetics accounted for the highest proportion, 31.59%, 15.09%, and 12.68%, respectively.Conclusions:Cosmetic contact dermatitis is the most common type of cosmetic adverse reaction. Patch testing is helpful in identifying the contact allergens in cosmetic adverse reaction.

Human milk oligosaccharides (HMOs) are the third largest solid component in human milk,followed by lactose and lipids.The importance of HMOs to infants has attracted more and more attention.The core structure of HMOs consists of galactose (Gal),glucose (Glc),N-acetylglucosamine (GlcAc),fucose (Fuc) and sialic acid (Sia) derived N-acetylneuraminic acid (Neu5Ac),which link with different groups that have different effects.HMOs could be used as prebiotics to regulate intestinal flora,as antiadhesives to resist pathogen adhesion,and as modulators of cell responses to regulate cellular inflammation.Through the mechanisms above,HMOs can affect many aspects of infant growth and development,such as relieving diarrhea,preventing respiratory infections,alleviating allergies,interfering with obesity,and even affecting the acquired immunodeficiency syndrome.This article will explain the structure of HMOs,the metabolism inside human body and the definite mechanism of action in process of infantile development and describe some related diseases.