OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

Objective To analyze the factors affecting pathological complete response(pCR)of triple-negative breast cancer(TNBC)patients after neoadjuvant chemotherapy,and construct a nomogram to forecast the pCR rate.Methods The clinical and pathological data of 348 TNBC patients who received neoadjuvant chemotherapy in the Air Force Medical University-Affiliated Xijing Hospital from May 2018 to May 2021 were collected and set as modeling set.The clinical and pathological data of 69 TNBC patients who received neoadjuvant chemotherapy in the Xi'an No.3 Hospital from May 2018 to May 2021 were collected and set as validation set.The clinical and pathological characteristics were compared between the modeling set and the validation set.In the modeling set,the independent risk factors of pCR in TNBC patients after neoadjuvant chemotherapy were screened by LASSO regression model analysis,and the nomogram model was constructed.Internal validation of the model was conducted using Bootstrap method,and the discrimination of the model was assessed by receiver operating characteristic(ROC)curve.The accuracy of the model was evaluated by the calibration curve and the clinical benefits and application value of the model were evaluated by clinical decision curve analysis(DCA).Results There were significant differences in surgical method and T stage between the patients in modeling set and validation set(P<0.05).The results of analysis of LASSO regression model showed that T stage,N stage,the use of platinum drugs and clinical efficacy evaluation were independent risk factors of pCR in TNBC patients after neoadjuvant chemotherapy(P<0.05).Based on the above variables,the nomogram models were constructed.In modeling set,area under curve(AUC)was 0.811(95%CI 0.763-0.859);in validation set,AUC was 0.801(95%CI 0.727-0.928).The Bootstrap method showed the C-index for internal validation was 0.79,indicating the model has good discrimination in both the modeling and validation sets.The calibration curve analysis showed that model predicted pCR rates had a good consistency with the actual observed values,and the DCA showed that model can bring clinical benefit.Conclusion The nomogram can accurately predict the pCR rates of TNBC patients after neoadjuvant chemotherapy and provide scientific basis for clinical diagnosis and treatment.

Objective:To analyze the construction of human resources in specialized public health institutions in China,with a view to providing reference for strengthening the construction of human resources in public health in China.Methods:Based on the data of China Health and Wellness Statistical Yearbook,descriptive statistical analysis,Gini coefficient and health resource agglomeration were used to analyze the quantity and quality of human resources in specialized public health institutions and the equity of human resource allocation in different regions of China from 2012 to 2021.Results:From 2012 to 2021,the average annual growth rate of the number of specialized public health institution personnel nationwide was 4.10%,and the average annual growth rate of the number of specialized public health institution personnel per 1 000 population was 3.71%.In 2021,the Gini coefficient of human resources in China's specialized public health institutions allocated by population was 0.1002,and the Gini coefficient of the allocation of human resources according to the geographic area was 0.6706,and 21 provinces'health resource agglomeration value were greater than 1.Conclusion:the total amount of human resources in China's specialized public health institutions has steadily increased during the decade,and the quality has been greatly improved,but there is still a gap with the expected development goal;the development of human resources in different specialized public health institutions is not balanced;demographic fairness is better than geographic fairness in the allocation of human resources in public health,and there are significant inter-provincial differences.

Hydration status refers to the balance between the intake and discharge of water in the body. When the ingested and discharged water are roughly equal and the body is in water balance, it is the normal hydration status, and when the water intake is too little or too much, it is the "dehydration" or "overhydration status". The hydration status of the body not only affects metabolism, but also affects the functions of the urinary system, cardiovascular system, nervous system, etc. In order to further clarify the relationship between body hydration status and decompression sickness (DCS), this paper reviewed relevant studies and analyzed the interaction between hydration and decompression safety during diving. The primary causes of dehydration in diving are "hyperbaric diuresis", "immersion diuresis", breathing dry gas, heat, and cold. Dehydration not only promotes the occurrence of DCS but also reduces the aerobic work efficiency and athletic performance of divers, as well as affects cognition and mood. A study found that appropriate rehydration before and during diving can reduce the risk of DCS, which possibly associates with the increase of blood volume, plasma surface tension, and vasoconstriction. Fluid therapy is also important for those who already have DCS. This paper analyzed the amount, nature, timing, and effect of rehydration involved in the above links, comprehensively sorted out the relationship between hydration and diving safety, summarized the existing problems, and provided reference for practical application and future research.

Objective:To investigate and analyze the current status of health management (physical examination) service capabilities of medical institutions in Tianjin in 2021.Methods:It was a cross-sectional study. Using the census method, a questionnaire survey was conducted to obtain the health management (physical examination) service capabilities of 86 medical institutions in Tianjin in 2021. The questionnaire covered the basic information of the institution, human resources and equipment, physical examination items carried out, the annual number of people receiving physical examination, the degree of informatization, and the completion of quality control indicators. In this survey, a total of 86 questionnaires were distributed and 86 valid questionnaires were collected (100%). Mann-Whitney U test and χ2 test were used to compare the differences of health management (physical examination) indicators between public and private medical institutions, and to analyze the current health management (physical examination) service capabilities of medical institutions in Tianjin. Results:Among the 86 medical institutions included in the analysis, 53 (61.6%) were public institutions and 33 (38.4%) were private medical institutions. In terms of basic information, the proportion of comprehensive hospitals and level-3 medical institutions belonging to public institutions, as well as the time of health management (physical examination) business development, were significantly higher than those of private medical institutions [62.3% vs 30.3%, 62.3% vs 0, 11 (7, 5) years vs 7 (5, 10) years], and the proportion of independent setup of the physical examination center and the business area of health management (physical examination) were significantly lower than those of private institutions[33.3% vs 98.1%, 1 011 (600, 1 000) m 2 vs 2 000 (1 395, 2 782) m 2] (all P<0.05). In terms of practitioners, there were 2 964 health management (physical examination) practitioners in Tianjin in 2021, aged 43 (35, 56) years. The proportion of male practitioners, part-time practitioners, nurses, practitioners with intermediate professional title, chief inspection physician, health management specialist in public institutions and the time engaged in health management work of employees were all significantly higher than those in private medical institutions [20.6% vs 17.5%, 20.7% vs 8.1%, 33.8% vs 23.4%, 40.7% vs 27.3%, 7.1% vs 3.9%, 13.8% vs 4.7%, 6 (3, 11) years vs 5 (3, 8) years] (all P<0.05). In terms of business development, the implementation rates of preventive medical management, mental health management, hypertension risk management, health management contract service, pulmonary nodule management, health management intervention plan, health risk assessment, and health education programs in public institutions were significantly higher than those in private medical institutions (24.5% vs 0, 28.3% vs 0, 35.8% vs 15.2%, 39.6% vs 15.2%, 41.5% vs 12.1%, 50.9% vs 18.2%, 66.0% vs 36.4%, 83.0% vs 42.4%), and the annual health physical examination person-times, group and individual physical examination person-times in public institutions were significantly lower than those in private institutions [18 625 (11 844, 27 998) to 38 384 (10 832, 46 927), 14 818 (8 803, 23 915) to 28 663 (4 982, 41 927), 2 179 (1 221, 3 588) to 5 784 (1 461, 12 156)] (all P<0.05). Among the six quality control indicators of health examination, the completion rates of waist-hip circumference measurement in both types of institutions were low (<40%). Conclusion:Compared with public institutions, the talent echelon construction and service capability of health management (physical examination) in private medical institutions in Tianjin still needs to be improved.

In the past few decades, microbubbles were widely used as ultrasound contrast agents in the field of tumor imaging. With the development of research, ultrasound targeted microbubble destruction technology combined with drug-loaded microbubbles can achieve precise drug release and play a therapeutic role. As a micron-scale carrier, microbubbles are difficult to penetrate the endothelial cell space of tumors, and nano-scale drug delivery system—nanobubbles came into being. The structure of the two is similar, but the difference in size highlights the unique advantages of nanobubbles in drug delivery. Based on the classification principle of shell materials, this review summarized micro/nanobubbles used for ultrasound diagnosis or treatment and discussed the possible development directions, providing references for the subsequent development.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Background::We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse model.Methods::In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups ( n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and hiPSC-CMs. Results::After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMs via enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significantly suppressed the production of malondialdehyde and lactate dehydrogenase and the reduction in glutathione content induced by hypoxia in both HUVECs and hiPSC-CMs in vitro. Conclusions::MLB significantly enhanced the potential of hiPSC-CMs in repairing injured myocardium by improving endothelial cell function via the NF-κB/ICAM1 pathway and inhibiting hiPSC-CMs apoptosis via the DUSP2/STAT3 pathway.