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

This study was aimed at exploring the infections and viral genetic characteristics in rodents from coastal cities in Fujian Province.Intestinal tissue samples were obtained from rodents in Ningde,Fuzhou,Quanzhou,and Zhangzhou city.The adenovirus DNA polymerase(DPOL)gene was analyzed by nested PCR,and the large(L)segment gene of arenavirus was as-sessed with RT-PCR.Homology and genetic characteristics were analyzed in bioinformatics software.A total of 152 rodents were captured and showed a murine adenovirus infection rate of 4.61％.The murine adenovirus infection rate was 5.26％in wild rodents and 4.21％in domestic rodents.Murine adenoviruses were detected in four rodent species:Rattus sladeni,Rattus nor-vegicus,Rattus tanezumi,and Rattus losea.This was the first time that murine adenovirus has been detected in Rattus slade-ni.Analysis of relevant factors revealed no significant differences in murine adenovirus infection rates by rodent species,sex,age,and habitat.Sequence analysis indicated that the adenoviruses infecting rodents in coastal cities of Fujian were Murine ade-novirus 2 and Murine adenovirus 3.A significant difference was observed in the sequences of murine adenoviruses with respect to those in other regions,with nucleic acid sequence identity ranging from 72.25％to 91.01％.No arenavirus was detected in any rodent specimens.Adenovirus infections were found in rodents in coastal cities of Fujian Province,but no arenavirus infec-tions were found.This study provides useful information to support further research on murine adenovirus and arenavirus in Fujian Province.

This study was aimed at exploring the infections and viral genetic characteristics in rodents from coastal cities in Fujian Province.Intestinal tissue samples were obtained from rodents in Ningde,Fuzhou,Quanzhou,and Zhangzhou city.The adenovirus DNA polymerase(DPOL)gene was analyzed by nested PCR,and the large(L)segment gene of arenavirus was as-sessed with RT-PCR.Homology and genetic characteristics were analyzed in bioinformatics software.A total of 152 rodents were captured and showed a murine adenovirus infection rate of 4.61％.The murine adenovirus infection rate was 5.26％in wild rodents and 4.21％in domestic rodents.Murine adenoviruses were detected in four rodent species:Rattus sladeni,Rattus nor-vegicus,Rattus tanezumi,and Rattus losea.This was the first time that murine adenovirus has been detected in Rattus slade-ni.Analysis of relevant factors revealed no significant differences in murine adenovirus infection rates by rodent species,sex,age,and habitat.Sequence analysis indicated that the adenoviruses infecting rodents in coastal cities of Fujian were Murine ade-novirus 2 and Murine adenovirus 3.A significant difference was observed in the sequences of murine adenoviruses with respect to those in other regions,with nucleic acid sequence identity ranging from 72.25％to 91.01％.No arenavirus was detected in any rodent specimens.Adenovirus infections were found in rodents in coastal cities of Fujian Province,but no arenavirus infec-tions were found.This study provides useful information to support further research on murine adenovirus and arenavirus in Fujian Province.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Using the concepts and methods of epigenetics and metabolomics, to investigate the overall action molecular mechanism of Chrysanthemi indici C (CIC), the anti-hepatitis B virus (HBV) active extracts from Flos chrysanthemi indici. The inhibitory effects of CIC on proliferation and hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg) and HBV-DNA of HepG2.2.15 cells were detected by CCK-8 and antigen kit. The DNA methyltransferases (DNMTs)/ten-eleven-translocation-2 (TET2) equilibrium was detected by ELISA. Illumina 850K methylation chip, pyrosequencing and qPCR were used to determine the action pathway and target of CIC by GO and KEGG analysis. Cell metabolites were extracted with 80% methanol, and the changes of differential metabolites, differential metabolic pathways and cell microenvironment were detected by LC-MS and other metabolomics methods. The results showed that CIC could inhibit the proliferation, HBsAg, HBeAg and HBV-DNA of HepG2.2.15 cells obviously, down-regulate DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3a (DNMT3a) and DNA methyltransferase 3b (DNMT3b), up-regulate TET2, and restore the balance of DNMTs/TET2. The action targets of CIC were phospholipase C gamma 2 (PLCG2), phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2), 5-hydroxytryptamine receptor 2B (HTR2B), nerve growth factor (NGF), mainly involved in lipid metabolism, inflammation mediated regulation of transient receptor potential (TRP), phospholipase D signaling and advanced glycation end product-receptor for AGE (AGE-RAGE) signaling in diabetic complications pathways. CIC could significantly affect fatty acid metabolism and had great influence on phenolic acid, alkaloid and lipid metabolites in cell microenvironment. These results suggest that the action mechanism of CIC may be the synergistic action of multiple pathways and multiple targets, including related inflammatory pathways, immune pathways and lipid metabolism, through regulating epigenetic expression balance and restoring the balance of cell microenvironment.

Aim To study the effects of calycosin on proliferation and migration of human triple-negative breast cancer MDA-MB-231 cells and the underlying mechanisms. Methods MDA-MB-231 cells were intervened by calycosin,and the proliferation ability was detected by CCK-8 method. The apoptosis and cycle of MDA-MB-231 cells were detected by flow cytometry. The effect of calycosin on the migration of MDA-MB-231 cells was observed using cell scratch. The mRNA expression of EMT related genes was detected by RT-PCR. The effects of calycosin on the expression of key proteins of Hippo pathway and EMT related proteins were detected by Western blot. Results Calycosin could significantly inhibit the proliferation,migration and apoptosis of MDA-MB-231 cells,and markedly inhibit the expression of Hippo signaling pathway and EMT related protein. Conclusion Calycosin may induce MDA-MB-231 cell apoptosis,block cell cycle and inhibit cell migration by inhibiting Hippo signaling pathway and EMT pathway.

Objective: To observe the dynamic impacts of shock waves on the severity of lung injury in rats with different injury distances. Methods: Simulate open-field shock waves; detect the biomechanical effects of explosion sources at distances of 40, 44, and 48 cm from rats; and examine the changes in the gross anatomy of the lungs, lung wet/dry weight ratio, hemoglobin concentration, blood gas analysis, and pathology. Results: Biomechanical parameters such as the overpressure peak and impulse were gradually attenuated with an increase in the injury distance. The lung tissue hemorrhage, edema, oxygenation index, and pathology changed more significantly for the 40 cm group than for the 44 and 48 cm groups. The overpressure peak and impulse were significantly higher for the 40 cm group than for the 44 and 48 cm groups ( < 0.05 or < 0.01). The animal mortality was significantly higher for the 40 cm group than for the other two groups (41.2% . 17.8% and 10.0%, < 0.05). The healing time of injured lung tissues for the 40 cm group was longer than those for the 44 and 48 cm groups. Conclusions The effects of simulated open-field shock waves on the severity of lung injuries in rats were correlated with the injury distances, the peak overpressure, and the overpressure impulse.
Animals ; Biomechanical Phenomena ; Blast Injuries ; etiology ; pathology ; Disease Models, Animal ; Explosions ; Lung Injury ; etiology ; pathology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Sangzhi alkaloids (SZ-A) are derived from traditional Chinese medicine Ramulus Mori, serving well as an innovative antidiabetic drug, due to α-glucosidase inhibition. To evaluate the potency of glucosidase inhibitory effect of SZ-A, the enzyme-based screening platforms, including sucrase, maltase and amylase were established, and IC₅₀ was calculated. The effects of SZ-A on postprandial blood glucose at a single dose, oral sucrose, starch and glucose loading were determined in normal ICR mice and alloxan-induced hyperglycemic mice. To confirm the anti-diabetic effects of SZ-A on glucose and lipid metabolism after long-term administration, the postprandial and fasting blood glucose, serum insulin, urinary glucose levels, glycosylated serum proteins and blood lipid levels were determined in high-fat fed C57 obese mice (pre-diabetic HFC57 mice) and diabetic rats induced by streptozotocin (STZ). The Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College approved all of the protocols for this research. We found that SZ-A exhibited a significant inhibitory effect on the sucrase and maltase. SZ-A showed no effect on amylase. In normal ICR mice and alloxan-induced hyperglycemic mice, SZ-A at a single dose significantly delayed and reduced the peak of blood glucose after sucrose or starch loading, but showed no effect on the increase of blood glucose after glucose loading. In STZ diabetic rats, SZ-A significantly reduced the postprandial or fasting blood glucose levels, glycosylated serum proteins and urinary glucose. SZ-A also reduced serum triglyceride (TG) and cholesterol (TC) levels after 3 weeks of treatment. SZ-A ameliorated the postprandial blood glucose or the fasting blood glucose elevation, and reduced the incidence of hyperglycemia in HFC57 mice. SZ-A decreased the basal insulin level, improved insulin sensitivity, and ameliorated glucose intolerance in pre-diabetic HFC57 mice. Our results indicated that SZ-A had a novel inhibitory activity on α-glucosidase, especially on disaccharidases. SZ-A at a single dose significantly reduced the peak of blood glucose elevation and delayed the increase of blood glucose in normal and diabetic mice after disaccharide and polysaccharide loading. Long-term SZ-A treatment improved glucose and lipid metabolic profiles by delaying carbohydrate absorption from the intestine and reduced the postprandial blood glucose levels in both pre-diabetic and diabetic animal models. Therefore, SZ-A application may display a beneficial role in preventing the development and complications of diabetes.

OBJECTIVETo investigate the effect of HBP-A on meniscal injuries and the expressions of genes associated with pathological hypertrophy and calcification of the meniscusinduced by abnormal loading.

METHODSBovine meniscus explants were subjected to 25% strain at 0.3 Hz for 3 h and treated with 0.6 mg/mL of HBP-A. The cell viability in the meniscus explants after 72 hin culture was determined using live/dead staining and the expression levels of genes associated with pathological hypertrophy and calcification of the meniscus (ANKH, ENPP1, ALP, MMP13, and IL-1) were measured using real-time PCR and Western blotting. The conditioned medium was collected for testing sulfated glycosaminoglycan (GAG) release.

RESULTSThe number of dead cells, loss of proteoglycan content, and the expressions of ANKH, ENPP1, ALP and MMP13, and IL-1 at both the mRNA and protein levels were all significantly lower in the meniscus explants treated with 0.6 mg/mL HBP-A than in the explants with only 25% abnormal pressure stimulation (n=3, P<0.05).

CONCLUSIONHBP-A can effectively alleviate meniscal injuries induced by abnormal loading and suppress the expressions of genes related with pathological hypertrophy and calcification of the meniscus, and can serve as a potential drug for treatment of knee osteoarthritis.

Animals ; Calcinosis ; drug therapy ; Cattle ; Glucans ; pharmacology ; Hypertrophy ; Menisci, Tibial ; drug effects ; Osteoarthritis, Knee ; drug therapy ; Real-Time Polymerase Chain Reaction ; Tibial Meniscus Injuries ; drug therapy

INTRODUCTIONAntimicrobial stewardship programmes (ASP) can reduce antibiotic use but patient safety concerns exist. We evaluated the safety of prospective carbapenem review and feedback and its impact on carbapenem use and patient outcomes.

MATERIALS AND METHODSAfter 3 months implementation of our ASP, we compared patients with and without acceptance of ASP recommendations on the use of carbapenems. Primary outcome was 30-day mortality. Secondary outcomes included duration of carbapenem use, length of hospitalisation, clinical response, microbiological clearance, 30-day readmission and mortality at discharge.

RESULTSOf 226 recommendations for 183 patients, 59.3% was accepted. De-escalation, switching to oral antibiotics and antibiotic cessation comprised 72% of recommendations. Patients with acceptance of ASP recommendations had lower 30-day mortality and higher end-of-therapy clinical response despite shorter carbapenem duration (P <0.05). Predictors of 30-day mortality were Pitt bacteraemia score (adjusted odds ratio [aOR] 1.39, 95% confidence interval [CI], 1.11 to 1.74; P = 0.004) and non-acceptance of ASP recommendations (aOR 2.84, 95% CI, 1.21 to 6.64; P = 0.016).

CONCLUSIONOur prospective carbapenem review and feedback mainly comprising of reducing carbapenem use is safe.

Carbapenems ; therapeutic use ; Drug Utilization ; standards ; Feedback ; Guideline Adherence ; statistics & numerical data ; Humans ; Patient Safety ; Pharmaceutical Services ; Treatment Outcome