Objective To investigate the therapeutic effects and mechanism of enalapril maleate tablet on doxorubicin-induced heart failure rats based on mitogen-activated protein kinase(MAPK)signaling pathway.Methods Eleven of the 40 male SD rats were randomly selected as the normal group(equivalent to 0.9％NaCl),and the remaining 29 were prepared with intraperitoneal injection of 3 mg·kg-1·w-1 doxorubicin to prepare heart failure model.After successful modeling,they were randomly divided into model group(n=15 cases)and experimental group(n=14 cases).Experimental group was given 1.8 mg·kg-1·d-1 enalapril maleate suspension for gavage;normal and model groups were given the same amount of 0.9％NaCl by gavage.After 8 weeks,the rats were subjected to cardiac ultrasound,the left ventricular ejection fractions(LVEF)of each group were recorded,the serum myocardial injury index level was detected by enzyme-linked immunosorbent assay,and the expression levels of mRNA and protein related to the MAPK signaling pathway were detected by real-time quantitative polymerase chain reaction and Western blot.Results The LVEF values of control,model and experimental groups were(77.85±3.34％)％,(41.39±2.87％)％and(60.10±6.53％)％;serum brain natriuretic peptide contents were(219.30±10.59),(333.90±61.19)and(260.00±16.10)pg·mL-1;the relative expression levels of Mapk8ip2 were 1.00±0.01,2.60±0.12 and 2.00±0.08;the relative expression levels of Mapk8ip3 were 1.00±0.00,6.77±1.04 and 3.66±0.54;the relative expression levels of Mapk1 were 1.00±0.00,4.40±0.14 and 2.71±0.24;the relative expression levels of Mapk3 were 1.00±0.01,7.83±0.34 and 2.71±0.24;the relative expression levels of P38-MAPK were 1.00±0.05,1.14±0.02 and 1.02±0.03;the relative expression levels of extracellular regulated protein kinase 1/2 protein were 1.00±0.07,1.49±0.03 and 1.16±0.10;the relative expression levels of c-Jun N-terminal kinase 1/2 protein were 1.00±0.03,1.65±0.19 and 1.14±0.01,respectively.Compared with the model group,the differences of above indexes in the normal and experimental groups were statistically significant(all P＜0.01).Conclusion Enalapril maleate tablets have therapeutic effects on rats with heart failure,and the mechanism may be achieved by regulating the MAPK signaling pathway.

Objective To compare the pharmacokinetics of crushed posaconazole enteric-coated tablets and oral suspension after intragastric administration in rabbits.Methods The experiment was designed in a randomized cross-over study.Six New Zealand rabbits were intragastrically administrated with crushed posaconazole enteric-coated tablets or suspension,and blood was collected at specific time points.The concentration of posaconazole in plasma was determined by high-performance liquid chromatography,and the pharmacokinetic parameters of both groups were calculated with DAS 2.0 software.Results The main pharmacokinetic parameters of posaconazole enteric-coated tablets and suspension were obtained as follows:AUC0-twere(40.03±5.04)and(49.92±16.09)μg·mL-1·h;AUC0-∞ were(44.00±4.50)and(51.10±16.80)μg·mL-1·h;t1/2 were(7.30±1.13)and(8.53±1.34)h;Cmrx were(3.12±0.57)and(2.78±0.60)μg·mL-1;apparent volume of distribution(Vd)were(2.40±0.34)and(2.59±0.76)L·kg-1;clearance rate(CL)were(0.23±0.02)and(0.22±0.08)L·h-1·kg.There were no statistic differences in AUC0-t,Cmax and Vd between posaconazole suspension and crushed enteric-coated tablets after intragastric administration(all P＞0.05).Conclusion There was no pharmacokinetic advantage for crushed enteric-coated tablets against oral suspension.

Objective:To build a systematic and standardized nutrition management plan for patients with chronic kidney disease.Methods:Based on the nutrition care procedure and model, a preliminary draft of a nutrition management plan for chronic kidney disease patients was developed through a literature search, quality evaluation, and group discussions. After two rounds of expert consultation and revision of the preliminary draft of the nutrition management plan, the final plan was formed.Results:A total of 32 experts were invited to complete two rounds of consultation. In two rounds of expert consultation, 32 questionnaires were distributed, and 32 and 31 valid questionnaires were collected, with valid response rates of 100.0% and 96.9%, respectively. The expert authority coefficients were 0.853 and 0.871, respectively. The final nutrition management plan for chronic kidney disease patients included six first-level items of nutrition management personnel: nutrition risk screening, nutrition assessment, nutrition treatment, nutrition monitoring, and nutrition health education, with 23 second-level and 52 third-level items.Conclusions:The constructed nutrition management plan for chronic kidney disease patients is scientific and can provide a reference for nutrition guidance.

AIM To analyze the constituents absorbed into blood and brain from Zhishe Tongluo Capsules.METHODS Sixteen rats were randomly assigned into four groups and given intragastric administration(3.1 g/kg),after which the cerebral ischemia-reperfusion injury(MACO)model was established,the blood and brain tissues were collected,and UHPLC-Q Exactive Focus MS/MS was adopted in the identification of prototype constituents.RESULTS Total 70 constituents were identified,20 of which were found in the blood,mainly including flavonoids,tanshinones and Ligusticum chuanxiong phthalides,and 7 of them could enter the brain through blood-brain barrier.Compared with the normal administration group,the MACO administration group demonstrated added constituents absorbed into blood containing 3-hydroxybenzoic acid,calycosin-7-glucoside,curcumenol,senkyunolide B,dihydrotanshinone I and cryptotanshinone;removed constituents absorbed into brain containing puerarin,elemicin,sedanolide,and added those containing salvianolic acid A,senkyunolide I,dihydrotanshinone I in the left brain tissues(infarcted side).CONCLUSION The constituents absorbed into blood and brain from Zhishe Tongluo Capsules,along with the enhanced absorptions of phthalides,quinones and phenols in MACO rats in vivo may be the active substances for treating cerebral infarction.

To explore the mechanism of the active ingredients of Qishiwei Zhenzhu Pills in inhibiting the hepatorenal toxicity of the zogta component based on serum pharmacochemistry and network pharmacology, thereby providing references for the clinical safety application of Qishiwei Zhenzhu Pills. The small molecular compounds in the serum containing Qishiwei Zhenzhu Pills of mice were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Then, by comprehensively using Traditional Chinese Medicines Systems Pharmacology(TCMSP), High-throughput Experiment-and Reference-guided Database(HERB), PubChem, GeneCards, SuperPred, and other databases, the active compounds in the serum containing Qishiwei Zhenzhu Pills were retrieved and their action targets were predicted. The predicted targets were compared with the targets of liver and kidney injury related to mercury toxicity retrieved from the database, and the action targets of Qishiwei Zhenzhu Pills to inhibit the potential mercury toxicity of zogta were screened out. Cytoscape was used to construct the active ingredient in Qishiwei Zhenzhu Pills-containing serum-action target network, and STRING database was used to construct the protein-protein interaction(PPI) network of intersection targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out on the target genes by the DAVID database. The active ingredient-target-pathway network was constructed, and the key ingredients and targets were screened out for molecular docking verification. The results showed that 44 active compounds were identified from the serum containing Qishiwei Zhenzhu Pills, including 13 possible prototype drug ingredients, and 70 potential targets for mercury toxicity in liver and kidney were identified. Through PPI network topology analysis, 12 key target genes(HSP90AA1, MAPK3, STAT3, EGFR, MAPK1, APP, MMP9, NOS3, PRKCA, TLR4, PTGS2, and PARP1) and 6 subnetworks were obtained. Through GO and KEGG analysis of 4 subnetworks containing key target genes, the interaction network diagram of active ingredient-action target-key pathway was constructed and verified by molecular docking. It was found that taurodeoxycholic acid, N-acetyl-L-leucine, D-pantothenic acid hemicalcium, and other active ingredients may regulate biological functions and pathways related to metabolism, immunity, inflammation, and oxidative stress by acting on major targets such as MAPK1, STAT3, and TLR4, so as to inhibit the potential mercury toxicity of zogta in Qishiwei Zhenzhu Pills. In conclusion, the active ingredients of Qishiwei Zhenzhu Pills may have a certain detoxification effect, thus inhibiting the potential mercury toxicity of zogta and playing a role of reducing toxicity and enhancing effect.
Animals ; Mice ; Medicine, Tibetan Traditional ; Network Pharmacology ; Molecular Docking Simulation ; Tandem Mass Spectrometry ; Toll-Like Receptor 4 ; Medicine, Chinese Traditional ; Mercury ; Drugs, Chinese Herbal/toxicity*

OBJECTIVES: Sepsis is a critical dysregulated host response with high mortality and current treatment is difficult to achieve optimal efficacy. Ozone therapy has been revealed to protect infection and inflammation-related diseases due to its role in antibiotic and immunoregulatory effect. Ozonated triglyceride is a key component of ozonated oil that is one of ozone therapy dosage form. However, the potential role of ozonated triglyceride in sepsis remains unclear. This study aims to explore the effect of ozonated triglyceride on septic mouse model and the molecular mechanism. METHODS: Intraperitoneal injection of lipopolysaccharide (LPS), cecal ligation and puncture (CLP) were applied to construct septic mouse model. The mouse serum was obtained for detection of cytokines, and lung tissues were collected for hematoxylin and eosin (HE) staining to evaluate the extent of lung injury in septic mouse with ozonated triglyceride treatment at different time and doses. The survival of septic mice was observed for 96 h and Kaplan-Meier analysis was used to analyze the survival rates. In addition, primary peritoneal macrophages and human acute monocytic-leukemia cell line (THP-1) were treated with inflammasome activators with or without ozonated triglyceride. The level of cytokines was detected by enzyme-linked immunosorbent assay (ELISA). The cleavage of caspase-1 and gasdermin-D (GSDMD) was detected by Western blotting. RESULTS: Ozonated triglyceride at different time and doses reduced the release of inflammasome-related cytokines [interleukin (IL)-1β and IL-18] (all P<0.05) but not pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-α (TNF-α) in septic mice (all P>0.05). Ozonated triglyceride significantly improved the survival rate of septic mice and reduced sepsis-induced lung injury (all P<0.05). Ozonated triglyceride significantly suppressed the canonical and non-canonical activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome (all P<0.05) but not affected absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasomes in vitro (all P>0.05). Ozonated triglyceride reduced the cleavage of caspase-1 and the downstream GSDMD. CONCLUSIONS Ozonated triglyceride presents a protect effect on sepsis lethality via reducing cytokines release and sepsis-related organ injury. The mechanism is that ozonated triglyceride specifically suppresses the activation of NLRP3 inflammasome. Ozonated triglyceride is a promising candidate for sepsis treatment.
Animals ; Humans ; Mice ; Caspase 1 ; Cytokines ; Disease Models, Animal ; Inflammasomes ; Lung Injury ; NLR Family, Pyrin Domain-Containing 3 Protein ; Ozone/therapeutic use* ; Sepsis/drug therapy*

Objective: To investigate the association between gestational diabetes mellitus (GDM) and preterm birth subtypes. Methods: Based on the cohort of pregnant women in Anqing Prefectural Hospital, the pregnant women who received prenatal screening in the first or second trimesters were recruited into baseline cohorts; and followed up for them was conducted until delivery, and the information about their pregnancy status and outcomes were obtained through electronic medical record system and questionnaire surveys. The log-binomial regression model was used to explore the association between GDM and preterm birth [iatrogenic preterm birth, spontaneous preterm birth (preterm premature rupture of membranes and preterm labor)]. For multiple confounding factors, the propensity score correction model was used to compute the adjusted association. Results: Among the 2 031 pregnant women with a singleton delivery, the incidence of GDM and preterm birth were 10.0% (204 cases) and 4.4% (90 cases) respectively. The proportions of iatrogenic preterm birth and spontaneous preterm birth in the GDM group (n=204) were 1.5% and 5.9% respectively, while the proportions in non-GDM group (n=1 827) were 0.9% and 3.2% respectively, and the difference in the proportion of spontaneous preterm birth between the two groups was significant (P=0.048). Subtypes of spontaneous preterm were further analyzed, and the results showed that the proportions of preterm premature rupture of membranes and preterm labor in the GDM group were 4.9% and 1.0% respectively, while the proportions in the non-GDM group were 2.1% and 1.1% respectively. It showed that the risk of preterm premature rupture of membranes in GDM pregnant women was 2.34 times (aRR=2.34, 95%CI: 1.16-4.69) higher than that in non-GDM pregnant women. Conclusions: Our results showed that GDM might increase the risk of preterm premature rupture of membranes. No significant increase in the proportion of preterm labor in pregnant women with GDM was found.
Infant, Newborn ; Female ; Pregnancy ; Humans ; Premature Birth ; Diabetes, Gestational ; Obstetric Labor, Premature ; Hospitals ; Iatrogenic Disease

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objective To observe the clinical efficacy of levofloxacin combined with levofloxacin scheme in the treatment of pulmonary tuberculosis patients with positive hepatitis B surface antigen(HBsAg)and its impact on drug-induced liver injury.Methods Pulmonary tuberculosis patients with positive HBsAg were divided into treatment group and control group according to the anti-tuberculosis treatment plan.The treatment group received 2HLZE/4HLE anti-tuberculosis regimen(levofloxacin 0.6 g,twice a week+isoniazid 0.3 g,qd+ethambutol hydrochloride 0.75 g,qd+pyrazinamide 0.5 g,tid)for 6 months,and the control group received 2HRZE/4HRE anti-tuberculosis regimen(levofloxacin 0.6 g,qd+isoniazid 0.3 g,qd+ethambutol hydrochloride 0.75 g,qd+pyrazinamide 0.5 g,tid)for 6 months.The sputum smear conversion rate,liver function indicators[glutamate pyruvate transaminase(GPT),glutamate oxaloacetate transaminase(GOT),serum total bilirubin(TBIL)],clinical efficacy,drug-induced liver injury,as well as the incidence of adverse drug reactions were compared between the two groups.Results A total of 41 patients were enrolled in the treatment group and 39 patients in the control group.After treatment,the clinical total effective rates in the treatment and control groups were 97.56％and 79.49％,which showed statistically significant difference(P＜0.05).After 4 months of treatment,the sputum smear conversion rates in the treatment group and the control group were 90.24％and 71.79％,respectively;after 6 months of treatment,the sputum smear conversion rates in the treatment group and the control group were 95.12％and 79.49％,respectively,both showing statistically significant differences(all P＜0.05).After 6 months of treatment,the GPT levels in the treatment group and the control group were(87.39±17.26)and(101.49±23.48)U·L-1,the GOT levels were(97.54±19.25)and(119.63±21.57)U·L-1,and the TBIL levels were(31.53±9.35)and(38.27±9.64)μmol·L-1,respectively,all showing statistically significant differences(all P＜0.05).The incidence of drug-induced liver injury in the treatment group and the control group was 19.51％and 41.03％respectively,and the time of liver injury occurrence was(12.98±2.26)and(10.23±1.95)days,both showing statistically significant differences(all P＜0.05).The total incidences of adverse reactions in the treatment group and the control group was 29.27％and 64.10％respectively,with statistically significant differences(P＜0.05).Conclusion Compared with the levofloxacin scheme,the levofloxacin combined with levofloxacin scheme can reduce the incidence and severity of drug-induced liver injury and improve the clinical treatment efficacy in pulmonary tuberculosis patients with positive HBsAg.

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.
Male ; Female ; Humans ; Adult ; Retrospective Studies ; Treatment Outcome ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Precursor Cells, T-Lymphoid ; Leukemia, Myeloid, Acute/drug therapy*