Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

Objective:To explore the risk factors of catheter-related thrombosis（CRT）in femoral vein indwelling catheter for patients undergoing artificial liver therapy.Methods:The clinical data 1 060 patients who received non biological artificial liver therapy with femoral vein catheterization at the Artificial Liver Center of the First Affiliated Hospital，Zhejiang University School of Medicine from February 26，2019 to March 30，2022 were retrospectively analyzed. During the treatment，CRT occurred in femoral vein indwelling catheter in 574 cases（54.2%，CRT group）and did not occurred in remaining 486 cases（non-CRT group）. The influencing factors of CRT were analyzed with multiple Logistic regression.Results:Univariate analysis showed that gender，D-dimer before and after catheterization，international normalized ratio（INR），total bilirubin，catheterization location，and catheter retention time were significantly associated with the occurrence of CRT（all P<0.05）. Multiple Logistic regression analysis showed that male gender（ OR=1.627，95% CI 1.233-2.148， P<0.001），right femoral vein catheterization（ OR=2.101，95% CI 1.130-3.908， P=0.019），catheter retention time（ OR=1.039，95% CI 1.003-1.077， P=0.035），D-dimer >500 μg/L FEU after catheterization（ OR=1.697，95% CI 1.191-2.416， P=0.003）and INR≥1.5（ OR=1.343，95% CI 1.001-1.801， P=0.049）were independent risk factors for CRT in femoral vein indwelling catheter for artificial liver therapy. Conclusion:The incidence of CRT is high in patients undergoing artificial liver therapy with femoral vein catheterization. In clinical practice，medical staff should early identify high-risk populations for CRT and take timely preventive measures.

Objective:To investigate the serum level of insulin-like growth factor binding protein 7 (IGFBP7) in patients with gastric cancer and its diagnostic significance.Methods:A total of 100 gastric cancer patients (gastric cancer group) including 49 patients with early gastric cancer (early gastric cancer group) , who were hospitalized in Sun Yat-sen University Cancer Center from May to December 2019 were selected as the research subjects, and 94 physical examination subjects during the same period were selected as the normal control group. The levels of serum IGFBP7 were detected by enzyme-linked immunosorbent assay. At the same time, the laboratory carcinoembryonic antigen (CEA) test results were collected. The relationships between the level of serum IGFBP7 and the clinicopathological features of gastric cancer patients were analyzed. The diagnostic value was evaluated by receiver operating characteristic (ROC) curve.Results:The level of serum IGFBP7 in the gastric cancer group was (1.595±0.159) ng/ml, and that in the normal control group was (1.850±0.328) ng/ml, with a statistically significant difference ( t=-0.26, P<0.001) , and among them, the level of serum IGFBP7 in the early gastric cancer group was (1.601±0.153) ng/ml, and there was a statistically significant difference compared with the normal control group ( t=-0.26, P<0.001) . The level of serum CEA in the gastric cancer group was 2.230 (2.043) ng/ml, and that in the normal control group was 1.805 (1.020) ng/ml, with a statistically significant difference ( U=0.45, P=0.004) , and among them, the level of serum CEA in the early gastric cancer group was 2.220 (1.780) ng/ml, and there was a statistically significant difference compared with the normal control group ( U=0.53, P=0.002) . There were no significant correlations between IGFBP7 and CEA level ( χ2=0.36, P=0.547) , age ( χ2=0.16, P=0.688) , gender ( χ2=0.97, P=0.326) , depth of invasion ( χ2=0.30, P=0.585) , lymph node metastasis ( χ2=0.17, P=0.684) , distant metastasis ( χ2=0.09, P=0.767) and TNM stage ( χ2=0.38, P=0.537) . ROC curve analysis showed that the area under the curve (AUC) of IGFBP7 for gastric cancer diagnosis was 0.84 (95% CI: 0.78-0.89) , the AUC of CEA for gastric cancer diagnosis was 0.62 (95% CI: 0.54-0.70) , and there was a statistically significant difference ( Z=4.33, P<0.001) . The AUC of IGFBP7 combined with CEA for gastric cancer diagnosis was 0.85 (95% CI: 0.79-0.90) . Compared with CEA alone, there was a statistically significant difference ( Z=4.97, P<0.001) . Compared with IGFBP7 alone, there was no statistically significant difference ( Z=1.41, P=0.159) . The AUC of IGFBP7 in the diagnosis of early gastric cancer was 0.84 (95% CI: 0.78-0.91) , the AUC of CEA in the diagnosis of early gastric cancer was 0.66 (95% CI: 0.56-0.75) , and there was a statistically significant difference ( Z=3.11, P=0.002) . The AUC of IGFBP7 combined with CEA in the diagnosis of early gastric cancer was 0.85 (95% CI: 0.78-0.91) . Compared with CEA alone, there was a statistically significant difference ( Z=3.54, P<0.001) . Compared with IGFBP7 alone, there was no statistically significant difference ( Z=1.19, P=0.232) . Conclusion:The serum IGFBP7 level of gastric cancer patients is lower than that of normal controls. Compared with CEA, serum IGFBP7 has better diagnostic value for gastric cancer.

OBJECTIVE: To validate the diagnosis of an infant with elevated urine 3-methylglutaconic acid (3-MGA) through sequencing of the CLPB gene. METHODS: Genomic DNA of the infant was sequenced by next generation sequencing (NGS), and candidate pathogenic variants were verified by Sanger sequencing and bioinformatics analysis. RESULTS: NGS has revealed that the infant has carried a c.1085G>A (p.Arg362Gln) and a c.1700A>C (p.Tyr567Ser) of the CLPB gene, which were respectively inherited from her parents. Among these, c.1085G>A (p.Arg362Gln) is a novel variant which was unreported previously, and based on the ACMG guidelines, it was predicted to be a possible pathogenic variant. CONCLUSION Compound heterozygous variants c.1085G>A (p.Arg362Gln) and c.1700A>C (p.Tyr567Ser) of the CLPB gene probably underlay the disease in this infant. Genetic testing has confirmed the diagnosis.

OBJECTIVE: To analyze the clinical and genetic characteristics of an infant girl featuring comprehensive developmental backwardness. METHODS: The patient was subjected to clinical examination, gas chromatography mass spectrometry and next-generation sequencing (NGS). RESULTS: The child was insensitive to sound, could not turn over, raise head, laugh or recognize his mother. Laboratory tests were all normal, but metabolic analysis suggested 3-methylglutaconic aciduria due to elevated 3-methylglutaconic acid and 3-methylglutaric acid. NGS has detected two compound heterozygous CLPB variants in the child, namely c.1085G>A and c.1700A>C, which were respectively inherited from her father and mother. Bioinformatic analysis predicted both variants to be pathogenic. The patient was diagnosed with 3-methylglutaconic aciduria type VII (MGCA7). CONCLUSION The MGCA7 in the child was probably caused by CLPB gene variants. NGS has provided a powerful diagnostic tool for this rare disorder.
Endopeptidase Clp ; genetics ; Female ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Metabolism, Inborn Errors ; genetics

OBJECTIVETo delineate the clinical and genetic characteristics of a girl featuring motor retardation, language retardation and regression, and light persisting diarrhea.

METHODSThe patient was clinically examined and tested by tandem mass spectrometry and next generation sequencing.

RESULTSThe proband could not stand and walk alone, and had light persisting diarrhea. She manifested language development retardation and regression. Laboratory tests were all normal, but the screening of metabolic disorders for urine and blood showed deficiency of short chain coenzyme A dehydrogenase due to elevated ethylmalonic acid and butyryl carnitine. By next generation sequencing, two compound heterozygous mutations of the ETHE1 gene, c.2T>A and c.488G>A, were discovered in the proband, which were respectively inherited from her father and mother. Bioinformatics analysis predicted both mutations to be pathogenic. The patient was diagnosed with ethylmalonic encephalopathy. Vitamin B1, B2, Coenzyme Q10, and L-carnitine were prescribed. The patient deteriorated and required liver transplantation at 4-year-1-month.

CONCLUSIONBased on the clinical and genetic analysis, the proband was diagnosed with ethylmalonic encephalopathy caused by ETHE1 gene mutation. Next generation sequencing has provided a powerful tool for the diagnosis of such disorders.

OBJECTIVETo explore the genetic cause of a Chinese boy with unexplained mental retardation, and analyze the pattern of inheritance for his family.

METHODSRoutine karyotyping, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH) were used to detect chromosome abnormalities in the patient and his families.

RESULTSChromosome analysis suggested that the proband and 7 affected individuals had an identical karyotype 46,XN,der(22)t(3;22)(q28;q13)pat, while his father and 5 other relatives carried a same karyotype of 46,XN,t(3;22)(q28;q13). His mother and other family members were normal. CMA analysis confirmed that the patient had a 9.0 Mb duplication at 3q28q29, in addition with a 1.7 Mb deletion at 22q13.3. Above results were confirmed by FISH.

CONCLUSIONThe abnormal phenotypes of the proband and his family members from five generations have conformed to those of 3q duplication and 22q13.3 deletion caused by unbalanced translocation involving chromosomes 3q and 22q. The presence of multiple patients in this family may be attributed to abnormal gametes produced by parental balanced translocations involving 3q and 22q.

Chromosome Deletion ; Chromosome Duplication ; Chromosomes, Human, Pair 22 ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; Cytogenetic Analysis ; methods ; Family Health ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Intellectual Disability ; genetics ; Karyotyping ; Male ; Pedigree ; Translocation, Genetic

Objective Investigate the Protective effect of paeoniflorin in rats with acute liver injury. Methods Male SD rats were randomly divided into normal group, model group, paeoniflorin in small, middle and high dose group (20 mg/kg, 40 mg/kg, 80 mg/kg), paeony glycoside group (50 mg/kg). Except normal group, the rest of groups were irradiated fractionally by VARIN 21-EX linear accelerator at right liver, The paeoniflorin group and paeony glycoside group were lavaged everyday after irradiation for corresponding drugs and doses. Normal group and model group give equal volume normal saline everyday. All rats were killed on 2nd and 4th weekend. Measure rats serum AST, ALT, hepatic tissue GSH, SOD, and HE staining score. Results The rats in model group liver tissue HE staining scores increased to(2.25±0.53)on 2nd weekend, The serum levels of AST, ALT increased to(112.83±19.20)U/L, (80±21.97)U/L, it significantly increased Compared with the normal group(63.06±7.15)U/L, (42.30±4.45)U/L, P<0.01. The liver GSH contents of paeoniflorin in each dosage groups rats were(60.89±8.43)U/mg, (67.84±9.05)U/mg, (71.92±8.11)U/mg on 2 nd weekend, Compared with the model group(37.32±11.25)U/mg, (90.54±12.12)U/mg, P<0.05或<0.01. Conclusions The irradiated rats go into acute liver injury on 2nd weekend, paeoniflorin has protective effect on acute liver injury in rats.

This paper is to report the polymorphism of raw materials of clopidogrel bisulfate at home and abroad. By the analysis of Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (p-XRD), samples are roughly classified into two groups, except one patent material. And the differential scanning calorimeter (DSC) examination showed more detailed information for these materials. The results of the study could provide comprehensive basis for the quality evaluation of clopidogrel bisulfate.
Calorimetry, Differential Scanning ; Crystallization ; Evaluation Studies as Topic ; Platelet Aggregation Inhibitors ; chemistry ; Spectroscopy, Fourier Transform Infrared ; Ticlopidine ; analogs & derivatives ; chemistry ; X-Ray Diffraction

Objective To explore the impact of intermittent androgen deprivation therapy on prostate volume and lower urinary tract symptoms (LUTS) in patients with prostate cancer combined with prostatic hyperplasia (BPH),and to evaluate the clinical effect of intermittent androgen deprivation therapy as compared with conventional drug in patients with BPH.Methods Patients with prostate cancer (n=57) and BPH (n=83) were respectively treated with intermittent androgen deprivation therapy and finasteride combined with alpha-receptor antagonist.Prostate volume,international prostate symptom score (IPSS),quality of life index (QOL) and maximum urinary flow rate (Qmax) in patients were observed before and 1,3,6 and 12 months after treatment.Results The improvements in prostate volume,IPSS,QOL and Qmax were higher in prostate cancer patients treated with intermittent androgen deprivation therapy than in BPH patients treated with finasteride combined with alpha-receptor antagonist (P ＜ 0.05).Conclusions Intermittent androgen deprivation therapy can significantly reduce prostate volume and improve LUTS in patients with prostate cancer,and has a better clinical effect than finasteride combined with alpha-receptor antagonist treatment.