Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Sennoside A(SA),a typical prodrug,exerts its laxative effect only after its transformation into rhei-nanthrone catalyzed by gut microbial hydrolases and reductases.Hydrolases have been identified,but reductases remain unknown.By linking a photoreactive group to the SA scaffold,we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling(ABPP).From lysates of an active strain,Bifidobacterium pseudocatenulatum(B.pseu-docatenulatum),397 proteins were enriched and subsequently identified using mass spectrometry(MS).Among these proteins,chromate reductase/nicotinamide adenine dinucleotide(NADH)phosphate(NADPH)-dependent flavin mononucleotide(FMN)reductase/oxygen-insensitive NADPH nitroreductase(nfrA)was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource(UniProt)database screening.We also determined that recombinant nfrA could reduce SA.Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

OBJECTIVE: To assess the clinical value of digital PCR (dPCR) for the prenatal diagnosis of common fetal aneuploidies. METHODS: A dPCR-based assay was developed for detecting trisomies 21, 18, and 13. A retrospective analysis was carried out on 173 amniotic fluid samples collected by the Prenatal Diagnosis Center of Taizhou Hospital between January 2017 and December 2023. By using chromosomal karyotyping as the gold standard, the diagnostic performance of the multiplex dPCR system was evaluated in a double-blind manner. This study has been approved by the Ethics Committee of Taizhou Hospital (Ethics No. K20250339). RESULTS: Chromosomal karyotyping has identified 59 cases of trisomy 21, 5 cases of trisomy 18, 2 cases of trisomy 13, 6 cases with chromosomal structural abnormalities or mosaicisms, and 101 cases with a normal karyotype. The dPCR results (Z-score cutoff = 4.0, CI = 99.997%) showed full concordance with karyotyping (sensitivity = 100%, specificity = 100%, Kappa = 1). Among the 6 structurally abnormal or mosaicism samples, dPCR has accurately detected 4 cases, but mis-classified 2 cases of trisomy 21 with very low-level mosaicisms (3.3%, 6.9%, respectively) as normal. CONCLUSION The established multiplex dPCR system demonstrated high diagnostic accuracy for common chromosomal aneuploidies, with results available within 24 hours. It can serve as an efficient supplementary tool to conventional chromosomal karyotyping, providing reliable support for time-sensitive clinical decision-making in prenatal diagnosis.
Humans ; Female ; Pregnancy ; Aneuploidy ; Prenatal Diagnosis/methods* ; Karyotyping ; Retrospective Studies ; Polymerase Chain Reaction/methods* ; Chromosome Disorders/genetics* ; Adult ; Trisomy 13 Syndrome/diagnosis* ; Trisomy 18 Syndrome/genetics* ; Down Syndrome/genetics*

Irreversible pulpitis is characterized by inflammation of the pulp, leading to secondary interstitial hypertension and blood circulation disorders. This study explores the development of one-way membrane decompression to alleviate interstitial hypertension in the inflamed pulp and prevent the invasion of oral microorganisms into the pulp tissue. Additionally, this technique aims to improve the microcirculation of the pulp tissue by consistently reducing the pressure within the pulp cavity. Once the inflamed pulp tissue is restored, permanent crown filling can be performed. In this paper, we present a case study involving a patient with irreversible pulpitis who underwent vital pulp treatment using the one-way decompressed membrane. A four-year follow-up evaluation revealed satisfactory outcomes.

The comprehensive detection and identification of active ingredients in complex matrices is a crucial challenge.Liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS)is the most prominent analytical platform for the exploration of novel active compounds from complex matrices.However,the LC-HRMS-based analysis workflow suffers from several bottleneck issues,such as trace content of target compounds,limited acquisition for fragment information,and uncertainty in interpreting relevant MS2 spectra.Lycibarbarspermidines are vital antioxidant active ingredients in Lycii Fructus,while the reported structures are merely focused on dicaffeoylspermidines due to their low content.To comprehensively detect the new structures of lycibarbarspermidine derivatives,a"depict"strategy was developed in this study.First,potential new lycibarbarspermidine derivatives were designed according to the biosynthetic pathway,and a comprehensive database was established,which enlarged the coverage of lycibarbarspermidine derivatives.Second,the polarity-oriented sample prep-aration of potential new compounds increased the concentration of the target compounds.Third,the construction of the molecular network based on the fragmentation pathway of lycibarbarspermidine derivatives broadened the comprehensiveness of identification.Finally,the weak response signals were captured by data-dependent scanning(DDA)followed by parallel reaction monitoring(PRM),and the efficiency of acquiring MS2 fragment ions of target compounds was significantly improved.Based on the integrated strategy above,210 lycibarbarspermidine derivatives were detected and identified from Lycii Fructus,and in particular,170 potential new compounds were structurally characterized.The integrated strategy improved the sensitivity of detection and the coverage of low-response components,and it is expected to be a promising pipeline for discovering new compounds.

Objective To explore the effect of Traditional Chinese Medicine's five-element music therapy com-bined with individualized emotional counseling intervention in patients with autoimmune liver disease of liver de-pression and spleen deficiency type.Methods 74 patients with autoimmune liver disease of liver depression and spleen deficiency type who were admitted to the hepatology department of a tertiary hospital from January 2021 to February 2022 were selected as research subjects,and they were divided into an experimental group and a control group by a random number table with 37 cases in each group.The control group was given routine treatment and nursing care,as well as Traditional Chinese Medicine's emotional nursing.The experimental group received Tradi-tional Chinese Medicine's five-element music therapy combined with individualized emotional counseling intervention on the basis of routine treatment and nursing care,with an intervention period of 4 weeks.The Generalized Anxiety Disorder Scale(GAD-7),Patient Health Questionnaire Depression Scale(PHQ-9)and Pittsburgh Sleep Quality Index(PSQI)were used to evaluate patients within 24 hours after admission and after 4 weeks of intervention.Results A total of 72 patients completed the study,with 36 in the experimental group and 36 in the control group.Before and after intervention,the scores of GAD-7,PHQ-9,and PSQI in the experimental group were compared,and the dif-ferences were statistically significant(P＜0.001).After the intervention,the GAD-7 score in the experimental group was(7.89±3.15),which was lower than(10.14±4.41)in the control group.The PHQ-9 score was(12.33±4.08)in the ex-perimental group,which was lower than(14.64±5.34)in the control group.The PSQI score was(12.39±3.06)points,which was lower than(14.22±3.37)in the control group,and the differences were statistically significant(P＜0.05).Conclusion The application of Traditional Chinese Medicine's five-element music therapy combined with individual-ized emotional guidance intervention can effectively improve the sleep quality and help alleviate negative emotions in patients with liver depression and spleen deficiency type of autoimmune liver disease.

AIM: To explore the pharmacokinetic interactions between sorafenib and dapagliflozin in rats and to provide some theoretical basis for the rational clinical use of the two drugs. METHODS: An ultra -performance liquid chromatography-tandem mass spectrometry (UPLC / MS / MS) method was developed for the simultaneous determination of sorafenib and dapagliflozin. Male SD rats were randomly divided into 5 groups (6 rats in each group), including 100 mg / kg sorafenib group, 0.5 mg / kg dapagliflozin group, 1 mg / kg dapagliflozin group, and 100 mg/kg sorafenib combined with 0.5 mg/kg dapagliflozin group and 100 mg/kg sorafenib combined with 1 mg / kg dapagliflozin group, for sorafenib and dapagliflozin drug interaction study. All samples were analyzed using a validated UPLC/ MS/MS method, and the main pharmacokinetic parameters were calculated by compartment model. RESULTS: 1 mg/kg dapagliflozin increased the C

Palbocicril, the first cyclin-dependent kinases 4 and 6 inhibitors, is a crucial milestone in the development history of antineoplastic drugs. It combined with aromatase inhibitor or fulvestrant as first-line, second-line or post-line therapy has good efficacy and safety for hormone receptor-positive, human epidermal growth factor receptor-2 negative locally advanced or metastatic breast cancer, which has a good application prospect. This article summarizes the clinical trials and safety studies related to palbociclib.

Liver fibrosis is a key step in the progression of chronic liver diseases to liver cirrhosis and even liver cancer. In recent years， a large number of studies have shown the necessity of intervening in the process of liver fibrosis， and various anti-liver fibrosis drugs and active ingredients have been discovered. Non-coding RNAs also play an important role in the process of liver fibrosis， and searching for upstream non-coding RNAs that can regulate signaling pathways can provide new insights for anti-liver fibrosis treatment. This article introduces the process of liver fibrosis mediated by the TGF-β， Wnt/β-catenin， PI3K/Akt/mTOR， NF-κβ， Hippo， and MAPK signaling pathways， lists the latest anti-liver fibrosis drugs or active components in each signaling pathway， and summarizes the research advances in anti-liver fibrosis targets and drugs mediated by related non-coding RNAs， so as to provide new research ideas and treatment methods for anti-liver fibrosis treatment.

Objective:To investigate the effect of problem-oriented nursing intervention in the self-management rehabilitation of patients with coronary heart disease after percutaneous coronary intervention (PCI).Methods:A total of 128 patients with coronary heart disease undergoing PCI operation in Changzhou Second People′s Hospital from January 2019 to January 2021 were selected and randomly divided into the observation group and the control group with 64 cases in each group. The control group was given routine self-management intervention, and the observation group was given problem-oriented self-management intervention. After 6 months of intervention, the indicators of self-management ability, cardiac function, and quality of life were compared between the two groups.Results:After 6 months of intervention, the observation group actually completed 58 cases, and the control group actually completed 62 cases. Before the intervention, there were no significant differences between the two groups in the scores of coronary self-management ability scale, cardiac function index and Seattle Angina Questionnaire ( P>0.05). Six months after intervention, the scores of disease knowledge management, symptom management, first aid management, daily life management, bad addiction management, treatment compliance, and self-management ability in the observation group were 16.34 ± 2.36, 13.36 ± 2.42, 12.26 ± 2.23, 17.45 ± 2.74, 16.52 ± 2.45, 12.16 ± 2.15, 103.54 ± 14.32, which were significant higher than those of in the control group, 14.32 ± 2.45, 12.45 ± 2.23, 10.75 ± 2.32, 16.05 ± 2.45, 15.24 ± 2.53, 10.36 ± 2.24, 94.09 ± 13.36 ( t=2.14-4.59, all P<0.05). After six months of intervention, the left ventricular end-systolic diameter (LVESD) and the left ventricular end-diastolic diameter(LVEDD) were (34.39 ± 6.75) mm and (52.60 ± 6.31) mm, which were significant lower than those of the control group, (38.56 ± 6.52) mm and (55.79 ± 5.74) mm ( t=3.52 and 2.90, both P<0.05). Left ventricular ejection fraction (LVEF) and left ventricular short-axis shortening rate (FS) in the observation group after 6 months intervention were (44.25 ± 3.65)% and (23.86 ± 2.41)%, which were significant higher than those of in the control group, (39.24 ± 3.52)% and (22.26 ± 2.51)%( t=7.65 and 3.56, both P<0.05). Six months after the intervention, the scores of the degree of body limitation, angina pectoris, stable angina pectoris attack degree, treatment satisfaction, disease cognition degree, quality of life score in the observation group were 73.09 ± 8.13, 68.21 ± 10.15, 74.10 ± 4.45, 79.36 ± 8.21, 76.53 ± 9.43, 72.26 ± 9.12, which were significant higher than those of in the control group, 64.15 ± 8.11, 59.38 ± 10.23, 63.51 ± 5.23, 62.45 ± 8.16, 67.68 ± 9.20, 63.44 ± 8.65 ( t=4.74-11.91, all P<0.05). Conclusion:Problem-oriented nursing intervention is helpful to promote the development of self-management ability of patients with coronary heart disease after PCI, promote the recovery of postoperative cardiac function, and improve the quality of life of patients.