The Mechanism of Jinkui Wenjing Tang in the Treatment of Anovulatory Dysfunctional Uterine Bleeding was Explored Through Network Pharmacology and Molecular Docking Technology.

Objectives: Jinkui Wenjing Tang (JKWJT), a Traditional Chinese Medicine prescription for gynecological menstrual adjustment, is also used to treat continuous uterine bleeding and abdominal pain. However, the mechanism of action, potential targets, and active ingredients of JKWJT in the treatment of anovulatory dysfunctional uterine bleeding (ADUB) remain unknown. Therefore, it is imperative to explore the molecular mechanism of JKWJT. Methods: The chemical composition and target of JKWJT were obtained by using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the SwissTargetPrediction website. ADUB-related targets were collected through the GeneCards database. The protein-protein interaction network was constructed from the target protein. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. The binding of the compounds in JKWJT and the potential therapeutic target molecules was verified by molecular docking. Finally, immunohistochemistry, Western Blotting, and qPCR were used for target expression validation within ADUB patient tissues. Results: The putative targets of JKWJT for the treatment of ADUB mainly involve ESR1, VEGFA, TNF, AR, OXTR, and PCNA. Functional enrichment analysis showed that the therapeutic effect of JKWJT on ADUB was correlated to response to estradiol, gland development, regulation of hormone levels as well as endocrine resistance, estrogen signaling pathway, HIF-1 signaling pathway, EGFR tyrosine kinase inhibitor resistance, MAPK signaling pathway, prolactin signaling pathway. Molecular docking showed that the target OXTR was expected to have a good binding affinity with 4 corresponding compounds (Girinimbin, icosa-11, 14, 17-trienoic acid methyl ester, Kanzonol F, and Obacunone). After treatment with JKWJT, OXTR relative protein expression and mRNA levels were significantly reduced in ADUB patients. Conclusion: In this study, the basic pharmacological effects, and mechanisms of JKWJT in the treatment of ADUB were elucidated, thus providing a clinical basis for the treatment of ADUB by JKWJT.

A three-channel thermal dissociation cavity ring-down spectrometer for simultaneous measurement of ambient total peroxy nitrates, total alkyl nitrates, and NO2.

A newly constructed thermal dissociation cavity ring-down spectrometer (TD-CRDS) for the simultaneous measurement of ambient total peroxy nitrates (ΣPNs, RO2NO2), total alkyl nitrates (ΣANs, RONO2), and NO2 was presented in this work. ΣPNs and ΣANs were detected as NO2 with the CRDS instrument after thermal dissociation. PNs and ANs completely dissociated at 180 °C and 360 °C, with conversion efficiencies of 96 % and 99 %, respectively. The effects of NO2 and NO on measurement in different temperatures and two types of thermal dissociation inlet (TDI) were further explored. The influence of ambient NO2 and NO on PNs and ANs in the improved TDI (TDI-2) was significantly improved. To further enhance the measurement accuracy, the consistency of the observed NO2 in the three channels was tested, which achieved good agreement. The detection limits of the TD-CRDS instrument for NO2, ΣPNs, and ΣANs were determined as 6.5, 6.8, and 8.6 pptv (10 s, 1σ), respectively. Observations of PNs and ANs were conducted in a suburban site in Hefei, China, from September 2-30, 2021, using the TD-CRDS instrument, and the consecutive time series of PNs and ANs were derived, verifying the capability of the TD-CRDS instrument for continuous field observations of ΣPNs and ΣANs.

Coarse particles compensate for missing daytime sources of nitrous acid and enhance atmospheric oxidation capacity in a coastal atmosphere.

Large missing sources of daytime atmospheric nitrous acid (HONO), a vital source of hydroxyl radicals (OH) through its photolysis, frequently exist in global coastal regions. In this study, ambient HONO and relevant species were measured at a coastal site in the Pearl River Delta (PRD), China, during October 2019. Relatively high concentrations (0.32 ± 0.19 ppbv) and daytime peaks at approximately 13:00 of HONO were observed, and HONO photolysis was found to be the dominant (55.5 %) source of the primary OH production. A budget analysis of HONO based on traditional sources suggested large unknown sources during the daytime (66.4 %), which had a significant correlation with the mass of coarse particles (PM2.5-10) and photolysis frequency (J(NO2)). When incorporating photolysis of the abundant nitrate measured in coarse particles with a reasonable enhancement factor relative to fine particles due to favorable aerosol conditions, the missing daytime sources of HONO could be fully compensated by coarse particles serving as the largest source at this coastal site. Our study revealed great potential of coarse particles as a strong daytime HONO source, which has been ignored before but can efficiently promote NOx recycling and thus significantly enhance atmospheric oxidation capacity.

Predictive model of the efficiency of hematopoietic stem cell collection in patients with multiple myeloma and lymphoma based on multiple peripheral blood markers.

INTRODUCTION: Autologous hematopoietic stem cell transplantation (ASCT) has gained extensive application in the treatment of lymphoma and multiple myeloma (MM). Plenty of studies demonstrate that peripheral blood indicators could be considered potential predictive biomarkers for hematopoietic stem cells (HSCs) collection efficiency, including white blood cell count (WBC), monocyte count (Mono), platelet count (PLT), hematocrit, and hemoglobin levels. Currently, clinically practical predictive models based on these peripheral detection indicators to quickly, conveniently, and accurately predict collection efficiency are lacking. METHODS: In total, 139 patients with MM and lymphoma undergoing mobilization and collection of ASCT were retrospectively studied. The study endpoint was successful collection of autologous HSCs. We analyzed the effects of clinical characteristics and peripheral blood markers on collection success, and screened variables to establish a prediction model. We determined the optimal cutoff value of peripheral blood markers for predicting successful stem cell collection and the clinical value of a multi-marker prediction approach. We also established a prediction model for collection efficacy. RESULTS: Univariate and multivariate logistic regression analyses showed that the mobilization regimen, Mono, PLT, mononuclear cell count (MNC), and peripheral blood CD34+ cell count (PB CD34+ counts) were significant predictors of successful collection of peripheral blood stem cells (PBSC). Two predictive models were constructed based on the results of multivariate logistic analyses. Model 1 included the mobilization regimen, Mono, PLT, and MNC, whereas Model 2 included the mobilization regimen, Mono, PLT, MNC, and PB CD34+ counts. Receiver operating characteristic (ROC) curve analysis showed that the PB CD34+ counts, Model 1, and Model 2 could predict successful HSCs collection, with cutoff values of 26.92 × 106/L, 0.548, and 0.355, respectively. Model 1 could predict successful HSCs collection with a sensitivity of 84.62%, specificity of 75.73%, and area under the curve (AUC) of 0.863. Model 2 could predict successful HSCs collection with a sensitivity of 83.52%, specificity of 94.17%, and AUC of 0.946; thus, it was superior to the PB CD34+ counts alone. CONCLUSION: Our findings suggest that the combination of the mobilization regimen, Mono, PLT, MNC, and PB CD34+ counts before collection has predictive value for the efficacy of autologous HSCs collection in patients with MM and lymphoma. Using models based on these predictive markers may help to avoid over-collection and improve patient outcomes.