ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group， a model group， and groups with different doses of Erjingwan （8，16，32 g·kg^-1）. The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum samples of mice， and biochemical tests were conducted to quantify the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione （GSH） in the serum. The protein and mRNA levels of SIRT1， Nrf2， B-cell lymphoma （Bcl-2）， and Bcl-2-associated X protein （Bax） were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultsAfter 4 weeks of drug intervention， the model group exhibited significant reductions in body weight and grip strength （P0.01） compared with the control group. Compared with the model group， all doses of Erjingwan increased the body weight in mice at week 8 （P0.01） and grip strength from week 6 （P0.01）. HE staining revealed clear muscle fiber structure in the control group， muscle fiber rupture and atrophy in the model group， and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group， collagen fiber proliferation and severe fibrosis in the model group， and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group （P0.01）. After intervention， the low-dose Erjingwan group exhibited a decreased TNF-α level （P0.05）， while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels （P0.01）. Biochemical assays revealed that the model group had decreased SOD and GSH levels （P0.01） and an increased MDA level （P0.01） compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels （P0.01） and decreases in MDA level （P0.01）， compared with the model group. WB and Real-time PCR results showed that compared with the control group， the model group presented down-regulated protein and mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 in the muscle tissue （P0.01） and up-regulated protein and mRNA levels of Bax （P0.01）. Compared with the model group， Erjingwan at different doses up-regulated the protein levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01） and down-regulated the protein and mRNA levels of Bax （P0.01） in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 （P0.05， P0.01）， and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01）. ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells， improved the antioxidant capacity， and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway， inflammatory response， and apoptosis network.

ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group， a model group， and groups with different doses of Erjingwan （8，16，32 g·kg^-1）. The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum samples of mice， and biochemical tests were conducted to quantify the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione （GSH） in the serum. The protein and mRNA levels of SIRT1， Nrf2， B-cell lymphoma （Bcl-2）， and Bcl-2-associated X protein （Bax） were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultsAfter 4 weeks of drug intervention， the model group exhibited significant reductions in body weight and grip strength （P0.01） compared with the control group. Compared with the model group， all doses of Erjingwan increased the body weight in mice at week 8 （P0.01） and grip strength from week 6 （P0.01）. HE staining revealed clear muscle fiber structure in the control group， muscle fiber rupture and atrophy in the model group， and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group， collagen fiber proliferation and severe fibrosis in the model group， and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group （P0.01）. After intervention， the low-dose Erjingwan group exhibited a decreased TNF-α level （P0.05）， while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels （P0.01）. Biochemical assays revealed that the model group had decreased SOD and GSH levels （P0.01） and an increased MDA level （P0.01） compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels （P0.01） and decreases in MDA level （P0.01）， compared with the model group. WB and Real-time PCR results showed that compared with the control group， the model group presented down-regulated protein and mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 in the muscle tissue （P0.01） and up-regulated protein and mRNA levels of Bax （P0.01）. Compared with the model group， Erjingwan at different doses up-regulated the protein levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01） and down-regulated the protein and mRNA levels of Bax （P0.01） in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 （P0.05， P0.01）， and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01）. ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells， improved the antioxidant capacity， and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway， inflammatory response， and apoptosis network.

Chronic lung allograft dysfunction (CLAD) is a common complication after lung transplantation, which severely impairs the long-term survival of patients. At present, effective therapeutic approaches remain lacking. Dysregulation of the lung microbiome acts as a pathogenic factor for a variety of pulmonary diseases. Accumulating studies have demonstrated that the compositional characteristics of the lung microbiome after lung transplantation are closely associated with CLAD. Therefore, this article reviews the definition of CLAD, characteristics of the lung microbiome, the influence of the lung microbiome on the occurrence and progression of CLAD, the potential mechanisms underlying the lung microbiome in the pathogenesis of CLAD, and microbiome-based intervention strategies for CLAD. It aims to provide novel insights for the prevention and treatment of CLAD following lung transplantation and further improve the prognosis of lung transplant recipients.

Purpose To explore the clinical value of real-time three-dimensional automatic left atrial quantification technology in evaluating left atrial volume and function in heart failure with preserved ejection fraction(HFpEF).Materials and Methods A total of 65 patients diagnosed as HFpEF at the Fourth Affiliated Hospital of Harbin Medical University from December 2021 to October 2023 were prospectively enrolled.The control group included 65 healthy subjects who underwent ultrasound examination during the same period and were matched with the HFpEF group in terms of age and gender.According to the New York Heart Association(NYHA)cardiac function classification,patients with NYHA grade Ⅰ+Ⅱ were classified into the HFpEF group A,and those with grade Ⅲ+Ⅳ into the HFpEF group B.Relevant clinical data,conventional ultrasound parameters and three-dimensional ultrasound parameters were recorded in both the HFpEF group and the control group.Left atrial volume parameters,longitudinal strain parameters and circumferential strain parameters were analyzed.The area under the receiver operating characteristic curve was used to compare the diagnostic efficacy of left atrial functional parameters for HFpEF.Results Compared with the control group,the HFpEF group exhibited significant abnormalities in cardiac structure and function.Specifically,left ventricular posterior wall thickness,interventricular septal thickness at end-diastole,and mean E/e′ were significantly increased(t=-5.127,-5.886,-16.670,all P<0.05),while the absolute value of left ventricular global longitudinal strain(LVGLS)and septal and lateral mitral annular e′ were significantly decreased(t=-17.092,40.279,45.412,all P<0.05).All left atrial volume parameters were significantly increased,whereas left atrial functional and strain parameters were significantly decreased(t=-13.632-6.912,all P<0.05).Compared with HFpEF group A,HFpEF group B showed lower left atrial total emptying fraction,left atrial expansion index,left atrial contraction strain and absolute value of LVGLS(t=2.062,3.545,-2.189,-2.586),as well as a higher left atrial minimum volume(t=-2.187),respectively(all P<0.05).Left atrial reservoir strain was negatively correlated with N-terminal pro-B-type natriuretic peptide and mean E/e′(r=-0.395,-0.626,both P<0.05),and positively correlated with the absolute value of LVGLS(r=0.602,P<0.05).The LASr and LAEI had high predictive value for HFpEF,with area under the curve of 0.898 and 0.817,cut-off values of 20.5%and 112%,sensitivities of 96.9%and 83.1%,specificities of 75.4%and 78.5%,and Youden indices of 0.723 and 0.616,respectively.Conclusion Real-time three-dimensional automatic left atrial quantification technology enables early and sensitive detection of left atrial dysfunction in HFpEF.Among the parameters derived,LASr(a strain parameter)and LAEI(a functional parameter)exhibit high diagnostic efficacy for HFpEF.

Objective:To compare the efficacy of active warming versus conventional warming during the perioperative period of robotic-assisted total hip arthroplasty (THA) for femoral neck fracture in elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 312 elderly patients with femoral neck fracture who underwent robot-assisted THA at Second Affiliated Hospital of Xi ′an Jiaotong University from January 2024 to January 2025, including 196 males and 116 females, aged 65-89 years [(77.0±7.3)years]. Among them, 156 patients received standardized thermal management (active warming group), involving the administration of pre-warmed intravenous fluids and use of an inflatable warming blanket preoperatively, combined application of a forced-air warming system and warmed fluids intraoperatively, and transfer to a temperature-controlled ward combined with a foot circulatory compression device postoperatively. The other 156 patients received conventional warming with cotton quilts (conventional warming group), involving no administration of pre-warmed intravenous fluids preoperatively, use of warmed fluids intraoperatively, and transfer to a standard ward without the use of a foot circulatory compression device postoperatively. Core body temperature was compared between the two groups at 30 minutes preoperatively, 30 minutes intraoperatively, immediately postoperatively, and at 1 hour, 1 day, 5 days, and 7 days postoperatively. Changes in the coagulation function, including prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), and the inflammatory marker C-reactive protein (CRP) were assessed at 1 day preoperatively and at 1, 5, and 7 days postoperatively. Length of hospital stay and incidence of postoperative complications (incision infection, deep vein thrombosis, cardiac complications, and unplanned reoperations) were also recorded. Results:The core body temperature at 30 minutes intraoperatively, immediately postoperatively and at 1 hour postoperatively was (36.77±0.17)℃, (36.29±0.14)℃, and (36.35±0.14)℃ in the active warming group, significantly higher than (36.12±0.27)℃, (35.49±0.25)℃, and (35.67±0.29)℃ in the conventional warming group ( P<0.01). No significant differences in body temperature were observed between the two groups at 30 minutes preoperatively, at 1, 5, or 7 days postoperatively ( P>0.05). At 1 day postoperatively, the PT, TT and APTT were (8.5±1.3)seconds, (10.0±0.9)seconds and (24.8±2.3)seconds, significantly lower than (9.7±1.3)seconds, (12.1±1.5)seconds and (29.2±2.7)seconds in the conventional warming group ( P<0.01). There were no significant differences in PT, TT, APTT or CRP levels between the two groups at 1 day preoperatively or at 5 and 7 days postoperatively ( P>0.05). The CRP level at 1 day postoperatively was (8.0±3.0)mg/L in the active warming group, significantly lower than (13.5±3.2)mg/L in the conventional warming group ( P<0.05). There were no significant differences in CRP between the two groups at 1 day preoperatively or at 5 and 7 days postoperatively ( P>0.05). The average length of hospital stay was (12.2±1.4)days in the active warming group, significantly shorter than (14.9±1.4)days in the conventional warming group ( P<0.01). The perioperative complication rate was 6.4% (10/156) in the active warming group, significantly lower than 17.9% (28/156) in the conventional warming group ( P<0.01). Conclusion:For elderly patients with femoral neck fracture operated via robot-assisted THA, active warming during the perioperative period can more effectively maintain intraoperative normothermia, improve early postoperative coagulation function, reduce inflammatory response, shorten the length of hospital stay, and decrease complication rate when compared with conventional warming.

Objective:To compare the efficacy of active warming versus conventional warming during the perioperative period of robotic-assisted total hip arthroplasty (THA) for femoral neck fracture in elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 312 elderly patients with femoral neck fracture who underwent robot-assisted THA at Second Affiliated Hospital of Xi ′an Jiaotong University from January 2024 to January 2025, including 196 males and 116 females, aged 65-89 years [(77.0±7.3)years]. Among them, 156 patients received standardized thermal management (active warming group), involving the administration of pre-warmed intravenous fluids and use of an inflatable warming blanket preoperatively, combined application of a forced-air warming system and warmed fluids intraoperatively, and transfer to a temperature-controlled ward combined with a foot circulatory compression device postoperatively. The other 156 patients received conventional warming with cotton quilts (conventional warming group), involving no administration of pre-warmed intravenous fluids preoperatively, use of warmed fluids intraoperatively, and transfer to a standard ward without the use of a foot circulatory compression device postoperatively. Core body temperature was compared between the two groups at 30 minutes preoperatively, 30 minutes intraoperatively, immediately postoperatively, and at 1 hour, 1 day, 5 days, and 7 days postoperatively. Changes in the coagulation function, including prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), and the inflammatory marker C-reactive protein (CRP) were assessed at 1 day preoperatively and at 1, 5, and 7 days postoperatively. Length of hospital stay and incidence of postoperative complications (incision infection, deep vein thrombosis, cardiac complications, and unplanned reoperations) were also recorded. Results:The core body temperature at 30 minutes intraoperatively, immediately postoperatively and at 1 hour postoperatively was (36.77±0.17)℃, (36.29±0.14)℃, and (36.35±0.14)℃ in the active warming group, significantly higher than (36.12±0.27)℃, (35.49±0.25)℃, and (35.67±0.29)℃ in the conventional warming group ( P<0.01). No significant differences in body temperature were observed between the two groups at 30 minutes preoperatively, at 1, 5, or 7 days postoperatively ( P>0.05). At 1 day postoperatively, the PT, TT and APTT were (8.5±1.3)seconds, (10.0±0.9)seconds and (24.8±2.3)seconds, significantly lower than (9.7±1.3)seconds, (12.1±1.5)seconds and (29.2±2.7)seconds in the conventional warming group ( P<0.01). There were no significant differences in PT, TT, APTT or CRP levels between the two groups at 1 day preoperatively or at 5 and 7 days postoperatively ( P>0.05). The CRP level at 1 day postoperatively was (8.0±3.0)mg/L in the active warming group, significantly lower than (13.5±3.2)mg/L in the conventional warming group ( P<0.05). There were no significant differences in CRP between the two groups at 1 day preoperatively or at 5 and 7 days postoperatively ( P>0.05). The average length of hospital stay was (12.2±1.4)days in the active warming group, significantly shorter than (14.9±1.4)days in the conventional warming group ( P<0.01). The perioperative complication rate was 6.4% (10/156) in the active warming group, significantly lower than 17.9% (28/156) in the conventional warming group ( P<0.01). Conclusion:For elderly patients with femoral neck fracture operated via robot-assisted THA, active warming during the perioperative period can more effectively maintain intraoperative normothermia, improve early postoperative coagulation function, reduce inflammatory response, shorten the length of hospital stay, and decrease complication rate when compared with conventional warming.

Purpose To explore the clinical value of real-time three-dimensional automatic left atrial quantification technology in evaluating left atrial volume and function in heart failure with preserved ejection fraction(HFpEF).Materials and Methods A total of 65 patients diagnosed as HFpEF at the Fourth Affiliated Hospital of Harbin Medical University from December 2021 to October 2023 were prospectively enrolled.The control group included 65 healthy subjects who underwent ultrasound examination during the same period and were matched with the HFpEF group in terms of age and gender.According to the New York Heart Association(NYHA)cardiac function classification,patients with NYHA grade Ⅰ+Ⅱ were classified into the HFpEF group A,and those with grade Ⅲ+Ⅳ into the HFpEF group B.Relevant clinical data,conventional ultrasound parameters and three-dimensional ultrasound parameters were recorded in both the HFpEF group and the control group.Left atrial volume parameters,longitudinal strain parameters and circumferential strain parameters were analyzed.The area under the receiver operating characteristic curve was used to compare the diagnostic efficacy of left atrial functional parameters for HFpEF.Results Compared with the control group,the HFpEF group exhibited significant abnormalities in cardiac structure and function.Specifically,left ventricular posterior wall thickness,interventricular septal thickness at end-diastole,and mean E/e′ were significantly increased(t=-5.127,-5.886,-16.670,all P<0.05),while the absolute value of left ventricular global longitudinal strain(LVGLS)and septal and lateral mitral annular e′ were significantly decreased(t=-17.092,40.279,45.412,all P<0.05).All left atrial volume parameters were significantly increased,whereas left atrial functional and strain parameters were significantly decreased(t=-13.632-6.912,all P<0.05).Compared with HFpEF group A,HFpEF group B showed lower left atrial total emptying fraction,left atrial expansion index,left atrial contraction strain and absolute value of LVGLS(t=2.062,3.545,-2.189,-2.586),as well as a higher left atrial minimum volume(t=-2.187),respectively(all P<0.05).Left atrial reservoir strain was negatively correlated with N-terminal pro-B-type natriuretic peptide and mean E/e′(r=-0.395,-0.626,both P<0.05),and positively correlated with the absolute value of LVGLS(r=0.602,P<0.05).The LASr and LAEI had high predictive value for HFpEF,with area under the curve of 0.898 and 0.817,cut-off values of 20.5%and 112%,sensitivities of 96.9%and 83.1%,specificities of 75.4%and 78.5%,and Youden indices of 0.723 and 0.616,respectively.Conclusion Real-time three-dimensional automatic left atrial quantification technology enables early and sensitive detection of left atrial dysfunction in HFpEF.Among the parameters derived,LASr(a strain parameter)and LAEI(a functional parameter)exhibit high diagnostic efficacy for HFpEF.

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

The " liver disease affecting to the spleen" theory first appeared in Nanjing and was further elaborated in Jingui Yaolue. This theory encapsulates the traditional Chinese medicine principles of the " unity of the five viscera" and the " preventive treatment of disease" . The theory emphasizes that the spleen is the pivotal point where depression may progress from a functional disorder to an organic disease. The liver governs the emotions and qi flow, whereas the spleen is responsible for qi, blood, and body. In the early stages of the disease, emotional disorders and qi flow disorders primarily affect the liver, manifesting as depression or low mood. As the condition progresses, the liver (Wood) overacts on the spleen (Earth), disrupting liver and spleen functions and causing qi and blood disharmony. This stage is marked by fatigue and psychomotor retardation. Prolonged illness depletes qi and blood, eventually involving all five viscera, disrupting the harmony of the five spirits, and affecting both body and spirit. At this advanced phase, intense emotional distress or agitation often arises, accompanied by a heightened risk of suicide. The disease progression follows a dynamic " qi-blood-spirit" pattern, in which depression begins in the liver, characterized by qi stagnation, then affects the spleen, involving blood disharmony. In later stages, the disease eventually affects all viscera, with profound effects on both physical and mental health. Treatment strategies should align with the disease stage. Early intervention should focus on regulating the flow of qi, treating the liver, and strengthening the spleen. In the middle stages, qi and blood should be harmonized while promoting the harmonized functions of the liver and spleen. In the later stages, treatment should harmonize the five viscera to restore balance between body and spirit. Guided by this theory, integrating modern medical understanding of the progression of depression from emotional to somatic symptoms and adopting a stage-based approach to treatment in clinical practice can yield effective therapeutic outcomes for managing depression and related disorders.

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.