BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.

Objective To explore the optimization strategy of Qishen Granules in treating coronary heart disease with heart failure(CHD-HF)based on data mining and the pathogenic"toxin"theory,and to predict its active components and mechanisms using network pharmacology.Methods Literature on traditional Chinese medicine(TCM)for treating CHD-HF was collected from relevant databases,and prescriptions were screened and established into a database according to inclusion and exclusion criteria.Frequency,association rules,and hierarchical clustering analyses were performed using the Ancient and Modern Medical Case Cloud Platform.Network pharmacology techniques were applied to screen potential targets of the optimized combination for treating CHD-HF,and carry out the targets and pathways enrichment analysis.Results A total of 336 articles and 339 prescriptions involving 191 herbs were included,with 12 herbs used more than 100 times.The core drug combinations for treating CHD-HF included Astragali Radix,Poria,Salviae Miltiorrhizae Radix et Rhizoma,Glycyrrhizae Radix et Rhizoma,Chuanxiong Rhizoma,etc,while commonly used detoxifying herbs included Leonuri Herb,Coptidis Rhizoma,etc.Association rule analysis yielded 10 two-item associations and 17 three-item associations;clustering analysis grouped the data into 5 categories.Based on data mining and the pathogenic"toxin"theory,the combination for treating CHD-HF was optimized to include Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Aconiti Lateralis Radix Praeparata,Glycyrrhizae Radix et Rhizoma,Coptidis Rhizoma,and Taraxaci Herba.Network pharmacology analysis identified 366 common targets between the optimized combination and CHD-HF,with 16 core targets screened out.Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed significant enrichment in pathways such as cancer pathways,lipid and atherosclerosis,Rap1 signaling pathway,hypoxia-inducible factor 1(HIF-1)signaling pathway,phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)signaling pathway,Ras signaling pathway,and mitogen-activated protein kinase(MAPK)signaling pathway.Conclusion TCM treatment for CHD-HF primarily focuses on replenishing qi and warming yang,activating blood circulation and resolving fluid retention.Based on data mining results and the pathogenic"toxin"theory,the formulation strategy of Qishen Granules for treating CHD-HF was optimized,potentially exerting therapeutic effects through anti-inflammatory,anti-apoptotic,and anti-hypoxia physiological processes.

Objective:This study investigates the utility of ultrasound in diagnosing eosinophilic fasciitis (EF).Methods:A retrospective analysis was conducted on the clinical and ultrasound data of 109 EF patients seen at the center between January 1, 2006, and March 31, 2024. The diagnostic efficacy of ultrasound for EF was evaluated by comparing forearm fascia ultrasound findings among EF patients, systemic sclerosis (SSc) patients, and healthy controls (HC).Results:Among the 109 EF patients (male-to-female ratio 2.2︰1), the median age of onset was 36 (29, 48) years, with a median disease duration of 7 (3, 12) months. The study also included 20 SSc patients [median age 49 (35, 61) years] and 20 HC individuals [median age 48 (29, 54) years]. Ultrasound assessments of forearm fascia in EF patients revealed a median fascial thickness of 1.9 (1.4, 2.4) mm. The median fascial thickness was 0.8 (0.7, 0.9) mm in SSc patients and 0.7 (0.5, 0.9) mm in HC individuals. Fascial thickness in EF patients was greater than in SSc ( Z=-11.16, P<0.001) and HC groups ( Z=-11.87, P<0.001). There was a correlation between fascia thickness and C-reactive protein ( r=0.148, P=0.004), erythrocyte sedimentation rate ( r=0.143, P=0.005), and immunoglobulin G ( r=0.120, P=0.020) in EF patients. Receiver operating characteristic (ROC) curve analysis demonstrated a sensitivity of 84.0% and specificity of 95.9% for EF diagnosis, with an area under the curve (AUC) of 0.921 and a cut-off value of 1.005 mm. Conclusion:Ultrasound detection of forearm fascial thickening (>1 mm) aids in diagnosing eosinophilic fasciitis, indicating that ultrasound is a supplementary diagnostic tool for EF.

Objective:To describe the temporal trend of disease burden of idiopathic epilepsy in China from 1990 to 2021 and predict the incidence of idiopathic epilepsy in China from 2022 to 2035 to provide references for the formulation of relevant health policies and measures.Methods:Based on data from the Global Burden of Disease Study 2021 (GBD 2021) database regarding idiopathic epilepsy in China, changes in disease burden from 1990 to 2021 were acquired. Disease burden was quantified using age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years (DALYs) rate (ASDR) and their 95% uncertain interval (UI). Temporal trend analysis was performed using a linear regression model to estimate the estimated annual percent change (EAPC) and annual percentage change (APC) in incidence of idiopathic epilepsy and their 95% CI. Additionally, incidence and number of patients with idiopathic epilepsy in China from 2022 to 2035 were predicted using Bayesian age-period-cohort model. Results:The ASIR of idiopathic epilepsy increased from 22.35 per 100,000 population in 1990 (95% UI: 15.04-30.92 per 100,000 population) to 28.19 per 100,000 population in 2021 (95% UI: 19.03-37.89 per 100,000 population), with an EAPC of 0.12% (95% CI: -0.10%-0.34%); ASPR of idiopathic epilepsy increased from 189.27 per 100,000 population in 1990 (95% UI: 132.48-252.95 per 100,000 population) to 214.71 per 100,000 population in 2021 (95% UI: 150.10-278.56 per 100,000 population), with an EAPC of -0.32% (95% CI: -0.57%-0.06%); ASMR of idiopathic epilepsy decreased from 1.86 per 100,000 population in 1990 (95% UI: 1.59-2.24 per 100,000 population) to 0.80 per 100,000 population in 2021 (95% UI: 0.67-1.00 per 100,000 population), with an EAPC of -2.96% (95% CI: -3.09%-2.82%); ASDR of idiopathic epilepsy decreased from 178.60 per 100,000 population in 1990 (95% UI: 143.44-220.63 per 100,000 population) to 101.39 per 100,000 population in 2021 (95% UI: 72.51-139.40 per 100,000 population), with an EAPC of -2.38% (95% CI: -2.54%-2.22%). The prediction model showed that by 2035, the prevalence of idiopathic epilepsy in China will be 28.27 per 100,000 (95% CI: 23.19-38.66), with an estimated 394,928 incident cases (95% CI: 324,037-540,128). Conclusions:From 1990 to 2021, the ASIR and ASPR of idiopathic epilepsy in China show an upward trend, while the ASMR and ASDR hace a decline trend. Incidence of idiopathic epilepsy in China is expected to remain stable over the next decade.

Objective:This study investigates the utility of ultrasound in diagnosing eosinophilic fasciitis (EF).Methods:A retrospective analysis was conducted on the clinical and ultrasound data of 109 EF patients seen at the center between January 1, 2006, and March 31, 2024. The diagnostic efficacy of ultrasound for EF was evaluated by comparing forearm fascia ultrasound findings among EF patients, systemic sclerosis (SSc) patients, and healthy controls (HC).Results:Among the 109 EF patients (male-to-female ratio 2.2︰1), the median age of onset was 36 (29, 48) years, with a median disease duration of 7 (3, 12) months. The study also included 20 SSc patients [median age 49 (35, 61) years] and 20 HC individuals [median age 48 (29, 54) years]. Ultrasound assessments of forearm fascia in EF patients revealed a median fascial thickness of 1.9 (1.4, 2.4) mm. The median fascial thickness was 0.8 (0.7, 0.9) mm in SSc patients and 0.7 (0.5, 0.9) mm in HC individuals. Fascial thickness in EF patients was greater than in SSc ( Z=-11.16, P<0.001) and HC groups ( Z=-11.87, P<0.001). There was a correlation between fascia thickness and C-reactive protein ( r=0.148, P=0.004), erythrocyte sedimentation rate ( r=0.143, P=0.005), and immunoglobulin G ( r=0.120, P=0.020) in EF patients. Receiver operating characteristic (ROC) curve analysis demonstrated a sensitivity of 84.0% and specificity of 95.9% for EF diagnosis, with an area under the curve (AUC) of 0.921 and a cut-off value of 1.005 mm. Conclusion:Ultrasound detection of forearm fascial thickening (>1 mm) aids in diagnosing eosinophilic fasciitis, indicating that ultrasound is a supplementary diagnostic tool for EF.

Objective:To describe the temporal trend of disease burden of idiopathic epilepsy in China from 1990 to 2021 and predict the incidence of idiopathic epilepsy in China from 2022 to 2035 to provide references for the formulation of relevant health policies and measures.Methods:Based on data from the Global Burden of Disease Study 2021 (GBD 2021) database regarding idiopathic epilepsy in China, changes in disease burden from 1990 to 2021 were acquired. Disease burden was quantified using age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years (DALYs) rate (ASDR) and their 95% uncertain interval (UI). Temporal trend analysis was performed using a linear regression model to estimate the estimated annual percent change (EAPC) and annual percentage change (APC) in incidence of idiopathic epilepsy and their 95% CI. Additionally, incidence and number of patients with idiopathic epilepsy in China from 2022 to 2035 were predicted using Bayesian age-period-cohort model. Results:The ASIR of idiopathic epilepsy increased from 22.35 per 100,000 population in 1990 (95% UI: 15.04-30.92 per 100,000 population) to 28.19 per 100,000 population in 2021 (95% UI: 19.03-37.89 per 100,000 population), with an EAPC of 0.12% (95% CI: -0.10%-0.34%); ASPR of idiopathic epilepsy increased from 189.27 per 100,000 population in 1990 (95% UI: 132.48-252.95 per 100,000 population) to 214.71 per 100,000 population in 2021 (95% UI: 150.10-278.56 per 100,000 population), with an EAPC of -0.32% (95% CI: -0.57%-0.06%); ASMR of idiopathic epilepsy decreased from 1.86 per 100,000 population in 1990 (95% UI: 1.59-2.24 per 100,000 population) to 0.80 per 100,000 population in 2021 (95% UI: 0.67-1.00 per 100,000 population), with an EAPC of -2.96% (95% CI: -3.09%-2.82%); ASDR of idiopathic epilepsy decreased from 178.60 per 100,000 population in 1990 (95% UI: 143.44-220.63 per 100,000 population) to 101.39 per 100,000 population in 2021 (95% UI: 72.51-139.40 per 100,000 population), with an EAPC of -2.38% (95% CI: -2.54%-2.22%). The prediction model showed that by 2035, the prevalence of idiopathic epilepsy in China will be 28.27 per 100,000 (95% CI: 23.19-38.66), with an estimated 394,928 incident cases (95% CI: 324,037-540,128). Conclusions:From 1990 to 2021, the ASIR and ASPR of idiopathic epilepsy in China show an upward trend, while the ASMR and ASDR hace a decline trend. Incidence of idiopathic epilepsy in China is expected to remain stable over the next decade.

We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m 2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.

Objective To explore the brain metabolic hormone homocysteine in patients with schizophrenia homocysteine(HCY),prolactin(PRL)in its correlation with cognitive function,mining of repetitive transcranial magnetic stimulation(rTMS)combined with olanzapine for the disease,in order to interpret the influence mechanism of brain metabolic hormones and cognitive function,at the same time,mining rTMS and olanzapine to enrich research in this field,to provide reference for related studies.Methods The data of 128 schizophrenia patients treated in the hospital from June 2021 to August 2023 were selected for retrospective analysis,divided into the observation group 72 cases combined rTMS with olanzapine and the control group 56 cases(olanzapine monotherapy).Serum serum HCY,PRL,positive and negative syndrome scale(PANSS),interleukin(IL)-12,tumor necrosis factor(TNF)-α and their associations were analyzed in both groups.The incidence of adverse effects was compared between the two groups.Results After treatment,the levels of PRL,HCY,IL-12,and TNF-α in the observation group were lower than those of the control group,with significant and statistically significant differences(P<0.05).Under the interaction,time point and between groups,the PANSS scores of the two groups changed due to the time passage of different treatment methods,but the observation group was lower than the control group,with significant differences(P<0.05).Treatment was negatively associated with HCY,PRL,IL-12,TNF-α,and PANSS,and HCY,PRL,IL-12,TNF-α,and PANSS were positively associated(P<0.05).The incidence of headache,impaired memory,drowsiness,and adverse reaction events in the observed group was lower than that in the control group,and the difference was significant(P<0.05).Conclusion After rTMS combined with olanzapine treatment,schizophrenia patients can reduce HCY and PRL hormone levels,alleviate inflammation,reduce adverse reactions,and improve cognitive function.

Objective The aim of this study was to investigate whether there are differences in the expression spectrums of RSK4 in different tumor cells and to predict the possible protein subtypes and their biological characteris-tics.Methods RNA was extracted from glioma cells GL261,ovarian cancer cells ID8,breast cancer cells 4T1 and 168FARN,colon cancer cells mc38 and CT26,gastric cancer cells MFC and lung cancer cells LLC1.The expres-sions and splicing isomers of RSK4 were detected by RT-PCR.The biological characteristics and functions of RSK4 were analyzed by bioinformatics.Results RT-PCR results showed that RSK4 was expressed in GL261,4T1,mc38,CT26,MFC and LLC1;and multiple splicing isomers were expressed in different tumor cells.Open reading frame analysis revealed RSK4 may encode at least 11 protein subtypes.Secondary structure analysis showed that these protein subtypes encoded by the splicing isomers were composed of α-helix,extended strand,β-turn and random coil,and had the same conserved domain.The results of protein interaction network enrichment analysis showed that RSK4 exerted kinase activity in the nucleus and cytoplasm mainly through the mTOR signaling pathway and long-term potentiation.Conclusions RSK4 has different expression spectrums in different tumor cells,and may produces a variety of protein isoforms with different nitrogen terminals,which can be involved in different biological processes through multiple signaling pathways.

In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe₃O₄@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe₃O₄@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe₃O₄@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T₂ magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe₃O₄@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.