ObjectivePhotoacoustic pump-probe imaging can effectively eliminate the interference of blood background signal in traditional photoacoustic imaging, and realize the imaging of weak phosphorescence molecules and their triplet lifetimes in deep tissues. However, background differential noise in photoacoustic pump-probe imaging often leads to large fitting results of phosphorescent molecule concentration and triplet lifetime. Therefore, this paper proposes a novel triplet lifetime fitting method for photoacoustic pump-probe imaging. By extracting the phase of the triplet differential signal and the background noise, the fitting bias caused by the background noise can be effectively corrected. MethodsThe advantages and feasibility of the proposed algorithm are verified by numerical simulation, phantom and in vivo experiments, respectively. ResultsIn the numerical simulation, under the condition of noise intensity being 10% of the signal amplitude, the new method can optimize the fitting deviation from 48.5% to about 5%, and has a higher exclusion coefficient (0.88>0.79), which greatly improves the fitting accuracy. The high specificity imaging ability of photoacoustic pump imaging for phosphorescent molecules has been demonstrated by phantom experiments. In vivo experiments have verified the feasibility of the new fitting method proposed in this paper for fitting phosphoometric lifetime to monitor oxygen partial pressure content during photodynamic therapy of tumors in nude mice. ConclusionThis work will play an important role in promoting the application of photoacoustic pump-probe imaging in biomedicine.

Objective To analyze the epidemiological characteristics and risk factors of chronic kidney disease in patients with 10 years of hypertension. Methods A total of 350 patients with 10 years or longer course of hypertension who underwent physical examination in the Second Affiliated Hospital of Air Force Medical University from June 2021 to June 2024 were selected. General information of the patients was collected through questionnaires. Renal function related indicators and imaging results were obtained through relevant laboratory tests and imaging examinations. Based on the results of renal function related indicators, the epidemiological characteristics of chronic kidney disease in hypertensive patients with 10 years of hypertension, as well as risk factors for chronic kidney disease in the hypertensive patients were identified. Results Among the 350 patients enrolled in this study, there were 71 (20.29%) with proteinuria, 32 (9.14%) with hematuria, and 40 (11.43%) with decreased renal function. A total of 80 (22.86%) cases with structural variations such as kidney stones and cysts were detected by renal B-mode ultrasound. There were 121 (34.57%) patients with hypertension and chronic kidney disease. There were statistically significant differences in gender, age, diabetes, hyperlipidemia and hyperuricemia between patients with chronic kidney disease and those without (P<0.05). Multivariate logistic regression analysis results showed that gender, age, diabetes, hyperlipidemia, and hyperuricemia were the risk factors for chronic kidney disease in patients with hypertension (P<0.05). Conclusion Patients with 10 years of hypertension have a high risk of chronic kidney disease, and the risk factors include gender, age, diabetes, hyperuricemia, and hyperlipidemia.

The success of implementation research is closely tied to the institution's pre-implementation readiness. This study aims to explore the organizational readiness for change (ORC) and its influencing factors on primary healthcare settings in the implementation of the "Shared Medical Appointment for Diabetes (SMART) in China: design of an optimization trial" and to enhance ORC and provide insights to support the effective implementation of the program.

Objective To screen ferroptosis genes related to the prognosis of cervical cancer and to construct a prognosis model. Methods Ferroptosis genes were obtained from FerrDb database, and cervical cancer related data were obtained from The Genome-Wide Association Study Catalog database and The Cancer Genome Atlas database. Transcriptome-Wide Association Study, colocalization analysis and differential expression analysis were conducted to screen out candidate ferroptosis genes; Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted on candidate genes. Univariate Cox regression analysis was used to further screen out genes related to the prognosis of cervical cancer. Kaplan-Meier method was used to analyze the relationship between genes and the overall survival of patients. The expression levels of genes in pan-cancer were analyzed through the TIMER database. Two prognostic models were conducted, Model 1 included age and tumor stage, while Model 2 incorporated age, tumor stage, and prognostic genes. The predictive capabilities of the two models were compared. Results A total of 91 candidate genes related to ferroptosis were obtained. Univariate Cox regression analysis showed that 15 genes were associated with the prognosis of cervical cancer. CA9, SCD, TFRC, QSOX1 and CDO1 were risk factors affecting the prognosis of cervical cancer patients (P＜0.05), while PTPN6, ALOXE3, HELLS, IFNG, MIOX, ALOX12B, DUOX1, ALOX15, AQP3 and IDO1 were protective factors (P＜0.05). The mRNA expression levels of the 15 genes showed significant upregulation or downregulation in at least 7 types of cancers, among which TFRC was associated with the largest number of cancer types. Kaplan-Meier analysis showed that HELLS, DUOX1 and ALOXE3 were associated with poor prognosis in cervical cancer. The AUC of the model 1 for predicting 1-year and 3-year overall survival rates of cervical cancer patients was 0.455 and 0.478, and the AUC of Model 2 was 0.854 and 0.595. Model 2 (C-index = 0.727) had better predictive ability than Model 1 (C-index = 0.502). Conclusion The prognostic model composed of 15 prognostic-related genes selected based on bioinformatics has better predictive performance for the survival outcomes of cervical cancer patients, providing important reference value for the prognostic assessment of cervical cancer patients.

OBJECTIVE To compare the efficacy， safety， and cost-effectiveness of two different formulations of short-acting recombinant human growth hormone （rhGH） in the treatment of patients with short stature. METHODS Data from patients with short stature treated with short-acting rhGH at the Leshan People’s Hospital from August 2016 to June 2023 were collected. Patients were divided into powder formulation group and aqueous formulation group based on the rhGH formulation used. The changes in growth-related efficacy indicators and the occurrence of adverse drug reactions were compared between two groups after 12 months of treatment； cost-effectiveness analysis and sensitivity analysis were used to compare the cost per unit of effect achieved； subgroup analysis was performed by dividing the patients into growth hormone deficiency （GHD） subgroup and idiopathic short stature （ISS） subgroup based on clinical diagnosis. RESULTS After 12 months of treatment， the height and the levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in serum in aqueous formulation group and powder formulation group were significantly increased compared to before treatment （P＜0.001）， but there was no statistically significant difference in the changes of the above indicators between the two groups（P＞0.05）. The analysis results of GHD and ISS subgroups were consistent with the overall population. In the overall population， the cost-effectiveness ratio of powder formulation group （2 582 yuan/cm） was significantly better than that of aqueous formulation group （6 729 yuan/cm）， with a statistically significant difference （P＜0.001）， and the result was consistent in the GHD and ISS subgroups as well as in the sensitivity analysis. No serious adverse drug reactions occurred in either powder formulation or aqueous formulation group， and there was no statistically significant difference in the incidence of various adverse reactions between two groups （P＞0.05）. CONCLUSIONS Short-acting rhGH powder and aqueous formulations have equivalent efficacy and safety， but the powder formulation has greater economic advantages.

ObjectiveAs a second messenger in intracellular signal transduction, Ca²⁺ plays an important role in cell migration. Previous studies have demonstrated that extracellular Ca²⁺ influx can promote electric field-guided cell migration, known as electrotaxis. However, the effect of intracellular Ca²⁺ flow on electrotaxis is unclear. Therefore, in this study, we investigate the effect of Ca²⁺ flux on the electrotaxis of Dictyostelium discoideum. MethodsThe electrotaxis of Dictyostelium discoideum was investigated by applying a direct current (DC) electric field. Cell migration was recorded using a real-time imaging system. Calcium channel inhibitors, the extracellular Ca²⁺ chelator EGTA, Ca²⁺-free DB buffer, and caffeine were applied to investigate the impact of intra- and extracellular Ca²⁺ flow on electrotaxis. The involvement of G proteins and ERK2 in directed cell migration mediated by endoplasmic reticulum Ca²⁺ release was explored using mutants. ResultsDictyostelium discoideum migrated toward the cathode in the electric field in a voltage-dependent manner. The intracellular Ca²⁺ concentration of the cells was significantly increased in the electric field. Inhibition of both extracellular Ca²⁺ influx and intracellular Ca²⁺ release suppressed cell electrotaxis migration. Inhibition of endoplasmic reticulum Ca²⁺ release induced by caffeine significantly impaired the electrotaxis of Dictyostelium discoideum. Deletion of Gα2, Gβ, Gγ, and Erk2 notably reduced the electrotaxis of the cells. Enhancing Ca²⁺ release mediated by caffeine restored the electrotaxis of the Gα2^-, Gβ ^-, and Erk2^- mutant cells partially or completely, but did not restore electrotaxis in the Gγ^- mutant cells. ConclusionCa²⁺ release from the endoplasmic reticulum regulates electrotaxis migration in Dictyostelium discoideum and is involved in the regulation of cell electrotaxis by G proteins and ERK2.

This study aimed to localize the workplace readiness questionnaire (WRQ) and validate its applicability for assessing readiness for implementation of evidence-based practices (EBP) in primary care settings in China. The localization of the instrument will provide a practical instrument for assessing organizational readiness for change (ORC).

This study aims to investigate the mechanism of Qingrun Decoction in alleviating hepatic insulin resistance in type 2 diabetes mellitus(T2DM) rats through the reprogramming of amino acid metabolism. A T2DM rat model was established by inducing insulin resistance through a high-fat diet combined with intraperitoneal injection of streptozotocin. The model rats were randomly divided into five groups: model group, high-, medium-, and low-dose Qingrun Decoction groups, and metformin group. A normal control group was also established. The rats in the normal and model groups received 10 mL·kg~(-1) distilled water daily by gavage. The metformin group received 150 mg·kg~(-1) metformin suspension by gavage, and the Qingrun Decoction groups received 11.2, 5.6, and 2.8 g·kg~(-1) Qingrun Decoction by gavage for 8 weeks. Blood lipid levels were measured in different groups of rats. Pathological damage in rat liver tissue was assessed by hematoxylin-eosin(HE) staining and oil red O staining. Transcriptome sequencing and untargeted metabolomics were performed on rat liver and serum samples, integrated with bioinformatics analyses. Key metabolites(branched-chain amino acids, BCAAs), amino acid transporters, amino acid metabolites, critical enzymes for amino acid metabolism, resistin, adiponectin(ADPN), and mammalian target of rapamycin(mTOR) pathway-related molecules were quantified using quantitative real-time polymerase chain reaction(qRT-PCR), Western blot, and enzyme-linked immunosorbent assay(ELISA). The results showed that compared with the normal group, the model group had significantly increased serum levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and resistin and significantly decreased ADPN levels. Hepatocytes in the model group exhibited loose arrangement, significant lipid accumulation, fatty degeneration, and pronounced inflammatory cell infiltration. In liver tissue, the mRNA transcriptional levels of solute carrier family 7 member 2(Slc7a2), solute carrier family 38 member 2(Slc38a2), solute carrier family 38 member 4(Slc38a4), and arginase(ARG) were significantly downregulated, while the mRNA transcriptional levels of solute carrier family 1 member 4(Slc1a4), solute carrier family 16 member 1(Slc16a1), and methionine adenosyltransferase(MAT) were upregulated. Furthermore, the mRNA transcription and protein expression levels of branched-chain α-keto acid dehydrogenase E1α(BCKDHA) and DEP domain-containing mTOR-interacting protein(DEPTOR) were downregulated, while mRNA transcription and protein expression levels of mTOR, as well as ribosomal protein S6 kinase 1(S6K1), were upregulated. The levels of BCAAs and S-adenosyl-L-methionine(SAM) were elevated. The serum level of 6-hydroxymelatonin was significantly reduced, while imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid levels were significantly increased. Compared with the model group, Qingrun Decoction significantly reduced blood lipid and resistin levels while increasing ADPN levels. Hepatocytes had improved morphology with reduced inflammatory cells, and fatty degeneration and lipid deposition were alleviated. Differentially expressed genes and differential metabolites were mainly enriched in amino acid metabolic pathways. The expression levels of Slc7a2, Slc38a2, Slc38a4, and ARG in the liver tissue were significantly upregulated, while Slc1a4, Slc16a1, and MAT expression levels were significantly downregulated. BCKDHA and DEPTOR expression levels were upregulated, while mTOR and S6K1 expression levels were downregulated. Additionally, the levels of BCAAs and SAM were significantly decreased. The serum level of 6-hydroxymelatonin was increased, while those of imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid were decreased. In summary, Qingrun Decoction may improve amino acid metabolism reprogramming, inhibit mTOR pathway activation, alleviate insulin resistance in the liver, and mitigate pathological damage of liver tissue in T2DM rats by downregulating hepatic BCAAs and SAM and regulating key enzymes involved in amino acid metabolism, such as BCKDHA, ARG, and MAT, as well as amino acid metabolites and transporters.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Insulin Resistance ; Diabetes Mellitus, Type 2/genetics* ; Male ; Liver/drug effects* ; Amino Acids/metabolism* ; Rats, Sprague-Dawley ; Humans ; Metabolic Reprogramming

To study the therapeutic effect and mechanisms of ethyl syringate(MD) on ulcerative colitis(UC), the MTT assay was used to detect the proliferation inhibition of RAW264.7 cells and HT-29 cells by different concentrations of MD(50, 100, 200, 400 μmol·L~(-1)). UC cell models were constructed by inducing RAW264.7 cells and HT-29 cells with lipopolysaccharide(LPS) and tumor necrosis factor-α(TNF-α). An animal model was established by inducing mice with 2.5% dextran sulfate sodium(DSS) to verify the therapeutic effect of MD on UC. A control group, a model group(LPS or TNF-α), and groups treated with different concentrations of MD(50, 100, 200, 400 μmol·L~(-1)) were set up in this study. Nitric oxide(NO) levels were measured using a NO detection kit. Intracellular reactive oxygen species(ROS) levels were assessed using a laser confocal microscope and ROS kit. Enzyme-linked immunosorbent assay(ELISA) was used to detect changes in the levels of interleukin-6(IL-6), TNF-α, interferon-γ(INF-γ), interleukin-10(IL-10), and myeloperoxidase(MPO) in cells and animal tissues. Western blot was used to detect the expression levels of phosphorylated Janus kinase 2(p-JAK2), Janus kinase 2(JAK2), phosphorylated signal transducer and activator of transcription 3(p-STAT3), signal transducer and activator of transcription 3(STAT3), zonula occludens-1(ZO-1), occludin, and claudin-1 in cells and animal tissues. The results showed that MD can improve the inflammatory response by inhibiting the production of NO and ROS and regulating the expression of inflammatory factors. It significantly reduced the disease activity index(DAI) in mice, improved the shortening of the colon, and repaired intestinal epithelial damage by inhibiting the activation of the JAK2/STAT3 pathway, thereby exerting anti-UC activity.
Animals ; Colitis, Ulcerative/chemically induced* ; Janus Kinase 2/genetics* ; STAT3 Transcription Factor/genetics* ; Mice ; Humans ; Signal Transduction/drug effects* ; Male ; RAW 264.7 Cells ; Reactive Oxygen Species/metabolism* ; Nitric Oxide/metabolism* ; HT29 Cells ; Salicylates/administration & dosage* ; Protective Agents/administration & dosage*

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*