Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

OBJECTIVES: To investigate the therapeutic effect of the natural compound niranthin on Crohn's disease-like colitis in mice and explore the underlying molecular mechanisms. METHODS: In a mouse model of colitis induced by 2,4,6-trinitro-benzenesulfonic acid (TNBS), the therapeutic effect of niranthin was evaluated by observing the changes in body weight, disease activity index (DAI), and colon length of the mice. The levels of inflammatory cytokines (IL-6, IL-1β, TNF-α, IL-17A and IL-10) in the intestinal mucosal tissue were detected using ELISA and quantitative real-time PCR (qRT-PCR). TUNEL staining and Western blotting were used to assess intestinal epithelial cell apoptosis and the expressions of Bcl-2 and Bax. The expression levels of tight junction proteins (ZO-1 and claudin-1) and the activation of the p38/JNK signaling pathway were investigated using Western blotting, and diprovocim intervention experiments were conducted to explore the molecular regulatory mechanism of niranthin. RESULTS: Niranthin treatment significantly increased body weight of TNBS-treated mice, lowered the DAI and histological inflammation scores, and increased colon length of the mice. The niranthin-treated mouse models showed obviously reduced protein and mRNA levels of IL-6, IL-1β, IL-17A, and TNF-α and upregulated expression of IL-10 in the colon tissue. TUNEL staining and Western blotting demonstrated that niranthin significantly inhibited intestinal epithelial cell apoptosis and activated the anti-apoptotic pathway in the mouse models. Niranthin treatment obviously upregulated the expression levels of ZO-1 and claudin-1 and downregulated the phosphorylation levels of p38 and JNK in the colon tissues of the mice. Diprovocim intervention obviously attenuated the inactivation of the p38/JNK signaling pathway induced by niranthin in the mouse models. CONCLUSIONS Niranthin ameliorates TNBS-induced Crohn's disease-like colitis in mice by inhibiting intestinal epithelial cell apoptosis and protecting the integrity of the intestinal barrier via regulating the activation of the p38/JNK signaling pathway.
Animals ; Apoptosis/drug effects* ; Mice ; Intestinal Mucosa/drug effects* ; Crohn Disease/drug therapy* ; MAP Kinase Signaling System/drug effects* ; Epithelial Cells/drug effects* ; Disease Models, Animal ; Signal Transduction/drug effects* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Male

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

ObjectiveTo observe the effects of Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the Haizao Yuhutang （HYT） on oxidative stress in the liver of goiter rats under the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020. MethodA total of 128 male Wistar rats were randomly divided into a blank group， a model group， a euthyrox group （20 μg·kg^-1）， a HYT group （12.06 g·kg^-1）， a HYT without Sargassum （HYT-H） group （9.90 g·kg^-1）， a HYT without Glycyrrhizae Radix et Rhizoma （HYT-G） group （10.26 g·kg^-1）， a HYT without Sargassum and Glycyrrhizae Radix et Rhizoma （HYT-HG） group （8.10 g·kg^-1）， and a Sargassum and Glycyrrhizae Radix et Rhizoma （HG） group （3.96 g·kg^-1）. The blank group was given deionized water by gavage， and the others were given propylthiouracil （PTU） to replicate the goiter pathological model. Euthyrox was taken as a positive control drug， and the rest of the Chinese medicine groups were given the corresponding decoction by gavage， the material was collected 12 hours after the last dose. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， and the contents of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， reactive oxygen species （ROS） in liver tissue were detected in each group. The pathological changes in the liver were observed via hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to detect the mRNA expressions of Kelch-like Ech-associated protein 1 （Keap1）， nuclear factor E₂-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， p53 and Caspase-3 in liver tissues. Western blot was adopted to detect the protein expressions of Nrf2 and HO-1 in liver tissues in oxidative stress-related signaling pathways. ResultCompared with control group， the model group showed significantly increased serum ALT level and contents of MDA and ROS in liver tissues （P<0.05， P<0.01）， significantly reduced activities of SOD and GSH-Px in the liver （P<0.01）， significantly increased mRNA expression of Keap1 （P<0.01）， and significantly decreased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. Compared with the model group， the HYT group manifested significantly reduced serum levels of AST， ALT， and ALP （P<0.05， P<0.01）， significantly reduced contents of MDA and ROS in liver tissue （P<0.01）， significantly increased the activities of SOD and GSH-Px （P<0.01）， significantly decreased mRNA expressions of Keap1， p53， and Caspase-3 （P<0.01）， and significantly increased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. ConclusionUnder the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020， Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the HYT on oxidative stress in the liver of goiter rats had different effects. The HYT that contains Sargassum and Glycyrrhizae Radix et Rhizoma has a protective effect on the liver of goiter rats， and the effect is better than that of the HG group， the euthyrox group， and the incomplete groups. Its mechanism may be related to activating the Nrf2/HO-1 signaling pathway to alleviate liver oxidative stress and inhibiting the p53/Caspase-3 signaling pathway to reduce hepatocyte apoptosis.

ObjectiveTo understand the process and influencing factors affecting the utilization of influenza vaccination services and vaccination decision-making among the elderly in Shanghai, to explore the delivery of influenza vaccination services and the difficulties faced by the health service system, and to provide guidance for optimizing immunization strategies. MethodsBased on the vaccine hesitancy determinants matrix, semi-structured personal interviews were conducted with stakeholders involved in influenza vaccination services in Shanghai from January to February 2024, using a purposive sampling method. Participants were included until thematic saturation was achieved. Interview data were audio-recorded, transcribed, coded, and organized using NVivo 20 software, and analyzed using the thematic framework method. ResultsA total of 25 interviewees were included, including 9 medical staff, 12 elderly people aged 60 and above, and 4 family members. The study found that Shanghai had a well-managed and standardized influenza vaccination service. However, the promotion of vaccine-related information at the grassroots level was passive and limited. Out-of-pocket payment of the vaccine and cultural beliefs of the elderly negatively impacted vaccination rates. Meanwhile, recommendations from family, friends, and medical staff facilitated vaccination, although the impact varied depending on the type of medical staff. Neighborhood committees in townships and streets played a crucial role in delivering vaccination information to the target population. Additionally, the internet, social media, and the COVID-19 vaccine had both positive and negative impacts on influenza vaccination. Strategic optimization of vaccination should prioritize price concessions, enhance publicity strategies, and improve awareness, professionalism, and willingness among medical and healthcare workers to recommend vaccination. ConclusionThe influenza vaccination service in Shanghai is well-managed and standardized. However, it is essential to consider the influence of family and other support systems on the elderly. It is also necessary to enhance the professionalism, service awareness, and willingness to recommend among the medical staff. Furthermore, systematic interventions and publicity efforts should be effectively integrated with social media and the functions of neighborhood committees.

ObjectiveTo investigate the mechanism of Zexie Decoction （泽泻汤） in inhibiting neuroinflammation and improving cognitive impairment mediated by high-calorie diet. MethodsTwenty seven C57BL/J mice were randomly divided into control group （n = 9）， model group （n = 9） and Zexie Decoction group （n = 9）. The mice in the model group and the Zexie Decoction group were fed with high-calorie diet to establish the model of cognitive impairment. Meanwhile， the mice in Zexie Decoction group were also fed with 0.36 g/（kg·d）Zexie Decoction， and the mice in the control group and model group were fed with the same volume of normal saline for 8 weeks. The body weight of mice was recorded at the same time every week； after intervention， oral glucose tolerance test （OGTT） and insulin tolerance test（ITT） commenced； the cognitive level of mice was detected by Morris water maze， open field test， new object recognition test and Y maze； magnetic resonance spectroscopy （MRS） was used to detect the expression of N-acetylaspartate （NAA）， choline （CHO）， lactic acid （Lac）， creatine （Cr）， lipid （Lip）， and myoInositol （mI） in left hippocampus， hypothalamus and cortex. Western blotting was used to detect the expression of synaptophysin （SYN）， synaptosome associated protein-25 （SNAP-25）， postsynaptic dense protein-95 （PSD-95）， tumor necrosis factor-α （TNF-α）， nuclear factor kappa B （NF-κB p65） and its phosphorylated form （P-NF-B p65） in mouse brain； Nissl's staining was used to detect the morphological changes of hippocampal neurons. ResultsCompared with the control group， body mass， blood glucose in oral glucose tolerance test， and blood glucose in insulin tolerance test increased in the model group； in the Morris water maze experiment， the total distance travelled and escape latency of the model group mice increased， the time spent in the platform area and the number of times traversing the platform decreased on days 3 and 4； in the open-field experiment， the number of times the model group mice entered the central area， the ratio of the time in the central area to the total time， and the ratio of the distance travelled in the central area to the total distance significantly decreased； in the new object recognition test， the frequency of new object recognition and recognition index were significantly lower in the model group mice； in the Y-maze test， the spontaneous alternation rate of mice in the model group was significantly lower （P＜0.05 or P＜0.01）； in the left hippocampus， hypothalamus， and cortex of mice in the model group， the CHO/Cr， NAA/Cr significantly decreased， and the mI/Cr， Lac/Cr and Lip/Cr significantly increased； SYN/β-actin， SNAP-25/β-actin and PSD-95/β-actin values significantly decreased， and p-NF-κB p65/NF-κB p65 and TNF-α/β-actin values significantly increased in brain tissue （P＜0.05 or P＜0.01）. Compared with the model group， the above indexes of mice in the Zexie Decoction group significantly improved （P＜0.05 or P＜0.01）. The results of Nissl staining showed that compared with the control group， the neurons in the dentate gyrus of the hippocampus in the model group were scattered and sparsely arranged， the density was significantly reduced， the nuclei of the cells had consolidation and shrinkage， the number of Nissl vesicles was reduced， and the staining became lighter； compared with the model group， the density of neurons in the hippocampal dentate gyrus region of the Zexie Decoction group increased， the wrinkling of nuclei improved， the cell gap narrowed， and the arrangement was slightly tight. Concusion The ameliorative effect of Zexie Decoction on cognitive function in mice with high-calorie diet-induced cognitive impairment may relate to the restructuring of glucose metabolism homeostasis， inhibition of neuroinflammation， reduction of neuronal damage， and enhancement of synaptic plasticity.

Objective To investigate the effects of high-calorie diet and age on brain function of ApoE-/-mice.Methods A total of 20 adult ApoE mice(8 months old)and elderly ApoE-/-mice(18 months old)were randomly divided into normal diet adult group,normal diet elderly group,high-calorie diet adult group,and high-calorie diet elderly group,with 5 animals in each group.The mice were fed with corresponding standard diet and high-fat diet for 8 weeks.Their body mass was monitored,and blood glucose was detected with glucose tolerance test.The relative contents of NAA and Cho in the hippocampus and hypothalamus were detected by Magnetic resonance spectroscopy.Y-Maze and open field tests were performed to detect cognitive function,and West-ern blotting was applied to detect the expression of synaptic associated protein 25(SNAP-25),synaptophysin,postsynaptic dense protein-95(PSD-95),iNOS and IL-1β.Results Compared with the normal diet adult group,the NAA content in the hippocampus,Cho and NAA contents in the hypothalamus,spontaneous alternation rate,and expression levels of SNAP-25,synaptophysin and PSD-95 in brain tissue(P＜0.05,P＜0.01)were decreased,and the expression of iNOS and IL-1β(P＜0.01)was increased in the high-calorie diet adult group.The normal diet elderly group had reduced contents of NAA in the hippocampus and Cho in the hypothalamus,and expression levels of SNAP-25,synaptophysin and PSD-95(P＜0.05,P＜0.01),and elevated expression of iNOS and IL-1β(P＜0.01)when compared with the normal diet adult group.Compared with the normal diet elderly group,high-calorie diet resulted in decreased Cho and NAA in both hippocampus and hy-pothalamus,central distance/total distance and down-regulation of SNAP-25,synaptophysin and PSD-95(P＜0.05,P＜0.01),and enhanced expression of iNOS and IL-1β(P＜0.01)in the elderly mice.Compared with the high-calorie diet adult group,the high-calorie diet elderly group had reduced NAA in hippocampus,central distance/total distance and average speed,and decreased expression of synaptophysin(P＜0.05,P＜0.01),and increased expression of iNOS and IL-1β(1.61±0.10 vs 1.35±0.13,2.04±0.08 vs 1.54±0.11,P＜0.05,P＜0.01).Conclusion High-calorie diet results in metabolic disorders and neuroinflammation,inhibits the expression of syn-aptic proteins,and thus leads to cognitive dysfunction in ApoE mice.Long-term high-calorie diet and ageing promote the decline of brain function in ApoE mice.

Objective:To compare the characteristics of background mucosa, lesion features, and the efficiency of endoscopic submucosal dissection(ESD)between elderly and non-elderly patients with early gastric cancer(EGC).Methods:This study retrospectively collected data on patients with EGC who underwent ESD treatment at Beijing Hospital from April 2020 to December 2022.The clinical characteristics, background mucosa, lesion features, ESD outcomes, and pathological results of the patients were analyzed to compare the differences between elderly and non-elderly patients.Results:A total of 100 patients with EGC were selected, comprising 57 patients in the elderly group and 43 patients in the non-elderly group, with a total of 111 lesions identified(64 lesions in the elderly group and 47 lesions in the non-elderly group).The proportion of patients with a history of chronic atrophic gastritis was significantly higher in the elderly group(89.5%、51/57)compared to the non-elderly group(74.4%、32/43), with a statistically significant difference( P=0.047).Additionally, the difference in the extent of atrophy between elderly patients with EGC and their non-elderly counterparts was statistically significant( P=0.022).Among these patients, the proportion of those classified as Kimura-Takemoto C0 to C1 in the elderly group(15.6%、10/64)was lower than that in the non-elderly group(40.4%、19/47).In contrast, the proportion of patients classified as C2 to C3 in the elderly group(65.6%、42/64)was higher than that in the non-elderly group(51.1%、24/47), and the proportion of those classified as O1 to O3 in elderly patients(12.5%、8/64)was also higher than in the non-elderly group(4.3%、2/47).Furthermore, the difference in the extent of intestinal metaplasia between elderly and non-elderly patients with early gastric cancer was statistically significant( P=0.007).The overall proportion of total intestinal metaplasia in elderly patients(85.9%、55/64)was significantly higher than that in non-elderly patients(61.7%、29/47).Notably, the proportion of patients exhibiting extensive intestinal metaplasia(intestinal metaplasia present in both the gastric antrum and gastric body)was greater in the elderly group(43.8%、28/64)compared to the non-elderly group(23.4%、11/47).The Kyoto gastric cancer risk endoscopic score for elderly patients with EGC was(2.43±1.28)points, significantly higher than that of the non-elderly group(1.72±1.41)points, with a statistically significant difference observed( t=2.778, P=0.006).No statistically significant differences were observed in the proportions of total resection rates, R0 resections, curative resections, or postoperative complications following ESD when comparing elderly patients with EGC to their non-elderly counterparts. Conclusions:The proportion of extensive atrophy and intestinal metaplasia was higher in the background mucosa of elderly patients with EGC, and correspondingly, the Kyoto endoscopic gastric cancer risk score was elevated.Therefore, endoscopic examinations for elderly patients with chronic atrophic gastritis should be conducted with greater care and comprehensiveness.

In order to understand the prevalence and genetic variation of H9N2 subtype avian influ-enza virus in Shandong,a total 492 tracheal and lung tissue samples collected from chicken farms with respiratory symptoms in partial areas in Shandong were detected by H9 subtype AIV real-time RT-PCR,and the positive samples were inoculated with chicken embryos for two generations.Whole genome sequences of the positive strains by applying Illumina Miaseq platform,and genetic evolution and mutation at positions associating with viral pathogenicity and transmissibility were analyzed.The results showed that there were 72 samples were positive for H9 subtype AIV among the 492 samples,with a positive rate of 14.63％.Thirty-four strains of H9 subtype AIV were ob-tained from the positive samples after passing through chicken embryo,meanwhile,the 34 isolates were all H9N2 subtype AIV by whole genome sequencing analysis.By analyzing the evolutionary tree of HA and NA genes,HA and NA genes of the 34 H9N2 AIV strains belonged to Y280-like branch and F/98-like branch,respectively.Meanwhile,based on above branches,there were obvious time node subbranch,which one was"isolates before 2013",another one was"isolates after 2013".The HA cleavage sites of thirty-four H9N2 strains were all 325PSRSSR↓GLF333,which met the se-quence characteristics of the lowly pathogenic avian influenza virus,and the HA receptor binding site 226 amino acid was leucine,which had the characteristics of blinding to a-2,6 mammalian sialic acid receptors.Among the internal amino acid sites that are key to mammalian adaptation,all strains had an I368V mutation in the PB1 gene that enhanced viral transmissibility in mammals and the PB2 genes of some strains were mutated to enhance the mammalian adaptation of I292 V and A588 V.The above results illustrated that the H9N2 subtype AIV gene segments in Shandong have different degrees of recombination and gene variation,so it is necessary to strengthen the monito-ring of virus variation.

Objective:This study aimed to evaluate the efficacy of decitabine (DAC) and identify factors influencing treatment responses in patients with primary immune thrombocytopenia (ITP) who had failed glucocorticoid therapy.Methods:Clinical data of 61 patients with glucocorticoid-resistant ITP who received DAC therapy (5 mg·m -2·d -1×3 d via intravenous infusion) for at least three cycles with 3-4-week intervals at the Department of Hematology, Qilu Hospital of Shandong University, from November 2015 to June 2021 were analyzed retrospectively. Results:The 61 patients comprised 20 males and 41 females, with a median age of 45 years (range: 15-81 years). Among them, 43 patients were glucocorticoid-dependent (glucocorticoid-dependent group), while 18 patients were glucocorticoid-resistant (glucocorticoid-resistant group). Following DAC treatment, 12 patients (19.67% ) achieved complete response (CR), and 16 patients (26.23% ) exhibited response (R), resulting in an overall response (OR) rate of 45.90% (28/61). Comparison between the OR group ( n=28) and the non-response (NR) group ( n=33) revealed significant differences in responses to glucocorticoids (dependent or resistant) and platelet counts before treatment ( χ2=8.789, P=0.003; z=-2.416, P=0.016). The glucocorticoid-dependent group showed higher platelet counts than the glucocorticoid-resistant group after the second and third cycles of DAC treatment ( P=0.032, 0.024). Moreover, the OR rates after the first, second, and third cycles of DAC treatment in the glucocorticoid-dependent group were all higher than those in the glucocorticoid-resistant group ( P=0.042, P=0.012, P=0.029). A significant correlation was observed between glucocorticoid dependence and responses to DAC treatment ( OR=9.213, 95% CI 1.937-43.820, P=0.005) . Conclusion:DAC demonstrates definitive efficacy with mild adverse effects in a subset of patients with glucocorticoid-resistant primary ITP. Glucocorticoid dependence and higher platelet counts before treatment are associated with a favorable response to DAC therapy.