Pulpitis is a common infective oral disease in clinical situations. The regulatory mechanisms of immune defense in pulpitis are still being investigated. Osteomodulin (OMD) is a small leucine-rich proteoglycan family member distributed in bones and teeth. It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells (hDPSCs). In this study, the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated. The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining. Intriguingly, the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens. The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide (LPS)-induced inflammation. A conditional Omd knockout mouse model with pulpal inflammation was established. LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice, whereas OMD administration exhibited a protective effect against pulpitis. Mechanistically, the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB (NF-κB) signaling pathway. Interleukin-1 receptor 1 (IL1R1), a vital membrane receptor activating the NF-κB pathway, was significantly downregulated in OMD-overexpressing hDPSCs. Additionally, the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking. In vivo, excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist. Overall, OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway. OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.
Pulpitis/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction ; Humans ; Mice ; Mice, Knockout ; Dental Pulp/metabolism* ; Disease Models, Animal ; Lipopolysaccharides

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

In recent years, the number of lung surgeries has increased year by year, and the number of patients with postoperative cough has also increased gradually. Chronic cough after lung surgery seriously affects patients' quality of life and surgical outcome, and has become one of the clinical problems that clinicians need to solve. However, there is currently no guideline or consensus for the treatment of chronic cough after lung surgery in China, and there is no standardized treatment method. Therefore, we searched databases such as PubMed, Web of Science, CNKI, and Wanfang databases ect. from 2000 to 2023 to collected relevant literatures and research data, and produced the first expert consensus on chronic cough after lung surgery in China by Delphi method. We gave 11 recommendations from five perspectives including timing of chronic cough treatment, risk factors (surgical method, lymph node dissection method, anesthesia method), prevention methods (preoperative, intraoperative, postoperative), and treatment methods (etiological treatment, cough suppressive drug treatment, traditional Chinese medicine treatment, and postoperative physical therapy). We hope that this consensus can improve the standardization and effectiveness of chronic cough treatment after lung surgery, provide reference for clinical doctors, and ultimately improve the quality of life of patients with chronic cough after lung surgery.

Objective To investigate the core drugs of traditional Chinese medicine(TCM)for the treatment of hypoxic pulmonary hypertension(HPH),and to verify the drug efficacy by hypoxia combined with Su5416(Hypoxia+Su5416,HySu)-induced PH mouse model.Methods Relevant literatures on TCM treatment of HPH in China Knowledge Network,Wanfang,Weipu were collected,screened and set up a database through the nerf criteria,and inputted into the software of traditional Chinese medicine inheritance assistance platform(V2.5)for the excavation of medication law.The HySu-PH mouse model was established,and the core drugs were evaluated for drug efficacy through force exhaustion exercise running table,blood oxygen saturation,right ventricular pressure,and right heart hypertrophy index test.Results The 102 relevant formulas for the treatment of HPH were screened,involving a total of 158 traditional Chinese medicines,and the top 5 drug frequencies were Salvia miltiorrhiza,Rhizoma Chuanxiong,Astragalus membranaceus,Draba hebecarpa,and Angelica sinensis,with the highest use of blood-activating and blood-stasis removing drugs,and deficiency-tonifying drugs in the categories of drugs used,and Salvia miltiorrhiza was the core drug used.HySu-PH mouse models were constructed and given 2 weeks of treatment with the danshen preparation Danshen injection.Danshen injection significantly elevated body weight(P<0.01),oxygen saturation(P<0.05),displacement of exhaustion(P<0.01),and duration of exhaustion(P<0.05),and lowered the right ventricular systolic blood pressure(P<0.01)and the right cardiac hypertrophy index(P<0.01).Conclusion Salvia miltiorrhiza is a core drug for the treatment of HPH,and the danshen preparation Danshen injection can effectively treat HySu-PH.

Objective Based on the pre-existing basis of effective treatment of hypoxia combined with Su5416-induced hypoxic pulmonary hypertension(HPH)by Salvia miltiorrhiza,to investigate the mechanism of Salvia miltiorrhiza in the treatment of HPH.Methods Using a network pharmacology approach to obtain the key pathways of Salvia miltiorrhiza for the treatment of HPH.The active ingredients of Salvia miltiorrhiza were collected to obtain the targets of the active ingredients.HPH disease targets were collected to obtain the intersection of Salvia miltiorrhiza component targets and HPH disease targets.Protein-Protein Interaction Networks(PPIs)were constructed and KEGG analysis was performed to obtain the key pathways of Salvia miltiorrhiza for HPH.Then used molecular biology to validate the key pathways.Results The 81 targets of Salvia miltiorrhiza for the treatment of HPH were obtained by network pharmacology,and PPI showed that drug component-disease common core targets included ATK1,TNF,EGFR,IL6,ESR1,and KEGG-enriched Pathway mainly included PI3K-AKT signaling pathway,HIF-1 signaling pathway,MAKP signaling pathway,TNF signaling pathway,JAK-STAT signaling pathway and so on.Molecular biological assays showed that Salvia miltiorrhiza had the effect of reducing lung tissue fibrosis and inhibiting the PI3K/AKT signalling pathway in HySu-PH mice.Conclusion Salvia miltiorrhiza has the effect of attenuating pulmonary fibrosis,and its mechanism of action is related to the inhibition of the PI3K/Akt signalling pathway.

Humans ; East Asian People ; Psoriasis/drug therapy* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Treatment Outcome ; Severity of Illness Index

Objective:To investigate the effect of hypoxia-inducible factor 1α (HIF-1α)/Bcl-2 and adenovirus E1B19kDa-interacting protein 3 (BNIP3)-mediated mitophagy on neuronal apoptosis after traumatic brain injury (TBI).Methods:HT22 cells (mouse hippocampal neurons) were chosen; oxygen-glucose deprivation/re-oxygenation (OGD/R) was used to establish in vitro TBI models. Expressions of HIF-1α and BNIP3 were regulated by HIF-1α, BNIP3-specific small interfering RNA (siRNA) or plasmid vector transfection. Experiment 1 was performed to investigate the effect of BNIP3-mediated mitophagy on neuronal apoptosis after TBI; HT22 cells were divided into 4 groups ( n=3): siRNA control group (normal culture after negative siRNA transfection), siRNA+TBI group (OGD/R after negative siRNA transfection), BNIP3-siRNA group (normal culture after BNIP3-siRNA transfection), and BNIP3-siRNA+TBI group (OGD/R after BNIP3-siRNA transfection); the expressions of mitochondrial autophagy related proteins such as HIF-1α, BNIP3, LC3-II, and P62 were detected by Western blotting, mitochondrial autophagosomes were observed by transmission electron microscopy, apoptosis was detected by TUNEL, and lactate dehydrogenase (LDH) activity in cell supernatant was determined by LDH kit. Experiment 2 was performed to investigate the effect of HIF-1α on BNIP3-mediated mitophagy and neuronal apoptosis after TBI; HT22 cells were divided into 8 groups ( n=3): siRNA control group (normal culture after negative siRNA transfection), siRNA+TBI group (OGD/R after negative siRNA transfection), HIF-1α-siRNA group (normal culture after HIF-1α-siRNA transfection), HIF-1α-siRNA+TBI group (OGD/R after HIF-1α-siRNA transfection), empty plasmid group (normal culture after pcDNA3.1[+] transfection), HIF-1α overexpression group (normal culture after HIF-1α plasmid transfection), empty plasmid+TBI group (OGD/R after empty plasmid transfection), HIF-1α overexpression+TBI group (OGD/R after HIF-1α plasmid transfection); the expressions of HIF-1α, BNIP3, LC3-II, P62, TOMM20 and COX IV, apoptosis rate and LDH activity in neurons of each group were determined. Results:(1) In Experiment 1, compared with siRNA control group, siRNA+TBI group had significantly increased BNIP3 expression and LC3-II/I ratio, significantly decreased P62, TOMM20 and COX IV expressions, and statistically increased apoptosis and LDH activity ( P<0.05); compared with siRNA+TBI group, BNIP3-siRNA+TBI group had significantly decreased BNIP3 expression and LC3-II/I ratio, significantly increased P62, TOMM20, and COX IV expressions, and significantly increased apoptosis and LDH activity ( P<0.05); under projective electron microscope, siRNA+TBI group had increased autophagosomes compared with siRNA control group, while BNIP3-siRNA+TBI group had decreased autophagosomes compared with siRNA+TBI group. (2) In Experiment 2, compared with siRNA+TBI group, HIF-1α-siRNA+TBI group had significantly decreased expressions of HIF-1α and BNIP3, and LC3-II/I ratio, significantly increased expressions of P62, TOMM20 and COX IV, and significantly increased apoptosis and LDH activity ( P<0.05); compared with empty plasmid+TBI group, HIF-1α overexpression+TBI group had statistically higher expressions of HIF-1α and BNIP3, and LC3-II/I ratio, significantly decreased expressions of P62, TOMM20 and COX IV, and significantly decreased apoptosis and LDH activity ( P<0.05). Conclusion:HIF-1α can mitigate TBI-induced neuronal apoptosis via promoting BNIP3-mediated mitophagy.

In view of numerous subtle features in fundus disease images,small sample sizes,and difficulties in diagnosis,both deep learning and medical imaging technologies are used to develop a fundus disease diagnosis model that integrates multi-scale features and hybrid domain attention mechanism.Resnet50 network is taken as the baseline network,and it is modified in the study.The method uses parallel multi-branch architecture to extract the features of fundus diseases under different receptive fields for effectively improving the feature extraction ability and computational efficiency,and adopts hybrid domain attention mechanism to select information that is more critical to the current task for effectively enhancing the classification performance.The test on ODIR dataset shows that the proposed method has a diagnostic accuracy of 93.2%for different fundus diseases,which is 5.2%higher than the baseline network,demonstrating a good diagnostic performance.

Objective:To investigate the physicochemical and biological properties of different magnesium modified calcium phosphate bone cements.Methods:The different magnesium modified calcium phosphate bone cements were divided into magnesium citrate, magnesium lactate, magnesium malate, magnesium phosphate and magnesium glycinate groups, each of which was added with different magnesium agents in the proportion of 0%, 1%, 3% and 5% of the total weight of calcium phosphate bone cements. The initial and final setting time, injectability, anti-collapse performance and compressive strength of different magnesium modified calcium phosphate bone cements were tested. Furthermore, the screened bone cement extracts were used to culture with third generation osteoblasts. Bioactivity assays were performed using the Cell Proliferation and Toxicity Assay Kit (CCK-8). Alkaline phosphatase (ALP) staining and Alizarin Red S (ARS) staining were performed on osteoblasts to observe the osteogenic activity of magnesium malate modified calcium phosphate bone cements.Results:The addition of different proportions of different magnesium agents led to the shortening of the initial and final setting time of modified calcium phosphate bone cements. Moreover, the final setting time of 5% magnesium malate modified calcium phosphate bone cements was the shortest (<40 minutes), which was significantly shorter compared with other magnesium agents in the same proportion (all P<0.05). With the addition of different magnesium agents in different proportions, the injectability of bone cements was gradually increased, and the injectability of 5% magnesium malate calcium phosphate bone cements reached the highest for (87.3±1.9)%, which was significantly increased compared with other magnesium agents in the same proportion (all P<0.05). The anti-collapse performance of bone cements was decreased with the addition of different magnesium agents in different proportions. Magnesium citrate, magnesium phosphate and magnesium glycinate modified calcium phosphate bone cements could not resist the flushing of deionized water. In particular, magnesium malate modified calcium phosphate bone cements had the best anti-collapse performance, with the maximum weight loss rate for only (9.8±2.3)% after 30 minutes of deionized water flushing, which was better than the rest of the groups (all P<0.05). The compressive strength of magnesium lactate and magnesium phosphate modified calcium phosphate bone cements showed a decrease compared with original calcium phosphate bone cements, while the compressive strength of magnesium citrate and magnesium malate modified calcium phosphate bone cements was significantly increased compared with original calcium phosphate bone cements, of which 3% magnesium malate modified calcium phosphate bone cements had the greatest compressive strength of (6.2±0.2)MPa, significantly higher than the rest of the groups (all P<0.05). The sieve test yielded magnesium malate modified calcium phosphate bone cement, which had a weight loss of (27.0±0.9)% at 35 days in vitro. The release of magnesium ions was increased with increasing magnesium malate dose in the in vitro environment of magnesium malate modified calcium phosphate bone cements in different ratios. A stable magnesium ion release was achieved within 35 days.Also, the pro-proliferative and osteogenic effects of modified calcium phosphate bone cements on osteoblasts were more obvious with increase of magnesium malate dose. For 5% magnesium malate modified calcium phosphate bone cements, the cell number, ALP staining area ratio and calcium nodule area ratio were significantly increased compared with the groups in the proportion of 0% and 1% magnesium malate (all P<0.05). Conclusions:Among magnesium citrate, magnesium lactate, magnesium malate, magnesium phosphate and magnesium glycinate modified calcium phosphate bone cements, magnesium malate modified calcium phosphate bone cements have relatively suitable setting time, excellent anti-collapse performance and mechanical strength. Meanwhile, 5% magnesium malate modified calcium phosphate bone cements have better biological activity among different ratios of magnesium malate modified calcium phosphate bone cements, suggesting a potential value for clinical application.