Periodontal disease is a risk factor for many systemic diseases such as Alzheimer's disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
Animals ; Female ; Porphyromonas gingivalis ; Pregnancy ; Mice ; Cleft Palate/etiology* ; Glycolysis

Myocardial infarction (MI) is the leading cause of cardiovascular disease-related death worldwide. Nonetheless, existing therapeutic approaches for MI are hampered by issues such as reliance on pharmacological agents and suboptimal patient adherence. Caffeic acid (CA) is a bioactive polyphenolic compound with important anti-inflammatory, anti-bacterial and anti-oxidant functions. Still, its specific role and mechanism in treating cardiovascular disease remain to be further studied. In recent years, a large number of studies have shown that the kelch-like ECH-associated protein 1/nuclear factor erythroid 2 related factor 2 (Keap1/Nrf2) pathway is a key factor in the occurrence and development of cardiovascular diseases. In this study, H₂O₂-induced oxidative stress model of H9c2 cells and left anterior descending branch (LAD) conjunctival induced acute myocardial infarction reperfusion (AMI/R) model were used to evaluate the protective effect of CA on the heart. The interaction between CA and Keap1 was analyzed by CA-labeled fluorescence probe, target fishing, isothermal titration calorimetry (ITC), protein crystallography and surface plasmon resonance (SPR). Our results suggested that CA binds Keap1 and degrades Keap1 in a p62-dependent manner, further promoting nuclear transcription of Nrf2 and thus effectively reducing oxidative stress. In addition, based on the three-dimensional eutectic structure, it was confirmed that CA directly targets Keap1 protein by interacting with residues M550 and N532, inducing conformation changes in Keap1 protein. We also found that the CA analog chlorogenic acid (GCA) can bind Keap1. In conclusion, this study elucidates a novel molecular mechanism and structural basis for the protective effects of CA against oxidative damage via the Keap1-Nrf2 pathway.

Objective To investigate the risk factors of postoperative complications in patients with spinal tuberculosis and analyze the value of prognostic nutritional index(PNI)in predicting these complications.Methods The clinical data of 156 patients with spinal tuberculosis who underwent surgery in the Affiliated Hospital of Zunyi Medical University from January 2018 to July 2022 were retrospectively analyzed.The patients were divided into a complication group and a non-complication group based on the presence or absence of postoperative complications.Baseline data,laboratory indicators,and surgery-related indicators were compared between the two groups.The risk factors for postoperative complications in spinal tuberculosis were analyzed,and receiver operating characteristic(ROC)curves were plotted to evaluate the predictive value of PNI for postoperative complications in the patients.Results Among all of 156 patients,68 contracted a total of 82 instances of postoperative complications,with an incidence of 43.59%.Coinfection with pulmonary tuberculosis,preoperative anti-tuberculosis treatment duration more than 4 weeks,surgical operation duration,and drainage days were identified as independent risk factors for postoperative complications in spinal tuberculosis(P<0.05).On the other hand,a higher PNI was found to be a protective factor against postoperative complications of the spinal tuberculosis(P<0.05).The area under the ROC curve for PNI predicting postoperative complications ofthe spinal tuberculosis was 0.805.Conclusion The risk of postoperative complications in patients with spinal tuberculosis is subject to such factors ascoexistence of pulmo-nary tuberculosis,preoperative anti-tuberculosis treatment duration,surgery duration,drainage duration,and preoperative PNI.Preoperative PNI has a certain value for predicting the postoperative complications in the patients.

Programmed cell death protein-1(PD-1)/programmed cell death ligand-1(PD-L1)has been considered to be one of the most promising targets for tumor immunotherapy.At present,both monoclonal antibody drugs and small molecule inhibitors targeting PD-1/PD-L1 are facing bottlenecks.Numerous researchers have tried to explore different strategies to block the PD-L1/PD-L1 pathway,hoping to improve the effects of tumor immunotherapy.This review focuses on the degraders,bifunctional molecules and covalent inhibitors that target PD-L1,aiming to provide inspiring insights for the development of anti-PD-1/PD-L1 drugs.

Objective:To explore the effect of continuous nursing based on Siebens domain management model in patients with Parkinson's disease after deep brain stimulation.Methods:From January 2021 to June 2022, convenience sampling was used to select 169 Parkinson's disease patients who underwent deep brain electrical stimulation in the Functional Neurosurgery of Beijing Tiantan Hospital as the study subject. The patients were divided into a control group of 84 cases and an observation group of 85 cases using the random number table method. The control group received routine continuous nursing, while the observation group received the continuous nursing based on Siebens domain management model on the basis of the control group. This study compared the Activity of Daily Living (ADL) Scale, Morisky Medication Adherence Scale (MMAS), 39-item Parkinson Disease Questionnaire (PDQ-39), Parkinson's Disease Sleep Scale (PDSS) scores, and unexpected program control rate between two groups of patients after six months of discharge.Results:After six months of discharge, the ability of daily living score, quality of life score, and sleep quality score of both groups of patients improved compared to before intervention ( P<0.05), and the medication adherence of the observation group patients improved compared to before intervention ( P<0.05), and the differences were statistically significant. The ability of daily living score, medication adherence, quality of life score, and sleep quality score of the observation group patients after six months were higher than those of the control group, and the differences were statistically significant ( P<0.05). Within six months after discharge, the unexpected program control rate of the observation group was statistically lower than that of the control group ( P<0.05) . Conclusions:In the treatment and discharge rehabilitation process of Parkinson's patients treated with deep brain electrical stimulation, adopting continuous nursing based on the Siebens domain management model can help ensure patient medication compliance, improve postoperative sleep quality and quality of life, reduce unexpected program control frequency, and have certain clinical practice value.

Objective:To investigate the status of vertebral compression fracture (VCF) in elderly patients with osteoporosis and analyze its influencing factors.Methods:A total of 222 elderly patients with osteoporosis admitted to Department of Spinal Surgery in Affiliated Hospital of Zunyi Medical University from March 2019 to March 2023 were selected as the research objects by the convenient sampling method, and clinical data of the patients were collected. Patients were divided into VCF group ( n=98) and non-VCF group ( n=124) based on whether or not VCF occurred. Logistic regression was used to analyze the influencing factors of VCF in elderly patients with osteoporosis. Results:The incidence of VCF in 222 elderly patients with osteoporosis was 44.1% (98/222). The results of Logistic regression analysis showed that a history of falls ( OR=2.968, 95% CI: 1.154-7.736, P=0.024), no history of osteoporosis drug treatment ( OR=4.707, 95% CI: 1.525-14.531, P=0.007), body mass index>24.0 kg/m 2 ( OR=4.586, 95% CI: 2.071-10.158, P<0.001), lower bone density T values ( OR=3.221, 95% CI: 2.194-4.731, P<0.001) and low albumin ( OR=0.828, 95% CI: 0.752-0.913, P<0.001) were risk factors for VCF in elderly patients with osteoporosis. Conclusions:The incidence of vertebral compression fracture is high in elderly patients with osteoporosis, among which a history of falls, no history of osteoporosis drug treatment, body mass index greater than 24 kg/m 2, lower bone density T-values and low albumin are the main influencing factors that affect the occurrence of vertebral compression fracture in elderly patients with osteoporosis. Clinical medical staff should pay attention to these risk factors, identify the risk of fractures in elderly patients early and take targeted intervention measures.

The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy. The resulting siR/PIO@RP enables self-regulation of its distribution in accordance with the physio/pathological state (low/high RAGE expression) of the target site via a feedback loop. siR/PIO@RP is capable of performing intricate tasks and goes beyond the capabilities of single-target therapeutic agents utilized in AD therapy, such as reducing cerebral Aβ load, relieving neuroinflammation, and alleviating the dysfunction of NVU. Overall, the current study provides proof of concept that normalizing NVU holds promise as a means of alleviating AD symptoms.

The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

[This corrects the article DOI: 10.1016/j.apsb.2021.04.022.].