Phosphodiesterase 8 (PDE8): Distribution and Cellular Expression and Association with Alzheimer's Disease.

Phosphodiesterase 8 (PDE8), as a member of PDE superfamily, specifically promotes the hydrolysis and degradation of intracellular cyclic adenosine monophosphate (cAMP), which may be associated with pathogenesis of Alzheimer's disease (AD). However, little is currently known about potential role in the central nervous system (CNS). Here we investigated the distribution and expression of PDE8 in brain of mouse, which we believe can provide evidence for studying the role of PDE8 in CNS and the relationship between PDE8 and AD. Here, C57BL/6J mice were used to observe the distribution patterns of two subtypes of PDE8, PDE8A and PDE8B, in different sexes in vivo by western blot (WB). Meanwhile, C57BL/6J mice were also used to demonstrate the distribution pattern of PDE8 in selected brain regions and localization in neural cells by WB and multiplex immunofluorescence staining. Furthermore, the triple transgenic (3×Tg-AD) mice and wild type (WT) mice of different ages were used to investigate the changes of PDE8 expression in the hippocampus and cerebral cortex during the progression of AD. PDE8 was found to be widely expressed in multiple tissues and organs including heart, kidney, stomach, brain, and liver, spleen, intestines, and uterus, with differences in expression levels between the two subtypes of PDE8A and PDE8B, as well as two sexes. Meanwhile, PDE8 was widely distributed in the brain, especially in areas closely related to cognitive function such as cerebellum, striatum, amygdala, cerebral cortex, and hippocampus, without differences between sexes. Furthermore, PDE8A was found to be expressed in neuronal cells, microglia and astrocytes, while PDE8B is only expressed in neuronal cells and microglia. PDE8A expression in the hippocampus of both female and male 3×Tg-AD mice was gradually increased with ages and PDE8B expression was upregulated only in cerebral cortex of female 3×Tg-AD mice with ages. However, the expression of PDE8A and PDE8B was apparently increased in both cerebral cortex and hippocampus in both female and male 10-month-old 3×Tg-AD mice compared WT mice. These results suggest that PDE8 may be associated with the progression of AD and is a potential target for its prevention and treatment in the future.

A Self-Powered Lactate Sensor Based on the Piezoelectric Effect for Assessing Tumor Development.

The build-up of lactate in solid tumors stands as a crucial and early occurrence in malignancy development, and the concentration of lactate in the tumor microenvironment may be a more sensitive indicator for analyzing primary tumors. In this study, we designed a self-powered lactate sensor for the rapid analysis of tumor samples, utilizing the coupling between the piezoelectric effect and enzymatic reaction. This lactate sensor is fabricated using a ZnO nanowire array modified with lactate oxidase (LOx). The sensing process does not require an external power source or batteries. The device can directly output electric signals containing lactate concentration information when subjected to external forces. The lactate concentration detection upper limit of the sensor is at least 27 mM, with a limit of detection (LOD) of approximately 1.3 mM and a response time of around 10 s. This study innovatively applied self-powered technology to the in situ detection of the tumor microenvironment and used the results to estimate the growth period of the primary tumor. The availability of this application has been confirmed through biological experiments. Furthermore, the sensor data generated by the device offer valuable insights for evaluating the likelihood of remote tumor metastasis. This study may expand the research scope of self-powered technology in the field of medical diagnosis and offer a novel perspective on cancer diagnosis.

ALKBH5-mediated m6A modification of IL-11 drives macrophage-to-myofibroblast transition and pathological cardiac fibrosis in mice.

Cardiac macrophage contributes to the development of cardiac fibrosis, but factors that regulate cardiac macrophages transition and activation during this process remains elusive. Here we show, by single-cell transcriptomics, lineage tracing and parabiosis, that cardiac macrophages from circulating monocytes preferentially commit to macrophage-to-myofibroblast transition (MMT) under angiotensin II (Ang II)-induced hypertension, with accompanying increased expression of the RNA N6-methyladenosine demethylases, ALKBH5. Meanwhile, macrophage-specific knockout of ALKBH5 inhibits Ang II-induced MMT, and subsequently ameliorates cardiac fibrosis and dysfunction. Mechanistically, RNA immunoprecipitation sequencing identifies interlukin-11 (IL-11) mRNA as a target for ALKBH5-mediated m6A demethylation, leading to increased IL-11 mRNA stability and protein levels. By contrast, overexpression of IL11 in circulating macrophages reverses the phenotype in ALKBH5-deficient mice and macrophage. Lastly, targeted delivery of ALKBH5 or IL-11 receptor α (IL11RA1) siRNA to monocytes/macrophages attenuates MMT and cardiac fibrosis under hypertensive stress. Our results thus suggest that the ALKBH5/IL-11/IL11RA1/MMT axis alters cardiac macrophage and contributes to hypertensive cardiac fibrosis and dysfunction in mice, and thereby identify potential targets for cardiac fibrosis therapy in patients.

Effectiveness of an Integrated Ambulatory Care Program in Health Care and Medication Use in Patients With Multimorbidity and Polypharmacy.

BACKGROUND AND OBJECTIVES: Multimorbidity increases risks, such as polypharmacy, inappropriate prescription, and functional decline. It also increases medical care utilization by older adults, placing a burden on health care systems. This study evaluated the effectiveness of an integrated ambulatory care program for health care and medication use in patients with multimorbidity and polypharmacy. METHODS: We conducted a retrospective clinical review of adults with multimorbidity and polypharmacy who attended an integrated ambulatory care program at a 1193-bed university hospital between July 1 and September 30, 2019. This program involves multidisciplinary teamwork, comprehensive assessments, medication reviews, and case management. Outcomes, including the frequency of outpatient visits, emergency department visits, hospitalizations, chronic prescription medications, potentially inappropriate medications (PIMs), health care costs, and total medical expenditure, were compared before and after the program. RESULTS: The mean age of participants (n = 134) at baseline was 74.22 ± 9.75 years. The mean number of chronic diagnoses was 9.45 ± 3.38. Participants included 72 (53.7%) women. At the 1-year follow-up, participants showed a significant decrease in the annual frequency of outpatient visits (19.78 ± 9.98 to 13.90 ± 10.22, P < .001), emergency department visits (1.04 ± 1.70 to 0.73 ± 1.40, P = .029), and chronic disease medications (10.71 ± 3.96 to 9.57 ± 3.67, P < .001) across all age groups. There was also a reduction in the annual number of PIMs (from 1.31 ± 1.01 to 1.12 ± 0.93, P = .002) among patients aged 65 years. However, no effects were observed on annual hospitalization, duration of hospital stay, or total health care expenditure, possibly due to the high disease-related treatment cost for certain participants. CONCLUSIONS: Expanding integrated ambulatory care programs in Taiwan may help patients with multimorbidity reduce their use of outpatient and emergency services, chronic prescriptions, and PIMs.

Implanted, Wireless, Self-Powered Photodynamic Therapeutic Tablet Synergizes with Ferroptosis Inducer for Effective Cancer Treatment.

The effective and targeted treatment of resistant cancer cells presents a significant challenge. Targeting cell ferroptosis has shown remarkable efficacy against apoptosis-resistant tumors due to their elevated iron metabolism and oxidative stress levels. However, various obstacles have limited its effectiveness. To overcome these challenges and enhance ferroptosis in cancer cells, we have developed a self-powered photodynamic therapeutic tablet that integrates a ferroptosis inducer (FIN), imidazole ketone erastin (IKE). FINs augment the sensitivity of photodynamic therapy (PDT) by increasing oxidative stress and lipid peroxidation. Furthermore, they utilize the Fenton reaction to supplement oxygen, generating a greater amount of reactive oxygen species (ROS) during PDT. Additionally, PDT facilitates the release of iron ions from the labile iron pool (LIP), accelerating lipid peroxidation and inducing ferroptosis. In vitro and in vivo experiments have demonstrated a more than 85% tumor inhibition rate. This synergistic treatment approach not only addresses the limitations of inadequate penetration and tumor hypoxia associated with PDT but also reduces the required medication dosage. Its high efficiency and specificity towards targeted cells minimize adverse effects, presenting a novel approach to combat clinical resistance in cancer treatment.

Stereotactic ablative radiotherapy and FAPα-based cancer vaccine suppresses metastatic tumor growth in 4T1 mouse breast cancer.

BACKGROUND AND PURPOSE: This study tested the hypothesis that a novel combination of stereotactic ablation radiotherapy (SABR) and a cancer vaccine against fibroblast activation protein-alpha (FAPα) can suppress established tumor growth and impede potential metastasis. METHODS: The poorly immunogenic metastatic mouse mammary carcinoma 4T1 was used as a model. Mice were randomly assigned to five treatment groups: (1) untreated control, (2) FAPα-based cancer vaccine, (3) SABR, (4) SABR + pCDH (lentiviral control vector), (5) SABR + FAPα-based cancer vaccine (SABR/FAPα-Vax). FAPα-based cancer vaccine were administered subcutaneously every week for a total of three treatments. SABR was delivered to the primary tumor by 3 × 8 Gy after the first vaccination. RESULTS: Consistent with the poorly immunogenic nature of 4T1, tumor-bearing mice receiving FAPα-based cancer vaccine or SABR monotherapy showed a modest reduction in tumor volume and increased animal lifespan. In contrast, SABR/FAPα-Vax was well-tolerated, significantly reduced tumor burden, and increased survival compared to monotherapy. The increased survival correlated with inhibition of extracellular matrix (ECM) production, tumor vascularization and lymphangiogenesis. SABR/FAPα-Vax also resulted in an abscopal effect capable of eliminating lung metastases. SABR/FAPα-Vax recruited and activated CD8 + T cells to attack tumor cells and FAPα + stromal cells, and initiated suppressor cell reprogramming, including facilitating macrophage polarization toward an anti-tumor (M1) state, as well as depleting myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). CONCLUSION: These findings provide a novel therapeutic combination of radiation and FAPα-based cancer vaccine with promising results against poorly immunogenic metastatic cancer. This study may pave the way to overcome the therapeutic resistance caused by FAPα + CAFs.

Effect of timing of enteral nutrition initiation on poor prognosis in patients after cardiopulmonary bypass: A prospective observational study.

OBJECTIVES: Current guidelines recommend that enteral nutrition (EN) be implemented as early as possible in patients after cardiopulmonary bypass (CPB), but the optimal time to initiate EN remains controversial. Therefore, the aim of this study was to investigate the effect of timing of EN initiation on poor prognosis in patients after CPB. METHODS: This was a prospective observational study with patients who underwent CPB in a tertiary hospital from September 1, 2021, to January 31, 2022. The patients were divided into three groups according to the timing of EN initiation: <24 h, 24 to 48 h, and >48 h. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals to identify independent risk factors for poor prognosis. RESULTS: The study included 579 patients, of whom 255 patients had EN initiated at <24 h (44%), 226 at 24 to 48 h (39%), and at >48 h (17%). With EN <24 h as a reference, multivariate logistic analysis showed that EN 24 to 48 h (OR, 1.854, P = 0.008) and EN >48 h (OR, 7.486, P <0.001) were independent risk factors for poor prognosis after CPB. Age (OR, 1.032, P = 0.001), emergency surgery (OR, 10.051; P <0.001), surgical time (OR, 1.006; P <0.001), and sequential organ failure assessment score (OR, 1.269; P = 0.001) also increased the risk for poor prognosis after CPB. CONCLUSIONS: Compared with early EN <24 h, EN 24 to 48 h and EN >48 h increased the risk for poor prognosis in patients after CPB.

Two-stage method of free gingival graft prior to periodontal regenerative surgery for the treatment of intrabony defects with insufficient keratinised tissue width: a study protocol for an open-label randomised controlled trial.

INTRODUCTION: Guided tissue regeneration (GTR) combined with bone grafting for periodontal regenerative surgery has ideal clinical results for intrabony defect. However, some sites of intrabony defects often suffer from insufficient keratinised gingival width, which affects the efficacy and long-term prognosis of periodontal tissue regeneration. Free gingival graft (FGG) is an effective surgical procedure to widen the keratinised gingiva, but there are few clinical studies on FGG prior to GTR combination with bone grafting to improve clinical outcomes. METHODS: This study is an open-label randomised controlled trial. 68 patients with periodontitis with at least one intrabony defect depth with ≥3 mm are recruited and randomly grouped. In the test group, FGG is performed first, followed by GTR and bone grafting 3 months later; while in the control group, only periodontal tissue regenerative procedures are performed. After completion of all procedures, the patients will be recalled at 3 months, 6 months and 12 months and the relevant clinical and radiographic examinations will be carried out and statistical analysis of the data will also be performed. The present research has received approval from the Ethics Committee of Shanghai Stomatological Hospital (No.2022-007) on 4 August 2022. DISCUSSION: Exploring the effectiveness of the two-stage approach of FGG prior to periodontal tissue regenerative surgery for the treatment of keratinised gingival width deficient intrabony defects can provide a high-level evidence-based basis for the formulation of relevant treatment strategies in clinical practice. ETHICS AND DISSEMINATION: The present research has received approval from the Ethics Committee of Shanghai Stomatological Hospital (No.2022-007) on 4 August 2022. The patients will be incorporated into this trial only after their written informed consent has been obtained. The study will be performed according to the 2013 revision of the Helsinki Declaration of 1975. Personal information of all subjects will be stored in the Department of Periodontology of Shanghai Stomatological Hospital. Data of the present research will be registered with the Clinical Trials Registry Platform. Additionally, we will disseminate the results through scientific journals. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR 2200063180. Registered on 1 September 2022.

A2AR-mediated lymphangiogenesis via VEGFR2 signaling prevents salt-sensitive hypertension.

AIMS: Excess dietary sodium intake and retention lead to hypertension. Impaired dermal lymphangiogenesis and lymphatic dysfunction-mediated sodium and fluid imbalance are pathological mechanisms. The adenosine A2A receptor (A2AR) is expressed in lymphatic endothelial cells (LECs), while the roles and mechanisms of LEC-A2AR in skin lymphangiogenesis during salt-induced hypertension are not clear. METHODS AND RESULTS: The expression of LEC-A2AR correlated with lymphatic vessel density in both high-salt diet (HSD)-induced hypertensive mice and hypertensive patients. Lymphatic endothelial cell-specific A2AR knockout mice fed HSD exhibited 17 ± 2% increase in blood pressure and 17 ± 3% increase in Na+ content associated with decreased lymphatic density (-19 ± 2%) compared with HSD-WT mice. A2AR activation by agonist CGS21680 increased lymphatic capillary density and decreased blood pressure in HSD-WT mice. Furthermore, this A2AR agonist activated MSK1 directly to promote VEGFR2 activation and endocytosis independently of VEGF as assessed by phosphoprotein profiling and immunoprecipitation assays in LECs. VEGFR2 kinase activity inhibitor fruquintinib or VEGFR2 knockout in LECs but not VEGF-neutralizing antibody bevacizumab suppressed A2AR activation-mediated decrease in blood pressure. Immunostaining revealed phosphorylated VEGFR2 and MSK1 expression in the LECs were positively correlated with skin lymphatic vessel density and A2AR level in hypertensive patients. CONCLUSION: The study highlights a novel A2AR-mediated VEGF-independent activation of VEGFR2 signaling in dermal lymphangiogenesis and sodium balance, which might be a potential therapeutic target in salt-sensitive hypertension.

Septin11 promotes hepatocellular carcinoma cell motility by activating RhoA to regulate cytoskeleton and cell adhesion.

Septins as GTPases in the cytoskeleton, are linked to a broad spectrum of cellular functions, including cell migration and the progression of hepatocellular carcinoma (HCC). However, roles of SEPT11, the new member of septin, have been hardly understood in HCC. In the study, the clinical significance and biological function of SEPT11 in HCC was explored. SEPT11 was screened out by combining ATAC-seq with mRNA-seq. Role of SEPT11 in HCC was further investigated by using overexpression, shRNA and CRISPR/Cas9-mediated SEPT11-knockout cells or in vivo models. We found RNA-seq and ATAC-seq highlights LncRNA AY927503 (AY) induced SEPT11 transcription, resulting in Rho GTPase activation and cytoskeleton actin aggregation. The GTP-binding protein SEPT11 is thus considered, as a downstream factor of AY, highly expressed in various tumors, including HCC, and associated with poor prognosis of the patients. In vitro, SEPT11 overexpression promotes the migration and invasion of HCC cells, while SEPT11-knockout inhibits migration and invasion. In vivo, SEPT11-overexpressed HCC cells show high metastasis incidents but don't significantly affect proliferation. Meanwhile, we found SEPT11 targets RhoA, thereby regulating cytoskeleton rearrangement and abnormal cell adhesion through ROCK1/cofilin and FAK/paxillin signaling pathways, promoting invasion and migration of HCC. Further, we found SEPT11 facilitates the binding of GEF-H1 to RhoA, which enhances the activity of RhoA. Overall, our study confirmed function of SEPT11 in promoting metastasis in HCC, and preliminarily explored its related molecular mechanism. SEPT11 acts as an oncogene in HCC, also draws further interest regarding its clinical application as a potential therapeutic target.

Identification of tumor antigens and immune subtypes in head and neck squamous cell carcinoma for mRNA vaccine development.

The mRNA vaccines have been considered effective for combating cancer. However, the core components of the mRNA vaccines against head and neck squamous cell carcinoma (HNSCC) and the effects remain unclear. Our study aims to identify effective antigens in HNSCC to develop mRNA vaccines for corresponding potential patients. Here, we analyzed alternative splicing and mutation of genes in TCGA-HNSCC samples and identified seven potential tumor antigens, including SREBF1, LUC7L3, LAMA5, PCGF3, HNRNPH1, KLC4, and OFD1, which were associated with nonsense-mediated mRNA decay factor expression, overall survival prognosis and the infiltration of antigen-presenting cells. Furthermore, to select suitable patients for vaccination, immune subtypes related to HNSCC were identified by consensus clustering analysis, and visualization of the HNSCC immune landscape was performed by graph-learning-based dimensionality reduction. To address the heterogeneity of the population that is suitable for vaccination, plot cell trajectory and WGCNA were also utilized. HNSCC patients were classified into three prognostically relevant immune subtypes (Cluster 1, Cluster 2, and Cluster 3) possessing different molecular and cellular characteristics, immune modulators, and mutation statuses. Cluster 1 had an immune-activated phenotype and was associated with better survival, while Cluster 2 and Cluster 3 were immunologically cold and linked to increased tumor mutation burden. Therefore, HNSCC patients with immune subtypes Cluster 2 and Cluster 3 are potentially suitable for mRNA vaccination. Moreover, the prognostic module hub genes screened seven genes, including IGKC, IGHV3-15, IGLV1-40, IGLV1-51, IGLC3, IGLC2, and CD79A, which could be potential biomarkers to predict prognosis and identify suitable patients for mRNA vaccines. Our findings provide a theoretical basis for further research and the development of anti-HNSCC mRNA vaccines and the selection of suitable patients for vaccination.

Role of TRPC6 in periodontal tissue reconstruction mediated by appropriate stress.

INTRODUCTION: The basis of orthodontic tooth movement (OTM) is the reconstruction of periodontal tissue under stress. Increasing the speed of OTM has always been the focus of attention. OBJECTIVES: Periodontal ligament stem cells (PDLSCs) are direct effector cells of mechanical force, but the mechanism by which PDLSCs sense mechanical stimuli is unclear. METHODS: Human PDLSCs (hPDLSCs) were analyzed in the presence or absence of force loading with the Flexcell loading system in vitro. Then, periodontal tissues were analyzed after mechanical stimulation in vivo. In addition, cells in a confined microenvironment were analyzed to observe changes in the cytoskeleton and migration. Finally, TRPC6-/- mice were used to further verify the effect of TRPC6. After force application, the OTM distance, bone marrow density (BMD), TRPC6 and COL1 expression, and TRAP staining were evaluated in periodontal tissues. RESULTS: RNA sequencing (RNA-seq) and western blot analyses revealed that TRPC6 was important during mechanical force application to hPDLSCs. Appropriate mechanical force application also induced TRPC6 activation in the OTM model and the confined microenvironment. Under a slightly confined microenvironment, treatment with the TRPC6 inhibitor SKF96365 and TRPC6 knockout decreased the migration speed of hPDLSCs and mouse bone marrow mesenchymal stem cells (mBMSCs). In addition, TRPC6-/- mice showed lower OTM distances and reduced osteogenic and osteoclastic differentiation. CONCLUSION: In summary, TRPC6 activation in PDLSCs mediated by appropriate mechanical force application contributes to periodontal tissue reconstruction. PDLSCs modulate periodontal tissue remodeling under appropriate mechanical stimulation through TRPC6; however, under excessive stress, alveolar bone and tooth roots are readily absorbed. Under this condition, environmental factors play a leading role, and the regulatory effect of TRPC6 is not obvious.

The development of a nomogram and the prognostic prediction value of patients with esophageal squamous cell carcinoma undergoing radical radiotherapy.

AIM: This study aimed to explore the role of the developed nomogram in the prognosis of esophageal squamous cell carcinoma (ESCC). METHODS: A total of 181 ESCC patients were randomly divided into a training cohort (n = 141) and a validation cohort (n = 40). Significant factors impacting overall survival (OS) were identified in the training set and integrated into the nomogram based on Cox proportional hazards regression. RESULTS: In the training cohort, the median OS in the high group (≥222) was 49.9 months and the median OS in the low group (<222) was 14.4 months. Multivariate analysis revealed that age, Karnofsky performance status score, tumor stage, chemotherapy, BMI, cervical esophageal carcinoma index and neutrophil to lymphocyte ratio were predictors of OS. CONCLUSION: The developed nomogram can effectively predict the survival prognosis of ESCC patients.

Sequential soft- and hard-tissue augmentation after clear aligner-mediated adjustment of traumatic occlusion: A case report.

BACKGROUND: Oral health and esthetic concerns have increasingly motivated adults with periodontitis to seek orthodontic care. Patients with periodontitis often have other dental complications that can make treatment more challenging or less likely to be successful. The predictability of multidisciplinary regenerative and orthodontic treatment approaches in a patient with periodontitis, thin periodontal phenotype, and anterior crossbite is described. CASE DESCRIPTION: A 35-year-old man was designated as having a high risk of experiencing soft-tissue recession owing to his thin periodontal phenotype. After the initial periodontal therapy, clear aligners were used to eliminate the anterior crossbite that was causing traumatic occlusion. In addition, a subepithelial connective tissue graft was used to alter the thin periodontal phenotype. Three months later, guided bone regeneration with corticotomy was performed to increase bone mass, and orthodontic traction was used at 2 weeks after surgery. Orthodontic treatment was continued until all the spaces had been closed. Clinical and radiographic evaluations conducted at the 6-month follow-up revealed substantial improvements in both the soft- and hard-tissue phenotypes. PRACTICAL IMPLICATIONS: Outcomes in this case indicate that sequential soft- and hard-tissue augmentation, after eliminating traumatic occlusion via using a clear aligner, may be a valuable approach for improving soft- and hard-tissue support in patients with periodontitis.

Polyurethane foam dressings ameliorating local adverse effects of azacitidine: a randomized controlled trial.

This study investigated the use of polyurethane foam dressings to prevent local adverse reactions of subcutaneous azacitidine injection. Patients receiving a subcutaneous azacitidine injection were randomly divided into experimental and control groups. A total of 55 patients were included in each group. A polyurethane foam dressing was used to cover the injection site of patients in the experimental group. Conventional treatment was used in the control group. Injection site pain and local skin reactions were assessed after the intervention in both groups. The score and duration of pain, the incidence and duration of local skin adverse reactions, and the incidence of severe reactions in the experimental group were significantly lower than in the control group (p < 0.05). Polyurethane foam dressing can effectively reduce local adverse reactions of subcutaneous injection of azacitidine, relieve pain, shorten the duration of local pain and adverse reactions, and improve the quality of nursing.

[Effect of keratinized gingival width on periodontal regenerative surgery for the treatment of intrabony defects: a retrospective study].

PURPOSE: To evaluate the effect of keratinized tissue width (KTW) on periodontal regenerative surgery for the treatment of intrabony defects. METHODS: The clinical data of 14 patients (44 intrabony defect sites) treated with periodontal regenerative surgery were retrospectively analyzed at baseline and 2-year of follow-up. Forty four sites were divided into KTW2 mm group and KTW≤2 mm group according to KTW at baseline. Periodontal clinical indicators of the 2 groups were analyzed by SPSS 25.0 software package. RESULTS: At 2-year post-treatment, probing depth (PD) and clinical attachment loss (CAL) in the 2 groups were decreased significantly compared with those at baseline(P<0.05). There was no significant difference in ΔPD, but ΔCAL in KTW2 mm group was significantly greater than that in KTW≤2 mm group. CONCLUSIONS: Periodontal regenerative surgery for the treatment of intrabony defects can effectively reduce periodontal pocket inflammation, decrease periodontal pocket depth and increase the level of attachment. When the width of the keratinized gingiva is insufficient(KTW≤2 mm), the regeneration of the attachment level obtained by surgery is limited, and the efficacy of regenerative surgery is poor.

Predictive modeling for 14-day unplanned hospital readmission risk by using machine learning algorithms.

BACKGROUND: Early unplanned hospital readmissions are associated with increased harm to patients, increased medical costs, and negative hospital reputation. With the identification of at-risk patients, a crucial step toward improving care, appropriate interventions can be adopted to prevent readmission. This study aimed to build machine learning models to predict 14-day unplanned readmissions. METHODS: We conducted a retrospective cohort study on 37,091 consecutive hospitalized adult patients with 55,933 discharges between September 1, 2018, and August 31, 2019, in an 1193-bed university hospital. Patients who were aged < 20 years, were admitted for cancer-related treatment, participated in clinical trial, were discharged against medical advice, died during admission, or lived abroad were excluded. Predictors for analysis included 7 categories of variables extracted from hospital's medical record dataset. In total, four machine learning algorithms, namely logistic regression, random forest, extreme gradient boosting, and categorical boosting, were used to build classifiers for prediction. The performance of prediction models for 14-day unplanned readmission risk was evaluated using precision, recall, F1-score, area under the receiver operating characteristic curve (AUROC), and area under the precision-recall curve (AUPRC). RESULTS: In total, 24,722 patients were included for the analysis. The mean age of the cohort was 57.34 ± 18.13 years. The 14-day unplanned readmission rate was 1.22%. Among the 4 machine learning algorithms selected, Catboost had the best average performance in fivefold cross-validation (precision: 0.9377, recall: 0.5333, F1-score: 0.6780, AUROC: 0.9903, and AUPRC: 0.7515). After incorporating 21 most influential features in the Catboost model, its performance improved (precision: 0.9470, recall: 0.5600, F1-score: 0.7010, AUROC: 0.9909, and AUPRC: 0.7711). CONCLUSIONS: Our models reliably predicted 14-day unplanned readmissions and were explainable. They can be used to identify patients with a high risk of unplanned readmission based on influential features, particularly features related to diagnoses. The operation of the models with physiological indicators also corresponded to clinical experience and literature. Identifying patients at high risk with these models can enable early discharge planning and transitional care to prevent readmissions. Further studies should include additional features that may enable further sensitivity in identifying patients at a risk of early unplanned readmissions.

HIF-1α activator DMOG inhibits alveolar bone resorption in murine periodontitis by regulating macrophage polarization.

Periodontitis is initiated by serious and sustained bacterial infection and ultimately results in chronic immune-mediated inflammation, tissue destruction, and bone loss. The pathogenesis of periodontitis remains unclear. Host immunological responses to periodontal bacteria ultimately determine the severity and mechanisms governing periodontitis progression. This study aimed to clarify the effect of the hypoxia-inducible factor-1α (HIF-1α) activator dimethyloxalylglycine (DMOG) on a mouse periodontitis model and its underlying role in macrophage polarization. qRT-PCR analysis showed that DMOG inhibited the M1-like polarization of both RAW264.7 macrophages and murine bone marrow macrophages (BMMs) and downregulated TNF-α, IL-6, CD86, and MCP-1 expression in vitro. Immunofluorescence staining and flow cytometry also confirmed the less percentage of F4/80 + CD86 + cells after DMOG treatment. The phosphorylation of NF-κB pathway was also inhibited by DMOG with higher level of HIF-1α expression. Furthermore, mice treated with DMOG showed decreased alveolar bone resorption in the experimental periodontitis model, with significant increases in alveolar bone volume/tissue volume (BV/TV) and bone mineral density (BMD). DMOG treatment of mice decreased the ratio of M1/M2 (CD86+/CD206+) macrophages in periodontal tissues, resulting in the downregulation of proinflammatory cytokines such as TNF-α and IL-6 and increased levels of anti-inflammatory factors such as IL-4 and IL-10. DMOG treatment promoted the number of HIF-1α-positive cells in periodontal tissues. This study demonstrated the cell-specific roles of DMOG in macrophage polarization in vitro and provided insight into the mechanism underlying the protective effect of DMOG in a model of periodontitis.

A multidisciplinary team nursing model in the treatment of patients undergoing transapical mitral valve clamping: a prospective study.

BACKGROUND: As a new surgical method for older adults with cardiac insufficiency, transapical mitral valve clamp surgery requires the cooperation of practitioners across multiple disciplines to ensure appropriate treatment and nursing care. This study aimed to explore the utility of a multidisciplinary team nursing model in the clinical treatment and nursing care of patients undergoing transapical mitral valve clamping. METHODS: Our sample of ten patients included four men (40%) and six women (60%), with a mean age of 71.4 ± 5.2 years. The multidisciplinary team comprised nurses that specialized in severe illness, cardiac health, rehabilitation, psychology, nutrition, and pain. The team engaged in comprehensive discussions regarding problems specific to the patients undergoing transapical mitral valve surgery, allowing them to formulate individualized nursing measures and implement precise policies. RESULTS: No serious postoperative complications occurred in any of the ten patients included in this study, and a significant improvement was noted in the cardiac status of all the patients. Color ultrasound findings at discharge indicated that the degree of reflux of all the patients was ≤2+. Among the ten patients, the Activity of Daily Living Scale scores at discharge were significantly higher than before the operation (69.0 ± 4.6 vs. 55.0 ± 5.8). In addition, the 6-min walking test results at discharge were significantly better than those observed before the operation (318.0 ± 21.7 m vs. 295.2 ± 18.4 m). CONCLUSIONS: Utilization of a multidisciplinary team allows nurses across various specialties to provide more comprehensive and systematic care for patients undergoing a mitral valve clamping operation, thus promoting patient recovery.

RéSUMé: CONTEXTE: en tant que nouvelle méthode chirurgicale pour le traitement de l'insuffisance cardiaque chez les personnes âgées, la chirurgie par pince de la valve mitral aiguë nécessite la collaboration de médecins multidisciplinaires pour assurer un traitement et des soins appropriés. OBJECTIFS: étudier l'application du modèle de soins en équipe multidisciplinaire dans le traitement clinique et les soins aux patients atteints de la valve mitral par pince. MéTHODE: sur 10 patients, 4 hommes (40%) et 6 femmes (60%) ont un âge moyen de 71.4 à 5.2 ans. L'équipe multidisciplinaire est. composée d'infirmiers spécialisés dans les maladies graves, la santé cardiaque, la réadaptation, la psychologie, la nutrition et la douleur. L'équipe a mené une discussion approfondie sur les problèmes spécifiques des patients soumis à une opération de la valve mitral transspiroptérale, a élaboré des mesures de soins personnalisées et a mis en œuvre des politiques précises. RéSULTATS: aucune complication postoperatoire grave n'a été observée chez les 10 patients de ce groupe, et les défaillances cardiaques ont été nettement améliorées chez tous les patients. Une double échographie en couleur a montré que le degré de regurgitation mitral était inférieur ou égal à 2+ dans 10 patients sortant de cette étude; Les scores sur l'échelle des activités de la vie quotidienne à la sortie de l'hôpital étaient nettement plus élevés dans 10 cas que dans le cas préopératoire (69.0 ± 4.6 contre 55.0 ± 5.8). En outre, les résultats d'un essai de marche de 6 min à la sortie de l'hôpital étaient nettement supérieurs à ceux observés avant l'opération (318.0 ± 21.7 m contre 295.2 ± 18.4 m). CONCLUSION: le recours à des équipes multidisciplinaires permet aux infirmiers/infirmières spécialisés de fournir des soins plus complets et systématiques aux patients soumis à la chirurgie par compression de la valve mitral, ce qui facilite leur réadaptation.

FAPI-04 PET/CT Using [18F]AlF Labeling Strategy: Automatic Synthesis, Quality Control, and In Vivo Assessment in Patient.

68Ga labeled FAPI is the current standard for FAPI-PET, but its batch activity is limited. [18F]AlF-NOTA-FAPI-04 is a promising alternative combining the advantages of a chelator-based radiolabeling method with the unique properties of fluorine-18. The objective of this study was to develop a quick automatic method for synthesis of [18F]AlF-NOTA-FAPI-04 using a AllinOne synthesis system, and perform PET imaging with [18F]AlF-NOTA-FAPI-04 on patients. [18F]AlF-NOTA-FAPI-04 was produced, and its quality control was conducted by HPLC equipped with a radioactive detector. [18F]AlF-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice (n = 3) and 4T1 breast cancer models (n = 3) to determine its biodistribution. Then [18F]AlF-NOTA-FAPI-04 and 18F-fluorodeoxyglucose (FDG) PET/CT imaging were performed in an invasive ductal carcinoma patient (female, 54 years old). The synthesis time of [18F]AlF-NOTA-FAPI-04 was about 25 min, and the radiochemical yield was 26.4 ± 1.5% (attenuation correction, n = 10). The radiochemical purity was above 99.0% and was above 98.0% after 6 h. The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was 49.41 ± 3.19 GBq/µmol. PET/CT imaging in mice showed that physiological uptake of [18F]AlF-NOTA-FAPI-04 was mainly in the biliary system and bladder, and [18F]AlF-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that [18F]AlF-NOTA-FAPI-04 obtained high tumor background ratio (TBR) value of 8.44 in segment V and VI, while TBR value was 2.55 by 18F-FDG. [18F]AlF-NOTA-FAPI-04 could be synthesized with high radiochemical yield and batch production by AllinOne module and show excellent diagnosis performance in cancer patients.