Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Dysregulation of p53 and phosphoinositide (PIPn) signaling are both key drivers of oncogenesis and metastasis. Our recent findings reveal a previously unrecognized interaction between these pathways, converging in the nucleus to form a PIPn-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIPn signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIPns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIPns in stabilizing p53 and activating de novo nuclear AKT signaling, which subsequently modulates key motility-related pathways. Understanding the unique operation and function of the PIPn-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.
Humans ; Tumor Suppressor Protein p53/metabolism* ; Signal Transduction ; Cell Movement ; Cell Nucleus/metabolism* ; Phosphatidylinositols/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Animals ; Neoplasms/pathology* ; Phosphatidylinositol 3-Kinases/metabolism*

Objective To explore the potential targets and mechanism of Gufang Granules in treating osteoporosis through network pharmacology,molecular dynamics simulations,and in vitro experiment validation.Methods The active components of Gufang Granules were obtained from the TCMSP database and literature,and their related targets were predicted using SwissTargetPrediction database.Core drug targets were selected through protein-protein interaction(PPI)network analysis and machine learning models,and the predictive performance of the models was assessed by drawing receiver operating characteristic(ROC)curves on independent validation datasets.Gene Set Enrichment Analysis(GSEA)was used to analyze the expression and pathways of core targets.Molecular dynamics(MD)simulations were applied to evaluate the structural stability and interactions of the compound-target complexes.Non-cytotoxic concentrations of Gufang Granules containing serum were determined by the CCK-8 assay.RAW264.7 cells were treated with low,medium,and high concentrations of drug containing serum,respectively.The number of osteoclasts was quantified using TRAP staining.The expression levels of relevant genes and proteins were analyzed through qRT-PCR and Western blot methods.Results A total of 251 potential active components and 1 078 related targets of Gufang Granules were identified.The high expressions of core targets SRC and TNF were mainly associated with osteoclast differentiation,MAPK signaling pathway and PI3K/Akt signaling pathway.MD simulations showed that the core active component Glabridin exhibited strong stability and interaction with the SRC and TNF target proteins.The number of TRAP positive cells in all concentration groups of Gufang Granules was significantly reduced compared to the RANKL group(P<0.01,P<0.001).The serum containing Gufang Granules significantly reduced the mRNA expression of NFATc1,CTSK,SRC and TNF-α,and also downregulated the protein expression of NFATc1,CTSK,p-SRC and TNF-α(P<0.05,P<0.01,P<0.001).Conclusion Gufang Granules may inhibit osteoclast differentiation by downregulating the expression of NFATc1,CTSK,p-SRC and TNF-α,thereby slowing the pathological progression of osteoporosis.

Objective To explore the occurrence of massive hemorrhage during curettage after secondary interventional embolization in patients with recurrent cesarean scar pregnancy(RCSP)and its related influencing factors.Methods A retrospective analysis was conducted on the clinical data of 48 patients with RCSP who were treated at Women and Children's Hospital of Ningbo University from January 2014 to December 2024.Patients were divided into massive hemorrhage group(hemorrhage volume≥200ml,n=12)and non-massive hemorrhage group(hemorrhage volume＜200ml,n=36)based on the amount of blood loss during uterine curettage.Univariate and multivariate Logistic regression analyses were used to determine the independent risk factors for massive hemorrhage during curettage after secondary interventional embolization in patients with RCSP.Results There were statistically significant differences in the number of induced abortions,the duration of amenorrhea,the level of serum β-human chorionic gonadotropin,the maximum diameter of gestational sac,the thickness of uterine scar myometrium,the fetal vascular pulsation,and the blood supply of gestational sac between two groups of patients(P＜0.05).The results of multivariate Logistic regression analysis showed that the duration of amenorrhea,the maximum diameter of gestational sac,and the thickness of uterine scar myometrium were all independent risk factors for massive hemorrhage during uterine curettage(P＜0.05).The area under the curve of duration of amenorrhea,maximum diameter of gestational sac,thickness of uterine scar myometrium and the combination of the three for predicting massive hemorrhage during curettage after secondary interventional RCSP were 0.797,0.885,0.748 and 0.914,respectively.Conclusion Patients with RCSP still have a relatively high risk of bleeding after uterine curettage following secondary interventional embolization.The duration of amenorrhea,the maximum diameter of gestational sac,and thickness of uterine scar myometrium are the key influencing factors affecting intraoperative bleeding.

Objective:To investigate the clinical efficacy and factors influencing treatment of pediatric noninfectious uveitis with Adalimumab (ADA).Methods:A retrospective clinical study. A total of 86 pediatric patients with non-infectious uveitis, diagnosed and treated with ADA at Department of Uveitis Specialist of Xi'an People's Hospital (Xi' an Fourth Hospital) from January 1, 2021 to December 31, 2023, were included in this study. The age of all patients was ≤16 years. Among them, 55 (63.95%, 55/86) patients received ADA combined with one immunosuppressive agent, 28 (32.56%, 28/86) patients received ADA combined with ≥2 immunosuppressive agents, and 3 (3.49%, 3/86) patients received ADA alone without any immunosuppressive agents. All patients underwent best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. The thickness of the retinal nerve fiber layer (RNFL) in the macular region was measured using an OCT device. The cumulative treatment effectiveness rate at 12 months post-treatment was evaluated using the Kaplan-Meier survival analysis. Multivariate analysis was performed using the Cox proportional hazards regression model, and the optimal predictive model was selected based on the Bayesian information criterion. The association between different treatment regimens and various clinical outcomes was assessed.Results:Among the 86 pediatric patients, 42 were male and 44 were female, with a mean age of (10.47±3.23) years. The distribution of uveitis types was as follows: anterior uveitis in 37 cases, intermediate uveitis in 15 cases, posterior uveitis in 10 cases, and panuveitis in 24 cases. Anterior chamber cells (ACC), keratic precipitates, and synechiae were present in 66, 55, and 38 cases, respectively. The cumulative treatment effectiveness at 12 months was 85.1% [95% confidence interval ( CI) 71.9-92.2], with a median time to treatment effectiveness of 3 months. Compared with baseline, after 6 months of treatment, the BCVA, RNFL thickness ( Z=?6.323, ?8.017), and the grading of ACC and vitreous haze ( χ2= ?6.917, ?5.027) showed significant improvement, with statistically significant differences ( P<0.05). Multivariate analysis revealed that ACC (hazard ratio=22.31, 95% CI 2.43-204.68) and anterior uveitis (hazard ratio=3.88, 95% CI 2.03-7.42) were significantly associated with treatment effectiveness ( P<0.05). Patients with ACC had a median time to treatment effectiveness of 2 months, with a 12-month cumulative treatment effectiveness of 95.5% (95% CI 86.3-98.5). Patients with anterior uveitis had a median time to treatment effectiveness of 2 months, with a 12-month cumulative treatment effectiveness of 97.3% (95% CI 81.3-99.6). Patients without anterior uveitis had a median time to treatment effectiveness of 5 months, with a 12-month cumulative treatment effectiveness of 76.7% (95% CI 54.1-88.2). The cumulative recurrence risk at 12 months was 15.6% (95% CI 6.2-24.1). Conclusion:ADA is safe and effective in treating pediatric non-infectious uveitis, and ACC and anterior uveitis are associated with response rate.

Objective:To explore the feasibility, safety, and effectiveness of a novel suture instrument for closure of full thickness defects of the gastric wall under gastroscopy.Methods:Ten pigs were used as experimental animals. Perforation model (30 mm in long diameter) was created in the stomach of each pig. The perforations were then closed by the novel suture instrument under gastroscopy. The completion time and efficacy of each perforation repair were recorded. The pigs were euthanized 14 days after the procedure. The healing condition was observed under gastroscopy. A postmortem examination was performed to observe the abdominal infection and healing condition of perforation. Ascites sample was taken for bacterial culture.The stomach biopsy were taken for histopathologic examination.Results:All gastric perforation models in the 10 pigs were established successfully. Endoscopic closure for the stomach perforation was technically successful in all 10 pigs. The procedure time was 34.10±10.32 minutes. All animals survived. Gastroscopy and necropsy showed that the perforation healed well with local adhesion. One pig developed abdominal infection. Ascites culture were negative in 9 cases, 1 bacterial infection was caused by Arcanobacterium pyogenes and Escherichiacoli. The pathology results showed that the muscular layer of the gastric wall defect in the entire group was well repaired. Conclusion:The novel suture instrument is safe and effective in repairing full-thickness gastric wall defects under ordinary single clamp gastroscopy, providing an experimental basis for further clinical research.

Objective:To compare the clinical efficacy and effects on cognitive function of magnetic seizure therapy (MST) and modified electroconvulsive therapy (MECT) in the treatment of major depressive episode (MDE).Methods:From January 1, 2019 to December 31, 2021, 40 patients who met the MDE diagnostic criteria in the fifth edition of the Diagnostic Statistical Manual of Mental Disorders (DSM-5) were selected in Shanghai Mental Health Center. Participants were randomly assigned to MECT therapy group (20 patients) and MST therapy group (20 patients) using the random number table method. Both groups received MECT or MST while using serotonin reuptake inhibitors (SSRIs), 3 times a week for 4 weeks. The 17-items Hamilton Depression Rating Scale (HAMD 17) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were performed before and after treatment. HAMD 17 reduction rate and effective rate were the main assessment indicators, while RBANS total score and factor scores were considered as the secondary assessment indicators. T-test was used to compare the reduction rate of HAMD 17 between the two groups, and corrected Chi-square test or Fisher′s exact probability method was used to compare the effective rate of treatment between the two groups. HAMD 17 scores and RBANS scores before and after treatment were compared using two-factor repeated measure ANOVA. Results:There were no significant differences in baseline HAMD 17 scores and RBANS scores between 2 groups( t=0.29, P=0.773; t=0.67, P=0.509). The treatment effective rate in the MECT group was 90% (18/20), and the average reduction rate of HAMD 17 was 67.9%. Meanwhile, the effective rate of MST group was 75% (15/20), and the average reduction rate of HAMD 17 was 60.9%. There was no significant difference in the reduction rate and effective rate of HAMD 17 between the two groups ( t=0.69, P=0.493; χ2=0.16, P=0.693). The total scores and factor scores of RBANS after treatment were lower than those before treatment, with statistical significance(total scores: F=19.29, P<0.001;immediate memory score: F=6.22, P=0.020; language function score: F=9.13, P=0.006;attention score: F=5.23, P=0.031;delayed memory score: F=35.90, P<0.001). There was no significant difference in the total scores and factor scores of RBANS before and after treatment in MST group(total scores: F=0.49, P=0.490;immediate memory score: F=2.25, P=0.147;language function score: F=1.22, P=0.280;attention score: F=0.23, P=0.640;delayed memory score: F=0.02, P=0.887). Conclusions:The efficacy of MST treatment and MECT treatment in treating MDE patients seems to be comparable. MDE patients receiving MST had less impact on cognitive function compared to those treated with MECT.

Melatonin is widely used as an over-the-counter medication to treat insomnia in children with autism spectrum disorder (ASD) and neurogenetic disorders (NGD). However, there is still a lack of research on its efficacy and safety, and clinical practice standards are to be established. In response, the International Pediatric Sleep Association (IPSA) convened an expert panel and developed a consensus statement:"Melatonin Use in Managing Insomnia in Children with Autism and Other Neurogenetic Disorders-an Assessment by the International Pediatric Sleep Association (IPSA)", which was published in Sleep Medicine, April 2024. The consensus focused on the efficacy and adverse effects of melatonin treatment for insomnia in children with ASD and NGD-including Smith-Magenis syndrome, Rett syndrome, Angelman syndrome, and tuberous sclerosis complex. It systematically reviews randomized controlled trials (RCTs) conducted between 2012 and 2022, and integrates current best clinical practices to formulate 10 consensus recommendations. Despite these contributions, the consensus has limitations: a small number of included RCTs, a lack of grading for evidence quality, and recommendation strength. Furthermore, the study population is primarily composed of children from Western countries. This article seeks to interpret the consensus to improve standardized use of melatonin for insomnia in Chinese children with ASD and NGD, and to provide a reference for the future development of localized evidence-based guidelines.

Objective To explore the potential targets and mechanism of Gufang Granules in treating osteoporosis through network pharmacology,molecular dynamics simulations,and in vitro experiment validation.Methods The active components of Gufang Granules were obtained from the TCMSP database and literature,and their related targets were predicted using SwissTargetPrediction database.Core drug targets were selected through protein-protein interaction(PPI)network analysis and machine learning models,and the predictive performance of the models was assessed by drawing receiver operating characteristic(ROC)curves on independent validation datasets.Gene Set Enrichment Analysis(GSEA)was used to analyze the expression and pathways of core targets.Molecular dynamics(MD)simulations were applied to evaluate the structural stability and interactions of the compound-target complexes.Non-cytotoxic concentrations of Gufang Granules containing serum were determined by the CCK-8 assay.RAW264.7 cells were treated with low,medium,and high concentrations of drug containing serum,respectively.The number of osteoclasts was quantified using TRAP staining.The expression levels of relevant genes and proteins were analyzed through qRT-PCR and Western blot methods.Results A total of 251 potential active components and 1 078 related targets of Gufang Granules were identified.The high expressions of core targets SRC and TNF were mainly associated with osteoclast differentiation,MAPK signaling pathway and PI3K/Akt signaling pathway.MD simulations showed that the core active component Glabridin exhibited strong stability and interaction with the SRC and TNF target proteins.The number of TRAP positive cells in all concentration groups of Gufang Granules was significantly reduced compared to the RANKL group(P<0.01,P<0.001).The serum containing Gufang Granules significantly reduced the mRNA expression of NFATc1,CTSK,SRC and TNF-α,and also downregulated the protein expression of NFATc1,CTSK,p-SRC and TNF-α(P<0.05,P<0.01,P<0.001).Conclusion Gufang Granules may inhibit osteoclast differentiation by downregulating the expression of NFATc1,CTSK,p-SRC and TNF-α,thereby slowing the pathological progression of osteoporosis.

Objective To explore the occurrence of massive hemorrhage during curettage after secondary interventional embolization in patients with recurrent cesarean scar pregnancy(RCSP)and its related influencing factors.Methods A retrospective analysis was conducted on the clinical data of 48 patients with RCSP who were treated at Women and Children's Hospital of Ningbo University from January 2014 to December 2024.Patients were divided into massive hemorrhage group(hemorrhage volume≥200ml,n=12)and non-massive hemorrhage group(hemorrhage volume＜200ml,n=36)based on the amount of blood loss during uterine curettage.Univariate and multivariate Logistic regression analyses were used to determine the independent risk factors for massive hemorrhage during curettage after secondary interventional embolization in patients with RCSP.Results There were statistically significant differences in the number of induced abortions,the duration of amenorrhea,the level of serum β-human chorionic gonadotropin,the maximum diameter of gestational sac,the thickness of uterine scar myometrium,the fetal vascular pulsation,and the blood supply of gestational sac between two groups of patients(P＜0.05).The results of multivariate Logistic regression analysis showed that the duration of amenorrhea,the maximum diameter of gestational sac,and the thickness of uterine scar myometrium were all independent risk factors for massive hemorrhage during uterine curettage(P＜0.05).The area under the curve of duration of amenorrhea,maximum diameter of gestational sac,thickness of uterine scar myometrium and the combination of the three for predicting massive hemorrhage during curettage after secondary interventional RCSP were 0.797,0.885,0.748 and 0.914,respectively.Conclusion Patients with RCSP still have a relatively high risk of bleeding after uterine curettage following secondary interventional embolization.The duration of amenorrhea,the maximum diameter of gestational sac,and thickness of uterine scar myometrium are the key influencing factors affecting intraoperative bleeding.