Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
Humans ; Dental Pulp/cytology* ; Nuclear Pore Complex Proteins/genetics* ; Cellular Senescence/genetics* ; Stem Cells/metabolism* ; Epigenesis, Genetic ; Cell Proliferation ; Cell Differentiation ; Histone-Lysine N-Methyltransferase/metabolism* ; Cells, Cultured ; Cellular Reprogramming ; Cell Movement ; Proteomics

Objective To observe the efficacy and safety of radiotherapy combined with programmed death receptor-1(PD-1)inhibitors and tyrosine kinase inhibitors(TKIs)for the treatment of microsatellite-stabilized(MSS)-type or mismatch-matched repair-normal(pMMR)-type colorectal cancer with liver metastases(CCLM).Methods Case data of 25 patients with MSS-type CCLM admitted to Jiangsu Provincial Cancer Hospital from April 2021 to August 2023 were retrospectively analyzed.They were divided into observation group(n = 12)and control group(n = 13).The observation group was given radiotherapy combined with PD-1 inhibitor and TKI treatment,and the control group was given TKI monotherapy.The baseline data,treatment effect,progression-free survival,and treatment-related adverse reactions of patients in the two groups were compared.Results The difference in baseline data between the two groups was not statistically significant(P＞0.05),the disease control rate(DCR)of the observation group was higher than that of the control group(P＜0.05),the progression-free survival(PFS)of the patients in the observation group was longer than that of the control group,but the difference was not statistically sig-nificant(P＞0.05),and the difference in the incidence of treatment-related adverse events(TRAE)between the two groups was not statistically significant(P＞0.05).Conclusion The treatment regimen of radiotherapy com-bined with PD-1 inhibitors and TKI drugs improved clinical efficacy and did not increase the incidence of adverse events when compared with TKI alone,which is a treatment regimen worthy of further validation.

ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF） and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1， 2010 to December 31， 2021， and according to the drug susceptibility results， the patients were divided into multidrug-resistant （MDR） bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic （ROC） curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection， sputum （27.7%） was the most common specimen for detection， followed by blood （24.6%）， urine （18.5%）， and ascites （17.7%）. Bacterial infections were dominated by Gram-negative bacteria （58.5%）. Of all bacteria， Escherichia coli （18.5%）， Klebsiella pneumoniae （14.6%）， and Enterococcus faecium （13.8%） were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin （72.2%）， penicillin （57.4%）， ampicillin （55.6%）， and ciprofloxacin （53.7%）， while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin （73.3%）， cefazolin （50.0%）， and cefepime （47.4%）. The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection （61.5%）. Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection， the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase （Z=2.089， P=0.037）， aspartate aminotransferase （Z=2.063， P=0.039）， white blood cell count （Z=2.207， P=0.027）， and monocyte count （Z=4.413， P<0.001）. The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection （odds ratio=7.120， 95% confidence interval ［CI］： 2.478‍ ‍—‍ ‍20.456，P<0.001） and had an area under the ROC curve of 0.686 （95%CI： 0.597‍ ‍—‍ ‍0.776） in predicting ACLF with MDR bacterial infection（P<0.001）， with the optimal cut-off value of 0.50×10⁹/L， a sensitivity of 0.725， and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria， with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.

The ChatGPT, a lite and conversational variant of Generative Pretrained Transformer 4 (GPT-4) developed by OpenAI, is one of the milestone Large Language Models (LLMs) with billions of parameters. LLMs have stirred up much interest among researchers and practitioners in their impressive skills in natural language processing tasks, which profoundly impact various fields. This paper mainly discusses the future applications of LLMs in dentistry. We introduce two primary LLM deployment methods in dentistry, including automated dental diagnosis and cross-modal dental diagnosis, and examine their potential applications. Especially, equipped with a cross-modal encoder, a single LLM can manage multi-source data and conduct advanced natural language reasoning to perform complex clinical operations. We also present cases to demonstrate the potential of a fully automatic Multi-Modal LLM AI system for dentistry clinical application. While LLMs offer significant potential benefits, the challenges, such as data privacy, data quality, and model bias, need further study. Overall, LLMs have the potential to revolutionize dental diagnosis and treatment, which indicates a promising avenue for clinical application and research in dentistry.
Dentistry ; Artificial Intelligence

Periodontitis is an inflammatory disease caused by bacterial infection directly, and the dysregulation of host immune-inflammatory response finally destroys periodontal tissues. Current treatment strategies for periodontitis mainly involve mechanical scaling/root planing (SRP), surgical procedures, and systemic or localized delivery of antimicrobial agents. However, SRP or surgical treatment alone has unsatisfactory long-term effects and is easy to relapse. In addition, the existing drugs for local periodontal therapy do not stay in the periodontal pocket long enough and have difficulties in maintaining a steady, effective concentration to obtain a therapeutic effect, and continuous administration always causes drug resistance. Many recent studies have shown that adding bio-functional materials and drug delivery systems upregulates the therapeutic effectiveness of periodontitis. This review focuses on the role of biomaterials in periodontitis treatment and presents an overview of antibacterial therapy, host modulatory therapy, periodontal regeneration, and multifunctional regulation of periodontitis therapy. Biomaterials provide advanced approaches for periodontal therapy, and it is foreseeable that further understanding and applications of biomaterials will promote the development of periodontal therapy.

Objective:To retrieve, evaluate and summarize relevant evidence of parastomal hernia prevention and management, so as to provide a reference for clinical nursing.Methods:We used computer systems to search and screen the related guidelines, evidence summary, recommended practices, expert consensus and systematic reviews on the prevention and management of parastomal hernia in the official websites of ostomy-related associations, guide networks, and databases. The research time limit was from the establishment of the database to July 2, 2020. Two systematically trained researchers evaluated the quality of the articles, and extracted data and evidence from the articles that met the quality standards.Results:A total of 9 articles were included, involving 6 guidelines, 1 recommended practice and 2 systematic reviews. A total of 15 best pieces of evidence were summarized, including 5 aspects, namely diagnostic standards, classification, risk factors, prevention and management.Conclusions:If medical personnel can accurately identify the risk factors of parastomal hernia, and carry out early prevention and management, it can reduce the incidence of parastomal hernia and/or alleviate the discomfort caused by parastomal hernia, thereby improving the patient's quality of life. It is suggested that clinical nursing staff can transform in a targeted manner according to specific clinical situations to improve the quality of clinical nursing.

Objective:To investigate the effect of internet nursing model on female patients who are undergoing in vitro fertilization-embryo transfer, improve the quality of nursing service in reproductive center.Methods:A total of 201 female patients undergoing in vitro fertilization-embryo transfer from April 2018 to December 2018 were divided into the intervention group(102 cases) and the control group(99 cases) by random digits table method. The patients in intervention group were treated with nursing care based on the internet platform, and the control group was given routine care. The duration of intervention was from the patients determined treatment plan to the time pregnancy test 14 days after embryo transfer. The Self-rating Anxiety Scale(SAS) and Self-rating Depression Scale(SDS), Fertility Quality of Life(FertiQoL), and Connor-Davidson Resilience Scale(CD-RISC) were used to evaluate the differences in anxiety and depression, quality of life, and psychological resilience before and after intervention. The outcome of in vitro fertilization-embryo transfer was observed in two groups.Results:After intervention, the score of SAS, SDS were 26.03±6.43, 28.79±5.26 in the intervention group, and 40.76±6.81, 36.13±6.27 in the control group, the difference were significant( t values were -15.77, -9.00, all P<0.01). After intervention,the dimensional scores of mental and physical, social relationship, tolerance to treatment in the FertiQoL were 68.21±18.34, 75.56±19.58, 69.14±18.91 in the intervention group, and 58.11±17.42, 67.24±19.27, 58.77±19.86 in the control group, the difference were significant( t values were 4.00, 3.04, 3.79, all P<0.01). After intervention,the dimensional scores of tough, optimistic in CD-RISC were 37.03±10.51, 14.02±3.25 in the intervention group, and 26.73±9.81, 10.13±3.41 in the control group, the difference were significant( t values were 7.17, 8.28, all P<0.01). The average number of high-quality embryos and clinical pregnancy rate were 1.79(0.59, 4.51), 49.02%(50/102) in the intervention group, and 1.22(0.36, 2.86) , 33.33% (33/99) in the control group, the difference were significant ( t value was 2.47, χ2 value was 5.10, all P<0.05). Conclusions:The new nursing model based on internet has positive significance for the treatment of female patients undergoing in vitro fertilization-embryo transfer, which can improve patients' anxiety and depression, improve their quality of life and enhance their psychological resilience.

Objective:To understand the clinical research knowledge, attitude and practice of pediatrics residents in standardized residency training, and to provide scientific basis for improving their capability of clinical medical scientific research.Methods:A self-complied questionnaire survey including demographic information, knowledge and attitudes toward capability of medical scientific research as well as personal interview was conducted in 22 pediatric residents during the standardized residency training from April to July, 2017. Data were analyzed by (mean±standard deviation) and percentage for description, and qualitative data were analyzed by classification and induction. SPSS 18.0 was used to analyze the data.Results:Firstly, the total score of basic knowledge in clinical scientific research was (54.14±23.06), with the scores between 31 and 60 being the most. Secondly, all these residents believed that capability of clinical medical scientific research was very important for them and clinical research training was necessary for them during the standardized residency training. Thirdly, the residents had the scientific research practices but no article published during the standardized residency training. Fourthly, the residents hoped to improve their capability of clinical scientific research by various means during the training.Conclusion:It is indicated that basic knowledge on capability of clinical medical research is still insufficient in standardized residency training of pediatrics residents, so relevant measures should be taken to cultivate their capability of clinical scientific research.

Purpose: Despite the rapid growing of cancer survivors, prior cancer history is a commonly adoptedexclusion criterion. Whether prior cancer will impact the survival of patients with advancedbreast cancer (ABC) remains uncertain. Materials and Methods: Patients with ABC diagnosed between 2004 and 2010 were identified using Surveillance,Epidemiology, and End Results (SEER) database. Timing, stage, and type were used to characterizeprior cancer. Multivariable analyses using propensity score–adjusted Cox regressionand competing risk regression were conducted to evaluate the prognostic effect of priorcancer on overall survival (OS) and breast cancer-specific survival (BCSS). Results: A total of 14,176 ABC patients were identified, of whom 10.5% carried a prior cancer history.The most common type of prior cancer was female genital cancer (32.4%); more than half(51.7%) were diagnosed at localized stage; most were diagnosed more than 5 years (42.9%)or less than 1 year (28.3%) prior to the index cancer. In multivariate analyses, patients withprior cancer presented a slightly worse OS (hazard ratio, 1.18; 95% confidence interval [CI],1.07 to 1.30; p=0.001) but a better BCSS (subdistribution hazard ratio, 0.64; 95% CI, 0.56to 0.74; p < 0.001). In subset analyses, no survival detriment was observed in patients withprior malignancy from head and neck or endocrine system, at in situ or localized stage, ordiagnosed more than 4 years. Conclusion Prior cancer provides an inferior OS but a superior BCSS for patients with ABC. It does notaffect the survival adversely in some subgroups and these patients should not be excludedfrom clinical trials.