An attractive smile is the goal and challenge of oral esthetic treatment.The characteristics of lips,teeth,and gingival are the three essential elements of smile esthetics.In the past,dentists mainly focused on"white esthetics"related to the hard tissue fea-tures.But recently,scholars have found that soft tissue esthetics plays a decisive role in the overall harmony and attractiveness of a smile.Currently,there is no standardized evaluation criterion or analytical process specifically addressing soft tissue esthetics in relation to smile attractiveness.This paper aims to propose key soft tissue variables in smile esthetics,summarize the facial soft tissue features and esthetic preferences of Chinese people,sort out clinical evaluation methods,and provide a reference for the oral clinical esthetic di-agnosis and treatment.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

OBJECTIVE: To compare the effectiveness and advantages of the double reverse traction reduction versus open reduction internal fixation for treating complex tibial plateau fractures. METHODS: A clinical data of 25 patients with Schatzker type Ⅴ or Ⅵ tibial plateau fractures, who met the selection criteria and were admitted between January 2019 and January 2023, was retrospectively analyzed. Thirteen patients underwent double reverse traction reduction and internal fixation (double reverse traction group), while 12 patients underwent open reduction and internal fixation (traditional open group). There was no significant difference in the baseline data (age, gender, injury mechanism, Schatzker classification, interval between injury and operation) between the two groups ( P>0.05). The effectiveness were evaluated and compared between the two groups, included operation time, intraoperative blood loss, incision length, hospital stay, full weight-bearing time, complications, fracture healing, Rasmussen radiological score (reduction quality), knee Hospital for Special Surgery (HSS) score, and knee flexion/extension range of motion. RESULTS: The double reverse traction group demonstrated significantly superior outcomes in operation time, intraoperative blood loss, hospital stay, incision length, and time to full weight-bearing ( P<0.05). Two patients in traditional open group developed incisional complications, while the double reverse traction group had no complication. There was no significant difference in the incidence of complication between the two groups ( P>0.05). All patients were followed up 24-36 months (mean, 30 months), with no significant difference in follow-up duration between groups ( P>0.05). Fractures healed in both groups with no significant difference in healing time ( P>0.05). At 6 months after operation, Rasmussen radiological scores and grading showed no significant difference between the two groups ( P>0.05); the double reverse traction group had significantly higher HSS scores compared to the traditional open group ( P<0.05). At 12 months after operation, knee flexion/extension range of motion were significantly greater in the double reverse traction group than in the traditional open group ( P<0.05). CONCLUSION Double reverse traction reduction offers advantages over traditional open reduction, including shorter operation time, reduced blood loss, minimized soft tissue trauma, and improved joint functional recovery. It is a safe and reliable method for complex tibial plateau fractures.
Humans ; Tibial Fractures/surgery* ; Fracture Fixation, Internal/methods* ; Male ; Female ; Traction/methods* ; Retrospective Studies ; Middle Aged ; Adult ; Open Fracture Reduction/methods* ; Treatment Outcome ; Range of Motion, Articular ; Fracture Healing ; Operative Time ; Length of Stay ; Blood Loss, Surgical ; Aged ; Tibial Plateau Fractures

The periodontal chart comprehensively and objectively records the periodontal status of each tooth in the entire dentition, which is an important basis and essential for the correct diagnosis of periodontal diseases and treatment plan formulation. This article describes in detail the content and clinical significance of the periodontal chart, the key points of the implementation of the clinical completion of the periodontal chart and the step-by-step training mode. This article, as the fourth chapter in the basic skills training series for periodontal diagnosis and treatment, aims to provide guidance for the standardization of periodontal chart recording and application in the clinic and teaching, so as to promote the standardization of Chinese periodontal diagnosis and treatment and bring it on par with the international advanced level.

Objective:To investigate the detection of the age and pathway and the etiology of sensorineural hearing loss in children, and to guide the early diagnosis. Methods:A retrospective analysis was conducted on the children who passed neonatal hearing screening but were diagnosed with sensorineural hearing loss in our department from January 2019 to September 2022. The clinical characteristics of 66 children with complete medical history, audiology examination, imaging examination and genetic detection of hearing loss were studied. The age group, detection route and degree of hearing loss were analyzed statistically. Results:①The children were aged from 7 months to 12 years old, and most of them were over 3 years old. ②The ways of detection were as follows: 23 cases（34.85%） due to abnormal hearing, 21 cases（31.82%） due to poor language, 15 cases（22.73%） found during physical examination, and 7 cases（10.61%） found with otitis media. Physical examination findings were concentrated in children aged ≤1 year old or 3-6 years old. ③Among the 56 cases, the degree of binaural hearing loss ranged from mild to severe, and most of those within 3 years of age had severe or above hearing loss. There were statistically significant differences in the degree of hearing loss distribution among different detection approaches（P<0.001）. Most children with hearing or language problems had moderate to severe or above hearing loss, and the proportion was significantly higher than that of children detected during physical examination or otitis media. ④There were 21 cases（31.82%） with a pathogenic mutation of GJB2 gene and 9 cases（13.64%） of large vestibular aqueduct syndrome, 7 of which were related to SLC26A4 gene mutation. There were 8 cases（12.12%） with high risk factors of hearing loss. There was 1 case（1.52%） with progressive speech loss after severe infection and high fever and 1 case（1.52%） with unilateral cochlear nerve dysplasia. Conclusion:Delayed hearing loss can occur at all ages and was not easy to be detected in time. The etiology was related to the mutation of deafness-related genes and the high risk factors of hearing loss. Combining hearing and gene screening in childhood, guiding parents to observe children's hearing response and language development, especially strengthening the follow-up of children with high risk factors for hearing loss, is conducive to the early diagnosis of delayed hearing loss.
Humans ; Hearing Loss, Sensorineural/genetics* ; Retrospective Studies ; Child ; Child, Preschool ; Infant ; Connexin 26 ; Male ; Female ; Connexins/genetics* ; Mutation ; Sulfate Transporters ; Hearing Tests

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Early neurological deterioration(END)occurs in patients with acute cerebral infarction after recombinant tissue-plasminogen activator(rt-PA)intravenous thrombolysis,which seriously affects the prognosis of patients and even causes death.However,there is no effective treatment.This report describes two patients with acute ischemic stroke presenting with right-sided limb weakness within 4.5 hours of onset.Brain CT ruled out cerebral hemorrhage and both patients were diagnosed with acute ischemic stroke.END occurred within 24 hours after intravenous thrombolysis with rt-PA.Reexamine Brain CT showed no evidence of cerebral hemorrhage.The patients were treated with continuous tirofiban infusion for 48 hours,overlapping with oral antiplatelet therapy for 4 hours and 6 hours,respectively.After discontinuation of tirofiban,no further neurological deterioration was observed.At the 3-month follow-up,there was no recurrence,and the modified Rankin scale(mRS)scores were 1 and 3,respectively.This study delineates the diagnostic and therapeutic trajectories of two paradigmatic cases to inform clinical decision-making for analogous presentations,thereby contributing to evidence-based management strategies.

Generative artificial intelligence technologies, represented by large language models, are poised to impact educational ecosystems comprehensively. This article focuses on the nursing education field, first introducing the basic concepts and evolution of large language models. It then outlines typical applications of this technology in enabling innovative practices in nursing education, showcasing its immense potential in reshaping content generation methods, teaching models, educational settings, and evaluation systems. Additionally, the article analyzes key challenges that may arise, including inadequate professional construction, alienation in teacher-student relationships, over-reliance on digital tools, and unequal access to technology. By examining the frontier applications and potential risks of large language models in nursing education, this work aims to inspire ideas and provide references for the digital transformation of nursing education.