Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

OBJECTIVES: This study aimed to evaluate the therapeutic effect of 1% povidone-iodine mouthwash combined with scaling and root planing in patients with stage Ⅰ/Ⅱ class A/B periodontitis, and to provide a basis for the clinical application of povidone-iodine mouthwash. METHODS: Seventy-five subjects were included in this trial and randomly divided into three groups. After full-mouth ultrasonic supragingival cleansing, scaling and root planing, the placebo group was treated with sodium chloride injection (NaCl group), the control group was treated with compound chlorhexidine mouthwash (CHX group), and the experimental group was treated with 1% povidone-iodine mouthwash (PVP-I group), and rinsed their mouths for 1 week, respectively. Subjects were tested at 1, 4, and 12 weeks after dosing for clinical indicators, microbial composition of supragingival plaque, gingival crevicular fluid inflammatory marker levels, and patient-reported outcomes. RESULTS: Sixty-three subjects completed the follow-up. After treatment, the clinical indicators, microbial indicators, and inflammatory indicators were all significantly improved (P<0.05). Comparisons among the groups showed that one week after treatment, the bleeding index and plaque index of the CHX group and the PVP-I group were lower than those of the NaCl group, and the plaque index of the CHX group was lower than that of the PVP-I group (P<0.05). There were no statistically significant differences in the other clinical indicators among the groups (P>0.05). Twelve weeks after treatment, the Shannon index of the CHX group was lower than that of the NaCl group (P<0.05), and there were no statistically significant differences in the other microbial indicators among the groups (P>0.05). Twelve weeks after treatment, the interleukin-10 concentration of the CHX group was higher than that of the NaCl group (P<0.05), and there were no statistically significant differences in the other inflammatory indicators among the groups (P>0.05). The PVP-I group had the highest scores in terms of taste and oral odor. There was no obvious staining on the tooth surfaces and mucosa in all three groups. CONCLUSIONS 1% PVP-I mouthwash combined with scaling and root planing can effectively reduce gingival inflammation and dental plaque, improve clinical symptoms in the short term. While its efficacy is not significantly inferior to that of chlorhexidine, PVP-I mouthwash is more acceptable to patients than chlorhexidine.
Humans ; Povidone-Iodine/administration & dosage* ; Mouthwashes/therapeutic use* ; Dental Scaling ; Root Planing ; Periodontitis/microbiology* ; Gingival Crevicular Fluid/chemistry* ; Anti-Infective Agents, Local/therapeutic use* ; Female ; Male ; Chlorhexidine/therapeutic use* ; Dental Plaque/microbiology* ; Middle Aged ; Adult

OBJECTIVE To study the chemical composition and the function of solid excipients in relieving the "nourishing and spleen-impairing" effect of Zhangbang nine steaming nine sun-dying Rehmanniae Radix(RR) by using UPLC-Q-TOF-MS technique. METHODS UPLC-Q-TOF-MS was used to collect the data of Zhangbang nine steaming nine sun-dying RR, and UNIFI platform and self-built database were used for the rapid qualitative analysis and identification of the chemical components of Zhangbang nine steaming nine sun-dying RR. The effect of solid excipients on the function of RR "nourishing and spleen-impairing" was investigated by establishing a mouse model of low gastric motility and measuring its gastric residual rate and small intestine propulsion rate. RESULTS The UPLC-Q-TOF-MS and UNFI platforms identified 76 chemical components in nine steaming nine sun-dying RR, including 9 iridoid glycosides, 11 phenylethyl glycosides, 31 flavonoids, 6 saccharides and 19 other compounds; the results of gastric emptying and small intestinal propulsion experiments on mice showed that Zhangbang nine steaming nine sun-dying RR had gastric emptying and intestinal propulsion effects. CONCLUSION This method can be used for the rapid identification and analysis of nine steaming nine sun-dying RR, which has solid excipients Citri Reticulatae Pericarpium and Amomi Fructus to alleviate the "nourishing and spleen-impairing" function of RR. This study can provide a reference for quality control and elucidation of the material basis of the medicinal effects of specialty beverage of Zhangbang nine steaming nine sun-dying RR.

Objective This study aimed to investigate the temporal and spatial changes in the expression of perios-tin during periodontal inflammation in mice.Methods A periodontitis model was constructed using silk thread ligation.Mice were randomly divided into five groups in-cluding control group,4-day ligation group,7-day liga-tion group,14-day ligation group,and self-healing group(thread removal for 14 days after 14-day ligation).Mi-cro-CT and histological staining were performed to char-acterize the dynamic changes in the mouse periodontal tissue in each group.RNAscope and immunohistochemical staining were used to analyze the pattern of changes in peri-ostin at various stages of periodontitis.The cell experiment was divided into three groups:control group,lipopolysac-charide(LPS)stimulation group(treated with LPS for 12 h),and LPS stimulation removal group(treated with LPS for 3 h followed by incubation with medium for 9 h).Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression of periostin,transforming growth factor-β1(TGF-β1),and matrix metalloproteinase 2(MMP2).Results Significant alveolar bone resorption was observed 7 days after ligation.With increasing duration of ligation,the damage to the mouse periodontal tissue was aggravated,which manifested as increased osteoclasts,widen-ing of the periodontal membrane space,and decreased alveolar bone height.Some degree of periodontal tissue repair was observed in the self-healing group.Periostin expression decreased at 4 and 7 days compared with the control group and increased at 14 days compared with 4 and 7 days.A significant recovery was found in the self-healing group.The qRT-PCR results showed that the expression of periostin and TGF-β1 in the LPS stimulation group decreased compared with that in the control group but significantly recovered in the LPS removal group.Conclusion Periostin expression in the PDL of mice showed a downward and upward trend with inflammation progression.The significant recovery of periostin expression after removing inflammatory stimuli may be related to TGF-β1,which is crucial to maintain the in-tegrity of the PDL.

Objective:To explore the current status of rumination in inpatients with metastatic prostate cancer (mPCa) under the disease coping mechanism, and analyzing its influencing factors.Methods:From March 2021 to December 2022, 267 mPCa inpatients at the Tenth People's Hospital of Tongji University were selected as the study subject using convenience sampling. The survey was conducted using the General Information Questionnaire, Chinese Version of Event Relate Rumination Inventory (C-ERI), Medical Coping Modes Questionnaire (MCMQ), International Prostate Symptom Score (IPSS), and Social Support Revalued Scale (SSRS), and the factors influencing the rumination in patients were analyzed.Results:This study collected 260 valid questionnaires, with an effective response rate of 97.4% (260/267). The total score of rumination in 260 mPCa patients was (31.08±6.46), with invasive rumination and purposeful rumination scores of (14.13±4.44) and (16.95±4.55), respectively. The initial prostate-specific antigen index, confrontation medical coping modes were the influencing factors of invasive rumination in mPCa patients ( P<0.05). The initial prostate-specific antigen index, course of disease, social support, and confrontation medical coping style were the influencing factors of purposeful rumination in mPCa patients ( P<0.05) . Conclusions:The rumination of mPCa patients is above the medium level, and is influenced by multiple factors under the disease coping mechanism. Clinical medical and nursing staff should combine the clinical situation and characteristics of mPCa patients, provide personalized interventions as early as possible, and assist patients in improving their positive cognitive processing abilities.

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.
Humans ; COVID-19 ; Sleep Initiation and Maintenance Disorders ; Crisis Intervention ; Psychosocial Intervention ; SARS-CoV-2 ; Mental Health ; Depression/epidemiology* ; Health Personnel/psychology* ; Anxiety/etiology*

Objective:To compare the efficacy of endoscopic submucosal dissection (ESD) and surgery for circumferential superficial esophageal squamous cell neoplasm.Methods:A retrospective analysis was performed on 153 patients with superficial esophageal squamous cell neoplasm who underwent ESD or surgery at Cancer Hospital, Chinese Academy of Medical Sciences from November 2013 to October 2021. There were 116 cases in ESD group and 37 cases in the surgical group. The en block resection rate, complete resection rate, operation time, perioperative complication incidence, postoperative quality of life, postoperative disease-free survival and overall survival were compared.Results:In the ESD group, the en block resection rate was 100.0% (116/116) and the complete resection rate was 96.6% (112/116). The longitudinal diameter of lesion had no significant correlation with complications or complete resection rate ( P>0.05). The operation time of the ESD group was significantly shorter than that of the surgical group (175.1±52.2 min VS 266.7±88.2 min, t=-5.991, P<0.001). There was no significant difference in the incidence of perioperative complications between the ESD group and surgical group [5.2% (6/116) VS 8.1% (3/37), P=0.452]. According to EORTC-QLQ-C30 and EORTC-QLQ-OES18, emotional function ( P=0.008),cognitive function ( P=0.013) and the total health level ( P<0.001) of the ESD group were significantly higher than those in the surgical group. Fatigue ( P=0.002), pain ( P<0.001), dyspnea ( P<0.001), insomnia ( P<0.001), anorexia ( P<0.001), diarrhea ( P<0.001) and reflux ( P<0.001) in the surgical group were significantly higher than those in ESD group. There was no significant difference in disease-free survival or overall survival between the two groups ( P>0.05). Polyglycolic acid combined with autologous esophageal mucosal transplantation combined with temporary esophageal stent implantation could reduce the rate of esophageal scar stenosis after ESD [53.3% (24/45) VS 100.0% (55/55), P<0.001] and significantly reduce the number of postoperative dilation [1.00 (0.00, 5.00) VS 9.00 (5.00, 14.00), P<0.001] compared with balloon dilation alone. Conclusion:ESD is superior to traditional surgery for the treatment of circumferential superficial esophageal squamous cell neoplasm because of high operational safety, shorter operation time, less trauma, better postoperative life quality. Postoperative esophageal stenosis can still be well cured after endoscopic treatment. Therefore, ESD can be used as the first choice for the treatment of circumferential superficial esophageal squamous cell neoplasm.

In the process of animal fat deposition, the proliferation and differentiation of pre-adipocytes and the change of lipid droplet content in adipocytes are regulated by a series of transcription factors and signal pathways. Although researchers have conducted in-depth studies on the transcriptional regulation mechanisms of adipogenesis, there are relatively few reports on post-transcriptional modification on mRNA levels. The modification of mRNA m⁶A regulated by methyltransferase, demethylase and methylation reading protein is a dynamic and reversible process, which is closely related to fat deposition in animals. Fat mass and obesity associated proteins (FTO) act as RNA demethylases that affect the expression of modified genes and play a key role in fat deposition. This article summarized the mechanism of FTO-mediated demethylation of mRNA m⁶A in the process of animal fat deposition, suggesting that FTO may become a target for effective treatment of obesity. Moreover, this review summarized the development of FTO inhibitors in recent years.
Adipocytes ; Adipogenesis/genetics* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Animals ; Obesity/genetics* ; RNA, Messenger/genetics*

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.