Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

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.

OBJECTIVES: This retrospective study aimed to investigate factors influencing positional changes of the condyle and temporomandibular joint (TMJ) following mandibular defect reconstruction with bone flaps, and to evaluate the biomechanical impacts of flap reconstruction on condylar positioning, thereby providing evidence for optimizing surgical protocols and TMJ functional rehabilitation. METHODS: A retrospective study was conducted on 90 patients undergoing mandibular segmental resection with immediate bone flap reconstruction at Guizhou Medical University Affiliated Stomatological Hospital (June 2019 to May 2024). After strict screening, 50 cases with complete data were analyzed. Clinical parameters (defect size, location, reconstruction method) and craniofacial CT scans at four timepoints [preoperative (T0), 7-10 days (T1), 3 months (T2), and 6 months (T3) postoperatively] were collected. Mimics 20 software facilitated 3D reconstruction for measuring TMJ anterior/posterior/superior joint spaces (Kamelchuk method) and calculating condylar position via the Pullinger index [Ln (posterior/anterior space)]. Vitral and Krisjane methods quantified mandibular linear parameters (ramus length, condylar pole distances to the sagittal plane, angulation) and glenoid fossa morphology. Statistical analyses were performed using SPSS 21.0. RESULTS: Mandibular defect size and location were significant factors influencing postoperative condylar position changes (P<0.05). Compared to preoperative measurements, postoperative condylar anterior, posterior, and superior joint spaces were significantly increased (P<0.001). The most pronounced anterior condylar displacement occurred within 7-10 days postoperatively (P<0.05). In patients with condyle resection, postoperative joint space and angle changes were significant; in patients with condyle preservation, only superior and anterior joint space changes were statistically significant (P<0.05). Additionally, from T1 to T2, the changes in condylar medial-lateral distance, superior joint space, and anterior joint space were negatively correlated with the preoperative condylar position. Compared with preoperative,in the T0-T1 period, condylar medial-lateral distance, posterior joint space, and articular tubercle angle changes were significantly negatively correlated with time (P<0.05). Notably, the angle between the condylar long axis and the coronal axis showed a sustained negative trend from T1 to T3 (P<0.05). CONCLUSIONS Condylar position changes after mandibular defect repair with bone flap reconstruction are associated with the size and location of the defect. Additionally, adaptive remodeling of the temporomandibular joint (TMJ) joint space occurs postoperatively. The phenomenon of anterior displacement of the condyle in the early postoperative period (7-10 days) shows a trend of reduction with prolonged follow-up time, and further sample size research is needed.
Humans ; Retrospective Studies ; Temporomandibular Joint/surgery* ; Mandibular Condyle/surgery* ; Male ; Female ; Adult ; Middle Aged ; Mandibular Reconstruction/methods* ; Mandible/surgery* ; Surgical Flaps ; Tomography, X-Ray Computed ; Young Adult ; Biomechanical Phenomena ; Aged ; Adolescent ; Imaging, Three-Dimensional

Objective:To establish an ultrasound radiomics model by integrating clinical, pathological, and conventional ultrasound features with radiomics characteristics, and to explore its clinical value in predicting endocrine resistance in hormone receptor(HR)-positive breast cancer.Methods:A retrospective analysis was performed on 478 patients with HR-positive breast cancer from January 2017 to December 2021 in the Second Affiliated Hospital of Harbin Medical University, of which 430 were resistant and 48 were sensitive. The clinical, pathological and immunohistochemical data and ultrasound images were collected.Firstly, the propensity score was used to process and match the data. Secondly, Logistic regression was used to screen clinical, pathological, and conventional ultrasound features associated with endocrine resistance. Then, PyRadiomics was used to extract the radiomic features of grayscale ultrasound images, and a series of methods such as Lasso regression were used to screen the radiomic features related to endocrine resistance. Seven machine learning methods such as random forest were used to build a radiomics model. Finally, clinical, pathological and ultrasound features were added to establish a clinical pathological model, a clinical pathological ultrasound model, a clinical pathological radiomics model and a combined model of the four features, and the model effectiveness was evaluated.Results:①Propensity score matching: 96 patients were matched, including 48 patients in the drug-resistant group and 48 patients in the sensitive group. ②Screening clinical pathological conventional ultrasound features related to endocrine resistance: lymph node metastasis, tumor diameter, posterior echo attenuation, and growth orientation were independent predictors of endocrine resistance (all P<0.05). ③Screening radiomics features related to endocrine resistance: 18 features such as Dependence Entropy. ④Establishing radiomics model: the machine learning model of random forest method (AUC=0.80) performed best. ⑤Radiomics model integrating clinical, pathological and conventional ultrasound features: the AUC of the clinical pathological model was 0.70, the AUC of the clinical pathological ultrasound model was 0.78, the AUC of the clinical pathological radiomics model was 0.82, and the AUC of the combined model was 0.86. Conclusions:The radiomics model established by the random forest method performs best in predicting endocrine resistance in HR-positive breast cancer. The model that integrates multiple features performs best in assessing endocrine resistance.which is expected to provide an objective basis for clinicians to predict endocrine resistance in HR-positive breast cancer.

Periodontal ligament stem cells(PDLSCs)have the potential for multidirectional differentiation and are the preferred seed cells for periodontal tissue regeneration.In recent years,a large number of studies have confirmed that PDLSCs also possess broad immunomodulatory properties.Therefore,in-depth exploration of their specific molecular mechanisms is of great significance for the treatment of periodontitis.The aim of this paper is to summarize the research progress on the regulation of PDLSCs on various immune cells and the effect of the inflammatory environment on the im-mune characteristics of PDLSCs to provide an important theoretical basis for the allotransplantation of PDLSCs and im-prove the therapeutic effect of periodontal tissue regeneration.Studies have shown that PDLSCs possess a certain degree of immunosuppressive effect on both innate and acquired immune cells,and inflammatory stimulation may lead to the im-pairment of the immunoregulatory properties of PDLSCs.However,current studies are mainly limited to in vitro cell tests and lack in-depth studies on the immunomodulatory effects of PDLSCs in vivo.In vivo studies based on cell lineage trac-ing and conditional gene knockout technology may become the main directions for future research.

Objective To investigate the predictive value of serum neuron-specific enolase (NSE), prognostic nutritional index (PNI) score, hepatic encephalopathy (HE) grading, and the integrated model for end-stage liver disease (iMELD) score in assessing the short-term (90-day) prognosis of patients with cirrhosis complicated by overt hepatic encephalopathy (HE). Methods A retrospective analysis was conducted on clinical data from 470 patients with cirrhosis and overt HE, and they were divided into survival group (n=359) and mortality group (n=111) based on their survival status 90 days after admission. The PNI and iMELD scores were calculated using patient demographics, blood routine tests, coagulation function, liver and renal function electrolyte levels, and serum NSE levels within 24 hours of admission, along with HE grading. Receiver operating characteristic (ROC) curves, multivariate Logistic regression analysis, and Kaplan-Meier survival curves were employed to evaluate influencing factors of short-term prognosis of patients with cirrhosis and overt HE. Results The mortality group exhibited significantly higher serum NSE levels, HE grades, and iMELD scores, while demonstrated lower PNI score compared to the survival group (P < 0.05). Multivariate Logistic regression analysis identified serum NSE, PNI score, HE grade, and iMELD score as independent predictors of short-term prognosis. The areas under the curve (AUCs) for serum NSE, PNI score, HE grade, and iMELD score in predicting short-term prognosis were 0.727, 0.717, 0.721, and 0.728, respectively, with cut-off values of 12.23 ng/mL, 34.05 ng/mL, and 39.26 points for serum NSE, PNI score, and iMELD score. A combined prediction model of four factors demonstrated the highest predictive performance, with an AUC of 0.919 and a cut-off value of 0.23. Kaplan-Meier survival analysis revealed that patients with combined score of serum NSE, PNI score, HE grade, and iMELD cut-off value < 0.23 had a significantly higher 90-day survival rate compared to those with cut-off value≥0.23 (Log-Rank=265.567, P < 0.001). Conclusion Serum NSE, PNI score, HE grade, and iMELD score exhibit good value in predicting the short-term prognosis of patients with cirrhosis and overt HE, with an even higher predictive value when used in combination.

Objective:To explore the effect of double-eyelid blepharoplasty by continuously double W-shape buried suture method through skin and conjunctiva.Methods:The data of patients received double-eyelid blepharoplasty by continuously double W-shape buried suture method through skin and conjunctiva in Department of Medical Aesthetic Surgery, People’s Hospital of Rizhao, and Department of Plastic Surgery, Yimeitiancheng’s Cosmetic and Plastic Hospital of Rizhao from January 2021 to June 2022 were retrospectively analyzed. Before the operation, the double eyelid line was designed and 5 points were evenly marked along the line as A, B, C, D and E (from the lateral to the internal). During the operation, 10 ml needle was used to puncture the 5 points marked on the double eyelid line. Starting from the outermost point A, the needle was inserted obliquely inward on the skin surface, and then the upper eyelid was turned over, and the stitches was stabed-out from the conjunctival surface of the upper margin of tarsus. The stitches was inserted again from the original point pierced on the conjunctival surface, and the stitches was stabed-out diagonally inward through the skin surface at the point B. The same method was used to penetrate points C, D and E successively. Then E, D, C, B and A points were penetrated in turn from the inside to the outside. The two suture ends were passed through the 3/8 arc round stitches, which was inserted from the point A and stabed-out skin surface of the outer orbital margin above the double eyelid line through the deep. The tightness was adjusted and tied the knotted. After the surgery, the surgical results and complications were observed, and patients’ satisfaction was evaluated before and 6 months after the surgery, which included four factors: eyelid curvature, width, smoothness, and symmetry, with a maximum score of 100. Higher scores indicated greater patients’ satisfaction. Measurement data were expressed as Mean±SD, and paired sample t-test was used to compare the satisfaction of the same patient before and after surgery. P<0.05 indicated statistically significant difference. Results:A total of 82 patients with 160 eyes were included, including 75 females and 7 males. The age ranged from 18 to 32 years old, with a mean of 25.4 years old. 78 cases were treated with both eyes and 4 with one eye. In the early postoperative period, 8 patients had local cyanosis and slight swelling of eyelid, which was improved after routine cold compress treatment. Two cases reported a foreign body sensation in the eyeball, which improved with application of levofloxacin for 1 week. The remaining patients had good eyelid morphology with no significant swelling or foreign body sensation. A total of 60 patients were followed up for 6 months, and their eyelid morphology appeared natural and aesthetically pleasing. The eyelid crease was smooth when opened, and there were no obvious surgical scars when closed. Only one patient had a shallow eyelid crease, which was satisfactorily repaired with additional suturing. None of the patients experienced external suture exposure or subcutaneous nodules. The patient satisfaction score was (58.15±5.07) before operation and (98.68±1.69) 6 months after operation, the difference was statistically significant ( t=-70.33, P<0.001). Conclusion:Double-eyelid blepharoplasty by continuously double W-shape buried suture method through skin and conjunctiva has the advantages of minimally invasion, simple performence, direct vision operation, with natural appearance of double eyelid, and high patient satisfaction.

Objective:To explore the effect of double-eyelid blepharoplasty by continuously double W-shape buried suture method through skin and conjunctiva.Methods:The data of patients received double-eyelid blepharoplasty by continuously double W-shape buried suture method through skin and conjunctiva in Department of Medical Aesthetic Surgery, People’s Hospital of Rizhao, and Department of Plastic Surgery, Yimeitiancheng’s Cosmetic and Plastic Hospital of Rizhao from January 2021 to June 2022 were retrospectively analyzed. Before the operation, the double eyelid line was designed and 5 points were evenly marked along the line as A, B, C, D and E (from the lateral to the internal). During the operation, 10 ml needle was used to puncture the 5 points marked on the double eyelid line. Starting from the outermost point A, the needle was inserted obliquely inward on the skin surface, and then the upper eyelid was turned over, and the stitches was stabed-out from the conjunctival surface of the upper margin of tarsus. The stitches was inserted again from the original point pierced on the conjunctival surface, and the stitches was stabed-out diagonally inward through the skin surface at the point B. The same method was used to penetrate points C, D and E successively. Then E, D, C, B and A points were penetrated in turn from the inside to the outside. The two suture ends were passed through the 3/8 arc round stitches, which was inserted from the point A and stabed-out skin surface of the outer orbital margin above the double eyelid line through the deep. The tightness was adjusted and tied the knotted. After the surgery, the surgical results and complications were observed, and patients’ satisfaction was evaluated before and 6 months after the surgery, which included four factors: eyelid curvature, width, smoothness, and symmetry, with a maximum score of 100. Higher scores indicated greater patients’ satisfaction. Measurement data were expressed as Mean±SD, and paired sample t-test was used to compare the satisfaction of the same patient before and after surgery. P<0.05 indicated statistically significant difference. Results:A total of 82 patients with 160 eyes were included, including 75 females and 7 males. The age ranged from 18 to 32 years old, with a mean of 25.4 years old. 78 cases were treated with both eyes and 4 with one eye. In the early postoperative period, 8 patients had local cyanosis and slight swelling of eyelid, which was improved after routine cold compress treatment. Two cases reported a foreign body sensation in the eyeball, which improved with application of levofloxacin for 1 week. The remaining patients had good eyelid morphology with no significant swelling or foreign body sensation. A total of 60 patients were followed up for 6 months, and their eyelid morphology appeared natural and aesthetically pleasing. The eyelid crease was smooth when opened, and there were no obvious surgical scars when closed. Only one patient had a shallow eyelid crease, which was satisfactorily repaired with additional suturing. None of the patients experienced external suture exposure or subcutaneous nodules. The patient satisfaction score was (58.15±5.07) before operation and (98.68±1.69) 6 months after operation, the difference was statistically significant ( t=-70.33, P<0.001). Conclusion:Double-eyelid blepharoplasty by continuously double W-shape buried suture method through skin and conjunctiva has the advantages of minimally invasion, simple performence, direct vision operation, with natural appearance of double eyelid, and high patient satisfaction.

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 investigate the role of microRNA-218 (miR-218) in regulating prostate cancer (PCa) cell stemness and epithelial-mesenchymal transition (EMT). 【Methods】 PCa cell line stably overexpressing miR-218 was constructed with lentivirus transfection. The expression of miR-218 was detected with real-time fluorescence quantitative polymerase chain reaction (q-PCR). The migration ability was detected with Transwell assay. The expression of EMT related proteins were detected with Western blot. The properties of cells were determined with colony formation and tumor sphere formation assays. 【Results】 The results of q-PCR showed that the mRNA level of miR-218 was significantly lower in PCa cell lines LNCaP and C4-2 than in BPH-1. Transwell assay showed that miR-218 inhibited the migration of PCa cells. Western blot showed that the expression of EMT related proteins were inhibited by miR-218. Colony formation and tumor sphere formation assays showed that overexpression of miR-218 significantly inhibited the properties of cells. 【Conclusion】 The expression of miR-218 is downregulated in PCa cell lines. miR-28 can inhibit cell migration, EMT and cancer stem cell properties.