AIM:To investigate the inhibitory effect of apolipoprotein A-I mimetic peptide D-4F on the scaven-ger receptor A1 ( SR-A1 ) in macrophage-derived foam cells induced by oxidized low-density lipoprotein ( ox-LDL ) . METHODS:RAW264.7 cells were pretreated with different concentrations (12.5, 25 and 50 mg/L) of D-4F or 50 mg/L inactive control peptide scrambled D-4F (sD-4F) for 1 h or endoplasmic reticulum stress (ERS) inhibitor 4-phenylbutyr-ic acid (5 mmol/L) for 30 min, followed by the treatment with 100 mg/L ox-LDL for 12 h.In addition, the cells were pre-treated with 50 mg/L D-4F or sD-4F for 1 h, and then stimulated with 2 mg/L tunicamycin (TM;an ERS inducer), for 4 h.The viability of the cells was measured by MTT assay, and the content of intracellular total cholesterol ( TC) was meas-ured by a tissue/cell TC assay.The protein and mRNA levels of SR-A1 and glucose-regulated protein 78 (GRP78) were analyzed by Western blotting and quantitative real-time PCR, respectively.The fluorescence intensity of DiI-ox-LDL in the cells was detected by a multifunctional microplate reader.RESULTS:D-4F significantly reduced ox-LDL-induced macro-phage injury and intracellular cholesterol accumulation, and attenuated the ox-LDL-induced expression of SRA1 and GRP78 in a dose-dependent manner.Additionally, D-4F significantly inhibited the TM-induced protein expression of SR-A1 and GRP78, and attenuated the uptake of ox-LDL by macrophages.CONCLUSION: D-4F reduces ox-LDL-induced macro-phage cholesterol accumulation and injury by inhibiting SR-A1 expression.The mechanism may be related to the inhibition of ERS signaling pathway mediated by GRP78.

Objective:To investigate the clinical effect of different surgical methods in the treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ).Methods:A total of 20 cases of BRONJ who were treated for surgical treatment from January 2013 to March 2019 were included for the retrospective analysis in this study. There were 14 males and 6 females in this study. The average age of onset was 65.4 years, including 67.4 years for males and 60.7 years for females. There were 9 patients in stage 1, 7 in stage 2, 3 in stage 3, and 1 patient with maxillary lesions in stage 2 and mandibular lesions in stage 3. For patients in stage 1 or stage 2 who had poor systemic conditions and could not tolerate general anesthesia or surgical trauma. Different surgical treatments should be performed according to the results of imaging evaluation. If completely dead bones were formed locally, sequestrectomy under local anesthesia was performed. For patients whose dead bones were not completely separated, partial jaw resection was performed. For stage 3 BRONJ patients with severe symptoms occurring in the mandible, such as the formation of intraoral and external fistulas, pathological fractures, or lesions involving the lower margin of the mandible, segmental osteotomy was usually performed when general conditions were stable.Results:Of the 20 patients, 6 cases (including 1 patient with lesions involving both maxilla and mandible) underwent sequestrectomy, 11 cases partial jaw resection and 4(including 1 patient with lesions involving both maxilla and mandible) mandibular segmental osteotomy. The patients were followed up for 1-67 months (mean 32.8 months). All the patients who underwent mandibular segmental osteotomy were recovered well and discharged. 6 patients were clinically asymptomatic after partial jawbone resection. The symptoms of the rest of the patients were alleviated, showing relieved pain, disappeared dead bone and so on, while the course of disease was significantly slowed down.Conclusions:Sequestrectomy and partial jaw resection can relieve symptoms and improve quality of life of patients, so that some patients can achieve clinical cure. Mandibular segmental osteotomy as a more effective treatment method, can be considered as the preferred treatment for stage 3 patients with lesions in the mandible and with good systemic condition.

Objective:To explore the methods and clinical effects of the surgery for treating maxillary medication-related osteonecrosis of the jaw (MRONJ).Methods:The clinical data including gender, age, stage of lesion, treatment method and prognosis of 28 patients with maxillary MRONJ who underwent surgical treatment in the Department of Oral and Maxillofacial Surgery of Medical School of Nanjing University from January 2013 to October 2020 were retrospectively analyzed. There were 20 males and 8 females. The mean age at onset was (65.6±11.1) years old. According to the guidelines of American Association of Oral and Maxillofacial Surgeons, the patients′ lesions were divided into 2 or 3 stages. Ten cases of stage 2 lesions were tightly sutured after partial jaw resection. Among them, 4 lesions were sutured directly with mucoperiosteal flaps, 4 lesions were covered by adjacent flaps and 2 lesions was covered by buccal fat pad flaps and adjacent flaps. Eighteen cases of stage 3 lesions were treated with sequestrectomy and drainage channels were formed. Patients were followed up regularly after the surgery, and the effect of surgical treatment was judged according to the clinical criteria such as clinical manifestations, local oral examination, imaging examination etc.Results:After follow-up for 12 to 52 months, the postoperative pain score (1.20±2.53) was significantly lower than preoperative pain score (6.70±0.95) ( P<0.05) in stage 2 patients. Eight patients′ mucosa healed completely without new dead bone formed. Two patients had recurrence and developed to stage 3 at the time of revisit. There were 18 cases of stage 3 lesions, which formed drainage channels after removal of the dead bone. The postoperative follow-up time was 2 to 67 months, and the symptoms of inflammation and infection disappeared. Postoperative pain score (3.40±0.51) was significantly lower than preoperative pain score (7.06±1.00) ( P<0.05). Conclusions:Soft tissue flap closure of wound after partial maxillectomy is an effective approach for the treatment of maxillary MRONJ stage 2 lesions, while maxillary stage 3 lesions could be treated for eliminating clinical symptoms and improving the quality of life when establishing unobstructed drainage after dead bone extraction.

Objective:To investigate the clinical effect of different surgical methods in the treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ).Methods:A total of 20 cases of BRONJ who were treated for surgical treatment from January 2013 to March 2019 were included for the retrospective analysis in this study. There were 14 males and 6 females in this study. The average age of onset was 65.4 years, including 67.4 years for males and 60.7 years for females. There were 9 patients in stage 1, 7 in stage 2, 3 in stage 3, and 1 patient with maxillary lesions in stage 2 and mandibular lesions in stage 3. For patients in stage 1 or stage 2 who had poor systemic conditions and could not tolerate general anesthesia or surgical trauma. Different surgical treatments should be performed according to the results of imaging evaluation. If completely dead bones were formed locally, sequestrectomy under local anesthesia was performed. For patients whose dead bones were not completely separated, partial jaw resection was performed. For stage 3 BRONJ patients with severe symptoms occurring in the mandible, such as the formation of intraoral and external fistulas, pathological fractures, or lesions involving the lower margin of the mandible, segmental osteotomy was usually performed when general conditions were stable.Results:Of the 20 patients, 6 cases (including 1 patient with lesions involving both maxilla and mandible) underwent sequestrectomy, 11 cases partial jaw resection and 4(including 1 patient with lesions involving both maxilla and mandible) mandibular segmental osteotomy. The patients were followed up for 1-67 months (mean 32.8 months). All the patients who underwent mandibular segmental osteotomy were recovered well and discharged. 6 patients were clinically asymptomatic after partial jawbone resection. The symptoms of the rest of the patients were alleviated, showing relieved pain, disappeared dead bone and so on, while the course of disease was significantly slowed down.Conclusions:Sequestrectomy and partial jaw resection can relieve symptoms and improve quality of life of patients, so that some patients can achieve clinical cure. Mandibular segmental osteotomy as a more effective treatment method, can be considered as the preferred treatment for stage 3 patients with lesions in the mandible and with good systemic condition.

Objective To establish an artificial intelligence(AI)diagnostic model for the histopathologic diagnosis of extramammary Paget's disease(EMPD)and to evaluate its efficiency for the diagnosis and differential diagnosis of EMPD.Methods All non-tumor skin disease patients who underwent skin tissue biopsy in Department of Dermatology of First Affiliated Hospital of Army Medical University from September 2003 to February 2023 were recruited,and their pathological data were collected,including EMPD,Bowen's disease(BD),squamous cell carcinoma(SCC),and epidermal hyperplasia and hypertrophy.With EMPD as the main research subject,the histopathological images of BD,SCC,and non-tumor skin diseases were included in the study.The histopathological data of 4 types of diseases was classified and diagnosed by ResNet101 and DenseNet121 deep learning neural networks,and the performance of these models was evaluated.Results The AUC values of the ResNet101 diagnostic model for the diagnosis of EMPD,BD,SCC and non-tumor skin diseases on the images at x20 magnification were 0.97,0.98,1.00 and 0.96,respectively,with an accuracy of 0.925±0.011,while the AUC values on the images at x40 magnification were 1.00,0.99,1.00 and 0.97,respectively,with an accuracy of 0.943±0.017.The AUC values of the DenseNet121 diagnostic model for the diagnosis of 4 diseases on the images at x20 magnification were 0.98,0.95,0.99 and 1.00,respectively,with an accuracy of 0.912±0.034,while the AUC values on the images at x40 magnification were 0.99,0.96,1.00 and 1.00,respectively,with an accuracy of 0.971±0.012.Our results indicated that the histopathologic diagnostic model could effectively differentiate EMPD from BD,SCC and non-tumor skin diseases at low power magnification.The FLPOs of ResNet101 was 786.6 M,and the parameter was 4.5 M;The FLPOs of DensNet121 was 289.7 M,and the parameter was 0.8M.Conclusion Our AI diagnostic model is of good effectiveness in the diagnosis and differential diagnosis of EMPD.DenseNet121 is recommended as the dermatopathological diagnostic model of this study.

Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the "read-on-ski" law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1 μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95% accuracy. The results obtained by the automated "read-on-ski" imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.
Humans ; Kidney ; Organoids ; Pluripotent Stem Cells