In the field of dental aesthetics,digital aesthetic design plays a crucial role in helping dentists to predict treatment outcomes vis-ually,as well as in enhancing the consistency of knowledge and understanding of aesthetic goals between dentists and patients.It serves as the foundation for achieving ideal aesthetic effects.However,there is no clear standard for this digital process currently in China and abroad.Many dentists lack of systematic understanding of how to carry out digital aesthetic design for treatment.To establish standardized processes for dental aesthetic design and to improve the homogeneity of treatment outcomes,Chinese Society of Digital Dental Industry(CSD-DI)convened domestic experts in related field to compile this consensus.This article elaborates on the key aspects of digital aesthetic data collection,integration steps,and the digital aesthetic design process.It also formulates a decision tree for dental aesthetics at macro level and outlines corresponding workflows for various clinical scenarios,serving as a reference for clinicians.

Alanine-serine-cysteine transporter 2 (ASCT2) is reported to participate in the progression of tumors and metabolic diseases. It is also considered to play a crucial role in the glutamate-glutamine shuttle of neuroglial network. However, it remains unclear the involvement of ASCT2 in neurological diseases such as Parkinson's disease (PD). In this study, we demonstrated that high expression of ASCT2 in the plasma samples of PD patients and the midbrain of MPTP mouse models is positively correlated with dyskinesia. We further illustrated that ASCT2 expressed in astrocytes rather than neurons significantly upregulated in response to either MPP⁺ or LPS/ATP challenge. Genetic ablation of astrocytic ASCT2 alleviated the neuroinflammation and rescued dopaminergic (DA) neuron damage in PD models in vitro and in vivo. Notably, the binding of ASCT2 to NLRP3 aggravates astrocytic inflammasome-triggered neuroinflammation. Then a panel of 2513 FDA-approved drugs were performed via virtual molecular screening based on the target ASCT2 and we succeed in getting the drug talniflumate. It is validated talniflumate impedes astrocytic inflammation and prevents degeneration of DA neurons in PD models. Collectively, these findings reveal the role of astrocytic ASCT2 in the pathogenesis of PD, broaden the therapeutic strategy and provide a promising candidate drug for PD treatment.

Objective To investigate the effect of SMAD family member 3(SMAD3) silenced by small interfering RNA (siRNA) on macrophage polarization and transforming growth factor β1 (TGF-β1)/ SMAD family signaling pathway in rheumatoid arthritis (RA). Methods RA macrophages co-cultured with rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were used as a cell model. TGF-β1 was used to stimulate macrophages, and SMAD3-specific siRNA (si-SMAD3) and negative control siRNA (si-NC) were transfected into human RA macrophages co-cultured in Transwell^TM chamber. The expression of SMAD3 mRNA was detected by real-time fluorescence quantitative PCR, and the expression of TGF-β1, SMAD3 and SMAD7 protein was detected by Western blot analysis. The contents of TGF-β1 and IL-23 in cell culture supernatant were determined by ELISA. Cell proliferation was detected by CCK-8 assay. Transwell^TM chamber was used to measure cell migration. Results Compared with the model group and the si-NC group, the expression of TGF-β1, SMAD3 mRNA and protein in RA macrophages decreased significantly after silencing SMAD3. In addition, the secretion of IL-23 decreased significantly, and the cell proliferation activity and cell migration were inhibited, with high expression of SMAD7. Conclusion Knockdown of SMAD3 can promote M2 polarization and SMAD7 expression in RA macrophages.
Humans ; Arthritis, Rheumatoid/genetics* ; Interleukin-23 ; Macrophages ; RNA, Messenger ; RNA, Small Interfering/genetics* ; Smad7 Protein/genetics* ; Transforming Growth Factor beta1/genetics* ; Smad3 Protein/genetics* ; Gene Silencing

Objective:This study is to understand the hot spots and trends in the recruitment of clinical trial subjects in China over the past 20 years, explore the existing problems and countermeasures, and provide scientific ideas for domestic clinical trial institutions to effectively solve the problem of subject recruitment.Methods:Bibliometric analysis was used to study the relevant literature from three major domestic databases from 2001 to 2021, analyzing key indicators such as annual publication volume, journal distribution, institutional distribution, regional distribution, and high-frequency keyword co-occurrence.Results:A total of 162 articles were selected. The results showed that the overall publication volume in this field showed an upward trend, and the research institutions were diversified, with a concentration of medical and pharmaceutical institutions and universities. The current research hotspots in this field focused on quality and efficiency improvement of subject recruitment, with themes of subject protection, ethical review, regulation development, standardized management, etc.Conclusions:The research in this field has made significant progress, but the overall research level is still relatively weak. Therefore, it is suggested that the country should play a role in macro-regulation, on the one hand, starting with top-level design, promoting the construction of a standardized management system for subject recruitment, continuously strengthening subject protection, and enhancing the effectiveness of scientific recruitment. On the other hand, releasing the potential of grassroots institutions and giving full play to the volume advantage by promoting the sinking of advantageous resources. Meanwhile, great importance should be attached to the development of Phase I clinical trials, giving full play to the strong internal energy of traditional medicine and promoting the development of Chinese traditional medicine. These multi-measures should provide a theoretical basis for exploring the transformation of ′clinical research hospitals′, and promote the high-quality development of new drug research and development in China.

Objective:To investigate the effect of subfibular ossicle excision on the clinical efficacy of Brostr?m procedure for chronic lateral ankle instability (CLAI).Methods:From March 2014 to December 2018, 76 patients were treated by the modified Brostr?m procedure using the suture anchor technique for CLAI at Department of Foot & Ankle Surgery, Wuhan Fourth Hospital. Of them, 33 had subfibular ossicles (SFO group) and 43 did not (NSFO group). In the SFO group, there were 19 males and 14 females, aged (28.4±8.6) years; in the NSFO group, there were 21 males and 22 females, aged (27.8±7.4) years. Subfibular ossicles were excised in the SFO group. The 2 groups were compared in terms of American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores and visual analogue scale (VAS) pain scores at preoperation and the final follow-up.Results:The 2 groups were comparable due to insignificant differences between them in their preoperative general data ( P>0.05). All the patients were followed up for 24 to 72 months (average, 28 months). The AOFAS ankle-hindfoot scores improved significantly from 54.5±3.4 to 95.7±2.1 in the SFO group and significantly from 56.2±2.7 to 95.2±2.4 in the NSFO group at the final follow-up; the VAS scores reduced significantly from 5.7±1.8 to 1.6±1.4 in the SFO group and significantly from 5.7±1.6 to 1.7±1.2 in the NSFO group at the final follow-up (all P<0.05). No significant differences were found between the 2 groups in terms of AOFAS or VAS scores at the final follow-up ( P>0.05). Conclusion:Since the modified Brostr?m procedure plus subfibular ossicle excision may result in similar good clinical efficacy as merely the modified Brostr?m procedure may for the CLAI patients without subfibular ossicle, subfibular ossicle excision should be suggested for the CLAI patients with subfibular ossicle.

Objective:To evaluate the role of miR-20a-5p in M1 microglia aggravating oxygen-glucose deprivation and restoration (OGD/R)-induced injury to neurons and the relationship with mitofusin2 (MFN2).Methods:The well-growing BV2 microglia (M0 type) were polarized into M1 phenotype by lipopolysaccharide (100 ng/ml) and IFN-γ (20 ng/ml) and identified by quantitative real-time polymerase chain reaction and immunofluorescence.The well-growing N2a cells were divided into 6 groups ( n=6 each) by the random number table method: control group (group C), OGD/R group, M0 microglia co-culture group (group M0), M1 microglia co-culture group (group M1), miR-20a-5p inhibitor transfection group (group I) and negative control group (group NC). The cells were routinely cultured in group C, and the cells were subjected to OGD for 3 h followed by restoration of oxygen-glucose supply to develop the model of OGD/R injury in group OGD/R.The cells were subjected to OGD for 3 h and were co-cultured with M0 microglia for 24 h during restoration of oxygen-glucose supply in group M0.The cells were subjected to OGD for 3 h and were co-cultured with M1 microglia for 24 h during restoration of oxygen-glucose supply in group M1.In group I and group NC, cells were transfected with miR-20a-5p inhibitor and negative control miRNA into M1 microglia, respectively, and N2a cells were subjected to OGD for 3 h and co-cultured with M1 microglia for 24 h during restoration of oxygen-glucose supply.The cell viability was determined by cell counting kit-8 assay, amount of lactate dehydrogenase (LDH) released was determined, the expression of miR-20a-5p and MFN2 mRNA was detected by quantitative real-time polymerase chain reaction, and MFN2 expression was detected by Western blot. Results:Compared with group C, the cell viability was significantly decreased, the amount of LDH released was increased, and the expression of MFN2 protein and mRNA was down-regulated in the other five groups, miR-20a-5p expression was significantly up-regulated in OGD/R, M0 and M1 groups, and miR-20a-5p expression was significantly down-regulated in group I ( P<0.05). There were no significant differences in the cell viability, amount of LDH released, and expression of miR-20a-5p, MFN2 protein and mRNA between group OGD/R and group M0 ( P>0.05). Compared with group OGD/R and group M0, the cell viability was significantly decreased, the amount of LDH released was increased, and the expression of MFN2 protein and mRNA was down-regulated, and miR-20a-5p expression was up-regulated in group M1 ( P<0.05). Compared with group M1, the cell viability was significantly increased, the amount of LDH released was decreased, the expression of MFN2 protein and mRNA was up-regulated, and miR-20a-5p expression was down-regulated in group I ( P<0.05). Conclusions:The mechanism by which M1 microglia aggravates OGD/R-induced damage to N2a cells may be related to the up-regulation of miR-20a-5p expression in M1 microglia and the inhibition of MFN2 expression in N2a cells.

Objective:To establish and evaluate a rapid nucleic acid detection method for SARS-CoV-2 based on COYOTE ? Flash20 real-time fluorescent quantitative PCR instrument. Methods:A rapid reaction system was constructed by using specific primer and probe sets targeting ORF1ab and N gene of SARS-CoV-2, and the sensitivity and specificity of the system were verified. At the same time, 108 clinical samples of COVID-19 were used to evaluate the application of this method.Results:The detection method did not require nucleic acid extraction, and the manual operation time was only one minute. After the sample was sent to the system, the test could be completed in 30 minutes. The detection limit of this method was 4×10 2 copies/ml. It had no cross-reactivity with other human coronaviruses (including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV and MERS-CoV) and other respiratory viruses. The evaluation of clinical sample application showed that the total coincidence rate with the conventional RT-qPCR which required nucleic acid extraction was 98.15%. Conclusions:Through the application evaluation of the rapid fluorescent quantitative PCR method of SARS-CoV-2, it was found that the method was simple, fast, specific and sensitive, and it was suitable for real-time and rapid detection needs in varieties of situations.

Objective:To investigate the clinical features and prognosis of low triiodothyronine syndrome (LT3S) in patients with acute myeloid leukemia (AML) .Methods:A total of two 236 patients with AML who presented at the Jiangsu Provincial Hospital between January 2013 and December 2019 were included, and their data were retrospectively reviewed. The patients were divided into two groups, including the LT3S group and the non-LT3S group, according to their serum thyroxine level. The clinical characteristics and prognosis of the two groups were compared.Results:Among the 236 patients, 62 (26.3%) patients had LT3S. Serum-free T3 level was positively correlated with albumin ( r=0.443, P<0.001) and hemoglobin ( r=0.187, P=0.005) levels and negatively correlated with C-reactive protein ( r=-0.406, P<0.001) and lactate dehydrogenase ( r=-0.274, P<0.001) levels. The overall survival (OS) (7.5 months vs 29.9 months, P<0.001) and progression-free survival (PFS) (2.0 months vs 24.0 months, P<0.001) were significantly shortened in the LT3S group compared with the non-LT3S group. After propensity score matching, the OS (9.6 months vs 30.4 months, P=0.010) and PFS (3.0 months vs 30.0 months, P=0.014) were still significantly reduced in the LT3S group compared with the non-LT3S group. Therefore, LT3S was an independent risk factor for OS ( HR=2.553, 95% CI 1.666-3.912, P<0.001) and PFS ( HR=1.701, 95% CI 1.114-2.597, P=0.014) in patients with AML. Subgroup analysis suggested that patients with LT3S had a worse prognosis in patients with AML who were obese, fragile, or treated with standard chemotherapy. Conclusions:The occurrence of LT3S reflects the poor clinical status and prognosis of patients with AML.

Objective:To evaluate the clinical application of an individualized 3D printed drill template to create a fibular channel in the anatomical reconstruction of the lateral ankle ligament for chronic lateral ankle instability.Methods:From October 2012 to June 2015, 15 patients with lateral ankle in-stability underwent surgery at Department of Foot and Ankle Surgery, The Fourth Hospital of Wuhan.They were 4 men and 11 women, with a mean age of 26.3 years (range, from 18 to 42 years).For each of them, anatomical reconstruction of the lateral ankle ligament was performed through a fibular channel which was created with the aid of an individualized 3D printed drill template.The American Orthopaedic Foot and Ankle Society (AOFAS) and Visual Analogue Scale (VAS) scores were used to assess the patients preoperation and at the last follow-up.Results:The 15 patients obtained a mean follow-up of 15.2 months (range, from 12 to 18 months).Their preoperative AOFAS scores (47.1±3.8) were increased to 88.3±4.7 at the last fol-low-up, and their preoperative VAS scores (5.8±1.8) decreased to 1.55±1.35 at the last follow-up, showing significant differences ( P<0.05).There were 11 excellent and 4 good cases by the AOFAS ankle-hindfoot scale.No significant complications were found. Conclusion:In the anatomical reconstruction of the lateral ankle ligament for chronic lateral ankle instability, an individualized 3D printed drill template can help create a fibular channel which exactly fits each individual, leading to positive therapeutic effects.

Objective:To explore the effectiveness of 3D printed individualized osteotomy template for the treatment of painful talocalcaneal coalition of Rozansky types Ⅲ-Ⅳ.Methods:From January 2016 to August 2018, a 3D printed individualized osteotomy template was used in 14 patients with painful talocalcaneal coalition at Department of Foot and Ankle Surgery, Wuhan Fourth Hospital. They were 8 males and 6 females, aged from 19 to 42 years (mean, 30.2 years). CT scan of full bilateral feet was conducted. The bone bridge to be resected was marked and an individualized template designed taking the CT scans of the healthy foot as mirror images. The 3D individualized templates were used to assist resection of talocalcaneal coalitions. Scores of visual analogue scale(VAS) and American Orthopaedic Foot and Ankle Society (AOFAS) and complications were recorded at the final follow-up.Results:The 14 patients obtained an average follow-up of 21.6 months. Their VAS and AOFAS ankle and hindfoot scores (2.3±0.7 and 86.5±4.5) at the final follow-up were significantly improved compared with their preoperative values (7.0±1.9 and 37.1±6.0) ( P<0.05). Their follow-up X-ray films showed no recurrence of talocalcaneal coalition or traumatic arthritis. Conclusion:A 3D printed individualized osteotomy template is an effective assistance in the treatment of talocalcaneal coalition because it can lead to accurate location of the talocalcaneal bridge and full osteotomy.