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.

Objective To investigate the age-specific cut-off values and diagnostic efficacy of anti-Muller hormone(AMH)in the diagnosis of polycystic ovary syndrome(PCOS).Methods The Serum AMH levels were measured by immunofluorescence assay in 2 187 patients with menstrual disorders aged 14-40 years in the hospital.Patients who met the Rotterdam criteria were classified as the PCOS group,while those who did not were classified as the control group.The generalized additive model(GAMs)and the area under the re-ceiver operating characteristic(ROC)curve(AUC)were used to establish the age interval and the corre-sponding cut-off values of AMH.The efficacy of AMH in diagnosing PCOS in each age interval was evaluated and compared with the cut-off values provided by the reagent manufacturer.Results Based on GAMs model,the age cut-off values for AMH in predicting PCOS were 21,28,and 35 years old,respectively.The cut-off val-ues for the prediction of PCOS in the age categories of 14-＜20,20-＜28,28-＜35,and 35-40 years were 8.28,8.02,6.70,3.96 ng/mL.The AUC was 0.97(95％CI:0.93-0.99),0.97(95％CI:0.95-0.98),0.98(95％CI:0.95-0.98),and 0.99(95％CI:0.98-0.99),the sensitivity was 0.87,0.87,0.91,and 1.00,and the specificity was 0.94,0.93,0.90,and 0.93,respectively.In all age groups,AMH level in PCOS group was higher than that in control group,and the difference was statistically significant(P＜0.001).Conclusion Ap-plication of age-specific cut-off values of AMH could elegantly assess the value of AMH in discriminating P-COS patients in all age categories.

Objective:To learn about the epidemiological and clinical characteristics of children with brucellosis, in order to provide reference for clinical diagnosis and treatment of brucellosis in children.Methods:Clinical data of children with brucellosis (aged ≤14 years) who visited the Department of Infectious Diseases at Beidahuang Industry Group General Hospital from December 2020 to December 2022 were retrospectively collected, and their epidemiological characteristics, clinical characteristics, laboratory tests, treatment and outcome were summarized and analyzed.Results:A total of 34 children with brucellosis were included, including 25 males (73.53%) and 9 females (26.47%), with a gender ratio of 2.78 ∶ 1.00. The median age was 8 years and 1 month, mainly in the age group of 6 to 14 years (19 cases, 55.88%). Epidemiological investigation showed that most of the affected children were rural residents (25 cases, 73.53%), with more contact with cattle/sheep (26 cases, 76.47%). The onset time was mainly concentrated in summer (15 cases, 44.12%) and spring (13 cases, 38.24%). The clinical symptoms were mainly fever (97.06%, 33/34) and arthralgia (64.71%, 22/34). In the laboratory tests, 25 cases (73.53%) had positive blood cultures, and the white blood cell count (WBC) of 30 cases (88.24%) was (4 - 10) × 10 9/L. Among the abnormalities of liver function, aspartate aminotransferase (AST) increased in 19 cases (55.88%), alanine aminotransferase (ALT) increased in 14 cases (41.18%) and γ-glutamyl transpeptidase (GGT) increased in 6 cases (17.65%). Among the myocardial enzymatic abnormalities, α-hydroxybutyrate dehydrogenase (HBDH) increased in 29 cases (85.29%), lactate dehydrogenase (LDH) increased in 27 cases (79.41%), and creatine kinase isoenzyme (CK-MB) increased in 8 cases (23.53%). After treatment, 25 children with positive blood culture turned negative. Conclusions:Children with brucellosis are mainly male, older and rural residents. The clinical manifestations are mainly fever and arthralgia. Doctors in relevant departments should conduct detailed epidemiological investigations and laboratory tests for such children in clinical work, in order to achieve early detection, diagnosis and treatment of pediatric brucellosis.

Objective:To investigate the timing and features of fine-needle aspiration biopsy (FNAB) guided by ultrasound for Bethesda Ⅲ thyroid nodules and to further optimize the puncture scheme.Methods:A retrospective analysis was conducted on data from patients who underwent rFNAB for Bethesda Ⅲ thyroid nodules at the China-japan Union Hospital of Jilin University Thyroid Surgery Department from Dec. 2020 to Dec. 2022. The study included 71 cases (73 nodules), consisting of 57 females and 14 males, with an average age of (45.7±10.4) years. Patients were grouped based on rFNAB results: Bethesda Ⅱ as the benign group ( n=21), Bethesda Ⅴ/Ⅵ as the malignant group ( n=39), and the remaining cases categorized as the indeterminate group ( n=13). Data on rFNAB results, puncture interval time, postoperative pathology, ultrasound features, and FNAB characteristics were recorded. Descriptive statistics were used for categorical data, presented as percentages and numbers, while continuous data were presented as mean ± standard deviation ( ± s). The χ2 test or Fisher's exact test was applied for analysis. Results:In this study, rFNAB was performed on 73 Bethesda Ⅲ thyroid nodules. The results showed that 60 nodules (82.2%) received a definite diagnosis, while 13 nodules (17.8%) were indeterminate. There was a statistically significant difference in the calcification classification between the malignant group and the benign group as well as the indeterminate group ( P<0.05). Among the malignant group, 29 patients underwent surgical treatment, with only 2 cases (8.0%) showing intermediate recurrence risk when surgery was performed more than three months after the initial FNAB. Upon reevaluation of the 31 initial FNAB samples from the malignant group, 9 samples (29.0%) exhibited mild cytological atypia, and 22 samples (71.0%) had poor quality specimens, mainly comprising fibrous and calcified components. Conclusions:For nodules initially classified as Bethesda Ⅲ, if suspicious ultrasound features persist or emerge, especially if microcalcifications are present, rFNAB should be performed after a follow-up period exceeding three months. However, during the puncture, multiple points should be targeted at the non-calcified areas of the nodule to enhance the accuracy and reliability of rFNAB.

Objective:To explore the effect of transcutaneous electrical nerve stimulation (TENS) on interleukin-33 (IL-33)/growth stimulation expressed gene 2 (ST2) signaling pathway in the dorsal root ganglia (DRGs) of rats modeling hyperalgesia (HP).Methods:This study consisted of two experiments. In the first, 30 Sprague-Dawley (SD) rats were randomly divided into a blank group, a Sham-HP group, an HP group, an antibody group and an inhibitor group, each of 6. HP was induced in all except the rats of the blank and Sham-HP groups by injecting carrageenan (Car) and prostaglandin E2 subcutaneously at the bottom of the left hind feet. The antibody and inhibitor groups were then given intrathecal injections of anti-ST2 antibody and a tumor necrosis factor α (TNF-α)-specific inhibitor, respectively. In the second experiment, 42 SD rats were randomly divided into a Sham-HP group, an HP group, a TENSⅠgroup, a TENS II group, a TENS I inhibitor group, a TENS II inhibitor group, and a Sham-TENS group, each of 6. All of the groups had HP induced as in experiment one. All of the rats except those in the Sham-HP, HP and Sham-TENS groups were then given TENS, and the TENS I and II inhibitor groups were offered intrathecal injection of TNF-α-specific inhibitors. Mechanical pain thresholds (MPTs) were documented 4h, 24h, 48h, 72h, 6d, 7d 4h, 7d 1h, and 7d after the Car injections. Western blotting was used to measure the protein expressions of IL-33, ST2 and TNF-α 6d after the Car injection in both experiments.Results:In experiment one, the average MPTs of the HP, antibody and inhibitor groups had decreased significantly 4 hours after the Car injection compared with the blank and Sham-HP groups. However, 7d 1h after the Car injection the value had increased significantly in the Sham-HP, antibody and inhibitor groups compared with the HP group, while the expressions of IL-33, ST2 and TNF-α had decreased significantly. In experiment two, by 4 hours after the Car injection, the average MPT of all the other groups had decreased significantly compared with the Sham-HP group. Moreover, by 7d 1h after the Car injection, the average MPTs of the groups receiving TENS had increased significantly, with significantly lower MPT in the TENS Ⅱ group than in group Ⅰ, on average. There was also significantly higher expression of IL-33, ST2 and TNF-α in group II. Compared with the TENS Ⅰ and Ⅱ groups, the average MPT was significantly higher in the TENS I and Ⅱ inhibitor groups, but IL-33, ST2 and TNF-α expression was lower.Conclusions:TENS can inhibit TNF-α expression, which influences the signals of the DRG IL-33/ST2 signaling pathway to reverse hyperalgesia. TENS combined with anti-TNF-α treatment is superior to TENS alone in treating hyperalgesia.

Background/Aims: Previous studies have shown that diet and physical activity can influence constipation. However, the combined effect of diet and physical activity on constipation remains unclear. Methods: Constipation was defined based on stool consistency and frequency, while overall diet quality was assessed using Healthy Eating Index (HEI)-2015 scores. Participants were categorized into low (metabolic equivalent [MET]-min/wk < 500) and high physical activitygroups (MET-min/wk ≥ 500). The association between diet and constipation across physical activity groups was analyzed using surveylogistic regression and restricted cubic splines. Results: Higher HEI-2015 scores were associated with reduced constipation risk in the high physical activity group when constipation was defined by stool consistency (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97-0.99). However, in the low physical activity group, increased HEI-2015 scores did not significantly affect constipation risk (OR, 1.01; 95% CI, 0.97-1.05). Similar results were found when constipation was defined based on stool frequency. In the high physical activity group, increased HEI-2015 scores were significantly associated with a reduced constipation risk (OR, 0.96; 95% CI, 0.94-0.98). Conversely, in the low physical activity group, increased HEI-2015 scores did not affect the risk of constipation (OR, 0.96; 95% CI, 0.90-1.03). Conclusions Our findings suggest that a higher HEI-2015 score is negatively associated with constipation among individuals with high physical activity levels but not among those with low physical activity levels. This association was consistent when different definitions of constipation were used. These results highlight the importance of combining healthy diet with regular physical activity to alleviate constipation.

Objective:To investigate the feasibility and advantages of unilateral primary hyperparathyroidism (PHPT) treated by transthyretal interosseous muscle approach surgery.Methods:Clinical data of 7 patients with unilateral PHPT treated by interstitial sternocleidomastoid muscle approach from Jan. 2021 to Feb. 2022 in the thyroid surgery of China-Japan Union Hospital of Jilin University were retrospectively analyzed, including preoperative blood calcium concentration, operation time, incision length, intraoperative parathyroid hormone (PTH) , blood calcium concentration and PTH value in the first month after surgery, abnormal sensation of the skin in the anterior cervical area, etc. The feasibility and advantages of interstitial sternocleidomastoid muscle approach surgery for unilateral PHPT were analyzed.Results:All 7 patients with unilateral PHPT were operated successfully. The PTH was 17.2-63.3 pg/ml on recheck 1 month after surgery, which were all within the normal range. The time from skin opening to resection of the diseased parathyroid gland was 20-35 min, and the length of the surgical incision was 3-4 cm. all patients were given intravenous and oral calcium therapy after surgery, and the blood calcium and PTH levels were within the normal range at 3-12 months of follow-up; the incision recovered well, and there was no significant sensory and functional abnormalities in the anterior neck area.Conclusion:The treatment of unilateral PHPT through the sternocleidomastoid interosseous approach can ensure the safety and efficacy of the operation while better protecting the sensory and motor functions of the anterior cervical region and improving the aesthetics of the surgical incision.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis

OBJECTIVE: To explore the anti-inflammatory effects of ethyl lithospermate in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine-derived macrophages and zebrafish, and its underlying mechanisms. METHODS: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays were performed to investigate the toxicity of ethyl lithospermate at different concentrations (12.5-100 µ mol/L) in RAW 264.7 cells. The cells were stimulated with LPS (100 ng/mL) for 12 h to establish an inflammation model in vitro, the production of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α (TNF-α) were assessed by enzyme linked immunosorbent assay (ELISA). Western blot was used to ascertain the protein expressions of signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB) p65, phospho-STAT3 (p-STAT3, Tyr705), inhibitor of NF-κB (IκB) α, and phospho-I κB α (p-IκB α, Ser32), and confocal imaging was used to identify the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705). Additionally, the yolk sacs of zebrafish (3 days post fertilization) were injected with 2 nL LPS (0.5 mg/mL) to induce an inflammation model in vivo. Survival analysis, hematoxylin-eosin (HE) staining, observation of neutrophil migration, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to further study the anti-inflammatory effects of ethyl lithospermate and its probable mechanisms in vivo. RESULTS: The non-toxic concentrations of ethyl lithospermate have been found to range from 12.5 to 100 µ mol/L. Ethyl lithospermate inhibited the release of IL-6 and TNF-α(P<0.05 or P<0.01), decreased IκBα degradation and phosphorylation (P<0.05) as well as the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705) in LPS-induced RAW 264.7 cells (P<0.01). Ethyl lithospermate also decreased inflammatory cells infiltration and neutrophil migration while increasing the survival rate of LPS-stimulated zebrafish (P<0.05 or P<0.01). In addition, ethyl lithospermate also inhibited the mRNA expression levels of of IL-6, TNF-α, IκBα, STAT3, and NF-κB in LPS-stimulated zebrafish (P<0.01). CONCLUSION Ethyl lithospermate exerts anti-Inflammatory effected by inhibiting the NF-κB and STAT3 signal pathways in RAW 264.7 macrophages and zebrafish.
Animals ; Mice ; NF-kappa B/metabolism* ; Lipopolysaccharides ; RAW 264.7 Cells ; Zebrafish ; NF-KappaB Inhibitor alpha/metabolism* ; Interleukin-6/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; STAT3 Transcription Factor/metabolism* ; Inflammation/metabolism* ; Anti-Inflammatory Agents/therapeutic use*

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15％ of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5％?49.7％ of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3％?17.9％, which was significantly higher than that (6.9％?7.4％) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.