Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective To investigate the biomechanical characteristics of the mandibular anterior teeth intrusion assisted by buccal mini-implants,so as to provide theoretical guidance for the clinical treatment of deep overbite and other conditions requiring intrusion of the mandibular anterior teeth.Methods A finite element model of implant screws,clear aligners(CAs)and mandibular complex including the mandibular dentition,periodontal ligament(PDL)and alveolar bone was constructed.The model was designed with 0.2 mm intrusion in the mandibular anterior teeth.Seven groups were set:without traction,30 g,50 g,100 g,150 g,200 g,and 250 g force groups.The stress and displacement of the teeth as well as the related stress distributions of PDL and CAs in each group after loading were analyzed.Results Without traction and under different traction forces,the mandibular anterior teeth tended to be tipped and intruded.With the increase of traction force,the increasing trend was manifested in the vertical displacement and labial displacement of the mandibular anterior teeth.When the traction force reached 200 g,the vertical displacement showed a significant increase,the subsequent increase then showed a tendency to flatten.The ratio of the labial tipping displacement to the intrusive displacement of the mandibular anterior teeth showed a decreasing trend with the increase of traction force.Within a reasonable force range,increasing traction force led to greater bodily intrusion of the anterior teeth.When the traction force was less than 150 g,the mandibular posterior teeth exhibited a tendency of extrusion.When the traction force of more than 150 g was applied,it showed a tendency of intrusion.The PDL stress was concentrated on the labial and cervical surface of the anterior teeth.Conclusions Intrusion efficiency of the mandibular anterior teeth has been effectively improved with CAs assisted by buccal mini-implants.Moreover,the traction force of the mini-implants has a significant impact on the movement of the mandibular anterior teeth.Based on a comprehensive analysis of factors such as the displacement trend of the mandibular dentition and the PDL stress,the optimal force value for buccal traction of the mini-implants to intrude the mandibular anterior teeth can be selected as 150-200 g force.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Aim To study the correlation between es-trogen metabolism function of intestinal flora and liver fibrosis disease phenotype and differential intestinal bacteria by fecal microbiota transplantation(FMT).Methods C57BL/6J male mice were divided into normal group(Control-M),liver fibrosis Model group(Model),FMT-1 group(normal mice fecal microbiota transplantation from liver fibrosis mice),and FMT-2 group(liver fibrosis mice fecal microbiota transplanta-tion from female mice).The model group was induced by high fat and high glucose combined with low dose of CCl4 for 16 weeks.In the FMT group,the bacteria were destroyed by mixed antibacterial solution and then the corresponding fecal microbiota solution was given.The model group was established in the FMT-2 group and the model group at the same time.Liver function(ALT,AST)was detected by biochemical methods;liver inflammation(IL-1α,IL-6)was detected by ELISA;liver pathology was detected by HE and Mas-son methods;the expressions of α-SMA,collagen Ⅰ,estrogen receptor ERα,ERβ and GPER were detected by Western blot;estrogen metabolic enzymes β-glucu-ronidase and β-glucosidase in intestinal flora were de-tected by double antibody sandwich assay;gut microbi-ota was detected by 16S rDNA method;the correlation between estrogen metabolic enzymes,estrogen receptors and disease phenotypes and disease-related differential bacteria was analyzed by Pearson correlation analysis.Results Liver function,inflammation and fibrosis in-dices were significantly higher in the model group than those in the control-M group and significantly lower in the FMT-2 group than in the model group;estrogen metabolic enzymes of the intestinal flora significantly increased in the model group compared to the control-M group and significantly decreased in the FMT-2 group compared to the model group;the model group showed a significant increase in ERβ and GPER and a significant decrease in ERα compared to the control-M group,while the FMT-2 group showed a significant de-crease in ERβ and GPER and a significant increase in ERα compared to the model group;the FMT-2 group increased the enterobacterial abundance and diversity reduced by modelling;estrogen metabolic enzymes,es-trogen receptor ERβ and GPER were all positively cor-related with the disease phenotype,while the opposite was true for ERα;estrogen metabolic enzymes were positively correlated with Allobaculum,Ruminococcus and Alistipes,and negatively correlated with Akkerman-sia,Lactobacillus and Prevotella.Conclusions Fecal microbiota transplantation in female mice can alleviate liver fibrosis in male mice,which is related to the im-provement of estrogen metabolism of intestinal flora.

Objective:To investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.

Objective To investigate the biomechanical characteristics of the mandibular anterior teeth intrusion assisted by buccal mini-implants,so as to provide theoretical guidance for the clinical treatment of deep overbite and other conditions requiring intrusion of the mandibular anterior teeth.Methods A finite element model of implant screws,clear aligners(CAs)and mandibular complex including the mandibular dentition,periodontal ligament(PDL)and alveolar bone was constructed.The model was designed with 0.2 mm intrusion in the mandibular anterior teeth.Seven groups were set:without traction,30 g,50 g,100 g,150 g,200 g,and 250 g force groups.The stress and displacement of the teeth as well as the related stress distributions of PDL and CAs in each group after loading were analyzed.Results Without traction and under different traction forces,the mandibular anterior teeth tended to be tipped and intruded.With the increase of traction force,the increasing trend was manifested in the vertical displacement and labial displacement of the mandibular anterior teeth.When the traction force reached 200 g,the vertical displacement showed a significant increase,the subsequent increase then showed a tendency to flatten.The ratio of the labial tipping displacement to the intrusive displacement of the mandibular anterior teeth showed a decreasing trend with the increase of traction force.Within a reasonable force range,increasing traction force led to greater bodily intrusion of the anterior teeth.When the traction force was less than 150 g,the mandibular posterior teeth exhibited a tendency of extrusion.When the traction force of more than 150 g was applied,it showed a tendency of intrusion.The PDL stress was concentrated on the labial and cervical surface of the anterior teeth.Conclusions Intrusion efficiency of the mandibular anterior teeth has been effectively improved with CAs assisted by buccal mini-implants.Moreover,the traction force of the mini-implants has a significant impact on the movement of the mandibular anterior teeth.Based on a comprehensive analysis of factors such as the displacement trend of the mandibular dentition and the PDL stress,the optimal force value for buccal traction of the mini-implants to intrude the mandibular anterior teeth can be selected as 150-200 g force.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Objective:To investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged