Objective:The aim of this study was to explore the molecular mechanisms of sulforaphane in the treatment of autism spectrum disorders (ASD), identify metabolomic biomarkers associated with efficacy and construct efficacy prediction models.Methods:Forty children with ASD who were treated in Second Xiangya Hospital of Central South University and Guangzhou Huiai Hospital were recruited from August 2016 to May 2019. The patients were randomly allocated into sulforaphane treatment group ( n=26) and placebo group ( n=14). The OSU Autism Rating Scale-DSM-Ⅳ (OARS-4) was used to assess the change in clinical symptoms of children with ASD at baseline, week 4, week 8 and week 12 of treatment. A generalized linear mixed model was used to compare the differences in OARS-4 scale scores between groups and time. Plasma samples were collected from patients before and after treatment for untargeted metabolomic detection using ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Differential metabolites were screened using ANOVA-component analysis, and metabolic pathway analysis was performed. Then, spearman correlation analysis was performed to find differential metabolites significantly associated with the efficacy of sulforaphane treatment, and finally Fisher′s discriminant analysis was used to screen for efficacy predictors. Result:After 12 weeks of treatment, the clinical symptoms improvement was significantly better in the sulforaphane group than in the placebo group ( F=14.11, P<0.001). There were differences in a total of 201 metabolites between the two groups, which were mainly significantly enriched in glycerophospholipid metabolism and primary bile acid biosynthesis pathways. Spearman′s correlation analysis showed that taurine, phosphatidylserine and lysophosphatidylserine were significantly positively associated with symptom changes in patients with ASD ( r=0.643, 0.401, 0.414, P<0.05 or 0.001), while lysophosphatidylethanolamine, sphingomyelin and triglyceride metabolites were significantly negatively associated with symptom changes ( r=-0.481--0.392, all P<0.05). Among them, sphingomyelin (d35∶1) and taurine entered the Fisher′s discriminant analysis model, which the accuracy of efficacy prediction was 84.6%(22/26). Conclusions:The molecular mechanism of sulforaphane in improving ASD related clinical symptoms may be related to cell membrane phospholipid metabolism. Sphingomyelin (d35∶1) and taurine may be possible predictors on the efficacy of sulforaphane in the treatment of ASD.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

Objective:The aim of this study was to explore the molecular mechanisms of sulforaphane in the treatment of autism spectrum disorders (ASD), identify metabolomic biomarkers associated with efficacy and construct efficacy prediction models.Methods:Forty children with ASD who were treated in Second Xiangya Hospital of Central South University and Guangzhou Huiai Hospital were recruited from August 2016 to May 2019. The patients were randomly allocated into sulforaphane treatment group ( n=26) and placebo group ( n=14). The OSU Autism Rating Scale-DSM-Ⅳ (OARS-4) was used to assess the change in clinical symptoms of children with ASD at baseline, week 4, week 8 and week 12 of treatment. A generalized linear mixed model was used to compare the differences in OARS-4 scale scores between groups and time. Plasma samples were collected from patients before and after treatment for untargeted metabolomic detection using ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Differential metabolites were screened using ANOVA-component analysis, and metabolic pathway analysis was performed. Then, spearman correlation analysis was performed to find differential metabolites significantly associated with the efficacy of sulforaphane treatment, and finally Fisher′s discriminant analysis was used to screen for efficacy predictors. Result:After 12 weeks of treatment, the clinical symptoms improvement was significantly better in the sulforaphane group than in the placebo group ( F=14.11, P<0.001). There were differences in a total of 201 metabolites between the two groups, which were mainly significantly enriched in glycerophospholipid metabolism and primary bile acid biosynthesis pathways. Spearman′s correlation analysis showed that taurine, phosphatidylserine and lysophosphatidylserine were significantly positively associated with symptom changes in patients with ASD ( r=0.643, 0.401, 0.414, P<0.05 or 0.001), while lysophosphatidylethanolamine, sphingomyelin and triglyceride metabolites were significantly negatively associated with symptom changes ( r=-0.481--0.392, all P<0.05). Among them, sphingomyelin (d35∶1) and taurine entered the Fisher′s discriminant analysis model, which the accuracy of efficacy prediction was 84.6%(22/26). Conclusions:The molecular mechanism of sulforaphane in improving ASD related clinical symptoms may be related to cell membrane phospholipid metabolism. Sphingomyelin (d35∶1) and taurine may be possible predictors on the efficacy of sulforaphane in the treatment of ASD.

Objective:This study aims to investigate the impact of individual and family factors on non-suicidal self-injury (NSSI) behaviors in adolescents with mood disorders.Methods:Adolescents with mood disorders were included according to the ICD-10 diagnostic criteria, while the NSSI behaviors were assessed according to the DSM-5. The patients were divided into mood disorders with ( n=147) and without NSSI group ( n=56). Healthy adolescents were included as the control group ( n=107). The General Information Questionnaire, the Generalized Anxiety Disorder-7, the Patient Health Questionnaire-9, the Emotion Regulation Difficulties Scale, the Childhood Trauma Questionnaire, and the Parenting Style Scale were assessed. The three groups were compared using the χ 2 test and the analysis of variance, while the difference between two groups was compared using the t-test. Multiple logistic regression was used to explore the influence of various factors on NSSI behaviors. Results:Patients in the mood disorder with NSSI group scored significantly higher on depression, difficulties in emotion regulation, emotional abuse, and parental control than those in the mood disorder without NSSI group and the healthy control group. The multiple logistic regression analysis revealed that NSSI behaviors were positively correlated with depression ( OR=1.407, P<0.001), emotional abuse ( OR=1.186, P=0.03), and maternal encourage autonomy ( OR=1.302, P=0.035), and negatively correlated with paternal encourage autonomy ( OR=0.805, P=0.038), maternal care ( OR=0.731, P=0.025), and adolescent′s age (OR=0.656, P<0.001); adolescent′s age ( OR=0.851, P=0.042), paternal age ( OR=0.891, P=0.049) and male gender ( OR=0.435, P=0.040) were negatively correlated with NSSI behaviors. Conclusions:Gender, age, depression level, emotion regulation ability, personality traits, and parenting style had significant effects on adolescents′ NSSI behaviors.

In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.
Mice ; Animals ; Hedgehog Proteins/genetics* ; Receptors, G-Protein-Coupled/metabolism* ; Cilia/metabolism* ; Cartilage/metabolism* ; Regeneration

Objective To explore the curative effect of day care unit on the efficacy,safety and satisfaction of elderly patients who underwent a cold snare polypectomy for the treatment colorectal polyps.Methods Clinical data from 454 elderly patients with 824 colorectal polyps(Diameter 4～10 mm)who received a polypectomy from Mar 2020 to Mar 2021 were collected.These patients were classified into three groups.The cold snare polypectomy group and hot snare polypectomy group in day care unit,and the cold snare polypectomy group in general wards.The clinical characteristics,adverse events,recurrence,hospitalization time,and expenses,were compared among three groups.Additionally,the patients'hospitalization satisfaction was investigated and analyzed.Results There were no significant differences in clinical characteristics,histopathology,and rates of postoperative bleeding,perforation,and recurrence among the 3 groups(P＞0.05),but the probability of immediate bleeding was higher in the cold snare polypectomy group.Moreover,coagulation syndrome was unique to the hot snare polypectomy group.The hot snare polypectomy group used the highest amount of endoclips,while the cold snare polypectomy group in the general wards used the least.Furthermore,the hospitalization time and expenses in the day care unit group were significantly lower than in the general wards group.However,the patients'satisfaction survey showed that the day care unit group scored lower than the general wards group(P＜0.05).Conclusions It is safe,cost-effective and effective for elderly patients with colorectal polyps using cold snare polypectomy technique under the day care unit mode,but the lack of communication with the patient's condition in a short period of time rather leads to a decrease in hospital satisfaction.

Objective:This study aims to investigate the impact of individual and family factors on non-suicidal self-injury (NSSI) behaviors in adolescents with mood disorders.Methods:Adolescents with mood disorders were included according to the ICD-10 diagnostic criteria, while the NSSI behaviors were assessed according to the DSM-5. The patients were divided into mood disorders with ( n=147) and without NSSI group ( n=56). Healthy adolescents were included as the control group ( n=107). The General Information Questionnaire, the Generalized Anxiety Disorder-7, the Patient Health Questionnaire-9, the Emotion Regulation Difficulties Scale, the Childhood Trauma Questionnaire, and the Parenting Style Scale were assessed. The three groups were compared using the χ 2 test and the analysis of variance, while the difference between two groups was compared using the t-test. Multiple logistic regression was used to explore the influence of various factors on NSSI behaviors. Results:Patients in the mood disorder with NSSI group scored significantly higher on depression, difficulties in emotion regulation, emotional abuse, and parental control than those in the mood disorder without NSSI group and the healthy control group. The multiple logistic regression analysis revealed that NSSI behaviors were positively correlated with depression ( OR=1.407, P<0.001), emotional abuse ( OR=1.186, P=0.03), and maternal encourage autonomy ( OR=1.302, P=0.035), and negatively correlated with paternal encourage autonomy ( OR=0.805, P=0.038), maternal care ( OR=0.731, P=0.025), and adolescent′s age (OR=0.656, P<0.001); adolescent′s age ( OR=0.851, P=0.042), paternal age ( OR=0.891, P=0.049) and male gender ( OR=0.435, P=0.040) were negatively correlated with NSSI behaviors. Conclusions:Gender, age, depression level, emotion regulation ability, personality traits, and parenting style had significant effects on adolescents′ NSSI behaviors.

Objective:To compare the population characteristics, the positive rate of screening, the detection rate of breast cancer, early diagnosis rate and the cost between the mass screening group and opportunistic screening group of breast cancer.Methods:This study is a prospective multicenter cohort study conducted from January 1, 2014 to December 31, 2016. The participants were enrolled for mass screening or opportunistic screening of breast cancer. After completing the questionnaire, all the participants received breast physical examination and breast ultrasound examination every year for 3 rounds by year. The participants′ characteristics and screening results of the two groups were compared by χ 2 test, Fisher exact test or Wilcoxon rank-sum test. Results:A total of 20 080 subjects were enrolled. In the mass screening group, 9 434 (100%), 8 111 (85.98%) and 3 940 (41.76%) cases completed the 3 rounds of screening, and 10 646 (100%), 6 209 (58.32%) and 2 988 (28.07%) cases in the opportunistic screening group, respectively. In the opportunistic screening group, the proportions of less than 3 months lactation (1 275/9 796 vs. 1 061/8 860, χ2=4.597, P=0.032), non-fertility (850/10 646 vs. 574/9 434, χ2=27.400, P<0.01), abortion history (6 384/10 646 vs. 5 062/9 434, χ2=81.232, P<0.01), postmenopausal (2 776/10 646 vs. 2 217/9 434, χ2=17.757, P<0.01), long-term oral contraceptives(>6 months) (171/10 646 vs. 77/9 434, χ2=25.593, P<0.01) and family history of breast cancer in first-degree relatives (464/10 646 vs. 236/9 434, χ2=51.257, P<0.01) were significantly higher than those in mass screening group. The positive rate of screening (514/10 646 vs. 128/9 434, χ2=194.736, P<0.01), the detection rate of breast cancer (158/10 646 vs. 13/9 434, χ2=107.374, P<0.01), and positive rate of biopsy (158/452 vs. 13/87, χ2=13.491, P<0.01) in the opportunistic screening group were significantly higher than those of the mass screening group. The early diagnosis rate of the mass screening group was significantly higher than the opportunistic screening group (10/12 vs. 66/141, χ2=5.902, P=0.015). The average cost for detecting each breast cancer case of the mass screening group was 215 038 CNY, which was 13.6 times of the opportunistic screening group (15 799 CNY/case). In the opportunistic screening group, the positive rate of biopsy in primary hospitals was significantly lower than that in large-volume hospitals (79/267 vs. 79/185, χ2=8.267, P=0.004), but there was no significant difference in the mass screening group (6/37 vs. 7/50, χ2=0.082, P=0.774). Conclusions:Breast cancer screening can improve early detection rate. Compared with the mass screening mode, the opportunistic screening mode has the advantages of higher proportion of high-risk factors, higher positive rate of screening, higher detection rate of breast cancer, higher positive rate of biopsy, and lower cost of screening. However, the early diagnosis rate of breast cancer of opportunistic screening is lower than that of mass screening. The positive rate of opportunistic screening in primary hospitals is lower than that of large-volume hospitals. The two screening modes have their own advantages and should be chosen according to local conditions of different regions in China.

Objective:To compare the population characteristics, the positive rate of screening, the detection rate of breast cancer, early diagnosis rate and the cost between the mass screening group and opportunistic screening group of breast cancer.Methods:This study is a prospective multicenter cohort study conducted from January 1, 2014 to December 31, 2016. The participants were enrolled for mass screening or opportunistic screening of breast cancer. After completing the questionnaire, all the participants received breast physical examination and breast ultrasound examination every year for 3 rounds by year. The participants′ characteristics and screening results of the two groups were compared by χ 2 test, Fisher exact test or Wilcoxon rank-sum test. Results:A total of 20 080 subjects were enrolled. In the mass screening group, 9 434 (100%), 8 111 (85.98%) and 3 940 (41.76%) cases completed the 3 rounds of screening, and 10 646 (100%), 6 209 (58.32%) and 2 988 (28.07%) cases in the opportunistic screening group, respectively. In the opportunistic screening group, the proportions of less than 3 months lactation (1 275/9 796 vs. 1 061/8 860, χ2=4.597, P=0.032), non-fertility (850/10 646 vs. 574/9 434, χ2=27.400, P<0.01), abortion history (6 384/10 646 vs. 5 062/9 434, χ2=81.232, P<0.01), postmenopausal (2 776/10 646 vs. 2 217/9 434, χ2=17.757, P<0.01), long-term oral contraceptives(>6 months) (171/10 646 vs. 77/9 434, χ2=25.593, P<0.01) and family history of breast cancer in first-degree relatives (464/10 646 vs. 236/9 434, χ2=51.257, P<0.01) were significantly higher than those in mass screening group. The positive rate of screening (514/10 646 vs. 128/9 434, χ2=194.736, P<0.01), the detection rate of breast cancer (158/10 646 vs. 13/9 434, χ2=107.374, P<0.01), and positive rate of biopsy (158/452 vs. 13/87, χ2=13.491, P<0.01) in the opportunistic screening group were significantly higher than those of the mass screening group. The early diagnosis rate of the mass screening group was significantly higher than the opportunistic screening group (10/12 vs. 66/141, χ2=5.902, P=0.015). The average cost for detecting each breast cancer case of the mass screening group was 215 038 CNY, which was 13.6 times of the opportunistic screening group (15 799 CNY/case). In the opportunistic screening group, the positive rate of biopsy in primary hospitals was significantly lower than that in large-volume hospitals (79/267 vs. 79/185, χ2=8.267, P=0.004), but there was no significant difference in the mass screening group (6/37 vs. 7/50, χ2=0.082, P=0.774). Conclusions:Breast cancer screening can improve early detection rate. Compared with the mass screening mode, the opportunistic screening mode has the advantages of higher proportion of high-risk factors, higher positive rate of screening, higher detection rate of breast cancer, higher positive rate of biopsy, and lower cost of screening. However, the early diagnosis rate of breast cancer of opportunistic screening is lower than that of mass screening. The positive rate of opportunistic screening in primary hospitals is lower than that of large-volume hospitals. The two screening modes have their own advantages and should be chosen according to local conditions of different regions in China.

Objective:To compare the clinical effect of Ilizarov frame and unilateral frame in the treatment of tibial segmental bone defect combined with soft tissue defect by open bone transport.Methods:A retrospective case-control study was conducted to analyze the clinical data of 32 patients with tibial segmental bone defect and soft tissue defect-up who underwent open bone transport technique in Tianjin Hospital from August 2008 to August 2016 and obtained complete followed-up. There were 22 males and 10 females, aged 22-64 years (mean, 36.8 years). Nineteen patients in the Ilizarov group showed the mean bone defect length of 7.9 cm and mean soft tissue defect area of 41.4 cm 2. Thirteen patients in the unilateral group showed the mean bone defect length of 7.8 cm and the mean soft tissue defect area of 39.2 cm 2. The results of fracture healing, wound healing time, radiological consolidation index, external fixation index, Association for the Study and Application of the Method of Ilizarov (ASAMI) bone and lower-limb function score and incidence of complications were compared between the groups. Results:All patients were followed up for 24 to 60 months [(32.6±1.3)months]. Bone healing was achieved in all patients. The wound healing time was (2.7±2.3)days in Ilizarov group and (2.4±1.8)days in unilateral group ( P>0.05). The consolidation index was (43.4±8.7)d/cm in Ilizarov group and (45.8±10.3)d/cm in unilateral group ( P>0.05). The external fixation index was (52.6±8.9)d/cm in Ilizarov group and (58.7±12.9)d/cm in unilateral group ( P<0.05). The results of ASAMI bone score was excellent in 10 patients, good in 6, fair in 2 and poor in 1 in Ilizarov group, with the excellent rate of 84%; and excellent in 6 patients, good in 4, fair in 2, and poor in 1 in unilateral group, with the excellent rate of 77%, with insignificant difference between two groups ( P>0.05). The results of ASAMI lower-limb function score was excellent in 8 patients, good in 7, fair in 3, poor in 1 in Ilizarov group, with the excellent rate of 79%; and excellent in 6, good in 3, fair in 3, poor in 1 in unilateral group, with the excellent rate of 69%, with insignificant difference between the two groups ( P>0.05). Incidence of axial deviation was zero in Ilizarov group versus 23% in unilateral group ( P<0.05). After operation, Ilizarov group had refracture in 1 patient and pin site infection in 5, and unilateral group had refracture in 1 patient and pin site infection in 1, showing no significant difference between the two groups ( P>0.05). Conclusions:Tibial segmental bone defect with soft tissue defect can be effectively treated by open bone transport with Ilizarov and unilateral frame. Ilizarov frame has better biomechanical properties and is more convenient for correction of poor postoperative axial alignment.