Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

To investigate the pharmacological substances basis and anti-vitiligo mechanism of Carum carvi L. (caraway) fruits, chemical and blood-absorbed components were identified using mass spectrometry combined with literature study and database analysis. A “blood-absorbed components–target genes–pathways” network was constructed through network pharmacology. The pharmacological effects of Carum carvi L. extract and its key blood-absorbed component, acacetin, were validated in vitro. 72 chemical components were identified in the extract, with 11 prototype blood-absorbed components and 26 metabolites being detected in the plasma of SD rats. 14 key active components and 24 key targets were predicted. In vitro experiments demonstrated that acacetin at 10 μmol/L exhibited melanogenesis-promoting and tyrosinase-activating effects compared with the positive control, significantly upregulating the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (tyrosinase, TYR). This study comprehensively analyzes the chemical and blood-absorbed components of Carum carvi L. and elucidates its pharmacological substances basis, which provides a theoretical foundation for the anti-vitiligo effects of acacetin.

Objective To investigate the value of multiple quantitative parameters derived from Hawk spectral CT in predicting lymph node metastasis in papillary thyroid carcinoma(PTC).Methods Preoperative Hawk spectral CT images of 57 cancerous foci from 44 PTC patients confirmed by surgery and pathology were retrospectively collected.All patients underwent lymph node dissection.Based on pathological results,the patients were categorized into metastatic group(26 patients with 35 cancerous foci)and non-metastatic group(18 patients with 22 cancerous foci).The CT morphological features of the primary PTC lesions included location,diameter,bite-cookie sign,and calcification,respectively.Quantitative parameters of Hawk spectral CT plain scan,arterial phase(AP)and venous phase(VP),including conventional CT values,virtual monoenergetic imaging(MonoE)CT values(40 keV,100 keV),effective atomic number(Zeff)and electron density(Rho),respectively.The rank sum test or chi-square test was used to compare the differences in CT morphological features and Hawk spectral CT quantitative parameters between the two groups.For parameters with significant differences,logistic regression was used to construct a combined model.Area under the curve(AUC),accuracy,sensitivity,and specificity were used to evaluate the effectiveness of the combined model.Results There was statistically significant difference in the diameter of the primary lesion between the metastatic group and the non-metastatic group(P＜0.05),and the diameter of the primary lesion in the metastatic group was larger than that in the non-metastatic group.The conventional CT value,MonoE CT values(40 keV,100 keV),Rho and Zeff in plain scan,AP-Rho,and VP-MonoE CT value(100 keV)of the primary lesion in the metastatic group were all significantly lower than those in the non-metastatic group(P＜0.05).The AUC,accuracy,sensitivity and specificity of the Hawk spectral CT plain scan parameter combination model were 0.765,0.754,0.800,and 0.682,respectively.The AUC,accuracy,sensitivity,and specificity of the Hawk spectral CT enhancement parameter combination model were 0.726,0.667,0.600,and 0.786,respectively.Conclusion Through the analysis of multiple quantitative parameters from Hawk spectral CT of PTC primary lesion,the primary lesion in the metastatic group exhibited significant differences from those in the non-metastatic group in multiple quantitative parameters,which can further improve the predictive efficacy for lymph node metastasis.

Objective To investigate the value of multiple quantitative parameters derived from Hawk spectral CT in predicting lymph node metastasis in papillary thyroid carcinoma(PTC).Methods Preoperative Hawk spectral CT images of 57 cancerous foci from 44 PTC patients confirmed by surgery and pathology were retrospectively collected.All patients underwent lymph node dissection.Based on pathological results,the patients were categorized into metastatic group(26 patients with 35 cancerous foci)and non-metastatic group(18 patients with 22 cancerous foci).The CT morphological features of the primary PTC lesions included location,diameter,bite-cookie sign,and calcification,respectively.Quantitative parameters of Hawk spectral CT plain scan,arterial phase(AP)and venous phase(VP),including conventional CT values,virtual monoenergetic imaging(MonoE)CT values(40 keV,100 keV),effective atomic number(Zeff)and electron density(Rho),respectively.The rank sum test or chi-square test was used to compare the differences in CT morphological features and Hawk spectral CT quantitative parameters between the two groups.For parameters with significant differences,logistic regression was used to construct a combined model.Area under the curve(AUC),accuracy,sensitivity,and specificity were used to evaluate the effectiveness of the combined model.Results There was statistically significant difference in the diameter of the primary lesion between the metastatic group and the non-metastatic group(P＜0.05),and the diameter of the primary lesion in the metastatic group was larger than that in the non-metastatic group.The conventional CT value,MonoE CT values(40 keV,100 keV),Rho and Zeff in plain scan,AP-Rho,and VP-MonoE CT value(100 keV)of the primary lesion in the metastatic group were all significantly lower than those in the non-metastatic group(P＜0.05).The AUC,accuracy,sensitivity and specificity of the Hawk spectral CT plain scan parameter combination model were 0.765,0.754,0.800,and 0.682,respectively.The AUC,accuracy,sensitivity,and specificity of the Hawk spectral CT enhancement parameter combination model were 0.726,0.667,0.600,and 0.786,respectively.Conclusion Through the analysis of multiple quantitative parameters from Hawk spectral CT of PTC primary lesion,the primary lesion in the metastatic group exhibited significant differences from those in the non-metastatic group in multiple quantitative parameters,which can further improve the predictive efficacy for lymph node metastasis.

Objective Pre-packaged space scallion pancakes are prone to quality deterioration during storage due to starch retrogradation and lipid oxidation,which affects their food safety and sensory characteristics.Therefore,investigating their quality changes during storage and predicting shelf life are of great significance for ensuring the quality of space food.Methods study conducted accelerated shelf-life tests at(37±1)℃ and(47±1)℃ under simulated spacecraft food storage conditions.Comprehensive analyses were performed,including physicochemical properties(acid value,peroxide value,carbonyl value),microbiological indicators(total bacterial count,coliforms),color parameters(L*,a*,b*,c*,h°),and texture characteristics(hardness,adhesiveness,etc.).XRD and FTIR were employed to verify starch retrogradation and lipid oxidation.Results Physicochemical properties:The acid value gradually decreased and stabilized with prolonged storage.The peroxide value increased rapidly at 37℃and 47℃,with samples stored at 47℃approaching the safety limit(0.25 g/100 g)within 40 days,while the carbonyl value exhibited a decreasing trend.Microbiological indicators:All samples met the requirements of GJB 4992A-2012.No microbial contamination was detected initially,with only minor bacterial growth observed in later stages,and no coliforms were detected throughout the storage period.Color changes:During storage at 20℃,the a*value increased by 91.67%,while b* and c* values showed significant increases.Meanwhile,L* and h° values decreased by 7.42%and 8.75%,respectively.Texture deterioration:Overall texture characteristics declined,and XRD and FTIR analyses confirmed aggravated starch retrogradation.Shelf-life prediction:Correlation analysis identified peroxide value as the key factor.The established prediction model had an error margin of less than 10%,with predicted shelf lives of 236,121,and 57 days at 20℃,37℃,and 47℃,respectively.Conclusion This study reveals the quality change patterns of space scallion pancakes during storage.The established shelf-life prediction model provides theoretical and methodological support for quality monitoring of pre-packaged space foods.

Objective To propose a high-precision deep learning-based image assessment method of osteosarcoma chemotherapy efficacy for clinical treatment,as existing methos have low accuracy of osteosarcoma assessment.Methods The low incidence of osteosarcoma led to the small scale of its imaging data and the problem of imbalance in data categories.This study combined deep learning with clinical medical information,combined the bone sarcoma generation module of BoneGAN and the scale lesion information capture module,and proposed OMLA-Net,a deep learning assessment network for chemotherapy effect of bone sarcoma based on multi-scale lesion attention network,which achieved computer-aided bone tumor assessment with integrated data augmentation and focused lesion information through pre-training and generalized loss training.Results In this study,40 cases of osteosarcoma MRI data were used as the basis for the comparison test on the generated dataset,and the OMLA-Net assessment outperformed the SOTA method Conv-LSTM-GAN in terms of the assessment effects such as accuracy and F1 scores,and the difference was statistically significant(Bootstrap statistical method P＜0.05);the subsequent K-fold cross-validation ablation experiments further demonstrated the effectiveness of each module proposed by OMLA-Net.Conclusion OMLA-Net can effectively perform the impact assessment of chemotherapy effect on osteosarcoma,which provides a new idea for subsequent clinical application.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective To investigate the application of synchronized immersion course(SIC)in teaching of clinical practice of surgery for eight-year program students.Methods A total of 94 eight-year program students in French class and 4+4 class who received SIC in the study of surgery in Ruijin Clinical School,Shanghai Jiao Tong University from September 2017 to June 2019 were selected as the pilot group.A total of 91 students in English class who were taught in the traditional way in the same period were selected as a horizontal control group.A total of 84 students in French class and 4+4 class who were studying from September 2015 to June 2017 were selected as the longitudinal control group.Teaching satisfaction evaluation,examination results and specialization choice were compared among students in each group to assess teaching effectiveness.Results The total score(3.8±0.3)and satisfaction rate(98.9%)of the questionnaire in the pilot group were better than those in the horizontal control group(3.6±0.4,90.1%)(P=0.001,P=0.008).For the case analysis station in objective structured clinical examination(OSCE),the mean score(86.2±6.9)and pass rate(97.9%)in the pilot group were better than those in the horizontal control group(79.7±11.4,89.0%)(P=0.001,P=0.014),as well as better than those in the longitudinal control group(79.5±13.5,88.1%)(P=0.001,P=0.009).For the history inquiry station,the mean score(86.3±10.7)and pass rate(96.8%)in the pilot group were better than those in the horizontal control group(81.4±11.6,86.8%)(P=0.003,P=0.013).The proportion of students choosing the surgical specialty was higher in the pilot group(55.3%)than in the horizontal control group(46.2%)and the longitudinal control group(44.0%)without statistically significant difference.Conclusions SIC can help eight-year program students strengthen their clinical thinking and practice skills.Meanwhile,SIC can increase students'satisfaction with teaching and their interest in surgery.

ObjectiveTo explore the risk of different levels of pre-pregnancy obesity on trimester-specific thyroid dysfunction. MethodsQuestionnaire information， blood samples， and urine samples from a 2017 pregnancy cohort study in Shanghai， China were collected. A total of 2 455 pregnant women were included in the analysis. Pre-pregnancy BMI was calculated based on the height and self-reported pre-pregnancy weight. Serum TSH， total thyroxine （TT4）， free thyroxine （FT4）， total triiodothyronine （TT3）， free triiodothyronine （FT3）， thyroid globulin antibody（TgAb）， and Thyroid peroxidase antibody （TPOAb） were measured using the electrochemiluminescence method. Urine iodine levels were measured using the acid digestion method. Levels of thyroid function indexes of pregnant women with different degrees of obesity during pre-pregnancy were compared， and trimester-specific thyroid dysfunction was evaluated according to the reference range of trimester-specific thyroid hormone established by this cohort. Multivariate logistic regressions analysis was used to assess the correlation between pre-pregnancy obesity and trimester-specific thyroid dysfunction. ResultsAs the degree of obesity increased， maternal levels of FT3 and TT3 gradually increased during pregnancy （P<0.001， P=0.001）， while FT4 levels gradually decreased （P=0.001）. Multivariate logistic regression analysis showed that compared with the normal weight group， pregnant women who were overweight or obesity before pregnancy had a significantly higher risk of hypothyroxinemia （OR=3.85， 95%CI： 2.08‒7.14， P<0.001） and high TT3 （OR=2.78， 95%CI： 1.45‒5.26， P=0.002） during pregnancy. ConclusionPre-pregnancy overweight or obesity can increase the risk of thyroid dysfunction during pregnancy.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.