Objective In this study,we investigated the correlation between the scores for different Liebowitz Social Anxiety Scale(LSAS)subscale models and the metabolic activity in specific regions of the brain using 18F-fluorodeoxyglucose(FDG)positron emission tomography/computed tomography(PET/CT)(18F-FDG PET),thereby improving the understanding of the neurobiological characteristics of social anxiety.Methods A total of 39 cognitively normal participants(29 men and 10 women,aged 30-63 years)were enrolled.All participants underwent LSAS assessment and brain 18F-FDG PET scanning.Correlations between metabolic activities in various brain regions and scores from the different LSAS subscales were analyzed accordingly.Results LSAS subscale scores were significantly correlated with metabolic activity in specific brain regions.In the Safren model,the score for the observation by others subscale was positively correlated with the left fusiform gyrus(P<0.001,false discovery rate[FDR]-corrected)and the left caudate tail(P<0.001,FDR-corrected),suggesting a close association between mood states related to observation by others and the metabolic activity in these regions.In the Baker model,the score for the eating and drinking subscale was negatively correlated with the right precuneus(P<0.001,FDR-corrected),while the score for the assertiveness subscale was positively correlated with the left caudate nucleus(P<0.001,FDR-corrected).These findings revealed the complex associative patterns between various mood and behavioral dimensions and metabolic activities in specific brain regions.Conclusion Social anxiety symptoms are closely associated with metabolic changes in specific brain regions,including the left insula,left caudate tail,and right precuneus.Moreover,different social situations activate distinct brain regions.Compared with individuals with social anxiety disorder,normal individuals exhibit involvement of fewer brain regions when experiencing social anxiety.These findings provide new experimental evidence for understanding the neural mechanisms underlying social anxiety.

Objective·To explore the value of combined diaphragm and intercostal muscle ultrasound assessment compared with conventional diaphragm ultrasound in predicting the weaning outcome in mechanically ventilated patients with sepsis.Methods·Mechanically ventilated patients with sepsis,consecutively admitted to the Department of Critical Care Medicine of Affiliated Hospital of Nantong University from October 2022 to December 2023,were selected.During the peri-weaning period,after the patient's sepsis condition improved and the patient passed the spontaneous breathing trial(SBT),ultrasound evaluation of respiratory muscles was performed by ultrasound qualified personnel with ultrasound qualification and experience in bedside ultrasound examination.Diaphragm excursion(DE),thickening fraction of diaphragm(TFD),and thickening fraction of intercostal muscle(TFic)were measured,respectively.The patients were divided into a successful weaning group(n=114)and a failed weaning group(n=24)according to the weaning results.Receiver operating characteristic(ROC)curves were used to analyze the value of diaphragm ultrasound and intercostal muscle ultrasound,alone and in combination,in predicting ventilator weaning outcome.Results·TFic and TFic/TFD were significantly higher in the failed weaning group during SBT than in the successful weaning group(all P<0.05).The areas under the ROC curve(AUROC)of DE,TFD,and TFic to predict weaning failure in mechanically ventilated patients with sepsis during the period of SBT were 0.689(0.591?0.776),0.657(0.557?0.747),and 0.769(0.676?0.846),respectively,whereas the combined indexes TFic/TFD and TFic&TFD_mix had AUROCs of 0.867(0.786?0.925)and 0.860(0.778?0.920),respectively.TFic/TFD with a cutoff value of>0.95 had a sensitivity of 86.7%and a specificity of 75.3%in predicting weaning failure,and TFic&TFD_mix with a cutoff value of>0.13 had a sensitivity of 86.6%and a specificity of 80.9%in predicting weaning failure.Moreover,the intercostal muscle ultrasonography method had an intra-observer intraclass correlation coefficient(ICC)of 0.890 and an extra-observer ICC of 0.876 for measurement reliability,which were both rated as good(P<0.001).Conclusion·Combined diaphragm and intercostal muscle ultrasonography provides a more comprehensive picture of the patient's overall respiratory muscles,and has a higher guiding value in predicting the weaning outcomes in mechanically ventilated patients with sepsis than diaphragm ultrasound alone.

Objective The objective of this study was to investigate the effects of maytansine on proliferation,migration,in-vasion,apoptosis and autophagy of human thyroid cancer C643 cells.Methods C643 cells were treated with different concentrations(0.049,0.195,0.781,3.125,12.5,50 and 200 μmol/L)of maytansine,the effect of maytansine on the proliferation of C643 cells was detected by the sulforhodamine B(SRB)method,and the concentration of subsequent experiments was determined.C643 cells in the logarithmic growth stage period were divided into the control group,low-dose group,mid-dose group and high-dose group.The effects of maytansine on migration and invasion abilities of C643 cells were detected by cell scratch and Transwell chamber assay;The levels of reactive oxygen species(ROS)were detected by 2′,7′-dichlorofluorescein diacetate(DCFH-DA)fluorescent probe experi-ment;The apoptosis rate of C643 cells was detected by flow cytometry;The expression of proteins related to apoptosis or autophagy was detected by Western blot.Results Maytansine at concentrations of 0.049,0.195,0.781,3.125,12.5,50 and 200 μmol/L could in-hibit the proliferation of C643 cells(P<0.05),and exhibited a significant concentration time dependence.The half maximal inhibitory concentrations(IC50)at 24,48 and 72 h were 54.255,5.193 and 0.647 μmol/L,respectively;The cell scratch and Transwell chamber results showed that maytansine at concentrations of 0.1,1 and 10 μmol/L could reduce the migration and invasion abilities of C643 cells(P<0.05 and P<0.01).The fluorescence probe results showed that maytansine at concentrations of 0.1,1 and 10μmol/L could increase the intracellular ROS levels of C643 cells(P<0.01).The flow cytometry results showed that maytansine at concentrations of 0.1,1 and 10 μmol/L could concentration dependently increase the apoptosis rate of C643 cells(P<0.01).The Western blot results showed that with the increase of maytansine concentrations,the expression of Bax protein related to apoptosis in C643 cells increased(P<0.05),the expression of Bcl-2 decreased(P<0.05),the expression of LC3Ⅱ/Ⅰ(P<0.05)and Beclin-1(P<0.01)increased,while the expression of p62 decreased(P<0.001).Conclusion Maytansine can inhibit the proliferation,migration and invasion of human thyroid cancer C643 cells,and induce the synergistic effect on apoptosis and autophagy by increasing intracellular ROS levels.

Objective·To explore the value of combined diaphragm and intercostal muscle ultrasound assessment compared with conventional diaphragm ultrasound in predicting the weaning outcome in mechanically ventilated patients with sepsis.Methods·Mechanically ventilated patients with sepsis,consecutively admitted to the Department of Critical Care Medicine of Affiliated Hospital of Nantong University from October 2022 to December 2023,were selected.During the peri-weaning period,after the patient's sepsis condition improved and the patient passed the spontaneous breathing trial(SBT),ultrasound evaluation of respiratory muscles was performed by ultrasound qualified personnel with ultrasound qualification and experience in bedside ultrasound examination.Diaphragm excursion(DE),thickening fraction of diaphragm(TFD),and thickening fraction of intercostal muscle(TFic)were measured,respectively.The patients were divided into a successful weaning group(n=114)and a failed weaning group(n=24)according to the weaning results.Receiver operating characteristic(ROC)curves were used to analyze the value of diaphragm ultrasound and intercostal muscle ultrasound,alone and in combination,in predicting ventilator weaning outcome.Results·TFic and TFic/TFD were significantly higher in the failed weaning group during SBT than in the successful weaning group(all P<0.05).The areas under the ROC curve(AUROC)of DE,TFD,and TFic to predict weaning failure in mechanically ventilated patients with sepsis during the period of SBT were 0.689(0.591?0.776),0.657(0.557?0.747),and 0.769(0.676?0.846),respectively,whereas the combined indexes TFic/TFD and TFic&TFD_mix had AUROCs of 0.867(0.786?0.925)and 0.860(0.778?0.920),respectively.TFic/TFD with a cutoff value of>0.95 had a sensitivity of 86.7%and a specificity of 75.3%in predicting weaning failure,and TFic&TFD_mix with a cutoff value of>0.13 had a sensitivity of 86.6%and a specificity of 80.9%in predicting weaning failure.Moreover,the intercostal muscle ultrasonography method had an intra-observer intraclass correlation coefficient(ICC)of 0.890 and an extra-observer ICC of 0.876 for measurement reliability,which were both rated as good(P<0.001).Conclusion·Combined diaphragm and intercostal muscle ultrasonography provides a more comprehensive picture of the patient's overall respiratory muscles,and has a higher guiding value in predicting the weaning outcomes in mechanically ventilated patients with sepsis than diaphragm ultrasound alone.

Objective The objective of this study was to investigate the effects of maytansine on proliferation,migration,in-vasion,apoptosis and autophagy of human thyroid cancer C643 cells.Methods C643 cells were treated with different concentrations(0.049,0.195,0.781,3.125,12.5,50 and 200 μmol/L)of maytansine,the effect of maytansine on the proliferation of C643 cells was detected by the sulforhodamine B(SRB)method,and the concentration of subsequent experiments was determined.C643 cells in the logarithmic growth stage period were divided into the control group,low-dose group,mid-dose group and high-dose group.The effects of maytansine on migration and invasion abilities of C643 cells were detected by cell scratch and Transwell chamber assay;The levels of reactive oxygen species(ROS)were detected by 2′,7′-dichlorofluorescein diacetate(DCFH-DA)fluorescent probe experi-ment;The apoptosis rate of C643 cells was detected by flow cytometry;The expression of proteins related to apoptosis or autophagy was detected by Western blot.Results Maytansine at concentrations of 0.049,0.195,0.781,3.125,12.5,50 and 200 μmol/L could in-hibit the proliferation of C643 cells(P<0.05),and exhibited a significant concentration time dependence.The half maximal inhibitory concentrations(IC50)at 24,48 and 72 h were 54.255,5.193 and 0.647 μmol/L,respectively;The cell scratch and Transwell chamber results showed that maytansine at concentrations of 0.1,1 and 10 μmol/L could reduce the migration and invasion abilities of C643 cells(P<0.05 and P<0.01).The fluorescence probe results showed that maytansine at concentrations of 0.1,1 and 10μmol/L could increase the intracellular ROS levels of C643 cells(P<0.01).The flow cytometry results showed that maytansine at concentrations of 0.1,1 and 10 μmol/L could concentration dependently increase the apoptosis rate of C643 cells(P<0.01).The Western blot results showed that with the increase of maytansine concentrations,the expression of Bax protein related to apoptosis in C643 cells increased(P<0.05),the expression of Bcl-2 decreased(P<0.05),the expression of LC3Ⅱ/Ⅰ(P<0.05)and Beclin-1(P<0.01)increased,while the expression of p62 decreased(P<0.001).Conclusion Maytansine can inhibit the proliferation,migration and invasion of human thyroid cancer C643 cells,and induce the synergistic effect on apoptosis and autophagy by increasing intracellular ROS levels.

OBJECTIVE Based on the G protein-coupled bile acid receptor(TGR5)/nucleotide binding oligomerization domain-like receptor 3(NLRP3) signaling pathway, to explore the mechanism of Huoxue Qingjieling in improving the inflammatory response of rats with nonalcoholic steatohepatitis(NASH). METHODS A total of 70 male SD rats were randomly divided into 5 groups, 20 rats in the control group, 20 rats in the model group, 10 rats in each of the atorvastatin positive drug group, the high-dose and low-dose groups of Huoxue Qingjieling. The control group was given normal feed, and the rest of the groups were given high-fat diet. Through model evaluation, it was determined that the NASH rat model was successfully established at the end of the 20th week. After successful modeling, the control group and the model group were given with normal saline by intragastric administration, the atorvastatin positive drug group, and the high and low dose groups of Huoxue Qingjieling were given corresponding drugs once a day for 4 weeks. At the end of the 24th week, the rats were killed, and the changes of body weight, wet liver weight and liver index was calculated. The serum was taken to test the triglyceride(TG), total cholesterol(TC), alanine aminotransferase(ALT), and aspartic acid aminotransferase(AST) levels by automatic biochemical analyzer. Pathological changes of liver tissues were observed by HE staining and oil red O staining. The expression levels of TGR5 and NLRP3 proteins were detected by Western blotting and immunofluorescence staining. ELISA detected the content of interleukin-18(IL-18) and interleukin-1β(IL-1β) in liver tissue. RESULTS Huoxue Qingjieling could significantly improve the general state of NASH rats. Every dose group could significantly reduce the body weight, liver wet weight and liver index of rats(P<0.01), and TG, TC content and ALT, AST activity levels of serum significantly decreased(P<0.01). The pathological results showed that Huoxue Qingjieling could significantly improve liver steatosis, inflammation and balloon-like. The expression of TGR5 protein was significantly increased(P<0.01), the expression of NLRP3 protein and the content of IL-18, IL-1β were significantly decreased(P<0.01, P<0.05). CONCLUSION Huoxue Qingjieling can significantly improve the state of NASH rats, inhibit liver steatosis and inflammation, and its mechanism may be closely related to the inhibition of TGR5/NLRP3 signaling pathway.

Objective:To investigate the mid-to-long term therapeutic effects of allogeneic bone composite prosthesis reconstruction in patients with large bone defects after the resection of distal femoral tumors.Methods:From June 2013 to December 2018, a total of 19 patients with malignant tumors of the distal femur who underwent reconstruction with allogeneic bone composite prosthesis in the Department of Bone Tumor, Shanghai General Hospital were retrospectively collected. There were 10 males and 9 females, aged 22.3±11 years (range, 11-42 years). The mean body mass index was 19.3±3.4 kg/m 2 (range, 14-27 kg/m 2). There were 18 cases of osteosarcoma and 1 case of Ewing's sarcoma. According to Ennecking staging, there were 17 cases of stage IIB and 2 cases of stage III. The intraoperative blood loss and operation time were recorded, and the prosthesis and patient survival conditions and postoperative complications were observed. The limb function was evaluated by the Musculoskeletal Tumor Society (MSTS) 93 function score. Results:All patients successfully completed the operation. The operation time was 187.3±39.8 min (range, 110-260 min), the intraoperative blood loss was 284.9±87.0 ml (range, 200-500 ml), and the blood transfusion volume was 327±213 ml (range, 100-800 ml). The remaining length of the proximal femur was 153.7±26.6 mm (range, 93-190 mm), and the length of allogeneic bone was 84.1±24.6 mm (range, 39-134 mm). Among the 19 patients, 9 patients (47%) achieved bony union with an average healing time of 16.7±4.8 months (range, 10-25 months), and 7 patients had delayed healing with an average healing time of 18.4±4.0 months (range, 15-25 months). The remaining 10 cases were nonunion between allogeneic bone and host bone. All patients were followed up for 80.7±20.2 months (range, 56-121 months). During the follow-up, 3 cases died due to pulmonary metastasis of bone tumors, and the time of death was 57 months, 63 months, and 59 months after surgery, respectively. At the last follow-up, the patient survival rate was 84% (16/19), and the MSTS 93 function score of the 16 patients was (24.3±2.4) points (range, 21-28 points), with an excellent rate of 100% (16/16). Seven patients underwent revision surgery, 3 cases were aseptic loosening, 3 cases were prosthesis stem fracture at the junction of the allograft bone and the host bone, and 1 case was periprosthetic infection, among which the patient with periprosthetic infection had poor local soft tissue conditions due to preoperative radiotherapy, and the infection was controlled after two revision surgeries. Five cases were revised with allogeneic bone composite prosthesis, and 2 cases were revised with short-stem giant prosthesis with cortical steel plate or locking nail. After revision, the remaining length of the proximal femur was 143.4±31 mm (range, 91-175 mm), and the length of the allograft bone was 92.6±26.6 mm (range, 61-123 mm). The 7 revised patients were still in follow-up. There were no cases of pulmonary infection, nerve injury, deep vein thrombosis or other complications after surgery.Conclusion:The survival period of patients after the surgery to reconstruct large bone defects following the resection of malignant tumors at the distal end of the femur using allogeneic bone composite prosthesis is satisfactory, and the limb function is good. However, the incidence of prosthesis complications is high, which can be reconstructed through revision.

Based on the pathogenesis of “tendon off-position and joint subluxation”， combined with modern ana-tomy and biomechanics， the characteristic manifestations of “tendon off-position” and “joint subluxation” of the knee and the intrinsic connection between them are clarified. Through sorting out the relationship between “tendon off-position and joint subluxation” and knee osteoarthritis （KOA） in modern research， it is believed that “tendon off-position and joint subluxation” is the key mechanism for the occurrence and development of KOA， and accordingly， it is proposed to take the diet as the guide， use bone manipulation for external diagnosis and treatment， use traditional Chinese medicine decoction for internal treatment， and use Daoyin exercise throughout the whole process as the strategy for KOA's comprehensive traditional Chinese medicine treatment to improve the clinical effectiveness.

OBJECTIVE To explore the mechanism of Xiaoyaosan in improving the abnormal glucose metabolism in chronic sleep deprivation(CSD) mice based on tyrosine hydroxylase/alpha-2a adrenergic receptor(TH/ADRA2A) signal pathway. METHODS Fifty six-week-old male C57BL/6 mice were randomly divided into two groups: 10 in the control group and 40 in the model group. The rats in the model group were deprived of sleep for 4 weeks by the method of multi-platform water environment. Fasting plasma glucose(FPG) and body mass were measured once a week for three consecutive weeks. Then, according to FPG, they were randomly divided into four groups, namely model group, guanethidine group(30 mg·kg-1·d-1) and Xiaoyaosan low and high dose groups(33.88, 101.64 g·kg-1·d-1). After grouping, continue modeling for a week. Then the drug was administered for 4 weeks. The control group and model group were treated with pure water of the same volume. Modeling continued during the administration period. On the 53rd day, blood was collected from the tail vein for the glucose tolerance test. On the 56th day, the expression of insulin(INS), noradrenaline(NE) and corticosterone(CORT) in serum was detected by ELISA. HE staining was used to observe the pathological changes of pancreatic islets. Detection of co expression of TH and INS in pancreatic tissues by immunofluorescence staining. Real-time PCR and Western blotting were used to detect the expression of ADRA2A mRNA and protein in the pancreas. RESULTS In the process of CSD modeling, compared with the initial body mass, the body mass of the model group mice decreased significantly at the end of the first week of modeling(P<0.05), and FPG increased significantly(P<0.01). After administration, compared with the control group, the glucose tolerance of the model group was significantly abnormal. The levels of NE, CORT and INS increased significantly(P<0.01), the expression level of ADRA2A mRNA and protein in the pancreas was significantly increased(P<0.01). Compared with the model group, Xiaoyaosan groups had better glucose tolerance, the levels of NE, CORT and INS decreased significantly(P<0.05), and the expression of ADRA2A mRNA and protein in the pancreas decreased significantly(P<0.05 or P<0.01). HE staining results showed that the number of cells in the islets of the model group was significantly reduced compared with the control group, and the situation was improved in all drug groups. The results of immunofluorescence staining showed that the protein content of TH in the model group increased, and the expression of TH in each group decreased after administration. CONCLUSION Xiaoyaosan can improve the abnormal glucose metabolism induced by CSD, and its mechanism may be related to the reduction of TH/ADRA2A expression.

Objective:To explore the construction and application methods of multicenter bone tumor-specific database.Methods:Experts from multiple centers including Shanghai General Hospital, Shanghai Changzheng Hospital, Zhongshan Hospital, Shanghai Sixth People's Hospital, Ruijin Hospital, Fudan University Shanghai Cancer Center and Shanghai Ninth People's Hospital established a standard dataset for bone tumors through research and discussion. Clinical data will be automatically collected and standardized according to standard fields. A database will be built and a users' interface will be developed to ensure secure data storage, while providing services such as exporting raw data, visualizing statistical analysis, establishing clinical queue research projects, et al. Finally, the bone tumor database will be shared by integrating with the Shenkang's Big Data Platform to achieve multi-center data integration.Results:A standard data set for bone tumors containing 603 fields has been established and published. An automated data collection system for bone tumors has been established, including complete data collection, data collation and visualization functions. The data categories include modules such as patients' electronic case information, laboratory information on blood routine, biochemistry and tumor markers, imaging information, surgery information, pathology information and radiotherapy records. Personal information such as patients' names and ID numbers are desensitized and encrypted and can be exported for further research. From 2015 to 2023, the total number of bone tumor cases collected in the database was 10,789. From 2015 to 2019, 112 cases of the osteosarcoma cohort were retrospectively analyzed for admission, with a statistical 5-year survival rate of 68%.Conclusion:A regional bone tumor specialty big data network and data sharing platform has been established, along with data sharing mechanisms and standards including data standards, security standards, and quality evaluation standards. This provides data and efficient new solutions for the construction of China's bone tumor database, as well as a research and development platform for standardized diagnosis and treatment of bone tumors and new technologies.