Objective:To investigate the value of an MRI and digital pathology images based omics nomogram for the prediction of recurrence risk in soft tissue sarcoma (STS).Methods:This was a retrospective cohort study. From January 2016 to March 2021, 192 patients with STS confirmed by pathology in the Affiliated Hospital of Qingdao University were enrolled, among which 112 patients in the Laoshan campus were enrolled as training set, and 80 patients in the Shinan campus were enrolled as validation set. The patients were divided into recurrence group ( n=87) and no recurrence group ( n=105) during follow-up. The clinical and MRI features of patients were collected. The radiomics features based on fat saturated T 2WI images and pathomics features based on digital pathology images of the lesions were extracted respectively. The clinical model, radiomics model, pathomics model, radiomics-pathomics combined model, and omics nomogram which combined the optimal prediction model and the clinical model were established by multivariate Cox regression analysis. The concordance index (C index) and time-dependent area under the receiver operating characteristic curve (t-AUC) were used to evaluate the performance of each model in predicting STS postoperative recurrence. The DeLong test was used for comparison of t-AUC between every two models. The X-tile software was used to determine the cut-off value of the omics nomogram, then the patients were divided into low risk ( n=106), medium risk ( n=64), and high risk ( n=22) groups. Three groups′ cumulative recurrence-free survival (RFS) rates were calculated and compared by the Kaplan-Meier survival curve and log-rank test. Results:The performance of the radiomics-pathomics combined model was superior to the radiomics model and pathomics model, with C index of 0.727 (95% CI 0.632-0.823) and medium t-AUC value of 0.737 (95% CI0.584-0.891) in the validation set. The omics nomogram was established by combining the clinical model and the radiomics-pathomics combined model, with C index of 0.763 (95% CI 0.685-0.842) and medium t-AUC value of 0.783 (95% CI0.639-0.927) in the validation set. The t-AUC value of omics nomogram was significantly higher than that of clinical model, TNM model, radiomics model, and pathomics model in the validation set ( Z=3.33, 2.18, 2.08, 2.72, P=0.001, 0.029, 0.037, 0.007). There was no statistical difference in t-AUC between the omics nomogram and radiomics-pathomics combined model ( Z=0.70, P=0.487). In the validation set, the 1-year RFS rates of STS patients in the low, medium, and high recurrence risk groups were 92.0% (95% CI 81.5%-100%), 55.9% (95% CI 40.8%-76.6%), and 37.5% (95% CI 15.3%-91.7%). In the training and validation sets, there were statistically significant in cumulative RFS rates among the low, medium, and high groups of STS patients (training set χ2=73.90, P<0.001; validation set χ2=18.70, P<0.001). Conclusion:The omics nomogram based on MRI and digital pathology images has favorable performance for the prediction of STS recurrence risk.

Objective To investigate the impact of type 2 inflammation markers blood eosinophils(EOS)and fractional exhaled nitric oxide(FeNO)on bronchodilator responsiveness(BDR)in patients with chronic obstructive pulmonary disease(COPD).Methods This study was conducted among 389 patients with an established diagnosis of COPD in our hospital from October,2019 to October,2023,who all underwent bronchial dilation test(BDT)of the large and small airways.Based on smoking history,blood EOS,and FeNO,these patients were divided group A(blood EOS<300/μL+FeNO<35 ppb+smoking history<20 pack-years),group B(blood EOS<300/μL+FeNO<35 ppb+smoking history≥20 pack-years),group C(blood EOS≥300/μL or FeNO≥35 ppb+smoking history≥20 pack-years),and group D(blood EOS≥300/μL or FeNO≥35 ppb+smoking history<20 pack-years)for analyzing the relationship between clinical indexes and BDR.Results BDR evaluation based on forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),and maximum mid-expiratory flow(MMEF)yielded consistent results,all showing a younger mean age,higher FeNO levels,and higher blood EOS counts and percentages in patients positive for BDT(P<0.05).The improvement value and improvement rate of FEV1 were significantly lower in group A than in group D.The improvement value and improvement rate of FEV1 as well as the improvement rate of MMEF were significantly lower in group B than in group D.In the overall patients,age and FeNO were significantly correlated with the improvement value and improvement rate of FEV1 and the improvement rate of MMEF(P<0.05).Conclusion Type 2 inflammation markers have different effects on BDR in the large and small airways of COPD patients,and their clinical significance needs further investigation.

Objective To investigate the impact of type 2 inflammation markers blood eosinophils(EOS)and fractional exhaled nitric oxide(FeNO)on bronchodilator responsiveness(BDR)in patients with chronic obstructive pulmonary disease(COPD).Methods This study was conducted among 389 patients with an established diagnosis of COPD in our hospital from October,2019 to October,2023,who all underwent bronchial dilation test(BDT)of the large and small airways.Based on smoking history,blood EOS,and FeNO,these patients were divided group A(blood EOS<300/μL+FeNO<35 ppb+smoking history<20 pack-years),group B(blood EOS<300/μL+FeNO<35 ppb+smoking history≥20 pack-years),group C(blood EOS≥300/μL or FeNO≥35 ppb+smoking history≥20 pack-years),and group D(blood EOS≥300/μL or FeNO≥35 ppb+smoking history<20 pack-years)for analyzing the relationship between clinical indexes and BDR.Results BDR evaluation based on forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),and maximum mid-expiratory flow(MMEF)yielded consistent results,all showing a younger mean age,higher FeNO levels,and higher blood EOS counts and percentages in patients positive for BDT(P<0.05).The improvement value and improvement rate of FEV1 were significantly lower in group A than in group D.The improvement value and improvement rate of FEV1 as well as the improvement rate of MMEF were significantly lower in group B than in group D.In the overall patients,age and FeNO were significantly correlated with the improvement value and improvement rate of FEV1 and the improvement rate of MMEF(P<0.05).Conclusion Type 2 inflammation markers have different effects on BDR in the large and small airways of COPD patients,and their clinical significance needs further investigation.

Background::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

Objective:To evaluate postoperative calcitonin level as a prognostic marker in long-term follow-up of medullary thyroid carcinoma(MTC).Methods:Clinical data of 146 MTC cases treated at Tianjin Medical University Cancer Institute and Hospital from Jan 2011 to Dec 2019 were reviewed retrospectively. The relationship between postoperative calcitonin and disease-free survival was analyzed. According to the level of calcitonin six months after operation, patients were divided into normal level group and elevated group.Results:The median tumor size in those 146 cases was (1.78±1.22)cm, and 81 cases had lymph node metastasis. After 6 months of follow-up, 89 cases had normal calcitonin, with median tumor size of (1.63±1.20)cm, and 35 cases had lymph node metastasis . After a median follow-up of 56 months, 78 patients had normal calcitonin, 11 patients had biochemical relapse, 3 patients had structural relapse, and no patients died. 57 cases had a higher calcitonin ,median tumor size (1.97±1.22)cm, 46 cases had lymph node metastasis, 5 cases had distant metastasis, 18 cases had structural recurrence, and 7 patients died. Univariate analysis showed that lymph node metastasis, TNM stage, preoperative calcitonin, lymph node dissection and postoperative calcitonin were correlated with long-term disease-free survival (all P < 0.05). Multivariate analysis showed that postoperative calcitonin and TNM stage were an independent prognosis factor for disease-free survival in MTC patients (all P < 0.05). Conclusion:Postoperative calcitonin is a independent prognostic marker for long-term disease-free survival in MTC patients.

The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.
Animals ; China ; Genomics ; Humans ; Male ; Pesticides ; Spodoptera/genetics* ; Transcriptome

Objective:To evaluate anatomical locking plate combined with bone cement intramedullary support in the treatment of proximal humeral fractures in the elderly.Methods:From May 2016 to July 2018, 19 geriatric proximal humeral fractures were treated with anatomical locking plate combined with bone cement intramedullary support at Department of Orthopaedics, General Hospital of Shenyang Northern Theater. There were 8 females and 5 males, with an average age of 71 years (from 60 to 84 years). All the fractures were closed. According to the Neer classification, there were 4 two-part, 5 three-part and 4 four-part fractures. At 6, 12, 18 and 36 weeks and one year postoperatively, anteroposterior and lateral X-ray films of the scapula were taken. At the last follow-up, the Constant-Murley shoulder score and the Disabilities of the Arm, Shoulder and Hand (DASH) score for the upper limb dysfunction were recorded.Results:The 13 patients were followed up for 3 to 12 months (6 months on average). Bony union was achieved in all the 13 patients. Local necrosis and deformation of the humeral head and partial screw perforation were observed one year after operation in 2 cases, but other patients reported no such complications or loosening of internal fixation. At the last follow-up, their mean Constant-Murley score was 82.6 (from 71 to 95) and their mean ADSH score 19.2 (from 9.2 to 48.1).Conclusion:Anatomical locking plate combined with bone cement intramedullary support may lead to fine early efficacy for the treatment of proximal humeral fractures in the elderly, since it can facilitate fracture reduction, promote rigid fixation and prevent loss of reduction.

To investigate the effects of on behavior and blood brain barrier (BBB) in Alzheimer's disease mice. Thirty-eight 4-month-old APP/PS1 double transgenic mice were randomly divided into three groups: model group, low-dose group and high-dose group. Saline, and 12 g·kg·d were given to each group by continuous gavage once a day for respectively. The changes in activities of daily live and fear conditioning memory behavior of mice were examined by nesting behavior test and fear conditioning test, respectively. The β-amyloid protein (Aβ) depositions in cortex and hippocampal CA1 area of mice were detected by thioflavin T staining. The CD34 and activities fibrinogen (Fib) immunofluorescence double staining were used to determine the vascular endothelial integrity and BBB exudation. Compared with model mice, activities of daily live were significantly improved in low-dose and high-dose groups (both <0.01), the fear memory ability was significantly increased in high-dose group (<0.01). The amount of Aβ deposition in cortex and hippocampal CA1 decreased significantly in high-dose group, the area ratio decreased significantly; the area ratio of Aβ deposition in hippocampal CA1 region in low-dose group also decreased (all <0.05). The proportions of CD34 positive area of cortex in low and high dose groups increased, the percentage of fibrinogen positive area decreased (all <0.05). The proportion of CD34 positive area in hippocampal CA1 region in high-dose group was significantly increased, the percentage of fibrinogen positive area decreased significantly (both <0.05). especially high-dose can improve the activities of daily live and fear conditioning memory function of APP/PS1 mice, reduce the deposition of Aβ in brain. The mechanism may be related to the reduction of BBB permeability and the protection of the integrity of BBB.
Alzheimer Disease ; Amyloid beta-Protein Precursor ; Animals ; Blood-Brain Barrier/metabolism* ; Disease Models, Animal ; Hippocampus/metabolism* ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic

Objective:To determine the therapeutic effect of in vitro cultivation of bezoar on a mouse model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. Method:BALB/c mice were randomly divided into six groups according to their weight grade： normal group， HCoV-229E infection group， cold and damp group， a mouse model combining disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome， and high and low dose group of in vitro cultivation of bezoar. The combination model of human coronavirus pneumonia with Yidu Xifei syndrome mice was established by the method of cold dampness condition stimulation+coronavirus HCoV-229E infection. In vitro cultivation of bezoar （0.128，0.064 g·kg^-1） was administrated by gavage for 3 days from the day of infection. The observation indexes included： general state observation of mice， inhibition rate of lung index and lung index of mice. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in the lung tissues of mice. Serum levels of motilin（MTL）， gastrin （GAS）， and cytokines interleukin（IL）-10，IL-6， tumor necrosis factor-α（TNF-α）and interferon-γ（IFN-γ） in lung tissue of mice were determined by enzyme-linked immunosorbent assay（ELISA）. The percentages of CD4⁺ T lymphocytes，CD8⁺ T lymphocytes and B lymphocytes in the blood of mice were determined by flow cytometry. Result:The high and low dose group of in vitro cultivation of bezoar can significantly improve the general condition of model mice. Compared with blank group， model group mice lung index increased significantly （P<0.01）， nucleic acids significantly increased expression of lung tissue in mice （P<0.01）， significantly higher serum MTL content in mice， GAS content significantly decreased （P<0.05，P<0.01）， lung tissue cells in the immune factor TNF-α， IL-10 and IL-6 were significantly increased （P<0.01）， peripheral blood lymphocyte CD4⁺ T cells in mice， The percentages of CD8⁺ T cells and B cells were significantly decreased （P<0.01）. Compared with model group， in vitro cultivation bezoar mice lung index of high and low dose group were significantly lower （P<0.01）， the lung tissue of mice express nucleic acid decreased significantly （P<0.01）， MTL content decreased significantly （P<0.01）， the lung tissue of mice in the IL-6， IL-10， the TNF-α， IFN-γ levels were significantly lower （P<0.01）， in vitro cultivation bezoar high dose group can significantly increase the CD4⁺ T cell percentage （P<0.05）， in vitro cultivation bezoar can to a certain extent reduce model mice lung inflammatory exudation， pulmonary interstitial edema， as well as blood stasis symptoms. Conclusion:In vitro cultivation of bezoar has a significant therapeutic effect on a mice model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. It can be treated by reducing the lung index of the model mice， improving the pathological damage of the lung tissue， adjusting the immune effective and inhibiting the clearing of inflammatory factors， and to provide a laboratory basis for clinical medication.