Artificial intelligence-based computer-aided diagnosis system supports diagnosis of lymph node metastasis in esophageal squamous cell carcinoma: A multicenter study.

Background: This study aimed to develop an artificial intelligence-based computer-aided diagnosis system (AI-CAD) emulating the diagnostic logic of radiologists for lymph node metastasis (LNM) in esophageal squamous cell carcinoma (ESCC) patients, which contributed to clinical treatment decision-making. Methods: A total of 689 ESCC patients with PET/CT images were enrolled from three hospitals and divided into a training cohort and two external validation cohorts. 452 CT images from three publicly available datasets were also included for pretraining the model. Anatomic information from CT images was first obtained automatically using a U-Net-based multi-organ segmentation model, and metabolic information from PET images was subsequently extracted using a gradient-based approach. AI-CAD was developed in the training cohort and externally validated in two validation cohorts. Results: The AI-CAD achieved an accuracy of 0.744 for predicting pathological LNM in the external cohort and a good agreement with a human expert in two external validation cohorts (kappa = 0.674 and 0.587, p < 0.001). With the aid of AI-CAD, the human expert's diagnostic performance for LNM was significantly improved (accuracy [95% confidence interval]: 0.712 [0.669-0.758] vs. 0.833 [0.797-0.865], specificity [95% confidence interval]: 0.697 [0.636-0.753] vs. 0.891 [0.851-0.928]; p < 0.001) among patients underwent lymphadenectomy in the external validation cohorts. Conclusions: The AI-CAD could aid in preoperative diagnosis of LNM in ESCC patients and thereby support clinical treatment decision-making.

CT-based radiomics to predict development of macrovascular invasion in hepatocellular carcinoma: A multicenter study.

BACKGROUND: Macrovascular invasion (MaVI) occurs in nearly half of hepatocellular carcinoma (HCC) patients at diagnosis or during follow-up, which causes severe disease deterioration, and limits the possibility of surgical approaches. This study aimed to investigate whether computed tomography (CT)-based radiomics analysis could help predict development of MaVI in HCC. METHODS: A cohort of 226 patients diagnosed with HCC was enrolled from 5 hospitals with complete MaVI and prognosis follow-ups. CT-based radiomics signature was built via multi-strategy machine learning methods. Afterwards, MaVI-related clinical factors and radiomics signature were integrated to construct the final prediction model (CRIM, clinical-radiomics integrated model) via random forest modeling. Cox-regression analysis was used to select independent risk factors to predict the time of MaVI development. Kaplan-Meier analysis was conducted to stratify patients according to the time of MaVI development, progression-free survival (PFS), and overall survival (OS) based on the selected risk factors. RESULTS: The radiomics signature showed significant improvement for MaVI prediction compared with conventional clinical/radiological predictors (P < 0.001). CRIM could predict MaVI with satisfactory areas under the curve (AUC) of 0.986 and 0.979 in the training (n = 154) and external validation (n = 72) datasets, respectively. CRIM presented with excellent generalization with AUC of 0.956, 1.000, and 1.000 in each external cohort that accepted disparate CT scanning protocol/manufactory. Peel9_fos_InterquartileRange [hazard ratio (HR) = 1.98; P < 0.001] was selected as the independent risk factor. The cox-regression model successfully stratified patients into the high-risk and low-risk groups regarding the time of MaVI development (P < 0.001), PFS (P < 0.001) and OS (P = 0.002). CONCLUSIONS: The CT-based quantitative radiomics analysis could enable high accuracy prediction of subsequent MaVI development in HCC with prognostic implications.

Seven cases of toxic encephalopathy associated with diquat poisoning / 中华急诊医学杂志

Objective:To improve the understanding of the clinical features of toxic encephalopathy associated with diquat poisoning.Methods:This study collected and analyzed the diagnosis and treatment process of 7 patients with acute diquat poisoning combined with central nervous system complications admitted to the First Affiliated Hospital of Zhengzhou University from April 2021 to April 2022. "Diquat" and "Poisoning" were used as keywords to search in CNKI, Wanfang database and PubMed database, and the literature of previous cases was reviewed for summary analysis.Results:Among the 7 patients in our hospital, there were 2 males and 5 females, with an average age of 31 years (range14-57) and an average dose of 23.14 g [(10-40)g]. During the treatment, 3 patients developed irritability and convulsions, 3 patients occurred coma, and one had generalized tonic-clonic seizures. Four patients died and 3 survived, of which 2 patients returned to normal life and study, and one remained abnormal mental behavior (currently in long-term follow-up). All three survivors developed neurological symptoms later than those who died, and were awake about 30 days after taking the drug.Conclusions:Toxic encephalopathy associated with diquat poisoning has rapid progression, poor prognosis and high mortality. This study found that the survival rate of patients with > 48 h of first onset of neurological symptoms is much higher than that of patients with ≤ 48 h of first onset of neurological symptoms, while sex, age, estimated oral dose, and type of presentation of neurological symptoms for the first time have little effect on the survival rate of hospital discharge. The earlier neurological symptoms appear, the greater the likelihood of a poor prognosis.

Optimization of β-globin Stable Expression Using the Third Generation Lentiviral Vector for β-thalassemia Therapy / 中国实验血液学杂志

OBJECTIVE@#To provide a research basis for a safe and effective cell therapy for β-thalassemia through optimization of HS4 region of the third generation lentiviral vector for stable expression of β-globin.@*METHODS@#The human β-globin HS4 region in the third generation lentiviral expression vector was optimized to construct the lenti-HBB, and the transcription and translation of β-globin gene were analyzed by RT-PCR and Western blot after the transduction of lenti-HBB in MEL cell line. Furthermore, the erythroid differentiation of CD34+ cells which were transduced lentiviral virus carrying human β-globin from normal human umbilical cord blood cells and peripheral blood cells of patients with β-thalassemia major were confirmed by colony formation assay, cell smear assay and flow cytometry. The safety and effectiveness of the optimized lenti-HBB were verified by NSG mouse in vivo test.@*RESULTS@#The human β-globin was expressed stably in the MEL cells, and CD34+ cells from health umbilical cord blood as well as PBMC from patient with β-thalassemia major transduced with lenti-HBB could be differentiated to mature red blood cells. The β-globin expression and differentiation in CD34+ cells were demonstrated successfully in the NSG mouse for about 35 months after post-transplant.@*CONCLUSION@#Stable β-globin expression through the optimization of HS4 from CD34+ in the third generation lentiviral vector is safe and effective for patients with severe β-thalassemia and other β-globin abnormal diseases.

A radiomics nomogram may improve the prediction of IDH genotype for astrocytoma before surgery.

OBJECTIVES: To develop and validate a radiomics nomogram to preoperative prediction of isocitrate dehydrogenase (IDH) genotype for astrocytomas, which might contribute to the pretreatment decision-making and prognosis evaluating. METHODS: One hundred five astrocytomas (Grades II-IV) with contrast-enhanced T1-weighted imaging (CE-T1WI), T2 fluid-attenuated inversion recovery (T2FLAIR), and apparent diffusion coefficient (ADC) map were enrolled in this study (training cohort: n = 74; validation cohort: n = 31). IDH1/2 genotypes were determined using Sanger sequencing. A total of 3882 radiomics features were extracted. Support vector machine algorithm was used to build the radiomics signature on the training cohort. Incorporating radiomics signature and clinico-radiological risk factors, the radiomics nomogram was developed. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess these models. Kaplan-Meier survival analysis and log rank test were performed to assess the prognostic value of the radiomics nomogram. RESULTS: The radiomics signature was built by six selected radiomics features and yielded AUC values of 0.901 and 0.888 in the training and validation cohorts. The radiomics nomogram based on the radiomics signature and age performed better than the clinico-radiological model (training cohort, AUC = 0.913 and 0.817; validation cohort, AUC = 0.900 and 0.804). Additionally, the survival analysis showed that prognostic values of the radiomics nomogram and IDH genotype were similar (log rank test, p < 0.001; C-index = 0.762 and 0.687; z-score test, p = 0.062). CONCLUSIONS: The radiomics nomogram might be a useful supporting tool for the preoperative prediction of IDH genotype for astrocytoma, which could aid pretreatment decision-making. KEY POINTS: • The radiomics signature based on multiparametric and multiregional MRI images could predict IDH genotype of Grades II-IV astrocytomas. • The radiomics nomogram performed better than the clinico-radiological model, and it might be an easy-to-use supporting tool for IDH genotype prediction. • The prognostic value of the radiomics nomogram was similar with that of the IDH genotype, which might contribute to prognosis evaluating.

Process of immunogenic cell death caused by disulfiram as the anti-colorectal cancer candidate.

BACKGROUND: Disulfiram (DSF), a drug widely used to control alcoholism, which has anticancer activity by inducing apoptosis in a copper (Cu)-dependent manner. Numerous evidences from mouse experiments indicated that some anti-cancer agents of chemotherapeutic drugs favor the induction of immunogenic cancer cell death (ICD) leading to tumor-specific immune responses. However, whether DSF could induce the colorectal tumor cells death and the mechanism involved in ICD regulatory remains elusive. The main objective of this study was to elucidate the effect of DSF/Cu on the apoptosis of colorectal cancer (CRC) cells and the expression of the two major ICD markers in CRC cells: calreticulin (CRT) and heat shock proteins (HSP) 70. METHODS: Firstly, the toxicity of DSF/Cu in HCT116, SW620 and HCT8 cells was assayed by MTT. Flow cytometry was utilized to detect the apoptosis effects. The effects of DSF/Cu on the expression of ICD-related molecules in tumor tissues were further verified in the CRC xenograft mouse model. RESULTS: The results showed that DSF/Cu increase apoptosis of these three cells in a dose dependent manner and significantly inhibited the proliferation at the concentration range from 0.05 to 1.6 µM. Furthermore, the expression of CRT and HSP70 on the cell surface also increased. The rate of transplanted tumors grew slowly, and the expression of CRT and HSP70 in colorectal cancer tissues was increased after treated with DSF/Cu. CONCLUSION: In conclusion, our results show that DSF/Cu exerts anti-colorectal cancer and its underlying mechanisms are associated with the enhancement of molecules expression of cell ICD. These results provide experimental evidence and theory basis of therapy for developing the DSF/Cu as the drug for CRC.

Research advances in nutritional assessment methods in children with chronic liver diseases / 中国当代儿科杂志

Malnutrition is commonly seen in children with chronic liver diseases, and there are interactions between them. Chronic liver diseases can cause malnutrition and this can affect the prognosis of children with chronic liver diseases. Due to the complexity of nutritional assessment in children with chronic liver diseases, there are still no unified standards for the diagnosis of malnutrition. Early identification of malnutrition and related intervention helps to improve the prognosis of children with chronic liver diseases. This article reviews the features of nutrition in children with chronic liver diseases and related nutritional assessment methods.

Systematic Investigation of High-Sensitivity Luminescent Sensing for Polyoxometalates and Iron(III) by MOFs Assembled with a New Resorcin[4]arene-Functionalized Tetracarboxylate.

A new family of resorcin[4]arene-based metal-organic frameworks (MOFs), namely, [Eu(HL)(DMF)(H2 O)2 ]⋅3 H2 O (1), [Tb(HL)(DMF)(H2 O)2 ] 3 H2 O (2), [Cd4 (L)2 (DMF)4 (H2 O)2 ] 3 H2 O (3) and [Zn3 (HL)2 (H2 O)2 ] 2 DMF⋅7 H2 O (4), have been constructed from a new resorcin[4]arene-functionalized tetracarboxylic acid (H4 L=2,8,14,20-tetra-ethyl-6,12,18,24-tetra-methoxy-4,10,16,22-tetra-carboxy-methoxy-calix[4]arene). Isostructural 1 and 2 exhibit charming 1D motifs built with the cup-like HL(3-) anions and rare earth cations. Compounds 3 and 4 show a unique sandwich-based 2D layer and a fascinating 3D framework, respectively. Remarkably, compounds 1 and 2 display intensive red and green emissions triggered by the efficient antenna effect of organic ligands under UV light. More importantly, systematic luminescence studies demonstrate that Ln-MOFs 1 and 2, as efficient multifunctional fluorescent materials, show highly selective and sensitive sensing of Fe(3+) , polyoxometalates (POMs), and acetone, which represents a rare example of a sensor for quantitatively detecting three different types of analytes. This is also an exceedingly rare example of Fe(3+) and POMs detection in aqueous solutions employing resorcin[4]arene-based luminescent Ln-MOFs. Furthermore, the possible mechanism of the sensing properties is deduced.

Regulation of matrix metalloproteinase-9 protein expression by 1alpha,25-(OH)2D3 during osteoclast differentiation

To investigate 1alpha,25-(OH)2D3 regulation of matrix metalloproteinase-9 (MMP-9) protein expression during osteoclast formation and differentiation, receptor activator of nuclear factor kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) were administered to induce the differentiation of RAW264.7 cells into osteoclasts. The cells were incubated with different concentrations of 1alpha,25-(OH)2D3 during culturing, and cell proliferation was measured using the methylthiazol tetrazolium method. Osteoclast formation was confirmed using tartrate-resistant acid phosphatase (TRAP) staining and assessing bone lacunar resorption. MMP-9 protein expression levels were measured with Western blotting. We showed that 1alpha,25-(OH)2D3 inhibited RAW264.7 cell proliferation induced by RANKL and M-CSF, increased the numbers of TRAP-positive osteoclasts and their nuclei, enhanced osteoclast bone resorption, and promoted MMP-9 protein expression in a concentration-dependent manner. These findings indicate that 1alpha,25-(OH)2D3 administered at a physiological relevant concentration promoted osteoclast formation and could regulate osteoclast bone metabolism by increasing MMP-9 protein expression during osteoclast differentiation.

Inhibitory effects of osteoprotegerin on osteoclast formation and function under serum-free conditions

The purpose of this study was to determine whether osteoprotegerin (OPG) could affect osteoclat differentiation and activation under serum-free conditions. Both duck embryo bone marrow cells and RAW264.7 cells were incubated with macrophage colony stimulatory factor (M-CSF) and receptor activator for nuclear factor kappaB ligand (RANKL) in serum-free medium to promote osteoclastogenesis. During cultivation, 0, 10, 20, 50, and 100 ng/mL OPG were added to various groups of cells. Osteoclast differentiation and activation were monitored via tartrate-resistant acid phosphatase (TRAP) staining, filamentous-actin rings analysis, and a bone resorption assay. Furthermore, the expression osteoclast-related genes, such as TRAP and receptor activator for nuclear factor kappaB (RANK), that was influenced by OPG in RAW264.7 cells was examined using real-time polymerase chain reaction. In summary, findings from the present study suggested that M-CSF with RANKL can promote osteoclast differentiation and activation, and enhance the expression of TRAP and RANK mRNA in osteoclasts. In contrast, OPG inhibited these activities under serum-free conditions.

Observation on the efficacy of acupuncture at key acupoints combined with rehabilitation therapy for spasmodic hemiplegia after cerebral infarction / 中国针灸

<p><b>OBJECTIVE</b>To assess the clinical efficacy of acupuncture at key acupoints combined with the routine rehabilitation training of limb function on spasmodic hemiplegia after cerebral infarction.</p><p><b>METHODS</b>Eighty-six cases were randomized into an acupuncture combined with rehabilitation group (group A, 44 cases) and a rehabilitation group (group B, 42 cases). In group A, the key acupoints were selected from head, face, chest, abdomen, shoulder, back, hands, feet and ankles such as Cuanzhu (BL 2), Danzhong (CV 17), Jianyu (LI 15) and Yanglao (SI 16) were stimulated with acupuncture. In combination, the routine limb rehabilitation training was applied, once every day. In group B, the routine limb rehabilitation training was applied alone. In both groups, 10 treatments made one session and 2 sessions were required totally. Before and after treatment, Fugl-Meyer scale and functional independent measurement (FIM) scale were adopted to assess the limb motor level and the activity of daily life in the patients respectively. The modified Ashworth scale was used to assess the effect of anti-spasm.</p><p><b>RESULTS</b>The total effective rate of anti-spasm was 90.9% (40/44) in the group A, which was superior to 73.8% (32/42) in the group B (P < 0.05). After 2 sessions of treatment, Fugl-Meyer score and FIM score were all improved in both groups (all P < 0.05) and the results in the group A were better than those in the group B (all P < 0.05). Additionally, the improvement of FIM score after the 1st session of treatment in the group A was better as compared with the group B, indicating the significant difference (P < 0.05).</p><p><b>CONCLUSION</b>Acupuncture at key acupoints combined with rehabilitation therapy effectively relieves the spasmodic condition of the patients with post-stroke spasmodic hemiplegia, improves the limb function and the life activity of the patients.</p>