Organ-on-a-chip for studying immune cell adhesion to liver sinusoidal endothelial cells: the potential for testing immunotherapies and cell therapy trafficking.

Immunotherapy has changed the landscape of treatment options for patients with hepatocellular cancer. Checkpoint inhibitors are now standard of care for patients with advanced tumours, yet the majority remain resistant to this therapy and urgent approaches are needed to boost the efficacy of these agents. Targeting the liver endothelial cells, as the orchestrators of immune cell recruitment, within the tumour microenvironment of this highly vascular cancer could potentially boost immune cell infiltration. We demonstrate the successful culture of primary human liver endothelial cells in organ-on-a-chip technology followed by perfusion of peripheral blood mononuclear cells. We confirm, with confocal and multiphoton imaging, the capture and adhesion of immune cells in response to pro-inflammatory cytokines in this model. This multicellular platform sets the foundation for testing the efficacy of new therapies in promoting leukocyte infiltration across liver endothelium as well as a model for testing cell therapy, such as chimeric antigen receptor (CAR)-T cell, capture and migration across human liver endothelium.

Long-term survival in patients with brain-only metastatic non-small cell lung cancer undergoing upfront intracranial stereotactic radiosurgery and definitive treatment to the thoracic primary site.

BACKGROUND AND PURPOSE: To evaluate modern clinical outcomes for patients with brain-only metastatic non-small cell lung cancer (NSCLC) treated with intracranial stereotactic radiosurgery (SRS) with or without definitive treatment of the primary site. MATERIALS AND METHODS: Patients with synchronously diagnosed NSCLC and brain-only metastatic disease treated with intracranial SRS at a single institution were retrospectively identified. Patients were stratified based on whether they did (A) or did not (B) receive definitive primary site treatment. Patient characteristics and clinical outcomes were compared. RESULTS: From 2008 to 2022, 103 patients were identified, 53 of whom received definitive primary site treatment. Median follow-up was 2.1 y (A) and 0.8 y (B) (p < 0.001). 28 (53 %) patients in Group A received immune checkpoint inhibitor (ICI) therapy versus 19 (38 %) in Group B (p = 0.13) and there were no other statistically significant baseline or treatment characteristic differences between the groups. 5-year local-PFS was 34.5 % (A) versus 0 % (B) (p < 0.001). 5-year regional-PFS was 33.0 % (A) versus 0 % (B) (p < 0.001). 5-year distant body-PFS was 34.0 % (A) versus 0 % (B) (p < 0.001). 5-year CNS-PFS was 14.7 % (A) versus 0 % (B) (p = 0.12). 5-year OS was 40.2 % (A) versus 0 % (B) (p = 0.001). 5-year CSS was 67.6 % (A) versus 0 % (B) (p = 0.002). On multivariable analysis, lack of definitive treatment to the primary site (HR = 2.40), AJCC T3-4 disease (HR = 2.73), and lack of ICI therapy (HR = 2.86) were significant predictors of death. CONCLUSION: Definitive treatment to the thoracic primary site in patients with brain-only metastatic NSCLC after intracranial radiosurgery was associated with slower progression of disease and improved survival.

[A multicenter prospective study on early identification of refractory Mycoplasma pneumoniae pneumonia in children].

Objective: To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods: The prospective multicenter study was conducted in Zhejiang, China from May 1st, 2019 to January 31st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results: A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95%CI 0.593-0.771, P<0.01). Conclusion: In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

[The method of determination for 2, 3-Butanedione in the air of workplace by high performance liquid chromatography with derivatization].

Objective: To establish a method for the determination of 2, 3-Butanedione (BUT) in the air of workplace, which including the process of collection by absorption in phosphoric acid aqueous solution and the process of analysis and detection by high performance liquid chromatography with derivatization. Methods: In October 2022, a porous glass plate absorption tube containing 10 ml of 0.01% phosphoric acid solution was used to collect BUT in the air of the workplace at a flow rate of 0.2 L/min. The absorption solution was derived by 2, 4-dinitrophenylhydrazine for 75 min and separated on a SB-C18 column (250 mm×4.6 mm, 5 µm) . At the column temperature of 30 ℃, the mixture of acetonitrile-water (V∶V, 1∶1) was eluted at the flow rate of 1.0 ml/min. It was detected by UV detector (λ=365 nm) , qualitatived by retention time and quantitatived by external standard. Results: It showed that BUT in phosphoric acid aqueous solution could be stored for at least 7 d at 4 ℃. There was a linear relationship within the determination range of 0.05-6.00 µg/ml, the linear regression equation was y=89.610x+0.133, r=0.9999. The sampling absorption efficiencies were 98.33%-100.00%, the detection limit of the method was 0.005 µg/ml, the minimum detection concentration was 0.016 mg/m(3) (based on V(0)=3.0 L) . The recovery rates were 95.96%-102.44%, the intra batch precision were 4.36%-7.78%, and the inter batch precision were 4.96%-6.06%. Conclusion: The method has the advantages of simple operation, high sensitivity and good accuracy. It can prevent the loss and degradation of BUT. It can be used for the determination of BUT in the air of workplace.

[Resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by maintaining mitochondrial homeostasis via enhancing SIRT1 expression].

OBJECTIVE: To investigate whether resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by enhancing the expression of silent information regulation 2 homolog 1 (SIRT1) to maintain mitochondrial homeostasis. METHODS: Rat cardiomyocytes H9c2 cells with or without lentivirus-mediated mRNA interference of SIRT1 were cultured in high glucose (HG) and treated with resveratrol for 72 h. The changes in superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, reactive oxygen species (ROS) level, and relative surface of the cells were examined, and the mRNA expressions of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) and protein expressions of SIRT1, mitochondrial fusion related proteins optic atrophy protein 1 (OPA1) and mitofusin 2, mitochondrial division related proteins dynamin-related protein 1 (DRP1) and fission protein 1 (FIS1), and mitophagy-related proteins BNIP3L and LC3 were detected using RT-qPCR and Western blotting. RESULTS: HG exposure significantly decreased SOD activity, increased MDA content, ROS production, relative cell surface, and the mRNA expressions of ANF and BNP in the cardiomyocytes; the protein expressions of SIRT1, OPA1, mitofusin 2 and BNIP3L and LC3-Ⅱ/LC3-Ⅰ ratio were all decreased and the protein expressions of DRP1 and FIS1 increased in HG-exposed cells (P<0.01). All these changes in HG-exposed cardiomyocytes were significantly alleviated by treatment with resveratrol (P<0.05). The protective effects of resveratrol against HG exposure in the cardiomyocytes were obviously attenuated by transfection of the cells with si-SIRT1 (P<0.05). CONCLUSION: Resveratrol inhibits hyperglycemia-induced cardiomyocyte hypertrophy by reducing oxidative stress, the mechanisms of which involve enhancement of SIRT1 protein expression, regulation of mitochondrial fusion and division balance, and promoting BNIP3L-mediated mitophagy to maintain mitochondrial homeostasis in the cells.

Expression of E-cadherin by CD8+ T cells promotes their invasion into biliary epithelial cells.

The presence of CD8+ T cells in the cytoplasm of biliary epithelial cells (BEC) has been correlated with biliary damage associated with primary biliary cholangitis (PBC). Here, we characterise the mechanism of CD8+ T cell invasion into BEC. CD8+ T cells observed within BEC were large, eccentric, and expressed E-cadherin, CD103 and CD69. They were also not contained within secondary vesicles. Internalisation required cytoskeletal rearrangements which facilitated contact with BEC. Internalised CD8+ T cells were observed in both non-cirrhotic and cirrhotic diseased liver tissues but enriched in PBC patients, both during active disease and at the time of transplantation. E-cadherin expression by CD8+ T cells correlated with frequency of internalisation of these cells into BEC. E-cadherin+ CD8+ T cells formed ß-catenin-associated interactions with BEC, were larger than E-cadherin- CD8+ T cells and invaded into BEC more frequently. Overall, we unveil a distinct cell-in-cell structure process in the liver detailing the invasion of E-cadherin+ CD103+ CD69+ CD8+ T cells into BEC.

Obstetric outcomes in Jehovah's Witnesses: case series over nine years in a London teaching hospital.

OBJECTIVES: The aim of the study is to assess obstetric and fetal outcomes of Jehovah's Witnesses (JWs) mothers in an inner city teaching hospital, as well as to examine the acceptance rates of various blood fractions and blood transfusion alternatives. METHODS: Case series to evaluate the maternal and fetal outcomes of JWs over a nine period between 2013 and 2021. RESULTS: There were 146 pregnancies extracted from our database, of which 10 were early pregnancy losses. Data from 136 deliveries > 24 weeks' gestation were assessed, with a mean maternal age and gestational age of 30.26 (± 5.4) years and 38.7 (± 5.3) weeks, respectively. 57% had normal vaginal deliveries, 8% had instrumental births and 35% had caesarean births. Mean estimated blood loss at caesarean was 575 (± 305.6) mls, while the overall mean estimated loss was 427.8 (± 299.8) mls. Cell salvage was performed in all caesarean sections but autologous transfusion was only necessary for 26%. Consultant presence was documented in 62% of caesarean births. The mean birthweight and 5-min Apgar scores were 3.31 (± 0.05) kg and 9.1 (± 0.09), respectively. There were no maternal deaths or admissions to the adult intensive care unit and the most serious complication was a uterine rupture following a trial of scar, after which the baby required cooling for hypoxic ischaemic encephalopathy. CONCLUSIONS: Pregnant JWs received obstetric care led by senior clinicians, with optimisation of haematinics, minimizing of blood loss at delivery and access to technology such as cell salvage.

Thyroid hormone receptor alpha modulates fibrogenesis in hepatic stellate cells.

OBJECTIVE: Progressive hepatic fibrosis can be considered the final stage of chronic liver disease. Hepatic stellate cells (HSC) play a central role in liver fibrogenesis. Thyroid hormones (TH, e.g. thyroxine; T4 and triiodothyronine; T3) significantly affect development, growth, cell differentiation and metabolism through activation of TH receptor α and/or ß (TRα/ß). Here, we evaluated the influence of TH in hepatic fibrogenesis. DESIGN: Human liver tissue was obtained from explanted livers following transplantation. TRα-deficient (TRα-KO) and wild-type (WT) mice were fed a control or a profibrogenic methionine-choline deficient (MCD) diet. Liver tissue was assessed by qRT-PCR for fibrogenic gene expression. In vitro, HSC were treated with TGFß in the presence or absence of T3. HSC with stable TRα knockdown and TRα deficient mouse embryonic fibroblasts (MEF) were used to determine receptor-specific function. Activation of HSC and MEF was assessed using the wound healing assay, Western blotting, and qRT-PCR. RESULTS: TRα and TRß expression is downregulated in the liver during hepatic fibrogenesis in humans and mice. TRα represents the dominant isoform in HSC. In vitro, T3 blunted TGFß-induced expression of fibrogenic genes in HSC and abrogated wound healing by modulating TGFß signalling, which depended on TRα presence. In vivo, TRα-KO enhanced MCD diet-induced liver fibrogenesis. CONCLUSION: These observations indicate that TH action in non-parenchymal cells is highly relevant. The interaction of TRα with TH regulates the phenotype of HSC via the TGFß signalling pathway. Thus, the TH-TR axis may be a valuable target for future therapy of liver fibrosis.

Effect of contact precautions on preventing meticillin-resistant Staphylococcus aureus transmission in intensive care units: a review and modelling study of field trials.

BACKGROUND: Contact precautions (CPs) have been widely implemented in hospitals, particularly in intensive care units (ICUs), as the standard approach for managing meticillin-resistant Staphylococcus aureus (MRSA). However, the effectiveness of CPs in preventing MRSA transmission remains a subject of debate. AIM: To assess the effectiveness of CPs in reducing MRSA transmission within ICUs. METHODS: A comprehensive analysis was conducted using data from 16 sets of parameters collected from 13 field studies investigating the effectiveness of CPs in ICUs, and an epidemiologic model was developed to simulate the dynamics of MRSA incidence in the hospital setting. FINDINGS: The analysis demonstrated a mean reduction of 20.52% (95% confidence interval -30.52 to 71.60%) in the MRSA transmission rate associated with the implementation of CPs. Furthermore, reducing the time-delay of screening tests and increasing the percentage of patients identified with MRSA through screening at admission were found to contribute to the effectiveness of CPs. CONCLUSION: Proper implementation of CPs, with a particular emphasis on early identification of MRSA-colonized/infected patients, demonstrated a strong association with reduced MRSA transmission within the hospital setting. However, further research is necessary to investigate the effectiveness and safety of decolonization and other interventions used in conjunction with CPs to mitigate the risk of infection among colonized patients.

Analysis of changes in serum high t-PINP/ß-CTX ratio and risk of re-fracture after vertebral osteoporotic fracture surgery.

OBJECTIVE: This study's aim was to investigate the expression changes of total type I procollagen amino-terminal peptide (t-PINP) and type I collagen C-terminal peptide (ß-CTX) in serum after vertebral osteoporotic fracture surgery and the clinical value of predicting the risk of refracture. PATIENTS AND METHODS: The clinical data of 100 patients with vertebral osteoporotic fractures treated in our hospital from January 2019 to January 2020 were retrospectively analyzed, and the patients were divided into the control group (patients without re-fracture, n = 68) and the observation group (patients with re-fracture, n = 32) according to whether they had re-fracture at 2-year follow-up. The risk factors of postoperative re-fracture were analyzed using Multivariate logistic regression analysis. The serum contents of t-PINP, ß-CTX, osteocalcin (BGP), and calcium (Ca) were measured. Bone mineral density (BMD) was measured by bone densitometer. The correlation between the t-PINP/ß-CTX ratio and the bone metabolic index was analyzed by Pearson correlation. The area under the curve (AUC), sensitivity, and specificity of t-PINP/ß-CTX in predicting the risk of re-fracture were determined by the receiver operating characteristic (ROC) curve. RESULTS: There was a significant difference in age, the number of vertebral bodies with initial fracture, and whether there was leakage of bone cement between the two groups (p < 0.05). Age, the number of vertebral bodies with primary fracture, and the leakage of bone cement were risk factors affecting re-fracture after operation (p < 0.05). Compared with those in the control group, the level of t-PINP and the ratio of t-PINP/ß-CTX were higher, and the ß-CTX level was lower in the observation group (p < 0.05). The BGP level was higher, and the levels of BMD and Ca were lower in the observation group than those in the control group (p < 0.05). Pearson correlation analysis showed that t-PINP had a positive correlation with BGP (r = 0.222, p < 0.05). ß-CTX was positively correlated with BMD and Ca (r = 0.230, 0.269, p < 0.05). The ratio of t-PINP/ ß-CTX was negatively correlated with BMD and Ca (r = -0.621 and -0.660, p < 0.05), but positively correlated with BGP (r = 0.517, p < 0.05). ROC curve analysis showed that the AUC of t-PINP, ß-CTX, and the ratio of t-PINP/ß-CTX in predicting the risk of re-fracture after vertebral osteoporotic fracture surgery was 0.724, 0.736, and 0.838, respectively. CONCLUSIONS: The t-PINP/ß-CTX ratio was significantly correlated with the bone metabolic indexes in patients with vertebral osteoporotic fractures. The detection of the changes in its index can help predict the risk of postoperative re-fracture, providing a new idea for clinical assessment of the risk of postoperative re-fracture.

Acromegaly presented with acne vulgaris: a retrospective study with 123 cases.

BACKGROUND: Acne vulgaris is a prevalent skin condition. We have found that some acromegaly patients have acne. However, no study has examined the relationship between acromegaly and acne. OBJECTIVE: To explore prevalence and correlation of adult acne in patients with acromegaly. METHODS: For this cross-sectional study, we collected questionnaires, clinical information, and laboratory test results of acromegaly patients from January 2022 to December 2022 at Huashan Hospital. Of the 133 questionnaires returned, 123 had valid responses. RESULTS: Of the 123 patients with acromegaly enrolled in this study, 54.5% had adult acne. No statistically significant difference was found in prevalence between male and female patients. 61.2% of adult acne patients reported late-onset acne. Late-onset acne patients first developed acne years before acromegaly diagnosis (mean of 5.6 years for male and 4.5 years for female patients). Some acne patients have received traditional anti-acne treatment. Moreover, 31% of the patients reported no improvement, and only 3.5% of patients claimed complete resolution of acne after treatment. Before acromegaly treatment, the prevalence of adult acne was 51.2%, with mild acne accounting for 73.0%, moderate acne accounting for 23.8%, and severe acne accounting for 3.2%. After acromegaly treatment, the prevalence of adult acne was significantly decreased to 37.4% (P = 0.007). An overall decrease in acne severity was noted, with 93.5%, 6.5%, and 0% having mild, moderate, and severe acne, respectively. A total of 83.6% of the patients had self-assessed acne remission, and 33.3% of the patients reported complete acne resolution. However, 9.0% of patients reported that their condition had worsened after acromegaly treatment. After treatment, GH, IGF-1, IGF-1 index, insulin levels, and HOMA-IR decreased significantly in all patients with acromegaly (P < 0.05). Acne remission correlated positively with IGF-1 levels, but not with GH levels. The relationship between acromegaly and acne remains to be elucidated. CONCLUSIONS: Our findings provide preliminary evidence of the high prevalence of adult acne in acromegaly patients, and a high rate of late-onset acne as well. Traditional anti-acne treatments are less effective. Acne could be considerably relieved by treating acromegaly. Acne remission positively correlated with IGF-1 decline as well, which revealed the correlation between acne and IGF-1.

[The role of intravoxel incoherent motion diffusion-weighted imaging in distinguishing diabetic nephropathy from non-diabetic renal disease in diabetic patients].

Objective: To investigate the intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in the differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) among patients with type 2 diabetes mellitus (T2DM). Methods: A diagnostic test. In this prospective study, patients with T2DM who underwent both IVIM-DWI and renal biopsy at the First Medical Center of Chinese PLA General Hospital between October 2017 and September 2021 were consecutively enrolled. IVIM-DWI parameters including perfusion fraction (f), pure diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were measured in the renal cortex, medulla, and parenchyma. Patients were divided into the DN group and NDRD group based on the renal biopsy results. IVIM-DWI parameters, clinical information, and diabetes-related biochemical indicators between the two groups were compared using Student's t-test or Mann-Whitney U test. The correlation of IVIM-DWI parameters with diabetic nephropathy histological scores were analyzed using Spearman's correlation analyzes. The diagnostic efficiency of IVIM-DWI parameters for distinguishing between DN and NDRD were assessed using the receiver operating characteristic (ROC) curves. Results: A total of 27 DN patients and 23 NDRD patients were included in this study. The DN group comprised 19 male and 8 female patients, with an average age of 52±9 years. The NDRD group comprised 16 male and 7 female patients, with an average age of 49±10 years. The DN group had a higher D* value in the renal cortex and a lower f value in the renal medulla than the NDRD group (9.84×10-3 mm2/s vs. 7.35×10-3 mm2/s, Z=-3.65; 41.01% vs. 46.74%, Z=-2.29; all P<0.05). The renal medulla D* value was negatively correlated with DN grades, interstitial lesion score, and interstitial fibrosis and tubular atrophy (IFTA) score (r=-0.571, -0.409, -0.409; all P<0.05) while the renal cortex f value was positively correlated with vascular sclerosis score (r=0.413, P=0.032). The renal cortex D* value had the highest area under the curve (AUC) for discriminating between the DN and NDRD groups (AUC=0.802, sensitivity 91.3%, specificity 55.6%). Conclusion: IVIM-derived renal cortex D* value can be used non-invasively to differentiate DN from NDRD in patients with T2DM that can potentially facilitate individualized treatment planning for diabetic patients.

Allisartan Isoproxil Promotes Uric Acid Excretion by Interacting with Intestinal Urate Transporters in Hyperuricemic Zebrafish (Danio rerio).

To evaluate the urate-lowering effect and potential drug targets of antihypertensive agent allisartan isoproxil (ALI) and its bioactive metabolite EXP3174, we developed an acute hyperuricemic zebrafish model using potassium oxonate and xanthine sodium salt. Losartan potassium served as the positive control (reference drug). In this model, ALI and losartan potassium exerted a greater urate-lowering effect than EXP3174 indicating that the latter is not the critical substance for elimination of uric acid. The quantitative real-time PCR showed that ALI upregulates the expression of intestinal urate transporters genes ABCG2, PDZK1, and SLC2A9 (p<0.01). Thus, we can suggest that this substance promotes uric acid excretion mainly by interacting with intestinal urate transporters.

Combining the triglyceride-glucose index and glycated hemoglobin A1c to assess the risk of preeclampsia in women with normal glucose tolerance: a cross-sectional study.

OBJECTIVE: This study aimed to explore the relationship between the triglyceride-glucose (TyG) index, glycated hemoglobin A1c (HbA1c), and preeclampsia in pregnant women without gestational diabetes mellitus (GDM). PATIENTS AND METHODS: This retrospective study included pregnancies with normal oral glucose tolerance tests (OGTTs) from March 2018 to February 2019. During the second trimester, serum lipids, fasting plasma glucose (FPG), and HbA1c were measured, and OGTTs were performed. Participants were classified into four groups based on their TyG index and HbA1c levels. Logistic regression analysis was done to determine the odds ratios (ORs), and receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of the TyG index and HbA1c to predict the risks of preeclampsia. RESULTS: Patients with preeclampsia exhibited higher TyG index and HbA1c levels (all p < 0.001). The incidence of preeclampsia increased with elevated TyG index and HbA1c levels individually. Furthermore, the highest incidence of preeclampsia was observed when both the TyG index and HbA1c levels were elevated. ROC curve analysis revealed that the combined TyG index and HbA1c displayed an area under the curve (AUC) of 0.689 in predicting the risk of preeclampsia. Even after adjusting for potential confounding factors, the risk of developing preeclampsia remained significantly higher. These associations were especially prominent in women aged ≥ 35 years or those with a normal BMI. CONCLUSIONS: The findings of this study indicate that increased TyG index and HbA1c levels are associated with a higher incidence and risk of preeclampsia in women with normal glucose tolerance during pregnancy. The TyG index and HbA1c levels may serve as potential markers for preeclampsia in individuals with normal OGTT results.

Using Proteome Microarray and Gene Expression Omnibus Database to Screen Tumour-Associated Antigens to Construct the Optimal Diagnostic Model of Oesophageal Squamous Cell Carcinoma.

AIMS: Autoantibodies against tumour-associated antigens (TAAs) are promising biomarkers for early immunodiagnosis of cancers. This study was designed to screen and verify autoantibodies against TAAs in sera as diagnostic biomarkers for oesophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: The customised proteome microarray based on cancer driver genes and the Gene Expression Omnibus database were used to identify potential TAAs. The expression levels of the corresponding autoantibodies in serum samples obtained from 243 ESCC patients and 243 healthy controls were investigated by enzyme-linked immunosorbent assay (ELISA). In total, 486 serum samples were randomly divided into the training set and the validation set in the ratio of 2:1. Logistic regression analysis, recursive partition analysis and support vector machine were performed to establish different diagnostic models. RESULTS: Five and nine candidate TAAs were screened out by proteome microarray and bioinformatics analysis, respectively. Among these 14 anti-TAAs autoantibodies, the expression level of nine (p53, PTEN, GNA11, SRSF2, CXCL8, MMP1, MSH6, LAMC2 and SLC2A1) anti-TAAs autoantibodies in the cancer patient group was higher than that in the healthy control group based on the results from ELISA. In the three constructed models, a logistic regression model including four anti-TAA autoantibodies (p53, SLC2A1, GNA11 and MMP1) was considered to be the optimal diagnosis model. The sensitivity and specificity of the model in the training set and the validation set were 70.4%, 72.8% and 67.9%, 67.9%, respectively. The area under the receiver operating characteristic curve for detecting early patients in the training set and the validation set were 0.84 and 0.85, respectively. CONCLUSIONS: This approach to screen novel TAAs is feasible, and the model including four autoantibodies could pave the way for the diagnosis of ESCC.

Association of interleukin-6 and CD4+ T cells and two-week prognosis of patients with COVID-19: a predictive role.

OBJECTIVE: The aim of this study was to determine the association of inflammation and immune responses with the outcomes of patients at various stages, and to develop risk stratification for improving clinical practice and reducing mortality. PATIENTS AND METHODS: We included 77 patients with primary outcomes of either death or survival. Demographics, clinical features, comorbidities, and laboratory tests were compared. Linear, logistic, and Cox regression analyses were performed to determine prognostic factors. RESULTS: The average age was 59 years (35-87 years). There were 12 moderate cases (16.2%), 42 severe cases (54.5%), and 23 critical cases (29.9%); and 41 were male (53.2%). Until March 20, 68 cases were discharged (88.3%), and nine critically ill males (11.7%) died. Interleukin-6 (IL-6) levels on the 1st day were compared with IL-6 values on the 14th day in the severe and the critically ill surviving patients (F=4.90, p=0.034, ß=0.35, 95% CI: 0.00-0.10), and predicted death in the critically ill patients (p=0.028, ß=0.05, OR: 1.05, 95% CI: 1.01-1.10). CD4+ T-cell counts at admission decreased the hazard ratio of death (p=0.039, ß=-0.01, hazard ratio=0.99, 95% CI: 0.98-1.00, and median survival time 13.5 days). CONCLUSIONS: The present study demonstrated that IL-6 levels and CD4+ T-cell count at admission played key roles of predictors in the prognosis, especially for critically ill patients. High levels of IL-6 and impaired CD4+t cells are seen in severe and critically ill patients with COVID-19.

Addressing extreme size mismatch in pediatric intestinal transplantation: Outcomes of intestinal length reduction.

BACKGROUND: Bench liver reduction, with or without intestinal length reduction (LR) (coupled with delayed closure and abdominal wall prostheses), has been a strategy adopted by our program for small children due to the limited availability of size-matched donors. This report describes the short, medium, and long-term outcomes of this graft reduction strategy. METHODS: A single-center, retrospective analysis of children that underwent intestinal transplantation (April 1993 to December 2020) was performed. Patients were grouped according to whether they received an intestinal graft of full length (FL) or following LR. RESULTS: Overall, 105 intestinal transplants were performed. The LR group (n = 10) was younger (14.5 months vs. 40.0 months, p = .012) and smaller (8.7 kg vs. 13.0 kg, p = .032) compared to the FL group (n = 95). Similar abdominal closure rates were achieved after LR, without any increase in abdominal compartment syndrome (1/10 vs. 7/95, p = .806). The 90-day graft and patient survival were similar (9/10, 90% vs. 83/95, 86%; p = .810). Medium and long-term graft survival at 1 year (8/10, 80% vs. 65/90, 71%; p = .599), and 5 years (5/10, 50% vs. 42/84, 50%; p = 1.00) was similar. CONCLUSION: LR of intestinal grafts appears to be a safe strategy for infants and small children requiring intestinal transplantation. This technique should be considered in the situation of significant size mismatch of intestine containing grafts.

[Comparison of diagnostic performance of Clear Cell Likelihood Score v1.0 and v2.0 for clear renal cell carcinoma].

OBJECTIVE: To compare the performance of Clear Cell Likelihood Score (ccLS) v1.0 and v2.0 in diagnosing clear cell renal cell carcinoma (ccRCC) from small renal masses (SRM). METHODS: We retrospectively analyzed the clinical data and MR images of patients with pathologically confirmed solid SRM from the First Medical Center of the Chinese PLA General Hospital between January 1, 2018, and December 31, 2021, and from Beijing Friendship Hospital of Capital Medical University and Peking University First Hospital between January 1, 2019 and May 17, 2021. Six abdominal radiologists were trained for use of the ccLS algorithm and scored independently using ccLS v1.0 and ccLS v2.0. Random- effects logistic regression modeling was used to generate plot receiver operating characteristic curves (ROC) to evaluate the diagnostic performance of ccLS v1.0 and ccLS v2.0 for ccRCC, and the area under curve (AUC) of these two scoring systems were compared using the DeLong's test. Weighted Kappa test was used to evaluate the interobserver agreement of the ccLS score, and differences in the weighted Kappa coefficients was compared using the Gwet consistency coefficient. RESULTS: In total, 691 patients (491 males, 200 females; mean age, 54 ± 12 years) with 700 renal masses were included in this study. The pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ccLS v1.0 for diagnosing ccRCC were 77.1%, 76.8%, 77.7%, 90.2%, and 55.7%, as compared with 80.9%, 79.3%, 85.1%, 93.4%, 60.6% with ccLS v2.0, respectively. The AUC of ccLS v2.0 was significantly higher than that of ccLS v1.0 for diagnosis of ccRCC (0.897 vs 0.859; P < 0.01). The interobserver agreement did not differ significantly between ccLS v1.0 and ccLS v2.0 (0.56 vs 0.60; P > 0.05). CONCLUSION: ccLS v2.0 has better performance for diagnosing ccRCC than ccLS v1.0 and can be considered for use to assist radiologists with their routine diagnostic tasks.

[Diagnostic value of multiparametric MRI-based models in the assessment of extra-prostatic extension of prostate cancer].

Objective: To evaluate the diagnostic value of multiparametric magnetic resonance imaging (mpMRI) based models in the assessment of extra-prostatic extension (EPE) of prostate cancer. Methods: This retrospective study included 168 consecutive men with prostate cancers [aged 48 to 82 (66.6±6.8) years] who underwent radical prostatectomy and preoperative mpMRI examinations at the First Medical Center of the PLA General Hospital from January 2021 to February 2022. According to European Society of Urogenital Radiology (ESUR) score, EPE grade and mEPE score, all cases were independently evaluated by two radiologists, with disagreement reviewed by a senior radiologist as the final result. The diagnostic performance of each MRI-based model for pathologic EPE prediction was assessed using receiver operating characteristic curve (ROC), and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. The weighted Kappa test was used to evaluate the inter-reader agreement of each MRI-based model. Results: A total of 62 (36.9%) prostate cancer patients had pathologic confirmed EPE after radical prostatectomy. The AUC of ESUR score, EPE grade and mEPE score for predicting pathologic EPE were 0.836 (95%CI: 0.771-0.888), 0.834 (95%CI: 0.769-0.887) and 0.785 (95%CI: 0.715-0.844), respectively. The AUC of ESUR score and EPE grade were both superior to that of mEPE score with significant differences (all P<0.05), while there was no significant difference between the ESUR score and EPE grade models (P=0.900). EPE grading and mEPE score had good inter-reader consistency, with weighted Kappa values of 0.65 (95%CI: 0.56-0.74) and 0.74 (95%CI: 0.64-0.84), respectively. The inter-reader consistency of ESUR score was moderate, and the weighted Kappa value was 0.52 (95%CI: 0.40-0.63). Conclusion: All MRI-based models showed good preoperative diagnostic value in predicting EPE, among which the EPE grade resulted in more reliable performance with substantial inter-reader agreement.