Intestinal CXCR6+ ILC3s migrate to the kidney and exacerbate renal fibrosis via IL-23 receptor signaling enhanced by PD-1 expression.

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.

Synthetic peptides that form nanostructured micelles have potent antibiotic and antibiofilm activity against polymicrobial infections.

The emergence of multidrug-resistant bacterial pathogens is a growing threat to global public health. Here, we report the development and characterization of a panel of nine-amino acid residue synthetic peptides that display potent antibacterial activity and the ability to disrupt preestablished microbial biofilms. The lead peptide (Peptide K6) showed bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus in culture and in monocultures and mixed biofilms in vitro. Biophysical analysis revealed that Peptide K6 self-assembled into nanostructured micelles that correlated with its strong antibiofilm activity. When surface displayed on the outer membrane protein LamB, two copies of the Peptide K6 were highly bactericidal to Escherichia coli. Peptide K6 rapidly increased the permeability of bacterial cells, and resistance to this toxic peptide occurred less quickly than that to the potent antibiotic gentamicin. Furthermore, we found that Peptide K6 was safe and effective in clearing mixed P. aeruginosa-S. aureus biofilms in a mouse model of persistent infection. Taken together, the properties of Peptide K6 suggest that it is a promising antibiotic candidate and that design of additional short peptides that form micelles represents a worthwhile approach for the development of antimicrobial agents.

Application of peripheral blood routine parameters in the diagnosis of influenza and Mycoplasma pneumoniae.

OBJECTIVES: Influenza and Mycoplasma pneumoniae infections often present concurrent and overlapping symptoms in clinical manifestations, making it crucial to accurately differentiate between the two in clinical practice. Therefore, this study aims to explore the potential of using peripheral blood routine parameters to effectively distinguish between influenza and Mycoplasma pneumoniae infections. METHODS: This study selected 209 influenza patients (IV group) and 214 Mycoplasma pneumoniae patients (MP group) from September 2023 to January 2024 at Nansha Division, the First Affiliated Hospital of Sun Yat-sen University. We conducted a routine blood-related index test on all research subjects to develop a diagnostic model. For normally distributed parameters, we used the T-test, and for non-normally distributed parameters, we used the Wilcoxon test. RESULTS: Based on an area under the curve (AUC) threshold of ≥ 0.7, we selected indices such as Lym# (lymphocyte count), Eos# (eosinophil percentage), Mon% (monocyte percentage), PLT (platelet count), HFC# (high fluorescent cell count), and PLR (platelet to lymphocyte ratio) to construct the model. Based on these indicators, we constructed a diagnostic algorithm named IV@MP using the random forest method. CONCLUSIONS: The diagnostic algorithm demonstrated excellent diagnostic performance and was validated in a new population, with an AUC of 0.845. In addition, we developed a web tool to facilitate the diagnosis of influenza and Mycoplasma pneumoniae infections. The results of this study provide an effective tool for clinical practice, enabling physicians to accurately diagnose and differentiate between influenza and Mycoplasma pneumoniae infection, thereby offering patients more precise treatment plans.

Enhancing thalassemia gene carrier identification in non-anemic populations using artificial intelligence erythrocyte morphology analysis and machine learning.

BACKGROUND: Non-anemic thalassemia trait (TT) accounted for a high proportion of TT cases in South China. OBJECTIVE: To use artificial intelligence (AI) analysis of erythrocyte morphology and machine learning (ML) to identify TT gene carriers in a non-anemic population. METHODS: Digital morphological data from 76 TT gene carriers and 97 controls were collected. The AI technology-based Mindray MC-100i was used to quantitatively analyze the percentage of abnormal erythrocytes. Further, ML was used to construct a prediction model. RESULTS: Non-anemic TT carriers accounted for over 60% of the TT cases. Random Forest was selected as the prediction model and named TT@Normal. The TT@Normal algorithm showed outstanding performance in the training, validation, and external validation sets and could efficiently identify TT carriers in the non-anemic population. The top three weights in the TT@Normal model were the target cells, microcytes, and teardrop cells. Elevated percentages of abnormal erythrocytes should raise a strong suspicion of being a TT gene carrier. TT@Normal could be promoted and used as a visualization and sharing tool. It is accessible through a URL link and can be used by medical staff online to predict the possibility of TT gene carriage in a non-anemic population. CONCLUSIONS: The ML-based model TT@Normal could efficiently identify TT carriers in non-anemic people. Elevated percentages of target cells, microcytes, and teardrop cells should raise a strong suspicion of being a TT gene carrier.

Application of next-generation sequencing on diagnosis of bloodstream infection caused by Mycoplasma hominis in a patient with ANCA-associated vasculitis.

BACKGROUND: Mycoplasma hominis is one of the main opportunistic pathogenic mycoplasmas in humans which has a major impact on patients with bloodstream infections. Because it is difficult to detect or isolate, rapid and accurate diagnosis using improved methods is essential and still challenging for patients with bloodstream infection. CASE PRESENTATION: In this case, we reported the application of next -generation sequencing for the diagnosis of bloodstream infection caused by Mycoplasma hominis in a patient with Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. After 9 days of combined treatment with levofloxacin, polymyxin B and meropenem, the patient's condition was gradually controlled and he was discharged without further complications. During the three-month outpatient follow-up, no recurrence of symptoms or clinical signs was reported. CONCLUSIONS: This successful application of next generation sequencing assisted the rapid diagnosis of Mycoplasma hominis bloodstream infection, provided a new perspective in the clinical approach and highlighted the potential of this technique in rapid etiological diagnosis.

Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii Pneumonia in critically pediatric patients.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of metagenomic next-generation sequencing (mNGS) for the diagnosis of Pneumocystis jirovecii Pneumonia (PCP) in critically pediatric patients. METHODS: Seventeen critically pediatric patients with PCP and sixty patients diagnosed with non-PCP pneumonia who were admitted in pediatric intensive care unit between June 2018 and July 2021 were enrolled. Conventional methods and mNGS for detecting Pneumocystis jirovecii (P. jirovecii) were compared. The patients' demographics, comorbidities, laboratory test results, antibiotic treatment response and 30 day mortality were analyzed. RESULT: The mNGS showed a satisfying diagnostic performance with a sensitivity of 100% in detecting P. jirovecii compared with Gomori methenamine silver staining (5.9%), serum (1,3)-ß-D-glucan (86.7%) and and LDH (55.6%). The diagnostic specificity of mNGS for PCP was higher than that of serum BDG (56.7%) and LDH (71.4%). In PCP group, over one thirds' cases had mixed infections. Compared with survivors, non-survivors had higher stringently mapped read numbers (SMRNs) in bronchoalveolar lavage fluid (BALF) sample (P < 0.05), suggesting SMRNs were closely associated with the severity of response. The detection for P. jirovecii by mNGS both in BALF and blood samples reached a concordance rate of 100%, and the SMRNs in the BALF were remarkably higher than that in blood samples. Initial antimicrobial treatment was modified in 88.2% of PCP patients based on the mNGS results. CONCLUSION: The mNGS is a potential and efficient technology in diagnosing PCP and shows a satisfying performance in the detection of co-pathogens. Both blood and BALF samples for mNGS are suggested for the presumptive diagnosis of PCP.

Development and validation of a nomogram for evaluating the prognosis of immunotherapy plus antiangiogenic therapy in non-small cell lung cancer.

BACKGROUND: With the combination therapy of PD-1/PD-L1 antibody and antiangiogenic drugs used widely in clinic, a novel method to estimate the prognosis of patients is needed. We aimed to develop a nomogram to examine prognosis of anti-PD-1/PD-L1 antibody plus bevacizumab in non-small cell lung cancer (NSCLC) patients. METHODS: We developed a nomogram using the cohort involving 204 NSCLC patients who treated with immunotherapy and anti-angiogenesis therapy. The nomogram was validated under the same conditions in another cohort with 69 patients. Prognostic factors were analyzed by Cox regression analysis. The nomogram was internally validated using bootstrap resampling and then externally validated. Performance was assessed using concordance index, calibration curve and decision curve analysis. Clinical utility was evaluated using receiver operation characteristic curve. RESULTS: Pleural metastasis (P = 0.001, HR = 2.980, 95%CI 1.521-5.837), ANC (P < 0.001, HR = 5.139, 95%CI 2.081-12.691), ALC (P = 0.010, HR = 0.331, 95%CI 0.142-0.771), B cells (P = 0.005, HR = 0.329, 95%CI 0.151-0.714), Treg cells (P = 0.002, HR = 2.934, 95%CI 1.478-5.826) were independent prognostic factors. The calibration curves showed good consistency and the C-index of nomogram were 0.808, 0.741 in training and external validation cohort, respectively. The area under the curve (AUC) in receiver operation characteristic curves (ROC) are 0.833 (P < 0.001) and 0.908 (P < 0.001), respectively. CONCLUSION: We build an accurate and convenient nomogram to predict long-time overall survival (OS) of NSCLC patients treated with PD-1/PD-L1 antibody and antiangiogenic drugs and validated this nomogram. The nomogram might be helpful to clinicians to estimate long-time OS of NSCLC patients treated with PD-1/PD-L1 antibody and antiangiogenic drugs.

Applying low coverage whole genome sequencing to detect malignant ovarian mass.

To evaluate whether low coverage whole genome sequencing is suitable for the detection of malignant pelvic mass and compare its diagnostic value with traditional tumor markers. We enrolled 63 patients with a pelvic mass suspicious for ovarian malignancy. Each patient underwent low coverage whole genome sequencing (LCWGS) and traditional tumor markers test. The pelvic masses were finally confirmed via pathological examination. The copy number variants (CNVs) of whole genome were detected and the Stouffers Z-scores for each CNV was extracted. The risk of malignancy (RM) of each suspicious sample was calculated based on the CNV counts and Z-scores, which was subsequently compared with ovarian cancer markers CA125 and HE4, and the risk of ovarian malignancy algorithm (ROMA). Receiver Operating Characteristic Curve (ROC) were used to access the diagnostic value of variables. As confirmed by pathological diagnosis, 44 (70%) patients with malignancy and 19 patients with benign mass were identified. Our results showed that CA125 and HE4, the CNV, the mean of Z-scores (Zmean), the max of Z-scores (Zmax), the RM and the ROMA were significantly different between patients with malignant and benign masses. The area under curve (AUC) of CA125, HE4, CNV, Zmax, and Zmean was 0.775, 0.866, 0.786, 0.685 and 0.725 respectively. ROMA and RM showed similar AUC (0.876 and 0.837), but differed in sensitivity and specificity. In the validation cohort, the AUC of RM was higher than traditional serum markers. In conclusion, we develop a LCWGS based method for the identification of pelvic mass of suspicious ovarian cancer. LCWGS shows accurate result and could be complementary with the existing diagnostic methods.

A case series of medically managed Candida parapsilosis complex prosthetic valve endocarditis.

BACKGROUND: In recent years, Candida parapsilosis is recognized as a species complex and is composed of Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis. Candida parapsilosis complex prosthetic valve endocarditis (PVE) is rare and the survival rate is still low despite of optimal therapeutic strategies. In our report, it is novel to report cases as Candida parapsilosis complex PVE at species and identify Candida parapsilosis using MALDI-TOF MS. Case presentation A series of 4 cases of Candida parapsilosis complex PVE from our institution was reported. Three were infected by Candida parapsilosis sensu stricto and one was infected by Candida metapsilosis. The condition of two cases got better and the other died. CONCLUSIONS: More attention should be paid to Candida parapsilosis complex PVE and early diagnosis and prompt antibiotic therapy may play a role in the treatment for Candida parapsilosis complex PVE. It is recommended to identify Candida parapsilosis complex at species level and MALDI-TOF MS as an easy, fast and efficient identification method is worth promoting in clinical microbiology.

A Novel Diagnosis Method Based on Methylation Analysis of SHOX2 and Serum Biomarker for Early Stage Lung Cancer.

OBJECTIVES: Lung cancer (LC) is often accompanied by significant methylation abnormalities. This study aimed to develop a decision tree (DT) accompanied the stature homeobox 2 gene (SHOX2) / prostaglandin E receptor 4 (PTGER4) gene DNA methylation with traditional tumor marker in the differential diagnosis of benign and malignant lung nodule. METHODS: We performed a study with 104 patients enrolled in the LC group and 36 patients in the benign lung diseases group. All the clinical data of these patients were collected through electronic medical record. Total Methylation (TM) status of both SHOX2 and PTGER4 was defined as methylation levels of SHOX2 plus methylation levels of PTGER4. One-way analysis was used to compare the concentrations of serum samples and t-test was used to compare pairwise mean values between groups. Receiver operating curve (ROC) was used to evaluate the diagnostic value. Furthermore, the strategy was validated in 19 LC patients and 11 patients with benign lung diseases. RESULTS: There were significant differences between the concentration of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA21 -1) and the methylation levels of SHOX2, PTGER4 and TM in lung benign diseases and cancer group. The AUCs of NSE, CEA, CYFRA21 -1, Methylation SHOX2, Methylation PTGER4 and TM were 0.721 (95% CI: 0.627-0.816), 0.753 (95% CI: 0.673-0.833) and 0.778(95% CI: 0.700-0.856), 0.851(0.786-0.916), 0.847(0.780-0.913) and 0.861(0.800-0.922) respectively. We developed a DT model with TM and CYFRA21 -1 used in this study, and the area under the curve (AUC) of DT was 0.921 and the sensitivity up to 0.856. In the validation cohort, the AUC of SHOX2, PTGER4 and TM was also much higher than traditional serum markers. CONCLUSIONS: Our results indicated that the DT model calculated from the TM and CYFRA21 -1 can accurately classify LC and benign diseases, which showed better diagnostic performance than traditional serum parameter.

Evaluation of Architect anti-HCV Signal to Cutoff Ratios for Predicting Hepatitis C Viremia Using COBAS AmpliPrep/COBAS TaqMan HCV Quantitative Test.

BACKGROUND: The aim of the study is to evaluate the significance of the Architect anti-HCV signal to cutoff (S/CO) ratios for predicting hepatitis C viremia and determine the optimal S/Co ratio value for Architect anti-HCV assay. METHODS: The results of patients who underwent HCV RNA quantitative assays because of positive anti-HCV from January 2015 to August 2019 were retrospectively analyzed, including S/Co ratio values, HCV RNA quantitative results, alanine aminotransferase (ALT), and aspartate transaminase (AST) values. Binary logistic regression and Spearman's correlation coefficient were used to analyze the collected data. Receiver-operating characteristics curve (ROC) was applied to analyze the predicting values of the indexes. RESULTS: In total, 811 patients were included in our study and HCV viremia was detected in 342 (42.1%) patients. There is no correlation between anti-HCV S/CO ratio and HCV RNA level. The samples with an S/Co ratio between 1 and 4 (271/271, 100%) were all HCV RNA negative. The area under the ROC curve of anti-HCV S/CO ratio was 0.8714 and the maximal Youden index was 0.681 at an optimal cutoff S/CO ratio value of 8.99. CONCLUSIONS: With the cutoff value of 1.0, the Architect anti-HCV assay showed excellent sensitivity but poor specificity in predicting HCV viremia. An S/Co ratio of 8.99 was optimal for further confirmation testing of HCV viremia.

Clinical performance of non-invasive prenatal testing for trisomies 21, 18 and 13 in twin pregnancies: A cohort study and a systematic meta-analysis.

INTRODUCTION: The objective of this study was to report on the clinical performance of non-invasive prenatal testing (NIPT) for trisomies 21, 18 and 13 in twin pregnancies and to define the performance of NIPT by combining our cohort study results with published studies in a systematic meta-analysis. MATERIAL AND METHODS: A cohort study was carried out in the First Affiliated Hospital of Sun Yat-sen University and Kanghua Hospital. Meanwhile, searches of PubMed, EMBASE, The Cochrane Library and Web of Science for all relevant peer-reviewed articles were performed with a restriction to English language publication before 15 June 2019. Quality assessments were conducted with the Quality Assessment Tool for Diagnostic Accuracy Studies-2 checklist. Data analysis, heterogeneity, subgroup analysis and publication bias were carried out using META-DISC 1.4 and STATA 12.0. RESULTS: In all, 141 twin pregnancies included in our cohort study; confirmation revealed one true-positive case for trisomy 21 and 140 true-negative cases. The sensitivity and specificity for trisomy 21 by NIPT were both 100%. Twenty-two eligible studies were enrolled in this meta-analysis together with our study. There were 199 cases of trisomy 21, 58 cases of trisomy 18, 14 cases of trisomy 13 and 6347 cases of euploids in total. For trisomy 21, NIPT showed the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.99, 1.00, 145.81, 0.06 and 1714.09, respectively. For trisomy 18, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.88, 1.00, 200.98, 0.19 and 483.68, respectively. CONCLUSIONS: The performance of NIPT for trisomy 21 in twin pregnancy was excellent and it was similar to that reported in singleton pregnancy. However, due to publication bias (trisomy 18) and small number of cases (trisomy 13), accurate assessment of the predictive performance of NIPT for trisomies 18 and 13 could not be achieved.

Differential diagnosis of tuberculous and malignant pleural effusions: comparison of the Th1/Th2 cytokine panel, tumor marker panel and chemistry panel.

The differentiation between tuberculous plural effusion (TPE) and malignant plural effusion (MPE) remains a major clinical challenge in the diagnosis and management of pleural effusions, especially in developing countries with a high incidence of tuberculosis. We aimed to evaluate the diagnostic value of cytokines, tumor markers and biochemical markers in the differentiation of TPE and MPE. Two hundred and forty-two patients were included, of whom 134 were diagnosed with MPE and 108 were diagnosed with TPE. In total, 12 markers were tested in pleural effusion samples from all subjects: Interleukin-2 (IL-2), Tumor necrosis factor alpha (TNF-α), Interferon (IFN)-γ, interleukins-4, 6, 10 (IL-4,6,10), cytokeratin-19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA), neuron specific enolase (NSE), adenosine deaminase (ADA), lactate dehydrogenase (LDH) and high sensitivity C- reactive protein (Hs-CRP). The diagnostic value of each marker was evaluated and compared by receiver operating characteristic (ROC) curves. In the 12 markers evaluated, TNF-α, IFN-γ, IL-6, CYFRA 21-1, CEA, ADA and Hs-CRP were significantly different between the TPE and MPE groups, and the areas under the ROC curves were 0.624, 0.942, 0.619, 0.808, 0.903, 0.842 and 0.917, respectively. IFN-γ showed a better diagnostic performance than the other markers. With a cut-off value of >2.45 pg/mL, the sensitivity and specificity of IFN-γ were 91.11 and 91.94%, respectively. TNF-α, IFN-γ, IL-6, CYFRA 21-1, CEA, ADA and Hs-CRP were useful in the differentiation between the TPE and MPE groups. IFN-γ showed a better diagnostic performance than the multitude of other markers evaluated in this study, which is satisfactory for the discrimination of TPE and MPE.

Performance evaluation of the DAAN HCV assay for quantification of hepatitis C virus RNA and its comparison with COBAS AmpliPrep/COBAS TaqMan HCV Quantitative Test, v2.0.

BACKGROUND: The Daan HCV RNA quantitative assay was a recently developed kit with high sensitivity for the detection of HCV RNA. We aimed to evaluate the analytical performance of the Daan HCV RNA quantitative assay and compare it with the COBAS AmpliPrep/COBAS TaqMan HCV Quantitative Test, v2.0. METHOD: WHO HCV RNA standard, NIBSC 06/102 standard, and CLSI EP documents were used to evaluate the precision, accuracy, linearity, anti-interference ability, and cross-reactivity of the Daan HCV RNA quantitative assay. Overall 198 clinical serum specimens were used to make comparison between the Daan HCV RNA quantitative assay and the Roche Cobas test. RESULTS: The within-run precision (Swithin ), and total precision (Stotal ) for 6.11 log IU/mL, 4.22 log IU/mL, and 2.32 log IU/mL HCV RNA were 0.13 and 0.15, 0.07 and 0.09, and 0.11 and 0.10, respectively. The linear range was 20-108  IU/mL, and the limit of detection was 15 IU/mL. It did not display any interference with commonly encountered conditions and cross-reactivity with some common virus. A good agreement was observed between the Daan HCV RNA quantitative assay and the Roche Cobas test. CONCLUSION: The Daan HCV RNA quantitative assay has shown satisfactory performances and excellent agreement with COBAS HCV Quantitative Test on clinical specimens with lower cost, which provides an alternative choice for the diagnosis and monitoring of HCV infection in developing countries.

High prevalence of breastmilk-acquired cytomegalovirus infection in jaundiced infants.

BACKGROUND: Our objective was to evaluate the prevalence and different diagnostic methods of breastmilk (BM)-acquired cytomegalovirus (CMV) infection in a pathologically jaundiced cohort. METHODS: A total of 400 infants confirmed with pathological jaundice at The People's Hospital of Qingyang City were screened for BM-acquired CMV infection between February 2018 and February 2019. A total of 300 infants were finally enrolled in our study. CMV infection was confirmed by detecting both CMV-DNA in various samples using FQ-PCR and CMV-IgM with chemiluminescence. Clinical and other laboratory data were collected from these infants during their hospitalization or regular visits. RESULTS: Ninety-eight (32.67%) subjects were confirmed to be BM CMV-DNA-positive, and 18 (18.37%) were diagnosed with a BM-acquired CMV infection. All 18 (100%) infants with a BM-acquired CMV infection were CMV-DNA-positive in urine, while 5 (27.78%) cases and 11 (61.11%) cases were confirmed in plasma and peripheral blood mononuclear cells (PBMCs), respectively. Only 6 (33.33%) infants were CMV-IgM-positive. Birthweight, direct bilirubin, aspartate aminotransferase, and the viral load in BM of the BM-acquired CMV group were higher than those in the non-infected group (P < .05). Low birthweight and viral load in BM were risk factors for BM-acquired CMV infection. Detecting CMV-DNA in urine samples exhibited better performance than the other methods for screening BM-acquired CMV infections. CONCLUSIONS: Our study found a high prevalence of BM-acquired CMV infection in jaundiced infants, and detecting CMV-DNA in a urine sample was the most sensitive method for disease screening.

Glomerular Parietal Epithelial Cells Infection Is Associated With Poor Graft Outcome in Kidney Transplant Recipients With BK Polyomavirus-Associated Nephropathy.

BACKGROUND: The purpose of this study was to investigate the effect of BK polyomavirus (BKPyV infection of glomerular parietal epithelial cells (GPECs) on graft outcome in kidney transplant recipients with BKPyV-associated nephropathy (BKPyVAN). METHODS: A total of 152 kidney transplant recipients with BKPyVAN were divided into 31 with (GPEC-positive group) and 121 without (GPEC-negative group) BKPyV-infected GPECs. Clinicopathological characteristics and allograft survival were compared between the groups. RESULTS: The GPEC-positive group had more patients with advanced-stage BKPyVAN than the GPEC-negative group (P < .001). At the last follow-up, the GPEC-positive group had a significantly higher serum creatinine level than the GPEC-negative group. The graft loss rate in the GPEC-positive group was higher than that in the GPEC-negative group (32.3% vs 12.4%; P = .008). Kaplan-Meier analysis showed that the graft survival rate in the GPEC-positive group was lower than that in the GPEC-negative group (log-rank test, P = .004). Multivariate Cox regression analysis demonstrated that BKPyV infection of GPECs was an independent risk factor for graft survival (hazard ratio, 3.54; 95% confidence interval, 1.43-8.76; P = .006). CONCLUSIONS: GPEC infection in patients with BKPyVAN indicates more-severe pathological damage and a rapid decline in renal function. BKPyV infection of GPECs is an independent risk factor for allograft loss.

Th17-associated cytokines multiplex testing indicates the potential of macrophage inflammatory protein-3 alpha in the diagnosis of biliary atresia.

BACKGROUND & AIMS: Biliary atresia (BA) is a neonatal obliterative cholangiopathy with high prevalence in south China. Accurate identification of BA among infants with obstructive jaundice is still difficult by noninvasive diagnostic tools. Th17 cells have been reported closely related with the development of BA, which suggest that Th17-associated cytokines were potential biomarkers for the diagnosis of BA patients. METHODS: In the training study, 76 infants who were divided into 2 groups, including BA group (n = 31) and non-BA jaundice group (n = 45). Clinical and routine laboratory data were collected from all subjects. Totally 25 Th17-associated cytokines were tested and compared between groups. The diagnostic value of each differential cytokine was evaluated by the area under the receiver operating characteristic curve (AUC). The best potential diagnostic biomarker was further validated in a cohort including 68 jaundice infants from our partnering institution in a blinded fashion. RESULTS: Data from the training study showed that gamma-glutamyl transferase (GGT) and clay stool would be helpful in the identification of BA patients in jaundice subjects. Th17-associated cytokines assay indicated that IL-17F, IL-10, macrophage inflammatory protein-3alpha (MIP3a), IL-22, IL-13, IL-33, IL-6, IL-17E, IL-27, IL-31, TNF-a and TNF-b were differentially expressed in BA patients, and the AUC of MIP3a was higher than other markers. MIP3a alone or combined with other laboratory data would significantly increase the diagnostic accuracy of BA. The diagnostic value of MIP3a was further confirmed in our validation study. CONCLUSION: MIP3a alone or combined with other laboratory data would significantly increase the diagnostic accuracy of BA.

The phenomena of balanced effect between α-globin gene and of ß-globin gene.

BACKGROUND: Thalassemias (TM) are the most common autosomal recessive disorders in Southeast Asian countries. Both α- and ß-thalassemia lead to a decrease or absence of globin chains. The most serious of the thalassemia syndromes is thalassemia major which is characterized by a transfusion dependent anemia and subsequent iron overload caused by repeated blood transfusions. It is preventive by genotyping the parents. A better understanding of the laboratory data will help provide an accurate diagnosis of thalassemia major, and prevention and controlling programs in routine laboratories. CASE PRESENTATION: The patient was a one-year-old boy born to non-consanguineous parents. He was referred to our outpatient clinic for hemolytic anemia after a cold. Hematological investigations revealed severe anemia (Hb57 g/dL). The red cells displayed microcytosis, hypochromia and misshapen erythrocytes (MCV48.8 fL, MCH15.7 pg). Capillary electrophoresis (CE) electropherogram revealed normal level of HbA2 (3.2%) and elevated HbF (35.1%). The patient was diagnosed with ß-TM, based on severe microcytosis, hypochromia, normal Hb A2 and high Hb F level but no Hb H inclusion at the first visit. Later our molecular analysis revealed compound heterozygosity for codons 41-42 (-TTCT) (HBB: c.126_129delCTTT, ß0) and IVS-II-654 (C > T) (HBB: c.316-197C > T, ß+) mutation and deletional Hb H (--SEA/-α3.7). Thus, a combination of Hb H disease and a compound heterozygosity of ß+/ß0-thalassemia (ß+/ß0-thal) was finally diagnosed. CONCLUSIONS: Genotype-phenotype analysis shows that heterozygous mutations in the ß-globin gene could affect not only hematological parameters, but also elevate HbA2 levels. These effects could be ameliorated by the coinheritance of Hb H disease, which may be explained by the phenomena of the α-globin gene and of the ß-globin gene balanced effect.

Prognostic value of pretreatment serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in patients with esophageal squamous cell carcinoma.

BACKGROUND: The levels of liver function tests (LFTs) are often used to assess liver injury and non-liver disease-related mortality. In our study, the relationship between pretreatment serum LFTs and overall survival (OS) was evaluated in esophageal squamous cell carcinoma (ESCC) patients. METHODS: Our purpose was to investigate the prognostic value of the preoperative alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in ESCC patients. A retrospective study was performed in 447 patients with ESCC, and follow-up period was at least 60 months until death. The prognostic significance of serum LFTs were determined by univariate and multivariate Cox hazard models. RESULTS: LFTs including ALT, AST, LSR, GGT, TBA and LDH were analyzed. Serum LSR (HR: 0.592, 95% CI = 0.457-0.768, p < 0.001 and GGT (HR: 1.507, 95% CI = 1.163-1.953, p = 0.002) levels were indicated as significant predictors of OS. The 5-year OS among patients with higher LSR levels was longer compared with those patients with decreased LSR levels, not only in the whole cohort but also in the subgroups stratified by pathological stage (T1-T2 subgroup, T3-T4 subgroup, N0 subgroup and M0 subgroup). We also found that patients with a higher GGT might predict worse OS than patients with a normal GGT, not only in the whole cohort but also in the subgroups stratified by pathological stage (T3-T4 subgroup and N1-N2 subgroup). CONCLUSIONS: Both increased levels of LSR and decreased levels of GGT might predict shorter overall survival in ESCC patients. Our findings suggest that serum LSR and GGT levels could be used as a key predictor of survival in patients with ESCC.

Evaluation of HE4 in the Diagnosis and Follow Up of Non-Small Cell Lung Cancers.

BACKGROUND: The aim of our study was to evaluate the performance of HE4 in the diagnosis and follow up in patients with non-small cell lung cancer (NSCLC). METHODS: Serum levels of HE4, CEA, and Cyfra 21-1 were analyzed in 146 patients suspected with NSCLC and 30 healthy subjects to evaluate their diagnostic performance. A one year follow up was performed in 61 patients confirmed with NSCLC after surgery eradication at the interval of 1 month, 3 months, 6 months, and 12 months. RESULTS: Our results showed that the area under the receiver operating characteristics curve (AUC) of HE4 was 0.761, which was similar with CEA. The sensitivity and specificity of HE4 was 0.82 and 0.62, respectively, at the level of 75.0 pmol/L. The AUC of HE4 was 0.70, 0.81, and 0.90 at 1 month, 3 months, and 6 months after surgery, respectively, which was significantly higher than CEA and Cyfra 21-1. CONCLUSIONS: Our finding indicates that HE4 is a potential marker for the diagnosis and follow up of NSCLC patients, which is complementary with CEA and Cyfra 21-1 and accurate in predicting NSCLC recurrence in early stage.