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Background: The intent of this research was to generate and investigate the D-dimer to lymphocyte ratio (DLR) capacity to forecast the risk and prognosis of colorectal cancer liver metastases (CRCLM)., Methods: From January 2010 to December 2019, 177 clinicopathologically confirmed colorectal cancer (CRC) patients (89 in the control group and 88 in the experimental group) were identified at the Affiliated Cancer Hospital of Guangxi Medical University. Multivariate Cox regression analysis was used to screen independent predictive diagnostic and prognostic factors of liver metastasis in CRC, and receiver operating characteristic (ROC) curves and Kaplan‒Meier (K‒M) curves were established to analyze the diagnostic and predictive prognostic efficacy of the DLR in the development of CRCLM., Results: Patients with CRCLM had higher DLR levels and D-dimer levels in their blood, with statistically significant differences (p < 0.001). DLR might be employed as a predictor for the development of CRCLM, according to ROC curve research (sensitivity 0.670, specificity 0.775, area under the curve 0.765). D-dimer, lymphocyte count CEA, CA125, and CA199 were not linked to prognosis in patients with CRCLM in Cox regression analysis of dichotomous variables. In contrast, DLR level was a possible risk factor for the prognosis of patients with CRCLM (HR = 2.108, p = 0.047), and age, T stage, and DLR level (DLR < 0.4) were connected with the prognosis of patients with CRCLM (p < 0.05)., Conclusion: DLR serves as a risk indicator for the development of CRCLM., (© 2023. The Author(s).)

Background: Both lymphopenia and thyroid dysfunction are commonly observed among COVID-19 patients. Whether thyroid function independently correlates with lymphocyte counts (LYM) remains to be elucidated., Methods: We included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to April 2021 who had thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and LYM measured on admission., Results: A total of 541 patients were included. Median LYM was 1.22 x 10 9 /L, with 36.0% of the cohort lymphopenic. 83 patients (15.4%) had abnormal thyroid function tests (TFTs), mostly non-thyroidal illness syndrome (NTIS). Patients with lymphopenia had lower TSH, fT4 and fT3 levels than those without. Multivariable stepwise linear regression analysis revealed that both TSH (standardized beta 0.160, p<0.001) and fT3 (standardized beta 0.094, p=0.023), but not fT4, remained independently correlated with LYM, in addition to age, SARS-CoV-2 viral load, C-reactive protein levels, coagulation profile, sodium levels and more severe clinical presentations. Among the 40 patients who had reassessment of TFTs and LYM after discharge, at a median of 9 days from admission, there were significant increases in TSH (p=0.031), fT3 (p<0.001) and LYM (p<0.001). Furthermore, patients who had both lymphopenia and NTIS were more likely to deteriorate compared to those who only had either one alone, and those without lymphopenia or NTIS (p for trend <0.001)., Conclusion: TSH and fT3 levels showed independent positive correlations with LYM among COVID-19 patients, supporting the interaction between the hypothalamic-pituitary-thyroid axis and immune system in COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lui, Lee, Chow, Lee, Tam, Pang, Ho, Cheung, Fong, Law, To, Lam, Tan, Woo, Hung and Lam.)

Background: Early identification of patients with severe coronavirus disease (COVID-19) at an increased risk of progression may promote more individualized treatment schemes and optimize the use of medical resources. This study is aimed at investigating the utility of the C-reactive protein to albumin (CRP/Alb) ratio for early risk stratification of patients., Methods: We retrospectively reviewed 557 patients with COVID-19 with confirmed outcomes (discharged or deceased) admitted to the West Court of Union Hospital, Wuhan, China, between January 29, 2020 and April 8, 2020. Patients with severe COVID-19 ( n = 465) were divided into stable ( n = 409) and progressive ( n = 56) groups according to whether they progressed to critical illness or death during hospitalization. To predict disease progression, the CRP/Alb ratio was evaluated on admission., Results: The levels of new biomarkers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, CRP/Alb ratio, and systemic immune-inflammation index, were higher in patients with progressive disease than in those with stable disease. Correlation analysis showed that the CRP/Alb ratio had the strongest positive correlation with the sequential organ failure assessment score and length of hospital stay in survivors. Multivariate logistic regression analysis showed that percutaneous oxygen saturation (SpO2), D-dimer levels, and the CRP/Alb ratio were risk factors for disease progression. To predict clinical progression, the areas under the receiver operating characteristic curves of Alb, CRP, CRP/Alb ratio, SpO2, and D-dimer were 0.769, 0.838, 0.866, 0.107, and 0.748, respectively. Moreover, patients with a high CRP/Alb ratio (≥1.843) had a markedly higher rate of clinical deterioration (log - rank  p < 0.001). A higher CRP/Alb ratio (≥1.843) was also closely associated with higher rates of hospital mortality, ICU admission, invasive mechanical ventilation, and a longer hospital stay., Conclusion: The CRP/Alb ratio can predict the risk of progression to critical disease or death early, providing a promising prognostic biomarker for risk stratification and clinical management of patients with severe COVID-19., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Yi Li et al.)

Data on the impact of lymphocytes and neutrophils on the incidence of liver dysfunction in COVID-19 patients are limited. This study aimed to investigate the lateral and longitudinal associations of lymphocyte ratio (LR) and neutrophil ratio (NR) on liver dysfunction in COVID-19 patients. We tested 1,409 blood samples from 245 COVID-19 patients in China between January 2020 and June 2021. The lateral U-shaped relationships, determined by smooth curve fitting and the piecewise-linear mixed-effect model, were observed between LR, NR, and AST and the incidence of AST-linked liver dysfunction, with the threshold cutoffs of 26.1 and 62.0, respectively. Over the 1,409 tests, the LR ≤ 26.1 and NR ≥ 62.0 related to the occurrence of mild liver dysfunction (HR: 1.36; 95% CI: 1.01, 1.82), moderate liver dysfunction (HR: 1.37; 95% CI: 1.01, 1.85), and severe liver dysfunction (HR: 1.72; 95% CI: 1.02, 2.90). For the patients with preexisting AST ≥ 35 U/L, the baseline LR ≤ 26.1 and NR ≥ 62.0 (b.LLCHN) groups had a fully adjusted 8.85-, 7.88-, and 5.97-fold increased risk of mild and moderate liver dysfunction after being hospitalized of 3, 6, and 9 days compared to the baseline LR > 26.1 and NR < 62.0 (b.normal) groups. Severe liver dysfunction only presents significant differences after being adjusted for age, sex, and BMI. Consistently, Kaplan-Meier analyses showed that b.LLCHN reflects a better predictive value for different subsequent magnitude liver dysfunctions after admission of 3 and 6 days. To improve liver function in patients with preexisting AST ≥35 U/L, future management strategies should pay more attention to baseline LR ≤ 26.1 and NR ≥ 62.0 patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Liu, Yu, Liu, Zhang, Wang, Miao, Li, Huang and Bao.)

To explore the characteristics of COVID-19 infection related kidney injury, we retrospectively collected cases of COVID-19 patients with definite clinical outcomes (discharge or death) and relevant laboratory results from Jan 3 to Mar 30, 2020 in Tongji hospital, Wuhan, China. 1509 patients were included, 1393 cases with normal baseline serum creatinine, and 116 cases with elevated baseline serum creatinine (EBSC). On admission, the prevalence of elevated serum creatinine, elevated blood urea nitrogen (BUN) and estimated glomerular filtration (eGFR) under 60 ml/min/1.73 m 2 were 7.7%, 6.6% and 7.2%, respectively. The incidence of in-hospital death in the patients with EBSC was 7.8%, which was significantly higher than those with normal serum creatinine (1.2%). Inflammatory, immunological, and organ damage indices were relatively higher in the EBSC group, in which lymphocytes, albumin, and hemoglobin were significantly lower. Kaplan-Meier analysis revealed age above 65 years, males, comorbidities (especially for cardiovascular disease and tumor patients), lymphocyte count < 1.5 × 10 9 /L, leukocyte count > 10 × 10 9 /L, EBSC, eGFR < 60 ml/min/1.73 m 2 were associated with in-hospital death. Multivariate Cox proportional hazard regression confirmed that EBSC (HR: 2.643, 95% CI: 1.111-6.285, P = 0.028), eGFR < 60 ml/min/1.73 m 2 (HR: 3.889, 95% CI: 1.634-9.257, P = 0.002), were independent risk factors after adjusting for age, sex, any comorbidity, leukocyte and lymphocyte count. Therefore, the prevalence of kidney injury in patients with COVID-19 was high and associated with in-hospital mortality. Early detection and effective intervention of kidney injury may reduce COVID-19 deaths., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Abstract: This study aimed to explore the significance and prognostic value of serum tumor-associated carbohydrate antigen 19-9 (CA19-9), D-dimer, and tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) in patients with pancreatic ductal adenocarcinoma (PDAC).Our study included 148 patients treated for PDAC at Northern Jiangsu People's Hospital Affiliated to Yangzhou University from January 2012 to December 2016. Cutoff prognostic values were predicted using the receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to assess the survival rates of patients. Univariate and multivariate COX regression analyses were used to evaluate the prognostic factors.The recommended cutoff values of neutrophil-lymphocyte rate (NLR), platelet-lymphocyte rate (PLR), CA19-9, and D-dimer were 2.04 (sensitivity, 0.59; specificity, 0.9; area under the ROC curve [AUC], 0.749; P < .001), 52.94 (sensitivity, 0.73; specificity, 0.95; AUC, 0.829; P < .001), 176.66 U/mL (sensitivity, 0.7; specificity, 0.9; AUC, 0.794; P < .001), and 1.18 mg/L (sensitivity, 0.82; specificity, 0.9; AUC, 0.845; P < .001), respectively. Positive TNFAIP3/A20 expression was considered as an inclusion criterion. Serum CA19-9 expression was related with lymph node metastasis (P = .010), tumor-lymph node-metastasis (TNM) stage (P < .001), and survival rate (P < .001). D-dimer was correlated with tumor differentiation grade (P = .014), tumor size (P = .045), TNM stage (P < .001), and survival rate (P < .001). TNFAIP3/A20 was correlated with tumor differentiation grade (P < .001), body mass index (BMI) (P < .001), TNM stage (P = .014), and survival rate (P < .001). Kaplan-Meier curves showed that PDAC patients had significant differences in CA19-9, D-dimer, and TNFAIP3/A20 expressions (P < .05). CA19-9, D-dimer, TNM stage, tumor differentiation grade, and TNFAIP3/A20 were independent prognostic markers for PDAC in univariate and multivariate COX analyses.CA19-9, D-dimer, and TNFAIP3/A20 were found to be independent prognostic markers for PDAC patients., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims/introduction: Chronic inflammation is an underlying feature of type 2 diabetes mellitus. Hypovitaminosis D is associated with type 2 diabetes mellitus, but whether it contributes to chronic inflammation is unclear. We examined the effects of vitamin D on various immune markers to evaluate its contribution to systemic inflammation in type 2 diabetes mellitus., Materials and Methods: We retrospectively analyzed data from type 2 diabetes mellitus patients, people with prediabetes and control patients without diabetes (n = 9,746). Demographic and clinical variables were evaluated using descriptive statistics and generalized linear regression. A stratified analysis based on total serum vitamin D was also carried out., Results: Neutrophil count was a significant predictor of 1,5-anhydroglucitol and glycated hemoglobin (HbA1c) in patients with prediabetes (1,5-anhydroglucitol: β = -0.719, P < 0.001 and HbA1c: β = -0.006, P = 0.002) and patients with diabetes (1,5-anhydroglucitol: β = 0.207, P = 0.004 and HbA1c: β = -0.067, P = 0.010). Lymphocyte count was a significant predictor of HbA1c in patients without diabetes (β = 0.056, P < 0.001) and patients with prediabetes (β = 0.038, P < 0.001). The neutrophil-to-lymphocyte ratio (NLR) was a significant predictor of HbA1c in patients without diabetes (β = -0.001, P = 0.032). No immune markers differed significantly based on vitamin D level among patients without diabetes (P> 0.05 for all). Among patients with prediabetes, those who were vitamin D-deficient had the highest NLR (P = 0.040). Among patients with diabetes, those who were vitamin D-deficient had the highest neutrophil count (P = 0.001), lowest lymphocyte count (P = 0.016) and highest NLR (P < 0.001)., Conclusions: The NLR is strongly influenced by serum vitamin D level. Given the high prevalence of hypovitaminosis D and elevated NLR among chronic disease patients and the elderly, our results suggest that clinical interpretation of NLR as a predictive marker of type 2 diabetes mellitus-related inflammation should consider vitamin D level, age and pre-existing morbidity., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Previous published prognostic models for COVID-19 patients have been suggested to be prone to bias due to unrepresentativeness of patient population, lack of external validation, inappropriate statistical analyses, or poor reporting. A high-quality and easy-to-use prognostic model to predict in-hospital mortality for COVID-19 patients could support physicians to make better clinical decisions., Methods: Fine-Gray models were used to derive a prognostic model to predict in-hospital mortality (treating discharged alive from hospital as the competing event) in COVID-19 patients using two retrospective cohorts (n = 1008) in Wuhan, China from January 1 to February 10, 2020. The proposed model was internally evaluated by bootstrap approach and externally evaluated in an external cohort (n = 1031)., Results: The derivation cohort was a case-mix of mild-to-severe hospitalized COVID-19 patients (43.6% females, median age 55). The final model (PLANS), including five predictor variables of platelet count, lymphocyte count, age, neutrophil count, and sex, had an excellent predictive performance (optimism-adjusted C-index: 0.85, 95% CI: 0.83 to 0.87; averaged calibration slope: 0.95, 95% CI: 0.82 to 1.08). Internal validation showed little overfitting. External validation using an independent cohort (47.8% female, median age 63) demonstrated excellent predictive performance (C-index: 0.87, 95% CI: 0.85 to 0.89; calibration slope: 1.02, 95% CI: 0.92 to 1.12). The averaged predicted cumulative incidence curves were close to the observed cumulative incidence curves in patients with different risk profiles., Conclusions: The PLANS model based on five routinely collected predictors would assist clinicians in better triaging patients and allocating healthcare resources to reduce COVID-19 fatality.

Background: Lymphoid neoplasms in serous effusions are uncommon, and the details of lymphoid neoplasms in serous effusions from China are still unclear., Methods: Between January 2004 and December 2019, all patients with lymphoid neoplasms in pleural effusions, ascites, and pericardial effusions in our hospital, were reviewed., Results: A total of 65 patients with lymphoid neoplasms were collected during this period. The top three neoplasms were diffuse large B-cell lymphoma (DLBCL) (n = 20, 30.7%), myeloma (n = 13, 20.0%), and T-lymphoblastic lymphoma (n = 7, 10.8%). In pleural effusions involving DLBCL, the cytomorphology of DLBCL cells was diverse; most pleural effusions were present during the tumor course (92.9%); bilateral pleural effusions were predominant (57.2%); and the median survival time was only 1.23 months after the effusion. In pleural effusions involving myeloma, 90.9% of cases (10/11) had a high ratio (> 1.0) of immature to mature plasma cells; paraprotein types of IgA (36.4%) and light chain λ (36.4%) were the most frequently found; bilateral pleural effusions were easily found (n = 10, 90.9%); and the median survival time was only 1.4 months after the effusion., Conclusion: In pleural effusions involving DLBCL, most of our patients with effusions are present during the tumor course, and bilateral pleural effusions are predominant. In pleural effusions involving myeloma, the paraprotein types of IgA and light chain λ are the most frequently found, and it has a high ratio of immature to mature plasma cells in pleural effusions., (© 2020 Wiley Periodicals LLC.)

To study the relationship between clinical indexes and the severity of coronavirus disease 2019 (COVID-19), and to explore its role in predicting the severity of COVID-19. Clinical data of 443 patients with COVID-19 admitted to our hospital were retrospectively analyzed, which were divided into nonsevere group (n = 304) and severe group (n = 139) according to their condition. Clinical indicators were compared between different groups. The differences in sex, age, the proportion of patients with combined heart disease, leukocyte, neutrophil-to-lymphocyte ratio (NLR), neutrophil, lymphocyte, platelet, D-dimer, C-reactive protein (CRP), procalcitonin, lactate dehydrogenase, and albumin on admission between the two groups were statistically significant (P  <  .05). Multivariate logistic regression analysis showed NLR and CRP were independent risk factors for severe COVID-19. Platelets were independent protective factors for severe COVID-19. The receiver operating characteristic (ROC) curve analysis demonstrated area under the curve of NLR, platelet, CRP, and combination was 0.737, 0.634, 0.734, and 0.774, respectively. NLR, CRP, and platelets can effectively assess the severity of COVID-19, among which NLR is the best predictor of severe COVID-19, and the combination of three clinical indicators can further predict severe COVID-19., (© 2020 Wiley Periodicals LLC.)

Objectives: The aim was to determine the clinical characteristics of COVID-19 patients because the SARS-CoV-2 virus continues to circulate in the population., Methods: This is a retrospective, multicentre, cohort study. Adult COVID-19 cases from four hospitals in Zhejiang were enrolled and clustered into three groups based on epidemiological history. First-generation patients had a travel history to Hubei within 14 days before disease onset; second-generation patients had a contact history with first-generation patients; third-generation patients had a contact history with second-generation patients. Demographic, clinical characteristics, clinical outcomes and duration of viral shedding were analysed., Results: A total of 171 patients were enrolled, with 83, 44 and 44 patients in the first-, second-, and third-generation, respectively. Compared with the first and second generations, third-generation patients were older (61.3 vs. 48.3 and 44.0 years, p < 0.001) and had more coexisting conditions (56.8% vs. 36.1% and 27.3%, p 0.013). At 7 ± 1 days from illness onset, third-generation patients had lower lymphocyte (0.6 vs. 0.8 and 0.8 × 109/L, p 0.007), higher C-reactive protein (29.7 vs. 17.1 and 13.8 mg/L, p 0.018) and D-dimer (1066 vs. 412.5 and 549 μg/L, p 0.002) and more lesions involving the pulmonary lobes (lobes ≥5, 81.8% vs. 53.0% and 34.1%, p < 0.001). The proportions of third-generation patients developing severe illness (72.7% vs. 32.5% and 27.3%, p < 0.001), critical illness (38.6% vs. 10.8% and 6.8%, p < 0.001) and receiving endotracheal intubation (20.5% vs. 3.6% and 2.3%, p 0.002) were higher than in the other two groups., Discussion: Third-generation patients were older, had more underlying comorbidities and had a higher proportion of severe or critical illness than first- and second-generation patients., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Clinical and laboratory data on patients with coronavirus disease 2019 (COVID-19) in Beijing, China, remain extremely limited. In this study, we summarized the clinical characteristics of patients with COVID-19 from a designated hospital in Beijing. In total, 55 patients with laboratory-confirmed SARS-CoV-2 infection in Beijing 302 Hospital were enrolled in this study. Demographic data, symptoms, comorbidities, laboratory values, treatments, and clinical outcomes were all collected and retrospectively analyzed. A total of 15 (27.3%) patients had severe symptoms, the mean age was 44.0 years (interquartile range [IQR], 34.0-56.0), and the median incubation period was 7.5 days (IQR, 5.0-11.8). A total of 26 (47.3%) patients had exposure history in Wuhan of less than 2 weeks, whereas 20 (36.4%) patients were associated with familial clusters. Also, eighteen (32.7%) patients had underlying comorbidities including hypertension. The most common symptom of illness was fever (45; 81.8%); 51 (92.7%) patients had abnormal findings on chest computed tomography. Laboratory findings showed that neutrophil count, percentage of lymphocyte, percentage of eosinophil, eosinophil count, erythrocyte sedimentation rate, albumin, and serum ferritin are potential risk factors for patients with a poor prognosis. A total of 26 patients (47.3%) were still hospitalized, whereas 29 (52.7%) patients had been discharged. Compared with patients in Wuhan, China, the symptoms of patients in Beijing are relatively mild. Older age, more comorbidities, and more abnormal prominent laboratory markers were associated with a severe condition. On the basis of antiviral drugs, it is observed that antibiotics treatment, appropriate dosage of corticosteroid, and gamma globulin therapy significantly improve patients' outcomes. Early identification and timely medical treatment are important to reduce the severity of patients with COVID-19., (© 2020 Wiley Periodicals LLC.)

This retrospective study aimed to analysis clinical characteristics and outcomes of cancer patients with novel coronavirus disease-19 (COVID-19). Medical records, laboratory results and radiologic findings of 52 cancer patients with COVID-19 were collected, clinical characteristics and outcomes were summarized. A total of 52 cancer patients with COVID-19 were included. Median age of 52 cancer patients with COVID-19 was 63 years (34-98). Thirty-three (63.5%) patients were mild and 19 (36.5%) were severe/critical. Lung cancer was the most frequent cancer type (10, 19.2%). The common symptoms were as follows: fever (25%), dry cough (17.3%), chest distress (11.5%), and fatigue (9.6%). There were 33 (63.5%) patients had comorbidities, the most common symptom was hypertension (17, 51.5%). Twenty-six (78.8%) patients developed pneumonia on admission. Lymphocytes (0.6 × 109/L) decreased in both mild and severe/critical patients. Median levels of D-dimer, C-reactive protein, procalcitonin, and lactate dehydrogenase were 2.8 mg/L, 70.5 mg/L, 0.3 ng/mL, and 318 U/L, respectively, which increased significantly in severe/critical patients compared with the mild patients. Interleukin-6 (12.6  pg/mL) increased in both mild and severe/critical patients, there was a significant difference between them. Complications were observed in 29 (55.8%) patients, such as liver injury (19, 36.5%), acute respiratory distress syndrome (9, 17.3%), sepsis (8, 15.4%), myocardial injury (8, 15.4%), renal insufficiency (4, 7.7%), and multiple organ dysfunction syndrome (3, 5.8%). Eleven (21.2%) patients with cancer died. The infection rate of severe acute respiratory syndrome coronavirus 2 in patients with cancer was higher than the general population, cancer patients with COVID-19 showed deteriorating conditions and poor outcomes., (© 2020 Wiley Periodicals LLC.)

Aim: This study examined the role of lymphocyte-to-monocyte ratio (LMR), an inflammatory biomarker, in predicting the severity of calcific aortic valve stenosis (CAVS) in a Chinese case-control study. Results: The LMR significantly decreased in the patients with CAVS compared with healthy controls. An inverse correlation was observed between the severity of stenosis and LMR in the patients. Additionally, the LMR was identified in the multivariate analysis as an independent predictor of severe CAVS. Conclusion: This study provides evidence of an inverse correlation between the severity of CAVS and LMR. LMR could potentially be applied as an independent predictor of severe CAVS and could be incorporated into a novel predictive model.

An epidemic caused by SARS-Coronavirus-2 (SARS-CoV-2) infection has appeared in Wuhan City in December 2019. The disease has shown a "clustering epidemic" pattern, and family-clustered onset has been the main characteristic. We collected data about 130 cases from 35 cluster-onset families (COFs) and 41 cases from 16 solitary-onset families (SOFs). The incidence of 2019 coronavirus disease (COVID-19) in COFs was significantly higher than that of SOFs. Our study also showed that patients with exposure to high-risk factors (respiratory droplets and close contact), advanced age, and comorbidities were more likely to develop COVID-19 in the COFs. In addition, advanced age and elevated neutrophil/lymphocyte ratio (NLR) were risk factors for death in patients with SARS-CoV-2 infection in the COFs., (Copyright © 2020. Published by Elsevier B.V.)

In December 2019, cases of severe coronavirus 2019 (COVID-19) infection rapidly progressed to acute respiratory failure. This study aims to assess the association between the neutrophil-to-lymphocyte ratio (NLR) and the incidence of severe COVID-19 infection. A retrospective cohort study was conducted on 210 patients with COVID-19 infection who were admitted to the Central Hospital of Wuhan from 27 January 2020 to 9 March 2020. Peripheral blood samples were collected and examined for lymphocyte subsets by flow cytometry. Associations between tertiles of NLR and the incidence of severe illness were analysed by logistic regression.Of the 210 patients with COVID-19, 87 were diagnosed as severe cases. The mean NLR of the severe group was higher than that of the mild group (6.6 vs. 3.3, P < 0.001). The highest tertile of NLR (5.1-19.7) exhibited a 5.9-fold (95% CI 1.3-28.5) increased incidence of severity relative to that of the lowest tertile (0.6-2.5) after adjustments for age, diabetes, hypertension and other confounders. The number of T cells significantly decreased in the severe group (0.5 vs. 0.9, P < 0.001). COVID-19 might mainly act on lymphocytes, particularly T lymphocytes. NLR was identified as an early risk factor for severe COVID-19 illness. Patients with increased NLR should be admitted to an isolation ward with respiratory monitoring and supportive care.

COVID-19 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The present study aimed to analyze the characteristics of severe COVID-19 and identify biomarkers for differential diagnosis and prognosis prediction. In total, 27 consecutive patients with COVID-19 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress. to mild COVID-19, the lymphocytes in the severe COVID-19 progressively decreased at the progression and the peak stages, but rebound in the recovery stage. The levels of C-reactive protein (CRP) in the severe group at the initial and progression stages were higher than those in the mild group. Correlation analysis showed that CRP (R = .62; P < .01), erythrocyte sedimentation rate (R = .55; P < .01) and granulocyte/lymphocyte ratio (R = .49; P < .01) were positively associated with the CT severity scores. In contrast, the number of lymphocytes (R = -.37; P < .01) was negatively correlated with the CT severity scores. The receiver-operating characteristic analysis demonstrated that area under the curve of CRP on the first visit for predicting severe COVID-19 was 0.87 (95% CI 0.10-1.00) at 20.42 mg/L cut-off, with sensitivity and specificity 83% and 91%, respectively. CRP in severe COVID-19 patients increased significantly at the initial stage, before CT findings. Importantly, CRP, which was associated with disease development, predicted early severe COVID-19., (© 2020 Wiley Periodicals, Inc.)

Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by the highly contagious severe acute respiratory syndrome coronavirus 2. The immunopathological characteristics of patients with COVID-19, either systemic or local, have not been thoroughly studied. In the present study, we analysed both the changes in the number of various immune cell types as well as cytokines important for immune reactions and inflammation. Our data indicate that patients with severe COVID-19 exhibited an overall decline of lymphocytes including CD4 + and CD8 + T cells, B cells and natural killer cells. The number of immunosuppressive regulatory T cells was moderately increased in patients with mild COVID-19. Interleukin-6 (IL-6), IL-10 and C-reactive protein were remarkably up-regulated in patients with severe COVID-19. In conclusion, our study shows that the comprehensive decrease of lymphocytes, and the elevation of IL-6, IL-10 and C-reactive protein are reliable indicators of severe COVID-19., (© 2020 John Wiley & Sons Ltd.)

Systemic lupus erythematosus (SLE) is a chronic systematic autoimmune disease. Current methods of diagnosing SLE or evaluating its activity are complex and expensive. Numerous studies have suggested that neutrophil-to-lymphocyte ratio (NLR) is closely correlated with the presence of SLE and its activity, suggesting that it may serve as a diagnostic and monitoring indicator for SLE. Therefore, we performed a meta-analysis to systematically assess the association between NLR and SLE. We performed a literature search until 12 April 2019 in the PubMed, Web of Science, and China National Knowledge Infrastructure databases. Cross-sectional studies comparing the NLR of SLE patients versus those of healthy controls, of active versus inactive SLE patients, and of SLE patients with versus without lupus nephritis were considered for inclusion. Mean intergroup NLR differences were estimated using standardized mean differences and their 95% confidence intervals. Study quality was assessed using the Agency for Healthcare Research and Quality instrument for cross-sectional studies. Fourteen studies with 1,781 SLE patients and 1,330 healthy controls were included in this meta-analysis. The pooled results showed that the NLR was significantly higher in SLE patients than in healthy controls, in active SLE patients than in inactive SLE patients, and in SLE patients with lupus nephritis than in those without lupus nephritis. NLR may be an indicator for monitoring disease activity and reflecting renal involvement in SLE patients. Nevertheless, more high-quality studies are warranted to further validate our findings.

Although many scholars have recently studied the relationships between the pretreatment neutrophil-to-lymphocyte ratio (NLR) and prognosis in patients with small cell lung cancer (SCLC), the conclusions have been inconsistent. Accordingly, in this meta-analysis, we attempted to assess the clinicopathological and prognostic value of the pretreatment NLR in SCLC. Related literature was searched using PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature, China National Knowledge Infrastructure (CNKI), and Wanfang databases. Each eligible study was extracted, and a meta-analysis was performed using hazard ratios (HRs) and 95% confidence intervals (95% CIs) to assess the prognostic value of NLR. Evaluation of the clinicopathological significance of NLR in SCLC used odds ratios (ORs) and 95% confidence intervals (95% CIs). We included a total of 20 studies with 21 outcomes (5141 patients) in this meta-analysis. The results showed that high pretreatment NLR was closely related to poorer progression free survival (PFS) and overall survival (OS) (PFS, HR = 1.55, 95% CI = 1.27-1.88, P < 0.0001; I2 = 0%; OS, HR = 1.40, 95% CI = 1.26-1.55, P < 0.00001; I2 = 64%). In addition, pretreatment NLR was significantly associated with clinical stage of SCLC (OR = 2.14, 95% CI = 1.35-3.39, P = 0.001). Our meta-analysis showed that high levels of pretreatment NLR were significantly associated with a more serious clinical stage and poorer PFS and OS in SCLC., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The purpose of the present study was to evaluate the prognostic value of a systemic immune-inflammation index (SII) and the relationship between SII and the effectiveness of postoperative treatment in patients with non-small cell lung cancer (NSCLC)., Methods: A total of 538 patients diagnosed with NSCLC who had undergone curative surgery were retrospectively enrolled in the study. Clinicopathologic and laboratory variables were collected. SII was defined as neutrophil × platelet/lymphocyte counts. Both univariate and multivariate analyses were performed to analyze the prognostic value of these factors., Results: The preoperative SII level was associated with sex, smoking history, histological type, lesion type, resection type, pathological stage, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), fibrinogen and bone metastasis (P<0.05). The univariate and multivariate analyses revealed that SII was an independent prognostic factor for disease-free survival (DFS, P=0.033) and overall survival (OS, P=0.020). Furthermore, the prognostic value of SII was also verified regardless of the histological type and pathological stage. The subgroup analysis demonstrated that patients with a high SII may benefit from adjuvant therapy (P=0.024 for DFS and P=0.012 for OS)., Conclusion: An increased preoperative SII may independently predict the poor DFS and OS in patients with resectable NSCLC. SII may help select NSCLC patients who might benefit from adjuvant chemotherapy., (© 2020 The Author(s).)

Recently, neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) are frequently used to evaluate disease progression and outcome. Here, we aim to analyze the associations between NLR or MLR and kidney function in undiagnosed hypertensive individuals from general population during routine health checkup. Liver function was analyzed for comparison. From 2011 to 2016, 53 939 examiners have registered for health checkup in Yanbian University Hospital, Yanbian, China. Among 15 219 participants who have complete datasets, 4997 individuals were hypertensive (HTN, SBP/DBP: ≥ 140/90 mm Hg). NLR, glucose, lipids (Chol, TG, LDL), kidney (CREA, BUN), and liver (AST, ALT, GGT, ALB, TBIL) functional parameters were significantly higher in HTN. Pearman correlation analysis showed that NLR was positively correlated with SBP and CREA only in HTN. MLR was associated with CREA in both HTN and non-HTN. NLR or MLR was associated with liver functions similarly in HTN and non-HTN. The authors then divided NLR or MLR into tertiles (NLR: 0-1.7276, 1.7276-3, >3; MLR: 0-0.1845, 0.1845-0.3, >0.3). NLR was positively associated with BUN at NLR >1.7276 and with CREA at all tertiles in HTN. MLR was correlated with CREA and BUN at high MLR in non-HTN. Further analysis showed that age or gender did not affect the associations of NLR and MLR with kidney function in HTN, but strong association was observed in male or aged (>65 years old) non-HTN group. These results showed that NLR could be used as a cost-effective predictor of kidney abnormality in HTN patients even in a general population., (© 2019 Wiley Periodicals, Inc.)

Background & Aims: Inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI), Prognostic Nutritional Index (PNI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and systemic immune-inflammation index (SII), are correlated with the survival of hepatocellular carcinoma (HCC) patients, while remain unclear for recurrent HCC. This study aimed to compare the prognostic value of inflammation-based prognostic scores for post-recurrence survival (PRS) in patients with early recurrent HCC (ErHCC, within 2 years after hepatectomy)., Methods: A total of 580 patients with ErHCC were enrolled retrospectively. The association between the independent baseline and the time-dependent variables and PRS was evaluated by cox regression. The prediction accuracy of the inflammation-based prognostic scores was assessed by time-dependent receiver operating characteristic (ROC) and Harrell's concordance index (C-index) analyses., Results: The GPS, mGPS, PI, PNI, NLR, PLR, LMR and SII were all related to the PRS of ErHCC patients, while only the SII (P < .001) remained an independent predictor for PRS in multivariate analysis (hazard ratio: 1.92, 95% confidence interval: 1.33-2.79). Both the C-index of the SII (0.65) and the areas under the ROC curves showed that the SII score was superior to the other inflammation-based prognostic scores for predicting the PRS of ErHCC patients., Conclusions: The SII is a useful prognostic indicator for PRS in patients with ErHCC after hepatectomy and is superior to the other inflammation-based prognostic scores in terms of prognostic ability., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To assess the utility of hematologic, inflammatory, and immunologic biomarkers for differentiating between ovarian cancer and endometriosis., Methods: Data were retrospectively reviewed from women diagnosed with ovarian cancer and endometriosis after ovarian cyst surgery in Zhejiang, China, 2014-2016. Serologic and hematologic biomarkers, including white blood cell count, lymphocyte count, neutrophil count, red blood cell count, hemoglobin, platelets, and D-dimer, albumin, globulin, cancer antigen 125 (CA125) and CA199 serum levels recorded pre-operatively were assessed by ROC curve and logistic regression analysis., Results: Overall, 49 women were diagnosed with ovarian cancer and 192 with endometriosis. For predicting ovarian cancer, the area under the curve (AUC) was 0.96 (95% confidence interval [CI], 0.94-0.99); sensitivity, 93.2%; specificity, 87.5%) for log(D-dimer), 0.95 (95% CI, 0.91-0.98; sensitivity, 81.3%; specificity, 96.3%) for log(CA125), and 0.92 (95% CI, 0.86-0.98; sensitivity, 92.6%; specificity, 79.2%) for neutrophil-to-lymphocyte ratio (NLR). The AUC for the combination of D-dimer, NLR, and CA125 was 0.96 (95% CI, 0.94-0.99; sensitivity, 91.6%; specificity, 89.6%)., Conclusion: Serum D-dimer, NLR, and CA125 were found to be potential diagnostic factors for ovarian cancer. Combined measurement of D-dimer, NLR, and CA125 might offer a convenient screening method., (© 2019 International Federation of Gynecology and Obstetrics.)

Objective: To evaluate the predictive value of preoperative peripheral inflammatory markers in patients with vocal fold leukoplakia., Methods: A retrospective study was performed of the patients diagnosed with vocal fold leukoplakia and who accepted carbon dioxide (CO 2 ) laser resection in our center in the last 10 years. We calculated the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) after collecting and analyzing the clinical, histopathological and laboratory data. The potential relation between blood indexes and clinical events as recurrence or canceration was evaluated., Results: A total of 589 patients were involved, including 300 cases without recurrence (group A), 198 with recurrence but not canceration (group B) and 91 transformed into squamous cancer (group C). Baseline analysis of NLR, PLR, and MLR showed no difference among the three groups before the first surgery. But all the indexes significantly elevated in groups B (P < 0.001, < 0.001, 0.023, respectively) and C (P = 0.009, 0.004, 0.007, respectively) in the last operation. The receiver-operating curve (ROC) analysis showed NLR as a potential marker of canceration of leukoplakia (AUC = 0.837) and the cutoff value was 2.505. When regrouping with pathological outcomes, severe dysplasia and squamous cell carcinoma (SCC) groups both revealed a higher level of NLR, PLR, and MLR comparing to the no dysplasia, mild dysplasia, and moderate dysplasia groups. NLR, PLR, and MLR in high-risk group (moderate, severe dysplasia and carcinoma) also elevated comparing to low-risk group (no dysplasia, mild dysplasia) (P = 0.039, 0.011, 0.007, respectively)., Conclusions: The peripheral inflammatory markers NLR, PLR, and MLR are closely connected with the development of vocal fold leukoplakia. NLR may be a potential marker to predict the poor outcomes (recurrence or canceration) of patients in first surgery.

Backgroud: To better identify patients with high mortality risk, we developed a systematic inflammation index (IPI) based on neutrophil to lymphocyte ratio (NLR) and albumin., Methods: The performance of pretreatment IPI was evaluated in patients with surgically resected non-metastatic colorectal cancer. IPI was predefined and compared with Glasgow Prognostic Score (GPS)/modified GPS in terms of discrimination and calibration abilities., Results: In multivariate analysis, patients with an IPI of 1 or 2 had 1.68(95%CI:1.15-2.44) or 3.56(95%CI:2.12-5.98)-fold increased cancer specific mortality risk(CSMR) respectively in comparison to patients with an IPI of 0. The prognostic significance was independent of tumor locations and nodal status. Compared with the GPS/mGPS, IPI had the higher c statistics and lower Akaike Information Criterion. IPI showed good calibration in predicting 1-year, 3-year and 5-year CSMR., Conclusions: IPI is readily available, independently prognostic and may reflect the host inflammation, immune and nutritional status that could have impact on cancer progression., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: In this study, we evaluated the prognostic values of hematological biomarkers in primary nasopharyngeal carcinoma (NPC) patients receiving definitive intensity-modulated radiotherapy (IMRT)., Methods: There were 427 NPC patients enrolled between January 2010 and March 2013 at Fudan University Shanghai Cancer Center. Pre-treatment absolute neutrophil count (ANC), platelet count (APC), lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were collected as prognostic biomarkers. The Kaplan-Meier method and log-rank test were utilized to calculate progression-free survival (PFS) and overall survival (OS). The Cox proportional hazard models were applied to assess variables., Results: ANC, APC and ALC were declined, while NLR and PLR were elevated significantly after therapy (P < 0.001 each). On multivariate analysis, pre-treatment NLR ≥ 2.32 was associated with shortened OS (P = 0.048) and PFS (P = 0.008), whereas PLR ≥ 123.0 was related with inferior OS (P = 0.032), yet it was not correlated with PFS (P = 0.161)., Conclusions: High pre-treatment NLR and PLR indicated poor survival in NPC patients treated with IMRT-based therapy. As easily accessible and economically feasible biomarkers, NLR and PLR can be applied into clinical practice, in combination with current TNM staging, to design a more personalized treatment in these patients.

Purpose: The systemic inflammatory response markers have been reported to be associated with the prognosis of various cancers. We conducted this meta-analysis of retrospective studies to evaluate and identify the prognostic impact of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) on ovarian cancer., Methods: PubMed, EMBASE, and China National Knowledge Infrastructure databases were included to search for eligible studies. The following terms were used: "neutrophil to lymphocyte ratio", "NLR", "platelet to lymphocyte ratio", "PLR", "ovarian cancer", "ovary cancer", "ovarian carcinoma", "ovary carcinoma", "ovarian neoplasm", "ovary neoplasm", "ovarian tumor", and "ovary tumor". The random-effects model was chosen to estimate the pooled HR with 95% CI. Heterogeneity between studies was assessed by Higgins I 2 value. The stability and heterogeneity of studies were analyzed by sensitivity analysis. Publication bias was examined by Egger's test and Begg's test with the funnel plots., Results: 13 studies consisting of 3467 patients were considered for meta-analysis. We found that the high NLR had a poor prognostic impact on OS and PFS in ovarian cancer, with a pooled HR 1.70, 95% CI 1.35-2.15 and HR 1.77, 95% CI 1.48-2.12, respectively. Similarly, the results showed the high PLR adversely affected OS and PFS in ovarian cancer, with a pooled HR 2.05, 95% CI 1.70-2.48 and HR 1.85, 95% CI 1.53-2.25, respectively., Conclusion: In conclusion, we found that both NLR and PLR had an unfavorable impact on PFS and OS of patients with ovarian cancer. Our meta-analysis supported that NLR/PLR could be effective prognostic predictors of ovarian cancer.

Several mitochondrial tRNA mutations have been associated with hypertension, but their pathophysiology remains poorly understood. In this report, we identified a novel homoplasmic 3253T→C mutation in the mitochondrial tRNA Leu(UUR) gene in a Han Chinese family with maternally inherited hypertension. The m.3253T→C mutation affected a highly conserved uridine at position 22 at the D-stem of tRNA Leu(UUR) , introducing a G-C base pairing (G13-C22) at the D-stem and a tertiary base pairing (C22-G46) between the D-stem and the variable loop. We therefore hypothesized that the m.3253T→C mutation altered both the structure and function of tRNA Leu(UUR) Using cytoplasmic hybrid (cybrid) cell lines derived from this Chinese family, we demonstrated that the m.3253T→C mutation perturbed the conformation and stability of tRNA Leu(UUR) , as suggested by faster electrophoretic mobility of mutated tRNA relative to the wild-type molecule. Northern blot analysis revealed an ∼45% decrease in the steady-state level of tRNA Leu(UUR) in the mutant cell lines carrying the m.3253T→C mutation, as compared with control cell lines. Moreover, an ∼35% reduction in aminoacylation efficiency of tRNA Leu(UUR) was observed in the m.3253T→C mutant cells. These alterations in tRNA Leu(UUR) metabolism impaired mitochondrial translation, especially for those polypeptides with a high proportion of Leu(UUR) codons, such as ND6. Furthermore, we demonstrated that the m.3253T→C mutation decreased the activities of mitochondrial complexes I and V, markedly diminished mitochondrial ATP levels and membrane potential, and increased the production of reactive oxygen species in the cells. In conclusion, our findings may provide new insights into the pathophysiology of maternally inherited hypertension., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Increasing evidence has suggested that the host inflammatory status is associated with prognosis of several solid tumors. Preoperative platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR), both acquired from routine blood tests, can reflect the status of systematic inflammation. However, whether they are correlated with clinical outcomes of esophageal carcinoma is still unknown. The purpose of this study was to determine the prognostic value of preoperative PLR and NLR in patients with resected esophageal squamous cell carcinoma (ESCC). Preoperative PLR and NLR were evaluated in 317 eligible ESCC patients from September 2008 to December 2010. Receiver operating characteristic curves were applied to establish optimal cutoff points. The prognostic values of PLR and NLR were determined by both univariate and multivariate analyses. The optimal cutoff value of preoperative PLR and NLR were 103.0 and 2.1, respectively. One hundred and ninety-seven (62.1%) patients showed high level of preoperative PLR, while 148 (46.7%) patients showed high level of preoperative NLR. Both elevated PLR (P < 0.001) and NLR (P = 0.009) were correlated with poor disease-specific survival in univariate analysis. However, only preoperative PLR (P = 0.003) had a significant correlation with prognosis in multivariate analysis. In subgroup analyses, the predictive value of PLR was significant for stage I (P = 0.008) and stage II (P = 0.044) patients, but not for stage III patients (P = 0.100). Preoperative PLR is easily obtained from a routine blood test and may provide additional prognostic information for ESCC patients, especially in the early stage., (© 2014 International Society for Diseases of the Esophagus.)

Background: Neutrophil-lymphocyte ratio (NLR) has been shown to be associated with prognosis in various solid tumors. This study aimed to evaluate the prognostic role of NLR in patients with laryngeal squamous cell carcinoma (LSCC)., Methods: A total of 141 LSCC patients were retrospectively reviewed. Patients' demographics were analyzed along with clinical and pathologic data. The optimal cutoff value of NLR was determined using receiver operating characteristic (ROC) curve analysis. The impact of the NLR and other potential prognostic factors on disease-free survival (DFS) and overall survival (OS) was assessed using the Kaplan-Meier method and multivariate Cox regression analysis., Results: The optimal cutoff value of the NLR was 2.17. In the NLR ≤ 2.17 group, the 1-, 3-, and 5-year DFS rates were 88.2, 73.9 and 69.1 %, respectively, while in the NLR > 2.17 group, the DFS rates were 83.0, 54.6 and 49.2 %, respectively. Correspondingly, the 1-, 3-, and 5-year OS rates were 98.9, 85.1 and 77.4 % in the NLR ≤ 2.17 group and 97.9, 63.8 and 53.3 % in the NLR > 2.17 group, respectively. The multivariate Cox proportional hazard model analysis showed that NLR > 2.17 was a prognostic factor for both DFS [hazard ratio (HR) = 1.869; 95 % confidence interval (CI) 1.078-3.243; P = 0.026] and OS (HR =2.177; 95 % CI 1.208-3.924; P = 0.010)., Conclusion: Our results showed that elevated preoperative NLR was an independent predictor of poor prognosis for patients with LSCC after surgical resection.

Aims: To explore the etiology of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) abnormalities in colorectal cancer., Methods: In total, 230 patients with histopathologically confirmed colorectal cancer from August 2009 to August 2011 were recruited to our study. The associations between lifestyles (smoking, alcohol and pickled food consumption) and pretreatment NLR and PLR were estimated using the Kruskal-Wallis tests and linear regression model., Results: The Kruskal-Wallis test showed a significant association between pickled food intake and pretreatment NLR but not PLR (P = 0.002, 0.057, respectively). Pairwise comparisons showed that, compared with those with a moderately frequent (2-3 times/week) and an infrequent (≤ once a week) intake of pickled food, high frequency (≥ four times/week) consumption of pickled food had a higher pretreatment NLR (P = 0.01, 0.007, respectively). Multivariate linear regression analysis showed pretreatment NLR increased significantly in high frequency (≥ four times/week) consumption of pickled food (P < 0.0001). No association between other lifestyle factors and pretreatment PLR was found., Conclusions: A higher frequency intake of pickled food possibly contributes to higher NLR, which may reflect a systemic inflammatory response in colorectal cancer., (© 2013 Wiley Publishing Asia Pty Ltd.)

Myopathy with anti-signal recognition particle antibodies (SRP) is generally thought to be immune-mediated necrotic myopathy in previous studies. We report the clinical and histopathological features of myopathy with anti-SRP antibodies in Chinese patients. Muscle biopsy and immunoblots for myositis antibodies were carried out in 123 patients with idiopathic inflammatory myopathy. Among them, 16 (13.0%) patients had anti-SRP antibodies. Age of onset ranged from 24 to 77 years, and the disease began insidiously. Fourteen of 16 patients presented with chronic progression of proximal limb weakness, with 6 having myalgia. Serum creatine kinase levels ranged from 400 to 9082 IU/L. Muscle biopsies showed necrotic and/or regenerative muscle fibers in all 16, infiltrates of lymphocytes in 11 and morphological features of muscular dystrophy in 7. Eleven patients showed focal or diffuse major histocompatibility complex class 1 expression in sarcolemma or cytoplasm of muscle fibers, with 9 showing deposition of membrane attack complex in necrotic muscle fibers and 2 around capillaries. These findings indicate that anti-SRP antibodies are most likely to be related to IMNM. Myopathy with anti-SRP antibodies is not infrequent in Chinese patients with idiopathic inflammatory myopathy., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background and Objectives: Previous studies have identified inflammatory features that enable the prediction of renal outcome of IgA nephropathy (IgAN); however, validation of these findings is still needed. This prospective study was performed to determine the characteristics of renal interstitial infiltration and tertiary lymphoid organ (TLO) neogenesis in a cohort of Chinese patients with IgAN., Design, Setting, Participants, & Measurements: Adult patients with IgAN were recruited into this study from June 2009 to June 2010. Inflammatory cells in renal biopsy tissues were detected by immunohistochemistry and immunofluorescence. Correlations between the density of interstitial inflammatory cells, grades of TLOs, and clinicopathologic features were evaluated. Of 152 eligible patients, 72 (47%) were successfully followed-up by telephone at 30 months after renal biopsy. Twelve patients were classified as the severe group and 60 patients were classified as the stable group, according to the progression of serum creatinine levels during the follow-up period. A comparison of the severity of interstitial infiltration and the frequency of TLO neogenesis between the two groups was performed., Results: The accumulation of interstitial inflammatory cells was correlated with decreased renal function, heavy proteinuria, and severe glomerular, interstitial, and arterial lesions in patients with IgAN. TLOs, identified as nodular inflammatory infiltrates containing organized DC-SIGN(+), CD4(+), CD8(+), and CD20(+) cells, were observed in 37.5% of patients. Patients with high-grade TLOs exhibited a high percentage of mesangial hypercellularity and crescents as well as severe interstitial and arterial lesions. Patients in the severe group exhibited more severe interstitial infiltration and a higher percentage of TLO neogenesis (83.3% versus 33.3%; P=0.001) compared with patients in the stable group., Conclusions: As contributors to an active local inflammatory response, the severity of interstitial infiltration and the frequency of TLO neogenesis are correlated with glomerular, interstitial, and arterial lesions as well as IgAN progression.

Clinical findings, pathological features and tripeptidyl peptidase 1 (TPP1) activity and genetic mutation analysis data of nine patients affected with the late-infantile form of neuronal ceroid lipofuscinoses (LINCL) in China are systematically reviewed with long-term follow-up. The patients were enrolled if curvilinear bodies were found on lymphocyte, skin or muscle specimens' examination, and/or reduction of tripeptidyl peptidase 1 (TPP1) activity were detected. CLN2 gene mutation were tested in five patients. The patients have onset age of 2-3.5 years, and most of them initially present partial seizure, and then progressed to deteriorated mental function, refractory myoclonic seizures, impaired vision, and ataxia with cerebellar atrophy. Discrete small vacuolated lymphocytes are found in 5-10% lymphocytes in 5 patients examined. Curvilinear bodies were found in vacuolated lymphocytes, in skin and muscle tissues. Tripeptidyl peptidase 1 (TPP1) activities are reduced in 5 patients with different CLN2 gene mutation. Detection of vacuolated lymphocytes may be a screen method for LINCL, ultrastructural examination of lymphocytes, combined with TPP1 activity assay, allowing for a definite and faster diagnosis and classification with minimal invasion., (Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: 22q11.2 microdeletion is the most common microdeletion in the global population. Congenital cardiac disease is the most frequently observed feature of this syndrome. The prognosis of patients with 22q11.2 copy number aberrations varies from those without 22q11.2 deletion or duplication., Methods: We enrolled 241 patients from Nanjing Drum Tower Hospital and Nanjing Sick Children's Hospital, 227 being scheduled for cardiac surgery, and 14 cases being fetuses aged from 24 to 36 gestational weeks. We performed karyotypic analysis and multiplex ligation-dependent probe amplification in all cases., Results: Karyotypic analysis demonstrated 3 cases with trisomy 21, and 1 case with mosaic trisomy 8 [47,XY,+8/46,XY(1:2)]. Multiplex ligation-dependent probe amplification analysis revealed 10 cases (4.15%) with changes in the number of copies within the region of 22q11.2, of which 7 cases were hemizygous interstitial microdeletion from CLTCL1 to LZTR1, 1 case with deletion of the region from CLTCL1 to PCQAP, and 2 cases with 22q11.2 duplication, one of which spanned from ZNF74 to LZTR1, and simultaneously showed trisomy 21 by karyotyping analysis, and the other spanned from HIC2 to TOP3B. The phenotypes of the cardiac lesions included 3 cases of ventricular septal defect, 3 of tetralogy of Fallot, 2 of combined ventricular and atrial septal defects, and 2 with pulmonary arterial stenosis., Conclusions: Patients with congenitally malformed hearts who are scheduled for cardiac surgery, as well as fetuses with congenital cardiac disease, should routinely undergo karyotypic analysis and examination for 22q11.2 aberrations. Multiplex ligation-dependent probe amplification has been proven to be a cost-effective diagnostic technique for 22q11 deletion syndrome.

Objectives: To study the pathologic feature of sudden cardiac death in Yunnan province and to investigate the role of myocarditis., Methods: During the period from 1991 to 2006, there were 29 cases of sudden cardiac death with autopsy performed. Fourteen of these cases were diagnosed to have myocarditis based on Dallas criteria and World Heart Federation's consensus. The clinical and pathologic findings were reviewed. The cardiac conduction system was examined in details by serial sectioning in 3 cases., Results: Fourteen cases suffered with myocarditis, which accounted for 48% of all cases of sudden cardiac death studied. The age of the deceased ranged from 8 to 68 years (mean = 30 years), with male-to-female ratio equaled to 9:5. Lymphocytic myocarditis and neutrophil myocarditis were the two major types, affecting 11 and 3 cases, respectively. The inflammatory infiltrates were often patchy rather than diffuse. The inflammatory foci were detected only in 8% to 42% (average = 20%) of the paraffin sections of the heart tissue. These lesions were usually located in the lateral wall of left ventricle and occasionally in interventricular septum and right ventricular wall. Myocardial injury was mild in most cases while patchy myocytolysis or coagulation necrosis was observed only in a few cases. Most of the lesions were relatively new and histologic evidence of myocardial repairing sometimes coexisted. Pericarditis and subacute endocarditis were also identified in 4 and 1 cases, respectively. Atrioventricular node was involved by myocarditis in 1 of the 3 cases examined for cardiac conduction system. Two cases showed gross evidence of cardiac dilatation (either left ventricle or biventricular). Respiratory tract and pulmonary infection was present in 5 cases., Conclusions: Myocarditis represents one of the major pathologic changes of sudden cardiac death occurring in Yunnan province. The inflammation is usually focal. Further studies are required for delineation of possible etiologies which may include virus, bacteria or exogenous toxin.

Aim: To reserve the rare Chinese familial adenomas polyp (FAP) family resource and to investigate the clinical features of FAP in Chinese for its diagnosis., Methods: Clinical features of patients with FAP were investigated. If there is any question, their medical records were verified. Blood sample was taken and lymphocyte immortal cell lines were established with modified EB-transformation methods. Congenital hypertrophy of retinal pigment epithelium (CHRPE) was checked by an experienced ophthalmologist., Results: Twenty seven families including 21 classical FAP (CFAP) families, 3 attenuated FAP (AFAP) families, and 3 suspected AFAP families were investigated. A total of 116 lymphocyte immortal cell lines were established from 26 families. In all the FAP families, colorectal cancer occurred at the mean age of 42.84 years. Of the 16 families checked, 15 (93.75%) had CHRPE. The mean number of patients suffering from colorectal neoplasm was 3.14 in CFAP families and 2.0 in AFAP families (P<0.01). The mean oldest age at diagnosis of FAP was 41.75 years in CFAP families, and 58.67 years in AFAP families, respectively (P<0.01). Mean age of development of colorectal cancer was 42.23 in CFAP and 57.33 years old in AFAP (P<0.01). Mean of the earliest age at diagnosis of FAP was 29.95 years in the FAP families with a positive family history and 46.80 years in the FAP families with a negative family history (P < 0.01). The ratio of extra-intestinal tumors to colorectal neoplasms was different in the two kinds of families with positive and negative family history (P<0.01)., Conclusion: Additional use of ciclosporin will effectively improve to establish lymphocyte immortal cell lines with modified EB- transformation methods. In Chinese FAP, there was a high frequency of CHRPE , and a later age at diagnosis and a later age of development of colorectal cancer in AFAP. And earlier age at diagnosis in FAP with positive family history was also found that will help to diagnose various kinds of FAP in Chinese.

The Epstein-Barr virus (EBV) BamHI A rightward transcripts (BARTs) were originally identified in C15 xenograft of nasopharyngeal carcinoma (NPC) and easily detected in a wide variety of EBV latent infection and EBV-associated tumors. It had been reported that p31 cosmid containing BARTs immortalized monkey epithelial cells, but which particular gene among BARTs family participates in the transformation procedure remains to be identified. RPMS1 is the only full-length cDNA confirmed so far and one of the most abundant spliced forms in BARTs family. To investigate the involvement of RPMS1 gene in NPC, we examined the expression of RPMS1 transcripts in NPC biopsies from Guangdong and its oncogenic potential. Our results revealed that RPMS1 mRNA preferentially expressed in primary NPC to non-carcinoma tissue of nasopharynx and peripheral blood lymphocytes (PBLs) of NPC patients. Furthermore, by introducing RPMS1 ORF into HEK293 cells, these transfectants enhanced the anchorage-independent growth and produced tumors in nude mice. These data imply that RPMS1 gene might play an important role in the development of NPC.

Histological observations of 20 occluded vas segments obstructed by the standard procedure of medical polyurethane-vas occlusion in 10 volunteers requesting vasectomy and of 20 vas segments with plugs removed from 10 vas-occluded men requesting vas reversal were carried out in order to elucidate the mechanism of vas occlusion by medical polyurethane (MPU). Twenty vas deferens in vasectomy group were ruptured, only a small amount of MPU elastomer remained within the vas lumen, most having leaked through to encircle the ruptured vas. Histomorphology of the removed vas segments from 10 vas-occluded men, who had undergone MPU-vas occlusion 4 years earlier, showed diffuse proliferation of connective tissue, fibrosis, or hyalinization of fibroplastic tissue and local infiltration of lymphocytes and macrophages. The vas lumen both proximal and distal to the plugs was completely blocked. Sperm granuloma, foreign body granuloma, proliferation of nerve fibers and local infiltration of lymphocytes were found in four vas-occluded men with painful nodules. These results suggest that the contraceptive mechanism of MPU-vas occlusion could be the result of secondary obstruction due to tissue proliferation by MPU irritation after the rupture of the vas deferens.