Prevalence and the age of onset patterns of stroke in Jiangsu Province, China.

OBJECTIVES: Little was known regarding the current age of onset patterns of stroke. This study aimed to examine the prevalence of stroke and explore the age of onset patterns of stroke in Jiangsu Province, China. MATERIALS AND METHODS: Participants were recruited from April 2012 to April 2013 in Jiangsu Province, China. Survival analysis models were used to evaluate the hazards of stroke by a single year of age. Kaplan-Meier analysis and the log-rank test were used to explore the disparities of the age of onset patterns of stroke. RESULTS: This population-based study was conducted among 39,887 participants aged ≥ 18 years in Jiangsu Province, China. Of the 740 (1.9%) events of stroke, 13.2% suffered from hemorrhagic stroke (HS) and 86.8% suffered from ischemic stroke (IS). The prevalence of HS and IS were 0.3% and 1.7%, respectively. The estimated mean age of onset of stroke was 71.98 (95% CI: 71.97-71.99) years by the survival model. Up to age of 45 years, the estimated hazards of stroke onset were at a relatively low level. From the age of 45 years, the increases in hazards accelerated and peaked at age 75 years. Urban, smoking, and drinking males had a higher risk of stroke than their counterparts (P < 0.05). However, no such difference was found among females. CONCLUSIONS: The findings emphasize the importance of implementing stroke prevention interventions in Jiangsu Province, China, especially for urban, smoking, and drinking males. It is of great significance to strengthen comprehensive management of health-related behaviors, including smoking cessation and moderate consumption of alcohol to have sustained beneficial effects on stroke risk. Chenlu He and Qian Chen contributed equally to this work.

Value of the prognostic nutritional index (PNI) in patients with newly diagnosed, CD5-positive diffuse large B-cell lymphoma: A multicenter retrospective study of the Huaihai Lymphoma Working Group.

BACKGROUND: CD5-positive diffuse large B-cell lymphoma (DLBCL) is a clinically rare subtype of DLBCL with aggressive clinical manifestations and a poor prognosis. It has been demonstrated that the prognostic nutritional index (PNI), an indicator of nutritional status and systemic inflammation, is a significant prognostic factor for several types of lymphoma. The objective of this multicenter retrospective study was to explore the prognostic value of the PNI in patients with CD5-positive DLBCL. METHODS: In total, 207 patients with CD5-positive DLBCL were recruited from 11 centers of the Huaihai Lymphoma Working Group. Maximally selected rank statistics analysis was used to identify optimal cutoff points for the PNI. A Cox proportional hazards model was used for univariable and multivariable analyses. Kaplan-Meier curves were used to calculate survival rates and draw survival curves, and the log-rank test was used to compare differences between groups. RESULTS: The median age at diagnosis was 61 years, and the 5-year overall survival rate was 47.5%. According to the maximally selected rank statistics analysis, a score of 49.7 was the optimal cutoff point for the PNI. Subgroup analysis showed that the PNI could re-stratify patients in BCL-2-negative, MYC-negative, high-intermediate-risk and high-risk International Prognostic Index, BCL-6-positive and BCL-6-negative, high Ki-67 score (≥0.9), Ann Arbor stage III/IV, Eastern Cooperative Oncology Group performance status ≥2, and germinal center B subgroups. Multivariable analysis revealed that PNI, age, Eastern Cooperative Oncology Group performance status, albumin level, and red blood cell count were independent prognostic factors for CD5-positive DLBCL. CONCLUSIONS: The PNI was a significant prognostic indicator for CD5-positive DLBCL and was able to re-stratify the prognosis for clinicopathologic subgroups of patients with CD5-positive DLBCL.

A Novel Prognostic Index Model for Adult Hemophagocytic Lymphohistiocytosis: A Multicenter Retrospective Analysis in China.

Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder with rapid progression and poor survival. Individual treatment strategy is restricted, due to the absence of precise stratification criteria. In this multicenter retrospective study, we aimed to develop a feasible prognostic model for adult HLH in China. A total of 270 newly diagnosed patients of adult HLH were retrieved from the Huaihai Lymphoma Working Group (HHLWG), of whom 184 from 5 medical centers served as derivation cohort, and 86 cases from 3 other centers served as validation cohort. X-Tile program and Maxstat analysis were used to identify optimal cutoff points of continuous variables; univariate and multivariate Cox analyses were used for variable selection, and the Kaplan-Meier curve was used to analyze the value of variables on prognosis. The C-index, Brier Score, and calibration curve were used for model validation. Multivariate analysis showed that age, creatinine, albumin, platelet, lymphocyte ratio, and alanine aminotransferase were independent prognostic factors. By rounding up the hazard ratios from 6 significant variables, a maximum of 9 points was assigned. The final scoring model of HHLWG-HPI was identified with four risk groups: low risk (≤3 pts), low-intermediate risk (4 pts), high-intermediate risk (5-6 pts), and high risk (≥7 pts), with 5-year overall survival rates of 68.5%, 35.2%, 21.3%, and 10.8%, respectively. The C-indexes were 0.796 and 0.758 in the derivation and validation cohorts by using a bootstrap resampling program. In conclusion, the HHLWG-HPI model provides a feasible and accurate stratification system for individualized treatment strategy in adult HLH.

Disparity analysis and prognostic value of pretreatment whole blood Epstein-Barr virus DNA load and Epstein-Barr encoding region status in lymphomas: A retrospective multicenter study in Huaihai Lymphoma Working Group.

Elevated Epstein-Barr virus (EBV) DNA load is common in lymphomas. However, it remains unclear whether the disparity in viral load and its prognostic value in lymphomas are correlated with Epstein-Barr encoding region (EBER) status. In this retrospective multicenter study, we collected the data of pretreatment whole blood EBV DNA (pre-EBV DNA) and EBER status and evaluated their disparity and prognostic values in lymphomas. A total of 454 lymphoma patients from December 2014 to August 2020 were retrospectively retrieved. Mann-Whitney U test, Kruskal-Wallis test and Bonferroni's adjustment were used to explore the disparity of EBV DNA and EBER status in lymphomas. Time-dependent receiver operating characteristic analysis and MaxStat analysis were used to determine optimal cutoff points of pre-EBV DNA load. Univariable and multivariable Cox proportional hazards models were established for the estimation of prognostic factors. The positive rate of EBV DNA in natural killer T-cell lymphoma (NKTL) patients was higher than that in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin lymphoma (HL) patients, and the median positive pre-EBV copy number of NKTL was also higher than that of FL and DLBCL. EBV DNA could clearly distinguish the prognosis of DLBCL, NKTL, HL and peripheral T-cell lymphoma, and the integration of EBER status and EBV DNA could differentiate the prognosis of HL patients. Multivariable results revealed that pre-EBV DNA load had an effect on the prognosis of NKTL, FL and DLBCL. The status of pre-EBV DNA and EBER were disparate. Whole blood pre-EBV DNA predicted the prognosis of lymphomas, and the combination of EBV and EBER status could differentiate the prognosis of HL.

The Value of Prognostic Nutritional Index (PNI) on Newly Diagnosed Diffuse Large B-Cell Lymphoma Patients: A Multicenter Retrospective Study of HHLWG Based on Propensity Score Matched Analysis.

INTRODUCTION: Immunonutritional status is associated with the survival of DLBCL. This multicenter retrospective study aimed to explore the prognostic value of Prognostic Nutrition Index (PNI) in DLBCL patients by using propensity score matched analysis (PSM). METHODS: A total of 990 DLBCL cases were recruited from 5 centers of Huaihai Lymphoma Working Group (HHLWG). A 1:1 PSM analysis was performed using the nearest-neighbor method, with a caliper size of 0.02. Cox regression analysis was used to examine factors associated with survival. RESULTS: The median age at diagnosis was 62 years and 52.5% were males, with the 3-y overall survival of 65.1%. According to the MaxStat analysis, 44 was the optimal cut-off point of PNI. After PSM analysis, a total of 282 patients in PNI < 44 group could be propensity matched to PNI ≥ 44 patients, creating a group of 564 patients. Multivariable analysis revealed that PNI, age, central nervous system involvement and International Prognostic Index (IPI) were independent prognostic factors for DLBCL. Kaplan-Meier analysis indicated that patients with low PNI in Ann Arbor Stage (III/VI), ECOG (<2), IPI (LR+LIR), GCB, and BCL-2 negative groups had a poor prognosis. DISCUSSION: PNI could accurately stratify the prognosis of DLBCL after PSM analysis.

Development and Validation of a Novel Prognostic Nomogram for CD5-Positive Diffuse Large B-Cell Lymphoma: A Retrospective Multicenter Study in China.

BACKGROUND: CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is a rare subtype of DLBCL with invasive clinical features and poor prognosis. Current clinical variables based on prognostic systems for DLBCL are inadequate to accurately stratify the prognosis of CD5+ DLBCL. METHODS: A total of 195 CD5+ DLBCL patients were retrospectively recruited from nine centers in Huaihai Lymphoma Working Group. MaxStat analysis was used to identify optimal cutoff points for continuous variables; univariable and multivariable Cox analyses were used for variable selection; Kaplan-Meier curve was used to analyze the value of variables on prognosis; and C-index, Brier score, and decision curve analysis were measured for predicting model performance. RESULTS: The derivation and validation cohorts consisted of 131 and 64 patients. Of the whole cohort, median age at diagnosis was 61 years, of whom 100 (51.28%) were males and the 5-year overall survival rate was 42.1%. MYC, BCL-2, and the coexpression of MYC/BCL-2 could distinguish the survival of CD5+ DLBCL. Multivariable analysis showed that age, IPI, red blood cell count, neutrophil count, MYC expression, and hepatosplenomegaly were independent predictors, and the prognostic nomogram was developed. The C-index of the nomogram was 0.809 in the derivation and 0.770 in the validation cohort. Decision curve analysis proved that compared with IPI, the specific nomogram showed a better identification in CD5+ DLBCL. CONCLUSION: The proposed nomogram provided a valuable tool for prognosis prediction in patients with CD5+ DLBCL.

Factors associated with stroke among patients with type 2 diabetes mellitus in China: a propensity score matched study.

OBJECTIVE: This study aimed to examine the prevalence of stroke and associated factors of stroke in patients with type 2 diabetes(T2DM) in China. METHODS: Participants were 18,013 T2DM patients recruited with stratified random cluster sampling method from December 2013 to January 2014 in China. Propensity score matching was used to eliminate confounding effects between groups and logistic regression analysis was used to examine factors associated with stroke among T2DM patients. RESULTS: Overall, the prevalence of stroke in the subjects with T2DM was 9.5%. After nearest neighbor matching, smoking (OR = 1.60, 95%CI: 1.26-2.03), hypertension (OR = 2.96, 95%CI: 2.55-3.43), dyslipidemia (OR = 2.00, 95%CI: 1.71-2.33), family history of stroke (OR = 2.02, 95%CI: 1.61-2.54), obesity (OR = 1.21, 95%CI: 1.01-1.45) and sleep duration < 6 h/day (OR = 1.44, 95%CI: 1.20-1.73) or > 8 h/day (OR = 1.22, 95%CI: 1.05-1.42) were positively associated with stroke, whereas drinking 1-3 days/week (OR = 0.64, 95%CI: 0.45-0.90) or daily (OR = 0.45, 95%CI: 0.33-0.60), effective exercise (OR = 0.65, 95%CI: 0.57-0.73) and underweight (OR = 0.30, 95%CI: 0.13-0.71) were negatively related to stroke. Besides, the risk of stroke increased substantially with accumulation of above seven modified risk factors. The odds ratio values of stroke in patients having ≥ 5 of the above seven risk factors was 14.39 (95% CI: 8.87-23.26). CONCLUSIONS: The prevalence of stroke was high among T2DM in China. It is of great significance to strengthen comprehensive management of health-related behaviors including smoking cessation, moderate alcohol consumption, effective exercise, 6-8 h of sleep duration, keeping normal weight and the prevention of hypertension and dyslipidemia to have sustained beneficial effects on improvements of stroke risk factors.

The Addition of Ferritin Enhanced the Prognostic Value of International Prognostic Index in Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous non-Hodgkin lymphoma, and the prognosis of DLBCL patients is widely affected by multivariables. Clinical-factors-based prognostic systems stratify the prognosis of DLBCL with certain limitations, and the value of ferritin on the prognosis of DLBCL is unclear. In this study, 225 cases were retrieved from 4 centers of Huaihai Lymphoma Working Group (HHLWG) as the derivation cohort, and 66 cases were from the other 6 centers of HHLWG as external validation cohort. X-Tile program divided ferritin into three groups when applying 175.00 and 391.90 µg/L as the optimal cutoff points. Based on multivariable analysis, ferritin appeared to be a stronger predictor. A total of three variables (ferritin, age, and lactate dehydrogenase) were included for the development of the nomogram. The C-indexes were 0.73 and 0.70 in the derivation and validation cohort, and the calibration curve showed the consistency between the nomogram prediction and the actual observation. In conclusion, Ferritin-based nomogram enhanced the prognostic value of IPI in DLBCL.

Highly enantioselective photo-polymerization enhanced by chiral nanoparticles and in situ photopatterning of chirality.

Chiral noble metal nanoparticles has recently gained great interest due to their potential applications including ultrasensitive chiral recognition and asymmetric synthesis. We anticipate that they could be utilized to induce asymmetric photo-polymerization reactions with high enantioselectivity and reactivity. Here, we report such a system. By employing silver nanoparticles modified with cysteine as the chiral inducer, polydiacetylene (PDA) with high chiral asymmetry was obtained from achiral diacetylene monomers triggered with unpolarized UV light. Furthermore, the helical sense of chirality can be controlled by varying the wavelength of UV irradiation. This enables a feasible and economical method to fabricate programmable 2D patterns of chiral PDA with tailored chirality distributions, such as smooth gradients in chirality and micropatterns with tailorable circularly polarized luminescence. Our finding not only opens a pathway for producing programmable chiroptical micropatterns, but also is highly valuable for deeper understanding of symmetry breaking in enantioselective photochemical reactions.

Potential Genes Associated with the Survival of Lung Adenocarcinoma Were Identified by Methylation.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. The purpose of this study is to search for genes related to the prognosis of LUAD through methylation based on a linear mixed model (LMM). METHODS: Gene expression, methylation, and survival data of LUAD patients were downloaded from the TCGA database. Based on the LMM model, the GEMMA algorithm was used to screen the predictive genes related to LUAD survival. The Cox model was used to further screen the predicted genes, and then, protein-protein interaction (PPI) network was constructed. Through the software plugin Cytoscape MCODE 3.8.0, the most closely related genes in the PPI network module were selected for in-depth biological function analysis to further explore the interaction and correlation between genes. RESULTS: We screened out 97 predictive genes from 18,834 genes and eliminated one gene associated with lung squamous cell carcinoma from previous studies, leaving 96 genes. The MCODE and the Kaplan-Meier curve analysis were used to finally identify two genes ASB16 and NEDD4 that are related to the prognosis of LUAD. CONCLUSIONS: The newly identified two genes associated with the prognosis of LUAD may provide a basis for the treatment of patients.

Enantioselective cytotoxicity of chiral polymer vesicles with linear and hyperbranched structures.

Herein, we study the enantioselective cytotoxicity of vesicles self-assembled by optically active linear polymers (LNPs) and hyperbranched polymers (HBPs). Compared to HBP vesicles, LNP vesicles exhibit properties such as a higher surface charge density and more violent interaction with simulated biomembranes which results in larger cytotoxicity against HeLa cells. Specifically, racemic-LNP vesicles exhibit the largest cytotoxicity of all. More interestingly, there is no significant enantioselective dependence of HBP vesicles on the abovementioned properties. Overall, we proved that the cytotoxicity of vesicles is deeply related to chirality and topological-structures. This research is of great fundamental value for the design of novel bio-interface materials.

Integrating PDA microtube waveguide system with heterogeneous CHA amplification strategy towards superior sensitive detection of miRNA.

Catalytic hairpin assembly (CHA) is a typical enzyme-free amplification strategy, in which the target can catalyze two hairpin probes to form a duplex and yield multiple outputs signal. However, the non-specific hybridization of two hairpin probes in CHA circuit usually occurred even in the absence of target, causing significant background leakage and impeding its practical applications in trace miRNA analysis. Herein, we proposed a novel heterogeneous CHA (hetero-CHA) design integrating with PDA microtube waveguide system, offering the advantages to enhance the target signal, but suppress the background leakage simultaneously. In hetero-CHA strategy, single-stranded targets are enriched nearby the surface of PDA microtube, facilitating the target-triggered CHA amplification and strand displacement reactions. In contrast, double-stranded DNA complexes formed by uncatalyzed hybridizations are isolated from PDA microtube, impeding the leakage signal. By combination with condensing enrichment effect, the proposed hetero-CHA probe exhibited high selectivity and sensitivity to miRNA target, giving a detection limit as low as 3.3 fM. More importantly, the proposed hetero-CHA probe can be applied directly to distinguish the expression of miRNA-21 in clinical serum of cancer patients (including lung, breast and pancreatic) from those of healthy human beings, favoring the cancer diagnosis and therapeutic evaluation.