Cytoplasmic Lipid Droplets Predict Worse Prognosis in Diffuse Large B-Cell Lymphoma: Next-Generation Sequencing Deciphering Lipogenic Genes.

Burkitt lymphoma is characterized by high cell turnover and numerous cytoplasmic vacuoles that are demonstrated to be lipid droplets (LDs) decorated by adipophilin. By contrast, cytoplasmic vacuoles are variably observed in diffuse large B-cell lymphoma (DLBCL) and less well characterized. In this study, we first validated in DLBCL that cytoplasmic vacuoles are indeed LDs by Oil-red-O stain, Bodipy fluorescent stain, and electron microscopy. Second, in a cohort of DLBCL patients (n=52) we showed that LDs in effusional lymphoma cells were associated with a poorer prognosis (P=0.029, log-rank test) and higher International Prognostic Index (IPI) score (94% vs. 66%, P=0.026) than those without. Moreover, using adipophilin as a surrogate marker for LDs, we found in another cohort of biopsy specimen (n=85) that expression of adipophilin by lymphoma cells predicted a poorer prognosis (P=0.007, log-rank test) and higher IPI score (63% vs. 30%, P=0.005). In addition, whole exome sequencing of effusional DLBCL cells showed LD-positive DLBCL shared genetic features with the MCD (MYD88 and CD79B mutations) subtype and highlighted OSBPL10 and CUBN as the most frequently mutated genes involved in lipogenesis. Whole transcriptome analysis by comparing effusional DLBCL cells with versus without LDs showed upregulation of EHHADH, SLC1A1, CD96, INPP4B, and RNF183 relevant for lymphoma lipogenesis and upregulation of epithelial-mesenchymal transition and KRAS signaling pathways. Higher expression of EHHADH and CD96 were validated in LD-positive clinical samples and LD-rich cell lines than LD-poor cells along with the known lipogenic gene, FASN. Our findings highlight the roles of LDs and adipophilin expression in DLBCL, suggest that these markers may predict prognosis and show that lipogenic genes may be potential therapeutic targets.

Frequent expression of PD-L1 in BLS-type diffuse large B-cell lymphoma: implications for aggressiveness and immunotherapy.

BLS-type diffuse large B-cell lymphoma (DLBCL) denotes an uncommon, aggressive variant of DLBCL presenting initially in bone marrow, liver and spleen without lymphadenopathy or mass lesion. Patients with BLS-type DLBCL present frequently with haemophagocytic syndrome which often leads to early patient demise. Programmed death ligand 1 (PD-L1) plays a negative regulatory role on effector T cells and is an important target of immunotherapy. Assessment of PD-L1 expression in BLS-type DLBCL may carry therapeutic implications and provide mechanistic insights. Standard immunohistochemical analysis for PD-L1 was performed in seven cohorts for this study: (1) DLBCL-not otherwise specified (NOS) (n=201); (2) Epstein-Barr virus (EBV)-positive DLBCL (n=26); (3) thymic (primary mediastinal) DLBCL (n=12); (4) intravascular LBCL (n=3); (5) high-grade B-cell lymphoma, NOS (n=12); (6) BLS-type DLBCL (n=37); and (7) systemic DLBCL involving bone marrow (n=28). We found that PD-L1 was positive in 12.9% of DLBCL-NOS cases, 46.2% of EBV-positive DLBCL, 91.7% of thymic LBCL, none of intravascular LBCL, 8.3% of high-grade B-cell lymphoma-NOS, and 56.8% of BLS-type DLBCL. By comparison, only 14.3% of bone marrow cases involved by systemic DLBCL were positive for PD-L1 (p<0.001). Interestingly, BLS-type DLBCL more frequently showed activated B-cell phenotype (86.5% vs 65.2%, p=0.010), a high Ki-67 proliferative index (97.1% vs 63.3%, p<0.001), MYC overexpression (90.9% vs 56.2%, p=0.023), presence of haemophagocytic syndrome (86.5% vs 4.0%, p<0.001), and poorer overall survival (p<0.001) than DLBCL-NOS. These data suggest that the poor prognosis of BLS-type DLBCL may be explained by both extrinsic tumour microenvironment factors and intrinsic genetic factors of tumour cells, such as PD-L1-associated inactivation of anti-tumour immunity for the former, and MYC pathway activation-related aggressiveness for the latter.

Clinical implications of PNA­sequencing as a complementary test for EGFR mutation analysis in human lung cancer.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the first-line regimen for the treatment of non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, false-negative results are occasionally observed, even with FDA-approved molecular tests. Such examples in have been reported in our pilot study showing a slightly upward-shifted amplification curve using commercial reverse transcription-quantitative (RT-q)PCR. Verification using peptide nucleic acid (PNA) clamping-sequencing, which has a sensitivity of ~0.1%, may allow better prediction of which patients will benefit from EGFR-TKI therapy. To confirm this hypothesis, samples were prospectively collected from 1,783 lung cancer cases diagnosed in National Cheng Kung University Hospital between 2012-2018. An independent lung cancer cohort of 1,944 cases was also recruited from other hospitals. The clinical significance of mutant-enriched PCR with PNA-sequencing was analyzed and patient outcomes were followed. A total of 17 of 34 cases (50%) were found to harbor EGFR mutations by PNA-sequencing. A total of 22 cases were discovered in the independent lung cancer cohort, and 14 of these (63.6%) cases had EGFR mutations. TKIs were administered to 14 of the 17 mutation-positive patients, and a partial response was observed in 4 cases and stable disease in 10 cases. Patients with EGFR mutations receiving a TKI regimen had a longer overall survival (OS) (median: 40.0 vs. 10.0 months) compared with those without treatment. The difference in OS was not significant. Based on the results of the present study, combining RT-qPCR with PNA-sequencing may be a practical supplementary technology in a clinical molecular laboratory for a subset of lung cancer patients in selection of EGFR TKI therapy.

Cross-Scale Fusion Transformer for Histopathological Image Classification.

Histopathological images provide the medical evidences to help the disease diagnosis. However, pathologists are not always available or are overloaded by work. Moreover, the variations of pathological images with respect to different organs, cell sizes and magnification factors lead to the difficulty of developing a general method to solve the histopathological image classification problems. To address these issues, we propose a novel cross-scale fusion (CSF) transformer which consists of the multiple field-of-view patch embedding module, the transformer encoders and the cross-fusion modules. Based on the proposed modules, the CSF transformer can effectively integrate patch embeddings of different field-of-views to learn cross-scale contextual correlations, which represent tissues and cells of different sizes and magnification factors, with less memory usage and computation compared with the state-of-the-art transformers. To verify the generalization ability of the CSF transformer, experiments are performed on four public datasets of different organs and magnification factors. The CSF transformer outperforms the state-of-the-art task specific methods, convolutional neural network-based methods and transformer-based methods. The source code will be available in our GitHub https://github.com/nchucvml/CSFT.

The experience of neoadjuvant chemotherapy versus upfront surgery in resectable pancreatic cancer: a cross sectional study.

BACKGROUND: Upfront resection (UR) followed by adjuvant chemotherapy remains the standard treatment for resectable pancreatic cancer. There is increasing evidence suggesting favourable outcomes toward neoadjuvant chemotherapy (NAC) followed by surgery. METHODS: All clinical staging with resectable pancreatic cancer patients treated at a tertiary medical centre from 2013 to 2020 were identified. The baseline characteristics, treatment course, surgery outcome and survival results of UR or NAC were compared. RESULTS: Finally, in 159 resectable patients, 46 patients (29%) underwent NAC and 113 patients (71%) received UR. In NAC, 11 patients (24%) did not receive resection, 4 (36.4%) for comorbidity, 2 (18.2%) for patient refusal and 2 (18.2%) for disease progression. In UR, 13 patients (12%) were unresectable intraoperatively; 6 (46.2%) for locally advanced and 5 (38.5%) for distant metastasis. Overall, 97% of patients in NAC and 58% of patients in UR completed adjuvant chemotherapy. As of data cut-off, 24 patients (69%) in NAC and 42 patients (29%) in UR were still tumour free. The median recurrence-free survival in NAC, UR with adjuvant chemotherapy and without adjuvant chemotherapy were 31.3 months (95% CI, 14.4-not estimable), 10.6 months (95% CI, 9.0-14.3) and 8.5 months (95% CI, 5.8-11.8), P =0.036; and the median overall survival in each group were not reached (95% CI, 29.7-not estimable), 25.9 months (95% CI, 21.1-40.5) and 21.7 months (12.0-32.8), P =0.0053. Based on initial clinical staging, the median overall survival of NAC was not significantly different from UR with a tumour less than or equal to 2 cm, P =0.29. NAC patients had a higher R0 resection rate (83% versus 53%), lower recurrence rate (31% versus 71%) and harvested median number lymph node (23 versus 15). CONCLUSION: This study demonstrates that NAC is superior to UR in resectable pancreatic cancer with better survival.

Variable radiographic and histologic presentations of amiodarone-related interstitial lung disease and the importance of avoiding re-exposure.

Amiodarone is a commonly used antiarrhythmic agent but exhibits potential pulmonary toxicity. In this case series, we describe the clinical, radiographic, and histologic manifestations of three patients who developed interstitial lung disease (ILD) following amiodarone treatment for variable lengths of time with different dosages. The presentations on computed tomographic images and in pulmonary pathology differed among the three patients. All three had immediate discontinuation of amiodarone and received treatment with systemic corticosteroids. One patient eventually died from ventilator-associated pneumonia after an initial improvement. The other two patients recovered well but later experienced ILD recurrence following brief re-exposure to amiodarone. Through this case series, we aim to demonstrate the variable features of amiodarone-related ILD, and highlight the importance of timely amiodarone cessation and avoiding re-exposure to prevent the progression and recurrence of ILD.

Impact of computed tomographic patterns and extent on clinical management and outcomes of patients with organising pneumonia.

Background: Organising pneumonia (OP) has variable clinical and radiographic presentations and unstandardised treatments. Most patients with OP have favourable outcomes, but some develop respiratory insufficiency, experience recurrence or die. In this study we investigated the impact of computed tomographic (CT) patterns and extent of OP on the diagnostic and therapeutic management that patients received, and that on the therapeutic response and prognosis (particularly the risk of respiratory insufficiency and death). Methods: We retrospectively studied 156 patients with OP followed at our hospital between 2010 and 2021. The diagnosis was confirmed histologically and verified by multidisciplinary specialists. We performed Firth's logistic regression to determine the relationship between CT features and aetiologies, management and outcomes including the risk of severe disease (defined as the need for supplemental oxygen or mechanical ventilation). We conducted Kaplan-Meier analyses to assess survival differences. Results: Patients exhibiting multilobe involvement or mixed patterns, or both, were more likely to have secondary OP and receive immunosuppressants. Higher proportions of these patients experienced recurrence. Compared to patients with single-lobe involvement and single-pattern, they also had an enhanced risk of severe disease (the adjusted odds ratio for patients who simultaneously had multilobe involvement and mixed patterns was 27.64; 95% confidence interval 8.25-127.44). Besides, these patients had decreased survival probabilities. Conclusion: Different CT features of OP impact patients' management and prognosis. When treating patients with OP exhibiting multilobe involvement or mixed patterns, or both, it is important to identify the possible causative aetiology and follow closely for adverse outcomes.

Investigation into the content of red material in EUS-guided pancreatic cancer biopsies.

BACKGROUND AND AIMS: The red material occupying the larger portion of the acquired sample in EUS fine-needle biopsy (FNB) is seldom investigated. We aimed to evaluate the composition of the red material. METHODS: Patients with a solid pancreatic mass who received EUS FNB from September 2020 to June 2021 were enrolled. The white or yellowish content with apparent bulk (white material) and the rest of pasta-like red content (red material) were separated immediately after puncture. Needle passes proceeded until 2 specimens with >4 mm of white material were obtained. An extra needle pass was conducted for DNA collection. The DNA amount, Kirsten rat sarcoma virus (K-ras) mutation type, and mutation allele frequency were compared between the white and red material. RESULTS: Forty patients were enrolled with 68 paired white and red materials. The diagnostic accuracy was slightly higher in the white material (92.5% vs 82.5%, P = .219). On the histology slides, the area of the tumor gland was comparable in both materials, but the total tissue area was larger in the red material (9.74 mm2 and 10.74 mm2 larger according to generalized linear model and generalized estimating equation, respectively; both, P < .001). The amount of DNA was significantly higher in the red material (2.99 [interquartile range, 1.59-7.29] µg vs .70 [interquartile range, .27-1.24] µg; P < .001). Common pancreatic adenocarcinoma K-ras mutation was identified at a rate of 85% for the white material and 95% for the red material. Regardless of whether red or white material was used, there was a high concordance of K-ras mutation types (34 of 40 [85%]) and a high correlation of mutation allele frequency (ρ = .66, P < .001). CONCLUSIONS: In EUS FNB, the red material contains a higher amount of tumor DNA and can be an alternative source for tumor DNA analysis.

Evolution of the Correa's cascade steps: A long-term endoscopic surveillance among non-ulcer dyspepsia and gastric ulcer after H. pylori eradication.

BACKGROUND: This study is aimed toward investigating the evolution of each Correa's step after Helicobacter pylori eradication in a long-term follow-up and exploring the factors correlated with a high-risk of gastric cancer. METHODS: A total of 1824 H. pylori-infected subjects were enrolled to receive screening endoscopy. Among them, 491 received surveillance endoscopy. The patients were divided into Correa's steps I to VI, from normal to gastric cancer. A group-based trajectory model was used to classify patients as persistent high-risk status or not. RESULTS: The prevalence rates of positive corpus-predominant gastritis index (CGI) were 20%-40% in all age groups and Correa's steps IV-V increased >35% after 50 years based on screening endoscopy. Successful eradication of H. pylori regressed CGI after the 1st year-and-thereafter (P < 0.05) and decreased Correa's step progression (Relative risk 0.66 [95% CI 0.49-0.89], P = 0.01); however, it did not regress OLGA and OLGIM. Not only in steps IV-V, but also in step III, the patients had a risk of developing gastric cancer (11.13-76.41 and 4.61 per 1000 person-years). Age (Hazard ratio 1.012 [1.003-1.020], P = 0.01), OLGA stages ≥ I (2.127 [1.558-2.903], P < 0.001), and OLGIM stages ≥ I (1.409 [1.119-1.774], P = 0.004) were correlated independently with a persistent high-risk status. CONCLUSION: The patients in Correa's steps III-V, but not I-II, were at risk of gastric cancer after H. pylori eradication. Age, OLGA stages ≥ I, and OLGIM stages ≥ I were independent factors correlated to a persistent high-risk of gastric cancer. The data may be useful when scheduling surveillance endoscopy for subjects in each Correa's step (NCT04527055).

Association between Metabolic Phenotypes of Body Fatness and Incident Stroke: A Prospective Cohort Study of Chinese Community Residents.

This study aimed to assess the association of body mass index (BMI)-based and waist circumference (WC)-based metabolic phenotypes with the risk of stroke among Chinese community residents. A total of 34,294 participants (mean ± standard deviation age: 56.05 ± 11.26 years) with no previous stroke diagnosis history were included in this cohort study. BMI-based metabolic phenotypes were classified into eight groups: metabolically healthy and normal weight (MHNW), metabolically healthy and underweight (MHUW), metabolically healthy and overweight (MHOW), metabolically healthy and obese (MHO), metabolically unhealthy and normal weight (MUNW), metabolically unhealthy and underweight (MUUW), metabolically unhealthy and overweight (MUOW), and metabolically unhealthy and obese (MUO). WC-based metabolic phenotypes were classified into four groups: metabolically healthy and normal WC (MHNWC), metabolically healthy and oversized WC (MHOWC), metabolically unhealthy and normal WC (MUNWC), and metabolically unhealthy and oversized WC (MUOWC). The association of these phenotypes with developing stroke events was examined using proportional hazards models. A total of 546 cases of first-stroke onset were recorded over a median follow-up time of 4.97 years. Compared with the reference group, the obesity phenotypes showed higher risks for stroke. The adjusted HRs (95% CIs) of MHUW, MHOW, MHO, MUNW, MUUW, MUOW, and MUO phenotypes were 1.01 (0.41, 2.49), 1.47 (1.09, 2.00), 1.33 (0.80, 2.22), 2.49 (1.87, 3.30), 3.92 (1.44, 10.72), 2.14 (1.64, 2.79), and 2.60 (1.91, 3.55), respectively. The adjusted HRs (95% CIs) of MHOWC, MUNWC, and MUOWC were 1.41 (1.02, 1.94), 2.25 (1.76, 2.87), and 2.16 (1.63, 2.87), respectively. The metabolic phenotypes defined by an alternative definition all showed significant positive associations (except for MHUW), with the adjusted HR ranging from 1.51 to 3.08 based on BMI and from 1.68 to 2.24 based on WC. The risk of stroke increased with the increase in metabolic abnormality numbers in different BMI and WC groups (all p trend < 0.001). The present study suggests that maintaining normal body weight or WC and improving metabolic health are of great significance in preventing cerebrovascular diseases.

Adherence to DASH Dietary Pattern and Its Association with Incident Hyperuricemia Risk: A Prospective Study in Chinese Community Residents.

Hyperuricemia represents a great burden on global public health, and it is important to provide effective guidance at the level of dietary patterns. We evaluated the association between the Dietary Approaches to Stop Hypertension (DASH) diet and the risk of hyperuricemia in a large-scale, community-based cohort in East China. In total, 45,853 participants that did not have either hyperuricemia nor gout were included and assigned a DASH dietary score based on their baseline dietary intake. They were then divided into five quintiles (Q1−Q5) according to their score, followed by cross-linkages with local health information systems and in-person surveys. Cox proportional hazards models were adopted to calculate hazard ratio (HR) and 95% confidence intervals (CIs). During a median follow-up of 4.54 years, 2079 newly diagnosed hyperuricemia cases were documented. Compared to the DASH Q1 group, the risk of incident hyperuricemia for the Q5 group was significantly reduced by 16% (HR: 0.84; 95% CIs: 0.72−0.97) in the adjusted model. The associations of DASH diet with hyperuricemia appeared stronger (P for interaction <0.001) among participants with 3−4 cardiometabolic diseases at baseline, compared with their counterparts. Our results suggest that the DASH diet could be taken into account in the recognition of risk population and the prevention of hyperuricemia.

Serum Metabolomics Profiling Reveals Metabolic Alterations Prior to a Diagnosis with Non-Small Cell Lung Cancer among Chinese Community Residents: A Prospective Nested Case-Control Study.

The present high mortality of lung cancer in China stems mainly from the lack of feasible, non-invasive and early disease detection biomarkers. Serum metabolomics profiling to reveal metabolic alterations could expedite the disease detection process and suggest those patients who are harboring disease. Using a nested case-control design, we applied ultra-high-performance liquid chromatography/mass spectrometry (LC-MS)-based serum metabolomics to reveal the metabolomic alterations and to indicate the presence of non-small cell lung cancer (NSCLC) using serum samples collected prior to disease diagnoses. The studied serum samples were collected from 41 patients before a NSCLC diagnosis (within 3.0 y) and 38 matched the cancer-free controls from the prospective Shanghai Suburban Adult Cohort. The NSCLC patients markedly presented cellular metabolism alterations in serum samples collected prior to their disease diagnoses compared with the cancer-free controls. In total, we identified 18 significantly expressed metabolites whose relative abundance showed either an upward or a downward trend, with most of them being lipid and lipid-like molecules, organic acids, and nitrogen compounds. Choline metabolism in cancer, sphingolipid, and glycerophospholipid metabolism emerged as the significant metabolic disturbance of NSCLC. The metabolites involved in these biological processes may be the distinctive features associated with NSCLC prior to a diagnosis.

Fish Consumption and Risk of Stroke in Chinese Adults: A Prospective Cohort Study in Shanghai, China.

Present studies on the association of fish consumption with risk of stroke have shown controversial results, and this association within the Chinese population remains unknown. We aimed to investigate the association between fish consumption and incidence of total stroke, ischemic stroke and hemorrhagic stroke among adults in China. We analyzed the data of 57,701 adults aged 20-74 years, with no history of stroke, in a prospective cohort study in Shanghai. Fish consumption was calculated from a food frequency questionnaire at baseline and divided into four categories (less than 300, 300-450, 450-600 and more than 600 g/week). Participant information was linked to health information systems in which stroke event information was collected up until 31 December 2021. The hazard ratios (HR) and 95% confidence intervals (CI) of the associations of fish consumption with risk of total stroke, ischemic stroke and hemorrhagic stroke were estimated using cox proportional hazards regression models. Dose-response relationships were estimated using restricted cubic spline analyses. During a median follow-up of 4.56 years, 807 newly developed stroke events were ascertained, including 664 ischemic stroke events and 113 hemorrhagic stroke events. Fish consumption of 300-450 g/week was associated with a reduced risk of total stroke (HR: 0.78, 95% CI: 0.64-0.94) and ischemic stroke (0.70 (0.57-0.88)) compared with fish consumption of less than 300 g/week, after adjustment for comprehensive covariates including sociodemographic characteristics, lifestyle, dietary patterns and disease histories. No significant association was found between fish consumption and hemorrhagic stroke. The findings of our study support the consumption level of fish recommended in the dietary guidelines.

Association between four nontraditional lipids and ischemic stroke: a cohort study in Shanghai, China.

BACKGROUND: The correlation between nontraditional lipids and ischemic stroke (IS) is inconsistent and controversial. This study aimed to examine the association of four nontraditional lipids with IS risk in Chinese adults. METHODS: This prospective community-based cohort study was performed in Songjiang District, Shanghai, China. The study began in 2016 and included 34,294 participants without stroke before the investigation. The association between nontraditional lipids (nonhigh-density lipoprotein cholesterol [non-HDL-C], total cholesterol/high-density lipoprotein cholesterol [TC/HDL-C], triglyceride [TG]/HDL-C, and low-density lipoprotein cholesterol [LDL-C]/HDL-C) and IS was studied with multivariate Cox regression models. The dose-response associations between these four serum lipids and IS were explored using restricted cubic spline (RCS) analysis. RESULTS: There were a total of 458 IS cases with 166,380 person-years of follow-up. Compared with the lowest tertiles, the highest tertiles of the nontraditional blood lipids showed greater IS risk after controlling for potential confounders. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were as follows: TC/HDL-C, 1.63 (1.28-2.07); TG/HDL-C, 1.65 (1.28-2.13); LDL-C/HDL-C, 1.51 (1.18-1.92); and non-HDL-C, 1.43 (1.13-1.81). The fully adjusted RCS curves presented a nonlinear relationship, and the risk increased when the TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C levels were > 3.47, > 0.92, and > 1.98, respectively. CONCLUSIONS: This community-based cohort study presents a positive association between the four nontraditional lipids and IS incidence. Maintaining relatively low lipid ratios can be beneficial for preventing stroke. Nontraditional lipids can be considered targets for managing blood lipids.

Improved survival with induction chemotherapy and conversion surgery in locally advanced unresectable pancreatic cancer: a single institution experience.

Both efficacy and tolerability are critical issues in choosing neoadjuvant chemotherapy in patients with unresectable locally advanced pancreatic cancer (LAPC). The optimal regimen and the impact of conversion surgery on patient survival remains insufficiently reported in Asain population. Therefore, we conducted a retrospective study aiming to evaluate the resection rate after different induction chemotherapy regimen and its impact toward survival. All patients with pancreatic cancer treated in our institute from 2013 to 2020, a total of 730 patients, were reviewed and 131 patients with LAPC were identified. For cohort homogeneity, 14 patients receiving induction concurrent chemoradiotherapy initially were excluded and 117 patients receiving induction chemotherapy were included in the study. Most patients (90 of 117, 77%) received triplet induction chemotherapy, including the combination of S1, leucovorin, oxaliplatin and gemcitabine (SLOG) in 48, modified FOLFIRINOX in 21 and the combination of gemcitabine, oxaliplatin, fluorouracil and leucovorin (GOFL) in 21. The tumor response rate (19%-33%), the surgical exploration rate (38%-52%) and the mOS (15.4-23.0 months) were not significantly different among the three triplets. Both GOFL and SLOG regimen had comparable efficacy and less neutropenia as compared to mFOLFIRINOX. Conversion surgery was performed in 34 of 117 (29%) patients after induction chemotherapy. The median overall survival (mOS) in patients with and without conversion surgery were 29.1 and 14.1 months, respectively (P<0.0001). Radiological response alone was not a reliable indicator of successful conversion surgery. Patients who underwent conversion surgery had significantly better survival and thus highlighted the importance of surgical exploration in all patients who did not have progressive disease after induction chemotherapy.

Obesity and Dyslipidemia in Chinese Adults: A Cross-Sectional Study in Shanghai, China.

This study examined the association of obesity and dyslipidemia according to body measurements among Chinese adults in Shanghai, a place in the process of rapid urbanization. Using the baseline data of the Shanghai Suburban Adult Cohort and Biobank study (SSACB), the subjects completed questionnaires and physical examinations, and fasting blood was collected for biochemical assays. We estimated the odds ratios (OR) and 95% confidence interval (CI) by multivariable logistic regression. The prevalence was 12.9% and 28.8% in both general and central obesity, respectively. Compared with the non-obese, the general or central obesity participants had a higher level of TC, TG, LDL-C and lower level of HDL-C. The OR (95%CI) for dyslipidemia was 1.79 (1.69-1.91) and 1.91 (1.83-2.00) in general or central obesity, respectively. Positive associations were also observed between obesity and high TC, high LDL-C, low HDL-C and high TG, with the adjusted OR ranging from 1.11 to 2.00. Significant modifying effect of gender, age, hypertension, and diabetes were found in the association of obesity and different forms of dyslipidemia. The findings of our study indicated that participants with obesity, including general or central obesity, have a higher prevalence of dyslipidemia and gender, age, hypertension, and diabetes might be potential modifiers of the association. More effective attention and interventions should be directed to managing body weight to reduce the prevalence of dyslipidemia.

Efficacy of Coxsackievirus A2 vaccine candidates correlating to humoral immunity in mice challenged with a mouse-adapted strain.

BACKGROUND: In recent years, Coxsackievirus A2 (CV-A2) has become one of the main serotypes of enterovirus species A associated with hand, foot and mouth disease (HFMD) in China. It has also caused HFMD epidemics in many countries all over the world. Currently, there are no effective, preventive vaccines against it. METHODS: A CV-A2 strain was isolated in RD cells and then adapted to grow in Vero cells. This is in compliance with guidelines for cell substrates allowed for human vaccines by the Chinese regulatory authority. Groups of newborn Kunming mice were inoculated on day 3 and day 9 using two formulations of candidate vaccines, empty particles and full particles. They were then challenged on day 14 at a lethal dose with a mouse-adapted strain. RESULTS: The mice in the control group all died within 14 days post-challenge whereas most of the mice in the candidate vaccine groups survived. It was found that the titers of neutralizing antibodies was dose-dependent in sera of immunized mice. The results also showed that the vaccine candidates stimulated a strong humoral immune response and protected the mice from disease and death. The virus loads in tissues or organs were significantly reduced and pathological changes were either weak or not observed in the immunized groups compared with those in Al(OH)3 control group. Preliminary mapping of the nucleotide and amino acid residues potentially related to cell tropism of the vaccine strain and virulence of the challenge strain was performed. CONCLUSION: The results showed that the RD cell-isolated and Vero cell-adapted CV-A2 strain is a promising vaccine candidate. This active immunization-challenge mouse model mimics the vaccination and then exposure to wildtype viruses, compared with passive immunization-challenge model, and is invaluable for efficacy evaluation in studies on multivalent vaccines containing CV-A2 against HFMD.

Two-dimensional metal-organic frameworks: from synthesis to bioapplications.

As a typical class of crystalline porous materials, metal-organic framework possesses unique features including versatile functionality, structural and compositional tunability. After being reduced to two-dimension, ultrathin metal-organic framework layers possess more external excellent properties favoring various technological applications. In this review article, the unique structural properties of the ultrathin metal-organic framework nanosheets benefiting from the planar topography were highlighted, involving light transmittance, and electrical conductivity. Moreover, the design strategy and versatile fabrication methodology were summarized covering discussions on their applicability and accessibility, especially for porphyritic metal-organic framework nanosheet. The current achievements in the bioapplications of two-dimensional metal-organic frameworks were presented comprising biocatalysis, biosensor, and theranostic, with an emphasis on reactive oxygen species-based nanomedicine for oncology treatment. Furthermore, current challenges confronting the utilization of two-dimensional metal-organic frameworks and future opportunities in emerging research frontiers were presented.