A potential pathway for identifying hypertension among urban residents aged 60+ years in China: the role of health insurance.

Background: Identification is the first step for treatment of hypertension. However, the awareness rate of hypertension was not high globally. This study aimed to examine the potential role of health insurance for early-identifying hypertension among urban older residents in China. Methods: In this cross-sectional study, urban residents aged 60+ years were chosen from Nanjing municipality of China in 2018. The outcome measure was hypertension status ("no hypertension," "diagnosed hypertension" or "un-diagnosed hypertension"). Independent variable was health insurance ("Urban Employee Basic Medical Insurance scheme, UEBMI" or "Urban Resident Basic Medical Insurance scheme, URBMI"). Logistic regression models were introduced to estimate odds ratio (OR) and 95% confidence interval (CI) to examine the association between health insurance and hypertension. Results: Totally, 19,742 participants completed the study. Among overall, URBMI and UEBMI participants, 47.2% (95%CI = 46.5, 47.9%), 38.4% (95%CI = 37.3, 39.6%) and 52.1% (95%CI = 51.2, 53.0%), separately, were diagnosed with hypertension, while the prevalence of un-diagnosed hypertension was 12.7% (95%CI = 12.2, 13.2%), 18.5% (95%CI = 17.6, 19.4%) and 9.6% (95%CI = 9.1, 10.1%), respectively. For overall participants, those with UEBMI were more likely to have hypertension identified (OR = 1.20; 95%CI = 1.11, 1.29) and at lower odds to experience un-diagnosed hypertension (OR = 0.68; 95%CI = 0.61, 0.76) compared to their counterparts with URBMI after control for potential confounders. Moreover, such associations of health insurance with diagnosed and un-diagnosed hypertension were also observed among participants stratified by age and gender. Conclusion: Favorable health insurance may be a pathway for identifying hypertension among urban older residents in China. This study has important public health implications that hypertension may be identified early through favorable health insurance policies for older residents in China.

Diagnostic status and epidemiological characteristics of community-acquired bacterial meningitis in children from 2019 to 2020: a multicenter retrospective study.

Community-acquired bacterial meningitis (CABM) is the main cause of morbidity and mortality in children. The epidemiology of CABM is regional and highly dynamic. To clarify the diagnostic status and epidemiological characteristics of children with CABM in this region, and pay attention to the disease burden, so as to provide evidence for the prevention and treatment of CABM. By retrospective case analysis, the clinical data of 918 CABM cases in children aged 0-14 years in Zhejiang Province from January, 2019 to December, 2020 were collected. The etiological diagnosis rate of CABM in children was 23.1%, the annual incidence rate 4.42-6.15/100,000, the annual mortality rate 0.06-0.09/100,000,the cure and improvement rate 94.4%, and the case fatality rate 1.4%. The total incidence of neuroimaging abnormalities was 20.6%. The median length of stay for CABM children was 20(16) days, with an average cost of 21,531(24,835) yuan. In addition, the incidence rate was decreased with age. Escherichia coli(E.coli) and group B Streptococcus agalactiae(GBS) were the principal pathogens in CABM infant<3 months(43.3%, 34.1%), and Streptococcus pneumoniae(S. pneumoniae) was the most common pathogen in children ≥ 3 months(33.9%). In conclusion, the annual incidence and mortality of CABM in children aged 0-14 years in Zhejiang Province are at intermediate and low level. The distribution of CABM incidence and pathogen spectrum are different in age; the incidence of abnormal neuroimaging is high; and the economic burden is heavy.

Meat, vegetable, and fruit consumption among urban and rural elders aged 60+ years in regional China: a population-level nutritional study.

The aim was to assess epidemiological characteristics of the most recent consumption patterns of meat, vegetable, and fruit among representative urban and rural residents aged 60+ years in regional China. In this cross-sectional survey conducted in mid-2018, participants aged 60+ years were randomly chosen from urban and rural communities in Nanjing municipality of China. Meat, vegetable, and fruit intake were assessed with a validated food frequency questionnaire. Multivariate logistic regression models were applied to compute odds ratio (OR) and 95 % confidence interval (CI) to investigate the association of socio-demographic characteristics with a likelihood of meeting intake recommendation. Among the 20 867 participants, 49⋅5 % were men and 45⋅0 % urban elders, and 6⋅5 % aged 80+ years. The mean values of consumption frequency of red meat, white meat, vegetable, and fruit were 2⋅99 ± 2⋅28, 1⋅37 ± 1⋅13, 5⋅24 ± 6⋅43, and 2⋅64 ± 2⋅91 times/week, respectively, among overall participants. Moreover, there were 14⋅9, 23⋅7, and 12⋅1 % of participants meeting intake recommendations of meat, vegetable, and fruit, separately, in this study. After adjustment for potential confounders, age, gender, residence area, and educational attainment each was associated with the likelihood of meeting intake recommendation of meat, vegetable, or fruit. The consumption frequency and proportion of participants meeting intake recommendations of meat, vegetable, or fruit were not high among elders in regional China. Socio-demographic characteristics were associated with intake recommendations of meat, vegetables, and fruit. It has public health implications that participants' socio-demographic attributes shall be considered for precision intervention on meat, vegetable, and fruit consumption in healthy eating campaigns among elders in China.

Assessing causality between osteoarthritis and gastrointestinal disorders: a Mendelian randomization study.

The association between osteoarthritis (OA) and gastrointestinal disorders was found in observational studies. However, the causality is still elusive. A bidirectional Mendelian randomization (MR) analysis using genome wide association studies data was conducted to assess the causal association between OA and gastrointestinal diseases [including peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), and inflammatory bowel disease (IBD)]. A two-step MR (TSMR) was conducted between OA, gastrointestinal diseases and drugs to explore the mediating effects of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids use. We used multivariable MR (MVMR) analysis to further validate the impact of prescription history on diseases. Results had statistical significance at a Bonferroni corrected P-value below 0.008. We observed that genetically predicted OA had a significant positive association with GORD [odds ratio (OR) = 1.26, P = 5e-05], but not with PUD or IBD. Regarding the other direction, gastrointestinal disorders as exposure had a null association with OA. Using TSMR, OA patients tended to increase the use of NSAIDs (OR = 1.45, P = 0.001) and opioids (OR = 1.77, P = 2e-05), but only the use of opioids increased the risk of GORD (OR = 1.43, P = 5e-09). Further MVMR analysis showed that the adverse effect of OA on GORD was significantly reduced after adjusting for opioids use (OR = 1.20, P = 0.038). This study provides evidence for the causal association between OA and increased risk of GORD, which is partly attributed to opioids use in OA patients but not NSAIDs.

Factors associated with afebrile presentation and delayed defervescence of bacterial meningitis in children under 3 years of age: a multi-centre retrospective analysis.

BACKGROUND: This multi-center study aimed to identify factors affecting fever and delayed defervescence in bacterial meningitis (BM) patients under 3 years of age because of the variability of fever in this patient population. METHODS: Only BM patients under 3 years treated at 49 centers in China from November 2018 to end-April 2021 were included in the study. Univariate and multivariate logistic regression analyses were performed to determine factors associated with afebrile presentation and fever of delayed defervescence. RESULTS: A total of 863 BM patients under 3 years were included in the study. Coagulase negative staphylococcus was associated with afebrile presentation (OR = 1.176), while septicaemia and ear-nose-throat infections were associated with fever (P < 0.05). The patients with fever were assigned into early and delayed defervescence groups based on defervescence time (less than and more than or equal to one week). Furthermore, Streptococcus agalactiae meningitis (OR = 1.124), concomitant gastrointestinal infection (OR = 1.276), encephalomalacia (or = 1.339), and subdural effusion (OR = 1.454) were independently associated with delayed defervescence (all P < 0.05). CONCLUSIONS: The findings can aid in the efficient utilization of fever in auxiliary diagnosis and evaluating the condition of the disease.

Advances in preparation and application of antibacterial hydrogels.

Bacterial infections, especially those caused by drug-resistant bacteria, have seriously threatened human life and health. There is urgent to develop new antibacterial agents to reduce the problem of antibiotics. Biomedical materials with good antimicrobial properties have been widely used in antibacterial applications. Among them, hydrogels have become the focus of research in the field of biomedical materials due to their unique three-dimensional network structure, high hydrophilicity, and good biocompatibility. In this review, the latest research progresses about hydrogels in recent years were summarized, mainly including the preparation methods of hydrogels and their antibacterial applications. According to their different antibacterial mechanisms, several representative antibacterial hydrogels were introduced, such as antibiotics loaded hydrogels, antibiotic-free hydrogels including metal-based hydrogels, antibacterial peptide and antibacterial polymers, stimuli-responsive smart hydrogels, and light-mediated hydrogels. In addition, we also discussed the applications and challenges of antibacterial hydrogels in biomedicine, which are expected to provide new directions and ideas for the application of hydrogels in clinical antibacterial therapy.

Research progress of polyphenols in nanoformulations for antibacterial application.

Infectious disease is one of the top 10 causes of death worldwide, especially in low-income countries. The extensive use of antibiotics has led to an increase in antibiotic resistance, which poses a critical threat to human health globally. Natural products such as polyphenolic compounds and their derivatives have been shown the positive therapeutic effects in antibacterial therapy. However, the inherent physicochemical properties of polyphenolic compounds and their derivatives limit their pharmaceutical effects, such as short half-lives, chemical instability, low bioavailability, and poor water solubility. Nanoformulations have shown promising advantages in improving antibacterial activity by controlling the release of drugs and enhancing the bioavailability of polyphenols. In this review, we listed the classification and antibacterial mechanisms of the polyphenolic compounds. More importantly, the nanoformulations for the delivery of polyphenols as the antibacterial agent were summarized, including different types of nanoparticles (NPs) such as polymer-based NPs, metal-based NPs, lipid-based NPs, and nanoscaffolds such as nanogels, nanofibers, and nanoemulsions. At the same time, we also presented the potential biological applications of the nano-system to enhance the antibacterial ability of polyphenols, aiming to provide a new therapeutic perspective for the antibiotic-free treatment of infectious diseases.

Effect of high-intensity ultrasonic time on structural, mechanical, and physicochemical properties of ß-conglycinin (7S)- Transglutaminase (TGase) composite edible films.

The ß-conglycinin (7S) was pre-treated with high-intensity ultrasonic (HIU) and subsequently formed into composite edible films with the transglutaminase (TGase) method. Effects of HIU pretreatment time (0, 5, 10, 15, and 20 min) on the conformation of 7S and structural and application properties of 7S-TGase films were evaluated. The analysis of 7S conformation results revealed that HIU pretreatment for 0-10 min significantly dissociated the 7S, exposed internal hydrophobic groups of protein, increased its intermolecular hydrogen bonds, and altered the protein secondary and tertiary structure. The structural properties of films were evaluated by SEM, XRD, and ATR-FTIR. SEM showed that HIU reduced film wrinkles and cracks and improved unevenness. XRD and ATR-FTIR indicated that the film obtained an enlarged crystallinity, and the amide I and amide II regions of films were peak-shifted which is usually associated with the formation of covalent bonds. Notably, analysis of intermolecular force showed that HIU facilitated the formation of hydrogen bonds, hydrophobic interactions, and ε-(γ-glutamyl) lysine bonds in 7S-TGase films. The above structural changes in 7S and films were beneficial for the application properties of films. Results indicated that 10 min HIU pretreatment effectively improved the mechanical properties and water resistance, reduced water vapor permeability and oxygen permeability, and decreased the opacity of 7S-TGase films. However, the color of the film was not affected by the HIU, with an overall bright and yellowish color.

Effect of High-Intensity Ultrasound Pretreatment on the Properties of the Transglutaminase (TGase)-Induced ß-Conglycinin (7S) Gel.

In this study, we investigated the effects of different high-intensity ultrasound (HIU) pretreatment times (0-60 min) on the structure of ß-conglycinin (7S) and the structural and functional properties of 7S gels induced by transglutaminase (TGase). Analysis of 7S conformation revealed that 30 min HIU pretreatment significantly induced the unfolding of the 7S structure, with the smallest particle size (97.59 nm), the highest surface hydrophobicity (51.42), and the lowering and raising of the content of the α-helix and ß-sheet, respectively. Gel solubility showed that HIU facilitated the formation of ε-(γ-glutamyl)lysine isopeptide bonds, which maintain the stability and integrity of the gel network. The SEM revealed that the three-dimensional network structure of the gel at 30 min exhibited filamentous and homogeneous properties. Among them, the gel strength and water-holding capacity were approximately 1.54 and 1.23 times higher than those of the untreated 7S gels, respectively. The 7S gel obtained the highest thermal denaturation temperature (89.39 °C), G', and G″, and the lowest tan δ. Correlation analysis demonstrated that the gel functional properties were negatively correlated with particle size and the α-helix, while positively with Ho and ß-sheet. By contrast, gels without sonication or with excessive pretreatment showed a large pore size and inhomogeneous gel network, and poor properties. These results will provide a theoretical basis for the optimization of HIU pretreatment conditions during TGase-induced 7S gel formation, to improve gelling properties.

UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats.

Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) promotes the maintenance of established patterns of DNA methylation in mammalian cells. Extensive methylation of connexin26 (COX26) during hearing impairment has been demonstrated. The present study aims to determine whether UHRF1 can induce the methylation of COX26 in cochlea damaged by intermittent hypoxia (IH). After the establishment of the cochlear injury model through IH treatment or isolation of the cochlea containing Corti's organ, pathological changes were observed via HE staining. Expressions of COX26 and UHRF1 were detected by quantitative reverse-transcription polymerase chain reaction and Western blot. The effect of COX26 methylation levels was analyzed by methylation-specific PCR (MSP). Phalloidin/immunofluorescence staining was used to observe structural changes. The binding relationship between UHRF1 and COX26 was verified by chromatin immunoprecipitation. IH caused cochlear damage, accompanied by increased methylation of COX26 and expression of UHRF1 in the cochlea of neonatal rats. CoCl2 treatment caused the loss of cochlear hair cells, downregulation and hypermethylation of COX26, abnormal upregulation of UHRF1, and disordered expressions of apoptosis-related proteins. UHRF1 in cochlear hair cells binds to COX26, and its knockdown upregulated COX26 level. Overexpressed COX26 partially alleviated the CoCl2-caused cell damage. UHRF1 induces COX26 methylation and aggravates the cochlear damage caused by IH.

Analysis of Serum Inflammatory Markers in Infants Under 6 Months of Age with Non-Syndromic Moderate and Severe Hearing Loss Associated with GJB2 Gene Mutations.

BACKGROUND The GJB2 gene is reported to be the main hereditary factor responsible for non-syndromic hearing impairment in infants. Several kinds of hearing loss have been linked to elevated inflammatory markers. This study aimed to evaluate serum levels of IL-2, IL-4, IL-6, IL-10, IL-17, alpha-TNF, and γ-IFN and the severity of hearing loss. MATERIAL AND METHODS Ninety newborns were divided into 3 groups: severe hearing impairment (31 infants), moderate hearing impairment (30 infants), and normal hearing (29 infants). Hearing screening was performed using otoacoustic emissions test. Mutations of the GJB2 gene were detected with Sanger sequencing. The patients had DNFB1 mutation. Seven blood inflammatory markers were tested using Cytometric Bead Array. We performed the t test to examine differences in expression of 7 inflammatory markers between sexes in the groups. The correlation between indicators within groups was studied using the Pearson correlation test. Correlation of different indicators among groups was studied using the Spearman correlation test. RESULTS When compared among the 3 groups (severe, moderate hearing impairment, and normal hearing group), we found that IL-10 had a positive correlation with the severity of GJB2-associated hearing loss, which was statistically significant (P<0.05). CONCLUSIONS This research aimed to assess the relationship of 7 serum inflammatory markers with GJB2-associated hearing loss in infants. Inflammatory marker IL-10 had a positive correlation with the severity of GJB2-associated infant hearing loss, and it might have the potential to become a future therapeutic target.

Effects of different dry heating temperatures on the spatial structure and amino acid residue side-chain oxidative modification of soybean isolated proteins.

Spatial structure and amino acid residue side-chain oxidative modification of soybean isolated protein (SPI) at different dry heating temperatures (70, 100, 130, 160 and 190 °C) were investigated, respectively in this study. The results showed that the dry heating promoted the formation of disulfide bonds and oxidative modification of SPI, such as carboxylation and hydroxylation under the below 160 °C. With increasing temperature, ß-sheet and α-helix shifted to random coil and ß-turn. The conformation of SPI changed, the solubility decreased and the particle size became smaller resulting from the combination of protein oxidation and chemical bond redistribution, but the structural integrity of SPI was better ensured below 130 °C. SPI was severely hydrolyzed at 190 °C. These results provide a theoretical basis for the study of protein modification by dry heating, which is a guideline for controlling the degree of protein denaturation in the food industry.

C-to-U RNA deamination is the driving force accelerating SARS-CoV-2 evolution.

Understanding the molecular mechanism underlying the rampant mutation of SARS-CoV-2 would help us control the COVID-19 pandemic. The APOBEC-mediated C-to-U deamination is a major mutation type in the SARS-CoV-2 genome. However, it is unclear whether the novel mutation rate u is higher for C-to-U than for other mutation types, and what the detailed driving force is. By analyzing the time course SARS-CoV-2 global population data, we found that C-to-U has the highest novel mutation rate u among all mutation types and that this u is still increasing with time (du/dt > 0). Novel C-to-U events, rather than other mutation types, have a preference over particular genomic regions. A less local RNA structure is correlated with a high novel C-to-U mutation rate. A cascade model nicely explains the du/dt > 0 for C-to-U deamination. In SARS-CoV-2, the RNA structure serves as the molecular basis of the extremely high and continuously accelerating C-to-U deamination rate. This mechanism is the driving force of the mutation, adaptation, and evolution of SARS-CoV-2. Our findings help us understand the dynamic evolution of the virus mutation rate.

Transnasal Endoscopic Orbital Decompression Combined with an Enhanced Recovery after Surgery Protocol in Graves Ophthalmopathy.

Objective: Although enhanced recovery after surgery (ERAS) was shown to improve patients' recovery after surgery and transnasal endoscopic orbital decompression has been associated with lesser risks of postoperative complications compared to other surgical techniques in treating Graves ophthalmopathy (GO), there are currently no clinical studies on the application of ERAS in transnasal endoscopic orbital decompression. This study aimed to investigate the potential effects of combining transnasal endoscopic orbital decompression with ERAS in the treatment of GO. Methods: A retrospective analysis was performed for 5 GO patients (10 eyes) treated with transnasal endoscopic orbital decompression from January 2021 to December 2021 at the Third Affiliated Hospital of Sun Yat-Sen University. All patients underwent ERAS, and the effects of ERAS on the postoperative complications and recovery of patients were evaluated. Results: Ophthalmological examination showed that GO patients had good correction of exophthalmos after surgery combined with ERAS. Specifically, the exophthalmos reduction in subjects was 0.9-2.1 mm, with a mean reduction of 1.23 mm. In addition, a visual acuity improvement of 0.15-0.4, with an average improvement of 0.23, was also observed. Further, the Scale of Quality of Life for Diseases with Visual Impairment (SQOL-DVI) showed that, compared with before surgery, the patients' QOL was significantly improved 2 weeks after surgery. Before surgery, there were 2 patients with diplopia and blurred vision, and after postoperative adaptive exercise, the symptoms of these 2 patients disappeared after 6 months of follow-up. As for the other 3 patients, they had no diplopia or blurred vision after surgery. Conclusion: This observational study found that transnasal endoscopic orbital decompression might be effective in treating GO, and ERAS might be considered an important adjunct to improving perioperative care and postoperative recovery.

Long-term outcomes and predictors of early response, late relapse, and survival for patients treated with bispecific LV20.19 CAR T-cells.

We previously reported results of a first-in-human trial of bispecific LV20.19 chimeric antigen receptor T-cell (CAR-T) therapy, demonstrating high response rates in patients with relapsed, refractory (R/R) B-cell malignancies. We now report two-year survival outcomes and predictors of early response, late relapse, and survival. Patients from the previously reported phase 1 dose escalation and expansion trial of LV20.19 CAR-T therapy (NCT03019055) treated at target dose of 2.5 × 106 cells/kg (n = 16) were included in this updated analysis. Two-year progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. The relationship of in-vivo CAR-T expansion, tumor burden, and effector: target ratio on early response (day 28) and late relapse (>180 days post-CAR-T) were assessed. Exact log-rank testing was performed to evaluate the impacts of clinical variables on survival outcomes. With a median of 31 months (range 27-40) of follow-up, two-year PFS and OS were 44% and 69%. Median PFS and OS were 15.6 months and not reached, respectively. For CAR-naïve large B-cell lymphoma patients (n = 8), two-year PFS and OS were 50% and 75%. No patient with progression experienced dual target antigen (CD19 or CD20) loss on post-relapse biopsy. Lower in vivo expansion was strongly associated with late relapse. Early treatment response was impeded by high metabolic tumor volume and low effector: target ratio. Bridging therapy and higher absolute lymphocyte count on day of CAR-T infusion were associated with inferior survival outcomes. In conclusion, this initial trial of LV20.19 CAR-T demonstrates a signal for favorable long-term outcomes for patients with R/R B-cell malignancies.

Osteoarthritis, coronary artery disease, and myocardial infarction: A mendelian randomization study.

Background: Observational studies indicate that osteoarthritis (OA) and coronary artery disease (CAD), as well as myocardial infarction (MI), are often diagnosed as comorbid diseases. We performed a bidirectional Mendelian randomization (MR) study to demonstrate whether there is a causal relationship between OA, CAD, and MI. Methods: We extracted single nucleotide polymorphisms (SNPs) related to OA in the Genetics of Osteoarthritis (GO) Consortium as instrumental variables to assess whether OA is associated with CAD and MI in the CARDIoGRAMplusC4D 1,000 Genomes genome-wide association study (GWAS). In the reverse MR, we used CAD-associated and MI-associated SNPs to the GWAS of OA to analyze their causality. These GWASs included 766,690 individuals of OA, 184,305 individuals of CAD, and 166,065 individuals of MI. MR was conducted using several methods, including the inverse variance weighted (IVW) method, the weighted median method, the MR-Egger method, and the MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) method. Results: The forward causal effect of OA on CAD and MI was not observed. In reverse analysis, no causal effect was discovered for CAD on the risk of OA. Notably, we observed a causal association between MI and total OA [IVW odds ratio (OR) = 0.95, 95% CI = 0.93, 0.98, P = 4E-04] and spine OA (IVW OR = 0.92, 95% CI = 0.88, 0.97, P = 0.001) but a null association between MI and knee OA, hip OA, hand OA, and thumb OA. Conclusion: This MR study identifies a potentially protective effect of genetically predicted MI on total and spine OA risks.

Effect of Baking Temperature and Time on Advanced Glycation End Products and Polycyclic Aromatic Hydrocarbons in Beef.

ABSTRACT: Beef is an important red meat that contains essential nutrients for human growth and development. Baking is a popular beef cooking method. Temperature and time play key roles in the final quality of beef. How temperature and time affect the changes of nutrients and the formation of harmful products in beef is not clear. The purpose of this study was to measure the content of water, fat, protein, ash, nitrite, total volatile base nitrogen, advanced glycation end products (AGEs) and their precursors, and polycyclic aromatic hydrocarbons (PAHs) at different temperatures (150, 190, 230, 270, and 310°C) for 20 min and at 190°C for different times (10, 20, and 30 min), so as to discuss the effect of different temperatures and times on beef nutrients and harmful products. The results showed that the moisture content of beef decreased with increased baking temperature and time, resulting in the increase of the relative content of fat, protein, and ash. The content of total volatile base nitrogen increased continuously. Compared with the control group, the content of glyoxal in beef decreased, whereas the content of methylglyoxal, pentosidine, and fluorescent AGEs increased, indicating the continuous accumulation of AGEs in beef. A total of 13 PAHs were identified by gas chromatography-mass spectrometry. The concentrations of 13 PAHs in beef increased with increases in baking temperature and time. The concentrations of BkP and BaP, which are the most carcinogenic to humans, were 0.36 and 0.35 µg/kg in raw meat, respectively; these were increased by high temperature and long baking times. After beef was baked at 270 and 310°C for 20 min, the concentration of BkP increased to 9.49 and 5.66 µg/kg, respectively, and the concentration of BaP increased to 5.45 and 4.42 µg/kg, respectively. After baking at 190°C for 30 and 40 min, the concentration of BkP increased to 4.81 and 24.20 µg/kg, respectively, and the concentration of BaP increased to 3.85 and 17.79 µg/kg, respectively.

Alcohol consumption and smoking in relation to psoriasis: a Mendelian randomization study.

BACKGROUND: Alcohol consumption and smoking have been reported to be associated with psoriasis risk. However, a conclusion with high-quality evidence of causality could not be easily drawn from regular observational studies. OBJECTIVES: This study aims to assess the causal associations of alcohol consumption and smoking with psoriasis. METHODS: Genome-wide association study (GWAS) summary-level data for alcohol consumption (N = 941 280), smoking initiation (N = 1 232 091), cigarettes per day (N = 337 334) and smoking cessation (N = 547 219) was obtained from the GSCAN consortium (Sequencing Consortium of Alcohol and Nicotine use). The GWAS results for lifetime smoking (N = 462 690) were obtained from the UK Biobank samples. Summary statistics for psoriasis were obtained from a recent GWAS meta-analysis of eight cohorts comprising 19 032 cases and 286 769 controls and the FinnGen consortium, comprising 4510 cases and 212 242 controls. Linkage disequilibrium score regression was applied to compute the genetic correlation. Bidirectional Mendelian randomization (MR) analyses were conducted to determine casual direction using independent genetic variants that reached genome-wide significance (P < 5 × 10-8 ). RESULTS: There were genetic correlations between smoking and psoriasis. MR revealed a causal effect of smoking initiation [odds ratio (OR) 1·46, 95% confidence interval (CI) 1·32-1·60, P = 6·24E-14], cigarettes per day (OR 1·38, 95% CI 1·13-1·67, P = 0·001) and lifetime smoking (OR 1·96, 95% CI 1·41-2·73, P = 7·32E-05) on psoriasis. Additionally, a suggestive causal effect of smoking cessation on psoriasis was observed (OR 1·39, 95% CI 1·07-1·79, P = 0·012). We found no causal relationship between alcohol consumption and psoriasis (P = 0·379). The reverse associations were not statistically significant. CONCLUSIONS: Our findings provide causal evidence for the effects of smoking on psoriasis risk. What is already known about this topic? Alcohol consumption and smoking have been reported to be associated with psoriasis risk. Whether alcohol consumption and smoking have a causal effect on psoriasis risk remains unclear. What does this study add? This Mendelian randomization study shows a causal association between smoking, but not alcohol consumption, and the risk of developing psoriasis. Restricting smoking could be helpful in reducing the burden of psoriasis.

Bispecific targeting of CD20 and CD19 increases polyfunctionality of chimeric antigen receptor T-cell products in B-cell malignancies.

BACKGROUND AIMS: Selective immune pressure contributes to relapse due to target antigen downregulation in patients treated with anti-CD19 chimeric antigen receptor (CAR) T cells. Bispecific lentiviral anti-CD20/anti-CD19 (LV20.19) CAR T cells may prevent progression/relapse due to antigen escape. Highly polyfunctional T cells within a CAR T-cell product have been associated with response in single-antigen-targeted anti-CD19 CAR T cells. METHODS: The authors performed a single-cell proteomic analysis to assess polyfunctional cells in our LV20.19 CAR T-cell product. Analysis was limited to those treated at a fixed dose of 2.5 × 106 cells/kg (n = 16). Unused pre-infusion CAR T cells were thawed, sorted into CD4/CD8 subsets and stimulated with K562 cells transduced to express CD19 or CD20. Single-cell production of 32 individual analytes was measured and polyfunctionality and polyfunctional strength index (PSI) were calculated. RESULTS: Fifteen patients had adequate leftover cells for analysis upon stimulation with CD19, and nine patients had adequate leftover cells for analysis upon stimulation with CD20. For LV20.19 CAR T cells, PSI was 866-1109 and polyfunctionality was 40-45%, which were higher than previously reported values for other CAR T-cell products. CONCLUSIONS: Stimulation with either CD19 or CD20 antigens resulted in similar levels of analyte activation, suggesting that this product may have efficacy in CD19- patient populations.