Mechanistic insights into the C-type lectin receptor CLEC12A-mediated immune recognition of monosodium urate crystal.

CLEC12A, a member of the C-type lectin receptor family involved in immune homeostasis, recognizes MSU crystals released from dying cells. However, the molecular mechanism underlying the CLEC12A-mediated recognition of MSU crystals remains unclear. Herein, we reported the crystal structure of the human CLEC12A-C-type lectin-like domain (CTLD) and identified a unique "basic patch" site on CLEC12A-CTLD that is necessary for the binding of MSU crystals. Meanwhile, we determined the interaction strength between CLEC12A-CTLD and MSU crystals using single-molecule force spectroscopy. Furthermore, we found that CLEC12A clusters at the cell membrane and seems to serve as an internalizing receptor of MSU crystals. Altogether, these findings provide mechanistic insights for understanding the molecular mechanisms underlying the interplay between CLEC12A and MSU crystals.

Latent Tuberculosis Infection Testing Practices in a Large US Integrated Healthcare System.

BACKGROUND: Tuberculosis (TB) is a public health threat, with >80% of active TB in the United States occurring due to reactivation of latent TB infection (LTBI). We may be underscreening those with high risk for LTBI and overtesting those at lower risk. A better understanding of gaps in current LTBI testing practices in relation to LTBI test positivity is needed. METHODS: This study, conducted between 1 January 2008 and 31 December 2019 at Kaiser Permanente Southern California, included individuals aged ≥18 years without a history of active TB. We examined factors associated with LTBI testing and LTBI positivity. RESULTS: Among 3 816 884 adults (52% female, 37% White, 37% Hispanic, mean age 43.5 years [standard deviation, 16.1]), 706 367 (19%) were tested for LTBI, among whom 60 393 (9%) had ≥1 positive result. Among 1 211 971 individuals who met ≥1 screening criteria for LTBI, 210 025 (17%) were tested for LTBI. Factors associated with higher adjusted odds of testing positive included male sex (1.32; 95% confidence interval, 1.30-1.35), Asian/Pacific Islander (2.78, 2.68-2.88), current smoking (1.24, 1.20-1.28), diabetes (1.13, 1.09-1.16), hepatitis B (1.45, 1.34-1.57), hepatitis C (1.54, 1.44-1.66), and birth in a country with an elevated TB rate (3.40, 3.31-3.49). Despite being risk factors for testing positive for LTBI, none of these factors were associated with higher odds of LTBI testing. CONCLUSIONS: Current LTBI testing practices may be missing individuals at high risk of LTBI. Additional work is needed to refine and implement screening guidelines that appropriately target testing for those at highest risk for LTBI.

A Propensity Score Approach and a Partitioned Approach for the Self-Controlled Case Series Design to Evaluate Safety of a 2-dose Vaccine Series: Application to myocarditis/pericarditis following mRNA COVID-19 vaccination.

The assumption that serious adverse events (SAEs) do not affect subsequent exposure might not hold when evaluating 2-dose vaccine safety through a self-controlled case series (SCCS) design. To address this, we developed: 1) propensity score SCCS (PS-SCCS) using a propensity score model involving SAEs during the risk interval after dose 1 (${R}_1\Big)$, and 2) partitioned SCCS (P-SCCS) estimating relative incidence (RI) separately for doses 1 and 2. In simulations, both provided unbiased RIs. Conversely, standard SCCS overestimated RI after dose 2. We applied these approaches to assess myocarditis/pericarditis risks after 2-dose mRNA COVID-19 vaccination in 12-39-year-olds. For BNT162b2, PS-SCCS yielded RIs of 1.85 (95% CI, 0.75-4.59) and 11.05 (95% CI, 6.53-18.68) 14 days after doses 1 and 2 respectively; standard SCCS provided similar RI after dose 1 and RI of 12.92 (95% CI, 7.56-22.09) after dose 2. For mRNA-1273, standard SCCS showed RIs of 1.96 (95% CI, 0.56-6.91) after dose 1 and 7.87 (95% CI, 3.33-18.57) after dose 2. As no mRNA-1273 recipients with SAEs during ${R}_1$ received dose 2, P-SCCS was used, yielding similar RI after dose 1 and RI of 6.48 (95% CI, 2.83-14.83) after dose 2. mRNA vaccines were associated with elevated myocarditis/pericarditis risks following dose 2 in 12-39-year-olds.

Ion-Molecule Co-Confining Ammonium Vanadate Cathode for High-Performance Aqueous Zinc-Ion Batteries.

Vanadium-based cathode materials have attracted great attention in aqueous zinc-ion batteries (AZIBs). However, the inferior ion transport and cyclic stability due to the strong Coulomb interaction between Zn2+ and the lattice limit their further application. In this work, CO2 molecules are in situ embedded in the interlayer structure of NH4V4O10 by decomposing excess H2C2O4·2H2O in the main framework, obtaining an ion-molecule co-confining NH4V4O10 for AZIB cathode material. The introduced CO2 molecules expanded the interlayer spacing of NH4V4O10, broadened the diffusion channel of Zn2+, and stabilized the structure of NH4V4O10 as the interlayer pillars together with NH 4 + ${\mathrm{NH}}_4^ + $ , which effectively improved the Zn2+ diffusion kinetics and cycle stability of the electrode. In addition, the binding between NH 4 + ${\mathrm{NH}}_4^ + $ and the host framework is stabilized via hydrogen bonds with CO2 molecules. NVO-CO2-0.8 exhibited excellent specific capacity (451.1 mAh g-1 at 2 A g-1), cycle stability (214.0 mAh g-1 at 10 A g-1 after 1000 cycles) and rate performance. This work provides new ideas and approaches for optimizing vanadium-based materials with high-performance AZIBs.

Boosting the Capacitor Performance of the Metal Organic Frameworks Derived V2O5 Nanoflower by Cu Doping.

Due to its ultrahigh theoretical capacitance, vanadium pentoxide (V2O5) is considered to be a valid candidate for advanced supercapacitors. However, because of the low electron/electrolyte transfer rate, the capacitive performance still remains to be improved. In this report, Cu doping is adopted to improve the capacitive performance by a two-steps strategy consisting of microwave-assisted solvothermal and postannealing treatments. The electrochemical results indicate that the Cu doping was beneficial for improving the specific capacitance, extending the potential window, and improving the rate ability and long-term stability of V2O5. Furthermore, the mechanism for the performance improvement is explained in detail by combining theoretical calculation and experiments. The results indicated that, compared with that of undoped V2O5, the larger interplanar spacing, better electrical conductivity, a larger proportion of V3+/V4+, and more abundant oxygen vacancies result in an improved capacitive performance. Our proposed Cu-doped V2O5 (Cu-V2O5) can be used as both a positive electrode and a negative electrode for the assembly of the symmetric supercapacitor, which can be used as an energy storage device for light emitting diode lamps.

C8-ceramide modulates microglia BDNF expression to alleviate postoperative cognition dysfunction via PKCδ/NF-κB signaling pathway.

Postoperative cognitive dysfunction (POCD) is a kind of serious postoperative complication in surgery with general anesthesia and it may affect patients' normal lives. Activated microglia are thought to be one of the key factors in the regulation of POCD process. Once activated, resident microglia change their phenotype and secrete kinds of cytokines to regulate inflammatory response in tissues. Among these secretory factors, brain-derived neurotrophic factor (BDNF) is considered to be able to inhibit inflammation response and protect nervous system. Therefore, the enhancement of BDNF expression derived from resident microglia is suggested to be potential treatment for POCD. In our study, we focused on the role of C8-ceramide (a kind of interventional drug) and assessed its regulatory effect on improving the expression of BDNF secreted from microglia to treat POCD. According to the results of our study, we observed that C8-ceramide stimulated primary microglia to up-regulate the expression of BDNF mRNA after being treated with lipopolysaccharide (LPS) in vitro. We proved that C8-ceramide had ability to effectively improve POCD of mice after being accepted carotid artery exposure and their abnormal behavior recovered better than that of mice from the surgery group. Furthermore, we also demonstrated that C8-ceramide enhanced the cognitive function of mice via the PKCδ/NF-κB signaling pathway. In general, our study has confirmed a potential molecular mechanism that led to the occurrence of POCD caused by surgery and provided a new clinical strategy to treat POCD.

A self-powered spiral droplet triboelectric sensor for real-time monitoring of patient infusion in nursing wards.

Monitoring of intravenous infusion together with an alarm system is significant for safety and automation operation in the process of clinical drug delivery for major medical institutions. However, there is still a lack of multifunctional sensors to monitor the whole infusion process, such as flow rate, drip rate, and temperature. Herein, we propose a self-powered droplet triboelectric sensor (SDTS) based on the principle of liquid-solid triboelectrification to monitor both intravenous infusion flow and infusion type. Such SDTS devices use two materials with different electrically charged properties to directly generate an electrical signal without any additional power supply, which is conducive to the formation of a large-scale detection system and for enhancing the convenience of medical treatment. The SDTS placed in a disposable infusion set has high potential application in clinical practice and is low cost and easy to prepare. Specifically, we demonstrate the feasibility of the detection of the current infusion flow rate and identification of the infusion medicine type according to the triboelectric signals, providing a new solution for real-time monitoring of patient infusion in nursing wards.

Cost-effectiveness of mepolizumab for severe eosinophilic asthma in China.

OBJECTIVE: To evaluate the economic value of mepolizumab as an add-on therapy to the standard of care (SoC) for patients with severe eosinophilic asthma in China. METHODS: A Markov model with three health conditions was constructed to calculate the incremental cost per quality-adjusted life year (QALY) in mepolizumab with SoC and SoC only groups from the perspective of the Chinese healthcare system throughout an entire lifespan. The model was populated with local costs, while efficacy parameters were obtained from the global Phase III MENSA trial and mortality was derived from two surveys. One-way and probabilistic sensitivity analyses were conducted. Additional scenario analysis was used to estimate the cost-effectiveness impact of changes in the price of mepolizumab. RESULTS: Over the lifetime treatment horizon, the incremental cost-effectiveness ratio (ICER) of mepolizumab plus SoC compared to SoC alone was $170 648.73 per QALY. Sensitivity analyses focused on these results. Scenario analysis showed that mepolizumab would require a price reduction of at least 82% to reach the current willingness-to-pay (WTP=$38 223.34/QALY) threshold. CONCLUSION: Mepolizumab is not a cost-effective healthcare resource in China at its current pricing.

Amorphous Thickness-Dependent Strengthening-Softening Transition in Crystalline-Amorphous Nanocomposites.

Core-shell crystalline-amorphous nanocomposites, featuring nanograins surrounded by thick amorphous boundaries, are promising nanoarchitectures for achieving exceptional strength through cooperative strengthening effects. However, a comprehensive understanding of the influence of characteristic sizes, particularly the amorphous thickness, on codeformation strengthening is still lacking, limiting the attainment of the strength limit. Here, we employ molecular dynamics simulations to investigate Cu-CuTa crystalline-amorphous nanocomposites with varying grain sizes and amorphous thicknesses. Our findings demonstrate significant strengthening effects in nanocomposites, effectively suppressing the Hall-Petch breakdown observed in traditional amorphous-free nanograined Cu. Intriguingly, we observe a maximum strength followed by a strengthening-softening transition dependent on the amorphous thickness, as exemplified by a representative nanocomposite featuring a 12.5 nm grain size and a critical amorphous thickness of 4 nm. Inspired by observed shifts in atomistic mechanisms, we developed a theoretical model encompassing variations in grain size and amorphous thickness, providing valuable insights into the size-strength relationship for crystalline-amorphous nanocomposites.

Evolutionary analysis of SLC10 family members and insights into function and expression regulation of lamprey NTCP.

The Na ( +)-taurocholate cotransporting polypeptide (NTCP) is a member of the solute carrier family 10 (SLC10), which consists of 7 members (SLC10a1-SLC10a7). NTCP is a transporter localized to the basolateral membrane of hepatocytes and is primarily responsible for the absorption of bile acids. Although mammalian NTCP has been extensively studied, little is known about the lamprey NTCP (L-NTCP). Here we show that L-NTCP follows the biological evolutionary history of vertebrates, with conserved domain, motif, and similar tertiary structure to higher vertebrates. L-NTCP is localized to the cell surface of lamprey primary hepatocytes by immunofluorescence analysis. HepG2 cells overexpressing L-NTCP also showed the distribution of L-NTCP on the cell surface. The expression profile of L-NTCP showed that the expression of NTCP is highest in lamprey liver tissue. L-NTCP also has the ability to transport bile acids, consistent with its higher vertebrate orthologs. Finally, using a farnesoid X receptor (FXR) antagonist, RT-qPCR and flow cytometry results showed that L-NTCP is negatively regulated by the nuclear receptor FXR. This study is important for understanding the adaptive mechanisms of bile acid metabolism after lamprey biliary atresia based on understanding the origin, evolution, expression profile, biological function, and expression regulation of L-NTCP.

Factors influencing physical activity levels in elderly community-dwelling convalescent stroke survivors: A cross-sectional study.

AIM: This study aimed to investigate factors affecting physical activity (PA) among elderly stroke survivors living in the community and assess the mediating role of exercise planning in the relationship between exercise self-efficacy and PA. METHODS: 300 participants were surveyed using questionnaires and scales, with data analyzed using SPSS 26.0. RESULTS: Univariate analysis identified sociological, disease-related factors, exercise self-efficacy, and exercise planning as influencing PA. Ordered logistic regression showed significant associations between PA, exercise self-efficacy (OR 1.093, 95 % CI 1.055-1.133, P < 0.001), and exercise planning (OR 1.296, 95 % CI 1.202-1.398, P < 0.001). Exercise planning partially mediated the relationship between exercise self-efficacy and PA, accounting for 64.86 % of the total effect. CONCLUSIONS: Multiple factors, including sociological and disease-related ones, as well as exercise self-efficacy and planning, influence PA in elderly stroke survivors. Exercise planning partially mediates the relationship between exercise self-efficacy and PA.

Multiple Chirality Switching of a Dye-Grafted Helical Polymer Film Driven by Acid & Base.

A stimuli-responsive multiple chirality switching material, which can regulate opposed chiral absorption characteristics, has great application value in the fields of optical modulation, information storage and encryption, etc. However, due to the rareness of effective functional systems and the complexity of material structures, developing this type of material remains an insurmountable challenge. Herein, a smart polymer film with multiple chirality inversion properties was fabricated efficiently based on a newlydesigned acid & base-sensitive dye-grafted helical polymer. Benefited from the cooperative effects of various weak interactions (hydrogen bonds, electrostatic interaction, etc.) under the aggregated state, this polymer film exhibited a promising acid & base-driven multiple chirality inversion property containing record switchable chiral states (up to five while the solution showed three-state switching) and good reversibility. The creative exploration of such a multiple chirality switching material can not only promote the application progress of current chiroptical regulation technologybut also provide a significant guidance for the design and synthesis of future smart chiroptical switching materials and devices.

Prevention of Neisseria gonorrhoeae With Meningococcal B Vaccine: A Matched Cohort Study in Southern California.

BACKGROUND: Neisseria gonorrhoeae is acquiring increasing resistance to available oral antibiotics, and current screening and treatment approaches have not decreased gonorrhea incidence. Although a gonorrhea-specific vaccine does not exist, N. gonorrhoeae shares much of its genome with Neisseria meningitidis, notably critical antigenic determinants including outer membrane vesicles (OMV). Prior observational studies have suggested that OMV-based meningococcal serogroup B vaccines confer protection against gonorrhea. METHODS: We conducted a matched cohort study from 2016 to 2020 to examine the association of OMV-containing recombinant meningococcal serogroup B vaccine (4CMenB) with gonorrhea infection among teens and young adults at Kaiser Permanente Southern California. Recipients of 4CMenB were matched in a ratio of 1:4 to recipients of non-OMV-containing polysaccharide-conjugate vaccine targeting serotypes A, C, W, and Y (MenACWY) who had not received 4CMenB and were followed for incident gonorrhea. We used Cox proportional hazards regression to compare gonorrhea rates among recipients of 4CMenB vs MenACWY, adjusting for potential confounders. We conducted the same analysis with chlamydia as a negative control outcome. RESULTS: The study included 6641 recipients of 4CMenB matched to 26 471 recipients of MenACWY. During follow-up, gonorrhea incidence rates per 1000 person-years (95% confidence intervals [CIs]) were 2.0 (1.3-2.8) for recipients of 4CMenB and 5.2 (4.6-5.8) for recipients of MenACWY. In adjusted analyses, gonorrhea rates were 46% lower among recipients of 4CMenB vs MenACWY (hazard ratio [HR], 0.54; 95% CI, .34-.86), but chlamydia rates were similar between vaccine groups (HR, 0.98; 95% CI, .82-1.17). CONCLUSIONS: These results suggest cross-protection of 4CMenB against gonorrhea, supporting the potential for vaccination strategies to prevent gonorrhea.

Effectiveness of Messenger RNA-1273 Vaccine Booster Against Coronavirus Disease 2019 in Immunocompetent Adults.

BACKGROUND: We conducted a prospective cohort study at Kaiser Permanente Southern California to evaluate the relative vaccine effectiveness (rVE) of a booster dose vs 2-dose primary series of messenger RNA (mRNA)-1273 in immunocompetent individuals. METHODS: Immunocompetent adults who received a booster dose of mRNA-1273 from October 2021 through December 2021 were matched 1:1 to randomly selected 2-dose mRNA-1273 recipients by age, sex, race/ethnicity, and second-dose date and followed up through January 2022. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), comparing outcomes (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection and coronavirus disease 2019 [COVID-19] hospitalization and hospital death) in the booster-dose and 2-dose groups. Adjusted rVE (%) was calculated as (1 - aHR) × 100. aHRs and rVE were also estimated by subgroup and month of follow-up. RESULTS: The study included 431 328 booster-dose vaccinated adults matched to 431 328 2-dose vaccinated adults. rVE was 61.3% (95% CI: 60.5%-62.2%) against SARS-CoV-2 infection, 89.0% (86.2%-91.2%) against COVID-19 hospitalization, and 96.0% (68.0%-99.5%) against COVID-19 hospital death. rVE against SARS-CoV-2 infection ranged from 55.6% to 66.7% across all subgroups. rVE against SARS-CoV-2 infection decreased from 67.1% (0 to <1 month of follow-up) to 30.5% (2 to <3 months). For COVID-19 hospitalization, rVE decreased from 91.2% (0 to <1 month) to 78.7% (2 to <3 months). CONCLUSIONS: Among immunocompetent adults, the mRNA-1273 booster conferred additional protection against SARS-CoV-2 infection and severe COVID-19 disease compared with the 2-dose mRNA-1273 primary series during periods of Delta and Omicron predominance.

Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2).

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is largely underdiagnosed and undertreated in China where few patients achieved recommended target levels of low density lipoprotein cholesterol (LDL-C). We conducted the first randomized, placebo-controlled clinical trial in Chinese patients with HeFH to assess the efficacy and safety of tafolecimab, a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody. METHODS: Patients diagnosed with HeFH by Simon Broome criteria and on a stable lipid-lowering therapy for at least 4 weeks were randomized 2:2:1:1 to receive subcutaneous tafolecimab 150 mg every 2 weeks (Q2W), tafolecimab 450 mg every 4 weeks (Q4W), placebo Q2W or placebo Q4W in the 12-week double-blind treatment period. After that, participants received open-label tafolecimab 150 mg Q2W or 450 mg Q4W for 12 weeks. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. Secondary endpoints included proportion of participants achieving ≥50% LDL-C reductions and proportion of participants with LDL-C <1.8 mmol/L at week 12 and 24, the change from baseline to week 12 in non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and lipoprotein(a) levels, as well as the change from baseline to week 24 in lipid levels. RESULTS: In total, 149 participants were randomized and 148 received at least one dose of the study treatment. At week 12, tafolecimab treatment induced significant reductions in LDL-C levels (treatment difference versus placebo [on-treatment estimand]: -57.4% [97.5% CI, -69.2 to -45.5] for 150 mg Q2W; -61.9% [-73.4 to -50.4] for 450 mg Q4W; both P <0.0001). At both dose regimens, significantly more participants treated with tafolecimab achieved ≥50% LDL-C reductions or LDL-C <1.8 mmol/L at week 12 as compared with corresponding placebo groups (all P <0.0001). Meanwhile, non-HDL-C, apolipoprotein B and lipoprotein(a) levels were significantly reduced in the tafolecimab groups at week 12. The lipid-lowering effects of tafolecimab were maintained till week 24. During the double-blind treatment period, the most commonly-reported adverse events in the tafolecimab groups included upper respiratory tract infection, increased blood creatine phosphokinase, increased alanine aminotransferase, increased aspartate aminotransferase and hypertension. CONCLUSIONS: Tafolecimab administered either 150 mg Q2W or 450 mg Q4W yielded significant and persistent reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with HeFH. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04179669.

Glutamine Induced High-Quality Perovskite Film to Improve the Efficiency of NIR Perovskite Light-Emitting Diodes.

Formamidine lead iodide (FAPbI3 ) is an important material for realizing high-performance near-infrared light-emitting diodes (NIR-LEDs). However, due to the uncontrollable growth of solution-processed films which usually causes low coverage, and poor surface morphology, the development of FAPbI3 -based NIR-LEDs is hindered, restraining its potential industrial applications. In this work, by employing glutamine (Gln) in perovskite precursor, the quality of FAPbI3 film is improved significantly. Due to the ameliorated solution process by the organic additive, the film coverage over the substrate is substantially enhanced. Meanwhile, the trap state of grain is largely reduced. Consequently, NIR perovskite LEDs are demonstrated with a maximum external quantum efficiency (EQE) of 15% with the emission peak at 795 nm, which is four times higher than the device with pristine perovskite film.

Enhanced ß-glucosidase in Western flower thrips affects its interaction with the redox-based strategies of kidney beans under elevated CO2.

ß-Glucosidase is validated as an elicitor for early immune responses in plants and it was detected in the salivary glands of Frankliniella occidentalis in previous research. Seven differentially expressed genes encoding ß-glucosidase were obtained by comparing the transcriptomes of F. occidentalis adults grown under two different CO2 concentrations (800 vs. 400 ppm), which might be associated with the differences in the interaction between F. occidentalis adults and its host plant, Phaseolus vulgaris under different CO2 levels. To verify this speculation, changes in defense responses based on the production and elimination of reactive oxygen species (ROS) in P. vulgaris leaves treated with three levels of ß-glucosidase activity under ambient CO2 (aCO2 ) and elevated CO2 (eCO2 ) were measured in this study. According to the results, significantly higher levels of ROS were noticed under eCO2 compared to aCO2 , which was caused by the increased ß-glucosidase activity in thrips due to increased cellulose content in P. vulgaris leaves under eCO2 . Together with the lower activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) in injured leaves under eCO2 , P. vulgaris leaves would be negatively affected on redox-based defense by eCO2 , thus facilitating thrips damage under climate change.

Metal organic framework-derived transition metal-doped CoSx nanocage for enhanced visible light-assisted methanol electrocatalytic oxidation.

Designing noble metal-free anode catalysts for visible light-assisted direct methanol fuel cells still remains a significant challenge. In this study, combining the photocatalytic and electrocatalytic properties of CoSx, a visible light-assisted methanol electrocatalytic oxidation strategy was provided. Doping engineering was employed to adjust the electronic structure of CoSx and improve their photoassisted methanol electrocatalytic oxidation activity. Using ZIF-67 as precursor, transition metal-doped CoSx (M-CoSx, M = Zn, Cu, Ni, and Cd) nanocage was synthesized by cation exchange and L-cysteine-controlled etching. Cd doping not only widens the light adsorption to the visible region but also enhances the separation efficiency of photogenerated electron-hole pairs. The electrochemical and photochemical results indicated that the strong oxidative photogenerated hole, OH˙, and O2˙- are beneficial for methanol electrocatalytic oxidation. The synergistic electrocatalytic and photocatalytic effect will be a practical strategy for improving the methanol electrocatalytic oxidation activity of noble metal-free semiconductor catalysts.

Cellular immunotherapy combined with platinum-based chemotherapy prolongs survival for non-small cell lung cancer patients.

Platinum-based chemotherapy is the primary treatment option for advanced non-small cell lung cancer (NSCLC) patients without a driver gene mutation, but its efficacy is still modest. Through a potential synergistic effect, autologous cellular immunotherapy (CIT) composed of cytokine-induced killer (CIK), natural killer (NK), and T cells might enhance it. NK cells exhibited in vitro cytotoxicity toward lung cancer cells (A549 cells) following platinum therapy. Using flow cytometry, the expression of MICA, MICB, DR4, DR5, CD112, and CD155 on lung cancer cells was assessed. In this retrospective cohort study, there were included 102 previously untreated stage IIIB/IV NSCLC patients ineligible for tyrosine kinase inhibitor (TKI) target therapy who received either chemotherapy alone (n=75) or combination therapy (n=27). The cytotoxicity of NK cells for A549 cells was increased obviously and a time-dependent enhancement of this effect was also observed. After platinum therapy, the levels of MICA, MICB, DR4, DR5, CD112, and CD155 on the surface of A549 cells were increased. In the combination group, the median PFS was 8.3 months, compared to 5.5 months in the control group (p=0.042); the median overall survival was 18.00 months, compared to 13.67 months in the combined group (p=0.003). The combination group had no obvious immune-related adverse effects. The combination of NK cells with platinum showed synergistic anticancer effects. Combining the two strategies increased survival with minor adverse effects. Incorporating CIT into conventional chemotherapy regimens may improve NSCLC treatment. However, additional evidence will require multicenter randomized controlled trials.

Risk for Shoulder Conditions After Vaccination: A Population-Based Study Using Real-World Data.

BACKGROUND: Although shoulder conditions have been reported as an adverse event after intramuscular vaccination in the deltoid muscle, epidemiologic data on shoulder conditions after vaccination are limited. OBJECTIVE: To estimate the risk for shoulder conditions after vaccination and assess possible risk factors. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Southern California, a large integrated health care organization. PARTICIPANTS: Kaiser Permanente Southern California members aged 3 years or older who had an intramuscular vaccination administered in the deltoid muscle between 1 April 2016 and 31 December 2017. MEASUREMENTS: A natural language processing (NLP) algorithm was used to identify potential shoulder conditions among vaccinated persons with shoulder disorder diagnosis codes. All NLP-identified cases were manually chart confirmed on the basis of our case definition. The characteristics of vaccinated persons with and without shoulder conditions were compared. RESULTS: Among 3 758 764 administered vaccinations, 371 cases of shoulder condition were identified, with an estimated incidence of 0.99 (95% CI, 0.89 to 1.09) per 10 000 vaccinations. The incidence was 1.22 (CI, 1.10 to 1.35) for the adult (aged ≥18 years) and 0.05 (CI, 0.02 to 0.14) for the pediatric (aged 3 to 17 years) vaccinated populations. In the adult vaccinated population, advanced age, female sex, an increased number of outpatient visits in the 6 months before vaccination, lower Charlson Comorbidity Index, and pneumococcal conjugate vaccine were associated with a higher risk for shoulder conditions. Among influenza vaccines, quadrivalent vaccines were associated with an increased risk for shoulder conditions. Simultaneous administration of vaccines was associated with a higher risk for shoulder conditions among elderly persons. LIMITATION: Generalizability to other health care settings, use of administrative data, and residual confounding. CONCLUSION: These population-based data suggest a small absolute risk for shoulder conditions after vaccination. Given the high burden of shoulder conditions, clinicians should pay attention to any factors that may further increase risks. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.