Pan-immune-inflammation and its dynamics: predictors of survival and immune-related adverse events in patients with advanced NSCLC receiving immunotherapy.

OBJECTIVES: Pan-immune-inflammation value (PIV) is defined by the neutrophil, platelet, monocyte, and lymphocyte counts and is associated with immune-checkpoint inhibitor (ICI) therapy outcomes in advanced non-small cell lung cancer (aNSCLC). However, PIV is dynamic under therapy and its longitudinal assessment may help predict efficacy. This study investigated the impact of baseline PIV and its dynamics on ICI efficacy and its immune-related adverse events (irAEs). The study additionally attempted to understand the biological significance of PIV. PATIENTS AND METHODS: This retrospective study analyzed the clinical data of 269 consecutive patients with aNSCLC. PIV was calculated at baseline and at weeks 3-4 to determine its association with overall survival (OS), progression-free survival (PFS), and irAEs. RESULTS: Results revealed that low baseline PIV was positively correlated with the incidence of irAEs. Moreover, a low PIV at baseline was significantly associated with a prolonged PFS (median PFS: 10 vs. 7 months, p = 0.0005) and OS (median OS: 29 vs. 21 months, p < 0.0001). When the PIV at baseline and weeks 3-4 was considered together, its low dynamics correlated with a higher incidence of irAEs (p = 0.001), a longer PFS (median PFS, 9 vs. 6 months, p = 0.012), and a longer OS (median OS; 28 vs. 21 months, p = 0.002). CONCLUSION: Thus, PIV at baseline and its dynamics are novel and potent predictors of irAEs, PFS, and OS in patients with aNSCLC receiving immunotherapy. Moreover, the PIV dynamics may be an effective, novel surrogate marker to dynamically observe the efficacy of immunotherapy.

Copper-Catalyzed Preparation of Benzo[3,4]indolo[1,2-b]isoquinoline-8-ones and Photoluminescence Exploration.

A facile synthesis of benzo[3,4]indolo[1,2-b]isoquinolin-8-ones is described. Under copper catalysis, the reaction proceeds with a high efficiency and a broad reaction scope. A deuteration experiment shows that the KIE value is 2.85. From the results on mechanism studies, copper-catalyzed C-H activation, intramolecular cis-addition of alkynes, and reductive elimination are involved. Moreover, this skeleton is indeed a new fluorophore, and its photophysical properties are also investigated.

Efficient Photodynamic Killing of Gram-Positive Bacteria by Synthetic Curcuminoids.

In our previous study, we have demonstrated that curcumin can efficiently kill the anaerobic bacterium Propionibacterium acnes by irradiation with low-dose blue light. The curcuminoids present in natural plant turmeric mainly include curcumin, demethoxycurcumin, and bisdemethoxycurcumin. However, only curcumin is commercially available. Eighteen different curcumin analogs, including demethoxycurcumin and bisdemethoxycurcumin, were synthesized in this study. Their antibacterial activity against Gram-positive aerobic bacteria Staphylococcus aureus and Staphylococcus epidermidis was investigated using the photodynamic inactivation method. Among the three compounds in turmeric, curcumin activity is the weakest, and bisdemethoxycurcumin possesses the strongest activity. However, two synthetic compounds, (1E,6E)-1,7-bis(5-methylthiophen-2-yl)hepta-1,6-diene-3,5-dione and (1E,6E)-1,7-di(thiophen-2-yl)hepta-1,6-diene-3,5-dione, possess the best antibacterial activity among all compounds examined in this study. Their chemical stability is also better than that of bisdemethoxycurcumin, and thus has potential for future clinical applications.

Conductive and antibacterial films by loading reduced graphene oxide/silver nanoparticles on cellulose nanofiber films.

The development of sustainable high-performance materials based on nanocellulose has received great attention in recent years. Herein, nanocellulose based composite films with highly electro-conductive and antibacterial properties have been developed by loading reduced graphene oxide (rGO)/silver nanoparticles (AgNPs) on cellulose nanofiber films via vacuum filtration process. The reduction effect of gallic acid on the chemical structure and electrical conductivity of rGO/AgNP composites was studied. Due to the strong reducibility of gallic acid, the obtained rGO/AgNPs exhibited a high electrical conductivity of 1549.2 S·m-1. Furthermore, the electrical conductivity, mechanical properties and antibacterial properties of the prepared rGO/AgNP-cellulose nanofiber films as a function of various proportions were investigated. The prepared composite film with a specific ratio of rGO/AgNPs to cellulose nanofibers as 7:3 exhibited the superior tensile strength of 28.0 MPa and the electrical conductivity of 1199.3 S·m-1. Meanwhile, compared with pure cellulose nanofiber films, rGO/AgNP-cellulose nanofiber films displayed strong antibacterial effect against Escherichia coli and Staphylococcus aureus. Therefore, this work demonstrated an effective approach for imparting structural and functional properties to cellulose nanofiber based films, which could hold great application prospects for flexible and wearable electronics.

Joint Contributions of Depression and Insufficient Sleep to Self-Harm Behaviors in Chinese College Students: A Population-Based Study in Jiangsu, China.

Self-harm in young people is common, and previous studies have shown that insufficient sleep or depression was associated with self-harm. However, the joint association of insufficient sleep and depression with self-harm is unknown. We employed representative population-based data from the "Surveillance for Common Disease and Health Risk Factors Among Students in Jiangsu Province 2019" project. College students reported their self-harm behavior over the past year. Rate ratios (RRs) and corresponding 95% confidence intervals (CIs) for self-harm in relation to sleep and depression were modeled using negative binomial regression with a sample population as an offset, adjusting for age, gender, and region. The instrumental variable approach was used for the sensitivity analyses. Of the study population, approximately 3.8% reported self-harm behaviors. Students with sufficient sleep experienced a lower risk of self-harm than those with insufficient sleep. Compared with students with sufficient sleep and the absence of depression, the adjusted risk of self-harm was elevated 3-fold (1.46-4.51) in those reporting insufficient sleep in the absence of depression, 11-fold (6.26-17.77) in those with sufficient sleep and definite depression, and 15-fold (8.54-25.17) in those with both insufficient sleep and definite depression. The sensitivity analyses indicate that insufficient sleep remained a contributing risk factor for self-harm. Lack of sleep in young people is significantly associated with self-harm, particularly in the presence of depression. The provision of mental health care and attention to sleep deprivation are particularly important for college students.

Mortality following fragility hip fracture in China: a record linkage study.

Mortality risk declined over time. Patients with fragility hip fracture experienced an approximate ninefold excess mortality, peaking shortly after fracture, in comparison with that of the general population. Continuous efforts in lowering the occurrence of hip fracture have the potential to improve the survival of the elderly population in China. PURPOSE: Hip fractures in older adults often lead to an elevated risk of death. However, few studies investigated mortality risk following hip fracture in mainland China. This retrospective cohort study aimed to evaluate the crude mortality and excess mortality after fragility hip fractures in Lishui residents aged 50 years and older. METHODS: Patients having a fragility hip fracture between October 2013 and August 2019 were identified from the Lishui District Inpatient Data Collection and followed up until August 2020. Death information was ascertained from the linked death registry records. We calculated the follow-up mortality rate and corresponding 95% confidence intervals (CIs) as well as the standard mortality ratios (SMRs) in comparison with the mortality rates of Lishui residents. RESULTS: During the study period, a total of 808 patients (63.4% females) with an average age of 75 years were admitted for fragility hip fractures. The 1st, 2nd, and 3rd year follow-up mortality rates were 16.51, 6.06, and 5.03 per 100 person-year, respectively. The SMRs were 8.46 (6.94, 9.97), 5.74 (4.86, 6.63), and 4.63 (3.98, 5.27) for the 1st, 2nd, and 3rd year following fragility hip fracture. CONCLUSION: Although mortality risk declined over time, patients with fragility hip fracture experienced an approximate ninefold excess mortality, peaking shortly after fracture, in comparison with that of the general population. Continuous efforts in lowering the occurrence of hip fracture have the potential to improve the survival of the elderly population in China.

Early signs of geographic spread of COVID-19: lessons learnt from outbreaks in Wuhan 2020 and Nanjing 2021.

BACKGROUND: Knowing the spatiotemporal pattern of the early geographic spread of coronavirus disease 2019 (COVID-19) would inform the preparedness for a possible recurrence of COVID-19. METHODS: We ascertained the number of confirmed cases during the early spread of COVID-19 during the Wuhan outbreak in 2020 and the Nanjing outbreak in 2021. RESULTS: We observed a speeding-up pattern of geographic spread, in particular to cities of no particular orientation then outflowing to commercial cities during the first month of both the Wuhan and Nanjing outbreaks. CONCLUSION: Re-emergence of COVID-19 indicates it is becoming endemic, with new outbreaks and a risk of increased transmission remaining a challenge to local public health institutions. Social distancing and lockdowns should continue in response to any potential widespread and focal outbreaks.