NPASS database update 2023: quantitative natural product activity and species source database for biomedical research.

Quantitative activity and species source data of natural products (NPs) are important for drug discovery, medicinal plant research, and microbial investigations. Activity values of NPs against specific targets are useful for discovering targeted therapeutic agents and investigating the mechanism of medicinal plants. Composition/concentration values of NPs in individual species facilitate the assessments and investigations of the therapeutic quality of herbs and phenotypes of microbes. Here, we describe an update of the NPASS natural product activity and species source database previously featured in NAR. This update includes: (i) new data of ∼95 000 records of the composition/concentration values of ∼1 490 NPs/NP clusters in ∼390 species, (ii) extended data of activity values of ∼43 200 NPs against ∼7 700 targets (∼40% and ∼32% increase, respectively), (iii) extended data of ∼31 600 species sources of ∼94 400 NPs (∼26% and ∼32% increase, respectively), (iv) new species types of ∼440 co-cultured microbes and ∼420 engineered microbes, (v) new data of ∼66 600 NPs without experimental activity values but with estimated activity profiles from the established chemical similarity tool Chemical Checker, (vi) new data of the computed drug-likeness properties and the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties for all NPs. NPASS update version is freely accessible at http://bidd.group/NPASS.

Influence of lack of blinding on the estimation of medication-related harms: a retrospective cohort study of randomized controlled trials.

BACKGROUND: Empirical evidence suggests that lack of blinding may be associated with biased estimates of treatment benefit in randomized controlled trials, but the influence on medication-related harms is not well-recognized. We aimed to investigate the association between blinding and clinical trial estimates of medication-related harms. METHODS: We searched PubMed from January 1, 2015, till January 1, 2020, for systematic reviews with meta-analyses of medication-related harms. Eligible meta-analyses must have contained trials both with and without blinding. Potential covariates that may confound effect estimates were addressed by restricting trials within the comparison or by hierarchical analysis of harmonized groups of meta-analyses (therefore harmonizing drug type, control, dosage, and registration status) across eligible meta-analyses. The weighted hierarchical linear regression was then used to estimate the differences in harm estimates (odds ratio, OR) between trials that lacked blinding and those that were blinded. The results were reported as the ratio of OR (ROR) with its 95% confidence interval (CI). RESULTS: We identified 629 meta-analyses of harms with 10,069 trials. We estimated a weighted average ROR of 0.68 (95% CI: 0.53 to 0.88, P < 0.01) among 82 trials in 20 meta-analyses where blinding of participants was lacking. With regard to lack of blinding of healthcare providers or outcomes assessors, the RORs were 0.68 (95% CI: 0.53 to 0.87, P < 0.01 from 81 trials in 22 meta-analyses) and 1.00 (95% CI: 0.94 to 1.07, P = 0.94 from 858 trials among 155 meta-analyses) respectively. Sensitivity analyses indicate that these findings are applicable to both objective and subjective outcomes. CONCLUSIONS: Lack of blinding of participants and health care providers in randomized controlled trials may underestimate medication-related harms. Adequate blinding in randomized trials, when feasible, may help safeguard against potential bias in estimating the effects of harms.

Prevalence of postprandial hypotension in older adults: a systematic review and meta-analysis.

BACKGROUND: Older adults with postprandial hypotension (PPH) increase susceptibility to falls, syncope, stroke, acute cardiovascular diseases and even death. However, the prevalence of this condition varies significantly across studies. We aimed to determine the prevalence of PPH in older adults. METHODS: Web of Science, PubMed, Cochrane Library, Embase and CINAHL were searched from their inception until February 2023. Search terms included 'postprandial period', 'hypotension' and 'postprandial hypotension'. Eligible studies were assessed using the Joanna Briggs Institute tool. Meta-analyses were performed among similar selected studies. RESULTS: Thirteen eligible studies were included, and data from 3,021 participants were pooled. The meta-analysis revealed a PPH prevalence of 40.5% [95% confidence interval (CI): 0.290-0.519] in older adults, and this was prevalent in the community (32.8%, 95% CI: 0.078-0.647, n = 1,594), long-term healthcare facility (39.4%, 95% CI: 0.254-0.610, n = 1,062) and geriatrics department of hospitals (49.3%, 95% CI: 0.357-0.630, n = 365). The pooled results showed significant heterogeneity (I2 > 90%), partially related to the different ages, sex, pre-prandial systolic blood pressure levels of participants, or the different criteria and methodology used to diagnose PPH. CONCLUSIONS: PPH is a prevalent condition in older adults. Further research is needed to confirm this result, and priority should be given to establishing international consensus on PPH diagnostic criteria and designing its diagnostic procedure.

Temporal and Spatial Signatures of Scylla paramamosain Transcriptome Reveal Mechanistic Insights into Endogenous Ovarian Maturation under Risk of Starvation.

Variability in food availability leads to condition-dependent investments in reproduction. This study is aimed at understanding the metabolic response and regulatory mechanism of female Scylla paramamosain in response to starvation in a temporal- and tissue-specific manner. The mud crabs were starved for 7 (control), 14, 28, and 40 days for histological and biochemical analysis in the hepatopancreas, ovary, and serum, as well as for RNA sequencing on the hepatopancreas and ovary. We further highlighted candidate gene modules highly linked to physiological traits. Collectively, our observations suggested that starvation triggered endogenous ovarian maturation at the expense of hepatopancreas mass, with both metabolic adjustments to optimize energy and fatty acid supply from hepatopancreas to ovary in the early phase, followed by the activation of autophagy-related pathways in both organs over prolonged starvation. These specific adaptive responses might be considered efficient strategies to stimulate ovarian maturation of Scylla paramamosain under fasting stress, which improves the nutritional value of female mud crabs and other economically important crustaceans.

The Monitoring and Cell Imaging of Fe3+ Using a Chromone-Based Fluorescence Probe.

A new structurally simple fluorescent CP probe based on chromone was designed and synthesized, and its structure was fully characterized using various analytical techniques. The CP probe displays a high selectivity and sensitivity for sensing Fe3+ with a "turn-off" fluorescence response over other metal ions in a DMSO/H2O (4:1, v/v) solution. The experiment results show that the CP probe is stable over a wide pH range of 2.0-12.0. The detection limit for Fe3+ was calculated to be 0.044 µmol•L-1. The molar ratio method indicated that the binding mode between the CP probe and Fe3+ is a 1:1 complex formation. HR-MS and density functional theory (DFT) calculations were also performed to further confirm the recognition mechanism. Both fluorescence imaging experiments and the MTT assay demonstrated that the CP probe was suitable for detecting intracellular Fe3+ and no significant cytotoxicity in living cells.

Self-Supported Pd Nanorod Arrays for High-Efficient Nitrate Electroreduction to Ammonia.

Electrochemical nitrate (NO3 - ) reduction to ammonia (NH3 ) offers a promising pathway to recover NO3 - pollutants from industrial wastewater that can balance the nitrogen cycle and sustainable green NH3 production. However, the efficiency of electrocatalytic NO3 - reduction to NH3 synthesis remains low for most of electrocatalysts due to complex reaction processes and severe hydrogen precipitation reaction. Herein, high performance of nitrate reduction reaction (NO3 - RR) is demonstrated on self-supported Pd nanorod arrays in porous nickel framework foam (Pd/NF). It provides a lot of active sites for H* adsorption and NO3 - activation leading to a remarkable NH3 yield rate of 1.52 mmol cm-2  h-1 and a Faradaic efficiency of 78% at -1.4 V versus RHE. Notably, it maintains a high NH3 yield rate over 50 cycles in 25 h showing good stability. Remarkably, large-area Pd/NF electrode (25 cm2 ) shows a NH3 yield of 174.25 mg h-1 , be promising candidate for large-area device for industrial application. In situ FTIR spectroscopy and density functional theory calculations analysis confirm that the enrichment effect of Pd nanorods encourages the adsorption of H species for ammonia synthesis following a hydrogenation mechanism. This work brings a useful strategy for designing NO3 - RR catalysts of nanorod arrays with customizable compositions.

Vacancy-Mediated Control of Local Electronic Structure for High-Efficiency Electrocatalytic Conversion of N2 to NH3.

Ambient electrocatalytic nitrogen (N2 ) reduction has gained significant recognition as a potential substitute for producing ammonia (NH3 ). However, N2 adsorption and *NN protonation for N2 activation reaction with the competing hydrogen evolution reaction remain a daunting challenge. Herein, a defect-rich TiO2 nanosheet electrocatalyst with PdCu alloy nanoparticles (PdCu/TiO2-x ) is designed to elucidate the reactivity and selectivity trends of N2 cleavage path for N2 -to-NH3 catalytic conversion. The introduction of oxygen vacancy (OV) not only acts as active sites but also effectively promotes the electron transfer from Pd-Cu sites to high-concentration Ti3+ sites, and thus lends to the N2 activation via electron donation of PdCu. OVs-mediated control effectively lowers the reaction barrier of *N2 H and *H adsorption and facilitates the first hydrogenation process of N2 activation. Consequently, PdCu/TiO2-x catalyst attains a high rate of NH3 evolution, reaching 5.0 mmol gcat. -1  h-1 . This work paves a pathway of defect-engineering metal-supported electrocatalysts for high-efficient ammonia electrosynthesis.

Gustatory stimulus interventions for older adults with dysphagia: a scoping review.

BACKGROUND: Gustatory stimulus interventions have been shown to improve swallowing function in older adults with dysphagia. However, the optimal intervention strategies as well as their effects and safety remain unclear. AIMS: To explore current evidence regarding gustatory stimulus interventions for dysphagia in older adults. METHODS: Nine electronic databases (PubMed, Web of Science, Embase, CINAHL, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, and Sinomed) were searched from their inception to August 2022. RESULTS: This review identified 263 articles, and 15 met the inclusion criteria. The types of gustatory stimulus interventions included spicy (n = 10), sour (n = 3), and mixed (sour-sweet) stimuli (n = 2), with most studies focusing on spicy stimuli. The most frequently reported spicy stimulus was capsaicin. Further, the most commonly reported intervention frequency was thrice a day before meals for 1-4 weeks. The stimuli concentrations and dosages could not be standardized due to the among-study heterogeneity. These studies reported 16 assessment tools and 42 outcomes, which mainly included videofluoroscopy and swallowing response time respectively. More than half of the included studies reported no adverse effects of gustatory stimulus interventions. CONCLUSION AND DISCUSSIONS: Gustatory stimulus interventions improved swallowing function in older adults with dysphagia. However, assessment tools and outcomes for dysphagia should be standardized in the future, and explore personalized interventions based on different diseases and their stages, to determine the most cost-effective interventions, and to prevent its complications.

Non-pharmacological interventions for older adults with postprandial hypotension: A scoping review.

BACKGROUND: Older adults frequently suffer from postprandial hypotension, associated with an increased risk of falls, syncope, acute cardiovascular and cerebrovascular diseases, and even death. Researchers use non-pharmacological interventions, but related literature is dispersed and lacks a latest summary. OBJECTIVE: The aim of this study was to map and examine non-pharmacological interventions currently employed to assist older adults with postprandial hypotension and lay a solid foundation for future studies. METHODS: This study adhered to the JBI methodology for scoping reviews and preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews. PubMed, Web of Science, Embase, Cochrane Library, CINAHL, SCOPUS, Chinese Biomedical Journal, China National Knowledge Infrastructure, VIP and WAN FANG Data were retrieved from their inception to 1 August 2022. RESULTS: Two randomized controlled trials and seven quasi-experimental studies were included. Small meals, exercise interventions, fibre with meals, green tea and water therapy have been reported to prevent postprandial hypotension effectively; however, position changes have been reported to have no impact on postprandial blood pressure decrease. Additionally, the blood pressure determination methods and test meals may affect observed trial effects. CONCLUSION: Large samples and long-term follow-up studies are needed to prove the efficacy and safety of existing non-pharmacological interventions. Future studies should develop a BP determination method based on the postprandial BP decline trajectory induced by a given test meal to improve the reliability of study results. RELEVANCE TO CLINICAL PRACTICE: This review broadly summarizes existing studies on developing and validating non-pharmacological interventions for older adults with postprandial hypotension. It also analyses special factors that may influence the trial effects. This may provide a useful reference for future research.

Spatial characteristics of change trends of air pollutants in Chinese urban areas during 2016-2020: The impact of air pollution controls and the COVID-19 pandemic.

Air pollution is a threat to public health in China, and several actions and plans have been implemented by Chinese authorities in recent years to mitigate it. This study examined the spatial distribution of changes in urban air pollutants (UAP) in 336 Chinese cities from 2016 to 2020 and their responses to air pollution controls and the COVID-19 pandemic. Based on the harmonic model, decreases in fine particles (PM2.5), inhalable particles (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO) levels were found in 90.7%, 91.9%, 75.2%, 94.3%, and 88.7% of cities, respectively, while an increase in ozone (O3) was found in 87.2% of cities. Notable spatial heterogeneity was observed in the air pollution trends. The greatest improvement in air quality occurred mainly in areas with poor air quality, such as Hebei province and its surrounding cities. However, some areas (i.e., Yunnan and Hainan provinces) with good air quality showed a worsening trend. During the 13th Five-Year Plan period (2016-2020), the remarkable effects of PM2.5 and SO2 pollution control plans were confirmed. Additionally, economic growth in 74.2% of the Chinese provinces decoupled from air quality after implementing pollution control measures. In 2020, several Chinese cities were locked down to reduce the spread of COVID-19. Except for SO2, the national air pollution in 2020 improved to a greater extent than that in 2016-2019; In particularly, the contribution of simulated COVID-19 pandemic to NO2 reduction was 66.7%. Overall, air pollution control actions improved urban PM2.5, PM10, SO2, and CO, whereas NO2 was reduced primarily because of the COVID-19 pandemic.

Redox-Regulated Magnetic Conversions between Ferro- and Antiferromagnetism in Organic Nitroxide Diradicals.

Redox-induced magnetic transformation in organic diradicals is an appealing phenomenon. In this study, we theoretically designed twelve couples of diradicals in which two nitroxide (NO) radical groups are connected to the redox-active couplers including p-benzoquinonyl, 1,4-naphthoquinyl, 9,10-anthraquinonyl, naphthacene-5,12-dione, pentacene-6,13-dione, hexacene-6,15-dione, pyrazinyl, quinoxalinyl, phenazinyl, 5,12-diazanaphthacene, 6,13-diazapentacene, and 6,15-diazahexacene. As evidenced at both the B3LYP and M06-2X levels of theory, the calculations reveal that the magnetic reversal can take place from ferromagnetism to antiferromagnetism, or vice versa, by means of redox method in these designed organic magnetic molecules. It was observed that p-benzoquinonyl, 1,4-naphthoquinyl, 9,10-anthraquinonyl, naphthacene-5,12-dione, pentacene-6,13-dione, and hexacene-6,15-dione-bridged NO diradicals produce antiferromagnetism while their dihydrogenated counterparts exhibit ferromagnetism. Similarly, pyrazinyl, quinoxalinyl, phenazinyl, 5,12-diazanaphthacene, 6,13-diazapentacene, and 6,15-diazahexacene-bridged NO diradicals present ferromagnetism while their dihydrogenated counterparts show antiferromagnetism. The differences in the magnetic behaviors and magnetic magnitudes of each of the twelve couples of diradicals could be attributed to their distinctly different spin-interacting pathways. It was found that the nature of the coupler and the length of the coupling path are important factors in controlling the magnitude of the magnetic exchange coupling constant J. Specifically, smaller HOMO-LUMO (HOMO: highest occupied molecular orbital, LUMO: lowest unoccupied molecular orbital) gaps of the couplers and shorter coupler lengths, as well as shorter linking bond lengths, can attain stronger magnetic interactions. In addition, a diradical with an extensively π-conjugated structure is beneficial to spin transport and can effectively promote magnetic coupling, yielding a large |J| accordingly. That is, a larger spin polarization can give rise to a stronger magnetic interaction. The sign of J for these studied diradicals can be predicted from the spin alternation rule, the shape of the singly occupied molecular orbitals (SOMOs), and the SOMO-SOMO energy gaps of the triplet state. This study paves the way for the rational design of magnetic molecular switches.

[Construction and Exploration of Model for Training Excellent Nursing Professionals].

The cultivation of excellent nursing professionals is an important guarantee of competent human resources essential to the implementation of the national strategy of Healthy China initiative. In the face of the health needs of the whole life cycle and the nursing development driven by emerging technologies, the training of excellence nursing professionals is confronted with new requirements and challenges. In order to cope with the new demands at home and abroad for the training of high-quality nursing staffs, meet the needs for health services that are based on precision, the whole population, the whole life cycle, and individualized care in the new era, and cultivate outstanding nursing staffs with clinical critical thinking skills, nursing decision-making skills, innovative research and practice ability, whole life cycle nursing knowledge and skills, and the ability to keep pace with the times, we wrote this paper to help clarify the needs and challenges of training excellent nursing staffs in China. Herein, taking "precision nursing of health and disease in the whole life cycle" as the core and utilizing the personnel training principle of emphasizing foundation, strengthening ability, improving quality, and promoting personality, we elaborated on the construction of the training model of excellent nursing staffs and suggested that efforts should be made in the following areas, setting up training objectives with a scientific orientation, setting up in a targeted way the knowledge system and the curriculum system, organizing the teaching mode reform into different types and implement them accordingly, making innovations in instructional methodology, and building up high-level teaching faculties. We explored for a path for training excellent nursing talents, a path that has Chinese characteristics and that can be further developed in a sustainable way, which will lay the foundation for attaining the strategic goal of Healthy China initiative.

[First-Class Nursing Discipline Construction Spearheads the Cultivation of First-Class Talents].

Cultivating first-class talents is a key task of the Double First-Class Initiative, a national plan to build a number of world-class universities and disciplines in China by the end of 2050. On the basis of reviewing the history of the development of the nursing discipline, we analyzed, herein, opportunities and challenges of nursing professional training under the strategic guidance of the Double First-Class Initiative. We proposed suggestions on the cultivation of first-class nursing professionals of the future by considering the following aspects, constructing a theoretical system of ideological and political education for nursing education with Chinese characteristics, exploring for ways to develop a nursing knowledge system and personnel training model around the axis of a life-course approach to health, building "nursing plus" interdisciplinary clusters to cultivate innovative talents with interdisciplinary integrated abilities, enhancing efforts to recruit and cultivate scientific and technological talents, optimizing in an all-round way the composition of qualified nursing personnel, gaining the support of first-class research platforms, and creating incubation centers for innovative and outstanding nursing professionals.

Timely stimulation of early embryo promotes the acquisition of pluripotency.

Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) are both pluripotent stem cells from early embryos. Another type of pluripotent stem cells, which are similar with EpiSCs and derive from pre-implantation embryos in feeder-free and chemically defined medium containing Activin A and basic fibroblast growth factors (bFGF), is termed as AFSCs. The pluripotency and self-renewal maintenance of ESCs rely on Leukemia inhibitory factor (LIF)/STAT/BMP4/SMAD signaling, while the pluripotency and self-renewal maintenance of EpiSCs and AFSCs rely on bFGF and Activin/Nodal signaling. However, the establishment efficiency of AFSCs lines is low. In this study, we stimulated early embryos by 2i/LIF (CHIR99021 + PD0325901 + LIF) and Activin A + bFGF respectively, to change the cell fate in inner cell mass (ICM). The "fate changed embryos" by 2i/LIF can efficiently produce AFSCs in feeder-free and chemically defined medium, but the efficiency of embryos treated with Activin A + bFGF were poor. The AFSCs from fate-changed embryos share similar molecular characteristics with conventional AFSCs and EpiSCs. Our results suggest that the advanced stimulation of 2i/LIF and the premature stimulation of Activin A + bFGF contribute to capturing the pluripotent stem cells in early embryos, and the FGF/MAPK signaling dominate early embryo development. Our study provides a new approach to capturing pluripotency from pre-implantation embryos.

Electrocardiographic localization of peripherally inserted central catheter tip position in critically ill patients with advanced cancer: An application study.

BACKGROUND: We compared the methods of electrocardiogram (ECG) and X-ray localization of the peripherally inserted central catheter (PICC) tip position, in order to find a more convenient, practical, and safe method. OBJECTIVE: To investigate the value of applying electrocardiographic localization of the PICC tip position in critically ill patients with advanced cancer in Hebei Province, China. METHOD: Enrolled 137 advanced cancers requiring PICC placement. The position of the catheter tip was localized with the bedside electrocardiogram in real time. Then, the localization was performed using a chest X-ray (the gold standard). The accuracy of electrocardiographic location was checked. RESULTS: Specific P waves were observed in 130 patients. No change in the P waves was observed for the remaining seven patients. The age of the latter group of patients was more advanced (87.29 [5.15] years), a significant difference to that of the 130 patients with specific P waves (71.58 [14.84] years) (t = -6.704, p < .001). Specific P waves not only involve ascendance in P waves but also ascendance in QRS waves. CONCLUSIONS: The use of an ECG to localize the PICC tip in critically ill patients with advanced cancer may replace the unnecessary use of chest X-rays. Specific P waves not only involve an increase in P waves but also an increase in QRS waves. If there is no change in the P wave, a chest X-ray film must be obtained. In elderly patients, because there is a possibility of catheter tip malposition, a comprehensive evaluation should be performed before surgery.

Identification and Evolution Analysis of the Complete Methyl Farnesoate Biosynthesis and Related Pathway Genes in the Mud Crab, Scylla paramamosain.

The sesquiterpenoid hormone methyl farnesoate (MF) plays a vital role during crustacean development, which is mainly evidenced by its varied titers during different developmental stages. However, the biosynthesis pathways of MF remain obscure to some extent. In this study, we identified the complete MF biosynthesis and related pathway genes in Scylla paramamosain, including three involved in acetyl-CoA metabolism, eight in the mevalonate pathway, five in the sesquiterpenoids synthesis pathway, and five in the methionine cycle pathway. Bioinformatics, genomic structure, and phylogenetic analysis indicated that the JH biosynthesis genes might have experienced evolution after species differentiation. The mRNA tissue distribution analysis revealed that almost all genes involving in or relating to MF syntheses were highly expressed in the mandibular organ (MO), among which juvenile hormone acid methyltransferase was exclusively expressed in the MO, suggesting that most of these genes might mainly function in MF biosynthesis and that the methionine cycle pathway genes might play a crucial regulatory role during MF synthesis. In addition, the phylogenetic and tissue distribution analysis of the cytochrome P450 CYP15-like gene suggested that the epoxidized JHs might exist in crustaceans, but are mainly synthesized in hepatopancreas rather than the MO. Finally, we also found that betaine-homocysteine S-methyltransferase genes were lost in insects while methionine synthase was probably lost in most insects except Folsomia candida, indicating a regulatory discrepancy in the methionine cycle between crustaceans and insects. This study might increase our understanding of synthetic metabolism tailored for sesquiterpenoid hormones in S. paramamosain and other closely related species.

The levels and related factors of compassion fatigue and compassion satisfaction among family caregivers: A systematic review and meta-analysis of observational studies.

Family caregivers play an increasingly important role in providing care services, especially for the aging population. Currently, evidence on compassion fatigue among family caregivers remains limited. Our study aims to assess the levels and related factors of compassion fatigue and compassion satisfaction in family caregivers. We searched nine electronic databases for published observational studies up to 7 October 2021. In our studies, the pooled mean scores of compassion fatigue and compassion satisfaction were 42.35 (95% CI: 28.45-56.24) and 36.41 (95% CI: 33.63-39.19), respectively. We considered background, role-related, and social psychological variables to influence the risk of compassion fatigue and compassion satisfaction. Current data suggest that overall compassion fatigue and compassion satisfaction levels were moderate, thus highlighting the potential risk of compassion fatigue for family caregivers. In the future, these findings can be used to develop programs that will mitigate compassion fatigue and improve compassion satisfaction in family caregivers.

The augment of regulatory T cells undermines the efficacy of anti-PD-L1 treatment in cervical cancer.

BACKGROUND: Immune checkpoint inhibitors have aroused great expectation of tumor eradication. However, the effect of anti-PD-L1 treatment for cervical cancer is unsatisfactory and the underlying antagonist to anti-PD-L1 efficacy is remained to be studied. Here, we investigated the anti-tumor effect of anti-PD-L1 treatment in cervical tumor model and identified the antagonist to the therapeutic efficacy of anti-PD-L1 treatment. RESULTS: We found that PD-L1 exhibited a moderate expression in both cervical tumor cell lines and clinical samples compared to other tumor types and the para-tumor tissue respectively. Interestingly, our results showed that the anti-PD-L1 treated mice were dichotomously divided into responsive and unresponsive group after five cycles of anti-PD-L1 treatment although all the mice had the same genome background. In addition, the unresponsive tumors showed less tumor necrosis area and higher immunosuppression activity induced by regulatory T cells (Tregs) population than the responsive ones. Furthermore, we found that anti-PD-L1 treatment autonomously upregulated Tregs proliferation and frequency in multiple immune organs, and, most importantly, Tregs depletion significantly depressed the tumor growth rate and tumor weight compared with either anti-PD-L1 or anti-CD25 treatment alone. Finally, we observed that the upregulating effector CD8+ T cell is associated with the better therapeutic effect of anti-PD-L1 therapy post Tregs depletion. CONCLUSIONS: Anti-PD-L1 treatment upregulates Tregs frequency and proliferation in tumor model, and the depletion of Tregs may be a useful adjuvant strategy for anti-PD-L1 therapy of cervical cancer.

Are preventive measures adequate? An evaluation of the implementation of COVID-19 prevention and control measures in nursing homes in China.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic has become a challenge for nursing homes in China. Nursing homes are particularly dangerous places in terms of the spread of COVID-19 given that they house vulnerable, high-risk populations. As such, several useful guidelines for coping with COVID-19 in nursing homes have been provided. However, the actual implementation rates of such guidelines are unknown. This study aims to document the adherence of nursing homes to the Ministry of Civil Affairs guidelines for COVID-19 prevention and control in nursing homes. METHODS: A cross-sectional study was conducted among 484 nursing homes in 136 cities of 28 provinces in China. A self-report questionnaire was created based on the Ministry of Civil Affairs guidelines for COVID-19 prevention and control in nursing homes (first edition). The questionnaire and the Transformational Leadership in the Public Sector Scale were sent to nursing home managers via the Wenjuanxing app online from February 7 to 29, 2020. Ultimately, 461 of 960 nursing homes participated, for a response rate of 48.0%. RESULTS: The average overall implementation rate of COVID-19 prevention and control measures was 80.0% (143.97/180). The average implementation rates for hygienic behaviour management and access management were lower, at 75.3 and 78.7%, respectively. Number of medical staff and transformational leadership score of nursing home's manager were associated with total implementation score (p < 0.05). A total of 69.8% (322/461) of the nursing home managers had serious resource problems, and inadequate protective supplies (72.0%) and staff shortages (47.7%) were the two primary problems. The nursing homes that located in urban, with large nursing home size, had hospital-nursing home cooperation and the transformational leadership score of manager> 60, had a lower risk of having serious resource problems. CONCLUSIONS: Overall, the implementation of prevention and control measures by nursing homes are insufficient during the epidemic in China. More medical staff, adequate resource, cooperation with hospitals, and higher transformational leadership of manager are required to improve the implementation rate. It is urgent for nursing homes to maintain the safety of residents and staff.

Predictors of acute cardiovascular events following acute exacerbation period for patients with COPD: a nested case-control study.

BACKGROUND: It has been noted that there is an increase in the incidence of acute cardiovascular events (CVEs) in patients with chronic obstructive pulmonary disease (COPD) during an acute exacerbation (AE), thereby causing increased inpatient mortality. Thus, we have tried to identify predictors of acute CVEs in patients with AECOPD via a nested case-control study. METHODS: A total of 496 cases hospitalized for AECOPD were included in this study, and followed-up for up to 6 months after discharge. Acute CVEs in the AE period were defined as a new or worsening acute coronary syndrome (ACS), arrhythmia, or left ventricular disfunction (LVD). Predictors of CVEs were selected from several variables, including baseline characteristics and treatments in the stable period as well as symptoms, laboratory tests, complications and treatments in the AE period. RESULTS: Thirty cases (6.05%) had acute CVEs, namely 2 had ACS, 13 had LVD and 19 experienced some form of arrhythmia. Four deaths were observed in the CVE group, with significantly increased death risk compared with the non-CVE group (P = 0.001, OR = 5.81). Moreover, patients who had CVEs were more prone to have re-exacerbation within 3 months. Multivariate analysis showed that previous LVD history (P = 0.004, OR = 5.06), 20% increase in heart rate (HR) (P = 0.003, OR = 10.19), electrolyte disturbance (P = 0.01, OR = 4.24) and diuretics (P = 0.002, OR = 6.37) were independent predictors of CVEs. In addition, usage of theophylline, fluoroquinolone and inhaled beta agonists in the AE period were not statistically associated with acute CVEs. CONCLUSIONS: Our preliminary study indicates that patients hospitalized for AECOPD with previous LVD history or increased HR need close observation and diuretics should be cautiously used with regular electrolyte monitoring. These findings need to be confirmed in a large cohort.