TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation.

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro, and in vivo analyses, we report that topoisomerase 1 (TOP1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Therapeutic treatment with two doses of topotecan (TPT), an FDA-approved TOP1 inhibitor, suppresses infection-induced inflammation in hamsters. TPT treatment as late as 4 days post-infection reduces morbidity and rescues mortality in a transgenic mouse model. These results support the potential of TOP1 inhibition as an effective host-directed therapy against severe SARS-CoV-2 infection. TPT and its derivatives are inexpensive clinical-grade inhibitors available in most countries. Clinical trials are needed to evaluate the efficacy of repurposing TOP1 inhibitors for severe coronavirus disease 2019 (COVID-19) in humans.

Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 relies on cellular RNA-binding proteins (RBPs) to replicate and spread, although which RBPs control its life cycle remains largely unknown. Here, we employ a multi-omic approach to identify systematically and comprehensively the cellular and viral RBPs that are involved in SARS-CoV-2 infection. We reveal that SARS-CoV-2 infection profoundly remodels the cellular RNA-bound proteome, which includes wide-ranging effects on RNA metabolic pathways, non-canonical RBPs, and antiviral factors. Moreover, we apply a new method to identify the proteins that directly interact with viral RNA, uncovering dozens of cellular RBPs and six viral proteins. Among them are several components of the tRNA ligase complex, which we show regulate SARS-CoV-2 infection. Furthermore, we discover that available drugs targeting host RBPs that interact with SARS-CoV-2 RNA inhibit infection. Collectively, our results uncover a new universe of host-virus interactions with potential for new antiviral therapies against COVID-19.

Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2.

The B.1.1.529/Omicron variant of SARS-CoV-2 was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally1. It is expected to become dominant in the coming weeks2, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations3 that pose a threat to the efficacy of current COVID-19 vaccines and antibody therapies4. This concern is amplified by the findings of our study. Here we found that B.1.1.529 is markedly resistant to neutralization by serum not only from patients who recovered from COVID-19, but also from individuals who were vaccinated with one of the four widely used COVID-19 vaccines. Even serum from individuals who were vaccinated and received a booster dose of mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies against all known epitope clusters on the spike protein, we noted that the activity of 17 out of the 19 antibodies tested were either abolished or impaired, including ones that are currently authorized or approved for use in patients. Moreover, we also identified four new spike mutations (S371L, N440K, G446S and Q493R) that confer greater antibody resistance on B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.

Clofazimine broadly inhibits coronaviruses including SARS-CoV-2.

The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile3-possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and-when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.

Anti-Epstein-Barr Virus BNLF2b for Mass Screening for Nasopharyngeal Cancer.

BACKGROUND: Population screening of asymptomatic persons with Epstein-Barr virus (EBV) DNA or antibodies has improved the diagnosis of nasopharyngeal carcinoma and survival among affected persons. However, the positive predictive value of current screening strategies is unsatisfactory even in areas where nasopharyngeal carcinoma is endemic. METHODS: We designed a peptide library representing highly ranked B-cell epitopes of EBV coding sequences to identify novel serologic biomarkers for nasopharyngeal carcinoma. After a retrospective case-control study, the performance of the novel biomarker anti-BNLF2b total antibody (P85-Ab) was validated through a large-scale prospective screening program and compared with that of the standard two-antibody-based screening method (EBV nuclear antigen 1 [EBNA1]-IgA and EBV-specific viral capsid antigen [VCA]-IgA). RESULTS: P85-Ab was the most promising biomarker for nasopharyngeal carcinoma screening, with high sensitivity (94.4%; 95% confidence interval [CI], 86.4 to 97.8) and specificity (99.6%; 95% CI, 97.8 to 99.9) in the retrospective case-control study. Among the 24,852 eligible participants in the prospective cohort, 47 cases of nasopharyngeal carcinoma (38 at an early stage) were identified. P85-Ab showed higher sensitivity than the two-antibody method (97.9% vs. 72.3%; ratio, 1.4 [95% CI, 1.1 to 1.6]), higher specificity (98.3% vs. 97.0%; ratio, 1.01 [95% CI, 1.01 to 1.02]), and a higher positive predictive value (10.0% vs. 4.3%; ratio, 2.3 [95% CI, 1.8 to 2.8]). The combination of P85-Ab and the two-antibody method markedly increased the positive predictive value to 44.6% (95% CI, 33.8 to 55.9), with sensitivity of 70.2% (95% CI, 56.0 to 81.4). CONCLUSIONS: Our results suggest that P85-Ab is a promising novel biomarker for nasopharyngeal carcinoma screening, with higher sensitivity, specificity, and positive predictive value than the standard two-antibody method. (Funded by the National Key Research and Development Program of China and others; ClinicalTrials.gov number, NCT04085900.).

Identifications of novel host cell factors that interact with the receptor-binding domain of the SARS-CoV-2 spike protein.

SARS-CoV-2 entry into host cells is facilitated by the interaction between the receptor-binding domain of its spike protein (CoV2-RBD) and host cell receptor, ACE2, promoting viral membrane fusion. The virus also uses endocytic pathways for entry, but the mediating host factors remain largely unknown. It is also unknown whether mutations in the RBD of SARS-CoV-2 variants promote interactions with additional host factors to promote viral entry. Here, we used the GST pull-down approach to identify novel surface-located host factors that bind to CoV2-RBD. One of these factors, SH3BP4, regulates internalization of CoV2-RBD in an ACE2-independent but integrin- and clathrin-dependent manner and mediates SARS-CoV-2 pseudovirus entry, suggesting that SH3BP4 promotes viral entry via the endocytic route. Many of the identified factors, including SH3BP4, ADAM9, and TMEM2, show stronger affinity to CoV2-RBD than to RBD of the less infective SARS-CoV, suggesting SARS-CoV-2-specific utilization. We also found factors preferentially binding to the RBD of the SARS-CoV-2 Delta variant, potentially enhancing its entry. These data identify the repertoire of host cell surface factors that function in the events leading to the entry of SARS-CoV-2.

Hollow Nanoreactors Unlock New Possibilities for Persulfate-Based Advanced Oxidation Processes.

As a novel type of catalytic material, hollow nanoreactors are expected to bring new development opportunities in the field of persulfate-based advanced oxidation processes due to their peculiar void-confinement, spatial compartmentation, and size-sieving effects. For such materials, however, further clarification on basic concepts and construction strategies, as well as a discussion of the inherent correlation between structure and catalytic activity are still required. In this context, this review aims to provide a state-of-the-art overview of hollow nanoreactors for activating persulfate. Initially, hollow nanoreactors are classified according to the constituent components of the shell structure and their dimensionality. Subsequently, the different construction strategies of hollow nanoreactors are described in detail, while common synthesis methods for these construction strategies are outlined. Furthermore, the most representative advantages of hollow nanoreactors are summarized, and their intrinsic connections to the nanoreactor structure are elucidated. Finally, the challenges and future prospects of hollow nanoreactors are presented.

Chemoproteomics-based profiling reveals potential antimalarial mechanism of Celastrol by disrupting spermidine and protein synthesis.

BACKGROUND: Malaria remains a global health burden, and the emergence and increasing spread of drug resistance to current antimalarials poses a major challenge to malaria control. There is an urgent need to find new drugs or strategies to alleviate this predicament. Celastrol (Cel) is an extensively studied natural bioactive compound that has shown potentially promising antimalarial activity, but its antimalarial mechanism remains largely elusive. METHODS: We first established the Plasmodium berghei ANKA-infected C57BL/6 mouse model and systematically evaluated the antimalarial effects of Cel in conjunction with in vitro culture of Plasmodium falciparum. The potential antimalarial targets of Cel were then identified using a Cel activity probe based on the activity-based protein profiling (ABPP) technology. Subsequently, the antimalarial mechanism was analyzed by integrating with proteomics and transcriptomics. The binding of Cel to the identified key target proteins was verified by a series of biochemical experiments and functional assays. RESULTS: The results of the pharmacodynamic assay showed that Cel has favorable antimalarial activity both in vivo and in vitro. The ABPP-based target profiling showed that Cel can bind to a number of proteins in the parasite. Among the 31 identified potential target proteins of Cel, PfSpdsyn and PfEGF1-α were verified to be two critical target proteins, suggesting the role of Cel in interfering with the de novo synthesis of spermidine and proteins of the parasite, thus exerting its antimalarial effects. CONCLUSIONS: In conclusion, this study reports for the first time the potential antimalarial targets and mechanism of action of Cel using the ABPP strategy. Our work not only support the expansion of Cel as a potential antimalarial agent or adjuvant, but also establishes the necessary theoretical basis for the development of potential antimalarial drugs with pentacyclic triterpenoid structures, as represented by Cel. Video Abstract.

Latent membrane protein 1 and macrophage-derived TNFα synergistically activate and mobilize invadopodia to drive invasion of nasopharyngeal carcinoma.

Invadopodia are actin-rich membrane protrusions that digest the matrix barrier during cancer metastasis. Since the discovery of invadopodia, they have been visualized as localized and dot-like structures in different types of cancer cells on top of a 2D matrix. In this investigation of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), a highly invasive cancer frequently accompanied by neck lymph node and distal organ metastases, we revealed a new form of invadopodium with mobilizing features. Integration of live-cell imaging and molecular assays revealed the interaction of macrophage-released TNFα and EBV-encoded latent membrane protein 1 (LMP1) in co-activating the EGFR/Src/ERK/cortactin and Cdc42/N-WASP signaling axes for mobilizing the invadopodia with lateral movements. This phenomenon endows the invadopodia with massive degradative power, visualized as a shift of focal dot-like digestion patterns on a 2D gelatin to a dendrite-like digestion pattern. Notably, single stimulation of either LMP1 or TNFα could only enhance the number of ordinary dot-like invadopodia, suggesting that the EBV infection sensitizes the NPC cells to form mobilizing invadopodia when encountering a TNFα-rich tumor microenvironment. This study unveils the interplay of EBV and stromal components in driving the invasive potential of NPC via unleashing the propulsion of invadopodia in overcoming matrix hurdles. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Discovery of an End-to-End Pattern for Contaminant-Oriented Advanced Oxidation Processes Catalyzed by Biochar with Explainable Machine Learning.

The utilization of biochar-catalyzed peroxymonosulfate in advanced oxidation processes (BC-PMS AOPs) is widely acknowledged as an effective and economical method for mitigating emerging contaminants (ECs). Especially, state-of-the-art machine learning (ML) technology has been employed to accurately predict the reaction rate constants of EC degradation in BC-PMS AOPs, primarily focusing on three aspects: performance prediction, operating condition optimization, and mechanism interpretation. However, its real application in specific degradation optimization targeting different ECs is seldom considered, hindering the realization of contaminant-oriented BC-PMS AOPs. Herein, we propose a hierarchical ML pipeline to achieve an end-to-end (E2E) pattern for addressing this issue. First, the overall XGB model, trained with the comprehensive data set, can perform well in predicting the reaction constants of EC degradation in BC-PMS AOPs, additionally providing the basis for further analysis of various ECs. Then, the submodels trained with different EC clusters can offer specific strategies for the selection of the optimum option for BC-PMS AOPs of specific ECs with different HOMO-LUMO gaps, thus forming an E2E operating pattern for BC-PMS AOPs. This study not only increases our understanding of contaminant-oriented optimization of AOPs but also successfully bridges the gap between ML model development and its environmental application.

Aeration-Free In Situ Fenton-like Reaction: Specific Adsorption and Activation of Oxygen on Heterophase Oxygen Vacancies.

Aeration accounts for 35-51% of the overall energy consumption in wastewater treatment processes and results in an annual energy consumption of 5-7.5 billion kWh. Herein, a solar-powered continuous-flow device was designed for aeration-free in situ Fenton-like reactions to treat wastewater. This system is based on the combination of TiO2-x/W18O49 featuring heterophase oxygen vacancy interactions with floating reduced graphene/polyurethane foam, which produces hydrogen peroxide in situ at the rates of up to 4.2 ppm h-1 with degradation rates of more than 90% for various antibiotics. The heterophase oxygen vacancies play an important role in the stretching of the O-O bond by regulating the d-band center of TiO2-x/W18O49, promoting the hydrogenation of *·O2- or *OOH by H+ enrichment, and accelerating the production of reactive oxygen species by spontaneous adsorption of hydrogen peroxide. Furthermore, the degradation mechanisms of antibiotics and the treatment of actual wastewater were thoroughly investigated. In short, the study provides a meaningful reference for potentially undertaking the "aeration-free" in situ Fenton reaction, which can help reduce or even completely eradicate the aeration costs and energy requirements during the treatment of wastewater.

Application of artificial intelligence in medical education: A meta-ethnographic synthesis.

With the advancement of Artificial Intelligence (AI), it has had a profound impact on medical education. Understanding the advantages and issues of AI in medical education, providing guidance for educators, and overcoming challenges in the implementation process is particularly important.The objective of this study is to explore the current state of AI applications in medical education.A systematic search was conducted across databases such as PsycINFO, CINAHL, Scopus, PubMed, and Web of Science to identify relevant studies. The Critical Appraisal Skills Programme (CASP) was employed for the quality assessment of these studies, followed by thematic synthesis to analyze the themes from the included research.Ultimately, 21 studies were identified, establishing four themes: (1) Shaping the Future: Current Trends in AI within Medical Education; (2) Advancing Medical Instruction: The Transformative Power of AI; (3) Navigating the Ethical Landscape of AI in Medical Education; (4) Fostering Synergy: Integrating Artificial Intelligence in Medical Curriculum.Artificial intelligence's role in medical education, while not yet extensive, is impactful and promising. Despite challenges, including ethical concerns over privacy, responsibility, and humanistic care, future efforts should focus on integrating AI through targeted courses to improve educational quality.

Suicide death, suicidal ideation and suicide attempt in patients with diabetes: A systematic review and meta-analysis.

AIMS: Diabetes has been indicated to be a risk factor for suicide. We aim to estimate the prevalence of suicide in patients with diabetes. DESIGN: A meta-analysis using PRISMA methodology was adopted to examine the incidence of suicide in diabetic patients. DATA SOURCES: From inception to October 2022, three online databases (PubMed, China National Knowledge Infrastructure and Web of Science) were used to search studies. REVIEW METHODS: We used random-effects model to analysis. And our primary outcome was the incidence of suicide death per 100 person-years, and other outcomes were prevalence of suicidal ideation and suicide attempt. To explore the sources of heterogeneity in our study, we performed subgroup and meta-regression analyses. RESULTS: The suicide death rate in diabetic patients was 0.027 per 100 person-years, with a higher rate for Type 1 Diabetes Mellitus compared to Type 2 Diabetes Mellitus. The prevalence of suicidal ideation in diabetes patients was 0.175, with a higher prevalence in Type 1 Diabetes Mellitus compared to Type 2 Diabetes Mellitus. The prevalence of suicide attempts in diabetes patients was 0.033, indicating a higher rate for Type 2 Diabetes Mellitus compared to Type 1 Diabetes Mellitus. CONCLUSIONS: The results indicate a high rate of suicide among people with diabetes, and this study identifies populations and regions at high risk for suicide. Our review emphasizes interventions in mental health and the improvement of suicide prevention programmes. IMPACT: The study investigated suicide death, suicidal ideation and suicide attempt in diabetic individuals. Suicide rates are elevated among diabetic patients, and various patient groups face distinct suicide risks. It is important to prioritize the mental well-being of diabetic individuals and enhance interventions, including personalized approaches, to inform public health efforts aimed at preventing and addressing suicide among diabetic patients. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.

Current Status of Nursing Home Distribution in China: A National Cross-Sectional Study.

AIMS: Population aging is a challenge that the whole world is facing, especially in China. This study aims to investigate the current distribution status of nursing homes in China using spatial epidemiology methods. DESIGN: Cross-sectional study in China. METHODS: The data were obtained from the Integrated Civil Affairs Government Service Platform 'China County Statistical Yearbook' for 2020 and the 'China City Statistical Yearbook' for 2020. Using global Moran's index to test the clustering of nursing homes, inter-group and intra-group Theil index was utilised to differentiate the sources of differences. The coupling coordination analysis was conducted to explore the coordination. Geographically weighted regression was utilised to investigate the impact of economic development and aging on nursing home resources. All analyses were conducted by Arcgis 10.8 and R Studio 4.3.2. RESULTS: Global Moran's index indicated that the distribution of nursing homes in China exhibited clustering. The Theil index values for institutions and beds at the national county were 0.32450 and 0.30675. However, upon comparing provinces and regions, it was found that the differences across the country mainly stem from within provinces (contribution rate: institutions 65.0%; beds 73.0%) and within regions (contribution rate: institutions 99.0%; beds 91.0%). The majority of districts and counties had a coupling coordination index of institutions and bed numbers, both of which were < 0.5. CONCLUSION: The development of nursing home resources in China has been rapid, generally presenting a balanced state, but further optimisation is needed. This study established a foundation for the targeted distribution of essential public services, focusing on nursing home healthcare resources tailored to the needs of older persons. IMPLICATIONS: The study underscored the urgent need for targeted elderly care policies, emphasising the optimisation of resource distribution to enhance the overall quality of care provided to the aging population. NO PATIENTS OR PUBLIC CONTRIBUTION: The study did not involve humans.

Higher socioeconomic status is associated with higher ultra-processed food intake: a cross-sectional analysis.

OBJECTIVE: To explore the differences in ultra-processed food (UPF) consumption across different socioeconomic status (SES) levels. METHODS: Data on UPF consumption (grams/day) were derived from the 2017-2018 National Health and Nutrition Examination Survey. The analysis controlled for age, marital status, race, and sex. A restricted cubic spline (RCS) model was applied to examine the nonlinear response curve. RESULTS: UPF consumption increased with higher poverty income ratio (PIR), the ratio of household income to the established poverty line. Compared to the low PIR group, the medium group showed a non-significant increase (ß = 34.23[95%CI: -28.81, 97.28], p = 0.287), while the high group exhibited a significant increase (ß = 115.15[95%CI: 43.53, 186.76], p = 0.002). A linear positive correlation was observed in RCS analysis (p-nonlinear = 0.166, p-overall < 0.001). CONCLUSIONS: The study highlights that higher SES is associated with greater consumption of UPF in the US. The findings suggest that policy interventions should take SES into consideration.

Does childhood parental death impact late life health directly and indirectly? Evidence from a National Survey in China.

Despite growing interest in understanding the impact of childhood parental death, less is known about its long-term effects on older adults. We investigated the mediating role of poor health perception in the relationship between childhood parental loss and late life health. A cross-sectional study using data from the 2016 China Longitudinal Aging Social Survey was conducted. Our final sample featured 8,547 older adults. The prevalence of childhood parental death was 9.8%. Results indicated a significant direct impact of childhood parental death on depression and cognitive function. Mediating effects were observed, with older adults who experienced childhood parental loss perceiving their health status as significantly worse. This, in turn, predicted higher levels of objective physical impairment, greater depression, and lower levels of cognitive function. Our study offers the first empirical evidence of the enduring negative effects of childhood parental death as well as the pivotal mediating role of poor health perception.

Empathy as a Mediator of the Relation between Peer Influence and Prosocial Behavior in Adolescence: A Meta-Analysis.

During adolescence, empathy and prosocial behavior contribute to the establishment of positive interpersonal relationships and social connections, promoting holistic development in youth. A substantial amount of research has provided compelling evidence that there is a relationship between peer relationships and empathy and prosocial behavior. Empathy, as a key mediating factor, links the influence of peers with prosocial behavior in adolescents, yet there is currently a lack of robust meta-analytic evidence regarding this mediating role. This study employed a two-stage structural equation modeling approach to synthesize existing research on peer influence, empathy, and prosocial behavior during adolescence. Systematic searches were conducted across three databases (PubMed, Web of Science, and PsycINFO), identifying a total of 49 studies, with a systematic assessment of study quality. The results indicated that empathy plays a mediating role between peer influence and prosocial behavior. Positive peer influence is positively correlated with empathy and prosocial behavior, while negative peer influence is negatively correlated with empathy and prosocial behavior, and empathy is positively correlated with prosocial behavior. This meta-analysis demonstrates that during adolescence, empathy mediates the connection between peer influence and prosocial behavior, representing a potential process that can explain the relationship between peer influence and prosocial behavior.

Suicide in China: The Trends and Differentials From 2002 to 2021.

OBJECTIVE: The objective of this study was to provide an updated analysis of suicide characteristics in China from 2002 to 2021, with the aim of informing the development of evidence-based suicide prevention strategies. METHODS: The Ministry of Health-Vital Registration System (MOH-VR) provided the data on suicide mortality, which enabled us to examine the average annual percentage change (AAPC) in suicide rates using a Poisson regression model. RESULTS: Notably, there has been a significant decline in suicide rates observed in both urban and rural areas. In the early years of the study period, higher suicide rates were observed among females compared to males; however, a shift occurred after 2005, with male suicide rates surpassing those of females. Except for 2005, rural areas consistently exhibited higher suicide rates than urban areas. Furthermore, suicide rates exhibited an increasing trend with age, irrespective of gender or region. CONCLUSION: These findings highlight a decreasing trend in suicide rates in China over the past two decades, although gender and regional disparities persist. Going forward, sustained efforts in suicide prevention, with a specific focus on mental health, are warranted.

Body mass index and pressure injuries risk in hospitalized adult patients: A dose-response analysis.

BACKGROUND: The association between underweight and pressure injuries (PIs) has been established in several studies. However, there is a lack of well-designed research investigating the connection between overweight and obesity with these injuries. OBJECTIVE: This meta-analysis aims to investigate the dose-response relationship between body mass index (BMI) and the risk of PIs in adult hospitalized patients. METHODS: PubMed, Web of Science, and MEDLINE Databases were searched from inception to May 2024. Observational articles with at least three BMI categories were included in the study. BMI was defined as underweight, normal weight, overweight, and morbid obesity for the meta-analysis. The non-linear relationship between BMI and the risk of PIs in hospitalized adults was investigated using restricted cubic spline models. Fractional polynomial modeling was used. RESULTS: Eleven articles reporting at least 3 categories of BMI met the inclusion criteria, including 31,389 participants. Compared to patients with normal weight, those with underweight, obesity, and morbid obesity exhibited an increased risk of PIs, with odds ratios of 1.70 (95%CI:1.50-1.91), 1.12 (95%CI:1.02-1.24), 1.70 (95%CI:1.13-2.55), respectively. A J-shaped dose-response model was established for the relationship between PI risk and BMI (Pnon-linearity < 0.001, Plinearity = 0.745). CONCLUSION: The J-shaped dose-response pattern revealed that underweight, obesity and morbid obesity heightened the risk of PIs in hospitalized adults. Lower and higher BMI values may signify an increased risk for PIs, particularly among the elderly with lower BMI, providing valuable guidance for medical staff.

The Effects of a Nonpharmacological Intervention Practice for Older Adults with Mild Cognitive Impairment and Their Family Caregivers in China.

Mild cognitive impairment (MCI) marks a critical phase in the progression to dementia. In our study, social workers utilized the Multicomponent Nonpharmacological Intervention Approach (MCNIA) to aid MCI participants (N = 52) and their caregivers, dividing into intervention and control groups. The intervention group underwent an additional regimen of non-pharmacological therapies besides pharmacological treatment. Our findings highlighted that: 1) MCNIA significantly enhanced cognitive and daily living abilities in the intervention group; 2) Caregivers experienced reduced burdens and improved social support; 3) Correlation analyses involving biomarkers indicated that MCNIA was particularly effective in alleviating depression in those with slightly more severe cognitive impairment.