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Advanced metastatic cardia cancer is an intractable malignance with poor prognosis. It is often accompanied by upper digestive tract obstruction, which seriously affects the quality of patients. Therefore, effective relief of eating obstruction is an important goal in the treatment of cardia cancer. Immune checkpoint inhibitors (ICIs) have shown significant efficacy in cardia cancer, but only a small percentage of patients will benefit from them due to immune resistance. Oncolytic viruses have been shown to enhance the efficacy of ICIs by altering the immune microenvironment. This indicates that oncolytic virus has the potential value of overcoming the immune resistance of cardia cancer. Here, we present a case with local recurrent and multiple metastatic cardia cancer accompanied by eating obstruction. After 4 cycles of chemotherapy plus ICI therapy, the patient´s metastases were significant shrink, but the recurrent carida lesion were almost unchanged. Then we implemented exploratory local injection of recombinant human adenovirus type 5(H101) into recurrent cardia lesion by painless gastroscopy. Surprisingly, the cardia lesion shrank significantly, and the eating obstruction was greatly relieved. We also observed a significant increase of infiltrated CD4+T cells in biopsy tissues after H101 treatment. Our study not only conformed the value of oncolytic viruses to reverse ICI resistance in patients with gastric cancer, but also revealed its underlying impact on immune microenvironment.

Ferroptosis is considered an effective method to overcome drug-resistant tumors. This study aims to use three FDA-approved biological materials, human serum albumin, D-α-tocopherol succinate, and indocyanine green, to construct a novel biocompatible nanomaterial named HTI-NPs, exploring its effect in drug-resistant breast cancer (MCF-7/ADR cells). The research results indicate that HTI-NPs can selectively inhibit the proliferation of MCF-7/ADR cells in vitro, accompanied by upregulating transferrin receptor, generating reactive oxygen species, and downregulating glutathione peroxidase 4. Under laser irradiation, HTI-NPs can promote ferroptosis by inhibiting glutathione expression through photodynamic therapy. Notably, HTI-NPs exhibit good inhibitory effects on MCF-7/ADR xenograft tumors in vivo. In conclusion, HTI-NPs represent a biocompatible nanomaterial that induces ferroptosis, providing new insights and options for treating drug-resistant breast cancer.

The human genome harbors many endogenous retroviral elements, known as human endogenous retroviruses (HERVs), which have been integrated into the genome during evolution due to infections by exogenous retroviruses. Accounting for up to 8% of the human genome, HERVs are tightly regulated by the host and are implicated in various physiological and pathological processes. Aberrant expression of HERVs has been observed in numerous studies on exogenous viral infections. In this review, we focus on elucidating the potential roles of HERVs during various exogenous viral infections and further discuss their implications in antiviral immunity.

Previous studies demonstrated that EV71-infected cells secrete extracellular vesicles (EVs), facilitating the transfer of viral components to recipient cells and thereby promoting virus spread. Considering lipid signaling plays a crucial role in EVs-mediated cell-to-cell communication, we compared the lipid profile of EVs secreted from uninfected and EV71-infected cells (EVs-Mock and EVs-EV71) using the human rhabdomyosarcoma (RD) cell model. These two groups of EVs were purified by using size exclusion chromatography (SEC), respectively, and evaluated by transmission electron microscopy (TEM), nanoparticle tracking technology (NTA), and Western blotting (WB). In-depth lipidomic analysis of EVs identified 1705 lipid molecules belonging to 43 lipid classes. The data showed a significant increase in the lipid content of EVs after EV71 infection. Meanwhile, we deeply analyzed the changes in lipids and screened for lipid molecules with significant differences compared EVs-EV71 with EVs-Mock EVs. Altogether, we report the alterations in the lipid profile of EVs derived from RD-cells after EV71 infection, which may affect the function of the EVs in the recipient cells.

BackgroundNatural killer (NK) cells are proposed to participate in coronary artery disease (CAD) development. However, little is known about how CAD patients’ NK cells respond to different stimulatory factors in terms of proliferation capability.Methods and resultsTwenty-nine CAD patients’ peripheral blood NK cells were isolated and individually treated with IL-2, IL-12, IL-15, IL-18, IL-21, cortisone acetate, hydrocortisone, or ascorbic acid for 36 hours, followed by cell cycle analysis using flow cytometry. The ratio of S and G2/M phase cell number to total cell number was defined as a proliferation index (PrI) and used for proliferative capability indication. The results showed that these eight factors resulted in different life cycle changes in the 29 NK cell samples. Remarkably, 28 out of 29 NK cell samples showed an obvious increase in PrI upon ascorbic acid treatment. The serum lactate dehydrogenase (LDH) level of the 29 CAD patients was measured. The results showed a negative correlation between serum LDH level and the CAD patients’ NK cell PrI upon stimulation of interleukins, but not the non-interleukin stimulators. Consistently, a retrospective analysis of 46 CAD patients and 32 healthy donors showed that the circulating NK cell number negatively correlated with the serum LDH level in CAD patients. Unexpectedly, addition of LDH to NK cells significantly enhanced the production of IFN-γ, IL-10 and TNF-α, suggesting a strong regulatory role on NK cell’s function.ConclusionAscorbic acid could promote the proliferation of the CAD patients’ NK cells; LDH serum level may function as an indicator for NK cell proliferation capability and an immune-regulatory factor.

ObjectiveWhite matter hyperintensity (WMH) in patients with cerebral small vessel disease (CSVD) is strongly associated with cognitive impairment. However, the severity of WMH does not coincide fully with cognitive impairment. This study aims to explore the differences in the dynamic functional network connectivity (dFNC) of WMH with cognitively matched and mismatched patients, to better understand the underlying mechanisms from a quantitative perspective.MethodsThe resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive function scale assessment of the patients were acquired. Preprocessing of the rs-fMRI data was performed, and this was followed by dFNC analysis to obtain the dFNC metrics. Compared the dFNC and dFNC metrics within different states between mismatch and match group, we analyzed the correlation between dFNC metrics and cognitive function. Finally, to analyze the reasons for the differences between the mismatch and match groups, the CSVD imaging features of each patient were quantified with the assistance of the uAI Discover system.ResultsThe 149 CSVD patients included 20 cases of “Type I mismatch,” 51 cases of Type I match, 38 cases of “Type II mismatch,” and 40 cases of “Type II match.” Using dFNC analysis, we found that the fraction time (FT) and mean dwell time (MDT) of State 2 differed significantly between “Type I match” and “Type I mismatch”; the FT of States 1 and 4 differed significantly between “Type II match” and “Type II mismatch.” Correlation analysis revealed that dFNC metrics in CSVD patients correlated with executive function and information processing speed among the various cognitive functions. Through quantitative analysis, we found that the number of perivascular spaces and bilateral medial temporal lobe atrophy (MTA) scores differed significantly between “Type I match” and “Type I mismatch,” while the left MTA score differed between “Type II match” and “Type II mismatch.”ConclusionDifferent mechanisms were implicated in these two types of mismatch: Type I affected higher-order networks, and may be related to the number of perivascular spaces and brain atrophy, whereas Type II affected the primary networks, and may be related to brain atrophy and the years of education.

AimTo investigate the efficacy and safety of combining Recombinant Human Endostatin Injection (marketed as Endo) with anti-PD-1 in elderly patients aged 80 and above with non-small cell lung cancer (NSCLC).MethodsRetrospective analysis of 181 patients with NSCLC aged 80 and above treated in the Department of Respiratory and Critical Care Medicine at Chaohu Hospital, affiliated with Anhui Medical University, from June 2019 to January 2024. Patients who received at least one cycle of combined Endo with anti-PD-1 were included based on inclusion criteria. Clinical and pathological data were collected, including complete blood count, liver and kidney function, electrocardiogram, coagulation function, thyroid function, cardiac enzymes, and whole-body imaging. Adverse events were recorded with a final follow-up on January 25, 2024. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with safety as a secondary endpoint.ResultsThis study involved 14 elderly patients with NSCLC aged over 80. Median progression-free survival (mPFS) was 102 days, and median overall survival (mOS) was 311 days. Subgroup analyses based on treatment cycles showed a non-significant 441-day mPFS increase in the long-term group (≥6 cycles, 5 patients) compared to the short-term group (

BackgroundBoth the mother and the infant are negatively impacted by macrosomia. Macrosomia is three times as common in hyperglycemic mothers as in normal mothers. This study sought to determine why hyperglycemic mothers experienced higher macrosomia. Methods: Hematoxylin and Eosin staining was used to detect the placental structure of normal mother(NN), mothers who gave birth to macrosomia(NM), and mothers who gave birth to macrosomia and had hyperglycemia (DM). The gene expressions of different groups were detected by RNA-seq. The differentially expressed genes (DEGs) were screened with DESeq2 R software and verified by qRT-PCR. The STRING database was used to build protein-protein interaction networks of DEGs. The Cytoscape was used to screen the Hub genes of the different group.ResultsThe NN group’s placental weight differed significantly from that of the other groups. The structure of NN group’s placenta is different from that of the other group, too. 614 and 3207 DEGs of NM and DM, respectively, were examined in comparison to the NN group. Additionally, 394 DEGs of DM were examined in comparison to NM. qRT-PCR verified the results of RNA-seq. Nucleolar stress appears to be an important factor in macrosomia, according on the results of KEGG and GO analyses. The results revealed 74 overlapped DEGs that acted as links between hyperglycemia and macrosomia, and 10 of these, known as Hub genes, were key players in this process. Additionally, this analysis believes that due of their close connections, non-overlapping Hubs shouldn’t be discounted.ConclusionIn diabetic mother, ten Hub genes (RPL36, RPS29, RPL8 and so on) are key factors in the increased macrosomia in hyperglycemia. Hyperglycemia and macrosomia are linked by 74 overlapping DEGs. Additionally, this approach contends that non-overlapping Hubs shouldn’t be ignored because of their tight relationships.

Macrophages and neutrophils are the main components of the innate immune system and play important roles in promoting angiogenesis, extracellular matrix remodeling, cancer cell proliferation, and metastasis in the tumor microenvironment (TME). They can also be harnessed to mediate cytotoxic tumor killing effects and orchestrate effective anti-tumor immune responses with proper stimulation and modification. Therefore, macrophages and neutrophils have strong potential in cancer immunotherapy. In this review, we briefly outlined the applications of macrophages or neutrophils in adoptive cell therapies, and focused on chimeric antigen receptor (CAR)-engineered macrophages (CAR-Ms) and neutrophils (CAR-Ns). We summarized the construction strategies, the preclinical and clinical studies of CAR-Ms and CAR-Ns. In the end, we briefly discussed the limitations and challenges of CAR-Ms and CAR-Ns, as well as future research directions to extend their applications in treating solid tumors.

BackgroundStudies have demonstrated that high iron status is positively associated with gestational diabetes mellitus (GDM), implying that iron overload and ferroptosis play important roles in the development of GDM. The aim of this study was to explore effective therapeutic drugs from traditional Chinese medicine (TCM)formulas for the treatment of GDM based on ferroptosis.MethodsIn this study, the presence of ferroptosis in the placenta was verified through clinical and experimental data, and key genes were subsequently screened for association with ferroptosis in the development of GDM. The analysis was based on transcriptome sequencing of datasets combined with differentially expressed genes (DEGs) analysis and weighted gene correlation network analysis (WGCNA); functional enrichment analysis was also performed. A protein−protein interaction (PPI) network was constructed and pivotal genes were identified using Cytoscape. Finally, traditional Chinese medicine (TCM)formulas related to treating GDM were collected, then the proteins corresponding to the key genes were molecularly docked with the small molecular structures of clinically proven effective herbal tonics, and molecular dynamic simulations were performed to select the best candidates for pharmacological compounds.ResultsElevated ferritin levels in patients with GDM were verified using clinical data. The presence of ferroptosis in placental tissues of patients with GDM was confirmed using electron microscopy and western blotting. Ninety-nine key genes with the highest correlation with ferroptosis were identified from DEGs and weighted gene co-expression network analysis (WGCNA). Analysis using the Kyoto Encyclopedia of Genes and Genomes demonstrated that the DEGs were primarily involved in the oxidative phosphorylation pathway. The key genes were further screened by PPI; two key genes, SF3B14 and BABAM1, were identified by combining the gene corresponding to protein structure and function, followed by molecular docking and molecular dynamic simulation. Coptis chinensis was proposed as the best candidate for herbal treatment at the molecular level.ConclusionThis data revealed the presence of ferroptosis in patients with GDM and identified possible modulatory roles of ferroptosis-related genes involved in the molecular mechanisms of GDM, providing new insights into the pathogenesis of GDM, which also provided new directions for the systematic optimization of TCM formulas for the management and targeted treatment of GDM.

BackgroundCerebral small vessel disease (CSVD) is a cluster of microvascular disorders with unclear pathological mechanisms. The microbiota-gut-brain axis is an essential regulatory mechanism between gut microbes and their host. Therefore, the compositional and functional gut microbiota alterations lead to cerebrovascular disease pathogenesis. The current study aims to determine the alteration and clinical value of the gut microbiota in CSVD patients.MethodsSixty-four CSVD patients and 18 matched healthy controls (HCs) were included in our study. All the participants underwent neuropsychological tests, and the multi-modal magnetic resonance imaging depicted the changes in brain structure and function. Plasma samples were collected, and the fecal samples were analyzed with 16S rRNA gene sequencing.ResultsBased on the alpha diversity analysis, the CSVD group had significantly decreased Shannon and enhanced Simpson compared to the HC group. At the genus level, there was a significant increase in the relative abundances of Parasutterella, Anaeroglobus, Megasphaera, Akkermansia, Collinsella, and Veillonella in the CSVD group. Moreover, these genera with significant differences in CSVD patients revealed significant correlations with cognitive assessments, plasma levels of the blood-brain barrier-/inflammation-related indexes, and structural/functional magnetic resonance imaging changes. Functional prediction demonstrated that lipoic acid metabolism was significantly higher in CSVD patients than HCs. Additionally, a composite biomarker depending on six gut microbiota at the genus level displayed an area under the curve of 0.834 to distinguish CSVD patients from HCs using the least absolute shrinkage and selection operator (LASSO) algorithm.ConclusionThe evident changes in gut microbiota composition in CSVD patients were correlated with clinical features and pathological changes of CSVD. Combining these gut microbiota using the LASSO algorithm helped identify CSVD accurately.

BackgroundAtrial fibrill ation (AF) is a predominant public health concern in older adults. Therefore, this study aimed to explore the global, regional, and national burden of AF in older adults aged 60–89 between 1990 and 2019.MethodsThe morbidity, mortality, disability-adjusted life years (DALYs), and age-standardized rates of AF were refined from the Global Burden of Diseases study 2019. The epidemiological characteristics were assessed based on numerical values, age-standardized rates per 100,000 person-years, and estimated annual percentage changes (EAPC).ResultsGlobally, a total of 33.31 million AF cases, 219.4 thousand deaths, and 65.80 million DALYs were documented in 2019. There were no appreciable changes in EAPC from 1990 to 2019. The disease burden of AF differed significantly across different territories and countries. At the national level, China exhibited the highest number of incident cases [818,493 (562,871–1,128,695)], deaths [39,970 (33,722–46,387)], and DALYs [1,383,674 (1,047,540–1,802,516)]. At the global level, high body mass index (BMI) and high systolic blood pressure (SBP) were two predominant risk factors contributing to the proportion of AF-related deaths.ConclusionAF in older adults remains a major public health concern worldwide. The burden of AF varies widely at both national and regional levels. From 1990 to 2019, the cases of incidences, deaths, and DALYs have shown a global increase. The ASIR, ASMR, and ASDR have declined in the high-moderate and high SDI regions; however, the burden of AF increased promptly in the lower SDI regions. Special attention should be paid to the main risk factors for high-risk individuals with AF, which can help control systolic blood pressure and body mass index within normal limits. Over all, it is necessary to illustrate the features of the global AF burden and develop more effective and targeted prevention and treatment strategies.

Even though uterine torsion is a rare obstetric complication in humans, it has been linked to severe complications like placental abruption, uterine rupture, foetal bradycardia, or even death. Here, we present a rare case of maternal shortening and prolonged foetal bradycardia. The patient suffered from congenital malformations of the female genital tract, which were classified as a complete bicorporeal uterus, a double “normal” cervix, and a longitudinal non-obstructing vaginal septum (U3b/C2/V1). The patient had an emergency caesarean section due to suspected placental abruption. Uterine torsion was found during the surgery, and the postoperative recovery was good. Obstetricians should be aware of the possibility of uterine torsion as a complication of pregnancy to avoid a delayed diagnosis of uterine torsion, especially in patients with genital malformations. During the surgery, there could be serious damage to blood vessels and tissues around the uterus due to an unclear surgical field, and difficulties in exposing the uterine body should be considered.

ObjectiveThis systematic review and meta-analysis compares the outcome between MMBC and unifocal breast cancer (UFBC), in order to provide a theoretical basis for the design of an appropriate clinical therapeutic strategy of MMBC patients.MethodsPubMed, Embase, The Cochrane Library, Web of science, CNKI, WanFang Data, CBM and VIP database were searched from inception to July 2021, and observational studies reporting the outcome of patients with MMBC and UFBC were included. We extracted or calculated the mortality rates of MMBC and UFBC patients; and obtained the hazard ratios; odds ratios; relative risks; and the corresponding 95% confidence intervals from the eligible studies. All the meta-analyses were conducted by using the Stata 15.0 software.Results31 eligible studies comprising a total of 15,703 individuals were included. The meta-analysis revealed that MMBC did not have a significant association with poor overall survival (HR=1.04, 95% CI=0.96-1.12), disease-free survival (HR= 1.07, 95% CI= 0.84-1.36), breast cancer-specific survival (HR=1.42, 95% CI= 0.89-2.27), recurrence-free survival (HR= 0.878, 95% CI= 0.652-1.182), local recurrence-free survival (HR= 0.90, 95% CI= 0.57-1.42), and contralateral breast cancer risk (RR= 0.908, 95% CI= 0.667-1.234). However, MMBC appeared to have a correlation with a slightly higher risk of death (OR=1.31, 95% CI=1.18-1.45).ConclusionPatients with MMBC appeared to have a higher risk of death, however, it may not be independently associated with poorer outcomes. Considering the inter-study heterogeneity and other limitations, our results need to be validated by further multicenter prospective studies with a large sample size in the future.

The World Health Organization (WHO) estimates that about one-third of people worldwide currently have a need for rehabilitation. This demand is expected to increase in the coming years due to changes in population health and characteristics. For example, with the intensification of global aging, the rehabilitation needs of patients with chronic diseases and disabilities, postoperative dysfunction, and cognitive impairment continue to grow, and emergencies such as conflicts, disasters, and epidemics may lead to a surge in rehabilitation needs. Early and sustained rehabilitation could reduce complications, improve function, and reduce disability in affected populations, but rehabilitation services are often underestimated due to underfunding and poor short-term outcomes. WHO sees rehabilitation as an essential part of achieving universal health coverage and the Sustainable Development Goals. With the development of China's economy and society and the trend of an aging population, the demand for rehabilitation therapists is growing rapidly. Since the development of rehabilitation education in China at the beginning of this century, great progress has been made in both the training mode and the number of people trained, especially in the construction of higher education of rehabilitation in related colleges and universities. Through descriptive qualitative analysis, this study collected information from national policy documents and official websites of colleges and universities on policies concerning degree systems, cultivating goals and ideas, courses, education internationalization, continuing education in practice, standardized training after graduation, the number of colleges and universities with rehabilitation therapy related majors in China, and summarizes the current situation of the development of rehabilitation personnel education in Chinese colleges and universities. Judging from the results, during the development of rehabilitation education, China has continuously improved in terms of policy support, educational goals and concepts, the number and quality of institutions, degree systems, and internationalization, while gradually adapting to China's development status. This also provides direction and feasible suggestions for China to improve the rehabilitation education development system and formulate a national rehabilitation education plan in the future to deal with the challenge of aging.

BackgroundFamily physicians play a key role in responding to the growing demand for primary healthcare due to aging. The work attitude of family physician team members (FPTMs) impacts their work efficiency and quality. Knowing how satisfied they are with their jobs can help identify potential directions and entry points for incentives. The purpose of this study is to analyze the job satisfaction status and influencing factors of grassroots health service personnel after the implementation of the family physician contract system in China.MethodsThe study conducted a cross-sectional survey with 570 FPTMs in three prefecture-level cities in the Shandong Province. Satisfaction was measured using 30 items across seven dimensions. Responses were recorded on a 5-point Likert scale. Descriptive statistical analysis was used to analyze the general information and satisfaction of FPTMs. Multiple linear regression analysis was used to analyze the factors influencing job satisfaction.ResultsThe overall job satisfaction among FPTMs was not high. Among the seven dimensions, interpersonal relationships had the highest satisfaction (4.10 ± 0.78), while workload had the lowest satisfaction (3.08 ± 0.56). The satisfaction levels of the three sample regions were different, and the results were opposite to their regional economic development levels. The results of the multifactor analysis showed that gender, income level, educational background, working years, daily working hours, number of training sessions per year and the proportion of performance pay had significant impact on overall job satisfaction.ConclusionsThe development of a family physician contract system has increased the workload of FPTMs. In addition to the implementation of the new policy, attention should be paid to the workload and working attitude of family physicians. The fundamental measures should focus on attracting more personnel to work at the grassroots level by accelerating education and training to solve the problem of insufficient health personnel at the grassroots level. Simultaneously, attention should be paid to the improvement of the medical staff's salary level and the need for self-promotion, such as training.

BackgroundDue to an increasing aging population, China has experienced a rapid expansion in its internal older migrant population who face greater health risks and who have a relatively high demand for health education. Public health education is an important means of preventing diseases and promoting health. However, many studies have focused on the utilization, with few studies examining the impact of public health education on the health of the older migrant population in China.ObjectivesThis study analyzed the impact of public health education on the health of the older migrant population in China.MethodsBased on data obtained from the National Migrant Population Health and Family Planning Dynamic Monitor Survey (2018), logistic models and propensity score matching were used to analyze the impact of public health education on the health of the older migrant population.ResultsThe self-assessed health of China's older migrant population was good, and the acceptance rate of public health education was 40.81%. The public health status of the older migrant population receiving public health education significantly improved (p < 0.05). After correcting for endogeneity among the variables, public health education increased the probability of improving the older migrant population's self-assessed health by 5.4–6.1% (p < 0.01). Heterogeneity analysis found that public health education had a greater impact on the health of older men with an education level of middle school and below, and especially on the older migrant population in the eastern region of China.ConclusionsPublic health education positively affected the health status of the older migrant population. The characteristics and preferences of the older migrant population involving different genders, regions, and educational levels need to be considered, public health education needs to be standardized, and appropriate education methods need to be adopted that suit the older migrant population. Reference suggestions are provided for improving the health level of the older migrant population.

BackgroundReliable and individualized biomarkers are crucial for identifying early cognitive impairment in subcortical small-vessel disease (SSVD) patients. Personalized brain age prediction can effectively reflect cognitive impairment. Thus, the present study aimed to investigate the association of brain age with cognitive function in SSVD patients and assess the potential value of brain age in clinical assessment of SSVD.Materials and methodsA prediction model for brain age using the relevance vector regression algorithm was developed using 35 healthy controls. Subsequently, the prediction model was tested using 51 SSVD patients [24 subjective cognitive impairment (SCI) patients and 27 mild cognitive impairment (MCI) patients] to identify brain age-related imaging features. A support vector machine (SVM)-based classification model was constructed to differentiate MCI from SCI patients. The neurobiological basis of brain age-related imaging features was also investigated based on cognitive assessments and oxidative stress biomarkers.ResultsThe gray matter volume (GMV) imaging features accurately predicted brain age in individual patients with SSVD (R2 = 0.535, p < 0.001). The GMV features were primarily distributed across the subcortical system (e.g., thalamus) and dorsal attention network. SSVD patients with age acceleration showed significantly poorer Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores. The classification model based on GMV features could accurately distinguish MCI patients from SCI patients (area under the curve = 0.883). The classification outputs of the classification model exhibited significant associations with MoCA scores, Trail Making Tests A and B scores, Stroop Color and Word Test C scores, information processing speed total scores, and plasma levels of total antioxidant capacity in SSVD patients.ConclusionBrain age can be accurately quantified using GMV imaging data and shows potential clinical value for identifying early cognitive impairment in SSVD patients.

As the global economy continues to integrate, COVID-19 is affecting businesses around the world, causing the financial system to become more complicated. The complicated relationship between various agents in the financial system makes potential hazards more easily transmitted. Most studies of systemic risks have focused on single-layer networks, and macroeconomic fluctuations have not been quantified in multi-layer models of financial networks. In this paper, three different macroeconomic shock scenarios (showing upward, downward, and random trends) are constructed to affect the firm’s business activities, and a multi-layer financial network model is developed to simulate systemic risk under macroeconomic fluctuations. Firms with medium and high leverage and small asset sizes, as well as banks with smaller asset sizes and fewer bank-firm credit linkages, are found to be more likely to default. The study also found that average firm leverage exhibits two inflection points, causing banks’ default probabilities to “rise, then fall, and then rise,” with the inflection point value being the lowest under the upward trend of macroeconomics. In addition, the higher the ratio of firm loans to total bank assets, the more likely the bank is to default. Appropriate loan maturity extension has also helped to reduce systemic risk, especially in light of the macroeconomic downward trend. Furthermore, improving the capital adequacy ratio can reduce the bank’s default probability under macroeconomic fluctuations.

BackgroundThe need for rehabilitation therapy has increased dramatically with the aging of the population, the prevalence of non-communicable diseases, and the increase in the number of disabilities. Rehabilitation therapists are crucial to provide high quality rehabilitation therapy; however, there is a significant shortage of these professionals in China. One of the effective strategies to address this challenge is using the norm of the workforce for rehabilitation therapy, which is an index for assessing the personnel required in a facility. This research aimed to create a rehabilitation therapist-required norm under institutional perspective in Shandong Province, China, based on the Workload Indicators of Staffing Needs (WISN) method, which was created by the World Health Organization (WHO) in 1998 to analyse staff utilization at various levels of the health care system.MethodsWe conducted descriptive and quantitative research from October to November 2020 in the rehabilitation department of a tertiary hospital in Weifang City, China. Focus groups, online interviews, and document reviews were conducted to gather data and calculations of the WISN method performed.ResultsAdmission assessment, pre-treatment evaluation, rehabilitation therapy, post-treatment evaluation, and health education for patients were identified as the main priority group activities. Interviews and analysis of documents summarized five factors related to rehabilitation therapists' health service activities. In this study, the annual working time of each therapist was 1,776 h per year. The WISN method calculations showed that the norm of rehabilitation therapists in this tertiary hospital was 23 therapists. As the department had 13 therapists, there was a shortage of 10 therapists based on the WISN calculation, with a ratio of 0.57, which represented the actual compared to the ideal number of therapists.ConclusionWorkload pressure was high for therapists in this tertiary hospital. This model revealed a demand for ten more therapists in the rehabilitation department. The WISN method can help hospital administrators in therapist workforce monitoring, including in regard to therapists. Therefore, the WISN method should be embraced as part of hospital human resource planning and recruitment strategies to meet increasing rehabilitation needs.

In our continuing efforts toward the design of novel pentacyclic triterpene derivatives as potential anti-influenza virus entry inhibitors, a series of homogeneous heptavalent glycyrrhetinic acid derivatives based on β-cyclodextrin scaffold were designed and synthesized by click chemistry. The structure was unambiguously characterized by NMR, IR, and MALDI-TOF-MS measurements. Seven conjugates showed sufficient inhibitory activity against influenza virus infection based on the cytopathic effect reduction assay with IC50 values in the micromolar range. The interactions of conjugate 37, the most potent compound (IC50 = 2.86 μM, CC50 > 100 μM), with the influenza virus were investigated using the hemagglutination inhibition assay. Moreover, the surface plasmon resonance assay further confirmed that compound 37 bound to the influenza HA protein specifically with a dissociation constant of 5.15 × 10−7 M. Our results suggest the promising role of β-cyclodextrin as a scaffold for preparing a variety of multivalent compounds as influenza entry inhibitors.

In the fields of public health policy and public health care, advanced educational programs are an important strategy in dealing with public health crises. The COVID-19 pandemic has exposed the global need for skilled public health leaders and managers to address complex public health challenges, which requires the strengthening of public health education at the highest levels. This paper is a qualitative case study of a special educational program for doctors of public health in China. The program's educational objectives are in line with epidemic prevention and control. With the goal of developing the world's leading national public health management system, the Chinese government established an advanced academic program for public health crisis management. The program offers doctoral students a multidisciplinary degree based upon the theoretical knowledge of crisis management, supported by advanced training in the foundational concepts, theories, and practices of public health, and the study of basic medicine which provides the theoretical support for developing essential clinical skills. Program graduates develop the theoretical, practical, and leadership-related capabilities required for the management of national emergencies. The program introduced in this paper meets current epidemic prevention and control needs and should be considered by public health policy makers, leaders, and scholars in the discussion of advanced public health policy and health care education in China, including the development of an internationally recognized Doctor of Public Health program.

Frequent financial crises and economic globalization have made systemic risk a growing Research Topic. This paper constructs a dynamic banking system model based on the bank-asset bilateral network. By collecting the balance sheet and portfolio data of 47 Chinese listed banks in 2018, the paper firstly empirically analyses the impact of external shocks, the price-cutting effect, and the proportion of various assets held by banks to their total assets on the systemic risk of the banking system. The risk preference coefficient and systemic shock are then introduced to construct the banks' quantitative portfolio strategy model to study its optimal investment. It has been found that the greater the external shock and the stronger the price-cutting effect, the higher the systemic risk. Moreover, the external shock and price-cutting effect will have a superimposed effect within a specific range, and systemic risk will increase significantly. The asset classes of the Chinese banking system have a different sensitivity to external shocks, among which loan assets are the most sensitive. Further studies reveal an inflection point of risk preference, resulting in banks' expected return “increasing first and then decreasing.” The higher the debt-asset ratio and the stronger the banks' risk tolerance, the more aggressive investment strategies banks can choose to achieve high returns. This paper provides a reference for the banking industry to react to shocks and analyze systemic risk.

Background: The population-based studies conducted thus far do not provide conclusive evidence of the link between diabetic retinopathy (DR) and stroke. The aim of the present systematic review was to determine whether DR is specifically associated with stroke.Methods: MEDLINE, Embase, and Web of Science were systematically searched from their inception to July 31, 2020. All cohort studies that reported associations between the presence of DR and incident stroke were included. The pooled hazard ratios (HRs), pooled risk ratios (RRs), and 95% confidence intervals (CIs) were calculated.Results: The meta-analysis included 19 cohort studies involving 81,452 diabetic patients. The pooled effect size of any DR related to stroke was 1.25 for HR (95% CI: 1.12–1.39; P < 0.0001) and 1.96 for RR (95% CI: 1.60–2.39; P < 0.0001). Subgroup analysis for the type of diabetes yielded pooled HR of 1.29 (95% CI: 1.10–1.50; P = 0.001) in patients with type 2 diabetes mellitus (T2DM). The pooled RR was 2.29 (95% CI: 1.77–2.96; P < 0.0001) in patients with T2DM. Two studies addressed the DR-related stroke among type 1 diabetes mellitus (T1DM) patients. One study found a significant association between DR and stroke (OR: 1.6; 95% CI: 1.1–2.3; P < 0.01), while the other did not identify an association between these two conditions (RR: 1.40; 95% CI: 0.62–2.18; P = 0.178).Conclusions: The presence of DR is associated with an increased risk of stroke in diabetic patients. This correlation is robust in T2DM patients but uncertain in T1DM patients. Our findings indicate that DR is an important biomarker for the prediction of stroke. To further validate the role of DR in stroke-risk stratification, additional research is required on the association between the stage of DR and stroke risk, and more studies including T1DM patients are necessary.

A 56-year-old male was diagnosed with right lung upper lobe squamous cancer with right hilar and mediastinum lymph node metastasis. After four cycles of neoadjuvant immunochemotherapy, reexamination by computed tomography showed progressive disease of the primary lesion. Then, the patient underwent a right lung upper lobectomy, and hilar and mediastinum lymph node dissection. Surgical pathology showed a partial response to immunochemotherapy. Single-cell RNA sequencing was used to characterize the infiltrating immune cell atlas after neoadjuvant immunochemotherapy; the most common infiltrating immune cell types were cytotoxic CD8+ T cells, monocyte-derived dendritic cells, and macrophages. Imaging mass cytometry revealed a transformation from cold to hot tumor after neoadjuvant immunochemotherapy. In this case study, we are the first to report a case of neoadjuvant immunochemotherapy pseudoprogression, proved by surgical pathology, single-cell RNA sequencing, and imaging mass cytometry. Both single-cell RNA sequencing and imaging mass cytometry revealed an activated immune microenvironment after neoadjuvant immunochemotherapy.

37662RM1 and 37662RM2 are two phenotypically different, carbapenem-resistant mutants of Acinetobacter baumannii 37662 isolate following selection with meropenem (MEM) at sub-inhibitory concentrations. 37662RM2 lacks capsule synthesis and shows dramatically increased biofilm formation, while 37662RM1 shows merely impaired capsule synthesis. Here we report that 37662RM1 and RM2 have transcription profiles that are different from those of their starting strain, 37662WT. There were far more differentially expressed genes in 37662RM2 than in 37662RM1. The capsule polysaccharide (CPS) synthesis-required genes (itrA2, gtr5, psaA, psaB, psaC, psaD, psaE, psaF, kpsS2, wzx, wzy, wza, wzb, and wzc) showed reduced transcription levels in 37662RM2, which may at least partially explain the loss of capsule synthesis. The csu operon genes responsible for pili assembly and their regulator genes bfmR-bfmS were over-expressed in 37662RM2. This result together with the established critical roles of these genes in biofilm formation provide solid evidence that up-regulation of csu and bfmR-bfmS should be considered responsible for the enhanced biofilm formation in 37662RM2. ISAba1 was found to insert into the intergenic region between the csu operon and the acrR gene and should be responsible for the significant up-regulation of acrR, which was proposed to be associated with biofilm formation. Genome sequencing revealed that the ISAba1 upstream blaOXA–508 (a new member of blaOXA–51-like) and acrR were duplicated, suggesting a replicative transposition event. Altogether, the phenotype divergence driven by MEM selection mainly occurs at the RNA level and the transposition of ISAba1 plays an important role in modulating gene expression to adapt to the environment.

Functional near-infrared spectroscopy (fNIRS) was used to test whether monitoring inhibition-related brain regions is a feasible method for detecting both infrequent liars and frequent liars. Thirty-two participants were divided into two groups: the deceptive group (liars) and the non-deceptive group (ND group, innocents). All the participants were required to undergo a simulated interrogation by a computer. The participants from the deceptive group were instructed to tell a mix of lies and truths and those of the ND group were instructed always to tell the truth. Based on the number of deceptions, the participants of the deceptive group were further divided into a infrequently deceptive group (IFD group, infrequent liars) and a frequently deceptive group (FD group, frequent liars). The infrequent liars exhibited greater neural activities than the frequent liars and the innocents in the left middle frontal gyrus (MFG) when performing the deception detection tasks. While performing deception detection tasks, infrequent liars showed significantly greater neural activation in the left MFG than the baseline, but frequent liars and innocents did not exhibit this pattern of neural activation in any area of inhibition-related brain regions. The results of individual analysis showed an acceptable accuracy of detecting infrequent liars, but an unacceptable accuracy of detecting frequent liars. These results suggest that using fNIRS monitoring of inhibition-related brain regions is feasible for detecting infrequent liars, for whom deception may be more effortful and therefore more physiologically marked, but not frequent liars.

The ESAT-6 secretion system (ESS) has been reported to contribute to the virulence and pathogenicity of several Staphylococcus aureus strains such as USA300 and Newman. However, the role of the ESS in community-associated S. aureus (CA-SA) lineage ST398 in China is not well understood. By comparing the ess locus of ST398 with the published S. aureus sequence in the NCBI database, we found one gene in the ess locus encoding a novel WXG superfamily protein that is highly conserved only in ST398. LC-MS/MS and Western blot analysis revealed that this protein is a novel secreted protein controlled by the ST398 ESS, and we named the protein EsxX. Although EsxX was not under the control of the accessory gene regulator like many other virulence factors and had no influence on several phenotypes of ST398, such as growth, hemolysis, and biofilm formation, it showed important impacts on immune evasion and virulence in ST398. An esxX deletion mutant led to significantly reduced resistance to neutrophil killing and decreased virulence in murine skin and blood infection models, indicating its essential contribution to the evasion of innate host defense and virulence to support the pathogenesis of ST398 infections. The function of this novel secreted protein EsxX might help us better understand the role of the ESS in the virulence and epidemic success of the CA-SA lineage ST398.

The highly successful epidemic of healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) ST239 is a growing concern worldwide, due to its progressive adaptation to the highly selective environment of the healthcare system. HA-MRSA ST239 display the reduced virulence and successfully colonize in hospital settings, while the emergent community-associated MRSA (CA-MRSA) maintain full virulence and cause infections in the community environment. Our aim was to investigate what enables S. aureus ST239 to be highly adaptive under hospital circumstances and gradually progress to a series of widespread invasive infections. We found that spa expression of HA-MRSA ST239 is much higher than that of CA-SA ST398. And we discovered that the highly production of staphylococcal protein A (SpA), having no concern with spa gene structure, enhances nasal colonization and cell adhesion in ST239. S. aureus ST239 defends against the adaptive immune response by resisting phagocytosis and inducing apoptosis of B cells through expression of surface-anchored and released protein A, facilitating its dissemination within the circulatory system to other organs. Protein A also plays another key role in subverting the host immune response through its ability to induce early shedding of TNF-α receptor 1 (TNFR1) from phagocytic cells. The increased levels of soluble TNFR1 present during experimental S. aureus ST239 infection may neutralize circulating TNF-α and impair the host inflammatory response. Protein A is also a virulence factor, as tested in our bacteremia model in mice, contributing to the durative tissue damage of abscess formation sites in ST239 infection. These functions of protein A eventually benefit to widespread infections of S. aureus ST239. We draw the conclusion that Staphylococcal Protein A may be a crucial determinant in the colonization and immune evasion of ST239 infections, contributing to persistent spread in the hospital settings. These results suggest that antibodies against protein A may provide insights into the development of novel treatments against S. aureus, especially HA-MRSA. [ABSTRACT FROM AUTHOR]