Organizational culture and turnover intention among primary care providers: a multilevel study in four large cities in China.

BACKGROUND: Primary health care plays an important role in providing populations with access to health care. However, it is currently facing unprecedented workforce shortages and high turnover worldwide. OBJECTIVE: This study examined the relationship between organizational culture and turnover intention among primary care providers in China. METHODS: A cross-sectional survey was administered in four large cities in China, Tianjin, Jinan, Shanghai, and Shenzhen, comprising 38 community health centers and 399 primary care providers. Organizational culture was measured using the Competing Value Framework model, which is divided into four culture types: group, development, hierarchy, and rational culture. Turnover intention was measured using one item assessing participants' intention to leave their current position in the following year. We compared the turnover intention among different organizational culture types using a Chi-square test, while the hierarchical logistic regression was used to examine the relationship between organizational culture and turnover intention. RESULTS: The study found that 32% of primary care providers indicated an intention to leave. Primary care providers working in a hierarchical culture reported higher turnover intention (43.18%) compared with those in other cultures (p < 0.05). Hierarchical culture was a predictor of turnover intention (OR = 3.453, p < 0.001), whereas rational culture had a negative effect on turnover intention (OR = 0.319, p < 0.05). CONCLUSIONS: Our findings inform organizational management strategies to retain a healthy workforce in primary health care.

Main findings: This study found that primary care physicians and nurses working in a hierarchical culture are more likely to report the intention to leave compared to other culture types, while those working in a rational culture are significantly less likely to report the intention to leave.Added knowledge: The dominant organizational culture identified in community health centers across eastern China is group culture, and organizational culture is a significant predictor of the turnover intention of primary care providers.Global health impact for policy and action: Future primary care reform should focus on managerial interventions in their efforts to retain health workers and, in particular, develop and implement strategies to cultivate and moderate rational culture.

Macrogenomics reveal the effects of inter-cropping perilla on kiwifruit: impact on inter-root soil microbiota and gene expression of carbon, nitrogen, and phosphorus cycles in kiwifruit.

Intercropping systems can improve soil fertility and health, however, soil microbial communities and functional genes related to carbon, nitrogen and phosphorus cycling under the intercropping system of mesquite and perilla have not been studied. Therefore, in the present study, different planting densities and varieties of Perilla frutescens (L.) Britt and kiwifruit were used for intercropping, and changes in soil microbial communities and carbon, nitrogen, and phosphorus cycling genes in kiwifruit inter-roots under inter-cropping conditions were investigated by macro-genome sequencing technology. The results showed that intercropping with Perill caused a decrease in most soil nutrients, soil enzyme activities, and had a significant impact on the microbial (bacteria and fungi) diversity. Inter-cropping increased the relative abundance of the dominant bacterial phylum "Proteobacteria" and "Actinobacteria" by 47 and 57%, respectively, but decreased the relative abundance of the dominant fungal phylum "Chordata" and "Streptophyta" by 11 and 20%, respectively, in the inter-root soil of kiwifruit, and had a significant impact on the microbial (bacteria and fungi) diversity. In addition, inter-cropping could greatly increase the inter-root soil carbon sequestration (PccA, korA/B/C/D, fhs, and rbcl/s), carbon degradation (abfD), organic nitrogen mineralization (GDH2), denitrification (napA/B, nirB, norB), organic phosphorus mineralization (phop, phn), and inorganic phosphorus solubilization (gcd, ppk) gene abundance. The gene co-occurrence network indicated that soil korB, nirB, and gnd key functional genes for carbon, nitrogen, and phosphorus cycling in kiwifruit inter-root soils and their expression was up-regulated in the inter-cropping group. Structural equation (SEM) further showed that soil total nitrogen, organic matter, total carbon and acid phosphatase had significant effects on microbial diversity (p < 0.05) and soil carbon cycling gene korB and phosphorus cycling gene purH (p < 0.001), while korB and purH had positive effects on kiwifruit quality. In conclusion, intercropping perilla in kiwifruit orchards changed the structure of bacterial and fungal communities in the inter-root soil of kiwifruit, but I believe that intercropping perilla stimulates carbon degradation, leading to carbon emission and serious loss of soil nutrients, and that prolonged intercropping may adversely affect the quality of kiwifruit, and thus its limitations should be noted in future studies.

Rutaecarpine Alleviates Early Brain Injury-Induced Inflammatory Response Following Subarachnoid Hemorrhage via SIRT6/NF-[Formula: see text]B Pathway.

Subarachnoid hemorrhage (SAH), a specific subtype of cerebrovascular accident, is characterized by the extravasation of blood into the interstice between the brain and its enveloping delicate tissues. This pathophysiological phenomenon can precipitate an early brain injury (EBI), which is characterized by inflammation and neuronal death. Rutaecarpine (Rut), a flavonoid compound discovered in various plants, has been shown to have protective effects against SAH-induced cerebral insult in rodent models. In our study, we used a rodent SAH model to evaluate the effect of Rut on EBI and investigated the effect of Rut on the inflammatory response and its regulation of SIRT6 expression in vitro. We found that Rut exerts a protective effect on EBI in SAH rats, which is partly due to its ability to inhibit the inflammatory response. Notably, Rut up-regulated Sirtuin 6 (SIRT6) expression, leading to an increase in H3K9 deacetylation and inhibition of nuclear factor-kappa B (NF-[Formula: see text]B) transcriptional activation, thereby mediating the inflammatory response. In addition, further data showed that SIRT6 was proven to mediate the regulation of Rut on the microglial inflammatory response. These findings highlight the importance of SIRT6 in the regulation of inflammation and suggest a potential mechanism for the protective effect of Rut on EBI. In summary, Rut may have the potential to prevent and treat SAH-induced brain injury by interacting with SIRT6. Our findings may provide a new therapeutic strategy for the treatment of SAH-induced EBI.

Suanzaoren decoction exerts its antidepressant effect via the CaMK signaling pathway.

Calmodulin-dependent protein kinases (CaMKs) are widely regarded as "memory molecules" due to their role in controlling numerous neuronal functions in the brain, and the CaMK signaling pathway plays a crucial role in controlling synaptic plasticity. Suanzaoren decoction (SZRD) can improve depression-like behavior and thus has potential benefits in the clinical treatment of depression; however, its mechanism of action is not fully understood. In this study, we found that key proteins in the CaMK signaling pathway were regulated by the decoction used to treat depression. The purpose of this research was to ascertain if the SZRD's therapeutic efficacy in the treatment of depression is associated with the modulation of key proteins in the CaMK signaling pathway. A rat model of depression was created by exposing the animals to chronic, unexpected, mild stress. Model rats were given intragastric administration of SZRD or fluoxetine every morning once a day. Protein and mRNA relative expression levels of CaM, CaMK I, and CaMK IV in the hippocampus were measured by Western blot, quantitative polymerase chain reaction, and immunohistochemistry in the hippocampus. Our findings demonstrated that SZRD significantly improved the mood of depressed rats. This indicates that SZRD, by modulating the CaMK signaling system, may alleviate depressive symptoms and lessen work and life-related pressures.

Managing the quality of primary health care in urban China: the impact of organizational and physician features.

BACKGROUND: Global health care quality improvement efforts have focussed on management practices. However, knowledge in primary care settings, especially in developing countries, such as China, is lacking. OBJECTIVE: To examine the organizational and physician features associated with health care quality in China's community health centres (CHCs). METHODS: We conducted a cross-sectional survey of 224 primary care physicians (PCPs) in 38 CHCs in Jinan, Tianjin, Shenzhen, and Shanghai. Clinical and prevention care quality with a 5-level scale (1 = never, 5 = always) reported by the PCPs were used to measure the quality of care. Two-level hierarchical linear models were estimated to examine the organization and physician-level variables associated with primary care quality. RESULTS: The average clinical care quality score was 4.08 and 3.59 for preventative care out of 5. At the organizational level, organizational culture and organizational support were the strongest predictors of physician-reported quality of care. At the physician level, professional fulfilment, psychological safety, and organizational citizenship behaviour were positively associated with care quality. CONCLUSIONS: Chinese CHCs clinical quality ranked high by PCPs, but the quality of preventative care provision required improvement. To improve primary care quality, managers of CHCs should implement optimal organizational structures, supportive organizational cultures, and strong organizational support at the organization level and cultivate high professional fulfilment, safe, and trustful relationships with colleagues at the physician level.

Adverse childhood experiences and subsequent physical and mental health among young adults: Results from six universities in China.

Research has shown that individuals with adverse childhood experiences (ACEs) are more likely to encounter heightened risks of physical and psychological challenges later in life. However, limited research has explored the comprehensive impact on the physical and mental health of young adults. Thus, we conducted a study to investigate the associations of ACEs with the physical and mental health of 18,723 college students in China. Their physical and mental health status was assessed using self-perceived health assessments, self-reported disease diagnoses, and the Generalized Anxiety Disorder-7-item scale. Results showed that 82.6 % of participants had experienced at least one ACE, with 10.7 % reporting exposure to four or more ACEs. Compared to participants with low ACEs exposure (≤ 1), participants with high ACEs exposure (≥ 4) had a nearly twofold increase in the odds of cardiometabolic diseases (OR [95 % CI] = 2.06 [1.55-2.74]) and fractures (2.32 [1.88-2.87]). Additionally, individuals with high ACE exposure exhibited a threefold increased odds of severe anxiety symptoms (3.78 [2.59-5.51]) and bipolar disorder/schizophrenia (3.38 [2.18-5.23]). These findings highlight ACEs as a significant risk factor for poor physical and mental health among young adults. Targeted support and interventions for individuals with multiple ACEs may help mitigate their long-term disease burden.

Variance, norms and cooperative behavior in public goods games.

This study examines the relationship between the variance of others' contributions, social norms (empirical and normative expectations), and cooperative behavior using a classic linear public goods game. The following results are observed. First, the variance of a participant's group members' contributions had a negative impact on their contributions, empirical expectations, and normative expectations. Second, deviations from the mean, whether negative or positive, were deemed less socially appropriate. Third, while there was a strong relationship between variance, social norms, and cooperative behavior, the mediating effect of social norms was found to be insignificant. Finally, there were some notable findings regarding behavior type. Although free riders and cooperators exhibited distinct behavioral patterns, their normative expectations were similar. Free riders expected others to cooperate, but their empirical expectations were significantly lower than cooperators' expectations, which were aligned with their actual contributions. These findings contribute to research on the relationship between distribution heterogeneity, social norms and cooperative behavior. Furthermore, these findings provide valuable insights into management practices.

Amelioration of nitroglycerin-induced migraine in mice via Wuzhuyu decoction: Inhibition of the MZF1/PGK1 pathway and activation of NRF2 antioxidant response.

ETHNOPHARMACOLOGICAL RELEVANCE: Migraine, a chronic and intricate disorder, manifests as recurrent episodic headaches accompanied by various neurological symptoms. Wuzhuyu Decoction (WZYD) is a traditional Chinese medical formula with promising effects in treating migraines; however, its underlying mechanisms have not yet been clarified. AIM OF STUDY: The study aimed to evaluate WZYD's effectiveness in migraine treatment and investigate the potential mechanism of WZYD's effects on migraine and oxidative stress. MATERIALS AND METHODS: Behavior tests and immunofluorescence assay for the intensity of migraine markers to assess the migraine-relieving effect of WZYD after chronic migraine model induced by nitroglycerin in mice. The impacts of WZYD on oxidative stress-related markers, including reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO1), and NAD (P)H quinone oxidoreductase 1 (NQO1) in brain tissue were examined. In addition, protein expression or mRNA levels of the MZF1/PGK1 were detected using Western blot or PCR, respectively. Finally, the MZF1 overexpression vector was constructed to the higher level of MZF1. The MZF1/PGK1 signaling pathway expression was evaluated by markers of oxidative stress including NRF2 and others in this series of experiments. RESULTS: Through murine model experimentation, we observed that WZYD effectively alleviates migraine symptoms, signifying its therapeutic efficacy. Mechanistically, WZYD emerges as a potent activator of the NRF2, acting as a robust defense against oxidative stress. In vitro investigations demonstrated that WZYD combats oxidative stress and curbs cell apoptosis induced by these detrimental conditions. Furthermore, by suppressing the transcriptional expression of PGK1, an influential player in the NRF2 pathway, WZYD effectively activates NRF2 signaling. Intriguingly, we have identified MZF1 as the mediator orchestrating the regulation of the PGK1/NRF2 pathway by WZYD. CONCLUSION: The study confirms the effectiveness of WZYD in alleviating migraine symptoms. Mechanistically, WZYD activated the NRF2 signaling pathway; moreover, the action of WZYD involved the down-regulation of PGK1 mediated by MZF1, which promoted the activation of the NRF2 pathway. This study advances our understanding of the intricate mechanisms driving WZYD's efficacy, paving the way for novel treatments in migraine management.

TIGIT: A potential immunotherapy target for gynecological cancers.

Gynecological cancer represents a significant global health challenge, and conventional treatment modalities have demonstrated limited efficacy. However, recent investigations into immune checkpoint pathways have unveiled promising opportunities for enhancing the prognosis of patients with cancer. Among these pathways, TIGIT has surfaced as a compelling candidate owing to its capacity to augment the immune function of NK and T cells through blockade, thereby yielding improved anti-tumor effects and prolonged patient survival. Global clinical trials exploring TIGIT blockade therapy have yielded promising preliminary findings. Nevertheless, further research is imperative to comprehensively grasp the potential of TIGIT-based immunotherapy in optimizing therapeutic outcomes for gynecological cancers. This review primarily delineates the regulatory network and immunosuppressive mechanism of TIGIT, expounds upon its expression and therapeutic potential in three major gynecological cancers, and synthesizes the clinical trials of TIGIT-based cancer immunotherapy. Such insights aim to furnish novel perspectives and serve as reference points for subsequent research and clinical application targeting TIGIT in gynecological cancers.

Fine particle trace elements at a mountain site in southern China: Source identification, transport, and health risks.

Trace elements in atmospheric particulate matter play a significant role in air quality, human health, and biogeochemical cycles. In this study, the trace elements (Ca, Al, K, Fe, Na, Mg, Zn, Pb, Mn, Ti, Cu, Cr, Sr, Ni) in PM2.5 samples collected at the summit of Mt. Lushan were analyzed to quantify their abundance, source, transport, and health risks. During the whole sampling period, the major trace elements was Ca, Al, and K. While the trace metals with the lowest concentrations were Sr, Ni, Rb, and Cd. The trace elements were influenced by air mass transport routes, exhibiting an increasing trend of crustal elements in the northwesterly airmass and anthropogenic elements (Zn, Mn, Cu, and Ni) in the easterly air masses. Construction dust, coal + biomass burning, vehicle emission, urban nitrate-rich + urban waste incineration emissions, and soil dust + industry emissions were common sources of PM2.5 on Mt. Lushan. Different air mass transport routes had various source contribution patterns. These results indicate that trace elements at Mt. Lushan are influenced by regional anthropogenic emissions and monsoon-dominated trace element transport. The total resulting cancer risk value that these elements posed were below the acceptable risk value of 1 × 10-6, while the non-carcinogenic risk value (1.72) was higher than the safety level, suggesting that non-carcinogenic effects due to these trace elements inhalation were likely to occur. Vehicle emission and coal + biomass burning were the common dominant sources of non-cancer risks posed by trace elements at Mt. Lushan.

The organization-level and physician-level factors associated with primary care physicians' confidence in pandemic response: A multilevel study in China.

Primary care physicians (PCPs) suffered from heavy workloads and health problems during COVID-19 pandemics, and building their confidence in pandemic response has great potential to improve their well-being and work performance. We identified the organizational factors associated with their confidence in pandemic response and proposed potential management levers to guide primary care response for the pandemic. We conducted a cross-sectional survey with 224 PCPs working in 38 community health centers in China. Guided by self-efficacy theory, organization-level factors (organizational structure and organizational culture) and physician-level factors (job skill variety, perceived organizational support, work-family conflict, and professional fulfillment) were selected, and two-level ordinal logit models were built to examine their association with PCPs' confidence in pandemic response. We found that hierarchical culture (OR = 3.51, P<0.05), perceived organizational support (OR = 2.36, P<0.05), job skill variety (OR = 1.86, P<0.05), and professional fulfillment (OR = 2.26, P<0.05) were positively associated with PCPs' confidence in pandemic response. However, the influence of organization structure and work-family conflict seemed limited. The study not only increases our understanding of the influence of organizational context on PCPs' pandemic response confidence, but also points out potential management levers for front-line primary care managers to enhance primary care pandemic response capacity.

Confusion cannot explain cooperative behavior in public goods games.

Some scholars find that behavioral variation in the public goods game is explained by variations in participants' understanding of how to maximize payoff and that confusion leads to cooperation. Their findings lead them to question the common assumption in behavioral economics experiments that choices reflect motivations. We conduct two experiments, in which we minimize confusion by providing participants with increased training. We also introduce a question that specifically assesses participants' understanding of payoff maximization choices. Our experimental results show that the distribution of behavior types is significantly different when participants play with computers versus humans. A significant increase in contributions is also observed when participants play with humans compared to when they play with computers. Moreover, social norms may be the main motive for contributions when playing with computers. Our findings suggest that social preferences, rather than confusion, play a crucial role in determining contributions in public goods games when playing with humans. We therefore argue that the assumption in behavioral economics experiments that choices reveal motivations is indeed valid.

The relationship between mobile phone addiction and non-suicidal self-injury: Findings from six universities in Shaanxi province, China.

BACKGROUND: Although the development and application of mobile phones have changed various aspects of people's lives, excessive use of mobile phones has also raised physical and mental health concerns. However, the relationship between mobile phone addiction (MPA) and non-suicidal self-injury (NSSI) is unclear. METHODS: A cross-sectional study was conducted (2022) among students from six universities to assess the relationship between MPA and NSSI. A Mobile Phone Addiction Tendency Scale (MPATS) was used to assess MPA, while NSSI was assessed via The Ottawa Self-Injury Inventory. Binary logistic regression models were used to assess the relationship between MPA and NSSI. RESULTS: A total of 18,723 college students (6531 males [34.9 %] and 12,192 females [65.1 %]) were included in the final analyses. The prevalence of NSSI during the past 12 months was 6.5 %. Furthermore, 5553 participants (29.7 %) met the MPA criteria (MPATS score ≥ 48), and the average MPATS score was 39.5 ± 13.0. MPA was associated with increased odds of NSSI after adjusting for socio-demographic characteristics, health-related characteristics, and relevant psychosocial variables (OR, 1.29; 95 % CI, 1.13-1.46). Moreover, gender did not affect the association of MPA and MPATS score with NSSI (P for interaction>0.05). The restricted cubic splines regression showed that a monotonically increasing risk of NSSI was associated with increasing MPATS score (P for non-linearity = 0.474). CONCLUSIONS: MPA is associated with increased odds of NSSI among college students, indicating that early examination, prevention, and intervention for MPA may prevent and control NSSI.

Dehydroevodiamine ameliorates neurological dysfunction after traumatic brain injury in mice via regulating the SIRT1/FOXO3a/Bim pathway.

BACKGROUND: Traumatic Brain Injury (TBI) poses a considerable public health challenge, resulting in mortality, disability, and economic strain. Dehydroevodiamine (DEDM) is a natural compound derived from a traditional Chinese herbal medicine. Prior studies have substantiated the neuroprotective attributes of this compound in the context of TBI. Nevertheless, a comprehensive comprehension of the exact mechanisms responsible for its neuroprotective effects remains elusive. It is imperative to elucidate the precise intrinsic mechanisms underlying the neuroprotective actions of DEDM. PURPOSE: The aim of this investigation was to elucidate the mechanism underlying DEDM treatment in TBI utilizing both in vivo and in vitro models. Specifically, our focus was on comprehending the impact of DEDM on the Sirtuin1 (SIRT1) / Forkhead box O3 (FOXO3a) / Bcl-2-like protein 11 (Bim) pathway, a pivotal player in TBI-induced cell death attributed to oxidative stress. STUDY DESIGN AND METHODS: We established a TBI mouse model via the weight drop method. Following continuous intraperitoneal administration, we assessed the neurological dysfunction using the Modified Neurological Severity Score (mNSS) and behavioral assay, followed by sample collection. Secondary brain damage in mice was evaluated through Nissl staining, brain water content measurement, Evans blue detection, and Western blot assays. We scrutinized the expression levels of oxidative stress-related indicators and key proteins for apoptosis. The intricate mechanism of DEDM in TBI was further explored through immunofluorescence, Co-immunoprecipitation (Co-IP) assays, real-time quantitative PCR (RT-qPCR), dual-luciferase assays and western blotting. Additionally, we further investigated the specific therapeutic mechanism of DEDM in an oxidative stress cell model. RESULTS: The results indicated that DEDM effectively ameliorated oxidative stress and apoptosis post-TBI, mitigating neurological dysfunction and brain injury in mice. DEDM facilitated the deacetylation of FOXO3a by up-regulating the expression of the deacetylase SIRT1, consequently suppressing Bim expression. This mechanism contributed to the alleviation of neurological injury and symptom improvement in TBI-afflicted mice. Remarkably, SIRT1 emerged as a central mediator in the overall treatment mechanism. CONCLUSIONS: DEDM exerted significant neuroprotective effects on TBI mice by modulating the SIRT1/FOXO3a/Bim pathway. Our innovative research provides a basis for further exploration of the clinical therapeutic potential of DEDM in the context of TBI.

Electronic health record and primary care physician self-reported quality of care: a multilevel study in China.

BACKGROUND: Health information technology is one of the building blocks of a high-performing health system. However, the evidence regarding the influence of an electronic health record (EHR) on the quality of care remains mixed, especially in low- and middle-income countries. OBJECTIVE: This study examines the association between greater EHR functionality and primary care physician self-reported quality of care. METHODS: A total of 224 primary care physicians from 38 community health centres (CHCs) in four large Chinese cities participated in a cross-sectional survey to assess CHC care quality. Each CHC director scored their CHC's EHR functionality on the availability of ten typical features covering health information, data, results management, patient access, and clinical decision support. Data analysis utilised hierarchical linear modelling. RESULTS: The availability of five EHR features was positively associated with physician self-reported clinical quality: share records online with providers outside the practice (ß = 0.276, p = 0.04), access records online by the patient (ß = 0.325, p = 0.04), alert provider of potential prescription problems (ß = 0.353, p = 0.04), send the patient reminders for care (ß = 0.419, p = 0.003), and list patients by diagnosis or health risk (ß = 0.282, p = 0.04). However, no association was found between specific features availability or total features score and physician self-reported preventive quality. CONCLUSIONS: This study provides evidence that the availability of EHR systems, and specific features of these systems, was positively associated with physician self-reported quality of care in these 38 CHCs. Future longitudinal studies focused on standardised quality metrics, and designed to control known confounding variables, will further inform quality improvement efforts in primary care.

Fenpropathrin disrupted the gills of common carp (Cyprinus carpio L.) through oxidative stress, inflammatory responses, apoptosis, and transcriptional alterations.

Fenpropathrin (FEN) is an extensively utilized synthetic pyrethroid insecticide frequently found in aquatic ecosystems. However, the adverse effects and potential mechanisms of FEN on aquatic species are poorly understood. In this work, common carp were treated with FEN at concentrations of 0.45 and 1.35 µg/L FEN for 14 days, after which the tissue structure, physiological alterations, and mRNA transcriptome of the gills were evaluated. Specifically, FEN exposure caused pathological damage to the gills of carp, downregulated the levels of claudin-1, occludin, and zonula occluden-1 (ZO-1), and inhibited Na+-K+-ATPase activity in the gills. In addition, FEN exposure promoted an increase in reactive oxygen species (ROS) levels and significantly upregulated the levels of malondialdehyde (MDA), 8-hydroxy-2 deoxyguanosine (8-OHdG), and protein carbonyl (PC) in the gills. Moreover, the inflammation-related indices (TNF-α, IL-1ß, and IFN-γ) and the apoptosis-related parameter caspase-3 were generally increased, especially in the 1.35 µg/L FEN group, and these indices were significantly greater than those in the control group. These findings suggest that FEN exposure can cause oxidative stress, the inflammatory response, and apoptosis in carp gills. Importantly, the results of RNA-seq analysis showed that 0.45 and 1.35 µg/L FEN could significantly interfere with multiple immune and metabolic pathways, including the phagosome, NOD-like receptor (NLR) signalling pathway, Toll-like receptor (TLR) signalling pathway, necroptosis, and arachidonic acid metabolism pathways, indicating that the effects of FEN on the gills of fish are intricate. In summary, our findings confirm the toxic effects of FEN on common carp gills and provide additional comprehensive information for evaluating the toxicity and underlying molecular mechanisms of FEN in aquatic organisms.

Wu-zhu-yu Decoction reduces early brain injury following subarachnoid hemorrhage in vivo and in vitro by activating the Nrf2 antioxidant system via SIRT6 targeting.

ETHNOPHARMACOLOGICAL RELEVANCE: Early brain damage (EBI) following subarachnoid hemorrhage (SAH) is a long-lasting condition with a high occurrence. However, treatment options are restricted. Wu-zhu-yu Decoction (WZYD) can treat headaches and vomiting, which are similar to the early symptoms of subarachnoid hemorrhage (SAH). However, it is yet unknown if WZYD can reduce EBI following SAH and its underlying mechanisms. AIM OF THE STUDY: This study aimed to investigate whether WZYD protects against EBI following SAH by inhibiting oxidative stress through activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling via Sirtuin 6 (SIRT6)-mediated histone H3 lysine 56 (H3K56) deacetylation. MATERIALS AND METHODS: In the current investigation, the principal components of WZYD were identified using high-performance liquid chromatography-diode array detection (HPLC-DAD). The SAH model in rats using the internal carotid artery plug puncture approach and the SAH model in primary neurons using hemoglobin incubation were developed. WZYD with different doses (137 mg kg-1, 274 mg kg-1, 548 mg kg-1) and the positive drug-Nimodipine (40 mg kg-1) were intragastrically administered in SAH model rats, respectively. The PC12 cells were cultured with corresponding medicated for 24h. In our investigation, neurological scores, brain water content, Evans blue leakage, Nissl staining, TUNEL staining, oxidative stress, expression of apoptosis-related proteins, and Nrf2/HO-1 signaling were evaluated. The interaction between SIRT6 and Nrf2 was detected by co-immunoprecipitation. SIRT6 knockdown was used to confirm its role in WZYD's neuroprotection. RESULTS: The WZYD treatment dramatically reduced cerebral hemorrhage and edema, and enhanced neurological results in EBI following SAH rats. WZYD administration inhibited neuronal apoptosis via reducing the expression levels of Cleaved cysteinyl aspartate specific proteinase-3(Cleaved Caspase-3), cysteinyl aspartate specific proteinase-3(caspase-3), and Bcl-2, Associated X Protein (Bax) and increasing the expression of B-cell lymphoma-2(Bal2). It also decreased reactive oxygen species and malondialdehyde levels and increased Nrf2 and HO-1 expression in the rat brain after SAH. In vitro, WZYD attenuated hemoglobin-induced cytotoxicity, oxidative stress and apoptosis in primary neurons. Mechanistically, WZYD enhanced SIRT6 expression and H3K56 deacetylation, activated Nrf2/HO-1 signaling, and promoted the interaction between SIRT6 and Nrf2. Knockdown of SIRT6 abolished WZYD-induced neuroprotection. CONCLUSIONS: WZYD attenuates EBI after SAH by activating Nrf2/HO-1 signaling through SIRT6-mediated H3K56 deacetylation, suggesting its therapeutic potential for SAH treatment.

Retrospective cohort study of neonatal blood transfusion in China.

BACKGROUND: Blood transfusion therapy is extremely important for certain neonatal diseases, but the threshold for neonatal blood transfusion is not the same in different countries. Until now, clinical studies to determine the suitable threshold for newborns in China are lacking. Therefore, it is of high importance to establish a multi-center cohort study to explore appropriate transfusion thresholds for newborns in China. METHODS: This retrospective cohort study investigated neonatal blood transfusion therapy administered from January 1, 2017 to June 30, 2018, with the aim of evaluating the effect of restricted and nonrestricted blood transfusion on neonatal health. The subjects were enrolled in 46 hospitals in China. A total of 5669 neonatal cases were included in the study. Clinical diagnosis and transfusion treatment of these neonates were collected and the data were retrospectively analyzed. The neonates were followed up 1 week and 1 month after leaving the hospital. The newborns' and their mothers' data were collected containing 280 variables in the database. The primary outcome of the study was mortality, and the secondary outcomes were complications, hospital stays, NICU hospital stays and hospital costs. RESULTS: Results from the < 1500 g group showed that there was a higher mortality rate in the restricted transfusion group (11.41%) when compared with the non-restricted transfusion group (5.12%) (P = 0.000). Among the secondary outcomes, the restricted transfusion group had fewer costs. Results from the 1500-2500 g group showed that the mortality rates of the restricted and non-restricted transfusion groups were 3.53% and 4.71%, respectively, however there was no statistical significance between the two groups (P = 0.345). Among the secondary outcomes, the restricted transfusion group had fewer hospital stays, NICU hospital stays and hospital costs. The incidence of necrotizing enterocolitis was lower in the restricted transfusion group (OR, 2.626; 95% confidence interval [CI], 1.445 to 4.773; P = 0.003). The results from the ≥ 2500 g restricted transfusion group suggested that the mortality rate of (3.02%) was significantly lower than that of non-restricted transfusion group (9.55%) (P = 0.000). Among the secondary outcomes, the restricted transfusion group had fewer hospital stays and hospital costs. The incidence of retinopathy of prematurity was lower in the restricted transfusion group (OR, 4.624; 95% confidence interval [CI], 2.32 to 9.216; P = 0.000). CONCLUSIONS: Current transfusion protocols for newborns weighing less than 1500 g may be inappropriate and lead to higher mortality. The current transfusion threshold performed better for the other two weight groups.

Endothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has impacted approximately 390 million people worldwide and the morbidity is increasing every year. However, due to the poor treatment efficacy of COPD, exploring novel treatment has become the hotpot of study on COPD. Endothelial progenitor cells (EPCs) aging is a possible molecular way for COPD development. We aimed to explore the effector whether intravenous administration of EPCs has therapeutic effects in COPD mice. METHODS: COPD mice model was induced by cigarette smoke exposure and EPCs were injected intravenously to investigate their effects on COPD mice. At day 127, heart, liver, spleen, lung and kidney tissues of mice were harvested. The histological effects of EPCs intervention on multiple organs of COPD mice were detected by morphology assay. Quantitative real-time PCR and Western blotting were used to detect the effect of EPCs intervention on the expression of multi-organ senescence-related indicators. And we explored the effect of EPCs systematically intervening on senescence-related USP7/p300 pathway. RESULTS: Compared with COPD group, senescence-associated ß-galactosidase activity was decreased, protein and mRNA expression of p16 was down-regulated, while protein and mRNA expression of cyclin D1 and TERT were up-regulated of multiple organs, including lung, heart, liver, spleen and kidney in COPD mice after EPCs system intervention. But the morphological alterations of the tissues described above in COPD mice failed to be reversed. Mechanistically, EPCs systemic administration inhibited the expression of mRNA and protein of USP7 and p300 in multiple organs of COPD mice, exerting therapeutic effects. CONCLUSIONS: EPCs administration significantly inhibited the senescence of multiple organs in COPD mice via down-regulating USP7/p300 pathway, which presents a possibility of EPCs therapy for COPD.

Full hardware implementation of neuromorphic visual system based on multimodal optoelectronic resistive memory arrays for versatile image processing.

In-sensor and near-sensor computing are becoming the next-generation computing paradigm for high-density and low-power sensory processing. To fulfil a high-density and efficient neuromorphic visual system with fully hierarchical emulation of the retina and visual cortex, emerging multimodal neuromorphic devices for multi-stage processing and a fully hardware-implemented system with versatile image processing functions are still lacking and highly desirable. Here we demonstrate an emerging multimodal-multifunctional resistive random-access memory (RRAM) device array based on modified silk fibroin protein (MSFP), exhibiting both optoelectronic RRAM (ORRAM) mode featured by unique negative and positive photoconductance memory and electrical RRAM (ERRAM) mode featured by analogue resistive switching. A full hardware implementation of the artificial visual system with versatile image processing functions is realised for the first time, including ORRAM mode array for the in-sensor image pre-processing (contrast enhancement, background denoising, feature extraction) and ERRAM mode array for near-sensor high-level image recognition, which hugely improves the integration density, and simply the circuit design and the fabrication and integration complexity.