Silk-protein-based gradient hydrogels with multimode reprogrammable shape changes for biointegrated devices.

Biocompatible and morphable hydrogels capable of multimode reprogrammable, and adaptive shape changes are potentially useful for diverse biomedical applications. However, existing morphable systems often rely on complicated structural designs involving cumbersome and energy-intensive fabrication processes. Here, we report a simple electric-field-activated protein network migration strategy to reversibly program silk-protein hydrogels with controllable and reprogrammable complex shape transformations. The application of a low electric field enables the convergence of net negatively charged protein cross-linking networks toward the anode (isoelectric point plane) due to the pH gradient generated in the process, facilitating the formation of a gradient network structure and systems suitable for three-dimensional shape change. These tunable protein networks can be reprogrammed or permanently fixed by control of the polymorphic transitions. We show that these morphing hydrogels are capable of conformally interfacing with biological tissues by programming the shape changes and a bimorph structure consisting of aligned carbon nanotube multilayers and the silk hydrogels was assembled to illustrate utility as an implantable bioelectronic device for localized low-voltage electrical stimulation of the sciatic nerve in a rabbit.

High-nitrogen-induced γ-aminobutyric acid triggers host immunity and pathogen oxidative stress tolerance in tomato and Ralstonia solanacearum interaction.

Soil nitrogen (N) significantly influences the interaction between plants and pathogens, yet its impact on host defenses and pathogen strategies via alterations in plant metabolism remains unclear. Through metabolic and genetic studies, this research demonstrates that high-N-input exacerbates tomato bacterial wilt by altering γ-aminobutyric acid (GABA) metabolism of host plants. Under high-N conditions, the nitrate sensor NIN-like protein 7 (SlNLP7) promotes the glutamate decarboxylase 2/4 (SlGAD2/4) transcription and GABA synthesis by directly binding to the promoters of SlGAD2/4. The tomato plants with enhanced GABA levels showed stronger immune responses but remained susceptible to Ralstonia solanacearum. This led to the discovery that GABA produced by the host actually heightens the pathogen's virulence. We identified the R. solanacearum LysR-type transcriptional regulator OxyR protein, which senses host-derived GABA and, upon interaction, triggers a response involving protein dimerization that enhances the pathogen's oxidative stress tolerance by activating the expression of catalase (katE/katGa). These findings reveal GABA's dual role in activating host immunity and enhancing pathogen tolerance to oxidative stress, highlighting the complex relationship between tomato plants and R. solanacearum, influenced by soil N status.

The c-Abl-RACK1-FAK signaling axis promotes renal fibrosis in mice through regulating fibroblast-myofibroblast transition.

BACKGROUND: Renal fibrosis is a prevalent manifestation of chronic kidney disease (CKD), and effective treatments for this disease are currently lacking. Myofibroblasts, which originate from interstitial fibroblasts, aggregate in the renal interstitium, leading to significant accumulation of extracellular matrix and impairment of renal function. The nonreceptor tyrosine kinase c-Abl (encoded by the Abl1 gene) has been implicated in the development of renal fibrosis. However, the precise role of c-Abl in this process and its involvement in fibroblast-myofibroblast transition (FMT) remain poorly understood. METHODS: To investigate the effect of c-Abl in FMT during renal fibrosis, we investigated the expression of c-Abl in fibrotic renal tissues of patients with CKD and mouse models. We studied the phenotypic changes in fibroblast or myofibroblast-specific c-Abl conditional knockout mice. We explored the potential targets of c-Abl in NRK-49F fibroblasts. RESULTS: In this study, fibrotic mouse and cell models demonstrated that c-Abl deficiency in fibroblasts mitigated fibrosis by suppressing fibroblast activation, fibroblast-myofibroblast transition, and extracellular matrix deposition. Mechanistically, c-Abl maintains the stability of the RACK1 protein, which serves as a scaffold for proteins such as c-Abl and focal adhesion kinase at focal adhesions, driving fibroblast activation and differentiation during renal fibrosis. Moreover, specifically targeting c-Abl deletion in renal myofibroblasts could prove beneficial in established kidney fibrosis by reducing RACK1 expression and diminishing the extent of fibrosis. CONCLUSIONS: Our findings suggest that c-Abl plays a pathogenic role in interstitial fibrosis through the regulation of RACK1 protein stabilization and myofibroblast differentiation, suggesting a promising strategy for the treatment of CKD.

Effect of sodium selenite on the synthesis of glucosinolates and antioxidant capacity in Chinese cabbage (Brassica rapa L.ssp.pekinensis).

Chinese cabbage (Brassica rapa ssp. pekinensis) is a globally cultivated and consumed leafy vegetable due to its abundant plant secondary metabolites and antioxidant compounds, including flavonoids, ascorbic acids, glucosinolates, and vitamins, which have been reported to confer health-promoting effects. Glucosinolates components in leaves of Chinese cabbage plantlets under different concentrations of sodium selenite (0, 30, and 50 µmol/L) were analyzed. Seven glucosinolates were identified and quantified using UHPLC-QTOF-MS. Finally, treatments with 30 and 50 µmol/L Na2SeO3 solution significantly increased the levels of total selenium content as well as total phenols, flavonoids, anthocyanins, and DPPH free radical scavenging ability in Chinese cabbage seedlings. Our results revealed that 30 µmol/L Na2SeO3 effectively enhanced aliphatic glucosinolate levels and total glucosinolate content while causing a significant reduction in indole glucosinolates. Furthermore, downregulation was observed for BrCYP79F1, BrBCAT4, and BrMAM1 genes associated with aliphatic glucosinolate synthesis. Conversely, BrMYB28 and BrCYP83A1 genes exhibited significant upregulation. Thus, the positive influence of Na2SeO3 on glucosinolate biosynthesis in Chinese cabbage can be attributed to the upregulation of key genes related to this process.

Clinical characteristics and factors for serious outcomes among outpatients infected with the Omicron subvariant BF.7.

To evaluate clinical characteristics and identify risk factors associated with severe outcomes in outpatients infected with the Omicron subvariant BF.7, data were collected from outpatients diagnosed with Corona Virus Disease 2019 from December 19, 2022 to January 5, 2023. Clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with serious outcomes. Variables with a p < 0.10 in the univariate analysis were included in the multivariate model. Our study analyzed 770 patients, of whom 380 (49.4%) were male, with a median age of 59. The most common symptoms reported were cough (71.2%), fever (64.7%), and sore throat (37.7%). Fever lasted an average of 5.93 ± 3.37 days for the general population and 10.64 ± 7.12 days for impaired-immunity patients. Most cases were mild (68.7%), followed by moderate (27.1%). Severe cases accounted for 2.2%, with 0.5% critically ill. Serious outcomes occurred in 4.2% of cases, with 11 deaths during follow-up. Underlying-diseases patients had a higher rate of serious outcomes. Factors associated with serious outcomes included receiving a three-dose vaccination (odds ratio [OR] = 0.324, 95% confidence interval [CI]: 0.113-0.932, p = 0.037), male gender (OR = 2.890, 95% CI: 1.107-7.548, p = 0.030), age (OR = 1.060, 95% CI: 1.024-1.097, p = 0.001), and chest tightness or dyspnea at the time of visit (OR = 4.861, 95% CI: 2.054-11.507, p < 0.001). Our study found that cough, fever, and sore throat were the most common symptoms reported by patients. Receiving a three-dose vaccination was protective, while male gender, age, and chest tightness or dyspnea were identified as risk factors for serious outcomes.

Oral azvudine for mild-to-moderate COVID-19 in high risk, nonhospitalized adults: Results of a real-world study.

Azvudine is recommended by Chinese health authorities for COVID-19 treatment but has not been tested in real-world clinical studies. This study aimed to evaluate the real-world effectiveness of Azvudine among COVID-19 nonhospitalized patients. This was a retrospective cohort study, looking at nonhospitalized patients who tested positive for SARS-CoV-2. Patients admitted between December 19, 2022 and January 5, 2023 were included. Those who received Azvudine treatment were in the Azvudine group, while those who received supportive treatment were the control group. The primary outcome was the disease progression rate by Day 28. Secondary outcomes were individual disease progression outcomes (death or COVID-19-related hospitalization) and duration of fever. The safety outcomes were assessed based on adverse events (AEs) overall, as well as AEs that were considered to be related to the drug. A total of 804 patients with high risk for progression were enrolled in our study. Among them, 317 (39.43%) received treatment with Azvudine. Our study found that Azvudine could reduce the rate of disease progression, as well as rate of COVID-19-related hospitalization in patients comparing the control group. Furthermore, if taken within 3 days of the onset of symptoms, it could also shorten the duration of fever. Despite a higher incidence of drug-related AEs compared to supportive treatment, the majority of these were mild. Azvudine has been found to be effective in reducing the rate of disease progression of COVID-19, albeit with a slight increase in AEs.

All-fiber cyan laser at 491.5 nm.

We report, for the first time to our knowledge, a compact continuous-wave all-fiber cyan laser. The all-fiber cavity consists of a 443-nm fiber-pigtail laser diode as pump source, a 4.5-cm single-clad Pr3+-doped fluoride fiber, and two custom-built dielectric-coated fiber-pigtail mirrors in the visible spectral region. Downconversion cyan lasing at 491.5 nm is directly achieved, providing a maximum output power of 97.5 mW with a slope efficiency of 23.7% and a power fluctuation of less than 0.41%. Such a compact all-fiber cyan laser may be of great significance to expand the color reproduction range of laser displays, and has potential applications in fluorescence imaging, underwater communication, and detection.

Foxp1 and Foxp4 Deletion Causes the Loss of Follicle Stem Cell Niche and Cyclic Hair Shedding by Inducing Inner Bulge Cell Apoptosis.

Quiescent hair follicle stem cells (HFSCs) reside in specialized bulge niche where they undergo activation and differentiation upon sensing niche-dependent signals during hair follicle (HF) homeostasis and wound repair. The underlying mechanism of HFSCs and bulge niche maintenance is poorly understood. Our previous study has reported that a transcription factor, forkhead box P1 (Foxp1), functions to maintain the quiescence of HFSCs. Here, we further discovered that forkhead box P4 (Foxp4), a close family member of Foxp1, had similar expression profiles in various components of HFs and formed a complex with Foxp1 in vitro and in vivo. The HF-specific deficiency of Foxp4 resulted in the precocious activation of HFSCs during hair cycles. In contrast to single Foxp1 or Foxp4 conditional knockout (cKO) mice, Foxp1/4 double cKO exerted an additive effect in the spectrum and severity of phenotypes in HFSC activation, hair cycling acceleration and hair loss, coupled with remarkable downregulation of fibroblast growth factor 18 (Fgf18) and bone morphogenetic protein 6 (Bmp6) expression in bulge cells. In addition, the double KO of Foxp1/4 induced the apoptosis of K6-positive (K6+) inner bulge cells, a well-established stem cell (SC) niche, thus resulting in the destruction of the bulge SC niche and recurrent hair loss. Our investigation reveals the synergistic role of Foxp1/4 in sustaining K6+ niche cells for the quiescence of HFSCs.

Stimuli-responsive composite biopolymer actuators with selective spatial deformation behavior.

Bioinspired actuators with stimuli-responsive and deformable properties are being pursued in fields such as artificial tissues, medical devices and diagnostics, and intelligent biosensors. These applications require that actuator systems have biocompatibility, controlled deformability, biodegradability, mechanical durability, and stable reversibility. Herein, we report a bionic actuator system consisting of stimuli-responsive genetically engineered silk-elastin-like protein (SELP) hydrogels and wood-derived cellulose nanofibers (CNFs), which respond to temperature and ionic strength underwater by ecofriendly methods. Programmed site-selective actuation can be predicted and folded into three-dimensional (3D) origami-like shapes. The reversible deformation performance of the SELP/CNF actuators was quantified, and complex spatial transformations of multilayer actuators were demonstrated, including a biomimetic flower design with selective petal movements. Such actuators consisting entirely of biocompatible and biodegradable materials will offer an option toward constructing stimuli-responsive systems for in vivo biomedicine soft robotics and bionic research.

The need for digital health education among next-generation health workers in China: a cross-sectional survey on digital health education.

BACKGROUND: Digital health is important for sustainable health systems and universal health coverage. Since the outbreak of COVID-19, many countries, including China, have promoted the introduction of digital health in their medical services. Developing the next generation of physicians with digital health knowledge and skills is a prerequisite for maximizing the potential of digital health. OBJECTIVE: We aimed to understand the perception of digital health among Chinese medical students, the current implementation of digital health education in China, and the urgent need of medical students. METHODS: Our cross-sectional survey was conducted online and anonymously among current medical students in China. We used descriptive statistical analysis to examine participant demographic characteristics and the demand for digital health education. Additional analysis was conducted by grouping responses by current participation in a digital health course. RESULTS: A total of 2122 valid responses were received from 467 medical schools. Most medical students had positive expectations that digital health will change the future of medicine. Compared with wearable devices (85.53%), telemedicine (84.16%), and medical big data (86.38%), fewer respondents believed in the benefits of clinical decision support systems (CDSS) (63.81%). Most respondents said they urgently needed digital health knowledge and skills, and the teaching method of practical training and internship (78.02%) was more popular than the traditional lecture (10.54%). However, only 41.45% wanted to learn about the ethical and legal issues surrounding digital health. CONCLUSIONS: Our study shows that the current needs of Chinese medical students for digital health education remain unmet. A national initiative on digital health education, is necessary and attention should be paid to digital health equity and education globally, focusing on CDSS and artificial intelligence. Ethics knowledge must also be included in medical curriculum. Students as Partners (SAP) is a promising approach for designing digital health courses.

The dualistic model of passion and the service quality of five-star hotel employees during the COVID-19 pandemic.

Given the generally stressful job demands of the hospitality industry during the COVID-19 pandemic, understanding the work passion and emotions of hotel employees is particularly important. Based on the conservation of resources theory and the job demands-resources model, this study develops a multiple mediation model to investigate how frontline hotel employees with different types of work passion choose emotional labor strategies under the effects of the COVID-19 pandemic and the impact of different choices on their service quality. A two-stage survey using data from 206 frontline employees of five-star hotels in China explored how work passion influences emotional labor and thereby affects emotional expression as well as service quality. The results showed emotional labor partially mediates the relationship between work passion and emotional expression, which in turn mediates the relationship between emotional labor and service quality during the COVID-19 pandemic. The theoretical and practical implications of this study are discussed.

Compact fiber-integrated scattering device based on mixed-phase TiO2 for speckle spectrometer.

A universal, repeatable, and controllable integration of single-mode optical fiber and mixed-phase TiO2 is used to manufacture a compact fiber-integrated scattering device. Based on the device, we achieve a high-performance and compact fiber-based speckle spectrometer, which has a resolution of 20 pm over a bandwidth of 15 nm, in the 1550 nm range. We test the capability of our proposed spectrometer to reconstruct narrow linewidth and broadband optical spectrums, and compare the performance with that of a traditional optical spectrum analyzer.

Direct growth of hBN/Graphene heterostructure via surface deposition and segregation for independent thickness regulation.

Hexagonal boron nitride/graphene (hBN/G) vertical heterostructures have attracted extensive attention, owing to the unusual physical properties for basic research and electronic device applications. Here we report a facile deposition-segregation technique to synthesize hBN/G heterostructures on recyclable platinum (Pt) foil via low pressure chemical vapor deposition. The growth mechanism of the vertical hBN/G is demonstrated to be the surface deposition of hBN on top of the graphene segregated from the Pt foil with pre-dissolved carbon. The thickness of hBN and graphene can be controlled separately from sub-monolayer to multilayer through the fine control of the growth parameters. Further investigations by Raman, scanning Kelvin probe microscopy and transmission electron microscope show that the hBN/G inclines to form a heterostructure with strong interlayer coupling and with interlayer twist angle smaller than 1.5°. This deposition-segregation approach paves a new pathway for large-scale production of hBN/G heterostructures and could be applied to synthesize of other van der Waals heterostructures.

Opioid exposure during pregnancy and the risk of congenital malformation: a meta-analysis of cohort studies.

BACKGROUND: Opioid exposure during pregnancy has increased alarmingly in recent decades. However, the association between prenatal opioid exposure and congenital malformation risk has still been controversial. We aim to assess the association between opioid exposure during pregnancy and the risk of congenital malformations. METHOD: PubMed, Embase, and Cochrane library of clinical trials were systematically searched to September 13th, 2021. Cohort studies reporting risk of congenital malformation after opioid exposure compared with non-exposure during pregnancy were included. Risk of studies was appraised with the ROBINS-I tool. Meta-analysis was conducted using the random-effects model. Subgroup analyses were conducted for the primary outcome based on indication, exposed period, whether adjusted data was used, and risk of bias assessment. Meta-regression was performed to evaluate the relation of publication year. MAIN RESULTS: Eighteen cohort studies with 7,077,709 patients were included. The results showed a significant increase in the risk of overall congenital malformation (RR = 1.30, 95%CI: 1.11-1.53), major malformation (RR = 1.57, 95%CI:1.11-2.22), central nervous system malformation (RR = 1.36, 95% CI:1.19-1.55), and limb malformation (RR = 2.27, 95%CI:1.29-4.02) with opioid exposure during pregnancy. However, the predictive interval conveyed a different result on overall congenital malformation (95%PI: 0.82-2.09) and major malformation (95%PI: 0.82-2.09). No association between opioid exposure and overall congenital malformation in the first trimester (RR = 1.12, 95%CI:0.97-1.31) and prescribed for analgesic or antitussive treatment (RR = 1.03, 95%CI:0.94-1.13) were observed. In subgroups that study provided data adjusted for confounders (RR = 1.06, 95%CI:0.93-1.20) or identified moderate or serious risk of bias (RR = 1.00, 95%Cl: 0.85-1.16; RR = 1.21, 95%Cl: 1.60-2.68), no association was found. CONCLUSION: Opioid exposed in the first trimester or prescribed for analgesic or antitussive treatment did not increase the risk of overall congenital malformation. The findings should be discussed in caution considering the situation of individual patients and weigh out its potential risk of congenital malformation. TRIAL REGISTRATION: Registration number: CRD42021279445 .

The effect of previous oral anticoagulant use on clinical outcomes in COVID-19: A systematic review and meta-analysis.

Data on the prognosis of patients treated with oral anticoagulation (OAC) prior to hospital admission for COVID-19 remains controversial and insufficient. Therefore, we endeavored to perform a systematic review and meta-analysis to evaluate the effect of chronic use of OAC prior to the diagnosis of COVID-19 on intensive care unit (ICU) admission and mortality. An electronic search of the Pubmed, Embase, Cochrane library databases was conducted. Meta-analysis and statistical analyses were completed with using the RevMan 5.3 and Stata 12.0. A total of 13 articles representing data from 1,266,231 participants were included in this study. The meta-analysis of unadjusted results showed no decrease in mortality (OR = 1.31, 95% CI: 0.99 to 1.73, P = 0.059) or ICU admission rate (OR = 0.71, 95% CI: 0.29 to 1.77, P = 0.46) in COVID-19 patients with prior OAC therapy at hospital admission compared to patients without prior use of OAC. Moreover, the meta-analysis of adjusted results showed no lower risk of mortality (OR = 1.08, 95% CI: 0.90 to 1.30, P = 0.415) or ICU admission (OR = 1.50, 95% CI: 0.72 to 3.12, P = 0.284) in patients with prior OAC use compared to patients without previous OAC use. In conclusion, the results of this study revealed that the use of OAC prior to hospital admission appeared to be ineffective in reducing the risk of intensive care need and mortality in COVID-19 patients. Randomized controlled trials are needed to evaluate and optimize the use of OAC in COVID-19 infection.

Opioid usage and COVID-19 prognosis: A systematic review and meta-analysis.

The COVID-19 pandemic continues to have profound health, social, psychological, and economic ramifications. Infection by COVID-19 has been of concern in people who use opioids, as opioid use has been known to mediate immunosuppression and is associated with respiratory depression and end-organ damage. With differing modalities of opioid usage, the association between opioids and COVID-19 outcomes is not well understood. We performed a comprehensive systematic search of seven health science databases, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data, up to December 15, 2021. We identified a total of five related articles, which were included in this study. The meta-analysis showed that opioids have a significant association with ICU admission for COVID-19 patients (OR = 5.41, 95%CI: 1.85 to 15.79, P = 0.002). Use of opioids was also associated with higher mortality among patients with COVID-19 compared to non-users (OR = 2.74, 95%CI: 1.34 to 5.62, P = 0.034), while use of opioids was not significantly associated with need for mechanical ventilation (OR = 3.68, 95%CI: 0.85 to 15.90, P = 0.081). Furthermore, the adjusted analysis indicated that COVID-19 patients with a history of opioid use were more likely to be admitted to the ICU (OR = 3.57, 95%CI: 3.05 to 4.17, P<0.001) and have higher mortality rates (OR = 1.72, 95%CI: 1.09 to 2.72, P = 0.02), while there was no significant association with need for mechanical ventilation (OR = 2.09, 95%CI: 0.77 to 5.64, P = 0.146). Significant heterogeneity existed across the included studies. Patients using opioids with COVID-19 were at higher risk of ICU admission and mortality. Prospective studies are required to confirm these findings.

Thermomechanical responses facilitating survival mechanisms in pronounced supercooled insects.

Cryopreservation can keep the bioactivity of biological specimens in long-term storage, but it is hard to retain the structural integrity due to serious thermomechanical stress during cooling and warming procedures, especially for complex living organisms. Few studies have reported on the thermomechanical stress of biological specimens in a pre-freezing supercooled state, which is a widespread phenomenon in slow-rate freezing cryopreservation. Here, we develop a thermomechanical coupling model to study transient thermal and mechanical fields of supercooled biological specimens experiencing freezing procedures. The results show that cryoprotectant accumulation in insects causes pronounced supercooled phenomena with severe deformation and thermomechanical stress in the initial state of phase transition. However, the loss of freezable water induced that final deformation and stress decrease, which is beneficial to organism survival after freezing. This numerical method is proved to be a guideline for optimizing slow-rate freezing cryopreservation protocols efficiently and economically. These results reveal survival mechanisms of insects with supercooled phenomena after freezing and assist researchers in exploring more valuable cryopreservation methods for biological specimens.

The Deficiency of SCARB2/LIMP-2 Impairs Metabolism via Disrupted mTORC1-Dependent Mitochondrial OXPHOS.

Deficiency in scavenger receptor class B, member 2 (SCARB2) is related to both Gaucher disease (GD) and Parkinson's disease (PD), which are both neurodegenerative-related diseases without cure. Although both diseases lead to weight loss, which affects the quality of life and the progress of diseases, the underlying molecular mechanism is still unclear. In this study, we found that Scarb2-/- mice showed significantly reduced lipid storage in white fat tissues (WAT) compared to WT mice on a regular chow diet. However, the phenotype is independent of heat production, activity, food intake or energy absorption. Furthermore, adipocyte differentiation and cholesterol homeostasis were unaffected. We found that the impaired lipid accumulation of Adiponectin-cre; Scarb2fl/fl mice was due to the imbalance between glycolysis and oxidative phosphorylation (OXPHOS). Mechanistically, the mechanistic target of rapamycin complex 1 (mTORC1)/ eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) pathway was down-regulated in Scarb2 deficient adipocytes, leading to impaired mitochondrial respiration and enhanced glycolysis. Altogether, we reveal the role of SCARB2 in metabolism regulation besides the nervous system, which provides a theoretical basis for weight loss treatment of patients with neurodegenerative diseases.

Delivery of Cationic Platinum Prodrugs via Reduction Sensitive Polymer for Improved Chemotherapy.

A cationic monofunctional platinum anticancer drug, phenanthriplatin (PhenPt(II)), exhibits promising anticancer effect on various cancer cell lines. Unlike the conventional platinum(II) drugs, PhenPt(II) is more likely to bind the N7 adenosine base of DNA in situ, and consequently resulting in a unique cellular response profile and unusual potency. However, since this drug is positively charged, it can easily bind to plasma protein that leads to rapid systematic clearance and deleterious toxicities, which greatly limits its in vivo application. Herein, a lipophilic phenanthriplatin (PhenPt(IV)) prodrug is synthesized. To further reduce its toxicity, a negatively charged polymer P1 with reduction responsiveness is assembled with PhenPt(IV) to form PhenPt(IV) NPs. In comparison to cisplatin, PhenPt(IV) NPs exhibit up to 30 times greater in vitro potency against various cancer cell lines. Additionally, in vivo, no obvious side effect is found on PhenPt(IV) NPs. Significant enhancement in tumor accumulation and improvement of drug efficacy in 4T1 tumor model are demonstrated. Taken together, this study provides a promising strategy for the clinical translation of phenanthriplatin.

Association of neutrophil-to-lymphocyte ratio and risk of cardiovascular or all-cause mortality in chronic kidney disease: a meta-analysis.

BACKGROUND: It is currently controversial whether neutrophil-to-lymphocyte ratio (NLR) has a prognostic role in patients with chronic kidney disease (CKD). We aimed to investigate whether NLR was an independent predictor of cardiovascular or all-cause mortality in CKD patients with or without hemodialysis by performing a meta-analysis. METHODS: Pubmed, Embase, and Cochrane Library databases are systematically searched for relevant literature that investigated NLR and subsequent cardiovascular or all-cause mortality risk in CKD with or without dialysis. Pooled hazard risk (HR) with 95% confidence interval (CI) was calculated for the high vs. low NLR category. RESULTS: A total of thirteen studies enrolling 116,709 patients were identified and analyzed. In summary, high NLR was associated with an increased risk of all-cause mortality (HR 1.93, 95% CI 1.87-2.00; P < 0.00001) and cardiovascular mortality (HR 1.45, 95% CI 1.18-1.79, P < 0.001). Subgroup analysis indicated that high NLR are independently associated with all-cause mortality risk in dialysis patients (HR 1.94, 95% CI 1.87-2.01; P < 0.00001). CONCLUSIONS: This meta-analysis indicates a high NLR is related to all-cause mortality and cardiovascular mortality in patients with chronic kidney disease. Dialysis patients with high NLR are candidates at high risk of mortality to allow for earlier interventions. Further large scale and more rigorously designed studies are warranted to confirm the prognostic value of NLR in the different stages of CKD.