Vancomycin trough concentration in adult patients with periprosthetic joint infection: A machine learning-based covariate model.

AIMS: Although there are various model-based approaches to individualized vancomycin (VCM) administration, few have been reported for adult patients with periprosthetic joint infection (PJI). This work attempted to develop a machine learning (ML)-based model for predicting VCM trough concentration in adult PJI patients. METHODS: The dataset of 287 VCM trough concentrations from 130 adult PJI patients was split into a training set (229) and a testing set (58) at a ratio of 8:2, and an independent external 32 concentrations were collected as a validation set. A total of 13 covariates and the target variable (VCM trough concentration) were included in the dataset. A covariate model was respectively constructed by support vector regression, random forest regression and gradient boosted regression trees and interpreted by SHapley Additive exPlanation (SHAP). RESULTS: The SHAP plots visualized the weight of the covariates in the models, with estimated glomerular filtration rate and VCM daily dose as the 2 most important factors, which were adopted for the model construction. Random forest regression was the optimal ML algorithm with a relative accuracy of 82.8% and absolute accuracy of 67.2% (R2 =.61, mean absolute error = 2.4, mean square error = 10.1), and its prediction performance was verified in the validation set. CONCLUSION: The proposed ML-based model can satisfactorily predict the VCM trough concentration in adult PJI patients. Its construction can be facilitated with only 2 clinical parameters (estimated glomerular filtration rate and VCM daily dose), and prediction accuracy can be rationalized by SHAP values, which highlights a profound practical value for clinical dosing guidance and timely treatment.

Changes in frailty and depressive symptoms among middle-aged and older Chinese people: a nationwide cohort study.

BACKGROUND AND AIMS: The older people bears a severe burden of disease due to frailty and depressive symptoms, however, the results of association between the two in the older Chinese people have been conflicting. Therefore, this study aimed to investigate the developmental trajectories and interactions of frailty and depressive symptoms in the Chinese middle-aged and older adults. METHODS: The study used four waves of data from 2011, 2013, 2015 and 2018 in the China Health and Retirement Longitudinal Study (CHARLS) database, focused on middle-aged and older people ≥ 45 years of age, and analyzed using latent growth models and cross-lagged models. RESULTS: The parallel latent growth model showed that the initial level of depressive symptoms had a significant positive predictive effect on the initial level of frailty. The rate of change in depressive symptoms significantly positively predicted the rate of change in frailty. The initial level of frailty had a significant positive predictive effect on the initial level of depressive symptoms, but a significant negative predictive effect on the rate of change in depressive symptoms. The rate of change in frailty had a significant positive predictive effect on the rate of change in depressive symptoms. The results of the cross-lagged analysis indicated a bidirectional causal association between frailty and depressive symptoms in the total sample population. Results for the total sample population grouped by age and gender were consistent with the total sample. CONCLUSIONS: This study recommends advancing the age of concern for frailty and depressive symptoms to middle-aged adults. Both men and women need early screening and intervention for frailty and depressive symptoms to promote healthy aging.

Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial.

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.

[Effect of Zhenwu Decoction on electrical remodeling of cardiomyocytes in heart failure via I_(to)/Kv channels].

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.

A Lamellar MXene (Ti3 C2 Tx )/PSS Composite Membrane for Fast and Selective Lithium-Ion Separation.

A two-dimensional (2D) laminar membrane with Li+ selective transport channels is obtained by stacking MXene nanosheets with the introduction of poly(sodium 4-styrene sulfonate) (PSS) with active sulfonate sites, which exhibits excellent Li+ selectivity from ionic mixture solutions of Na+ , K+ , and Mg2+ . The Li+ permeation rate through the MXene@PSS composite membrane is as high as 0.08 mol m-2 h-1 , while the Li+ /Mg2+ , Li+ /Na+ , and Li+ /K+ selectivities are 28, 15.5, and 12.7, respectively. Combining the simulation and experimental results, we further confirm that the highly selective rapid transport of partially dehydrated Li+ within subnanochannels can be attributed to the precisely controlled interlayer spacing and the relatively weaker ion-terminal (-SO3 - ) interaction. This study deepens the understanding of ion-selective permeation in confined channels and provides a general membrane design concept.

Oppositely Charged Ti3 C2 Tx MXene Membranes with 2D Nanofluidic Channels for Osmotic Energy Harvesting.

Membrane-based reverse electrodialysis (RED) is considered as the most promising technique to harvest osmotic energy. However, the traditional membranes are limited by high internal resistance and low efficiency, resulting in undesirable power densities. Herein, we report the combination of oppositely charged Ti3 C2 Tx MXene membranes (MXMs) with confined 2D nanofluidic channels as high-performance osmotic power generators. The negatively or positively charged 2D MXene nanochannels exhibit typical surface-charge-governed ion transport and show excellent cation or anion selectivity. By mixing the artificial sea water (0.5 m NaCl) and river water (0.01 m NaCl), we obtain a maximum power density of ca. 4.6 Wm-2 , higher than most of the state-of-the-art membrane-based osmotic power generators, and very close to the commercialization benchmark (5 Wm-2 ). Through connecting ten tandem MXM-RED stacks, the output voltage can reach up 1.66 V, which can directly power the electronic devices.

Antibiotics Separation with MXene Membranes Based on Regularly Stacked High-Aspect-Ratio Nanosheets.

The uncontrolled release of antibiotics and pharmaceuticals into the environment is a worldwide increasing problem. Thus, highly efficient treatment technologies for wastewater are urgently needed. In this work, seven kinds of typical antibiotics (including water and alcohol soluble ones) are successfully separated from the corresponding aqueous and ethanolic solutions using highly regular laminated membranes. Our membranes are assembled with 2-4 µm titanium carbide nanosheets. The solvent permeance through such titanium carbide membrane is one order of magnitude higher than that through most polymeric nanofiltration membranes with similar antibiotics rejection. This high flux is due to the regular two-dimensional (2D) structure resulting from the large aspect ratio of titanium carbide nanosheets. Moreover, the electrostatic interaction between the surface terminations and the antibiotics also affects the rejection and enhances the antifouling property. Such 2D titanium carbide membranes further broaden the application scope of laminated materials for separation and purification of high value added drugs in academia and industry.

Late administration of high-frequency electrical stimulation increases nerve regeneration without aggravating neuropathic pain in a nerve crush injury.

BACKGROUND: High-frequency transcutaneous neuromuscular electrical nerve stimulation (TENS) is currently used for the administration of electrical current in denervated muscle to alleviate muscle atrophy and enhance motor function; however, the time window (i.e. either immediate or delayed) for achieving benefit is still undetermined. In this study, we conducted an intervention of sciatic nerve crush injury using high-frequency TENS at different time points to assess the effect of motor and sensory functional recovery. RESULTS: Animals with left sciatic nerve crush injury received TENS treatment starting immediately after injury or 1 week later at a high frequency(100 Hz) or at a low frequency (2 Hz) as a control. In SFI gait analysis, either immediate or late admission of high-frequency electrical stimulation exerted significant improvement compared to either immediate or late administration of low-frequency electrical stimulation. In an assessment of allodynia, immediate high frequency electrical stimulation caused a significantly decreased pain threshold compared to late high-frequency or low-frequency stimulation at immediate or late time points. Immunohistochemistry staining and western blot analysis of S-100 and NF-200 demonstrated that both immediate and late high frequency electrical stimulation showed a similar effect; however the effect was superior to that achieved with low frequency stimulation. Immediate high frequency electrical stimulation resulted in significant expression of TNF-α and synaptophysin in the dorsal root ganglion, somatosensory cortex, and hippocampus compared to late electrical stimulation, and this trend paralleled the observed effect on somatosensory evoked potential. The CatWalk gait analysis also showed that immediate electrical stimulation led to a significantly high regularity index. In primary dorsal root ganglion cells culture, high-frequency electrical stimulation also exerted a significant increase in expression of TNF-α, synaptophysin, and NGF in accordance with the in vivo results. CONCLUSION: Immediate or late transcutaneous high-frequency electrical stimulation exhibited the potential to stimulate the motor nerve regeneration. However, immediate electrical stimulation had a predilection to develop neuropathic pain. A delay in TENS initiation appears to be a reasonable approach for nerve repair and provides the appropriate time profile for its clinical application.

The causal relationship between sleep disturbances and the risk of frailty: a two-sample Mendelian randomization study.

OBJECTIVE: Adequate sleep is closely related to people's health. However, with increasing age, the quality of sleep worsens. At the same time, among elderly individuals, frailty is also a disturbing factor, which makes elderly individuals more vulnerable to negative factors. To explore the relationship between the two, we conducted this study. METHODS: In this paper, independent genetic variations related to insomnia, sleep duration and daytime sleepiness were selected as IVs, and related genetic tools were used to search published genome-wide association studies for a two-sample Mendelian randomization (TSMR) analysis. The inverse-variance weighted (IVW) method was used as the main Mendelian randomization analysis method. Cochran's Q test was used to test heterogeneity, MR‒Egger was used to test horizontal pleiotropy, and the MR-PRESSO test was used to remove outliers. RESULTS: According to our research, insomnia (OR = 1.10, 95% CI 1.03-1.17, P = 2.59e-97), long sleep duration (OR = 0.66, 95% CI 0.37-1.17, P = 0.02), short sleep duration (OR = 1.30, 95% CI 1.22-1.38, P = 2.23e-17) and daytime sleepiness (OR = 1.49, 95% CI 1.25-1.77, P = 0.96e-4) had a bidirectional causal relationship with frailty. CONCLUSIONS: Our research showed that there is a causal relationship between sleep disturbances and frailty. This result was obtained by a TSMR analysis, which involves the use of genetic variation as an IV to determine causal relationships between exposure and outcome. Future TSMR studies should include a larger sample for analysis.

Integrative analysis of histone acetyltransferase KAT2A in human cancer.

The high incidence of mutations and the crucial roles of KAT2A in cancer development have received increased attention. Nevertheless, a systematic comparison of the heterogeneity and dynamics across different cancer types has not been conducted. Hence, a deep analysis using public databases was performed to clarify the contributions of KAT2A and its correlation with tumorigenesis. The raw data regarding KAT2A expression in cancer patients and healthy controls were obtained from The Cancer Genome Atlas (TCGA). Sexually dimorphic manner, genomic alterations, and expression pattern of KAT2A, as well as the association of the KAT2A with survival, were retrieved from UALCAN, cBioportal, and TISIDB databases. Additionally, the Protein-Protein Interaction (PPI) analysis was conducted using the STRING database. The human protein atlas was used to obtain the staining results of protein levels in cancer and normal samples. The correlation between KAT2A and its potential target drugs was determined using TISIDB and HISTome2. Compared to the normal tissues, CHOL and TGCT tumors presented significantly high KAT2A expression, which was positively correlated with BLCA, BRCA, CESC, CHOL, COAD, ESCA, HNSC, KICH, KIRP, LIHC, LUAD, LUSC, READ, STAD, and THCA. However, no significant difference was detected between normal and tumor tissues for the sex difference pattern of KAT2A expression. The PPI analysis indicated that TADA3, CCDC101, TRRAP, SUPT3H, MYC, TADA2A, and USP22 levels were positively correlated with KAT2A expression, while TADA2B and ATXN7 were negatively correlated. A positive link of KAT2A with cancer isotypes and significant connections of the KAT2A expression to poor overall and disease-free survival were also observed. Further validation was conducted using immunohistochemistry (IHC) staining, qPCR, and Western blot. Some potential HAT inhibitory drugs of KAT2A were also determined, but more work and clinical trials are required before their application.

A neutral rhenium-biimidazole complex for the selective recognition of fluoride ions.

The neutral rhenium(I)-biimidazole complex [Re(CO)3(biimH)(1,4-NVP)] (1) was designed and synthesized by a one-pot reaction of Re2(CO)10, 2,2'-biimidazole (biimH2) and 4-(1-naphthylvinyl)pyridine (1,4-NVP). The structure of 1 was characterized by various spectroscopic techniques including IR, 1H NMR, FAB-MS, and elemental analysis and further confirmed by a single-crystal X-ray diffraction analysis. The mononuclear complex 1, a relatively simple structure with an octahedral geometry, is comprised of facial-arranged carbonyl groups, one chelated biimH monoanion, and one 1,4-NVP. Complex 1 shows the lowest energy absorption band at around 357 nm and an emission band at 408 nm in THF. The luminescent characteristics of 1 combined with the hydrogen bonding ability of the partially coordinated monoionic biimidazole ligand permits the complex to selectively recognize fluoride ions (F-) in the presence of other halides through a dramatic luminescence enhancement. The recognition mechanism of 1 can be convincingly explained in terms of H-bond formation and proton abstraction upon the addition of F- ions by 1H and 19F NMR titration experiments. The electronic properties of 1 were further supported by time dependent density functional theory (TDDFT) computational studies.

Control of light-promoted [2+2] cycloaddition reactions by a remote ancillary regulatory group that is covalently attached to rhenium rectangles.

The high-yielding self-assembly of three neutral rhenium(I) rectangles, [Re(2)(CO)(6)(L)(bpe)](2) (1 a, L=2,2'-biimidazolate (biim); 1 b, L=2,2'-bisbenzimidazolate (bbim); 1 c, L=2,2'-bis(4,5-dimethylimidazolate) (bdmim); bpe=trans-1,2-bis(4-pyridyl)ethylene), under hydrothermal conditions is described. The rectangles were structurally characterized by spectroscopic techniques and further confirmed by single-crystal X-ray diffraction. Upon irradiation with a Hg lamp at 365 nm, the bpe ligands of rectangles 1 a and 1 b underwent [2+2] photocycloaddition reactions to produce [{(Re(CO)(3))(2)L}(2)(4,4'-tpcb)(2)] (2 a, L=biim; 2 b, L=bbim; 4,4'-tpcb=1,2,3,4-tetrakis(4-pyridyl)cyclobutane) through a single-crystal-to-single-crystal (SCSC) transformation. However, rectangle 1 c, which contained methyl groups on the 2,2'-biimidazolate ligand, failed to undergo cycloaddition, even after prolonged irradiation. This result indicates that the light-induced cycloaddition reaction can be preferentially controlled by the remote regulatory substituents, which are attached onto the same backbone of the rectangle complex. This transformation is the first reported utilization of a remote ancillary regulatory ligand that is covalently attached onto a coordination compound to control the [2+2] cycloaddition reaction.

Ultrasonic-assisted extraction, fatty acids identification of the seeds oil and isolation of chemical constituent from oil residue of Belamcanda chinensis.

Belamcanda chinensis is a common garden herb. The extraction technology of B. chinensis seed oil (BSO) was optimized by ultrasonic-assisted extraction (UAE) method, the composition, relative content of main fatty acids and physicochemical properties of BSO were determined, and the isolation, identification and determination of chemical constituent in BSO residue (BSOR) were also investigated. The optimum process conditions of BSO by UAE were optimized as ultrasound time 14 min, extraction temperature 42℃, the ultrasound power 413 W and the liquid-solid ratio 27:1 mL/g. Under this condition, the extraction yield was 22.32 % with the high contents of linoleic acid and oleic acid in BSO. Ten compounds were isolated and identified from BSOR, and belamcandaoid P (9) was a new compound. The contents of the determined compounds were all at high level in B. chinensis seed. The study provided a certain scientific reference for the comprehensive development and utilization of B. chinensis seeds.

Ultrasonic-assisted extraction and adsorption separation: Large-scale preparation of trans-ε-Viniferin, suffruficosol B and trans-Gnetin H for the first time.

In this study, a Standard Operating Procedure (SOP) for the large-scale extraction, enrichment, and separation of suffruticosol B (SB), trans-ε-Viniferin (TV), trans-gnetin H (TG) from oil tree peony seeds shell (PSS) was successfully constructed. The ultrasonic-assisted extraction (UAE), macroporous adsorption resin (MAR), and column chromatography (CC) were employed to extract, enrich and separate SB, TV and TG from PSS, and the conditions were optimized. The results implied that SB (1.6937 g), TV (0.5884 g) and TG (3.8786 g) with the purity of 99.67 %, 99.32 % and 98.54 %, respectively, were obtained after the extraction, enrichment and separation. The total yields of the SB, TV and TG were 0.61 mg/g, 0.02 mg/g and 6.64 mg/g with the total extraction rates at 70.55 %, 69.77 % and 78.36 %, respectively. This is the first report on the large-scale extraction, enrichment and separation of oligostilbenes. The SOP in this paper could produce high purity SB, TV and TG, and provide a new idea for PSS as a new oligostilbene resource. The study expands the new development and research field of PSS and provides theoretical support for the green utilization of oil tree peony.

Pharmacological Perturbation of Mechanical Contractility Enables Robust Transdifferentiation of Human Fibroblasts into Neurons.

Direct cell reprogramming, also called transdifferentiation, is valuable for cell fate studies and regenerative medicine. Current approaches to transdifferentiation are usually achieved by directly targeting the nuclear functions, such as manipulating the lineage-specific transcriptional factors, microRNAs, and epigenetic modifications. Here, a robust method to convert fibroblasts to neurons through targeting the cytoskeleton followed by exposure to lineage-specification surroundings is reported. Treatment of human foreskin fibroblasts with a single molecule inhibitor of the actomyosin contraction, can disrupt the cytoskeleton, promote cell softening and nuclear export of YAP/TAZ, and induce a neuron-like state. These neuron-like cells can be further converted into mature neurons, while single-cell RNA-seq shows the homogeneity of these cells during the induction process. Finally, transcriptomic analysis shows that cytoskeletal disruption collapses the original lineage expression profile and evokes an intermediate state. These findings shed a light on the underestimated role of the cytoskeleton in maintaining cell identity and provide a paradigm for lineage conversion through the regulation of mechanical properties.

Pharmacological regulation of tissue fibrosis by targeting the mechanical contraction of myofibroblasts.

Fibrosis can occur in almost all tissues and organs and affects normal physiological function, which may have serious consequences, such as organ failure. However, there are currently no effective, broad-spectrum drugs suitable for clinical application. Revealing the process of fibrosis is an important prerequisite for the development of new therapeutic targets and drugs. Studies have shown that the limiting of myofibroblast activation or the promoting of their elimination can ameliorate fibrosis. However, it has not been reported whether a direct decrease in cell contraction can inhibit fibrosis in vivo. Here, we have shown that (-)-blebbistatin (Ble), a non-muscle myosin Ⅱ inhibitor, displayed significant inhibition of liver fibrosis in different chronic injury mouse models in vivo. We found that Ble reduced the stiffness of fibrotic tissues from the early stage, which reduced the extent of myofibroblast activation induced by a stiffer extracellular matrix (ECM). Moreover, Ble also reduced the activation of myofibroblasts induced by TGF-ß1, which is the most potent pro-fibrotic cytokine. Mechanistically, Ble reduced mechanical contraction, which inhibited the assembly of stress fibers, decreased the F/G-actin ratio, and led to the exnucleation of YAP1 and MRTF-A. Finally, we verified its broad-spectrum antifibrotic effect in multiple models of organ fibrosis. Our results highlighted the important role of mechanical contraction in myofibroblast activation and maintenance, rather than just a characteristic of activation, suggesting that it may be a potential target to explore broad-spectrum drugs for the treatment of fibrotic diseases.

Supported MXene/GO Composite Membranes with Suppressed Swelling for Metal Ion Sieving.

Novel two-dimensional (2D) membranes have been utilized in water purification or seawater desalination due to their highly designable structure. However, they usually suffer from swelling problems when immersed in solution, which limits their further applications. In this study, 2D cross-linked MXene/GO composite membranes supported on porous polyamide substrates are proposed to improve the antiswelling property and enhance the ion-sieving performance. Transition-metal carbide (MXene) nanosheets were intercalated into GO nanosheets, where the carboxyl groups of GO combined the neighboring hydroxyl terminal groups of MXene with the formation of -COO- bonds between GO and MXene nanosheets via the cross-linking reaction (-OH + -COOH = -COO- + H2O) after heat treatment. The permeation rates of the metal ions (Li+, Na+, K+, Al3+) through the cross-linked MXene/GO composite membrane were 7-40 times lower than those through the pristine MXene/GO membrane. In addition, the cross-linked MXene/GO composite membrane showed excellent Na+ rejection performance (99.3%), which was significantly higher than that through pristine MXene/GO composite membranes (80.8%), showing improved ion exclusion performance. Such a strategy represents a new avenue to develop 2D material-derived high-performance membranes for water purification.

Long-term effects of Xuezhikang on blood pressure in hypertensive patients with previous myocardial infarction: data from the Chinese Coronary Secondary Prevention Study (CCSPS).

Several previous trials from Western population studies have showed that statins may help reduce blood pressure (BP). However, randomized clinical data is limited. Xuezhikang, a partially extract of red yeast rice, contains a family of naturally occurring statins, and has a marked impact on lipids, but it is unknown whether Xuezhikang has any effect on BP during long-term follow-up in the Chinese population. This is a post-hoc subgroup analysis of a randomized, double-blinded, placebo-controlled, parallel group clinical trial, Chinese Coronary Secondary Prevention Study (CCSPS). A total of 2704 hypertensive patients with previous myocardial infarction (MI) were assigned either to placebo (n = 1341) or to Xuezhikang (n = 1363) daily for an average of 4.5 years. The primary outcome was the unadjusted changes in mean arterial pressure (MAP) from baseline to 6 months. We also assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure. Analysis of covariance was used to calculate the adjusted effects of treatment on changes in these outcomes at 6, 12, 24, and 48 months post-randomization, after controlling for potential confounders. This analysis included 2704/4870 (55.5%) hypertensive patients for whom BP was measured at baseline and at least one follow-up visit after randomization. Median duration of the follow-up was 4.5 years (54 months), and 25 patients (0.92%) were lost to the last follow-up because of adverse effects. The results showed that the unadjusted and adjusted changes in MAP, SBP, DBP, or pulse pressure from baseline were not significantly different for Xuezhikang or placebo recipients at 6, 12, 24, and 48 months after randomization. In this post-hoc subgroup analysis, we failed to demonstrate any significant reducing effects of Xuezhikang on BP in Chinese hypertensive patients with previous MI, suggesting that further prospective study on the effects of statins on BP would be needed, especially in high-risk patients.

Beneficial impact of Xuezhikang on cardiovascular events and mortality in elderly hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS).

Coronary heart disease, hypertension, and dyslipidemia are highly prevalent and commonly coexist in people who are middle-aged and older. Previous data suggested that lowering cholesterol concentrations in individuals at high risk of cardiovascular disease improved clinical outcomes. Xuezhikang, a partial extract of red yeast rice containing statin, has a marked impact on lipids. The purpose of this study, therefore, was to evaluate the impact of Xuezhikang on reducing cardiovascular events and mortality in elderly Chinese hypertensive patients with a history of myocardial infarction (MI) enrolled in the Chinese Coronary Secondary Prevention Study. In this randomized trial, 1530 elderly hypertensive patients (> or = 65-years-old) with previous MI were assigned either to placebo (n = 758) or to Xuezhikang (n = 772) daily for an average of 4.5 years. The primary endpoint was recurrent coronary events; the secondary endpoint was all-cause mortality and other clinical events, including adverse effects. There were 68 cases of coronary events (8.8%) detected in the Xuezhikang group and 108 cases (14.3%) in the placebo group (38.2% risk reduction by Xuezhikang therapy). Death from coronary heart disease (CHD) totaled 49 cases in the Xuezhikang group (6.4%) and 68 cases in the placebo group (9.0%), indicating that Xuezhikang significantly decreased the risk of CHD death by 29.2%. Our study demonstrated that Xuezhikang therapy could effectively and safely reduce cardiovascular events and all-cause death in Chinese elderly hypertensive patients with previous MI. This finding may have an important implication for the treatment of elderly hypertensive patients with CHD.

Self-Crosslinked MXene (Ti3C2Tx) Membranes with Good Antiswelling Property for Monovalent Metal Ion Exclusion.

A 2D membrane-based separation technique has been increasingly applied to solve the problem of fresh water shortage via ion rejection. However, these 2D membranes often suffer from a notorious swelling problem when immersed in solution, resulting in poor rejection for the monovalent metal ion. The design of the antiswelling 2D lamellar membranes has been proved to be a big challenge for highly efficient desalination. Here a kind of self-crosslinked MXene membrane is proposed for ion rejection with an obviously suppressed swelling property, which takes advantage of the hydroxyl terminal groups on the MXene nanosheets by forming Ti-O-Ti bonds between the neighboring nanosheets via the self-crosslinking reaction (-OH + -OH = -O- + H2O) through a facile thermal treatment. The permeation rates of the monovalent metal ions through the self-crosslinked MXene membrane are about two orders of magnitude lower than those through the pristine MXene membrane, which indicates the obviously improved performance of the ion exclusion by self-crosslinking between the MXene lamellae. Moreover, the excellent stability of the self-crosslinked MXene membrane during the 70 h long-term ion separation also demonstrates its promising antiswelling property. Such a facile and efficient self-crosslinking strategy gives the MXene membrane a good antiswelling property for metal ion rejection, which is also suitable for many other 2D materials with tunable surface functional groups during membrane assembly.