Coagulation abnormalities associated with CAR-T-cell therapy in haematological malignancies: A review.

Chimeric antigen receptor (CAR)-T-cell therapy has demonstrated considerable efficacy and safety in the treatment of patients with relapsed/refractory haematological malignancies. Owing to significant advances, CAR-T-cell therapeutic modality has undergone substantial shifts in its clinical application. Coagulation abnormalities, which are prevalent complications in CAR-T-cell therapy, can range in severity from simple abnormalities in coagulation parameters to serious haemorrhage or disseminated intravascular coagulation associated with life-threatening multiorgan dysfunction. Nonetheless, there is a lack of a comprehensive overview concerning the coagulation abnormalities associated with CAR-T-cell therapy. With an aim to attract heightened clinical focus and to enhance the safety of CAR-T-cell therapy, this review presents the characteristics of the coagulation abnormalities associated with CAR-T-cell therapy, including clinical manifestations, coagulation parameters, pathogenesis, risk factors and their influence on treatment efficacy in patients receiving CAR-T-cell infusion. Due to limited data, these conclusions may undergo changes as more experience accumulates.

Effect of Salt Substitution on Cardiovascular Events and Death.

BACKGROUND: Salt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain. METHODS: We conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia. RESULTS: A total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001). The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80 to 1.37; P = 0.76). CONCLUSIONS: Among persons who had a history of stroke or were 60 years of age or older and had high blood pressure, the rates of stroke, major cardiovascular events, and death from any cause were lower with the salt substitute than with regular salt. (Funded by the National Health and Medical Research Council of Australia; SSaSS ClinicalTrials.gov number, NCT02092090.).

Cost-Effectiveness of a Household Salt Substitution Intervention: Findings From 20 995 Participants of the Salt Substitute and Stroke Study.

BACKGROUND: SSaSS (Salt Substitute and Stroke Study), a 5-year cluster randomized controlled trial, demonstrated that replacing regular salt with a reduced-sodium, added-potassium salt substitute reduced the risks of stroke, major adverse cardiovascular events, and premature death among individuals with previous stroke or uncontrolled high blood pressure living in rural China. This study assessed the cost-effectiveness profile of the intervention. METHODS: A within-trial economic evaluation of SSaSS was conducted from the perspective of the health care system and consumers. The primary health outcome assessed was stroke. We also quantified the effect on quality-adjusted life-years (QALYs). Health care costs were identified from participant health insurance records and the literature. All costs (in Chinese yuan [¥]) and QALYs were discounted at 5% per annum. Incremental costs, stroke events averted, and QALYs gained were estimated using bivariate multilevel models. RESULTS: Mean follow-up of the 20 995 participants was 4.7 years. Over this period, replacing regular salt with salt substitute reduced the risk of stroke by 14% (rate ratio, 0.86 [95% CI, 0.77-0.96]; P=0.006), and the salt substitute group had on average 0.054 more QALYs per person. The average costs (¥1538 for the intervention group and ¥1649 for the control group) were lower in the salt substitute group (¥110 less). The intervention was dominant (better outcomes at lower cost) for prevention of stroke as well as for QALYs gained. Sensitivity analyses showed that these conclusions were robust, except when the price of salt substitute was increased to the median and highest market prices identified in China. The salt substitute intervention had a 95.0% probability of being cost-saving and a >99.9% probability of being cost-effective. CONCLUSIONS: Replacing regular salt with salt substitute was a cost-saving intervention for the prevention of stroke and improvement of quality of life among SSaSS participants.

Experience with 2 years' intervention to progressively reduce salt supply to kitchens in elderly care facilities-challenges and further research: post hoc analysis of the DECIDE-Salt randomized clinical trial.

BACKGROUND: Progressive reduction of sodium intake is an attractive approach for addressing excessive salt intake, but evidence for this strategy in real practice is limited. We aimed to determine the feasibility, effectiveness, and safety of a progressive sodium intake reduction intervention in real-world setting. METHODS: We randomized 48 residential elderly care facilities in China, with 1612 participants aged 55 years and older, to either progressive reduction (PR, 24 facilities) or no reduction (NR, 24 facilities) of the supply of study salt to the kitchens of these facilities for 2 years. The primary efficacy outcome was systolic blood pressure (SBP) at any scheduled follow-up visit. Secondary efficacy outcomes included diastolic blood pressure (DBP) at any scheduled follow-up visit, and major adverse cardiovascular events (comprising non-fatal stroke, non-fatal myocardial infarction, hospitalized non-fatal heart failure, or vascular death) and total mortality. The perception of food saltiness, the addition of out-of-study salt in meals, and 24-h urinary sodium excretion were used as process indicators. RESULTS: Pre-specified analysis per randomization found no effect of the intervention on the 2-year overall mean systolic and diastolic blood pressure (SBP, DBP) and any other outcomes. However, post hoc analysis showed that the intervention effect on blood pressure varied over multiple follow-up visits (p for interaction < 0.046) and presented favorable differences at the 24-month visit (SBP = - 3.0 mmHg, 95%CI = - 5.6, - 0.5; p = 0.020; DBP = - 2.0 mmHg, 95%CI - 3.4, - 0.63; p = 0.004). The effect on 24-h sodium was non-significant (- 8.4 mmol, 95%CI = - 21.8 to 4.9, p = 0.216), though fewer participants with NR than with PR reported food tasting bland (odds ratio 0.46; 95%CI 0.29 to 0.73; p = 0.001). Reporting of bland food taste and other process measures indicated that intervention delivery and adherence were not fully achieved as designed. CONCLUSIONS: The experience of this real-world study demonstrated that achieving acceptability and sustainability of the progressive sodium intake reduction strategy among older adults was challenging, but it has shown potential for effectiveness in these and potentially other residential settings if the lessons of DECIDE-Salt are applied in further studies. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03290716).

Acid-Triggered H2O2 Self-Supplying Nanoplatform for 19F-MRI with Enhanced Chemo-Chemodynamic Therapy.

The real-time tracking and efficacy evaluation of therapeutic nanoplatforms especially in deep-tissues is of great importance but faces challenges. Meanwhile, chemodynamic therapy (CDT), relying on Fenton reaction by converting H2O2 into toxic hydroxyl radicals (•OH), has drawn wide interests in the fabrication of nanozymes for tumor therapy, while endogenous H2O2 is usually insufficient for effective CDT. Here, we report the pH-responsive multifunctional nanoplatforms consisting of copper peroxide (CP) nanoparticles, paclitaxel (PTX) and perfluoro-15-crown-5-ether (PFCE), for 19F magnetic resonance imaging guided and enhanced chemo-chemodynamic synergetic therapy with self-supplied H2O2 stemmed from the decomposition of CP nanoparticles under acid conditions in tumor. The decomposition of CP nanoparticles further promotes the release of PTX for enhanced chemotherapy. Both in vitro and in vivo results indicate that the efficient generation of •OH and drug release effectively inhibits tumor growth. Furthermore, 19F MRI signal can clearly track the fate of nanoplatforms in tumor and guide tumor treatment. This work provides a promising strategy for the rational design and construction of multifunctional nanoplatforms for imaging-guided synergistic therapy of deep seated tumor.

(3+1)-Dimensional Modulated Structure and Tb3+-Doped Luminescence for Vanadate Na3La(VO4)2.

A modulated structure with symmetrical characteristic higher than three-dimensional is a fascinating crystallographic type, and it is randomly encountered by researchers. Herein, we prepared 0.1 mm level single crystals of Na3La(VO4)2 and determined its structure to be a (3 + 1)-dimensional modulated structure using the X-ray diffraction analysis method for single crystals. Its super space group was determined to be Pca21(0ß0)000. On the other hand, we introduced Tb3+ into the Na3La(VO4)2 host lattice to fabricate phosphors Na3La1-x(VO4)2:xTb3+ and studied their photoluminescence properties. Interestingly, for the strong absorption of the Na3La(VO4)2 host lattice in the range of 200-400 nm, the traditional 330-385 nm light is unable to efficiently excite Tb3+ ions in the Na3La(VO4)2 host to generate luminescence of Tb3+. Instead, Na3La1-x(VO4)2:xTb3+ is suitable to be excited by 487 nm to generate emitting light at 543, 584, and 622 nm, due to Tb3+ characteristic 4f → 4f transitions of 5D4 → 7FJ (J = 5, 4, 3). Hence, the Tb3+-doped Na3La(VO4)2 phosphors have potential applications for white-light-emitting diodes.

Fluorescence Lifetime-Based Luminescent Thermometry Material with Lifetime Varying over a Factor of 50.

Recently, the growing demand for temperature detection is pushing forward the flourishing development of noncontact optical thermometry. Herein, a new red phosphor Sr2InTa1-xO6:xMn4+ (SIT:xMn4+) was first constructed and systematically investigated. Based on the fairly rapid decline of the lifetime from 0.403 to 0.008 ms by increasing the temperature from 25 to 450 K, a noncontact optical thermometer can be made from phosphor SIT:0.003Mn4+ with Sr = 1.396% K-1 at 375 K and Sa = 0.0012 K-1 at 300 K. Because the luminescence is based on the outermost 3d orbits of Mn4+, the lifetime of SIT:xMn4+ is quite sensitive to the temperature, leading to a rapid decline of the lifetime with the increase in temperature. Moreover, multiple rounds of variable-temperature studies were performed to demonstrate the stability and reversibility of SIT:0.003Mn4+. This work suggests that Mn4+-phosphors are promising candidates for application as optical thermometric material.

Self-assembled peptide hydrogel scaffolds with VEGF and BMP-2 enhanced in vitro angiogenesis and osteogenesis.

OBJECTIVES: The reconstruction of bone defects remains a major clinical issue. Our study aims to investigate the ability of RATEA16 (RA, [CH3CONH] RADARADARADARADA-[CONH2]) for the sustained delivering VEGF and BMP-2 to promote angiogenesis and osteogenesis in bone reconstruction. MATERIALS AND METHODS: We prepared and investigated the characterization of RATEA16. The survival of human umbilical vein endothelial cells (HUVECs) and human stem cells of the apical papilla (SCAPs) encapsulated in RATEA16 hydrogel was detected. Then, we established RA-VEGF/BMP-2 drug delivery systems and measured their drug release pattern. The effects of RA-VEGF scaffolds on HUVECs angiogenesis were investigated in vitro. Then, osteoblastic differentiation capacity of SCAPs with RA-BMP-2 scaffolds was analyzed by ALP activity and expression of osteoblast-related genes. RESULTS: A porous nanofiber microstructure endowed this scaffold with the ability to maintain the survival of HUVECs and SCAPs. The RA-VEGF/BMP-2 drug delivery systems exhibited several advantagesin vitro: injectability, biodegradability, good biocompatibility, and noncytotoxicity. Released rhVEGF165 /BMP-2 were proved to promote angiogenesis of HUVECs as well as osteogenesis of SCAPs abilities. CONCLUSION: RATEA16 loading with VEGF and BMP-2 might be a potential clinical strategy for tissue engineering, especially in bone reconstruction, due to its ability of delivering growth factors effectively and efficiently.

Early platelet elevation after complete remission as a prognostic marker of favourable outcomes in favourable- and intermediate-risk acute myeloid leukaemia: A retrospective study.

OBJECTIVES: Platelet (PLT) recovery after chemotherapy is associated with the prognosis of patients with acute myeloid leukaemia (AML). This study aimed to explore the prognostic significance of early high PLT values in patients with de novo non-M3 AML who achieved first complete remission (CR). METHODS: A total of 206 patients with de novo non-M3 AML were analysed in this retrospective study. A receiver operating characteristic (ROC) curve was used to determine the optimal PLT cut-off. The overall survival (OS) and relapse-free survival (RFS) were assessed using Kaplan-Meier and Cox regression analyses. RESULTS: 312×109 /L was confined as the cut-off of the PLT count. The estimated 3-year OS of patients with high PLT was higher than that of their counterparts (72.3% vs. 34.6%, p = 0.001). In subgroup analysis, patients with high PLT had better OS in the favourable- and intermediate-risk (non-adverse-risk) AML (p = 0.001). The estimated 3-year RFS for the high and low PLT groups was 75.1% and 45.7% respectively (p = 0.078). Multivariate analyses revealed that high PLT count was an independent favourable variable for OS (HR = 0.264, p < 0.001) and RFS (HR = 0.375, p = 0.011) in the non-adverse-risk group. CONCLUSION: Our results showed that early high PLT count recovery at first CR in non-adverse-risk AML patients is a positive prognostic marker for survival outcomes.

Designing a Polyphosphate Polymorph of CsMg(PO3)3 as Host Lattice for Preparing Single Mn2+-Oxidation Doped Phosphor in the Open Environment.

Within Mn-activated phosphors, the oxidation state of Mn dopant strongly depends on the structural features of the host lattice. This paper reported a new polymorph of CsMg(PO3)3 (CMP) with a complicated three-dimensional (3D) framework of [Mg(PO3)3]∞ that is constructed by MgO6 octahedra and 1D infinite [PO3]∞ chains. Then we prepared a series of red phosphors CsMg1-x(PO3)3:xMn2+ (CMP:xMn2+) by high temperature solid state reactions in the open air. Powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and photoluminescence (PL) studies revealed the single Mn2+-oxidation. Under 404 nm light exciting, CMP:0.2Mn2+ can emit single-band emission at around 630 nm with full-width at half-maximum (fwhm) of 70 nm. Besides, CMP:0.2Mn2+ possesses excellent thermostability up to 450 K. These features indicate that CMP:0.2Mn2+ is suitable to be used for LED backlight display. Moreover, this work suggests that a host lattice with suitable structure feature can form single Mn2+-oxidation and is rigid enough to protect Mn2+ from being oxidized by O2 at high temperature.

Impact of salt substitute and stepwise reduction of salt supply on blood pressure in residents in senior residential facilities: Design and rationale of the DECIDE-Salt trial.

BACKGROUND: High sodium intake has been considered as the leading dietary risk factor for deaths and disability-adjusted life-years among older adults. High-quality randomized trials to evaluate the effects of practical sodium reduction strategies are needed. METHODS: The study is a cluster randomized trial with a 2 × 2 factorial design conducted in 48 senior residential facilities in northern China. These facilities are randomly assigned (1:1:1:1) to 1 of 4 groups: stepwise salt supply control (SSSC) in which 5%-10% of the study salt supply in the institutional kitchens will be reduced every 3 months, replacing normal salt with salt substitute (SS); SSSC only; SS only; or neither SSSC nor SS. The interventions last for 2 years with follow-up every 6 months. The primary outcome is the change in systolic blood pressure from baseline to 24 months. Secondary outcomes include the incidence of hyperkalemia, hyponatremia, cardiovascular events, and death. CURRENT STATUS: The study has recruited and randomized 48 senior residential facilities with 1,606 participants. Mean age at baseline was 71 years, and 76% are male. Both types of salt intervention were initiated in the study facilities between January and April 2018. CONCLUSION: The study is well placed to define the effects of 2 practical and scalable sodium reduction strategies for blood pressure reduction and will provide important new data about safety of these strategies among older adults in China.

Interim effects of salt substitution on urinary electrolytes and blood pressure in the China Salt Substitute and Stroke Study (SSaSS).

The Salt Substitute and Stroke Study is an ongoing 5-year large-scale cluster randomized trial investigating the effects of potassium-enriched salt substitute compared to usual salt on the risk of stroke. The study involves 600 villages and 20,996 individuals in rural China. Intermediate risk markers were measured in a random subsample of villages every 12 months over 3 years to track progress against key assumptions underlying study design. Measures of 24-hour urinary sodium, 24-hour urinary potassium, blood pressure and participants' use of salt substitute were recorded, with differences between intervention and control groups estimated using generalized linear mixed models. The primary outcome of annual event rate in the two groups combined was determined by dividing confirmed fatal and non-fatal strokes by total follow-up time in the first 2 years. The mean differences (95% CI) were -0.32 g (-0.68 to 0.05) for 24-hour urinary sodium, +0.77 g (+0.60 to +0.93) for 24-hour urinary potassium, -2.65 mmHg (-4.32 to -0.97) for systolic blood pressure and +0.30 mmHg (-0.72 to +1.32) for diastolic blood pressure. Use of salt substitute was reported by 97.5% in the intervention group versus 4.2% in the control group (P<.0001). The overall estimated annual event rate for fatal and non-fatal stroke was 3.2%. The systolic blood pressure difference and the annual stroke rate were both in line with the statistical assumptions underlying study design. The trial should be well placed to address the primary hypothesis at completion of follow-up.

Thermally Stable Phosphor KBa2(PO3)5:Eu2+ with Broad-Band Cyan Emission Caused by Multisite Occupancy of Eu2.

The relationship between the structure and properties is always a hot topic in the luminescent material field. In this work, a new phosphor KBa2(PO3)5:Eu2+ (KBP:Eu) was prepared by a high-temperature solid-state reaction method and characterized by X-ray diffraction, energy-dispersive X-ray spectroscopy, photoluminescence (PL), and electroluminescence studies. The polyphosphate host KBP offers three lattice environments (K1, Ba1, and Ba2) for Eu2+ ions to realize broad-band emission from 380 to 700 nm under 345 nm excitation. The distributions of Eu2+ in the three lattice sites can be proven by low-temperature PL and transient fluorescence spectroscopy. Furthermore, temperature-dependent luminescence studies for phosphor KBP:0.02Eu reveal that its luminescence intensity at 150 °C retains about 97% of the initial value at 25 °C. By composing a 365 nm UV chip and KBP:0.02Eu, CaAlSiN3:Eu2+ phosphors, a warm white-light-emitting diode (WLED) was obtained with a correlated color temperature of 5146 K and chromaticity coordinates (0.3404, 0.3384). Therefore, KBP:Eu phosphor is a potential cyan-emitting phosphor used for high-power WLEDs.

Lignocellulose pretreatment in a fungus-cultivating termite.

Depolymerizing lignin, the complex phenolic polymer fortifying plant cell walls, is an essential but challenging starting point for the lignocellulosics industries. The variety of ether- and carbon-carbon interunit linkages produced via radical coupling during lignification limit chemical and biological depolymerization efficiency. In an ancient fungus-cultivating termite system, we reveal unprecedentedly rapid lignin depolymerization and degradation by combining laboratory feeding experiments, lignocellulosic compositional measurements, electron microscopy, 2D-NMR, and thermochemolysis. In a gut transit time of under 3.5 h, in young worker termites, poplar lignin sidechains are extensively cleaved and the polymer is significantly depleted, leaving a residue almost completely devoid of various condensed units that are traditionally recognized to be the most recalcitrant. Subsequently, the fungus-comb microbiome preferentially uses xylose and cleaves polysaccharides, thus facilitating final utilization of easily digestible oligosaccharides by old worker termites. This complementary symbiotic pretreatment process in the fungus-growing termite symbiosis reveals a previously unappreciated natural system for efficient lignocellulose degradation.

Atractylenolide II reverses the influence of lncRNA XIST/miR-30a-5p/ROR1 axis on chemo-resistance of colorectal cancer cells.

This investigation was conducted to elucidate whether atractylenolide II could reverse the role of lncRNA XIST/miR-30a-5p/ROR1 axis in modulating chemosensitivity of colorectal cancer cells. We totally collected 294 pairs of colorectal cancer tissues and adjacent normal tissues and also purchased colorectal cancer cell lines and human embryonic kidney cell line. 5-fluorouracil, cisplatin, mitomycin and adriamycin were designated as the chemotherapies for colorectal cell lines, and atractylenolides were arranged as the Chinese drug. The expressions of XIST, miR-30a-5p and ROR1 were quantified with aid of qRT-PCR or Western blot, and luciferase reporter gene assay was implemented to determine the relationships among XIST, miR-30a-5p and ROR1. Our results demonstrated that XIST and ROR1 expressions were dramatically up-regulated, yet miR-30a-5p expression was down-regulated within colorectal cancer tissues (P < 0.05). The overexpressed XIST and ROR1, as well as under-expressed miR-30a-5p, were inclined to promote viability and proliferation of colorectal cells under the influence of chemo drugs (P < 0.05). In addition, XIST could directly target miR-30a-5p, and ROR1 acted as the targeted molecule of miR-30a-5p. Interestingly, atractylenolides not only switched the expressions of XIST, miR-30a-5p and ROR1 within colorectal cancer cells but also significantly intensified the chemosensitivity of colorectal cancer cells (P < 0.05). Finally, atractylenolide II was discovered to slow down the viability and proliferation of colorectal cancer cells (P < 0.05). In conclusion, the XIST/miR-30a-5p/ROR1 axis could be deemed as pivotal markers underlying colorectal cancer, and administration of atractylenolide II might improve the chemotherapeutic efficacy for colorectal cancer.

Dietary Sodium Reduction Reduces Albuminuria: A Cluster Randomized Trial.

OBJECTIVES: The objective of the study was to assess the impact of sustained dietary salt reduction on albuminuria in nearly 2000 community-dwelling adults. DESIGN AND METHODS: The present study is a prespecified secondary analysis of the China Rural Health Initiative Salt Reduction Study cluster randomized trial undertaken in 120 villages in rural China. Villages were randomized to a sodium reduction program of education and access to reduced-sodium salt substitute or control. Urinary albumin-to-creatinine ratio (uACR) and albuminuria (uACR ≥22.1 or 31.0 mg/g for men and women, respectively) were assessed at 18 months in a stratified random sample of predominantly older individuals living in participating rural villages. RESULTS: A total of 2,566 participants from 119 villages provided 1,903 eligible urine samples. The sodium reduction program reduced sodium intake by an equivalent of 0.82g of salt/day (0.06-1.68 g) (322 [24-661] mg sodium/day). The mean uACR was 8.85 (8.05-9.82) mg/g (1.00 [0.91-1.11] mg/mmol) in intervention participants compared with 10.53 (9.73-11.33) mg/g (1.19 [1.10-1.28] mg/mmol) in control participants (p=0.008). The corresponding odds ratio for albuminuria was 0.67 (0.46-0.99). CONCLUSIONS: Dietary sodium reduction was associated with significantly lower uACR and less albuminuria after 18 months. Whether CKD progression can be slowed by dietary sodium reduction should be a global research priority. CLINICALTRIALS.GOV: NCT01259700.

Multifunctionality assessment of the land use system in rural residential areas: Confronting land use supply with rural sustainability demand.

By applying an integrated framework, we developed a new way to quantify the multifunctionality of rural residential land: analyzing the reciprocal relationships between the structure and function of land use, as well as identifying the demand of rural sustainability for residential land functions. In the assessment of the rural residential land functions from the supply and demand perspectives by establishing an indicators system, the results show that there are five substantial functions of rural residential land, i.e., residential, public service, industrial, commercial and ecological function, and a potential function. Unbalanced development patterns between function supply and demand are clearly observed at multilevel: at the regional level, demand exceeding supply refers to the public service, commercial, and ecological function, especially for ecological function; at the town level, the spatial pattern of the difference is closely linked with topographic features; the inferior and complex topographic condition always is associated with inadequate function supply. Strategies based on the arrangements of rural residential land use structure, including function conversion and function enhancement, have been adopted to balance the supply and demand of land functions. Together, alternative strategies (e.g., industrial allocation, population introduction, and location choices) also need to be recognized by policymakers to achieve rural sustainable development.

Monomeric catechin and dimeric procyanidin B2 against human norovirus surrogates and their physicochemical interactions.

Plant polyphenols have shown antiviral activity against several human pathogens, but their physicochemical interactions are not well-understood. The objectives of this study were to compare the antiviral activity between monomeric catechin and dimeric procyanidin B2 (PB2) using cultivable human norovirus surrogates (feline calicivirus (FCV-F9) and murine norovirus (MNV-1)) and to understand their potential antiviral mechanism using virus-like particles (VLPs) and the P domain of human norovirus GII (HNoV GII.4). Surrogate viruses at 5 log PFU/mL were treated with 0.5-5 mg/mL monomeric catechin monohydrate, PB2 or phosphate buffered saline (PBS, pH 7.2; control) at 37 °C over 24 h. Infectivity was determined using plaque assays and data from triplicate experiments were statistically analyzed. PB2 at 0.5 mg/mL and 1 mg/mL reduced FCV-F9 to undetectable levels after 3 h and MNV-1 by 0.21 and 1.23 log PFU after 24 h, respectively. Monomeric catechins at 1 mg/mL reduced FCV-F9 to undetectable levels after 6 h and MNV-1 titers to undetectable levels after 24 h. In addition, PB2 was shown to directly bind the P domain, the main capsid structure of HNoVs in the ratio of 1:1 through spontaneous interactions. Electrostatic interactions played a dominant role between PB2 and the P domain. PB2 significantly altered tertiary but not secondary structures of VLPs. Transmission electron microscopy demonstrated that PB2 aggregated VLPs, further indicating interactions between them. These findings indicate that PB2 causes structural changes of the P domain of VLPs, mainly through direct interaction leading to HNoV inactivation.

Statistical analysis of factors affecting re-operative times in paediatric patients with scar deformity after deep second-degree burn injury.

Deep second-degree burn injuries pose a challenge for treating scar deformity in developing paediatric patients. Some patients underwent several re-operations during their development. There was no literature reporting which factors affect re-operative times. In this article, we intend to analyse possible influential factors that are responsible for re-operative times in paediatric patients with scar deformity after deep second-degree burn injuries. From 2010 to 2016, 177 paediatric cases with a history of deep second-degree burn injury who underwent re-operation once, twice, and equal to or more than thrice were recruited to this study, with age ranging from 0 to 18 years. The following factors were analysed: age, gender, size of scar, method for reconstruction, location, postoperative anti-scar treatment, preschool group, school group, combined deformity, and combined method for reconstruction. One-way ANOVA and multi-way ANOVA analysis were used as statistical tools to analyse the above factors and re-operative times. There were 83 male cases and 94 female cases, with an average age of 7.47 years. Statistical significance was achieved for the size of scar (P = 0.000), operation method (P = 0.001), and combined deformity (P = 0.026) under 1-way ANOVA in different re-operative times. The operation methods for the head and neck area (P < 0.05) and the lower extremities (P < 0.05) are critical factors for multi-factor variance analysis in different re-operative times. Multivariate logistic regression analysis also demonstrated that the size of scar was an independent risk factor for the number of operations. Combined operative method was a protective risk factor for the number of operations. There was no statistical significance obtained for other factors. Size of scar, operation method, and combined operation method are the risk factors for re-operative times, while operation methods for the head and neck area and lower extremities are the critical factors for re-operative times. We can use the combined method to resolve scar-related problems in order to reduce re-operative times.

Rationale, design, and baseline characteristics of the Salt Substitute and Stroke Study (SSaSS)-A large-scale cluster randomized controlled trial.

Lowering sodium intake with a reduced-sodium, added potassium salt substitute has been proved to lower blood pressure levels. Whether the same strategy will also reduce the risks of vascular outcomes is uncertain and controversial. The SSaSS has been designed to test whether sodium reduction achieved with a salt substitute can reduce the risk of vascular disease. The study is a large-scale, open, cluster-randomized controlled trial done in 600 villages across 5 provinces in China. Participants have either a history of stroke or an elevated risk of stroke based on age and blood pressure level at entry. Villages were randomized in a 1:1 ratio to intervention or continued usual care. Salt substitute is provided free of charge to participants in villages assigned to the intervention group. Follow-up is scheduled every 6months for 5years, and all potential endpoints are reviewed by a masked adjudication committee. The primary end point is fatal and nonfatal stroke, and the 2 secondary endpoints are total major cardiovascular events and total mortality. The study has been designed to provide 90% statistical power (with 2-sided α = .05) to detect a 13% or greater relative risk reduction for stroke. The power estimate assumes a primary outcome event rate of 3.5% per year and a systolic blood pressure difference of 3.0mm Hg between randomized groups. Recruitment is complete and there are 20,996 participants (about 35 per village) that have been enrolled. Mean age is 65years and 49% are female. There were 73% enrolled on the basis of a history of stroke. The trial is well placed to describe the effects of salt substitution on the risks of vascular disease and death and will provide important policy-relevant data.