Oral anticoagulants status after acute ischemic stroke and prognosis in patients with atrial fibrillation.

OBJECTIVES: To investigate the oral anticoagulants (OACs) use after acute ischemic stroke (AIS) and prognosis of patients with atrial fibrillation (AF). METHODS: This was a real-world follow-up research of AIS patients with AF admitted to 5 hospitals in northwestern China. We visited these individuals every 6 months to check the type, dosage of OACs, and to record IS recurrence, bleeding, and death events and modified Rankin Scale (mRS) scores until December 2022. When one of the following occurring first was endpoint: IS recurrence, death or study end. Patients were divided into continuous anticoagulation group and non-continuous anticoagulation group based on whether they continued to take OACs from the moment they were discharged until the endpoint. We further analyzed the association between anticoagulation persistence and outcomes. RESULTS: Among all 250 patients with OACs indication, 147 patients (58.8 %) received OACs at discharge. Only 37.9 % of patients (39/103) started OACs after discharge. Of the 147 patients treated with OACs, 21.8 % (32/147) discontinued anticoagulation after discharge. 239 of the 250 patients had completed the median 40-month follow-up with 91 patients in continuous anticoagulation group and 148 patients in non-continuous anticoagulation group. In the multivariate COX regression, non-continuous anticoagulation was an independent risk factor for poor prognosis (mRS>2) in AIS patients with AF (1.452[1.011, 2.086], p = 0.043). CONCLUSIONS: This study revealed an upward trend in the use rate of OACs, but low OACs rates that meet guideline-based criteria and low anticoagulation persistence in AF patients after AIS in the northwestern China. Discontinuous anticoagulation was associated with an increased risk of poor prognosis in these patients.

Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8+ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

[Effect of Biochar with Phosphorus Fertilizer on Soil Nutrients, Enzyme Activity, and Nutrient Uptake of Alfalfa].

Biochar is widely used in agricultural production practices as a soil conditioner that can be used both alone and jointly with chemical fertilizer. However, there are few studies on the effects of the combined application of biochar and phosphate fertilizer with different particle sizes on soil and plants. In this experiment, pot experiments were used to study the effects of biochar with different particle sizes on soil nutrients, enzyme activity, and Alfalfa nutrient absorption under two phosphorus levels (according to diameter, the biochar was divided into C1:>1 mm and C2:<0.01 mm). This study showed that the combined application of biochar and phosphorus significantly improved soil nutrients, enzyme activity, and Alfalfa nutrient absorption. Among them, the C2 treatment significantly increased the soil available phosphorus content and phosphatase activity (P<0.05), whereas the C1 treatment had a significant effect on ammonium nitrogen, nitrate nitrogen, urease, and catalase activities (P<0.05). Moreover, the differences in nutrients and enzymes among biochar treatments with different particle sizes were affected by soil phosphorus levels. At the P0 level, there was no significant difference in ammonium nitrogen and nitrate nitrogen contents between the C1 and C2 treatments. At the P1 level, the contents of NH4+-N and NO3--N in the C1 treatment were 24.19% and 18.68% higher than those in the C2 treatment (P<0.05), but there was no significant difference between the C1 and C2 treatments. Phosphorus addition significantly increased the N and P contents of Alfalfa above ground and in the ground (P<0.05), but there was no significant effect on the nutrient content of Alfalfa between different particle sizes of biochar. In conclusion, biochar and phosphate fertilizer can be used as an effective means of soil improvement. In addition, when using biochar for soil improvement, the impact of particle size on soil nutrients and soil enzymes should be considered.

Preparation, characterization, identification, and antioxidant properties of fermented acaí (Euterpe oleracea).

Fermentation technology was used to prepare the acaí (Euterpe oleracea) fermentation liquid. The optimal fermentation parameters included a strain ratio of Lactobacillus paracasei: Leuconostoc mesenteroides: Lactobacillus plantarum = 0.5:1:1.5, a fermentation time of 6 days, and a nitrogen source supplemental level of 2.5%. In optimal conditions, the ORAC value of the fermentation liquid reached the highest value of 273.28 ± 6.55 µmol/L Trolox, which was 55.85% higher than the raw liquid. In addition, the FRAP value of the acaí, as well as its scavenging ability of DPPH, hydroxyl, and ABTS free radicals, increased after fermentation. Furthermore, after fermentation treatment, the microstructure, basic physicochemical composition, amino acid composition, γ-aminobutyric acid, a variety of volatile components, and so on have changed. Therefore, fermentation treatment can significantly improve the nutritional value and flavor of the acaí. This provides a theoretical basis for the comprehensive utilization of acaí.

Genetic analysis of neonates with abnormal isovaleryl carnitine metabolism / 中华实用儿科临床杂志

Objective:To explore the genetic causes of abnormal isovaleryl carnitine (C5) metabolism in newborns.Methods:Retrospective study.The screening and clinical follow-up data of 34 neonates with elevated C5 levels shown by the tandem mass spectrometry test in Children′s Hospital, Zhejiang University School of Medicine from January 2018 to December 2021 were collected.Afterwards, their ethylenediaminetetraacetic acid (EDTA) anticoagulant venous blood was collected to extract genomic DNA.A total of 79 genes related to genetic metabolic diseases, such as ACADSB, IVD and ACADM, were captured by liquid-phase capture technology.High-throughput sequencing and bioinformatics analysis were used to acquire gene variation information and the genes were categorized by American College of Medical Genetics and Genomics classification standard.According to the results of genetic analysis, the newborns with C5 elevation were divided into 3 groups: non-mutation group(11 cases), ACADSB mutation group(16 cases) and IVD mutation group(7 cases). Wilcoxon rank sum test was performed to analyze the difference between these groups. Results:Among 34 neonates, 6 ACADSB variants were detected in 16 cases, and 2 of them [c.461G>A (p.G154E), c.746delC(p.P249Lfs*15)] were novel variants.Eleven IVD variants were detected in 7 cases, and 7 of them [c.118A>G(p.N40D), c.296-10C>G, c.302A>G(p.Y101C), c.537G>A(p.M179I), c.667C>T(p.R223W), c.983A>G(p.K328R), c.1147+ 5G>A] were never reported before.There was no significant difference in the C5 concentration in initial screening among the three groups ( P>0.05). Conclusions:Mutations in ACADSB and IVD genes are the main causes of augmented C5 levels in neonatal screening.For newly discovered genetic variants, functional prediction by multiple bioinformatics analysis software is recommended.And it is also important to carry out clinical follow-up and evaluation.

Newborn screening for ornithine transcarbamylase deficiency in Zhejiang Province and the follow-up analysis / 中华实用儿科临床杂志

Objective:To investigate the incidence, clinical characteristics and prognosis of ornithine transcarbamylase deficiency(OCTD) in newborns in Zhejiang Province.Methods:A retrospective research was conducted.A total of 4 261 036 newborns from Department of Genetics and Metabolism, Children′s Hospital, Zhejiang University School of Medicine, between January 2009 and December 2021 were screened for inherited metabolic disorders using tandem mass spectrometry.OCTD was confirmed by urine organic acid and OTC gene analysis.Patients with OTCD received guidance on diet and lifestyle management, and were treated with citrulline and arginine.Long-term follow-up was performed.Their growth and intellectual development were evaluated. Results:A total of 7 patients with OCTD were diagnosed, with an incidence of 1.6/1 million.All patients were males.Two patients had neonatal-onset OCTD, and the other 5 had late-onset OCTD.Symptoms occurred several times in 6 patients, inducing hyperammonemia and hepatic impairment.One patient had no clinical manifestation.One patient died in the neonatal period.Blood citrulline levels were decreased in 7 patients to varying degrees.Uracil levels were increased in 4 patients, and 1 of them was complicated with elevated orotic acid levels.All patients had hemizygote variations in the OTC gene, including 6 missense variations(c.604C>T, c.386G>A, c.779T>C, c.1019C>T, c.594C>G, c.931G>A) and 1 intron variation(c.514-35C>G). Two variants(c.594C>G, c.514-35C>G) were never reported previously. Conclusions:The OTCD incidence by newborn screening is low with 1.6/1 million in Zhejiang province.All patients are males and present hypocitrullinemia.The clinical manifestations of OTCD are highly heterogeneous.The neonatal-onset form is severe and survivors always suffer serious sequelae.The late-onset form is mostly manifested with hyperammonemia and hepatic impairment.There may be association between phenotype and genotype.Two novel OTC variants are identified, which further expands the mutational spectrum.

A multi-center study of biochemical and hotspot gene screening for neonatal genetic metabolic diseases / 中华实用儿科临床杂志

Objective:To investigate the efficiency of biochemical screening and hotspot gene screening in the detection of neonatal inherited metabolic diseases.Methods:This was a prospective multi-center study.The study was carried out on 21 442 neonatal samples collected from 12 hospitals in 10 provinces from November 2020 to November 2021.The results of biochemical screening and hotspot gene screening were analyzed jointly.Biochemical screening methods included glucose-6-phosphate dehydrogenase deficiency enzyme activity assay and neonatal tandem mass spectrometry.Genetic screening analysis involved 135 genes associated with 75 neonatal diseases.Results:Of all the 21 442 neonates enrolled in the study, 21 205 were subject to biochemical screening.A total of 813 cases were positive in the initial screening, and 0.45% of them (95 cases) were diagnosed after recall.All the 21 442 neonates underwent gene screening.About 168 positive cases were detected in the initial screening, and 0.73% (156 cases) of them were confirmed finally.Biochemical and genetic screening improved the detection sensitivity of such diseases as primary carnitine deficiency, neonatal intrahepatic cholestasis caused by citrin deficiency, and 2-methylbutyrylglycinemia.Moreover, biochemical and genetic screening enabled the detection of more diseases, including the common single-gene genetic diseases such as thalassemia and Wilson disease.Conclusions:In neonatal screening, the combination of biochemical screening and gene screening expands the number of diseases detected and improve screening efficiency.

Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor-associated macrophages

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

Long-term follow-up of children with carbamoyl phosphate synthase 1 deficiency detected in newborn screening / 浙江大学学报·医学版

OBJECTIVES@#To investigate genotype-phenotype characteristics and long-term prognosis of neonatal carbamoyl phosphate synthetase 1 (CPS1) deficiency among children through newborn screening in Zhejiang province.@*METHODS@#The clinical and follow-up data of children with CPS1 deficiency detected through neonatal screening and confirmed by tandem mass spectrometry and genetic testing in Zhejiang Province Newborn Disease Screening Center from September 2013 to August 2023 were retrospectively analyzed.@*RESULTS@#A total of 4 056 755 newborns were screened and 6 cases of CPS1 deficiency were diagnosed through phenotypic and genetic testing. Ten different variations of CPS1 genewere identified in genetic testing, including 2 known pathogenic variations (c.2359C>T and c.1549+1G>T) and 8 unreported variations (c.3405-1G>T, c.2372C>T, c.1436C>T, c.2228T>C, c.2441G>A, c.3031G>A, c.3075T>C and c.390-403del). All patients had decreased citrulline levels (2.72-6.21 μmol/L), and varying degrees of elevated blood ammonia. The patients received restricted natural protein intake (special formula), arginine and supportive therapy after diagnosis, and were followed-up for a period ranging from 9 months to 10 years. Three patients experienced hyperammonemia, and one patient each had attention deficit hyperactivity disorder, transient facial twitching and increased muscle tone. One patient died, while the other five surviving patients had normal scores of the Ages & Stages Questionnaires (ASQ) and Griffiths Development Scales up to the present time; 4 cases had combined height or weight lag and one case was normal in height and weight.@*CONCLUSIONS@#Low citrulline levels and hyperammonemia are common in CPS1 deficiency patients in Zhejiang. Most gene variants identified were specific to individual families, and no hotspot mutations were found. Early diagnosis through newborn screening and following standardized treatment can significantly improve the prognosis of the patients.

B3GALT4 remodels the tumor microenvironment through GD2-mediated lipid raft formation and the c-met/AKT/mTOR/IRF-1 axis in neuroblastoma.

BACKGROUND: Beta-1,3-galactosyltransferase-4 (B3GALT4) plays a critical regulatory role in tumor biology. However, the role of B3GALT4 in modulating the tumor microenvironment (TME) of neuroblastoma (NB) remains unknown. METHODS: Public datasets and clinical NB samples were collected to evaluate the expression and clinical significance of GD2 and B3GALT4 in NB patients. CCK-8, colony formation, and transwell assays and experiments in tumor-bearing mouse models were conducted to investigate the function of B3GALT4. Flow cytometry, ELISA, immunohistochemistry, immunofluorescence, western blotting, and chemotaxis assays were conducted to ascertain the immunomodulatory mechanism of B3GALT4. The combined therapeutic effect of the lipid raft inhibitor MßCD and anti-GD2 mAb was validated in a murine model of NB. RESULTS: GD2 was overexpressed in NB tissues and high expression of GD2 was associated with poor prognosis in NB patients. B3GALT4 was downregulated in NB tissues, and low expression of B3GALT4 indicated poor prognosis in NB patients. Silencing B3GALT4 significantly enhanced tumor progression both in vitro and in vivo. Meanwhile, the overexpression of B3GALT4 increased the recruitment of CD8+ T lymphocytes via the chemokines CXCL9 and CXCL10. Additionally, B3GALT4 regulated NB-cell GD2 expression and lipid raft formation. Mechanistically, B3GALT4 regulated the expression of CXCL9 and CXCL10 via the c-Met signaling in the lipid rafts and the downstream AKT/mTOR/IRF-1 pathway. The lipid raft inhibitor, MßCD, attenuated B3GALT4 deficiency-induced tumor progression and immune evasion. Last, MßCD combined with anti-GD2 mAb treatment significantly enhanced the antitumor effect and the infiltration of CD8+ T cells. CONCLUSIONS: Upregulation of B3GALT4 promotes the secretion of CXCL9 and CXCL10 to recruit CD8+ T lymphocytes via the GD2-mediated lipid rafts and the c-Met/AKT/mTOR/IRF-1 pathway. Moreover, lipid raft inhibitors may enhance the efficacy of anti-GD2 immunotherapy for NB.

[Bibliometric analysis on key elements of clinical application of acupoint catgut embedding therapy in recent ten years].

OBJECTIVE: To analyze the characteristics of acupoint catgut embedding methods, tools, catgut types, and the treatment cycles in the clinical research in recent ten years both at home and abroad, so as to summarize its regularities and to provide technical references for further studies. METHODS: Articles about clinical researches on catgut embedding therapy published in recent ten years (from January 1, 2010 to December 31,2020) were retrieved from the databases of CNKI, Wanfang, VIP, and PubMed by using key words of "acupoint embedding" "acupoint catgut embedding" and "catgut implantation at acupoint". According to the inclusion and exclusion criteria, a new database was established for analyzing the data mentioned above. RESULTS: 1) A total of 1 196 articles were collected, including 15 English articles and 1 181 Chinese articles, presenting a fluctuating increasing trend in recent ten years. 2) The commonly used acupoint embedding methods included disposable catgut embedment needle method (399 times, 38.89%) and disposable syringe needle catgut embedding method (347 times, 33.82%), for which two or multiple methods were mentioned in the same one article. 3) The most frequently used top two tools for catgut embedding were the dispo-sable catgut embedment needle (463 times, 43.03%) and disposable syringe needle (406 times,37.73%), with a significant increase in the application of disposable syringe needle. The most commonly used size of tools included No. 7 (283 times, 39.86%), No. 9 (196 times, 27.61%) and No. 8 (109 times, 15.35%). 4) The most frequently implanted surgical suture was still the common catgut (671 times, 58.15%) despite of a reduction in clinical application year by year, and the types of the implanted suture materials were gradually enriched since 2018, such as the absorbable surgical suture, polyethylprolactide(PGLA), collagen protein thread, polydioxanone(PPDO), etc. The commonly used implanted catgut size was 3-0 (227 times, 30.15%), 2-0 (176 times, 23.37%), 4-0 (131 times, 17.40%), 0 (103 times, 13.68%), with the commonly used catgut length being 1 cm (332 times, 35.55%), 1.5 cm (103 times, 11.03%), 1-2 cm (92 times, 9.85%) and 2 cm (92 times, 9.85%). 5) The intervals of the catgut implantation were 7 days (313 times, 28.95%), 14 days (262 times, 24.24%), 10 days (174 times, 16.10%), and 15 days (162 times, 14.99%). CONCLUSION: In recent ten years, clinical research on acupoint catgut embedding is growing rapidly, and the embedding methods, tools, implanted sutures, and embedding intervals are various, which may provide certain technical references for the future researches and suggest an urgent need of formulation of the standardized and unified standards in this field.

Flavonoid Synthesis and Metabolism During the Fruit Development in Hickory (Carya cathayensis).

Hickory (Carya cathayensis) kernel is rich in powerful bioactive flavonoids, which can remove excess free radicals in the human body and play an important role in regulating the physiological metabolism of the plant. This study investigated the changes of flavonoids in hickory exocarp and embryo during development. In this study, 72 DEGs involved in the regulation of flavonoid biosynthesis in fruits were identified, and TT4, CCoAOMT1, UGT71D1, C4H, F3H, TT8, FLS1, and LDOX were identified as the core genes of flavonoid biosynthesis. A total of 144 flavonoid-related metabolites were detected by metabolite analysis. Transcriptome and metabolome analysis combined to construct the flavonoid biosynthesis regulatory pathway in the development stage of hickory fruit. Our results provide a theoretical basis for the exploration and regulation of functional genes related to flavonoid biosynthesis and metabolism in hickory and other plants and the breeding of new walnut varieties.

Erratum: Author correction to "A nanocleaner specifically penetrates the blood‒brain barrier at lesions to clean toxic proteins and regulate inflammation in Alzheimer's disease" Acta Pharmaceutica Sinica B 12, (2021) 4032-4044

[This corrects the article DOI: 10.1016/j.apsb.2021.04.022.].

Co-delivery of photosensitizer and diclofenac through sequentially responsive bilirubin nanocarriers for combating hypoxic tumors

Considering that photodynamic therapy (PDT)-induced oxygen consumption and microvascular damage could exacerbate hypoxia to drive more glycolysis and angiogenesis, a novel approach to potentiate PDT and overcome the resistances of hypoxia is avidly needed. Herein, morpholine-modified PEGylated bilirubin was proposed to co-deliver chlorin e6, a photosensitizer, and diclofenac (Dc). In acidic milieu, the presence of morpholine could enable the nanocarriers to selectively accumulate in tumor cells, while PDT-generated reactive oxidative species (ROS) resulted in the collapse of bilirubin nanoparticles and rapid release of Dc. Combining with Dc showed a higher rate of apoptosis over PDT alone and simultaneously triggered a domino effect, including blocking the activity and expression of lactate dehydrogenase A (LDHA), interfering with lactate secretion, suppressing the activation of various angiogenic factors and thus obviating hypoxia-induced resistance-glycolysis and angiogenesis. In addition, inhibition of hypoxia-inducible factor-1α (HIF-1α) by Dc alleviated hypoxia-induced resistance. This study offered a sequentially responsive platform to achieve sufficient tumor enrichment, on-demand drug release and superior anti-tumor outcomes in vitro and in vivo.

Closed Reduction for the Treatment of Grade IV Supination-External Rotation Fracture of the Ankle Joint: A Retrospective Analysis.

OBJECTIVE: To investigate the curative effect of closed reduction and external fixation in the treatment of grade IV supination-external rotation fractures of the ankle joint. METHODS: Fifty-six patients treated with closed reduction and external fixation from February 2016 to March 2020 were included in this retrospective study, all with sprains. After receiving nerve block anesthesia, the patient underwent closed reduction under C-arm fluoroscopy, and the ankle joint was fixed in a dorsiflexion-inversion position with casting and splints after the end of the fracture met the reduction standard by fluoroscopy. One week and four weeks after the reduction treatment, oblique axial and coronal MR scans of the ankle joint were performed to determine the degree of injury and healing of the inferior tibiofibular syndesmosis; anteroposterior and lateral X-rays of the ankle joint (including the ankle acupoints) were regularly reviewed to observe the fracture alignment and healing. Combined with the images and physical examination, the patients were instructed to undergo ankle weight-bearing rehabilitation training when they met the clinical healing standard, and at the last follow-up, the Mazur ankle evaluation and grading system were used for evaluation. After the reduction, the images were evaluated according to the Leeds standard. The image healing of fracture was evaluated by callus growth criteria. RESULTS: The follow-up period of patients ranged from 11 to 58 months, with an average of 26.8 months. The clinical healing time was (8.51 ± 2.12) weeks. The excellent and good rating after reduction was 82.1%, and the excellent and good rating during clinical fracture healing was 73.2%, according to the Leeds imaging evaluation. According to the Mazur ankle evaluation and grading system, the excellent and good rating was 75.0%. Pairwise comparison of callus images at 4, 6 and 12 weeks showed statistically significant differences (P < 0.05), suggesting callus growth at different time periods. A total of 56 patients had anterior inferior tibial fibular ligament (AITFL) injuries (grade II-III), among which 11 patients had AITFL injuries combined with grade II injuries of the interosseous ligament (IOL) and 4 patients had AITFL injuries combined with grade III injuries of the IOL. CONCLUSIONS: Most of the patients with grade IV supination-external rotation fracture of the ankle joint had good prognosis after closed reduction and plaster combined with splint fixation. For patients with IOL injury who had poor prognosis, open reduction and internal fixation therapy is appropriate.

A nanocleaner specifically penetrates the blood‒brain barrier at lesions to clean toxic proteins and regulate inflammation in Alzheimer's disease

Insurmountable blood‒brain barrier (BBB) and complex pathological features are the key factors affecting the treatment of Alzheimer's disease (AD). Poor accumulation of drugs in lesion sites and undesired effectiveness of simply reducing A

Rates and Anticoagulation Treatment of Known Atrial Fibrillation in Patients with Acute Ischemic Stroke: A Real-World Study.

INTRODUCTION: Known atrial fibrillation (AF) rate and appropriate prescription of oral anticoagulants (OACs) in acute ischemic stroke (AIS) patients with AF in China are not as well known as in Western countries. METHODS: Known AF and unknown AF, rate and adequacy of OACs use of AIS patients with AF attending five hospitals from April 2018 to August 2019 in the northwest region of China were investigated. RESULTS: A total of 344 patients were enrolled. Of these, 237 (AF-known group; 237/344, 68.9%) and 107 patients (AF-unknown group; 107/344, 31.1%) were diagnosed with AF before and after AIS during this hospitalization, respectively. In the AF-known group with echocardiography results (178 patients, including 103 female and 75 male patients), 154 of overall, 88 of female and 66 of male patients, respectively, were indicated to be taking OACs. However, the actual OACs proportion was much lower [overall (30.5%, 47/154); female (31.8%, 28/88) and male (28.8%, 19/66) patients] than indicated. Only one female patient met the guideline-based criteria for OACs. As for patients diagnosed with massive cerebral infraction (MCI; 43.0%, 148/344), the known AF rate was 65.5% (97/148). Among the MCI patients in the AF-known group with echocardiography results (61 patients), 50 patients had an OACs indication. However, only 22.0% (11/50) of these patients took OACs, and none met the guideline-based criteria for OACs. CONCLUSIONS: This study revealed a low known AF rate, low OACs use rate and low rate of meeting the guideline-based criteria for OACs in AIS patients with AF in the northwest region of China. These findings indicated the importance of AF as a public health problem in China.

Strain Conditions Monitoring on Corroded Prestressed Steel Strands in Beams Based on Fiber Bragg Grating Sensors.

Fiber Bragg Grating (FBG) sensors, with excellent properties, have been widely adopted to monitor the mechanical parameters in civil engineering in recent years. On the other hand, the current study on fatigue performance of corroded prestressed steel strands is still limited, and this is mainly because the long-term strain conditions monitoring is difficult to conduct. Based on the aforementioned considerations, a total of six beam specimens were fabricated in this study. The loading mode of four points bending was adopted in the form of sinusoidal waves in the experiments. On basis of the experimental results, it can be concluded that the fatigue life of the beam decreases sharply with the increase of the corrosion rate of steel strands. Besides, with the increase of the maximum fatigue load, the fatigue life of the beam will decrease significantly. Furthermore, the existing fatigue damage of steel strand inside the beam before corrosion may further accelerate its fatigue failure. As a result, the fatigue life of the beam is reduced because of the stress concentration. Under the same external load, the strain increment and the residual strain of steel strands in the stages of loading and unloading after corrosion increase significantly compared with other stages, while the existing residual strain always shows an increasing trend at various static loading stages. Therefore, the corrosion of steel strand seriously affects not only its mechanical properties, but also its fatigue performance. Finally, the FBG sensors are capable of measuring the steel strand strain, as well as the long-term strain conditions.

GSH-responsive SN38 dimer-loaded shape-transformable nanoparticles with iRGD for enhancing chemo-photodynamic therapy

Accurate tumor targeting, deep penetration and superb retention are still the main pursuit of developing excellent nanomedicine. To achieve these requirements, a stepwise stimuli-responsive strategy was developed through co-administration tumor penetration peptide iRGD with shape-transformable and GSH-responsive SN38-dimer (d-SN38)-loaded nanoparticles (d-SN38@NPs/iRGD). Upon intravenous injection, d-SN38@NPs with high drug loading efficiency (33.92 ± 1.33%) could effectively accumulate and penetrate into the deep region of tumor sites with the assistance of iRGD. The gathered nanoparticles simultaneously transformed into nanofibers upon 650 nm laser irradiation at tumor sites so as to promote their retention in the tumor and burst release of reactive oxygen species for photodynamic therapy. The loaded d-SN38 with disulfide bond responded to the high level of GSH in tumor cytoplasm, which consequently resulted in SN38 release and excellent chemo-photodynamic effect on tumor.

Novel ACADVL variants resulting in mitochondrial defects in long-chain acyl-CoA dehydrogenase deficiency / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The pathogenesis of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is highly heterogeneous and still unclear. Additional novel variants have been recently detected in the population. The molecular and cellular effects of these previously unreported variants are still poorly understood and require further characterization. To address this problem, we have evaluated the various functions and biochemical consequences of six novel missense variants that lead to mild VLCAD deficiency. Marked deficiencies in fatty acid oxidation (FAO) and other mitochondrial defects were observed in cells carrying one of these six variants (c.541C>T, c.863T>G, c.895A>G, c.1238T>C, c.1276G>A, and c.1505T>A), including reductions in mitochondrial respiratory-chain function and adenosine triphosphate (ATP) production, and increased levels of mitochondrial reactive oxygen species (ROS). Intriguingly, higher apoptosis levels were found in cells carrying the mutant VLCAD under glucose-limited stress. Moreover, the stability of the mutant homodimer was disturbed, and major conformational changes in each mutant VLCAD structure were predicted by molecular dynamics (MD) simulation. The data presented here may provide valuable information for improving management of diagnosis and treatment of VLCAD deficiency and for a better understanding of the general molecular bases of disease variability.