Prevalence and Risk Factors of Stroke in Inpatients with Type 2 Diabetes Mellitus in China

Objective The prevalence and the cluster characteristics of risk factors of stroke were assessed in a Chinese diabetic population.Methods Clinical data of 30693 inpatients who were diagnosed with type 2 diabetes mellitus(T2DM)and admitted between 2013 and 2018 were retrospectively analyzed.The age-standardized prevalence of stroke was estimated using the 2010 Chinese population census data,and risk factors were analyzed by multiple imputation and regression.Results The crude and standardized prevalence rates of stroke in patients with T2DM were 34.4%and 21.5%,respectively,and 85.2%of the stroke patients had ischemic stroke.Nearly half of the patients who experienced stroke had clusters of more than 4 risk factors.Compared with no-risk-factor clustering,the risk of stroke significantly increased 3-4 times in the presence of more than 4 risk-factor clusters(P<0.001).Hypertension was the most common major risk factor for ischemic stroke[odds ratio(OR),2.34;95%confidence interval(CI),2.18-2.50]and hemorrhagic stroke(OR,3.68;95%CI 2.95-4.59;P<0.001).Moreover,a 1-standard-deviation increase in fasting blood glucose(FBG)was significantly negatively correlated with ischemic stroke risk,and the same change in FBG was significantly associated with an 8%increased risk of hemorrhagic stroke.Conclusion The prevalence of stroke in patients with T2DM is rather high,and the clustering of risk factors is associated with the development of stroke in T2DM patients.Risk factors differ in different stroke subtypes.Identifying risk factors for a specific high-risk group is necessary.

Fuzzy Sliding Mode Control for the Vehicle Height and Leveling Adjustment System of an Electronic Air Suspension

The accurate control for the vehicle height and leveling adjustment system of an electronic air suspension(EAS) still is a challenging problem that has not been effectively solved in prior researches. This paper proposes a new adaptive controller to control the vehicle height and to adjust the roll and pitch angles of the vehicle body(leveling control) during the vehicle height adjustment procedures by an EAS system. A nonlinear mechanism model of the full?car vehicle height adjustment system is established to reflect the system dynamic behaviors and to derive the system optimal control law. To deal with the nonlinear characters in the vehicle height and leveling adjustment processes, the nonlinear system model is globally linearized through the state feedback method. On this basis, a fuzzy sliding mode controller(FSMC) is designed to improve the control accuracy of the vehicle height adjustment and to reduce the peak values of the roll and pitch angles of the vehicle body. To verify the effectiveness of the proposed control method more accurately, the full?car EAS system model programmed using AMESim is also given. Then, the co?simulation study of the FSMC performance can be conducted. Finally, actual vehicle tests are performed with a city bus, and the test results illustrate that the vehicle height adjustment performance is effectively guaranteed by the FSMC, and the peak values of the roll and pitch angles of the vehicle body during the vehicle height adjustment procedures are also reduced significantly. This research proposes an effective control methodology for the vehicle height and leveling adjustment system of an EAS, which provides a favorable control performance for the system.

S-adenosylmethionine in treatment of cholestasis after total parenteral nutrition: laboratory investigation and clinical application

Objective: To observe the effects of S-adenosylmethio-nine (SAMe) in the treatment of cholestasis after totalparenteral nutrition (TPN).Methods: Thirty SD rats were randomly divided intocontrol group, hypercalorie group, hypercalorie+SAMegroup, sepsis group and sepsis+SAMe group to com-pare their states of cholestasis. Sixteen patients re-ceived SAMe because of cholestasis after prolongedTPN, and the therapeutic efficacy was observed.Results: Bile flow was obviously decreased and theserum levels of total bile acid and gamma-glutamyltranspeptidase(γ-GT) were markedly increased in thehypercalorie and sepsis groups. Meanwhile, hepatocytefatty degeneration, dilatation of cholangioles, and bilesludge could be seen microscopically. SAMe adminis-tration in the hypercalorie+SAMe and sepsis+SAMegroups could increase the bile flow, decrease theserum levels of total bile acid and γ-GT, reduce thepathological damage to the liver, and clear the bilesludge in the cholangioles. Cholestasis and abnormalliver function were the main manifestations of the 16patients before SAMe administration. After SAMe treat-ment for 3 weeks, serum levels of total bilirubin, al-kaline phosphatase(AKP), γ-GT, alanine aminotrans-ferase(ALT), and aspartate aminotransferase(AST)were obviously decreased, and normalized in the 4thweek.Conclusion: SAMe could prevent and treat cholestasiswithout discontinuation of TPN.

Idarucizumab reverses dabigatran-induced anticoagulation in treatment of gastric bleeding:A case report

BACKGROUND The drug instructions for dabigatran recommend adjusting the dosage to 110 mg twice daily for patients with bleeding risk,and performing at least one renal function test per year for patients with moderate renal impairment.However,owing to chronic insidiously worsening renal insufficiency,dabigatran can still accumulate abnormally,necessitating therapy with idarucizumab to reverse the anticoagulation due to severe erosive gastritis with widespread stomach mucosal bleeding.CASE SUMMARY A 76-year-old woman with a history of atrial fibrillation who took dabigatran 110 mg twice daily as directed to lessen the chance of stroke,was transported to the hospital with hematemesis and melena.Laboratory findings revealed severe lifethreatening,blood-loss-induced anemia with a hemoglobin(Hb)level of 41.0 g/L and marked coagulation abnormalities with thrombin time(TT)>180 s,most likely caused by dabigatran-induced metabolic disorder.Aggressive acid suppressive,hemostatic,and blood transfusion therapy resulted in the misconception that the bleeding was controlled,with subsequent rebleeding.Idarucizumab was administered in a timely manner to counteract dabigatran’s anticoagulant impact,and 12 h later,TT was determined to be 17.4 s,which was within the normal range.Finally,the patient had no active bleeding signs and laboratory findings showed an Hb level of 104 g/L and TT of 17.7 s.CONCLUSION Renal function,coagulation function,and dabigatran concentration should be regularly monitored in older patients.Proton pump inhibitor and dabigatran coadministration is still controversial in preventing upper gastrointestinal tract bleeding.

Preparation of double-shell Si@SnO_(2)@C nanocomposite as anode for lithium-ion batteries by hydrothermal method

Silicon is one of the most promising anode materials for lithium-ion batteries(LIBs), but it suffers from pulverization and hence poor cycling stability due to the large volume variation during lithiation/delithiation. The core-shell structure is considered as an effective strategy to solve the expansion problem of silicon-based anodes. In this paper, the double-shell structured Si@SnO_(2) @C nanocomposite with nano-silicon as the core and SnO_(2) , C as the shells is synthesized by a facile hydrothermal method.Structural characterization shows that Si@SnO_(2) @C nanocomposite is composed of crystalline Si, crystalline SnO_(2) and amorphous C, and the contents of them are 42.1wt%, 37.8 wt% and 20.1 wt%, respectively. Transmission electron microscope(TEM) observations confirm the double-shell structure of Si@SnO_(2) @C nanocomposite, and the thicknesses of the SnO_(2) and C layers are 20 and 7 nm. The Si@SnO_(2) @C electrode exhibits a high initial discharge capacity of 2777 mAh·g^(-1)at 100 mA·g^(-1)and an excellent rate capability of 340 mAh·g^(-1)at 1500 mA·g^(-1). The outstanding capacity retention is 50.2% after 300 cycles over a potential of 0.01 to 2.00 V(vs. Li/Li+) at 500 mA·g^(-1). The resistance of solid electrolyte interphase(SEI) film(Rf) and charge transfer resistance(Rct) of Si@SnO_(2) @C are 7.68and 0.82 Ω, which are relatively smaller than those of Si@C(21.64 and 2.62 Ω). It is obviously seen that the SnO_(2) shell can reduce the charge transfer resistance, leading to high ion and electron transport efficiency in the Si@SnO_(2) @C electrode. The incorporation of SnO_(2) shell is attributed to the enhanced rate capability and cycling performance of Si@SnO_(2) @C nanocomposite.

Effect of Electroacupuncture on NLRP3 Inflammasome and Morphology of Uterine in Rats with Primary Dysmenorrhea Based on Meridian Acupoint Viscera Correlation Theory

Objective:To explore the relationship between acupoints and the uterus in primary dysmenorrhea(PDM)and observe the effects of electroacupuncture(EA)on NLRP3 inflammasome and morphology of uterine tissues in rats.Materials and Methods:Rats were divided into four groups:Control,PDM,EA,and nonacupoint EA(sham)groups.Writhing reactions in the rats were carefully monitored.Prostaglandin E2(PGE2)and prostaglandin F2α(PGF2α)levels in the rat serum were measured using the enzyme-linked immunosorbent assay.To assess the damage,the histomorphology of the rat uterus was examined using the optical and electron microscopy.Western blotting was performed to determine the nucleotide-binding oligomerization domain carboxy-terminal leucine-rich repeat domain and amino-terminal pyrin domaincontaining protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),and cysteinyl aspartate specific proteinase-1(caspase-1),interleukin-1β(IL-1β),and IL-18.Results:Compared with the control group,the PDM group exhibited significant increases in both writhing times and scores,with a high pathological score of the uterine tissue.Serum PGF2αlevels were significantly elevated,whereas PGE2 levels were significantly reduced.In addition,the expression levels of NLRP3,ASC,caspase-1,IL-1β,and IL-18 significantly increased(P<0.001).The EA group showed opposite effects from the PDM group(all P<0.05).The sham group exhibited significantly higher writhing time,serum PGF2αlevels,and expression levels of NLRP3,ASC,caspase-1,IL-1β,and IL-18 than the EA group.In contrast,serum PGE2 levels in the sham group were significantly lower than those in the EA group(all P<0.05).Conclusions:NLRP3 infiammasome activation in PDM triggers pathological inflammation.Sanyinjiao(SP6)and Guanyuan(CV4)had specific effects on PDM.EA of SP6 and CV4 may treat PDM by inhibiting inflammation and protecting the morphological structure of the uterus.

An Alternative Low-Cost Strategy for Simultaneous Sensitive Detection of Adjacent ESR1 Mutations in Single Circulating Tumor Cell

ESR1 mutation is of great clinical significance and being promoted as a marker of resistance to endocrine therapy in breast cancers.However,it is a challenging task to detect ESR1 mutations from traditional biopsies and cell-free DNA(cfDNA),especially for polyclonal mutations.This is mainly attributed to massive wild-type background and the low-abundance of the mutations.Here,using one-step single-cell amplification coupling with pyrosequencing,we developed and validated an original strategy for simultaneous sensitive detection of adjacent ESR1 mutations in single circulating tumor cell(CTC)from breast cancers.Unlike expensive single-cell sequencing used in previous studies,the strategy does not require complicated two-step amplification or high-cost single-cell amplification kits.Three pivotal parts involved in the strategy are collection of CTCs from whole blood of breast cancer patients,one-step single-cell amplification and pyrosequencing of single-cell amplicons.To achieve better e fficiency of one-step single-cell amplification for pyrosequencing,a set of experimental conditions were thoroughly trialed.The developed strategy enabled a highly specific detection of the ESR1 hotspot mutations from large wild-type background with the specificity as low as 1%and a high sensitivity of two copies of artificial samples or single-cell level and pretty good quantitative accuracy(R^(2)≥0.9888).Using this strategy,141 single CTCs from 11 cases of breast cancer patients were identified and collected,126 of which were successfully analyzed with a high rate of 89.4%.These results indicate that the cost-effective and reliable strategy could be used for clinical management,showing promising application in the treatment decision-making of breast cancer patients.

KLF17 promotes human naive pluripotency through repressing MAPK3 and ZIC2

The pluripotent state of embryonic stem cells(ESCs)is regulated by a sophisticated network of transcription factors.High expression of KLF17 has recently been identified as a hallmark of naive state of human ESCs(h ESCs).However,the functional role of KLF17 in naive state is not clear.Here,by employing various gain and loss-of-function approaches,we demonstrate that KLF17 is essential for the maintenance of naive state and promotes the primed to naive state transition in h ESCs.Mechanistically,we identify MAPK3 and ZIC2 as two direct targets repressed by KLF17.Overexpression of MAPK3 or ZIC2 partially blocks KLF17 from promoting the naive pluripotency.Furthermore,we find that human and mouse homologs of KLF17 retain conserved functions in promoting naive pluripotency of both species.Finally,we show that Klf17 may be essential for early embryo development in mouse.These findings demonstrate the important and conserved function of KLF17 in promoting naive pluripotency and reveal two essential transcriptional targets of KLF17 that underlie its function.

Au-Catalyzed 1,3-Acyloxy Migration/Cyclization Cascade:A Direct Strategy toward the Synthesis of Functionalized Abietane-Type Diterpenes

A direct strategy toward the synthesis of functionalized abietane-type diterpenes and related polycyclic molecules was developed through an Au-catalyzed 1,3-acyloxy migration/cyclization/electrophilic aromatic substitution cascade.Unlike the known polyene-type cyclization strategies for the construction of abietane-type diterpene skeletons,propargylic ester groups were used for the cyclization process,which can readily lead to the key skeleton with C2 and C3 functionalization.As a demonstration of the potential application of this tandem reaction,a collective total synthesis of(±)-2-ketoferruginol,(±)-fleuryinol B,(±)-salviol,(±)-2β-acetoxyferruginol,and(±)-2β-acetoxysugiyl methyl ether was achieved.Among these molecules,(±)-fleuryinol B and(±)-2β-acetoxyferruginol were synthesized for the first time.