Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective To study the accuracy and safety of oral mucosal exfoliated cell specimens used in the bedside rapid detection of MTHFR C677T genotype by using the fluorescent probe method.Methods The outpatients and inpatients with hypertension visited and admitted in the department of cardiovascular medicine of this hospital from January 2019 to September 2020 were selected.The plasma homocysteine (Hcy) level in all patients was detected in the laboratory,a total of 482 hypertensive patients with Hcy≥10 μmol/L were se-lected,and the oral mucosal cells and whole blood sample were collected in all patients,and the genotypes of the above specimens were detected by the oral mucosal exfoliative cell fluorescent probe method and whole blood sample contrast reagents.If the two test results were inconsistent,the "gold standard" Sanger sequen-cing method was used to detect the whole blood sample for the final determination of MTHFR C677T geno-type.The coincidence rate was compared between the two detection methods,and the probability of adverse e-vents during the samples collection was observed and recorded.The accuracy and safety of fluorescence probe method for detecting MTHFR C677T genotype in the patients with oral mucosa exfoliation was evaluated.Re-sults The oral mucosal exfoliated cell samples and whole blood samples from 482 hypertensive patients were successfully collected,and no obvious adverse reactions occurred during the sampling process.The incidence rate of total mutation of MTHFR C677T gene detected by the fluorescence probe method and contrast reagent all were 73.23％ (353/482),the coincidence rate of homozygous wild type (CC type) in MTHFR C677T gene detected by the two methods was 100.00％ (95％CI:97.11-100.00),which of heterozygous mutant type (CT type) was 99.14％ (95％CI:96.91-99.76),which of homozygous mutant type (TT type) was 99.17％(95％CI:95.47-99.85),the total coincident rate of MTHFR C677T genotype was 99.38％ (95％CI:98.19-99.79)and the detection results consistency Kappa value was 0.9902.Conclusion The detection of MTHFR C677T gene mutation in oral mucosal exfoliated cells by fluorescent probe method is simple with less invasion,moreover which is rapid,safe and accurate.

Transdermal preparations can effectively avoid the first-pass effect and have good clinical medication compliance.Transfersomes(TF),as a novel deformable lipid vesicle with good skin penetration efficiency and encapsulation rate,exert their efficacy by maintaining stable plasma concentration in vivo.They are novel transdermal absorption preparations with great development prospects.This article summarized the current research on TF,including the preparation technology,evaluation indexes,and clinical application,and prospected its research prospects.

Polyethylene terephthalate (PET) is one of the most widely used synthetic polyester. It poses serious threat to terrestrial, aquatic ecosystems and human health since it is difficult to be broken down and deposited in the environment. The biodegradation based on enzymatic catalysis offers a sustainable method for recycling PET. A number of PET hydrolases have been discovered in the last 20 years, and protein engineering has increased their degradation capabilities. However, no PET hydrolases that are practical for widespread industrial use have been identified. Screening of PET hydrolase using conventional detection techniques is laborious and inefficient process. Effective detection techniques are required to promote the commercialization of PET hydrolases. Using efficient detection techniques to screen potent industrial enzymes is essential for supporting the widespread industrial implementation of PET hydrolases. To define PET hydrolase, scientists have created a number of analytical techniques recently. The detection techniques that can be used to screen PET hydrolase, including high performance liquid chromatography, ultraviolet absorption spectrometric, and fluorescence activated droplet sorting method, are summarized in this study along with their potential applications.
Humans ; Polyethylene Terephthalates ; Ecosystem ; Biodegradation, Environmental ; Catalysis ; Hydrolases

Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.

Preoperative neoadjuvant therapy has become a hot topic in the treatment of locally advanced esophageal cancer (EC) in recent years. Accumulated evidences have demonstrated that neoadjuvant therapy combined with surgery could significantly improve the survival of patients with locally advanced EC compared with the surgery alone. The importance of neoadjuvant chemotherapy (nCT) and neoadjuvant chemoradiotherapy (nCRT) has been widely recognized and included in the guidelines. For locally advanced EC, especially for esophageal adenocarcinoma, both nCT and nCRT can significantly prolong the survival of patients than the surgery alone. Currently, whether the supplement of radiotherapy can bring more benefits to patients compared with nCT alone remains a hot topic. Besides, it is generally believed that the operation should be performed at 2-8 weeks after neoadjuvant therapy, whereas the optimal time interval remains debated. In this article, the research progress and existing problems in the preoperative neoadjuvant treatment of locally advanced EC were summarized.

Objective To compare the operative results of removing large olfactory groove meningiomas(diameter≥3 cm)using either a unilat?eral or bilateral subfrontal approach ,and to determine whether there is an advantage in the unilateral approach. Methods Sixty?nine cases of large olfactory groove meningioma,treated in our department,by either a unilateral or bilateral subfrontal approach microsurgery were retrospec?tively reviewed. Removal grading,post?operative complications,and other clinical indices were evaluated. Results Total resection(Simpson Ⅰ or Ⅱ)was achieved in all the cases. There were lesser complications with use of the unilateral subfrontal approach. Conclusion Patients with ol?factory groove meningioma have a good prognosis when a unilateral subfrontal approach is used for surgery.

Objective To investigate the efficacy of micro?surgery for the treatment of medulla oblongata cavernomas. Methods A retrospective analysis was conducted on the clinical data of 21 patients with cavernous hemangioma who received micro?surgical treatment. Of the 21 patients, 13 were men and 8 women,aged 22 to 63 years. The preoperative Karnofsky performance status(KPS)score was 76.5 ± 10.2. The main clinical manifestations included sensory disorder and difficulty swallowing etc. According to the location of the lesions ,the posterior transchoroidal fissure approach was employed for 16 patients;far?lateral approach,5 patients. Electrophysiological monitoring and nervous system navigation were supple?mentarily adopted in both types of surgery. Further ,KPS scoring was conducted to evaluate the patients 'quality of life. Results The medulla cav?ernous hemangioma was excised in all cases. For 17 patients with primary neurological disorders ,their symptoms were alleviated or resolved;4 pa?tients had severe symptoms and 8 presented with new clinical symptoms. A follow?up visit was conducted 8 to 97 months post?surgery(average 47.6 months). All patients were found capable of caring for themselves in daily life and performing simple or normal learning and working activities without recurrence or bleeding. The mean postoperative KPS score was 83.7 ± 15.5. Conclusion Patients with medulla cavernous hemangioma bleeding or severe symptoms should actively seek surgical treatment. Repeated bleeding is the absolute indication for surgery. Surgical skills ,elec?trophysiological monitoring,and nervous system navigation can reduce nervous system damage and protect the brainstem. The patient's quality of life is expected to significantly improve after surgery.

In recent years,it has been reported that the osteopontin attracts great attention for its roles in tumor growth and metastasis.In many tumors,osteopontin plays an important role in promoting tumor growth,metastasis and enhancing adhesion and migration abilities.In particular,in hepatocellular carcinoma,osteopontin has very satisfactory sensitivity and specificity in early diagnosis and is relatively effective on prognosis prediction.Suppression osteopontin expression will inhibit liver cancer growth and metastasis,indicating that the osteopontin stays a new target for liver cancer treatment and possesses intangible clinical potential.

Objective To study the expressions of hypoxia inducible factor (HIF)-1 and angiopoietin (Ang)-2 in repeated gastrointestinal bleeding due to vascular malformation, and the efficacy of treatment with thalidomide. Methods Twenty-five patients with repeated gastrointestinal bleeding due to vascular malformation confirmed by capsule endoscopy or enteroscopy were collected and 18 subjects without severe diseases were served as controls. Ten patients with gastrointestinal vascular malformation, who received 25 mg of thalidomide 4 times daily for 4 months and were followed up for at least one year, were also enrolled. The serum samples from all participauts were detected for expressions of HIF-1 and Ang-2 using enzyme-linked immunosorbent assay (ELISA).The expressions of HIF-1 and Ang-2 were compared between angiodysplasia group and control group.The expressions of HIF-1 and Ang-2 were comparatively evaluated before and after treatment with thalidomide in treatment group. Results The expressions of HIF-1 and Ang-2 in vascular malformation group [( 113. 84 ± 26. 66 ) ng/ml and ( 652. 11 ± 140. 39) ng/ml, respectively] were significantly higher than that of control group [(43.28±17.30) ng/ml and (265.60±53.88) ng/ml,respectively, P=0. 000]. The expression of HIF-1 was positively associated with that of Ang-2. (r=0. 700, P= 0. 000). There was no difference in expressions of HIF-1 and Ang-2 before and after treatment with thalidomide (P=0. 498 and =0. 136, respectively). However, significant reduction of Ang-2 [(113. 80±73. 60) ng/ml(P=0. 003)] was found in 8 effectively treated patients after thalidomide treatment. Conclusions HIF-1 and Ang-2 might play an important role in the formation of vascular malformation. The extent of Ang-2 reduction after thalidomide treatment may be helpful in evaluating its efficacy or prognosis.