Impact of Adverse Health Conditions on Clinical Outcomes of Older People with Atrial Fibrillation: Insights from a Prospective Cohort Study.

Objective: To evaluate the impact of adverse health conditions, including multimorbidity, frailty, malnutrition, cognitive impairment, and polypharmacy, on clinical outcomes in older people with atrial fibrillation (AF). Patients and Methods: This prospective cohort study focused on patients aged 65 years and older with AF. They were admitted to the hospital between September 2018 and April 2019 and followed up for 1 year. We evaluated these participants for adverse health conditions including multimorbidity, frailty, malnutrition, cognitive impairment, and polypharmacy. The primary clinical outcome measured was a combination of all-cause mortality or rehospitalization. Results: 197 older patients (≥65 years) with AF (mean age, 77.5±7.1 years; 57.4% men) were enrolled. During 1-year follow-up, Primary endpoint events (all-cause mortality or rehospitalization) occurred in 82 patients (41.6%). Compared with the non-event group, the Charlson comorbidity index (CCI) was higher (2.5±1.9 vs 1.7±1.3, p=0.004), more heart failure (32.9% vs 17.4%, p=0.01) and chronic kidney disease (17.1% vs 7.0%, p=0.03), with lower systolic blood pressure (125.3±18.3 mmHg vs 132±17.9 mmHg, p=0.005) in the event group. On multivariate Cox regression showed that the CCI was associated with a higher odds ratio of the composite outcome of all-cause mortality and rehospitalization (HR: 1.26; 95% CI: 1.02-1.56, p=0.03). Other adverse health conditions showed no significant association with the composite outcome of all-cause mortality and rehospitalization. Conclusion: Among adverse health conditions in older people with AF, multimorbidity appears to be a significant determinant of adverse clinical outcomes. Clinical Trial Registration: ChiCTR1800017204; date of registration: 07/18/2018.

Synthesis and Biological Evaluation of Novel Biased Mu-Opioid Receptor Agonists.

This study explored the potential of a series of PZM21 analogues for pain treatment. Specifically, the hydroxyphenyl ring of PZM21 was replaced with a naphthyl ring, the thienyl ring was substituted with either a phenyl ring or furan rings, and the essential dimethylamine and urea groups were retained. These compounds aimed to enhance safety and minimize the adverse effects associated with opioid drugs. The research findings suggest that compound 6a does not induce ß-arrestin recruitment at low-nanomolar concentrations but exhibits significant analgesic effects in established mouse models. Compared to morphine, 6a shows advantages in alleviating respiratory depression and minimizing physical dependence. Molecular docking studies underscore the pivotal role of the D147 amino acid residue in the analgesic mechanism of 6a. Consequently, 6a is a compelling candidate for the development of safer opioid analgesics and warrants further attention.

Crystal-Rigidifying Strategy in Hybrid Manganese Halide to Achieve Narrow Green Emission and High Structural Stability.

Although organic-inorganic hybrid Mn2+ halides have advanced significantly, achieving high stability and narrow-band emission remains enormously challenging owing to the weak ionic nature and soft crystal lattice of the halide structure. To address these issues, we proposed a cationic engineering strategy of long-range cation π···π stacking and C-H···π interactions to simultaneously improve the crystal structural stability and rigidity. Herein, two organic zero-dimensional (0D) manganese halide hybrids of (BACQ)2MnX4 [BACQ = 4-(butylamino)-7-chloroquinolin-1-ium; X = Cl and Br] were synthesized. (BACQ)2MnX4 display strong green-light emissions with the narrowest full width at half-maximum (fwhm) of 39 nm, which is significantly smaller than those of commercial green phosphor ß-SiAlON:Eu2+ and most of reported manganese halides. Detailed Hirshfeld surface analyses demonstrate the rigid environment around the [MnX4]2- units originating from the interactions between [BACQ]+. The rigid crystal structure weakens the electron-phonon coupling and renders narrow fwhm of these manganese halides, which is further confirmed by temperature-dependent emission spectra. Remarkably, (BACQ)2MnX4 realizes outstanding structural and luminescence stabilities in various extreme environments. Benefiting from the excellent performance, these Mn2+ halides are used to assemble light-emitting diodes with a wide color gamut of 105% of the National Television System Committee 1931 standard, showcasing the advanced applications in liquid-crystal-display backlighting.

Acupoint selection rules of acupuncture for Tourette syndrome in children. / 针刺治疗儿童Tourette综合征选穴规律.

OBJECTIVES: To explore the rules of acupoint selection and compatibility of acupuncture for Tourette syndrome(TS) in children. METHODS: The relevant literature regarding acupuncture for Tourette syndrome in children included in CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science and Cochrane Library from the establishment of the database to March 31st, 2023 was retrieved.The information of acupuncture prescription, syndrome type, meridian affinity was extracted to set up database. The Microsoft Excel 2019 was used for descriptive statistical analysis, SPSS modeler18.0 was for association rule analysis, lantern5.0 was for latent structure analysis and comprehensive clustering. RESULTS: ①A total of 80 literature was included, and 112 acupuncture prescriptions were extracted, involving 104 acupoints, with a cumulative frequency of 859 times.②The acupoints with high use frequency were Taichong(LR 3), Baihui(GV 20), Fengchi(GB 20), Hegu(LI 4), Sishencong(EX-HN 1), Sanyinjiao(SP 6) and Zusanli(ST 36).③In the treatment of TS with acupuncture, the governor vessel acupoints were the most frequently used, the proportion of acupoints on the head, face, neck and lower limbs was higher. ④The association rule analysis showed that Fengchi(GB 20)-Hegu(LI 4) and Taichong(LR 3)-Hegu(LI 4) had the highest support degree, both were 47.32%.⑤Five comprehensive clustering models were obtained by analyzing the latent structure of high-frequency acupoints, corresponding to yin deficiency disturbing wind, liver hyperactivity and spleen deficiency, liver yang transforming into wind, phlegm-heat harassing the interior and qi stagnation transformed fire. CONCLUSIONS: Acupuncture for TS in children is based on the principle of soothe the liver and extinguish the wind, regulating qi and blood, and paying attention to regulating spirit and qi. The core acupoints are Fengchi(GB 20), Hegu(LI 4), Taichong(LR 3), Baihui(GV 20), Sanyinjiao(SP 6) , Zusanli(ST 36), acupoints should be selected according to different syndrome in clinical.

Efficacy and safety of consolidation durvalumab after chemoradiation therapy for stage III non-small-cell lung cancer: a systematic review, meta-analysis, and meta-regression of real-world studies.

Background: The current review aimed to pool real-world evidence on the efficacy and toxicity of consolidation durvalumab for stage III unresectable non-small cell lung cancer (NSCLC) after curative chemoradiotherapy. Methods: PubMed, CENTRAL, ScienceDirect, Embase, and Google Scholar were searched for observational studies reporting the use of durvalumab for NSCLC till 12th April 2022. Twenty-three studies with 4,400 patients were included. Results: The pooled 1-year overall survival (OS) and progression-free survival rates (PFS) were 85% (95% CI: 81%-89%) and 60% (95% CI: 56%-64%) respectively. Pooled incidence of all-grade pneumonitis, grade ≥3 pneumonitis and discontinuation of durvalumab due to pneumonitis were 27% (95% CI: 19%-36%), 8% (95% CI: 6%-10%) and 17% (95% CI: 12%-23%) respectively. The pooled proportion of patients experiencing endocrine, cutaneous, musculoskeletal, and gastrointestinal adverse events was 11% (95% CI: 7%-18%), 8% (95% CI: 3%-17%), 5% (95% CI: 3%-6%), and 6% (95% CI: 3%-12%), respectively. Conclusion: Meta-regression indicated that performance status significantly influenced PFS, while age, time to durvalumab, and programmed death-ligand 1 status significantly affected pneumonitis rates. Real-world evidence suggests that the short-term efficacy and safety of durvalumab are consistent with that of the PACIFIC trial. The congruence of results lends support to durvalumab use in improving outcomes of unresectable stage III NSCLC. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022324663, identifier CRD42022324663.

Genetic Factors Influencing Warfarin Dose in Han Chinese Population: A Systematic Review and Meta-Analysis of Cohort Studies.

OBJECTIVE: To investigate the association of single nucleotide polymorphisms (SNPs) of various genes known to influence mean daily warfarin dose (MDWD) in the Han Chinese population. METHODS: The study is a systematic review and meta-analysis. Selected studies retrieved by searching Pubmed, Embase (Ovid), Medline, CNKI, Wanfang data, and SinoMed (from their inception to 31 August 2022) for the cohort studies assessing genetic variations that may possibly influence MDWD in Chinese patients were included. RESULT: A total of 46 studies including a total of 10,102 Han Chinese adult patients were finally included in the meta-analysis. The impact of 20 single nucleotide polymorphisms (SNPs) in 8 genes on MDWD was analyzed. The significant impact of some of these SNPs on MDWD requirements was demonstrated. Patients with CYP4F2 rs2108622 TT, EPHX1 rs2260863 GC, or NQO1 rs1800566 TT genotype required more than 10% higher MDWD. Furthermore, patients with ABCB1 rs2032582 GT or GG, or CALU rs2290228 TT genotype required more than 10% lower MDWD. Subgroup analysis showed that patients with EPHX1 rs2260863 GC genotype required 7% lower MDWD after heart valve replacement (HVR). CONCLUSION: This is the first systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) of various genes known to influence MDWD besides CYP2C9 and VKORC1 in the Han Chinese population. CYP4F2 (rs2108622), GGCX (rs12714145), EPHX1 (rs2292566 and rs2260863), ABCB1 (rs2032582), NQO1 (rs1800566), and CALU (rs2290228) SNPs might be moderate factors affecting MDWD requirements. REGISTERED INFORMATION: PROSPERO International Prospective Register of Systematic Reviews (CRD42022355130).

Genetic variants influenced the risk of bleeding and pharmacodynamics of rivaroxaban in patients with nonvalvular atrial fibrillation: A multicentre prospective cohort study.

INTRODUCTION: Individual variability of rivaroxaban was observed in clinical application. This study aimed to identify genetic variants associated with the variability of pharmacodynamics and bleeding risk of rivaroxbaban in patients with nonvalvular atrial fibrillation (NVAF). MATERIALS AND METHODS: From June 2017, and July 2019, this study enrolled 257 patients with NVAF receiving rivaroxaban. Pharmacodynamics was assessed by determining anti-Factor Xa (anti-FXa) level 3 h after rivaroxaban administration as peak concentration. Whole-exome sequencing was performed to detected single nucleotide polymorphisms (SNPs). This study was registered (NCT03161496). RESULTS: The bleeding events within 12 months were significantly related to the peak anti-FXa level (p = .027). SUSD3 rs76292544 was associated with 12-month bleeding events (odds ratio [OR]: 4.20, 95% confidence interval [CI]: 2.17-8.14, p = 6.43×10-5 ). Five SNPs including NCMAP rs4553122 (p = 2.29×10-5 ), PRF1 rs885821 (p = 7.02×10-5 ), PRKAG2 rs12703159 (p = 7.97×10-5 ), PRKAG2 rs13224758 (p = 8.70×10-5 ), and POU2F3 rs2298579 (p = 8.24×10-5 ) were associated with peak anti-FXa level. Genetic variants of 52 SNPs from 36 genes including GOT2 rs14221 and MMP13 rs640198 were potentially related to 12-month bleeding events caused by rivaroxaban's efficacy. CONCLUSIONS: Peak anti-FXa level was associated with risk of bleeding events in patients with NVAF receiving rivaroxaban. SUSD3 rs76292544 was suggestively associated with 12-month bleeding events and five SNPs (NCMAP rs4553122, PRF1 rs885821, PRKAG2 rs12703159, rs13224758 and POU2F3 rs2298579) were suggestively associated with peak anti-FXa level.

Syntheses and fluorescence properties of lanthanide isostructural complexes derived from aspartic acid.

To protect ecosystem balance and human health, the development of fluorescent sensing materials with high sensitivity and portability has attracted wide attention in several decades. Herein, six lanthanide isostructural complexes {[Ln(µ6-Hcaa)(H2O)]Cl}n (H3caa = N-(4-carboxylbenzyl)-L-aspartic acid, Ln3+ = Ce3+ (1), Pr3+ (2), Nd3+ (3), Sm3+ (4), Eu3+ (5), and Tb3+ (6)) with optical properties based on aspartic acid derivative (H3caa) were synthesized by the solvothermal method and characterized in detail. It is worth noting that complex 6 can not only specifically recognize Cr(VI) with very low detection limits (LODs) of 3.66 nM (Cr2O72-) & 5.35 nM (CrO42-) but also selectively recognize TCs with LODs of 0.24 µM (CTC = chlortetracycline) and 0.25 µM (TC = tetracycline) based on the method of fluorescence detection. In addition, the identification of Cr(VI) and TCs by visual colorimetry may be realized through the combination of a smartphone and portable test strips. This study suggests that complex 6 is a good optical material for detecting heavy metals and antibiotic contaminants in aqueous systems and broadens the development of amino acid derivatives.

A Zn-coordination polymer for the quantitative and selective colorimetric detection of residual tetracycline in aqueous solution and urine.

A one-step solvothermal synthesis provides a functional crystalline one-dimensional Zn-coordination polymer (Zn-CP) with excellent stability in aqueous solution over a wide range of temperature and pH. Zn-CP is a rapid, highly sensitive and selective sensor for detecting tetracycline (TC). Quantitative TC detection is based on the ratio of fluorescence intensities I530/I420, with a limit of detection (LOD) of 5.51 nM in aqueous solution and 47.17 nM in human urine. The characteristics of colorimetric TC sensing by Zn-CP are highly favorable for application because the color of Zn-CP changes in the visible part of the spectrum from blue-purple to yellow-green upon addition of TC. Conversion of these colors into an RGB signal is simply achieved with an app for the smart phone and provides LODs of 8.04 nM and 0.13 µM TC in water and urine, respectively. Our suggested sensing mechanisms assume that the fluorescence intensity of Zn-CP@TC at 530 nm is enhanced by energy transfer of Zn-CP to TC, while the fluorescence of Zn-CP at 420 nm is quenched by photoinduced electron transfer (PET) from TC to the organic ligand in Zn-CP. These fluorescence properties make Zn-CP a convenient, low-cost, rapid and green detection device for monitoring TC under physiological conditions and in aqueous media.

SSRI/SNRI -induced Hyponatremia: A Case Series of 26 Patients in a Single Institution from 2018 to 2020.

Antidepressant medications are widely used by patients with depression or a depressive disorder. In spite of a generally favorable safety profile of selective serotonin reuptake inhibitors or serotonin - norepinephrine reuptake inhibitors (SSRI/SNRI), several cases of a possible connection between SSRI/SNRI and hyponatremia have been reported. To describe the clinical characteristics of patients with hyponatremia after SSRI/SNRI exposure, and to examine the association between SSRI/SNRI exposure and the presence of hyponatremia in a Chinese population. A retrospective single-center case series study. We performed a retrospective evaluation of inpatients with SSRI/SNRI-induced hyponatremia from a single institution in China between 2018 and 2020. Clinical data were obtained through review of medical records. Patients who met the initial inclusion criteria but did not develop hyponatremia acted as controls. The study was approved by the Clinical Research Ethics Board of Beijing Hospital (Beijing, P.R. China). We identified 26 patients with SSRI/SNRI-induced hyponatremia. The incidence rate of hyponatremia was 1.34% (26/1937) in the study population. The mean age at diagnosis was 72.58 (±12.84) years, with a male: female ratio of 1:1.42. The duration between SSRI/SNRI exposure and the onset of hyponatremia was 7.65 (±4.88) days. The minimum serum sodium level was 2328.23 (±107.25) mg/dL in the study group. Seventeen patients (65.38%) received sodium supplements. Four patients (15.38%) switched to another antidepressant. Fifteen patients (57.69%) recovered by the time of discharge. There were significant differences in serum potassium, serum magnesium and serum creatinine level between the two groups (p < 0.05). The rate of use of sertraline was significantly higher in the study group compared with the control group (p < 0.05). This pattern was not found in other SSRI/SNRI (p > 0.05). The results of our study show that SSRI/SNRI exposure, in addition to hyponatremia, may also affect the level of serum potassium, serum magnesium and serum creatinine. A history of hyponatremia and exposure to SSRI/SNRI may be potential risk factors for the development of hyponatremia. Future prospective studies are needed to validate these findings.

Three-Dimensional Carbon Foam Modified with Mg3N2 for Ultralong Cyclability of a Dendrite-Free Li Metal Anode.

Uncontrolled growth of lithium dendrites and huge volume change during the lithium plating/stripping process as well as poor mechanical properties of the solid electrolyte interphase (SEI) are key obstacles to the development of a stable Li metal anode. Here, an ultralight Mg3N2-modified carbon foam (CF-Mg3N2) was fabricated as a collector to address these issues. The calculated results show that the CF-Mg3N2 composite is relatively stable in terms of energy. Based on the synergistic effect of the three-dimensional skeleton and the lithiophilic nature of Mg3N2, homogeneous lithium deposition/stripping was realized around the foam carbon skeleton with an extremely low nucleation overpotential (∼9.3 mV) and high retention of Coulombic efficiency (99.3%) as well as long cyclability (700 cycles and 3000 h in half and symmetrical cells, respectively). Meanwhile, Mg3N2-CF@Li//LiFePO4 full cells also showed better rate capability and more stable cycling capability than CF@Li//LiFePO4 and Li//LiFePO4 cells, exhibiting extreme practicality. Accordingly, the design concept mentioned in this work provides a far-reaching influence on the development of a stable Li metal anode.

Risk factors of dapagliflozin-associated diabetic ketosis/ketoacidosis in patients with type 2 diabetes mellitus: A matched case-control study.

OBJECTIVE: To investigate the risk factors of dapagliflozin-associated diabetic ketosis/ketoacidosis (DK/DKA) in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: A case-control study was conducted in a general hospital in China from 2018 to 2021. T2DM patients who developed DK/DKA after dapagliflozin treatment were identified. Each patient in the DA/DKA group was matched with a patient in the non-DK/DKA group in terms of the baseline characteristics. Receiver operating characteristic (ROC) curve analysis and logistic regressions were performed. RESULTS: Out of 1,684 hospitalized patients taking dapagliflozin, 170 were diagnosed with dapagliflozin-associated DK/DKA. A total of 137 cases were matched with 137 controls. The mean time-to-onset (TTO) of DK/DKA was 28.59 days. Logistic regression showed that current drinking (OR = 7.656, p < 0.001), T2DM duration ≥ 7.625 years (OR = 2.399, p = 0.017), acute ST-elevations myocardial infarction (STEMI) (OR = 12.770, p = 0.028), acute infection (OR = 2.862, p = 0.043), insulin dose reduction/cessation before dapagliflozin exposure (OR = 6.751, p < 0.001), and a major plus or major operation (OR = 2.652, p = 0.022) were risk factors for dapagliflozin-associated DK/DKA. Furthermore, T2DM duration ≥ 7.625 years (p = 0.046) and acute STEMI (p < 0.001) were independently associated with more severe DK/DKA. CONCLUSION: Current drinking, long T2DM duration, STEMI, acute infection, insulin deficiency, and major operation are the risk factors associated with DK/DKA in T2DM patients. Furthermore, long T2DM duration and STEMI were associated with more severe DK/DKA situations.

Genetic variations in relation to bleeding and pharmacodynamics of dabigatran in Chinese patients with nonvalvular atrial fibrillation: A nationwide multicentre prospective cohort study.

INTRODUCTION: To identify the potential factors responsible for the individual variability of dabigatran, we investigated the genetic variations associated with clinical outcomes and pharmacodynamics (PD) in Chinese patients with nonvalvular atrial fibrillation (NVAF). MATERIALS AND METHODS: Chinese patients with NVAF taking dabigatran etexilate with therapeutic doses were enrolled. The primary (bleeding events) and secondary (thromboembolic and major adverse cardiac events) outcomes for a 2-year follow-up were evaluated. Peak and trough PD parameters (anti-FIIa activity, activated partial thromboplastin time and prothrombin time) were detected. Whole-exome sequencing, genome-wide sequencing and candidate gene association analyses were performed. RESULTS: There were 170 patients with NVAF treated with dabigatran (110 mg twice daily) who were finally included. Two single-nucleotide polymorphisms (SNPs) were significantly related with bleeding, which include UBASH3B rs2276408 (odds ratio [OR] = 8.79, 95% confidence interval [CI]: 2.99-25.83, p = 7.77 × 10-5 at sixth month visit) and FBN2 rs3805625 (OR = 8.29, 95% CI: 2.87-23.89, p = 9.08 × 10-5 at 12th month visit), as well as with increased trends at other visits (p < .05). Furthermore, minor allele carriers of 16 new SNPs increased PD levels, and those of one new SNP decreased PD values (p < 1.0 × 10-5 ). Lastly, 33 new SNPs were found to be associated with bleeding and PD among 14 candidate genes. Unfortunately, the low number of secondary outcomes precluded further association analyses. CONCLUSIONS: Genetic variations indeed affected bleeding and PD in Chinese patients with NVAF treated with dabigatran. The functions of these suggestive genes and SNPs might further be explored and verified in more in vivo and in vitro investigations.

Population pharmacokinetic analysis for dabigatran etexilate in Chinese patients with non-valvular atrial fibrillation.

We aimed to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model from healthy Chinese subjects and real-world non-valvular atrial fibrillation (NVAF) patients. We also investigated meaningful intrinsic and extrinsic factors and related biomarkers for bleeding events. We characterized the integrated PK/PD models based on rich PK/PD data [dabigatran concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), and anti-factor IIa (anti-FIIa) activity] from 118 healthy volunteers and sparse PD data [APTT, PT, and anti-FIIa] from 167 patients with NVAF after verifying the model extrapolation performance. We also documented the correlations between PD biomarkers and clinically relevant bleeding events over one year. Next, we used the final integrated PK/PD model (a two-compartment, linear model with first-order absorption) to evaluate the influence of dosage and individual covariates on PD parameters. The age, high-density liptein cholesterol (HDL-C), and creatinine clearance (CrCL) improved the PK model fit. The linear direct-effects PD model described the correlation between APTT, PT, and anti-FIIa and plasma concentration. CrCL improved the PD model fit. Anti-FIIa was more sensitive to the increase in dabigatran exposure than APTT and PT in the PD model. Therefore, fixed dabigatran doses could be prescribed for patients with NVAF without adjusting for age and HDL-C. We observed an elevated bleeding tendency with higher peak and trough values of APTT, PT, and anti-FIIa. Randomized studies should be performed to evaluate the efficacy and safety of low-dose dabigatran in Chinese patients with NVAF.

Sensitive SERS detection of oral squamous cell carcinoma-related miRNAs in saliva via a gold nanohexagon array coupled with hybridization chain reaction amplification.

In this work, a highly specific and sensitive method for the detection of dual miRNAs was successfully developed by a hybridization chain reaction (HCR) amplification coupled with surface-enhanced Raman scattering (SERS) on Au-Ag hollow nanoparticles (Au-Ag HNPs) and a gold nanohexagon (AuNH) array. Two Raman reporter-labelled and hairpin DNA-modified Au-Ag HNPs acted as SERS probes (Au-Ag HNPs@4-MBA@HP1-1, Au-Ag HNPs@4-MBA@HP2-1, Au-Ag HNPs@DTNB@HP1-2, and Au-Ag HNPs@DTNB@HP2-2), and the hairpin DNA-modified AuNH array acted as the capture substrate. The HCR process could be triggered by the presence of target miRNAs, and long DNA hybridization chains on the substrate were formed by self-assembly rapidly, causing significant signal enhancement. Using the mentioned strategy, a low detection limit (LOD) of 6.51 aM for miR-31 and 6.52 aM for miR-21 in human saliva were obtained, showing the biosensor's remarkable sensitivity. The proposed biosensor also displays a significant specificity in detecting target miRNAs by introducing different interfering factors. This method has been successfully applied to detect and identify miR-21 and miR-31 in saliva from oral squamous cell carcinoma (OSCC) patients and healthy subjects. The results were consistent with those of the traditional test method in detecting target miRNAs, which confirmed the good accuracy of our method. Hence, the new assay method has great potential to be a valuable platform for detecting miRNAs in the early diagnosis of OSCC.

Association of stress hyperglycemia ratio and in-hospital mortality in patients with coronary artery disease: insights from a large cohort study.

BACKGROUND: Stress hyperglycemia is strongly associated with poor clinical outcomes in patients with acute coronary syndrome (ACS). Recently, the stress hyperglycemia ratio (SHR) has been proposed to represent relative hyperglycemia. Studies regarding the relationship between SHR and mortality in coronary artery disease (CAD) are limited. This study aimed to clarify the association between SHR and in-hospital mortality in patients with CAD. METHODS: A total of 19,929 patients with CAD who were hospitalized in Beijing Hospital were enrolled in this study. Patients with an estimated glomerular filtration rate < 30 ml/min, cancer, or missing blood glucose/HbA1c data were excluded; therefore, 8,196 patients were included in the final analysis. The patients were divided into three groups based on tertiles of SHR: T1 group (SHR < 0.725, n = 2,732), T2 group (0.725 ≤ SHR < 0.832, n = 2,730), and T3 group (SHR ≥ 0.832, n = 2,734). The primary endpoint was in-hospital mortality. RESULTS: The overall in-hospital mortality rate was 0.91% (n = 74). After adjusting for covariates, SHR was significantly associated with in-hospital mortality in patients with CAD [odds ratio (OR) = 17.038; 95% confidence interval (CI) = 9.668-30.027; P < 0.001], and the T3 group had a higher risk of in-hospital mortality (OR = 4.901; 95% CI = 2.583-9.297; P < 0.001) compared with T1 group. In the subgroup analysis, the T3 group had an increased risk of mortality among patients with pre-diabetes mellitus (pre-DM) (OR = 9.670; 95% CI = 1.886-49.571; P = 0.007) and diabetes mellitus (DM) (OR = 5.023; 95% CI = 2.371-10.640; P < 0.001) after adjustments for covariates. The relationship between SHR and in-hospital mortality among patients with ACS and chronic coronary syndrome was consistent with the main finding. SHR and in-hospital mortality exhibited a dose-response relationship, and the risk of in-hospital mortality increased when the SHR index was above 1.20. Moreover, the area under the curve of SHR for predicting in-hospital mortality in patients with CAD was 0.741. CONCLUSION: SHR is significantly associated with in-hospital mortality in patients with CAD. SHR may be an effective predictor of in-hospital mortality in patients with CAD, especially for those with pre-DM and DM.

Discovery and Structural Explorations of G-Protein Biased µ-Opioid Receptor Agonists.

Compounds that activate only the G-protein signalling pathway represent an effective strategy for making safer opioids. In the present study, we report the design, synthesis and evaluation of two classes of novel PZM21 derivatives containing the benzothiophene ring and biphenyl ring group respectively as biased µ-opioid receptor (µOR) agonists. The new compound SWG-LX-33 showed potent µOR agonist activity and produced µOR-dependent analgesia. SWG-LX-33 does not activate the ß-arrestin-2 signalling pathway in vitro even at high concentrations. Computational docking demonstrated the amino acid residue ASN150 to be critical for the weak efficacy and potency of µOR agonists in arrestin recruitment.

Bibliometric analysis of hypoxia inducible factor prolyl hydroxylase inhibitor in anemia.

Objective: This study aimed to explore the global research status, hot topics, and future prospects in the field of the hypoxia inducible factor prolyl hydroxylase inhibitor (HIF-PHI) by bibliometric analysis. Methods: The literatures about HIF-PHI were downloaded from the Web of Science Core Collection and Pubmed database from inceptions to January.10th. 2022. The VOSviewer 1.6.18 was used to explore the bibliometric networks and research priorities of HIF-PHI. Results: A total of 409 papers about HIF-PHI were included, involving 1,674 authors from 548 institutions in 43 countries. The number of HIF-PHI literatures showed an upward trend, with steady growth from 2016 to 2020 and rapid growth in 2021. Tadao Akizawa, Masaomi Nangaku and Alexander R Cobitz published the most literatures. The United States, Japan and China contributed the most publications. The three most contributed institutions are Astellas Pharma Inc., the Showa University and Glaxosmithkline. Therapeutic Apheresis and Dialysis, American Journal of Nephrology and Clinical Pharmacology in Drug Development are the most productive journals. The main hot topics of HIF-PHI field are anemia, chronic kidney disease, hif-phi, epoetin and roxadustat. Conclusion: The United States and Japan are dominant in the field of HIF-PHI research. The discovery and clinical application of HIF-PHI is a great boon for patients with renal anemia. However, due to the short clinical application time of HIF-PHI, and its long-term efficacy and safety still need time to prove. In addition, more cooperation should be carried out between European and American countries and Asian countries to better prove the clinical value of HIF-PHI.

Seven Ln(III) coordination polymers with two kinds of geometric coordination but the same 3D topological property: luminescence sensing and magnetic property.

Two series of seven lanthanide metal coordination polymers (Ln-CPs) formulated as {[Ln(dttpa)1.5(H2O)2]·H2O}n [Ln = La3+ (1), Ce3+ (2), Nd3+ (3), Sm3+ (4) and Eu3+ (5)] and {[Ln (dttpa)1.5(H2O)]·xH2O}n [Ln = Tb3+ (6) and Er3+ (7), x = 0.75] have been successfully constructed using Ln3+ ions and 2,5-di(1H-1,2,4-triazol-1-yl)terephthalic acid (H2dttpa) via a hydrothermal method. Their 3D structures are fully characterised by Fourier transform infrared (FT-IR) spectroscopy, X-ray single-crystal analyses, powder diffraction analyses (PXRD), elemental analyses (EAs) and thermogravimetric analyses (TGAs). All Ln-CPs display the same topological property with the point symbol of {42·84}{44·62}2{49·66}2, and crystallize in the triclinic space group P1̄. Interestingly, Eu-CP (5) effectively sensitizes the visible emission of Tb3+ and shows high selectivity and stable response with the lowest detection limit of 9.88 nM. Furthermore, Tb-CP (6) acts as a good luminescence sensor to detect nitrobenzene (NB) with a detection limit of 12.5 nM. In addition, the magnetic susceptibility measurement for Er-CP (7) further shows that compounds constructed by dttpa2- are a kind of promising functional material.

Three-Dimensional Echocardiography and Coagulation Function Detection in the Prognosis Evaluation of Patients with Acute Myocardial Infarction.

This research was aimed at discussing the application value of coagulation function detection and three-dimensional echocardiography in the prognosis evaluation of acute myocardial infarction (AMI) patients. 72 patients with AMI were divided into the recovered group (good recovery) and unrecovered group (poor recovery) according to the results of postoperative ultrasonography. The left ventricular parameters of the patients were detected by three-dimensional ultrasound, and the coagulation function was also detected. The results showed that 3 months after surgery, the regional end-systolic volume (rESV) and regional end-diastolic volume (rEDV) of the left ventricle in the patients were smaller than the measured values 1 week after surgery. The left ventricular regional ejection fraction (rEF) was greater than the value measured 1 week after surgery, and all the differences were statistically significant (P < 0.05). For the end-systolic volume (ESV), end-diastolic volume (EDV), and ejection fraction (EF) (%), the two-dimensional ultrasound results were significantly lower than the three-dimensional ultrasound results, and there were significant differences (P < 0.05). Tmsvle6-Dif% of the recovered patients was 14.99 ± 9.88 and 14.37 ± 9.78 3 months and 6 months after surgery, respectively. These were smaller than 30.91 ± 18.63 and 33.51 ± 17.96 of the unrecovered patients; the differences were of statistical significance (P < 0.05). Tmsvl6-SD% of recovered patients was 3.69 ± 2.47 and 3.61 ± 1.83 3 months and 6 months after surgery, respectively, which were also smaller than 7.38 ± 4.06 and 7.96 ± 2.82 of unrecovered patients, showing statistically significant difference (P < 0.05). The postoperative Tmsvle6-Dif% and Tmsvl6-SD% of the recovered group were lower than those of the unrecovered patients, with the statistically significant differences (P < 0.05). The level of coagulation factors in the recovered group was also significantly lower than that in the unrecovered group with the difference statistically significant (P < 0.05). The results suggested that three-dimensional echocardiography played an important role in the evaluation of cardiac conditions in AMI patients. The level of coagulation factors varied with the AMI condition of patients, and there was an obvious relationship between them, which could provide a reference value for the prognosis evaluation of patients.