Computational Exploration of the Thermal Rearrangement of Basketene: One Forbidden versus Two Allowed Pericyclic Reactions.

The thermal rearrangement of basketene to Nenitzescu's hydrocarbon has been explored using density functional theory (M06-2X and ωB97X-D) and DLPNO-CCSD(T) quantum mechanics. Both the sequential thermally allowed retro Diels-Alder followed by Cope rearrangement and the thermally forbidden retro-[2 + 2] cycloaddition were studied. The controlling role of orbital symmetry rather than reaction thermodynamics is demonstrated.

Risk factors for self-reported medication adherence in community-dwelling older patients with multimorbidity and polypharmacy: a multicenter cross-sectional study.

BACKGROUND: Medication nonadherence is a significant public health problem as it contributes to poor clinical outcomes and increased healthcare costs. Older patients with multimorbidity and polypharmacy often have low medication adherence. These patients also have a high prevalence of potentially inappropriate medication (PIM) use. AIM: To explore risk factors related to medication nonadherence in older patients with multimorbidity and polypharmacy and examine the association between medication nonadherence and PIM use. METHOD: A multicenter cross-sectional study was conducted from May to December 2019 in 16 tertiary hospitals from 12 provinces and cities in China. Data were collected from outpatients 65 years or older with multimorbidity and polypharmacy. The PIMs were evaluated using the 2019 Beers Criteria. Self-reported medication adherence was assessed using the Visual Analog Scale (VAS). RESULTS: A total of 773 outpatients were recruited. The prevalence of medication nonadherence was 31.8%. In the univariate analysis, nonadherence was significantly associated with sex, cognitive impairment, stroke, visiting the same physicians, self-administration of medication, the percentage of drug costs ≥ 10% of the medical expenses, and PIMs for the alimentary tract and metabolism. In the multivariate analysis, the results almost paralleled those of the univariate associations. Notably, the use of PIM was significantly associated with medication adherence. CONCLUSION: Several factors that influence medication adherence were identified. Targeted interventions can be implemented to improve medication adherence, such as encouraging self-administering medications and reducing medication expenses.

Acute pulmonary embolism presenting with electrocardiographic signs and serum biomarkers of ST-segment elevation myocardial infarction: a case report.

Acute pulmonary embolism (APE) with ST-segment elevation and an upward T-wave is rare, and only a few cases have been reported to date. We herein present a case involving a man in his early 70s with an 8-hour history of dyspnea. Serial electrocardiography (ECG) demonstrated ST-segment elevation in leads V1 to V3 with an upward T-wave, laboratory tests revealed a high serum concentration of high-sensitivity cardiac troponin I, and signs of acute myocardial infarction were present. However, emergency coronary angiography revealed normal coronary arteries. A subsequent computed tomography scan of the pulmonary arteries showed findings consistent with APE. The patient's chest tightness was relieved after catheter-directed thrombolysis. Postoperative ECG showed that the ST-segment in leads V1 to V3 had fallen back and that the T-wave was inverted. The patient was discharged on rivaroxaban therapy. Clinically, the ECG findings of ST-segment elevation and an upward T-wave in APE can be easily misdiagnosed as acute myocardial infarction. Physicians should maintain clinical suspicion through risk stratification to identify APE.

Comparison of survival outcomes between clinical trial participants and non-participants of patients with advanced non-small cell lung cancer: A retrospective cohort study.

Background: Clinical trials for advanced non-small cell lung cancer (NSCLC) have been conducted extensively. However, the effect of participation in clinical trials on survival outcomes remains unclear. This study aimed to assess whether participation in clinical trials was an independent prognostic factor for survival in patients with advanced NSCLC. Methods: We analyzed the medical records of patients aged ≥18 years who were newly diagnosed with stage IIIB or IV NSCLC and received chemotherapy or immunotherapy from September 2016 to June 2020 in this retrospective cohort study. To reduce the impact of confounding factors, propensity score matching (PSM) was performed. The Kaplan-Meier method and log-rank test were used to calculate and compare the overall survival (OS) and progression-free survival (PFS) of the patients. Finally, Cox proportional hazards regression was employed to examine the correlation between clinical trial participation and survival outcomes. Results: The study enrolled 155 patients in total, of which 62 (40.0 %) patients participated in NSCLC clinical trials. PSM identified 50 pairs of patients in total. The median PFS and OS of clinical trial participants and non-participants were 17.2 vs. 13.9 months (p = 0.554) and 32.4 vs. 36.5 months (p = 0.968), respectively. According to the results of multivariate Cox proportional hazards regression analysis, clinical trial participation was not an independent prognostic factor for advanced NSCLC patients (HR: 0.89, 95 % CI: 0.50-1.61; p = 0.701). Conclusions: The clinical trial participants with advanced NSCLC displayed similar survival outcomes compared with the non-participating patients in this cohort.

Aldehyde dehydrogenase 2 and NOD-like receptor thermal protein domain associated protein 3 inflammasome in atherosclerotic cardiovascular diseases: A systematic review of the current evidence.

Inflammation and dyslipidemia underlie the pathological basis of atherosclerosis (AS). Clinical studies have confirmed that there is still residual risk of atherosclerotic cardiovascular diseases (ASCVD) even after intense reduction of LDL. Some of this residual risk can be explained by inflammation as anti-inflammatory therapy is effective in improving outcomes in subjects treated with LDL-lowering agents. NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation is closely related to early-stage inflammation in AS. Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme of toxic aldehyde metabolism located in mitochondria and works in the metabolism of toxic aldehydes such as 4-HNE and MDA. Despite studies confirming that ALDH2 can negatively regulate NLRP3 inflammasome and delay the development of atherosclerosis, the mechanisms involved are still poorly understood. Reactive Oxygen Species (ROS) is a common downstream pathway activated for NLRP3 inflammasome. ALDH2 can reduce the multiple sources of ROS, such as oxidative stress, inflammation, and mitochondrial damage, thereby reducing the activation of NLRP3 inflammasome. Further, according to the downstream of ALDH2 and the upstream of NLRP3, the molecules and related mechanisms of ALDH2 on NLRP3 inflammasome are comprehensively expounded as possible. The potential mechanism may provide potential inroads for treating ASCVD.

Smooth muscle liver kinase B1 inhibits foam cell formation and atherosclerosis via direct phosphorylation and activation of SIRT6.

Foam cell formation is a hallmark of the early phase of atherosclerosis. Growing evidence has demonstrated that vascular smooth muscle cells (VSMCs) comprise a considerable proportion of foam cells. Liver kinase B1 (LKB1) plays a crucial part in cardiovascular diseases. However, the role of LKB1 in VSMC-derived foam cell formation and atherosclerosis remains unclear. To explore the effects of LKB1 on VSMC-derived foam cell formation and atherosclerosis, we generated smooth muscle-specific LKB1 knockout (LKB1SMKO) mice by crossbreeding LKB1flox/flox mice with SM22α-CreERT2 mice. LKB1 expression decreased in plaque-loaded aortas and oxidized low-density lipoprotein (oxLDL)-treated VSMCs. Compared with controls, atherosclerosis development was exacerbated in LKB1SMKO mice via the promotion of VSMC-derived foam cell formation. Conversely, LKB1 overexpression inhibited lipid uptake and foam cell formation in VSMCs. Mechanistically, LKB1 binds to SIRT6 and directly phosphorylates and activates it, thereby reducing lectin-like oxLDL receptor-1 (LOX-1) via SIRT6-dependent histone deacetylation. Finally, adeno-associated virus (AAV)-mediated LOX-1 deficiency in smooth muscle ameliorated atherosclerosis in LKB1SMKO mice. Our findings suggest that LKB1 may modulate VSMC-derived foam cell formation and atherosclerosis via the phosphorylation and activation of SIRT6.

Tai Chi Chuan modulates heart rate variability during abdominal breathing in elderly adults.

Tai Chi Chuan (TCC) practice is currently intentionally applied in clinical populations, especially those with cardiovascular diseases because of its potential benefits on the autonomic nervous system. The long-term effect of TCC practice on heart rate variability (HRV) remains largely unknown. In this study, we recruited 23 TCC practitioners whose experience averaged approximately 21 years and 19 controls matched by age, sex and education to examine the effect of TCC practice on the autonomic nervous system during a resting state and during an abdominal breathing state. HRV was measured by traditional electrocardiogram (ECG) recording. The results showed that the low frequency, total power frequency, and normalized low frequency components and the low-frequency/high-frequency ratio were significantly higher, whereas the normalized high frequency was significantly lower in the TCC practitioners relative to controls during the abdominal breathing state. However, we did not detect any significant difference in the HRV measures during the resting state between the two groups. Additionally, TCC experience did not correlate with HRV components either in the abdominal state or the resting state in the TCC group. Considering all of these findings, we suggest that TCC improves vagal activity and the balance between sympathetic and parasympathetic activity during the relaxation state. This study also provides direct physiological evidence for the role of TCC practice in relaxation.

A suicidal DNA vaccine expressing the fusion protein of peste des petits ruminants virus induces both humoral and cell-mediated immune responses in mice.

Peste des petits ruminants (PPR), a highly contagious disease induced by PPR virus (PPRV), affects sheep and goats. PPRV fusion (F) protein is important for the induction of immune responses against PPRV. We constructed a Semliki Forest virus (SFV) replicon-vectored DNA vaccine ("suicidal DNA vaccine") and evaluated its immunogenicity in BALB/c mice. The F gene of PPRV was cloned and inserted into the SFV replicon-based vector pSCA1. The antigenicity of the resultant plasmid pSCA1/F was identified by indirect immunofluorescence and western blotting. BALB/c mice were then intramuscularly injected with pSCA1/F three times at 14-d intervals. Specific antibodies and virus-neutralizing antibodies against PPRV were quantified by indirect ELISA and microneutralization tests, respectively. Cell-mediated immune responses were examined by cytokine and lymphocyte proliferation assays. The pSCA1/F expressed F protein in vitro and induced specific and neutralizing antibody production, and lymphocyte proliferation in mice. Mice vaccinated with pSCA1/F had increased IL-2 and IL-10 levels after 24-h post first immunization. IFN-γ and TNF-α levels increased from that time point and gradually decreased thereafter. Thus, the Semliki Forest virus replicon-vectored DNA vaccine expressing the F protein of PPRV induced both humoral and cell-mediated immune responses in mice. This could be considered as a novel strategy for vaccine development against PPR.

[Improvement of islet ß-cell function after sleeve gastrectomy with ileal interposition duodenojejunal bypass in non-obese type 2 diabetes mellitus].

OBJECTIVE: To investigate the improvement of islet ß-cell function after sleeve gastrectomy with ileal interposition duodenojejunal bypass operation in non-obese type 2 diabetes mellitus. METHODS: Clinical data of 54 non-obese type 2 diabetes mellitus cases undergoing sleeve gastrectomy with ileal interposition duodenojejunal bypass operation in our hospital from March 2009 to October 2011 were retrospectively analyzed. Fasting glucose, glycosylated hemoglobin(HbA1c), fasting insulin, body mass index(BMI), insulin resistance index(HOMA-IR), homeostasis model ß-cell function(HOMA-ß), early phase insulin secretion index (DelteI30/DelteG30) and area under curve of insulin(AUCINS) were measured before operation, and 1, 3, 6, 12, 24 months after operation with standard oral glucose tolerance test(OGTT). RESULTS: At 24 months after operation, HbA1c decreased from preoperative (8.2±0.8)% to postoperative (6.3±0.1)%(P<0.01), as did the fasting glucose [(9.2±0.6) mmol/L vs. (5.9±0.5) mmol/L, P<0.01] and HOMA-IR (2.1±0.6 vs. 0.8±0.3, P<0.01). The postoperative BMI was not significantly different from the preoperative level. HOMA-ß increased (28.4±9.2 vs. 56.3±12.8, P<0.05). DelteI30/DelteG30 increased after surgery (0.8±0.2 vs. 1.8±0.7, P<0.01). AUCINS was (42.6±17.1) mIU/L, (31.5±18.6) mIU/L, (34.71±12.9) mIU/L, (49.2±16.3) mIU/L, (78.3±21.7) mIU/L, (74.8±15.2) mIU/L before operation and at postoperative 1 month, 3 months, 6 months, 12 months, 24 months, respectively, indicating an increase in AUCINS 6 months later. Linear correlation analysis showed that HbA1c was negatively correlated with HOMA-ß, DelteI30/DelteG30 and AUCINS (r=-0.628, P<0.01; r=-0.571, P<0.01; r=-0.606, P<0.01), and positively correlated with HOMA-IR (r=0.784, P<0.01). CONCLUSIONS: Sleeve gastrectomy with ileal interposition duodenojejunal bypass can improve islet ß cells function. It plays an important role in the surgical treatment of diabetes.

[Impact of sleeve gastrectomy with ileal interposition duodenojejunal bypass operation on lipid metabolism in non-obese type 2 diabetes mellitus patients].

OBJECTIVE: To evaluate the effect of sleeve gastrectomy with ileal interposition duodenojejunal bypass operation on lipid metabolism in non-obese type 2 diabetes mellitus patients. METHODS: Twenty-nine non-obese patients with type 2 diabetes mellitus underwent sleeve gastrectomy with ileal interposition duodenojejunal bypass operation. All the patients were subjected to the measurement of total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), homeostatic model assessment for insulin resistance (Homa-IR), glycosylated hemoglobin (HbA1c) at postoperative 12th month. RESULTS: Twelve months after ileal interposition duodenojejunal bypass operation, the blood glucose was controlled without taking hypoglycemic drugs in 28 patients (96.5%) and HbA1c decreased from (8.4±1.3)% to (6.5±1.6)% (P<0.01). Dyslipidemia were corrected in 25 cases (86.2%). TC became normal in 84.2% (15/19), and TG became normal in 82.3% (14/17). HDL became normal in 66.6% (8/12). LDL became normal in 31.2% (5/16). TC/HDL ratio decreased from 5.6±1.2 to 2.8±1.0 (P<0.01). TG/HDL ratio decreased from 3.2±1.3 to 1.5±0.8 (all P<0.01). CONCLUSION: Sleeve gastrectomy with ileal interposition duodenojejunal bypass is an effective operation for the correction of dyslipidemia in non-obese patients with type 2 diabetes mellitus.