Targeted drug delivery of engineered mesenchymal stem/stromal-cell-derived exosomes in cardiovascular disease: recent trends and future perspectives.

In recent years, stem cells and their secretomes, notably exosomes, have received considerable attention in biomedical applications. Exosomes are cellular secretomes used for intercellular communication. They perform the function of intercellular messengers by facilitating the transport of proteins, lipids, nucleic acids, and therapeutic substances. Their biocompatibility, minimal immunogenicity, targetability, stability, and engineerable characteristics have additionally led to their application as drug delivery vehicles. The therapeutic efficacy of exosomes can be improved through surface modification employing functional molecules, including aptamers, antibodies, and peptides. Given their potential as targeted delivery vehicles to enhance the efficiency of treatment while minimizing adverse effects, exosomes exhibit considerable promise. Stem cells are considered advantageous sources of exosomes due to their distinctive characteristics, including regenerative and self-renewal capabilities, which make them well-suited for transplantation into injured tissues, hence promoting tissue regeneration. However, there are notable obstacles that need to be addressed, including immune rejection and ethical problems. Exosomes produced from stem cells have been thoroughly studied as a cell-free strategy that avoids many of the difficulties involved with cell-based therapy for tissue regeneration and cancer treatment. This review provides an in-depth summary and analysis of the existing knowledge regarding exosomes, including their engineering and cardiovascular disease (CVD) treatment applications.

Mediating the Role of Perceived Social Support Between Frailty and Self-Perceived Burden in Elderly Patients with Diabetes.

Objective: To explore the mediating effects of perceived social support between frailty and self-perceived burden (SPB) in elderly patients with diabetes and to provide a theoretical basis for reducing that burden. Methods: A total of 169 elderly patients with diabetes who were hospitalised in the endocrinology department of a third-class hospital in Wuxi between May 2020 and July 2022 were included in this study using the convenience sampling method. Patients were assessed by the general information questionnaire, the Chinese version of the Tilburg frailty inventory (TFI), the Self-Perceived Burden Scale (SPBS) and the Perceived Social Support Scale (PSSS). The SPSS 22.0 software was used for Pearson's correlation analysis and multiple linear regression analysis. Model four of the SPSS PROCESS was used for mediating the effect analysis. Results: The SPBS of elderly patients with diabetes was positively correlated with the TFI (P < 0.01) and negatively correlated with the PSSS (P < 0.01). The results of the Bootstrap test showed that the mediating effect of the PSSS on the relationship between the TFI and the SPBS in elderly patients with diabetes was 0.296 (95% CI: 0.007, 0.066), and the mesomeric effect accounted for 17.3% of the total effect. Conclusion: The debilitation of elderly patients with diabetes can be reduced by decreasing their SPB through perceived social support. This can be achieved through comprehensive interventions by nurses.

Identification of cellular senescence-associated genes as new biomarkers for predicting the prognosis and immunotherapy response of non-small cell lung cancer and construction of a prognostic model.

Background: Globally, lung carcinoma remains the leading cause of death, with its associated morbidity and mortality rates remaining elevated. Despite the slow advancement of treatment, the outlook remains bleak. Cellular senescence represents a halt in the cell cycle, encompassing a range of physiological and pathological activities, along with diverse phenotypic alterations, including variations in secretory phenotype, macromolecular harm, and metabolic disturbances. Research has revealed its vital function in the formation and growth of tumors. This study aimed to examine cellular senescence-related mRNAs linked to the outlook of non-small cell lung cancer (NSCLC) and to formulate a predictive risk framework for NSCLC. Methods: We acquired the NSCLC expression data from The Cancer Genome Atlas (TCGA) to examine mRNAs linked to cellular senescence. Both single-variable and multiple-variable cox proportion risk assessments were utilized to determine the traits of cellular senescence-related mRNAs linked to NSCLC prognosis. Subsequently, the prognostic model for cellular senescence-related mRNAs was integrated with clinical-pathological characteristics to create a prognostic nomogram. Furthermore, the study delved into the risk-oriented predictive model, examining immune infiltration and responses to immunotherapy among both high and low-risk categories. Results: Utilizing both univariate and multivariate Cox proportion risk assessments, a risk model comprising 12 mRNAs associated with cellular aging was ultimately developed: IGFBP1, TLR3, WT1, ID1, PTTG1, ERRFI1, HEPACAM, MAP2K3, RAD21, NANOG, PRKCD, SOX5. Univariate analysis and multivariate analysis illustrated that the risk score served as a standalone indicator for prognosis, and the hazard ratio (HR) of the risk score were 1.182 (1.139-1.226) (p < 0.001) and 1.162 (1.119 - 1.206) (p < 0.001), respectively. Individual prognoses were forecasted using nomogram, c-index, and principal component analysis (PCA). Furthermore, the risk-oriented model revealed notable statistical variances in immune infiltration and response to immunotherapy among the high and low risk categories. Conclusions: This study shows that mRNAs related to cell senescence associated with prognosis are reliable predictors of NSCLC immunotherapy reaction and prognosis.

Fixed-point algorithms for solving the critical value and upper tail quantile of Kuiper's statistics.

Kuiper's statistic is a good measure for the difference of ideal distribution and empirical distribution in the goodness-of-fit test. However, it is a challenging problem to solve the critical value and upper tail quantile, or simply Kuiper pair, of Kuiper's statistics due to the difficulties of solving the nonlinear equation and reasonable approximation of infinite series. In this work, the contributions lie in three perspectives: firstly, the second order approximation for the infinite series of the cumulative distribution of the critical value is used to achieve higher precision; secondly, the principles and fixed-point algorithms for solving the Kuiper pair are presented with details; finally, finally, a mistake about the critical value cnα for (α,n)=(0.01,30) in Kuiper's distribution table has been labeled and corrected where n is the sample capacity and α is the upper tail quantile. The algorithms are verified and validated by comparing with the table provided by Kuiper. The methods and algorithms proposed are enlightening and worth of introducing to the college students, computer programmers, engineers, experimental psychologists and so on.

A nomogram model based on the systemic immune-inflammation index to predict the risk of venous thromboembolism in elderly patients after hip fracture: A retrospective cohort study.

Background and objectives: Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and secondary pulmonary embolism (PE), represents a significant complication post-hip fracture in the elderly. It is a prevalent cause of VTE-related complications, prolonged hospitalization, and mortality. This study aimed to investigate the potential of the systemic immune-inflammation index (SII) as a predictive marker for VTE in older patients following hip fracture. Methods: The study was structured as an observational, analytical, retrospective cohort analysis. A total of 346 elderly patients diagnosed with hip fracture were included. We retrospectively collated clinical and laboratory data for these patients. Using the bootstrap method, the patients were divided in a 7:3 ratio into a training cohort (DVT group = 170 patients; no-DVT group = 72 patients) and an internal validation cohort (DVT group = 81 patients; no-DVT group = 23 patients). In the training cohort, relevant indices were initially identified using univariate analysis. Subsequently, least absolute shrinkage and selection operator logistic analysis was employed to determine significant potential independent risk factors (P < 0.05). A dynamic online diagnostic nomogram was developed, with its discriminative ability assessed using the area under the receiver operating characteristic curve (AUC). The nomogram's accuracy was further appraised using calibration plots. The clinical utility of the nomogram was evaluated through decision curve analysis (DCA) and corroborated by internal validation within the training set. Results: SII emerged as the sole independent risk factor identified from the multivariate logistic analysis of the training cohort and was incorporated into the VTE diagnostic nomogram for older patients' post-hip fracture. The nomogram demonstrated AUC values of 0.648 in the training cohort and 0.545 in the internal testing cohort. Calibration curves corroborated the close alignment of the nomogram's predicted outcomes with the ideal curve, indicating consistency between predicted and actual outcomes. The DCA curve suggested that all patients could derive benefit from this model. These findings were also validated in the validation cohort. Conclusion: The systemic immune-inflammation index is a robust predictor of venous thromboembolism in elderly patients following hip fracture, underscoring its potential as a valuable tool in clinical practice.

Evolutionary trajectory of diverse SARS-CoV-2 variants at the beginning of COVID-19 outbreak.

Despite extensive scientific efforts directed toward the evolutionary trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans at the beginning of the COVID-19 epidemic, it remains unclear how the virus jumped into and evolved in humans so far. Herein, we recruited almost all adult coronavirus disease 2019 (COVID-19) cases appeared locally or imported from abroad during the first 8 months of the outbreak in Shanghai. From these patients, SARS-CoV-2 genomes occupying the important phylogenetic positions in the virus phylogeny were recovered. Phylogenetic and mutational landscape analyses of viral genomes recovered here and those collected in and outside of China revealed that all known SARS-CoV-2 variants exhibited the evolutionary continuity despite the co-circulation of multiple lineages during the early period of the epidemic. Various mutations have driven the rapid SARS-CoV-2 diversification, and some of them favor its better adaptation and circulation in humans, which may have determined the waxing and waning of various lineages.

Topological Nature of Radiation Asymmetry in Bilayer Metagratings.

Manipulating radiation asymmetry of photonic structures is of particular interest in many photonic applications such as directional optical antenna, high efficiency on-chip lasers, and coherent light control. Here, we proposed a term of pseudopolarization to reveal the topological nature of radiation asymmetry in bilayer metagratings. Robust pseudopolarization vortex with an integer topological charge exists in P-symmetry metagrating, allowing for tunable directionality ranging from -1 to 1 in synthetic parameter space. When P-symmetry breaking, such vortex becomes pairs of C points due to the conservation law of charge, leading to the phase difference of radiation asymmetry from π/2 to 3π/2. Furthermore, topologically enabled coherent perfect absorption is robust with customized phase difference at will between two counterpropagating external light sources. This Letter can not only enrich the understanding of two particular topological photonic behaviors, i.e., bound state in the continuum and unidirectional guided resonance, but also provide a topological view on radiation asymmetry, opening an unexplored avenue for asymmetric light manipulation in on-chip laser, light-light switch, and quantum emitters.

Water-soluble 4-(dimethylaminomethyl)heliomycin exerts greater antitumor effects than parental heliomycin by targeting the tNOX-SIRT1 axis and apoptosis in oral cancer cells.

The antibiotic heliomycin (resistomycin), which is generated from Streptomyces resistomycificus, has multiple activities, including anticancer effects. Heliomycin was first described in the 1960s, but its clinical applications have been hindered by extremely low solubility. A series of 4-aminomethyl derivatives of heliomycin were synthesized to increase water solubility; studies showed that they had anti-proliferative effects, but the drug targets remained unknown. In this study, we conducted cellular thermal shift assays (CETSA) and molecular docking simulations to identify and validate that heliomycin and its water-soluble derivative, 4-(dimethylaminomethyl)heliomycin (designated compound 4-dmH) engaged and targeted with sirtuin-1 (SIRT1) in p53-functional SAS and p53-mutated HSC-3 oral cancer cells. We further addressed the cellular outcome of SIRT1 inhibition by these compounds and found that, in addition to SIRT1, the water-soluble 4-dmH preferentially targeted a tumor-associated NADH oxidase (tNOX, ENOX2). The direct binding of 4-dmH to tNOX decreased the oxidation of NADH to NAD+ which diminished NAD+-dependent SIRT1 deacetylase activity, ultimately inducing apoptosis and significant cytotoxicity in both cell types, as opposed to the parental heliomycin-induced autophagy. We also observed that tNOX and SIRT1 were both upregulated in tumor tissues of oral cancer patients compared to adjacent normal tissues, suggesting their clinical relevance. Finally, the better therapeutic efficacy of 4-dmH was confirmed in tumor-bearing mice, which showed greater tNOX and SIRT1 downregulation and tumor volume reduction when treated with 4-dmH compared to heliomycin. Taken together, our in vitro and in vivo findings suggest that the multifaceted properties of water-soluble 4-dmH enable it to offer superior antitumor value compared to parental heliomycin, and indicated that it functions through targeting the tNOX-NAD+-SIRT1 axis to induce apoptosis in oral cancer cells.

Body mass index influence on short-term perioperative results in robotic-assisted laparoscopic partial nephrectomy: a comprehensive systematic review and meta-analysis.

The objective of this meta-analysis was to evaluate the perioperative outcomes of robotic-assisted partial nephrectomy (RAPN) in obese and non-obese patients. Through March 2024, we executed an exhaustive search in internationally acclaimed databases such as PubMed, Cochrane Library, and Web of Science, limiting our scope to publications in English. We discarded review articles, protocols lacking empirical data, conference abstracts, and materials not pertinent to our research. Our analytical framework utilized the Cochran-Mantel-Haenszel method alongside a random-effects model for evaluating dichotomous variables' mean differences, expressed through odds ratios (OR) with 95% confidence intervals (CI). We established statistical significance at a P value below 0.05. The comprehensive meta-analysis incorporated data from eight cohort studies, collectively assessing 3657 patients. Findings indicated that, relative to individuals of normal weight, those in the obese category had prolonged operative durations (WMD - 25.68 95% CI - 42.07 to - 9.29; P = 0.002), increased estimated blood loss (WMD - 48.55ml, 95% CI - 78.27 to - 18.83; P = 0.001), and longer warm ischemia times (WMD - 1.11, 95% CI - 2.03 to - 0.19; P = 0.02). However, no significant disparities were observed in hospital stay duration, intraoperative and total postoperative complications, severe postoperative complications, or alterations in postoperative estimated glomerular filtration rate (eGFR). Our findings conclude that robotic-assisted partial nephrectomy (RAPN) represents a viable and safe surgical approach for obese patients. This assertion is backed by the observation that crucial metrics, including postoperative renal function alterations, surgical complication rates, and hospitalization duration, exhibit no substantial variances when juxtaposed with counterparts of normal weight.

Associations of vegetable and fruit intake with cognitive function and its decline: Two longitudinal studies.

OBJECTIVES: Previous studies suggested protective associations of vegetables and fruits (VF) intake with cognitive function, but evidence on specific types of VF was insufficient. METHODS: The current study included 4066 participants from 1997 to 2006 in the China Health and Nutrition Survey (CHNS) and 6170 participants from 2013 to 2020 in the Health and Retirement Study (HRS). Dietary intake (using 3-day 24-h dietary recalls in CHNS and food frequency questionnaire in HRS) and cognitive function (using the Telephone Interview for Cognitive Status-Modified, TICS-m) were measured. Linear mixed-effects models were used to estimate the beta coefficients (ß) and the 95% confidence intervals (CI) to evaluate the association of VF with cognitive function (z-score) and its decline. RESULTS: Highest intake of total VF was associated with better cognitive function and slower cognitive decline. Differences in cognitive function z-score between the highest and lowest tertiles of VF consumption were 0.039 (95% CI: 0.002, 0.076) for CHNS and 0.063 (95% CI: 0.026, 0.100) for HRS. The corresponding differences in annual cognitive decline were 0.011 (95% CI: 0.002, 0.021) and 0.012 (95% CI: 0.003, 0.020) units respectively. Vegetables and fruits showed independent associations with cognitive function and its decline. In specific VF subgroups, when comparing the highest to the lowest tertile intake, cruciferous vegetables (ß = 0.058, 95% CI: 0.017, 0.100 in CHNS and ß = 0.067, 95% CI: 0.032, 0.101 in HRS) and green leafy vegetables (ß = 0.036, 95% CI: -0.001, 0.073 in CHNS and ß = 0.082, 95% CI: 0.046, 0.117 in HRS) was associated with better cognitive function in both cohorts. Similarly, higher intake of dark-colored vegetables (ß = 0.019, 95% CI: 0.008, 0.030 for red/yellow vegetables in CHNS and ß = 0.004, 95% CI: 0.001, 0.007 for green leafy vegetables in HRS) were associated with slower cognitive decline in subsequent years. Moreover, rigorous sensitivity analyses confirmed the stability of the results. CONCLUSIONS: Our findings support the potential beneficial roles of VF, especially cruciferous vegetables, green leafy vegetables, and red/yellow vegetables, in maintaining cognitive function and slowing cognitive decline in middle-aged and older adults.

Associations between interleukin-13, interleukin-4 and their receptor gene polymorphisms and susceptibility to atopic dermatitis in a Chinese Han population.

Background Atopic dermatitis (AD) is a common skin condition that occurs due to a combined effect of immune dysregulation, skin barrier dysfunction, changes in the cutaneous microbiome, and genetic factors. Recent data from both clinical trials and real-world studies indicate that dupilumab, a biological agent that inhibits interleukin 4 receptor-α is an effective drug in the treatment of AD, which further suggests the important role of IL-13 and IL-4 in the pathogenesis of AD. Objectives To assess the association between gene polymorphisms of IL-13, IL-13 receptor, IL-4, and IL-4 receptor and susceptibility to AD. Methods The single nucleotide polymorphisms (SNPs) of the above-mentioned genes were detected by single base extension (SNaPshot) assay. The association between these SNPs and AD risk was analysed using SPSS software. Results Two hundred and seventy-one subjects including 130 patients with AD and 141 healthy controls were enrolled. There were statistical differences between AD patients and controls in genotype distribution at rs2265753, rs6646259, and rs2254672 of the IL-13 receptor gene (P all < 0.001). Subjects with CG at rs2265753, AG at rs6646259 and TG at rs2254672 had increased risks for AD (P all < 0.001), and subjects with GG at rs2265753, rs6646259, and rs2254672 had reduced risks for AD (P all < 0.001). Limitation This was a single-centre and single-race study, with a relatively small sample size. Conclusions Findings from this study show that rs2265753, rs6646259 and rs2254672 of the IL-13 receptor gene are associated with susceptibility to AD.

Anti-lung cancer synergy of low-dose doxorubicin and PD-L1 blocker co-delivered via mild photothermia-responsive black phosphorus.

We have previously identified a latent interaction mechanism between non-small cell lung cancer cells (NSCLCC) and their associated macrophages (TAM) mediated by mutual paracrine activation of the HMGB1/RAGE/NF-κB signaling. Activation of this mechanism results in TAM stimulation and PD-L1 upregulation in the NSCLCC. In the present work, we found that free DOX at a low concentration that does not cause DNA damage could activate the HMGB1/RAGE/NF-κB/PD-L1 pathway byinducing oxidative stress. It was thus proposed that a combination of low-dose DOX and a PD-L1 blocker delivered in the NSCLC tumor would achieve synergistic TAM stimulation and thereby synergetic anti-tumor potency. To prove this idea, DOX and BMS-202 (a PD-L1 blocker) were loaded to black phosphorus (BP) nanoparticles after dosage titration to yield the BMS-202/DOX@BP composites that rapidly disintegrated and released drug cargo upon mild photothermal heating at 40 °C. In vitro experiments then demonstrated that low-dose DOX and BMS-202 delivered via BMS-202/DOX@BP under mild photothermia displayed enhanced tumor cell toxicity with a potent synergism only in the presence of TAM. This enhanced synergism was due to an anti-tumor M1-like TAM phenotype that was synergistically induced by low dose DOX plus BMS-202 only in the presence of the tumor cells, indicating the damaged tumor cells to be the cardinal contributor to the M1-like TAM stimulation. In vivo, BMS-202/DOX@BP under mild photothermia exhibited targeted delivery to NSCLC graft tumors in mice and synergistic anti-tumor efficacy of delivered DOX and BMS-202. In conclusion, low-dose DOX in combination with a PD-L1 blocker is an effective strategy to turn TAM against their host tumor cells exploiting the HMGB1/RAGE/NF-κB/PD-L1 pathway. The synergetic actions involved highlight the value of TAM and the significance of modulating tumor cell-TAM cross-talk in tumor therapy. Photothermia-responsive BP provides an efficient platform to translate this strategy into targeted, efficacious tumor therapy.

Social isolation and the risk of Parkinson disease in the UK biobank study.

Parkinson disease (PD) has become one of the most rapidly growing causes of disability among the older population and social isolation is a major concern in the PD community. However, the relationship between social isolation and future risk of PD remains unclear. This study included 192,340 participants aged 60 or older who were free of dementia and PD at baseline from the UK Biobank study. Social isolation was measured using a composite score derived from three questions on number in household, frequency of friend/family visits, and leisure/social activities. Incident PD cases were identified through electronic health records. Multivariable-adjusted Cox regression models were used to compute the hazard ratio (HR) and 95% confidence interval (CI). Among the 192,340 participants (mean [standard deviation] age, 64.2 [2.9] years; 103,253 [53.7%] women), 89,075 (46.3%) participants were in the least isolated group and 26,161 (13.6%) were in the most isolated group. Over a median follow-up of 12.5 years, 2048 incident PD cases were documented. Compared to the least isolated group, the multivariable-adjusted HRs (95% CIs) for PD were 1.00 (0.91-1.10) for the moderately isolated group and 1.19 (1.05-1.36) for the most isolated group (P-trend = 0.04). The observed association was independent of the genetic susceptibility to PD and consistent in subgroup analyses. Social isolation was associated with a higher risk of PD regardless of genetic risk. Our findings highlighted the importance of developing screening and intervention strategies for social isolation among older adults to reduce the risk of PD.

Upgrading CO2 to sustainable aromatics via perovskite-mediated tandem catalysis.

The directional transformation of carbon dioxide (CO2) with renewable hydrogen into specific carbon-heavy products (C6+) of high value presents a sustainable route for net-zero chemical manufacture. However, it is still challenging to simultaneously achieve high activity and selectivity due to the unbalanced CO2 hydrogenation and C-C coupling rates on complementary active sites in a bifunctional catalyst, thus causing unexpected secondary reaction. Here we report LaFeO3 perovskite-mediated directional tandem conversion of CO2 towards heavy aromatics with high CO2 conversion (> 60%), exceptional aromatics selectivity among hydrocarbons (> 85%), and no obvious deactivation for 1000 hours. This is enabled by disentangling the CO2 hydrogenation domain from the C-C coupling domain in the tandem system for Iron-based catalyst. Unlike other active Fe oxides showing wide hydrocarbon product distribution due to carbide formation, LaFeO3 by design is endowed with superior resistance to carburization, therefore inhibiting uncontrolled C-C coupling on oxide and isolating aromatics formation in the zeolite. In-situ spectroscopic evidence and theoretical calculations reveal an oxygenate-rich surface chemistry of LaFeO3, that easily escape from the oxide surface for further precise C-C coupling inside zeolites, thus steering CO2-HCOOH/H2CO-Aromatics reaction pathway to enable a high yield of aromatics.

A single-cell atlas of lung homeostasis reveals dynamic changes during development and aging.

Aging is a global challenge, marked in the lungs by function decline and structural disorders, which affects the health of the elderly population. To explore anti-aging strategies, we develop a dynamic atlas covering 45 cell types in human lungs, spanning from embryonic development to aging. We aim to apply the discoveries of lung's development to address aging-related issues. We observe that both epithelial and immune cells undergo a process of acquisition and loss of essential function as they transition from development to aging. During aging, we identify cellular phenotypic alternations that result in reduced pulmonary compliance and compromised immune homeostasis. Furthermore, we find a distinctive expression pattern of the ferritin light chain (FTL) gene, which increases during development but decreases in various types of lung cells during the aging process.

Association of cardiovascular disease prevalence with BMD and fracture in men with T2DM.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are predisposed to cardiovascular disease (CVD). Bone mineral density (BMD) is linked to CVD, but most studies focused on women. Our analysis aims to explore the association of BMD and fracture with the prevalence of CVD in men with T2DM. METHODS: In this retrospective cross-sectional study, 856 men with T2DM were enrolled. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The CVD outcome was determined as the sum of the following conditions: congestive heart failure, coronary heart disease, angina pectoris, myocardial infarction, the requirement for coronary artery revascularization, and stroke. The relationship between BMDs and CVD was investigated by restricted cubic spline curves and logistic regression models. RESULTS: A total of 163 (19.0%) patients developed CVD. The restricted cubic spline curve revealed a linear and negative association between FN-BMD, TH-BMD, and CVD. After full adjustments for confounding covariates, the odds ratios were 1.34 (95% confidence interval [CI] [1.11-1.61], p < .05), 1.3 (95% CI [1.05-1.60], p < .05), and 1.26 (95% CI [1.02-1.55], p < .05) for each 1-SD decrease in BMDs of L2-4, FN and TH, respectively. T-scores of < -1 for BMD of L2-4 and FN were independently associated with CVD (p < .05). Subgroup analyses further supported our findings. CONCLUSIONS: The prevalence of CVD was inversely correlated with BMD levels in men with T2DM, particularly at the FN. We hypothesized that monitoring FN-BMD and early intervention would help reduce CVD risk in men with T2DM, especially those with hypertension.

The effect of refined psychological pain nursing combined with IMB nursing on the pain, sleep and quality of life of patients after cervical cancer surgery.

To explore the effect of refined psychological pain nursing combined with information-motivation-behavioral (IMB) care model on the pain, sleep and quality of life of patients after cervical cancer surgery, so as to provide reference and basis for the nursing of patients after cervical cancer surgery. The clinical data of 798 postoperative cervical cancer patients who were nursing in our hospital from January 2018 to December 2022 were included in this retrospective study and divided into the control group (n = 382) and observation group (n = 416) according to the different care methods. The control group used refined psychological pain nursing, and on this basis, the observation group used IMB nursing to observe and compare the differences in pain, sleep and quality of life between the 2 groups. There was no significant difference in pain between the 2 groups before nursing (P > .05). After nursing, the pain of both groups was significantly improved. The scores of NRS, VAS, and PSEQ of the observation group were significantly better than those of the control group (P < .001). After nursing, the quality of life scores such as emotion, cognition, society, and overall health were significantly higher in the observation group than those of the control group, while physical, fatigue, nausea, vomiting, and pain were significantly lower than those of the control group (P < .05). The negative emotion score of the observation group was significantly lower than that of the control group (P < .001). The residual urine volume and urinary tract infection rate of the observation group were significantly lower than those of the control group (P < .05). The bladder function was significantly better than that of the control group (P < .05). The analgesic effect of refined psychological pain nursing combined with IMB nursing on patients after cervical cancer surgery is better than that of refined psychological pain nursing alone, which can promote pain recovery and further improve the quality of life and sleep quality of patients.

Biotransformation and disposition characteristics of HSK7653, a novel long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes.

AIM: To investigate the metabolism and disposition characteristics of HSK7653 in healthy male Chinese participants. METHODS: A single oral dose of 80 µCi (25 mg) [14C]HSK7653 capsules was administered to six healthy participants, and blood, plasma, urine and faeces were collected. Quantitative and qualitative analysis was conducted to investigate the pharmacokinetics, blood-to-plasma ratio, mass balance and metabolism of HSK7653. RESULTS: The drug was well absorbed and reached a maximum concentration at 1.25 h. The drug-related components (HSK7653 and its metabolites) were eliminated slowly, with a half-life (t1/2) of 111 h. Unchanged HSK7653 contributed to more than 97% of the total radioactivity in all plasma samples. The blood-to-plasma ratio (0.573-0.845) indicated that HSK7653 did not tend to distribute into blood cells. At 504 h postdose, up to 95.9% of the dose was excreted, including 79.8% in urine and 16.1% in faeces. Most of the radioactivity (75.5% dose) in excreta was unchanged HSK7653. In addition, nine metabolites were detected in urine and faeces. The most abundant metabolite was M6-2, a dioxidation product of HSK7653, which accounted for 4.73% and 2.63% of the dose in urine and faeces, respectively. The main metabolic pathways of HSK7653 in vivo included oxidation, pyrrole ring opening and sulphonamide hydrolysation. CONCLUSION: HSK7653 was well absorbed, slightly metabolized and slowly excreted in humans. The high plasma exposure and long t1/2 of HSK7653 may contribute to its long-lasting efficacy as a long-acting dipeptidyl peptidase-4 inhibitor.

Molecular-Sieving Separation of Methanol/Benzene Azeotrope by a Flexible Metal-Organic Framework.

Separation of methanol/benzene azeotrope mixtures is very challenging not only by the conventional distillation technique but also by adsorbents. In this work, we design and synthesize a flexible Ca-based metal-organic framework MAF-58 consisting of cheap raw materials. MAF-58 shows selective methanol-induced pore-opening flexibility. Although the opened pores are large enough to accommodate benzene molecules, MAF-58 shows methanol/benzene molecular sieving with ultrahigh experimental selectivity, giving 5.1 mmol g-1 high-purity (99.99%+) methanol and 2.0 mmol g-1 high-purity (99.97%+) benzene in a single adsorption/desorption cycle. Computational simulations reveal that the preferentially adsorbed, coordinated methanol molecules act as the gating component to selectively block the diffusion of benzene, offering a new gating adsorption mechanism.