Intervention effect of Lycium barbarum polysaccharide on lead-induced kidney injury mice and its mechanism: A study based on the PI3K/Akt/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional medicinal application of Lycium barbarum is centered on the improvement of eyesight, as well as the nourishment of liver and kidney functions. Lycium barbarum polysaccharide (LBP), serving as the principal active constituent of Lycium barbarum, has been identified as the main contributor to these beneficial effects. Previous studies have indicated that Lycium barbarum polysaccharide exhibits a renoprotective effect against lead-induced injury, but its mechanism and efficacy remain unclear. AIM OF THE STUDY: The objective of this study was to examine the effectiveness of LBP in preventing lead-induced renal injury and investigate both the toxic mechanism of lead-induced renal injury and the efficacy mechanism of LBP against it, with a focus on the PI3K/AKT/mTOR signaling pathway. MATERIALS AND METHODS: The drug effect and mechanism of LBP on lead-induced kidney injury were investigated by administering positive drugs and LBP to mice with established lead-induced kidney injury. RESULTS: The renal function of mice with lead-induced renal injury was significantly restored, renal tissue lesions and renal mitochondrial damage were delayed, a disorder of hematological parameters induced by lead was improved, the increase of lead-induced renal index was reduced, and the body weight of mice with lead-induced renal injury was increased by the LBP intervention, as revealed by the results of pharmacodynamic experiments. Based on PI3K /AKT /mTOR signaling pathway, the toxic mechanism of lead-induced kidney injury and the pharmacodynamic mechanism of LBP against lead-induced kidney injury were studied. The results showed that lead could activate the TLR4 receptor, and then activate PI3K /AKT /mTOR signaling pathway, inhibit autophagy of kidney tissue cells, and enhance apoptosis of kidney tissue cells to induce kidney injury; LBP inhibits the activation of TLR4 receptor, which in turn inhibits the PI3K/AKT/mTOR signaling pathway, enhances the autophagy of kidney tissue cells, reduces the apoptosis of kidney tissues, and delays lead-induced kidney injury.

Degradation of Cyclin-Dependent Kinase 9/Cyclin T1 by Optimized Microtubule-Associated Protein 1 Light Chain 3 Beta-Recruiting Coumarin Analogs.

Autophagy is an efficient and attractive protein degradation pathway in addition to the ubiquitin-proteasome system. Herein, systematic optimization of coumarin analogs linked with the CDK9 inhibitor SNS-032 is reported that may bind to cyclin-dependent kinase 9 (CDK9) and microtubule-associated protein 1 light chain 3 beta (LC3B) simultaneously, which leads to the selective autophagic degradation of targeted CDK9/cyclin T1 and is different from the PROTAC degrader THAL-SNS-032. Further mechanism studies revealed an autophagy-lysosome pathway, where the degraders possibly formed a ternary complex with CDK9 and LC3B. In addition, degrader 10 showed antitumor efficacy in vivo. Our work optimized a potent LC3B recruiter and demonstrated the feasibility of autophagy-tethering compounds (ATTECs), which could be applied for the degradation of diverse intracellular pathogenic proteins to treat related diseases.

Probing the Activity Enhancement of Carbocatalyst with the Anchoring of Atomic Metal.

Enhanced catalysis for organic transformation is essential for the synthesis of high-value compounds. Atomic metal species recently emerged as highly effective catalysts for organic reactions with high activity and metal utilization. However, developing efficient atomic catalysts is always an attractive and challenging topic in the modern chemical industry. In this work, we report the preparation and activity enhancement of nitrogen- and sulfur-codoped holey graphene (NSHG) with the anchoring of atomic metal Pd. When employed as the catalyst for nitroarenes reduction reactions, the resultant Pd/NSHG composite exhibits remarkably high catalytic activity due to the co-existence of dual-active components (i.e., catalytically active NSHG support and homogeneous dispersion of atomic metal Pd). In the catalytic 4-nitrophenol (4-NP) reduction reaction, the efficiency (turnover frequency) is 3.99 × 10-2 mmol 4-NP/(mg cat.·min), which is better than that of metal-free nitrogen-doped holey graphene (NHG) (2.3 × 10-3 mmol 4-NP/(mg cat.·min)) and NSHG carbocatalyst (3.8 × 10-3 mmol 4-NP/(mg cat.·min)), the conventional Pd/C and other reported metal-based catalysts. This work provides a rational design strategy for the atomic metal catalysts loaded on active doped graphene support. The resultant Pd/NSHG dual-active component catalyst (DACC) is also anticipated to bring great application potentials for a broad range of organic fields, such as organic synthesis, environment treatment, energy storage and conversion.

Digital twin-driven dynamic monitoring system of the upper limb force.

Digital twin represents the core technology to realize the dynamic monitoring of complex industrial systems. However, the human body, as the most complex system in the physical world, digital twin is rarely applied in it. In this study, we successfully demonstrated a digital twin in the human biomedical application by proposing a dynamic monitoring system of the upper limb force. In this system, the real upper limb drives the motion of the virtual one in real-time and dynamically updates the force. Meanwhile, the virtual upper limb feeds back the monitoring-results of the force to the controller of the real upper limb via immersive virtual reality interaction. Experimental results of the typical motions of the upper limb revealed that the proposed system functioned interactively in real-time in a non-invasive manner, while ensuring the accurate solving of the muscle force. In conclusion, our digital twin-driven system is of great importance for rehabilitation medicine, biomechanical scientific research and physical training, promoting the application of the digital twin in the human biomedical field.

FGF2 Alleviates Microvascular Ischemia-Reperfusion Injury by KLF2-mediated Ferroptosis Inhibition and Antioxidant Responses.

An essential pathogenic element of acute limb ischemia/reperfusion (I/R) injury is microvascular dysfunction. The majority of studies indicates that fibroblast growth factor 2 (FGF2) exhibits protective properties in cases of acute I/R injury. Albeit its specific role in the context of acute limb I/R injury is yet unknown. An impressive post-reperfusion increase in FGF2 expression was seen in a mouse model of hind limb I/R, followed by a decline to baseline levels, suggesting a key role for FGF2 in limb survivability. FGF2 appeared to reduce I/R-induced hypoperfusion, tissue edema, skeletal muscle fiber injury, as well as microvascular endothelial cells (ECs) damage within the limb, according to assessments of limb vitality, Western blotting, and immunofluorescence results. The bioinformatics analysis of RNA-sequencing revealed that ferroptosis played a key role in FGF2-facilitated limb preservation. Pharmacological inhibition of NFE2L2 prevented ECs from being affected by FGF2's anti-oxidative and anti-ferroptosis activities. Additionally, silencing of kruppel-like factor 2 (KLF2) by interfering RNA eliminated the antioxidant and anti-ferroptosis effects of FGF2 on ECs. Further research revealed that the AMPK-HDAC5 signal pathway is the mechanism via which FGF2 regulates KLF2 activity. Data from luciferase assays demonstrated that overexpression of HDAC5 prevented KLF2 from becoming activated by FGF2. Collectively, FGF2 protects microvascular ECs from I/R injury by KLF2-mediated ferroptosis inhibition and antioxidant responses.

Differential regulation of hippocampal transcriptome by circulating estrogen.

Estrogen (E2) modulates the synaptic structure and plasticity in the hippocampus. Previous studies showed that E2 fluctuations during various phases of the menstrual cycle produce subtle neurosynaptic changes that impact women's behavior, emotion, and cognitive functions. In this study, we explored the transcriptome of the hippocampus via RNA-seq (RNA-sequencing) between proestrus (PE) and diestrus (DE) stages in young female rats to determine the effect of E2 of PE and DE stages on hippocampal gene expression. We identified 238 genes (at 1.5-fold-change selection criteria, FDR adjusted p-value < 0.05) as differentially expressed genes (DEGs) that responded to E2 between PE and DE stages. Functional analysis based on Gene Ontology (GO) revealed that a higher E2 level corresponded to an increase in gene transcription among most of the DEGs, suggesting biological mechanisms operating differentially in the hippocampus of female rats between PE and DE stages in the estrus cycle; while analysis with Kyoto Encyclopedia of Genes and Genomes database (KEGG) found that the DEGs involving neuroactive ligand-receptor interaction, antigen processing, cell adhesion molecules, and presentation were upregulated in PE stage, whereas DEGs in pathways relating to bile secretion, coagulation cascades, osteoclast differentiation, cysteine and methionine metabolism were upregulated in DE stage of the estrus cycle. The high-fold expression of DEGs was confirmed by a follow-up quantitative real-time PCR. Our findings in this current study have provided fundamental information for further dissection of neuro-molecular mechanisms in the hippocampus in response to E2 fluctuation and its relationship with disorders.

SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop.

BACKGROUND: Sec23 homolog A (SEC23A), a core component of coat protein complex II (COPII), has been reported to be involved in several cancers. However, the role of SEC23A in gastric cancer remains unclear. METHODS: The expression of SEC23A in gastric cancer was analyzed by using qRT-PCR, western blotting and IHC staining. The role of SEC23A in ER stress resistance was explored by functional experiments in vitro and vivo. The occupation of STAT3 on the SEC23A promoter region was verified by luciferase reporter plasmids and CHIP assay. The interaction between SEC23A and ANXA2 was identified by Co-IP and mass spectrometry analysis. RESULTS: We demonstrated that SEC23A was upregulated in gastric cancer and predicted poor prognosis in patients with gastric cancer. Mechanistically, SEC23A was transcriptional upregulated by ER stress-induced pY705-STAT3. Highly expressed SEC23A promoted autophagy by regulating the cellular localization of ANXA2. The SEC23A-ANXA2-autophay axis, in turn, protected gastric cancer cells from ER stress-induced apoptosis. Furthermore, we identified SEC23A attenuated 5-FU therapeutic effectiveness in gastric cancer cells through autophagy-mediated ER stress relief. CONCLUSION: We reveal an ER stress-SEC23A-autophagy negative feedback loop that enhances the ability of gastric cancer cells to resist the adverse survival environments. These results identify SEC23A as a promising molecular target for potential therapeutic intervention and prognostic prediction in patients with gastric cancer.

Deep reinforcement learning-aided autonomous navigation with landmark generators.

Mobile robots are playing an increasingly significant role in social life and industrial production, such as searching and rescuing robots, autonomous exploration of sweeping robots, and so on. Improving the accuracy of autonomous navigation of mobile robots is a hot issue to be solved. However, traditional navigation methods are unable to realize crash-free navigation in an environment with dynamic obstacles, more and more scholars are gradually using autonomous navigation based on deep reinforcement learning (DRL) to replace overly conservative traditional methods. But on the other hand, DRL's training time is too long, and the lack of long-term memory easily leads the robot to a dead end, which makes its application in the actual scene more difficult. To shorten training time and prevent mobile robots from getting stuck and spinning around, we design a new robot autonomous navigation framework which combines the traditional global planning and the local planning based on DRL. Therefore, the entire navigation process can be transformed into first using traditional navigation algorithms to find the global path, then searching for several high-value landmarks on the global path, and then using the DRL algorithm to move the mobile robot toward the designated landmarks to complete the final navigation, which makes the robot training difficulty greatly reduced. Furthermore, in order to improve the lack of long-term memory in deep reinforcement learning, we design a feature extraction network containing memory modules to preserve the long-term dependence of input features. Through comparing our methods with traditional navigation methods and reinforcement learning based on end-to-end depth navigation methods, it shows that while the number of dynamic obstacles is large and obstacles are rapidly moving, our proposed method is, on average, 20% better than the second ranked method in navigation efficiency (navigation time and navigation paths' length), 34% better than the second ranked method in safety (collision times), 26.6% higher than the second ranked method in success rate, and shows strong robustness.

Increased production and anti-senescence activity of exopolysaccharides in Ganoderma lingzhi by co-overexpression of ß-1,3-glucan synthase and UDP-glucose pyrophosphorylase.

A ß-1,3-glucan synthase gene (gls) was cloned and overexpressed in Ganoderma lingzhi. The content of intracellular polysaccharides (IPS) in G. lingzhi overexpressing gls was 22.36 mg/100 mg dry weight (DW), 19 % higher than those in the wild-type (WT) strain. Overexpression of gls did not affect the expression of the phosphoglucomutase gene and the UDP-glucose pyrophosphorylase gene (ugp) in the polysaccharide biosynthesis. The gls and ugp were then simultaneously overexpressed in G. lingzhi for the first time. The combined overexpression of these two genes increased the IPS content and exopolysaccharides (EPS) production to a greater extent than the overexpression of gls independently. The maximum IPS content of the overexpressed strain was 24.61 mg/100 mg, and the maximum EPS production was 1.55 g/L, 1.31- and 1.50-fold higher than that in the WT strain, respectively. Moreover, the major EPS fractions from the overexpression strain contained more glucose (86.7 % and 72.5 %) than those from the WT strain (78.2 % and 62.9 %). Furthermore, the major fraction G+U-0.1 from the overexpression strain exhibited stronger antioxidant and anti-senescence activities than the WT-0.1 fraction from the WT strain. These findings will aid in the hyperproduction and application of Ganoderma polysaccharides and facilitate our understanding of mushroom polysaccharide biosynthesis.

Word self-update contrastive adversarial networks for text-to-image synthesis.

Synthesizing realistic fine-grained images from text descriptions is a significant computer vision task. Although many GANs-based methods have been proposed to solve this task, generating high-quality images consistent with text information remains a difficult problem. These existing GANs-based methods ignore important words due to the use of fixed initial word features in generator, and neglect to learn semantic consistency between images and texts for discriminators. In this article, we propose a novel attentional generation and contrastive adversarial framework for fine-grained text-to-image synthesis, termed as Word Self-Update Contrastive Adversarial Networks (WSC-GAN). Specifically, we introduce a dual attention module for modeling color details and semantic information. With a new designed word self-update module, the generator can leverage visually important words to compute attention maps in the feature synthesis module. Furthermore, we contrive multi-branch contrastive discriminators to maintain better consistency between the generated image and text description. Two novel contrastive losses are proposed for our discriminators to impose image-sentence and image-word consistency constraints. Extensive experiments on CUB and MS-COCO datasets demonstrate that our method achieves better performance compared with state-of-the-art methods.

Study on the influence of urban tree canopy on thermal environment in Luoping County.

Urban forest is an integral part of the complex urban ecosystem, and tree canopy plays a key role in improving urban climatic environment. Urban Tree Canopy (UTC) is strongly linked to urban thermal environment and living quality of residents. In this study, Luoping County, a mountainous county in southwest China, was selected as the study area to uncover the inner connections between tree canopy and thermal environment, and provide relevant scientific references for the construction of livable forest cities in similar areas. Through eCongnition Developer, ENVI and ArcGIS software, the distribution of Land Surface Temperature (LST) and land cover types in the study area was extracted, 63 patches with super-large and extra-large tree canopy coverage selected, to explore the regulatory effect of UTC patches on urban thermal environment based on SPSS software. Results showed that the highest LST in the research area was 37.63 â„ƒ, the lowest 24.73 â„ƒ, and the average 30.83 â„ƒ. Among the land cover types, the area of buildings and impervious surfaces was 1615.71 hm2, accounting for 55.76% of the total study area, which was the largest proportion and with widespread distribution; the area of grassland and water body was 57.48 hm2 and 12.35 hm2, respectively, taking up 1.98% and 0.43%, with a smaller proportion. Mean LST: impervious surface > bare land > grassland > tree canopy > water body. By increasing the area and perimeter of the patch covered by tree canopy, the cooling rate of the patch can be increased while the temperature inside the patch can be reduced. The relationship between the area and cooling rate is closer than that between perimeter and cooling rate. The increase of perimeter has a stronger alleviation effect on the internal temperature of the patch, whereas, the increase of area has a weaker effect in this respect.

N-Heterocyclic Nitrenium-Catalyzed Photohomolysis of CF3SO2Cl for Alkene Trifluoromethylation.

N-Heterocyclic nitreniums (NHNs) have been utilized as Lewis acid catalysts to activate substrates with lone pairs. Alternative to their conventional applications, we have discovered that NHNs can also serve as charge transfer complex catalysts. Herein, we present another potential of NHNs by utilizing a weak interaction between NHNs and CF3SO2Cl. The method promotes CF3SO2Cl to undergo photohomolysis, resulting in the CF3 radical. Mechanistic studies suggested that the weak interaction could be due to the π-hole effect of NHNs.

Unraveling and characterization of novel T3SS effectors in Edwardsiella piscicida.

Type III secretion system (T3SS) facilitates survival and replication of Edwardsiella piscicida in vivo. Identifying novel T3SS effectors and elucidating their functions are critical in understanding the pathogenesis of E. piscicida. E. piscicida T3SS effector EseG and EseJ was highly secreted when T3SS gatekeeper-containing protein complex EsaB-EsaL-EsaM was disrupted by EsaB deficiency. Based on this observation, concentrated secretomes of ΔesaB strain and ΔesaBΔesaN strain were purified by loading them into SDS-PAGE gel for a short electrophoresis to remove impurities prior to the in-the gel digestion and mass spectrometry. Four reported T3SS effectors and two novel T3SS effector candidates EseQ (ETAE_2009) and Trx2 (ETAE_0559) were unraveled by quantitative comparison of the identified peptides. EseQ and Trx2 were revealed to be secreted and translocated in a T3SS-dependent manner through CyaA-based translocation assay and immunofluorescent staining, demonstrating that EseQ and Trx2 are the novel T3SS effectors of E. piscicida. Trx2 was found to suppress macrophage apoptosis as revealed by TUNEL staining and cleaved caspase-3 of infected J774A.1 monolayers. Moreover, Trx2 has been shown to inhibit the p65 phosphorylation and p65 translocation into the nucleus, thus blocking the NF-κB pathway. Furthermore, depletion of Trx2 slightly but significantly attenuates E. piscicida virulence in a fish infection model. Taken together, an efficient method was established in unraveling T3SS effectors in E. piscicida, and Trx2, one of the novel T3SS effectors identified in this study, was demonstrated to suppress apoptosis and block NF- κB pathway during E. piscicida infection. IMPORTANCE Edwardsiella piscicida is an intracellular bacterial pathogen that causes intestinal inflammation and hemorrhagic sepsis in fish and human. Virulence depends on the Edwardsiella type III secretion system (T3SS). Identifying the bacterial effector proteins secreted by T3SS and defining their role is key to understanding Edwardsiella pathogenesis. EsaB depletion disrupts the T3SS gatekeeper-containing protein complex, resulting in increased secretion of T3SS effectors EseG and EseJ. EseQ and Trx2 were shown to be the novel T3SS effectors of E. piscicida by a secretome comparison between ∆esaB strain and ∆esaB∆esaN strain (T3SS mutant), together with CyaA-based translocation assay. In addition, Trx2 has been shown to suppress macrophage apoptosis and block the NF-κB pathway. Together, this work expands the known repertoire of T3SS effectors and sheds light on the pathogenic mechanism of E. piscicida.

(+)- and (-)-Tedanine, a pair of new enantiomeric indolone alkaloids from the marine sponge Tedania sp.

(+)- and (-)-Tedanine [(+)-1 and (-)-1], a pair of new enantiomeric indolone alkaloids, along with nine compounds (2-10) were isolated from the marine sponge Tedania sp. The structures of (+)-1 and (-)-1 including absolute configurations were determined by spectroscopic analysis and quantum chemical calculation. Compounds (+)-1 and (-)-1 were the first examples of indolone alkaloids isolated from this genus. In addition, the cytotoxic and antibacterial activities of these compounds were also evaluated.

Hydrogen-rich saline alleviates cardiomyocyte apoptosis by reducing expression of calpain1 via miR-124-3p.

AIMS: Molecular hydrogen has been exhibited a protective function in heart diseases. Our previous study demonstrated that hydrogen-rich saline (HRS) could scavenge free radicals selectively and alleviate the inflammatory response in the myocardial ischaemia/reperfusion (I/R) injury, but the underlying mechanism has not been fully clarified. METHODS AND RESULTS: Adult (10 weeks) C57BL/6 male mice and neonatal rat cardiomyocytes were used to establish I/R and hypoxia/reoxygenation (H/R) injury models. I/R and H/R models were treated with HRS to classify the mechanisms of cardioproctective function. In this study, we found that miR-124-3p was significantly decreased in both I/R and H/R models, while it was partially ameliorated by HRS pretreatment. HRS treatment also alleviated ischaemia-induced apoptotic cell death and increased cell viability during I/R process, whereas silencing expression of miR-124-3p abolished this protective effect. In addition, we identified calpain1 as a direct target of miR-124-3p, and up-regulation of miR-124-3 produced both activity and expression of calpain1. It was also found that compared with the HRS group, overexpression of calpain1 increased caspase-3 activities, promoted cleaved-caspase3 and Bax protein expressions, and correspondingly decreased Bcl-2, further reducing cell viability. These results illustrated that calpain1 overexpression attenuated protective effect of HRS on cardiomyocytes in H/R model. CONCLUSIONS: The present study showed a protective effect of HRS on I/R injury, which may be associated with miR-124-3p-calpain1 signalling pathway.

Efficient biosynthesis of Vibegron intermediate using a novel carbonyl reductase based on molecular modification of hydrogen bonding network regulation.

Vibegron is a novel, potent, highly selective ß3-adrenergic receptor agonist for the treatment of overactive bladder with higher therapeutic capacity and lower side effects. Methyl(2S,3R)-2-((tert-butoxycarbonyl)amino)-3-hydroxy-3-phenylpropanoate ((2S,3R)-aminohydroxy ester) is a key chiral intermediate for the synthesis of Vibegron. A novel carbonyl reductase from Exiguobacterium sp. s126 (EaSDR6) was isolated using data mining technology from GenBank database with preferable catalytic activity. Hydrogen bond network regulation was performed using site-directed saturation mutagenesis and combination mutagenesis. The mutant EaSDR6A138L/S193A was obtained with the activity improvement by 4.58 folds compared with the wild type EaSDR6. The Km of EaSDR6A138L/S193A was decreased from 1.57 mM to 0.67 mM, kcat was increased by 2.17 folds, and the overall catalytic efficiency kcat/Km was increased by 5.07 folds. The organic-aqueous biphasic bioreaction system for the asymmetric synthesis of (2S,3R)-aminohydroxy ester was constructed for the first time. Under the substrate concentration of 150 g/L, the yield of (2S,3R)-aminohydroxy ester was > 99.99%, the e.e. was > 99.99%, and the spatiotemporal yield was 1.55 g/(L·h·g DCW) after 12 h reaction. While the substrate concentration was increased to 200 g/L and the reaction lasted for 36 h, the yield of (2S,3R)-aminohydroxy ester was > 99.99%, the e.e. was > 99.99% and the spatiotemporal yield was 1.05 g/(L·h·g DCW). The substrate concentration and spatiotemporal yield were higher than ever reported.

Rhesus macaques show increased resistance to repeated SHIV intrarectal exposure following a heterologous regimen of rVSV vector vaccine expressing HIV antigen.

Despite the human immunodeficiency virus (HIV) pandemic continuing worldwide for 40 years, no vaccine to combat the disease has been licenced for use in at risk populations. Here, we describe a novel recombinant vesicular stomatitis virus (rVSV) vector vaccine expressing modified HIV envelope glycoproteins and Ebola virus glycoprotein. Three heterologous immunizations successfully prevented infection by a different clade SHIV in 60% of non-human primates (NHPs). No trend was observed between resistance and antibody interactions. Resistance to infection was associated with high proportions of central memory T-cell CD69 and CD154 marker upregulation, increased IL-2 production, and a reduced IFN-γ response, offering insight into correlates of protection.

Association between all-cause mortality and trajectories across quality and duration of sleep and cognitive function: based on Group-Based Multivariate Trajectory modeling.

BACKGROUND: Sleep duration and quality are associated with cognition, but the interaction of the 3 indicators and their association with all-cause mortality is unclear. METHODS: We used data from the Chinese Longitudinal Healthy Longevity Survey from 2005-2018 to identify latent trajectories of sleep duration, sleep quality, and cognitive function. Secondly, the multinomial logistic model was adopted to determine predictors of trajectory groups. Finally, the Cox regression model was used to examine the association between these trajectory groups and all-cause mortality. RESULTS: A total of 5046 adults (49% women) with an average age of 76.34 were included in the study. The median follow-up period was 11.11 years, during which 1784 (35%) participants died. We identified 4 latent groups among older adults: 'Good-performance' (51%), 'Decreasing' (26%), 'Oversleep & cognitive impairment' (12%), and 'Sleep-deprived' (11%). Individuals in the 'Decreasing' had a 51% increased risk of all-cause mortality (HR = 1.51, 95% CI: 1.25 - 1.81, p < .001). Individuals in the 'Oversleep & cognitive impairment' had a 170% increased risk of all-cause mortality (HR = 2.7 95% CI: 2.13 - 3.43, p < .001). Women had a higher risk of all-cause mortality regardless of trajectory group (47-143% men VS. 74-365% women). Both urban and rural areas have a similarly increased risk of all-cause mortality (48-179%). CONCLUSIONS: Our study reveals the latent trajectories across sleep duration, sleep quality, and cognitive function in older Chinese and further explores their association with death. These findings provide a rational basis for cognitive interventions and reduce all-cause mortality.

Therapy by physician-pharmacist combination and economic returns for cancer pain management in China: a cost-effectiveness analysis.

Objective: To examine whether joint management of cancer pain by physicians and pharmacists in clinics provides economic advantages from the perspective of the Chinese healthcare system. Methods: From February 2018 to March 2020, 100 patients who visited the joint cancer pain clinic at the Xiangya Hospital of Central South University were included. These patients were randomly assigned to either the control or intervention groups. The control group received regular outpatient services from a physician, while the intervention group received regular outpatient services from a physician and medication education provided by a pharmacist. The study considered various direct costs, including drug expenses, physician-pharmacist outpatient services, adverse event management, consultations, examinations, and readmissions. The outcome indicators considered were the cancer pain control rate and the reduction in pain scores. Decision tree modeling, single-factor sensitivity analysis, and probabilistic sensitivity analysis were performed to evaluate the cost-effectiveness of joint physician-pharmacist outpatient services compared to physician-alone outpatient services. Results: The intervention group showed a significantly higher cancer pain control rate than the control group (0.69 vs. 0.39, p = 0.03). In the decision tree model, the intervention group had a significantly lower pain score than the control group (0.23 vs. 0.14). The cost per person in the intervention group was $165.39, while it was $191.1 per person in the control group. The univariate sensitivity analysis showed that the cost of self-management for patients in the control group was identified as the primary sensitivity factor. Probabilistic sensitivity analysis indicated that the joint clinic group had a favorable incremental cost-effectiveness compared to the physician clinic group. In addition, the probabilistic sensitivity analysis demonstrated an absolute advantage in the incremental cost-effectiveness of the joint clinic group over the outpatient physician group. Conclusion: The participation of pharmacists in joint cancer pain clinic services led to improved pain management for patients, demonstrating a clear advantage in terms of cost-effectiveness.