Bifurcation and hybrid control of a discrete eco-epidemiological model with Holling type-III.

In this paper, a three dimensional discrete eco-epidemiological model with Holling type-III functional response is proposed. Boundedness of the solutions of the system is analyzed. Existence condition and stability of all fixed points are discussed for the proposed model. Furthermore, we obtained the transcritical bifurcation surfaces of the system by bifurcation theory. Based on the explicit criteria for the Neimark Sacker bifurcation and flip bifurcation, we obtained that the system undergoes these two types of bifurcations at the positive fixed point. Then we apply a hybrid control strategy that based on both parameter perturbation and a state feedback strategy to control the Neimark-Sacker bifurcation. Finally, some numerical simulations are carried out to support the analytical results.

The causal relationship between blood cell indices and 28-day mortality in sepsis: a retrospective study and bidirectional Mendelian randomization analysis.

BACKGROUND: Despite emerging evidence linking blood cell indices (BCIs) to sepsis mortality, the inconsistency of observational studies obscures the clarity of these associations. This study aims to clarify the causal influence of BCIs on 28-day mortality rates in sepsis patients. METHODS: Utilizing univariable and multivariable Mendelian randomization (MR) analyses, we examined the impact of BCIs on sepsis mortality by analyzing data from extensive genome-wide association studies. The inverse-variance weighted (IVW) method was our primary analytic tool, complemented by several robustness checks to mitigate pleiotropy, including weighted median, mode-based estimates, MR-Egger regression, and MR-PRESSO. Subsequently, we conducted a retrospective study to further explore the correlation between platelet indices and 28-day mortality of sepsis using real-world data. RESULTS: Our findings highlight a significant causal relationship between platelet distribution width (PDW) and 28-day mortality in sepsis, with the univariable Mendelian randomization approach yielding an odds ratio of 1.12 (95% CI, 1.06-1.26; P < 0.05). Multivariable analysis further substantiated PDW's robust association with mortality risk (OR 1.23; 95% CI, 1.03-1.48; P < 0.05). Conversely, our analysis did not uncover significant correlations between the genetic predispositions to other BCIs-including red blood cell count, erythrocyte distribution width, platelet count, mean platelet volume, white blood cell count, neutrophil count, neutrophil percentage, lymphocyte count, and lymphocyte percentage-and 28-day mortality in sepsis. Additionally, an inverse MR analysis did not establish a causal impact of 28-day mortality in sepsis on PDW (OR 1.00; 95% CI, 1.00-1.07; P = 0.29). Moreover, a similar result was observed in the retrospective study. CONCLUSIONS: The study underscores the independent causal role of PDW in predicting 28-day mortality in sepsis, suggesting its potential utility in early patient assessment, risk stratification, and tailoring of therapeutic interventions.

Efficacy and Safety of Compound Kushen Injection for Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials with Trial Sequential Analysis.

BACKGROUNDS: Colorectal cancer (CRC) is one of the common malignant tumors, with a gradually increasing incidence. Due to late detection and poor sensitivity to chemotherapy, it has become a difficult problem in tumor prevention and treatment at present. Exploring or discovering new combinations is a significant strategy for the treatment of CRC. Compound kushen injection (CKI) is a traditional Chinese medicine injection extracted from Sophora flavescens Ait. and Smilax glabra Roxb., which is widely used in the comprehensive treatment of CRC in China. This systematic review is aimed to ascertain the clinical efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC based on available data. On this basis, the specific application of CKI in combination with chemotherapy in clinical practice is further discussed. METHODS: PubMed, Web of Science, the Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang Database, Chinese Biomedicine Database Searches, the Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched systematically, from inception to April 20, 2024. We adopted the ROB2 tool to assess quality of the included trials, Stata 16 for data analysis, and evaluated the publication bias with the funnel plot and Egger's test. The quality of the evidence was justified according to GRADE. We also used trial sequential analysis (TSA) to calculate the final required sample size in this meta-analysis and to verify whether the results present a reliable conclusion. The protocol for this systematic review was registered on PROSPERO (CRD42022380106) and has been published. RESULTS: Sixteen trials that examined 1378 patients were included in this study. Meta-analysis revealed that compared with chemotherapy, objective response rate (ORR, RR = 1.30, 95% CI: 1.18-1.44), disease control rate (DCR, RR = 1.08, 95% CI: 1.03-1.13), and KPS score improvement rate were improved (RR = 1.18, 95% CI: 1.07-1.31) by the combination of CKI and chemotherapy in patients with advanced CRC. Additionally, CKI combined with chemotherapy was associated with lower adverse reactions such as leukopenia (RR = 0.74, 95% CI: 0.62-0.87), thrombocytopenia (RR = 0.68, 95% CI: 0.49-0.94), gastrointestinal reactions (RR = 0.72, 95% CI: 0.55-0.94), and liver damage (RR = 0.48, 95% CI: 0.30-0.79), higher CD4+ ratio (MD = 9.70, 95% CI:8.73-10.68) and CD4+/CD8+ ratio (MD = 0.25, 95% CI: 0.22-0.28), and lower CD8+ T cell ratio (MD = -5.25, 95% CI: -5.94 to -4.56). Subgroup analysis demonstrated that ORR and DCR in patients with advanced CRC were improved when CKI combined with FOLFOX and 5Fu + L-OHP. Both 15 and 20 ml/day of CKI combined with FOLFOX provided a significant effect in ORR. Moreover, ORR was improved when the accumulated CKI dose reached 280 ml per course and 420 ml in total. 7 days/course as well as 14 days/course of CKI combined with FOLFOX were effective durations in ORR. As for DCR, 7 days/course of CKI combined with FOLFOX could improve efficacy. Furthermore, CKI + FOLFOX may be useful in ORR and DCR for at least 4 cycles of combination therapies. The TSA showed that firm results in ORR and DCR were established and additional trials were unlikely to change the results. CONCLUSION: CKI combined with chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, DCR, performance status, ADR reduction, and immune function in patients with CRC. However, more rigorously designed, large-scale, and multi-center RCTs are needed in the future.

Identification and Expression Profile of NCED Genes in Arachis hypogaea L. during Drought Stress.

Peanut (Arachis hypogaea L.) is an important crop that provides essential proteins and oils for human and animal consumption. 9-cis-epoxycarotenoid dioxygenase (NCED) have been found can play a vital role in abscisic acid (ABA) biosynthesis and may be a response to drought stress. Until now, in Arachis hypogaea, no information about the NCED gene family has been reported and the importance of NCED-related drought tolerance is unclear. In this study, eight NCED genes in Arachis hypogaea, referred to as AhNCEDs, are distributed across eight chromosomes, with duplication events in AhNCED1 and AhNCED2, AhNCED3 and AhNCED4, and AhNCED6 and AhNCED7. Comparative analysis revealed that NCED genes are highly conserved among plant species, including Pisum sativum, Phaseolus vulgaris, Glycine max, Arabidopsis thaliana, Gossypium hirsutum, and Oryza sativa. Further promoter analysis showed AhNCEDs have ABA-related and drought-inducible elements. The phenotyping of Arachis hypogaea cultivars NH5 and FH18 demonstrated that NH5 is drought-tolerant and FH18 is drought-sensitive. Transcriptome expression analysis revealed the differential regulation of AhNCEDs expression in both NH5 and FH18 cultivars under drought stress. Furthermore, compared to the Arachis hypogaea cultivar FH18, the NH5 exhibited a significant upregulation of AhNCED1/2 expression under drought. To sum up, this study provides an insight into the drought-related AhNCED genes, screened out the potential candidates to regulate drought tolerance and ABA biosynthesis in Arachis hypogaea.

Efficacy and safety of compound kushen injection for treating advanced colorectal cancer: A protocol for a systematic review and meta-analysis.

Introduction: Compound Kushen Injection (CKI) is a traditional Chinese medicine extracted from Sophora flavescens Aiton and Heterosmilax japonica Kunth. Widely utilized in China for the comprehensive treatment of colorectal cancer (CRC), this study aims to systematically assess the efficacy and safety of CKI when combined with chemotherapy for the treatment of advanced CRC, based on available data. Methods: Randomized controlled trials investigating the efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC will be comprehensively searched from databases, including PubMed, Web of Science, Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang, Chinese Biomedicine Database Searches, Chinese Clinical Trial Registry, and ClinicalTrials.gov until November 2022. Two independent reviewers will screen the studies, assess the risk of bias, and extract data in duplicate. The ROB2 tool will be employed to assess the quality of included studies. Stata 16 will be used for data analysis, and publication bias will be assessed using funnel plots and Egger's test. The quality of evidence will be evaluated according to GRADE, and trial sequence analysis (TSA) will be utilized to calculate the final total sample size required for the meta-analysis. The results of this systematic review will be published in a peer-reviewed journal. The proposed review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022380106). Discussion: This systematic review will integrate current evidence on CKI in advanced CRC and analyze the clinical efficacy and safety of CKI combined with different chemotherapy regimens, providing valuable guidance on the use of CKI in CRC patients.

Comparison of the adherence of nontypeable haemophilus influenzae to lung epithelial cells.

OBJECTIVE: Nontypeable Haemophilus influenzae (NTHi) plays an important role in respiratory tract infections, and adherence to lung epithelial cells is the first step in lung infections. To explore the role of NTHi in childhood lung infections, a comparative study was conducted on the adherence of strains isolated from sputum culture and bronchoalveolar lavage fluid to A549 lung epithelial cells. METHODS: Haemophilus influenzae strains were obtained from the sample bank of Shenzhen Children's Hospital, and identified as NTHi via PCR detection of the capsule gene bexA. NTHi obtained from healthy children's nasopharyngeal swabs culture were selected as the control group, and a comparative study was conducted on the adherence of strains isolated from sputum culture or bronchoalveolar lavage fluid of patients to A549 cells. RESULTS: The adherence bacterial counts of NTHi isolated from the nasopharyngeal cultures of healthy children to A549 cells was 58.2 CFU. In patients with lung diseases, NTHi isolated from bronchoalveolar lavage fluid was 104.3 CFU, and from sputum cultures was 115.1 CFU, both of which were significantly higher in their adherence to A549 cells compared to the strains isolated from the healthy control group. There was no significant difference in adherence between the strains isolated from sputum cultures and bronchoalveolar lavage fluid (t = 0.5217, p = 0.6033). CONCLUSION: NTHi played an important role in childhood pulmonary infections by enhancing its adherence to lung epithelial cells.

A clade of Streptococcus pneumoniae clonal complex 320 with increased tolerance to ß-lactam antibiotics in a Chinese metropolitan city.

OBJECTIVES: We characterized the population structure and features of clinical Streptococcus pneumoniae isolates associated with invasive pneumococcal disease (IPD) from 2009 to 2017 in a Chinese metropolitan city using a whole-genome sequencing approach. METHODS: Seventy-nine pneumococcal strains, including 60 serogroup-19 strains from children enduring IPD from a paediatric hospital in Shenzhen, were subjected to whole-genome sequencing. Population structure was characterized through phylogenetic analysis, sequence typing, serotyping, virulence factor, and antimicrobial drug resistance (AMR) gene profiling, combining the publicly available related WGS data. Clinical demography and antibiotic susceptibility profiles were compared among different populations to emphasize the higher-risk populations. Genetic regions associated with AMR gene mobilization were identified through comparative genomics. RESULTS: These IPD strains mainly belonged to clonal complex 320 (CC320) and were composed of serotypes 19A and 19F. In addition to sporadic possible importation-related isolates (ST320), we identified an independent clade, CC320_SZpop (ST271), that predominantly circulated in Shenzhen and possibly expanded its range. Clinical features and antibiotic susceptibility analysis revealed that CC320_SZpop might manifest much higher pathogenicity and tolerance to ß-lactams. Specific virulence factors in Shenzhen isolates of CC320_SZpop were identified. Furthermore, an ca. 40 kb hotspot genomic region enduring frequent recombination was identified, possibly associated with the divergence of S. pneumoniae strains. CONCLUSION: A novel pneumococcal clade, CC320_SZpop, circulating in Shenzhen and other regions in China, possibly under expansion, was found and deserves more study and surveillance. Our study also emphasizes the importance of continuous genomic surveillance of clinical S. pneumoniae isolates, especially IPD isolates.

Molecular characteristics and antimicrobial resistance of invasive pneumococcal isolates from children in the post-13-valent pneumococcal conjugate vaccine era in Shenzhen, China.

OBJECTIVES: This study aimed to evaluate the molecular epidemiology and antimicrobial resistance of invasive pneumococcal isolates from children in Shenzhen, China, in the early stage of the pneumococcal 13-valent conjugated vaccine (PCV-13) era from 2018 to 2020. METHODS: Invasive pneumococcal strains were isolated from hospitalized children with invasive pneumococcal diseases (IPDs) from January 2018 to December 2020. The serotype identification, multilocus sequence typing (MLST), and antibiotic susceptibility tests were performed on all culture-confirmed strains. RESULTS: Sixty-four invasive strains were isolated mainly from blood (70.3%). Prevalent serotypes were 23F (28.1%), 14 (18.8%), 19F (15.6%), 6A/B (14.1%), and 19A (12.5%), with a serotype coverage rate of 96.9% for PCV13. The most common sequence types (STs) were ST876 (17.1%), ST271 (10.9%), and ST320 (7.8%). Half of the strains were grouped in clonal complexes (CCs): CC271 (21.9%), CC876 (20.3%), and CC90 (14.1%). Meningitis isolates showed a higher resistance rate (90.9% and 45.5%) to penicillin and ceftriaxone than the rate (3.8% and 9.4%) of non-meningitis isolates. The resistance rates for penicillin (oral), cefuroxime, and erythromycin were 53.13%, 73.4%, and 96.9%, respectively. The dual ermB and mefA genotype was found in 81.3% of erythromycin-resistant strains. The elevated minimum inhibitory concentration (MIC) of ß-lactam antibiotics and dual-genotype macrolide resistance were related mainly to three major serotype-CC combinations: 19F-CC271, 19A-CC271, and 14-CC876. CONCLUSION: Invasive pneumococcus with elevated MICs of ß-lactams and increased dual ermB and mefA genotype macrolide resistance were alarming. Expanded PCV13 vaccination is expected to reduce the burden of paediatric IPD and to combat antibiotic-resistant pneumococcus in Shenzhen.

Dual-Fuel Propelled Nanomotors with Two-Stage Permeation for Deep Bacterial Infection in the Treatment of Pulpitis.

Bacterial infection-induced inflammatory response could cause irreversible death of pulp tissue in the absence of timely and effective therapy. Given that, the narrow structure of root canal limits the therapeutic effects of passive diffusion-drugs, considerable attention has been drawn to the development of nanomotors, which have high tissue penetration abilities but generally face the problem of insufficient fuel concentration. To address this drawback, dual-fuel propelled nanomotors (DPNMs) by encapsulating L-arginine (L-Arg), calcium peroxide (CaO2 ) in metal-organic framework is developed. Under pathological environment, L-Arg could release nitric oxide (NO) by reacting with reactive oxygen species (ROS) to provide the driving force for movement. Remarkably, the depleted ROS could be supplemented through the reaction between CaO2 with acids abundant in the inflammatory microenvironment. Owing to high diffusivity, NO achieves further tissue penetration based on the first-stage propulsion of nanomotors, thereby removing deep-seated bacterial infection. Results indicate that the nanomotors effectively eliminate bacterial infection based on antibacterial activity of NO, thereby blocking inflammatory response and oxidative damage, forming reparative dentine layer to avoid further exposure and infection. Thus, this work provides a propagable strategy to overcome fuel shortage and facilitates the therapy of deep lesions.

The safety and effectiveness of a self-made negative pressure suction device in the treatment of chronic wounds.

INTRODUCTION: Chronic wounds are wounds that are not healed or have no healing tendency for more than 1 month due to various factors. In clinical nursing, chronic wounds are often not properly treated, and the treatment efficiency is low. Therefore, it is very important to explore effective methods to deal with chronic wounds. OBJECTIVE: To explore the effect of a self-made negative pressure suction device (NPSD) in the nursing of chronic wounds in the elderly. METHODS: A total of 50 elderly patients with chronic wounds who were hospitalised in our hospital from January 2020 to December 2022 were selected as participants by convenient sampling. According to the random number table method, they were divided into a control group and an observation group, with 25 people in each group. The control group was treated with chloroplast foam dressing, debridement gel and alginate dressing. The observation group was treated with a self-made NPSD on the basis of the control group. The wound healing of the two groups was observed. RESULTS: After the intervention of the self-made NPSD, the granulation tissue coverage rate and wound volume reduction rate of the observation group were significantly increased (p < 0.05), and the positive rate of bacterial infection was significantly decreased (p < 0.05). After 3 months of intervention, the total effective rate of the observation group was significantly higher than that of the control group (χ2  = 3.869, p = 0.0492). CONCLUSION: The self-made NPSD can effectively promote the healing of a chronic wound.

BTN2A2, a new biomarker and therapeutic target for glioma.

BACKGROUND: Protein casein 2A2 (BTN2A2) is a costimulatory molecule first identified in antigen-presenting cells. Studies have shown the involvement of BTN2A2 in immunity. However, the exact role and the mechanism of BTN2A2 in tumors are still unclear. METHODS: First, we performed real-time PCR to measure BTN2A2 expression in glioma cell lines. Next, we performed Genes Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to understand the mechanism of BTN2A2 in glioma. Next, we used the "ESTIMATE", "ssGSEA" and "CIBERSORT" algorithms to analyze the correlation between BTN2A2 and immune cell infiltration (ICI). Finally, we performed immunohistochemistry, growth curve, transwell, and colony formation assays to determine the functions of BTN2A2 in glioma. RESULTS: Our results showed an increase in BTN2A2 expression levels in glioma tissues and cells. Next, we determined that BTN2A2 was correlated with the prognosis of patients with glioma. Then, using the ESTIMATE, ssGSEA, and CIBERSORT algorithms, we discovered that BTN2A2 was significantly associated with immune cell infiltration (ICI) in glioma. We observed an increase in BTN2A2 expression levels with an increase in the patient's tumor grade. Furthermore, BTN2A2 significantly enhanced the proliferative and migratory abilities of glioma cells. CONCLUSIONS: Our results showed a significant increase in BTN2A2 expression levels in glioma cells and tissues. Furthermore, the prognosis of patients expressing high BTN2A2 levels was poor. Moreover, BTN2A2 was correlated with progression and ICI in patients with glioma. Together, this indicates that BTN2A2 could be a therapeutic target for patients with glioma.

Simulation of morphology for oil droplets in aqueous solution controlled by electric fields.

This study investigate the morphology of oil-in-water at high density ratio controlled by electric field. We incorporated the electric field into the Lattice Boltzmann method (LBM). The focus is on the modified lattice Boltzmann color gradient model simulate the evolution of the oil-in-water and analyze the relation between morphologies and electric field parameters. The results show that the stretching, merging and even breaking can be regulated by electric field strength, conductivity, dielectric constant, oil-water density ratio and droplet radius. Simulation results showed that the larger dielectric constant resulted in the smaller deformation, and the larger conductivity related to the greater deformation. Meanwhile, the larger radius droplet is easier to deform and break, and the higher density droplet is less likely to break. And this paper also gives the morphology of the stretching and destabilization of the droplets at each stage. These results are in good agreement with the relevant theoretical and experimental results.

Use of Dyna-computed tomography-assisted neuroendoscopic hematoma evacuation in the treatment of hypertensive intracerebral hemorrhage.

The purpose of this study was to evaluate and summarize the technical characteristics and clinical efficacy of using Dyna-computed tomography (CT)-assisted neuroendoscopic hematoma evacuation to treat hypertensive intracerebral hemorrhage (HICH). We treated 42 consecutive patients with HICH who underwent neuroendoscopic hematoma evacuation in our department from March 1, 2020, to May 31, 2022. Patients were divided into two groups: Dyna-CT-assisted neuroendoscopic group (n = 18) and neuroendoscopic group (n = 24). Retrospective data, treatment efficacy, and outcomes were collected and compared between these two groups. The operative time in the Dyna-CT-assisted neuroendoscopic group was significantly shorter than the operative time in the neuroendoscopic group (mean time 131.6 ± 13.51 vs. 156.6 ± 19.25 min, P < 0.001). Dyna-CT-assisted neuroendoscopic group had significantly less intraoperative blood loss than the neuroendoscopic group (46.94 ± 10.42 vs. 106.46 ± 23.25, P = 0.003). Meanwhile, patients who underwent Dyna-CT-assisted neuroendoscopic had a comparable hematoma clearance rate to those who underwent neuroendoscopic (89.36 ± 7.31 vs. 68.87 ± 19.44%, P = 0.006). The incidence of complications in the Dyna-CT-assisted neuroendoscopic group (5.5%) was lower than in the neuroendoscopic group (12.5%), but the difference was not statistically significant (P = 0.129). Patients who underwent Dyna-CT-assisted neuroendoscopic hematoma evacuation had better 6-month functional outcomes, and the difference was significant (P = 0.004). Furthermore, multivariable analysis showed that younger age, smaller hematoma volume, and Dyna-CT-assisted neuroendoscopic were predictors of favorable 6-month outcomes in HICH patients. In the treatment of HICH, Dyna-CT-assisted hematoma evacuation appears to be safer and more effective than neuroendoscopic hematoma evacuation. Dyna-CT-assisted neuroendoscopic hematoma evacuation in hybrid operating rooms may improve the clinical effect and outcomes of patients with HICH.

Study on the Genome and Mechanism of Tigecycline Resistance of a Clinical Chryseobacterium indologenes Strain.

Purpose: Chryseobacterium indologenes is a clinically relevant microorganism that has been on the rise, with multidrug-resistant (MDR) strains being reported. C. indologenes carrying tet(X2) has been demonstrated to be resistant to the antibiotic tigecycline, yet, sensitive to all other members of the tetracycline family. This inconsistency in resistance prompts an inquiry into the contribution of tet(X2) to tigecycline resistance in C. indologenes. Materials and Methods: In this study, we report on a comprehensive analysis of the genomic mechanisms underlying tigecycline resistance in a MDR C. indologenes strain (CI3125) that was resistant to tigecycline but sensitive to tetracycline, doxycycline, and minocycline. We used whole-genome sequencing, quantitative reverse transcription PCR, Western blot, antibiotic-degrading tests, and efflux pump inhibiting tests to reveal the mechanism of tigecycline resistance in C. indologenes and elucidate the inconsistency in the antibiotic resistance mechanism for the tetracycline family. Results: Our findings demonstrate that CI3125 carries 60 antibiotic resistance genes distributed on 6 different genetic islands (GIs), with the potential for horizontal transfer. Notably, the tet(X2) gene is located on GI06 of CI3125. Genetic environment analysis of tet(X2) showed that all tet(X2) genes in Flavobacterium and Bacteroides share a conservative and functional ribosome-binding site upstream. Contrary to expectation, our RT-qPCR showed that tet(X2) was not transcribed in CI3125, and Western blot suggested the absence of tet(X2) protein in CI3125. Rather, we demonstrate that minimum inhibitory concentration values for tigecycline decreased two- to eight-folds in the presence of five different efflux pump inhibitors [1-(1-naphthyl- methyl)-piperazine, phenyl-arginine-ß-naphthylamide, verapamil, reserpine, and carbonyl cyanide 3-chlorophenylhydrazone]. This finding provides evidence for the involvement of efflux pumps in tigecycline resistance, which is likely to be a universal mechanism among C. indologenes. Our study proposes that the inconsistency in resistance to the tetracycline family in CI3125 may be ascribed to the silence of tet(X2) and the functions of efflux pumps for tigecycline. Conclusions: Overall, our results highlight the importance of genomic approaches in understanding the underlying mechanisms of antibiotic resistance in clinically relevant microorganisms. While tet(X2) in CI3125 is silent, our findings suggest that it may be horizontally spread through GIs. Hence, our findings have significant implications for the management of C. indologenes infections in clinical settings.

Pan-cancer analysis reveals that G6PD is a prognostic biomarker and therapeutic target for a variety of cancers.

Background: Despite accumulating evidence revealing that Glucose-6-phosphate dehydrogenase (G6PD) is highly expressed in many tumor tissues and plays a remarkable role in cancer tumorigenesis and progression, there is still a lack of G6PD pan-cancer analysis. This study was designed to analyze the expression status and prognostic significance of G6PD in pan-cancer. Methods: G6PD expression data were obtained from multiple data resources including the Genotype-Tissue Expression, the Cancer Genome Atlas, and the Tumor Immunity Estimation Resource. These data were used to assess the G6PD expression, prognostic value, and clinical characteristics. The ESTIMATE algorithms were used to analyze the association between G6PD expression and immune-infiltrating cells and the tumor microenvironment. The functional enrichment analysis was also performed across pan-cancer. In addition, the GDSC1 database containing 403 drugs was utilized to explore the relationship between drug sensitivity and G6PD expression levels. Furthermore, we also performed clinical validation and in vitro experiments to further validate the role of G6PD in hepatocellular carcinoma (HCC) cells and its correlation with prognosis. The R software was used for statistical analysis and data visualization. Results: G6PD expression was upregulated in most cancers compared to their normal counterparts. The study also revealed that G6PD expression was a prognostic indicator and high levels of G6PD expression were correlated with worse clinical prognosis including overall survival, disease-specific survival, and progression-free interval in multiple cancers. Furthermore, the G6PD level was also related to cancer immunity infiltration in most of the cancers, especially in KIRC, LGG, and LIHC. In addition to this, G6PD expression was positively related to pathological stages of KIRP, BRCA, KIRC, and LIHC. Functional analysis and protein-protein interactions network results revealed that G6PD was involved in metabolism-related activities, immune responses, proliferation, and apoptosis. Drug sensitivity analysis showed that IC50 values of most identified anti-cancer drugs were positively correlated with the G6PD expression. Notably, in vitro functional validation showed that G6PD knockdown attenuated the phenotypes of proliferation in HCC. Conclusion: G6PD may serve as a potential prognostic biomarker for cancers and may be a potential therapeutic target gene for tumor therapy.

Effect of traditional Chinese medicine on postoperative depression of breast cancer: a systematic review and meta-analysis.

Background: Depression is one of the common complications in patients with postoperative breast cancer (BC). Conventional therapies for postoperative depression of BC always have modest treatment outcomes and undesirable side effects. Clinical practice and many studies have shown that traditional Chinese medicine (TCM) has a good effect on postoperative depression of BC. This meta-analysis aimed to assess the clinical effect of TCM as an add-on treatment for postoperative depression of BC. Methods: A systematic and thorough search was conducted on eight online electronic databases up to 20 July 2022. The control group received conventional therapies, and intervention groups received what control groups received plus TCM treatment. Review Manager 5.4.1 was used for statistical analysis. Results: Nine RCTs involved 789 participants who met the inclusion standards. The results showed the intervention group was better at decreasing the score of the Hamilton rating scale for depression (HAMD) (mean difference, MD = -4.21, 95% CI -5.54 to -2.88) and the self-rating depression scale (SDS) (MD = -12.03, 95% CI -15.94 to -8.13), improving clinical efficacy (RR = 1.25, 95% CI 1.14-1.37), increasing the levels of 5-hydroxytryptamine (5-HT) (MD = 0.27, 95% CI 0.20-0.34), dopamine (DA) (MD = 26.28, 95% CI 24.18-28.77), and norepinephrine (NE) (MD = 11.05, 95% CI 8.07-14.04), and influencing the immune index, including the levels of CD3+ (MD = 15.18, 95% CI 13.61-16.75), CD4+ (MD = 8.37, 95% CI 6.00-10.74), and CD4+/CD8+ (MD = 0.33, 95% CI 0.27-0.39). The level of CD8+ (MD = -4.04, 95% CI -11.98 to 3.99) had no obvious difference between the two groups. Conclusion: The meta-analysis stated that a therapeutic regimen involving TCM could better improve the depression status in postoperative BC.

SIRT6 is an epigenetic repressor of thoracic aortic aneurysms via inhibiting inflammation and senescence.

Thoracic aortic aneurysms (TAAs) develop asymptomatically and are characterized by dilatation of the aorta. This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective treatments. The current understanding of the pathogenesis of TAA is still limited, especially for sporadic TAAs without known genetic mutation. Sirtuin 6 (SIRT6) expression was significantly decreased in the tunica media of sporadic human TAA tissues. Genetic knockout of Sirt6 in mouse vascular smooth muscle cells accelerated TAA formation and rupture, reduced survival, and increased vascular inflammation and senescence after angiotensin II infusion. Transcriptome analysis identified interleukin (IL)-1ß as a pivotal target of SIRT6, and increased IL-1ß levels correlated with vascular inflammation and senescence in human and mouse TAA samples. Chromatin immunoprecipitation revealed that SIRT6 bound to the Il1b promoter to repress expression partly by reducing the H3K9 and H3K56 acetylation. Genetic knockout of Il1b or pharmacological inhibition of IL-1ß signaling with the receptor antagonist anakinra rescued Sirt6 deficiency mediated aggravation of vascular inflammation, senescence, TAA formation and survival in mice. The findings reveal that SIRT6 protects against TAA by epigenetically inhibiting vascular inflammation and senescence, providing insight into potential epigenetic strategies for TAA treatment.

Sirtuin 2 deficiency aggravates ageing-induced vascular remodelling in humans and mice.

AIMS: The mechanisms underlying ageing-induced vascular remodelling remain unclear. This study investigates the role and underlying mechanisms of the cytoplasmic deacetylase sirtuin 2 (SIRT2) in ageing-induced vascular remodelling. METHODS AND RESULTS: Transcriptome and quantitative real-time PCR data were used to analyse sirtuin expression. Young and old wild-type and Sirt2 knockout mice were used to explore vascular function and pathological remodelling. RNA-seq, histochemical staining, and biochemical assays were used to evaluate the effects of Sirt2 knockout on the vascular transcriptome and pathological remodelling and explore the underlying biochemical mechanisms. Among the sirtuins, SIRT2 had the highest levels in human and mouse aortas. Sirtuin 2 activity was reduced in aged aortas, and loss of SIRT2 accelerated vascular ageing. In old mice, SIRT2 deficiency aggravated ageing-induced arterial stiffness and constriction-relaxation dysfunction, accompanied by aortic remodelling (thickened vascular medial layers, breakage of elastin fibres, collagen deposition, and inflammation). Transcriptome and biochemical analyses revealed that the ageing-controlling protein p66Shc and metabolism of mitochondrial reactive oxygen species (mROS) contributed to SIRT2 function in vascular ageing. Sirtuin 2 repressed p66Shc activation and mROS production by deacetylating p66Shc at lysine 81. Elimination of reactive oxygen species by MnTBAP repressed the SIRT2 deficiency-mediated aggravation of vascular remodelling and dysfunction in angiotensin II-challenged and aged mice. The SIRT2 coexpression module in aortas was reduced with ageing across species and was a significant predictor of age-related aortic diseases in humans. CONCLUSION: The deacetylase SIRT2 is a response to ageing that delays vascular ageing, and the cytoplasm-mitochondria axis (SIRT2-p66Shc-mROS) is important for vascular ageing. Therefore, SIRT2 may serve as a potential therapeutic target for vascular rejuvenation.