Research and Analysis of Molecules such as CD28, CD45RA, CD45RO, CD38, HLA-DR, and CD57 on T Cells in Multiple Myeloma.

BACKGROUND: For many years it has been postulated that the immune system controls the progress of multiple myeloma (MM). However, the phenotypes of T cells in MM remain to be elucidated. In this study, we compared the phenotypes of T cells, which were obtained from the peripheral blood, in MM patients with those in healthy donors (HD). The expression of CCR7, CD57, CD28, HLA-DR, CD38, CD45RA, and CD45RO were assessed on T cells from MM patients and HDs using multicolor flow cytometry (MFC). METHODS: For this study, 17 newly diagnosed MM patients were selected, and 20 healthy people were selected as a control group. MFC was used to detect the markers on T cells. RESULTS: We detected significant increases in the expression levels of HLA-DR, CD38, and CD57on CD8+ T cells, significant decreases in the expression levels of CD28 and CD45RA on CD8+ T cells, and a decrease of CD4+ effec-tor T cells in MM patients, compared to the HD group. CONCLUSIONS: Our study shows that the accumulation of peripheral CD8+CD57+T cells, CD8+CD38high T cells, and CD8+HLA-DR+CD38high T cells is reflective of an ongoing antitumor T cell response and a progressive immune dysfunction in MM. During chemotherapy, the recovery of immune function can be monitored by detecting the proportion of activated molecules of T lymphocytes.

Construction of Immune-Related Diagnostic Model for Latent Tuberculosis Infection and Active Tuberculosis.

Background: Tuberculosis (TB) is one of the most infectious diseases caused by Mycobacterium tuberculosis (M. tb), and the diagnosis of active tuberculosis (TB) and latent TB infection (LTBI) remains challenging. Methods: Gene expression files were downloaded from the GEO database to identify the differentially expressed genes (DEGs). The ssGSEA algorithm was applied to assess the immunological characteristics of patients with LTBI and TB. Weighted gene co-expression network analysis, protein-protein interaction network, and the cytoHubba plug-in of Cytoscape were used to identify the real hub genes. Finally, a diagnostic model was constructed using real hub genes and validated using a validation set. Results: Macrophages and natural killer cells were identified as important immune cells strongly associated with TB. In total, 726 mRNAs were identified as DEGs. MX1, STAT1, IFIH1, DDX58, and IRF7 were identified as real hub immune-related genes. The diagnostic model generated by the five real hub genes could distinguish active TB from healthy controls or patients with LTBI. Conclusion: Our study may provide implications for the diagnosis and drug development of M. tb infections.

Effectiveness of eHealth interventions for HIV prevention, testing and management: An umbrella review.

BACKGROUND: Human immunodeficiency virus (HIV) infection has become a major contributor to the global burden of disease. Globally, the number of cases of HIV continues to increase. Electronic health (eHealth) interventions have emerged as promising tools to support disease self-management among people living with HIV. The purpose of this umbrella review is to systematically evaluate and summarize the evidence and results of published systematic reviews and meta-analyses on the effectiveness of eHealth interventions for HIV prevention, testing and management. METHODS: PubMed, Embase and the Cochrane Library were searched for reviews. The methodological quality of the included studies was assessed using AMSTAR-2. RESULTS: A total of 22 systematic reviews were included. The methodological quality of the reviews was low or critically low. EHealth interventions range from Internet, computer, or mobile interventions to websites, programs, applications, email, video, games, telemedicine, texting, and social media, or a combination of them. The majority of the reviews showed evidence of effectiveness (including increased participation in HIV management behaviours, successfully changed HIV testing behaviours, and reduced risk behaviours). EHealth interventions were effective in the short term. CONCLUSIONS: Ehealth interventions have the potential to improve HIV prevention, HIV testing and disease management. Due to the limitations of the low methodological quality of the currently available systematic reviews, more high-quality evidence is needed to develop clear and robust recommendations.

Nanoparticles as an antidote for poisoned gold single-atom catalysts in sustainable propylene epoxidation.

The development of sustainable and anti-poisoning single-atom catalysts (SACs) is essential for advancing their research from laboratory to industry. Here, we present a proof-of-concept study on the poisoning of Au SACs, and the antidote of Au nanoparticles (NPs), with trace addition shown to reinforce and sustain propylene epoxidation. Multiple characterizations, kinetics investigations, and multiscale simulations reveal that Au SACs display remarkable epoxidation activity at a low propylene coverage, but become poisoned at higher coverages. Interestingly, Au NPs can synergistically cooperate with Au SACs by providing distinct active sites required for H2/O2 and C3H6 activations, as well as hydroperoxyl radical to restore poisoned SACs. The difference in reaction order between C3H6 and H2 (nC3H6-nH2) is identified as the descriptor for establishing the volcano curves, which can be fine-tuned by the intimacy and composition of SACs and NPs to achieve a rate-matching scenario for the formation, transfer, and consumption of hydroperoxyl. Consequently, only trace addition of Au NPs antidote (0.3% ratio of SACs) stimulates significant improvements in propylene oxide formation rate, selectivity, and H2 efficiency compared to SACs alone, offering a 56-fold, 3-fold, and 22-fold increase, respectively, whose performances can be maintained for 150 h.

CCDC28A deficiency causes sperm head defects, reduced sperm motility and male infertility in mice.

Mature spermatozoa with normal morphology and motility are essential for male reproduction. The epididymis has an important role in the proper maturation and function of spermatozoa for fertilization. However, factors related to the processes involved in spermatozoa modifications are still unclear. Here we demonstrated that CCDC28A, a member of the CCDC family proteins, is highly expressed in testes and the CCDC28A deletion leads to male infertility. We found CCDC28A deletion had a mild effect on spermatogenesis. And epididymal sperm collected from Ccdc28a-/- mice showed bent sperm heads, acrosomal defects, reduced motility and decreased in vitro fertilization competence whereas their axoneme, outer dense fibers, and fibrous sheath were all normal. Furthermore, we found that CCDC28A interacted with sperm acrosome membrane-associated protein 1 (SPACA1) and glycogen synthase kinase 3a (GSK3A), and deficiencies in both proteins in mice led to bent heads and abnormal acrosomes, respectively. Altogether, our results reveal the essential role of CCDC28A in regulating sperm morphology and motility and suggesting a potential marker for male infertility.

Disease-induced changes in bacterial and fungal communities from plant below- and aboveground compartments.

The plant microbes are an integral part of the host and play fundamental roles in plant growth and health. There is evidence indicating that plants have the ability to attract beneficial microorganisms through their roots in order to defend against pathogens. However, the mechanisms of plant microbial community assembly from below- to aboveground compartments under pathogen infection remain unclear. In this study, we investigated the bacterial and fungal communities in bulk soil, rhizosphere soil, root, stem, and leaf of both healthy and infected (Potato virus Y disease, PVY) plants. The results indicated that bacterial and fungal communities showed different recruitment strategies in plant organs. The number and abundance of shared bacterial ASVs between bulk and rhizosphere soils decreased with ascending migration from below- to aboveground compartments, while the number and abundance of fungal ASVs showed no obvious changes. Field type, plant compartments, and PVY infection all affected the diversity and structures of microbial community, with stronger effects observed in the bacterial community than the fungal community. Furthermore, PVY infection, rhizosphere soil pH, and water content (WC) contributed more to the assembly of the bacterial community than the fungal community. The analysis of microbial networks revealed that the bacterial communities were more sensitive to PVY infection than the fungal communities, as evidenced by the lower network stability of the bacterial community, which was characterized by a higher proportion of positive edges. PVY infection further increased the bacterial network stability and decreased the fungal network stability. These findings advance our understanding of how microbes respond to pathogen infections and provide a rationale and theoretical basis for biocontrol technology in promoting sustainable agriculture. KEY POINTS: • Different recruitment strategies between plant bacterial and fungal communities. • Bacterial community was more sensitive to PVY infection than fungal community. • pH and WC drove the microbial community assembly under PVY infection.

Development of a "Rigid-Flexible" Structure at the Interface Through Aramid Nanofibers@MXene to Enhance Mechanical Properties of Carbon Fiber/Polyamide Composites.

With the increasing development of nanomaterials, the construction of multiscale nanostructured interphase has emerged as a viable technique to reinforce carbon fiber-reinforced polymer composites. Here, "flexible" aramid nanofibers (ANFs) were first introduced on the surface of carbon fibers (CF) by electrophoretic deposition (EPD), and then "rigid" MXene sheets were grafted by ultrasonic impregnation. This feasible two-step treatment introduces a hierarchical "rigid-flexible" structure at the CF/polyamide (PA) interface. Results showed that this "rigid-flexible" multilayer structure improved the roughness, chemical bonding, mechanical interlocking, and wettability of CF/PA composites. At the same time, the modulus variation between the fiber and the matrix is significantly smoothed due to the increased thickness of the interfacial layer, increasing the payload transfer from the PA matrix to the fiber and decreasing the stress concentration. Compared to the desized CF, the interlaminar shear strength (ILSS) and tensile strength of the modified CF-ANF@MX0.2/PA composite increased by 50.02 and 36.11%, respectively. This innovative interfacial design and feasible treatment method facilitate the construction of firmly interacting interfacial layers in CF/PA composites, offering broad prospects for the production of high-performance CF/PA composites.

Corrigendum: The influence of physical education courses integrated with civic education on prosocial behavior among college students: the chain mediating effect of cultural confidence and self-esteem.

[This corrects the article DOI: 10.3389/fpsyg.2023.1217290.].

Rhizosphere microbial community enrichment processes in healthy and diseased plants: implications of soil properties on biomarkers.

Plant health states may influence the distribution of rhizosphere microorganisms, which regulate plant growth and development. In this study, the response of rhizosphere bacteria and fungi of healthy and diseased plants compared to bulk microbes was analyzed using high-throughput sequencing. Plant adaptation strategies of plants under potato virus Y (PVY) infection have been studied from a microbial perspective. The diversity and community structure of bacteria and fungi varied between bulk and rhizosphere soils, but not between healthy and diseased rhizosphere soils. A LEfSe analysis revealed the significant differences between different treatments on bacterial and fungal community compositions and identified Roseiflexaceae, Sphingomonas, and Sphingobium as the bacterial biomarkers of bulk (BCK), healthy rhizosphere (BHS), and diseased rhizosphere (BIS) soils, respectively; Rhodotorula and Ascomycota_unidentified_1_1 were identified as the fungal biomarkers of bulk (FCK) and healthy rhizosphere (FHS) soils. Bacterial networks were found to be more complex and compact than fungal networks and revealed the roles of biomarkers as network keystone taxa. PVY infection further increased the connectedness among microbial taxa to improve rhizosphere microbial community stability and resistance to environmental stress. Additionally, water content (WC) played an apparent influence on bacterial community structure and diversity, and pH showed significant effects on fungal community diversity. WC and pH greatly affected the biomarkers of bacterial rhizosphere communities, whereas the biomarkers of bulk bacterial communities were significantly affected by soil nutrients, especially for Sphingobium. Overall, the rhizosphere microbial community enrichment processes were different between healthy and diseased plants by changing the community compositions and identifying different biomarkers. These findings provide insight into the assemblage of rhizosphere microbial communities and soil physicochemical properties, which contributes to a deeper understanding of the establishment of an artificial core root microbiota to facilitate plant growth and bolstering resistance mechanisms. This knowledge contributes to a deeper understanding of the establishment of an artificial core root microbiota, thereby facilitating plant growth and bolstering resistance mechanisms.

AML with RUNX1::RUNX1T1 Cooperating two Mutations Relapsed Quickly after Achieving CR.

BACKGROUND: Acute myeloid leukemia (AML) with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 has a relatively favorable prognosis with a high complete remission rate and long disease-free survival. METHODS AND RESULTS: Here we describe a patient who had AML with t(8;21)(q22;q22.1); RUNX1::RUNX1T1. Cooperating mutations including KRAS and ASXL1, and with other abnormal karyotype del(17) and with a myelomonocytic differentiation. CONCLUSIONS: The patient relapsed despite achieving a morphologic complete remission (CR).

Bortezomib modulated the autophagy-lysosomal pathway in a TFEB-dependent manner in multiple myeloma.

OBJECTIVE: To explore the involvement of TFEB-mediated autophagy-lysosomal mechanisms in multiple myeloma (MM) during bortezomib treatment. METHODS: MM cells were exposed to bortezomib or subjected to TFEB knockdown. CCK assay was used to assess the cell proliferation. Western blotting and fluorescent staining were conducted to examine autophagy and lysosomes. The TFEB expression pattern was analyzed, and whole transcriptome sequencing was carried out. Additionally, TFEB target genes were predicted using the GTRD(http://gtrd.biouml.org/) website, and pathway analysis was performed. RESULTS: Bortezomib demonstrated a dose-dependent and time dependent inhibition of cell proliferation. In MM cells treated with bortezomib, LC3B, Beclin-1, TFEB, and Lamp1 exhibited upregulation in a time- and concentration-dependent manner. LysoTracker dye labeling showed an increase in lysosomes in the bortezomib-treated group. Moreover, bortezomib elevated the expression of lysosome-associated factor Lamp1. Bortezomib promoted the nuclear translocation of TFEB, leading to decreased cytoplasmic TFEB and increased nuclear TFEB. TFEB gene silencing reversed bortezomib's inhibitory effect on MM cell lines, significantly reducing autophagosome expression and lysosome numbers. Furthermore, bioinformatic analysis identified the MAPK pathway as a potential downstream target of TFEB. CONCLUSION: Bortezomib effectively inhibits MM cell proliferation and induces autophagy, partly through TFEB-mediated mechanisms, with potential involvement of the MAPK pathway.

Automated highway pavement crack recognition under complex environment.

The pavement is vulnerable to damage from natural disasters, accidents and other human factors, resulting in the formation of cracks. Periodic pavement monitoring can facilitate prompt detection and repair the pavement diseases, thereby minimizing casualties and property losses. Due to the presence of numerous interferences, recognizing highway pavement cracks in complex environments poses a significant challenge. Nevertheless, several computer vision approaches have demonstrated notable success in tackling this issue. We have employed a novel approach for crack recognition utilizing the ResNet34 model with a convolutional block attention module (CBAM), which not only saves parameters and computing power but also ensures seamless integration of the module as a plug-in. Initially, ResNet18, ResNet34, and ResNet50 models were trained by employing transfer learning techniques, with the ResNet34 network being selected as a fundamental model. Subsequently, CBAM was integrated into ResBlock and further training was conducted. Finally, we calculated the precision, average recall on the test set, and the recall of each class. The results demonstrate that by integrating CBAM into the ResNet34 network, the model exhibited improved test accuracy and average recall compared to its previous state. Moreover, our proposed model outperformed all other models in terms of performance. The recall rates for transverse crack, longitudinal crack, map crack, repairing, and pavement marking were 88.8%, 86.8%, 88.5%, 98.3%, and 99.9%, respectively. Our model achieves the highest precision of 92.9% and the highest average recall of 92.5%. However, the effectiveness in detecting mesh cracks was found to be unsatisfactory, despite their significant prevalence. In summary, the proposed model exhibits great potential for crack identification and serves as a crucial foundation for highway maintenance.

Comparative Proteomic Analysis of Aqueous Humor Reveals Biochemical Disparities in the Eyes of High Myopic Patients.

Myopia accounts for a significant proportion of visual lesions worldwide and has the potential to progress toward pathological myopia. This study aims to reveal the difference in protein content in aqueous humor between high myopic and nonhigh myopic patients, as well as better understand the dysregulation of proteins in myopic eyes. Aqueous humor was collected for liquid chromatograph mass spectrometer (LC/MS) analysis from 30 individual eyes that underwent phacoemulsification and intraocular lens (IOL) implantation. Results showed that a total of 190 differentially expressed proteins were identified, which revealed their involvement in cell metabolism, immune and inflammatory response, and system and anatomical structure. Further analysis focused on 15 intensively interacted hub proteins, encompassing functions related to complement cascades, lipoprotein metabolism, and fibrin biological function. Subsequent validations demonstrated elevated levels of APOE (apolipoprotein E), C3 (complement 3), and AHSG (α-2-HS-glycoprotein) in the high myopia group (31 eyes of cataracts and 45 eyes of high myopia with cataracts). AHSG had a significant positive correlation with axial length in high myopic patients, with good efficacy in distinguishing between myopic and nonmyopic groups. AHSG may be a potential indicator of the pathological severity and participator in the pathological progress of high myopia. This study depicted differential expression characteristics of aqueous humor in patients with high myopia and provided optional information for further experimental research on exploring the molecular mechanisms and potential therapeutic targets for high myopia. Data are available via ProteomeXchange with the identifier PXD047584.

Ultra-sensitive fluorescent detection of strychnine based on carbon dot self-assembled gold nanocage sensing probe.

The ultra-sensitive detection of strychnine is crucial to provide powerful evidence in strychnine poisoning cases. In this study, a novel fluorescent carbon dots (CDs) self-assembled gold nanocage (AuNCs) composite is synthesized for the ultra-sensitive detection of strychnine using molecularly imprinted polymer sensing technology (MIPs-CDs@AuNCs). With strong loading and delivery capability of AuNCs, the CDs could be loaded into AuNCs, where the anisotropy of CDs could significantly decrease and the fluorescence of the MIPs-CDs@AuNCs probe gained lower relative standard deviation (RSD). Moreover, the fluorescence response of MIPs-CDs@AuNCs to target strychnine was observed to be more significant than MIPs-CDs without gold nanocages. Under optimal conditions, the developed MIPs-CDs@AuNCs fluorescence strategy showed good linear relationship at the concentration of strychnine from 3 ng mL-1 to 200 ng mL-1 with the limit of detection as low as 1 ng mL-1. Besides, real blood samples were analyzed without complex pre-preparation procedure to investigate the performance of the proposed molecularly imprinted fluorescence probe, and satisfactory results were obtained with absolute deviations between -1.16 ng mL-1 and 1.28 ng mL-1, which exhibited a great potential for the detection of strychnine in health care work.

Feasibility of a Mobile Health Intervention for Providing a Continuum of HIV Services for MSM: Pilot Study of the WeTest Program in 3 Cities in China.

BACKGROUND: Men who have sex with men (MSM) in China have a high risk for HIV infection but experience suboptimal rates of HIV testing and service engagement due to various social and structural barriers. We developed a mobile health (mHealth) intervention entitled "WeTest-Plus" (WeTest+) as a user-centered "one-stop service" approach for delivering access to comprehensive information about HIV risk, HIV self-testing, behavioral and biomedical prevention, confirmatory testing, treatment, and care. OBJECTIVE: The goal of the current study was to investigate the feasibility of WeTest+ to provide continuous HIV services to high-risk MSM. METHODS: Participants completed a 3-week pilot test of WeTest+ to examine acceptability, feasibility, and recommendations for improvement. Participants completed a structured online questionnaire and qualitative exit interviews facilitated by project staff. "Click-through" rates were assessed to examine engagement with online content. RESULTS: 28 participants were included, and the average age was 27.6 years (standard deviation = 6.8). Almost all participants (96.4%) remained engaged with the WeTest+ program over a 3-week observational period. The majority (92.9%) self-administered the HIV self-test and submitted their test results through the online platform. Overall click-through rates were high (average 67.9%). Participants provided favorable comments about the quality and relevance of the WeTest+ information content, the engaging style of information presentation, and the user-centered features. CONCLUSION: This pilot assessment of WeTest+ supports the promise of this program for promoting HIV self-testing and linkage to in-person services for MSM in China. Findings underscore the utility of a user-centered approach to mHealth program design.

Semi-Infinitely Constrained Markov Decision Processes and Provably Efficient Reinforcement Learning.

We propose a novel generalization of constrained Markov decision processes (CMDPs) that we call the semi-infinitely constrained Markov decision process (SICMDP). Particularly, we consider a continuum of constraints instead of a finite number of constraints as in the case of ordinary CMDPs. We also devise two reinforcement learning algorithms for SICMDPs that we refer to as SI-CMBRL and SI-CPO. SI-CMBRL is a model-based reinforcement learning algorithm. Given an estimate of the transition model, we first transform the reinforcement learning problem into a linear semi-infinitely programming (LSIP) problem and then use the dual exchange method in the LSIP literature to solve it. SI-CPO is a policy optimization algorithm. Borrowing ideas from the cooperative stochastic approximation approach, we make alternative updates to the policy parameters to maximize the reward or minimize the cost. To the best of our knowledge, we are the first to apply tools from semi-infinitely programming (SIP) to solve constrained reinforcement learning problems. We present theoretical analysis for SI-CMBRL and SI-CPO, identifying their iteration complexity and sample complexity. We also conduct extensive numerical experiments to illustrate the SICMDP model and demonstrate that our proposed algorithms are able to solve complex control tasks leveraging modern deep reinforcement learning techniques.

STS â ¡A inhibited angiogenesis of lung adenocarcinoma by activating FOXO3 to inhibit CXCL1/STAT3/VEGF pathway.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most popular type of lung cancer. Sulfotanshinone IIA sodium (STS IIA) has been proven to have an anticancer effect. However, its role in LUAD and its underlying mechanism remain unclear. OBJECTIVE: To investigate the role and mechanism of STS IIA in LUAD angiogenesis. METHODS: The mRNA levels of genes, including forkhead box O3 (FOXO3) and chemokine C-X-C motif ligand 1 (CXCL1), were detected by qRT-PCR. The levels of proteins, including FOXO3, CXCL1, and vascular endothelial growth factor (VEGF), were measured by Western blot. The proliferation and angiogenesis of human umbilical vein endothelial cells (HUVECs) were detected by the EdU assay and the tubule formation assay, respectively. The binding relationship between FOXO3 and CXCL1 was detected by dual-luciferase reporter assay. RESULTS: Our results illustrated that different concentrations of STS IIA inhibited the proliferation and angiogenesis of HUVECs. FOXO3 regulated the proliferation and angiogenesis of HUVECs inhibited by STS ⅡA via targeting CXCL1. Subsequently, we proved that exogenous CXCL1 alleviated the inhibition of proliferation and angiogenesis of HUVECs regulated by STS IIA via activating the STAT3/VEGF pathway. Finally, we found that STS IIA inhibited the angiogenesis of lung adenocarcinoma though FOXO3 to inhibit the CXCL1/STAT3/VEGF pathway. CONCLUSION: Our study finally elucidated the underlying molecular mechanism by which STS ⅡA inhibits LUAD angiogenesis.

Effects of aerobic exercise or Tai Chi Chuan interventions on problematic mobile phone use and the potential role of intestinal flora: A multi-arm randomized controlled trial.

BACKGROUND: Problematic use of mobile phones (PMPU) has been described as a serious public health issue. METHODS: This study was a parallel three-arm randomized controlled trial and has completed registration (ClinicalTrials.gov Identifier: NCT05843591). Ninety college students with PMPU were randomly assigned to the aerobic exercise group (AE group, n = 30), the Tai Chi Chuan group (TCC group, n = 30), or the wait-list control group (WLC group, n = 30). At the end of the intervention, stool samples from the study participants were collected for biological analysis based on 16 S rDNA amplicon sequencing technology. The primary outcome was addiction symptoms assessed by the Smartphone Addiction Scale-Short Version (SAS-SV). The secondary outcomes are emotional symptoms, physical symptoms, and flora species. RESULTS: Compared with the WLC group, the AE and TCC groups showed reductions in PMPU levels, physical and mental fatigue, but there was no difference between the two groups. Moreover, the effect of increasing self-esteem embodied in the TCC group was not present in the AE group. Compared to the WLC group, the relative abundance of Bacteroidaceae and Bacteroides were lower in the AE group, while the relative abundance of Erysipelotrichaceae and Alistipes were lower in the TCC group. And the relative abundance of Bacteroidaceae, Bacteroides, and Alistipes were significantly and negatively correlated with the decline in PMPU scores. CONCLUSION: AE or TCC is an effective, safe and efficient intervention for college students with PMPU, providing some physiological and psychological benefits and having some impact on their intestinal flora.

Gut microbiota, circulating cytokines and dementia: a Mendelian randomization study.

BACKGROUND: Some studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear. METHODS: Gut microbiota, cytokines, and five dementia types, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson's disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia. RESULTS: There were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors. CONCLUSIONS: Gut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia.

The Efficacy and Safety of Diazepam for Intraoperative Blood Pressure Stabilization in Hypertensive Patients Undergoing Vitrectomy Under Nerve Block Anesthesia: A Prospective, Single-Center, Double-Blind, Randomized, Controlled Trial.

Purpose: To evaluate the effectiveness and safety of diazepam in maintaining stable intraoperative blood pressure (BP) in hypertensive patients undergoing vitrectomy under nerve block anesthesia. Methods: A total of 180 hypertensive patients undergoing vitrectomy with nerve block anesthesia were randomized into two groups. The intervention group was given oral diazepam 60 min before operation, while the control group was given oral placebo 60 min before operation. The primary outcome is the effective rate of intraoperative BP control, defined as systolic blood pressure (SBP) during the operation maintained < 160 mmHg at all timepoints. The logistic regression model will be performed to analyze the compare risk factors for ineffective BP control. Results: The effective rate of intraoperative SBP control in the diazepam group was significant higher than that in the placebo group from 15 min to 70 min of the surgery (P < 0.05). The proportion of patients with SBP ≥180 mmHg at any timepoint from operation to 1 h postoperation was higher in the placebo group (12.22%) than in the diazepam group (2.22%) (P = 0.0096). We observed that the change in SBP from baseline consistently remained higher in the placebo group than in the diazepam group. In the logistic regression analysis, age, years of diagnosed hypertension and SBP 1h before surgery were significant risk factors for ineffective BP control. Conclusion: This study provides robust evidence supporting the effectiveness of oral diazepam as a pre-surgery intervention in maintaining stable blood pressure during vitrectomy in hypertensive patients. Trial Registration: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2100041772.