Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS: Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS: A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS: The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.

Spatiotemporal topological correspondence between blood oxygenation and glucose metabolism revealed by simultaneous fPET-fMRI in brain's white matter.

White matter (WM) makes up half of the human brain. Compelling functional MRI evidence indicates that white matter exhibits neural activation and synchronization via a hemodynamic window. However, the neurometabolic underpinnings of white matter temporal synchronization and spatial topology remain unknown. By leveraging concurrent [18F]FDG-fPET and blood-oxygenation-level-dependent-fMRI, we demonstrated the temporal and spatial correspondences between blood oxygenation and glucose metabolism in the human brain white matter. In the temporal scale, we found that blood-oxygenation-level-dependent signals shared mutual information with FDG signals in the default-mode, visual, and sensorimotor-auditory networks. For spatial distribution, the blood-oxygenation-level-dependent functional networks in white matter were accompanied by substantial correspondence of FDG functional connectivity at different topological scales, including degree centrality and global gradients. Furthermore, the content of blood-oxygenation-level-dependent fluctuations in the white matter default-mode network was aligned and liberal with the FDG graph, suggesting the freedom of default-mode network neuro-dynamics, but the constraint by metabolic dynamics. Moreover, the dissociation of the functional gradient between blood-oxygenation-level-dependent and FDG connectivity specific to the white matter default-mode network revealed functional heterogeneities. Together, the results showed that brain energy metabolism was closely coupled with blood oxygenation in white matter. Comprehensive and complementary information from fMRI and fPET might therefore help decode brain white matter functions.

The implications from the interplay of neoadjuvant chemoradiotherapy and the immune microenvironment in rectal cancer.

Neoadjuvant chemoradiotherapy (nCRT) is recommended for the treatment of locally advanced rectal cancer. Even though the combination of nCRT and immune checkpoint inhibitors (ICIs) has received much attention, the specific combination modes and dose fractions in radiotherapy (RT) are still indistinct. This review focuses on the immunological mechanism involved in nCRT, the clinical efficacy, the immunological effect of different combined strategies, concurrent or sequential nCRT plus ICIs, long-course RT and short-course RT. This review discusses the impact of nCRT on tumor immunity and summarizes the availability of different dose fractions in RT and distinct combined strategies, aiming at providing clues for optimal neoadjuvant therapy options that maximize efficacy and minimize side effects.

Radiotherapy (RT) and/or chemotherapy before surgery is the most common therapeutic strategy for patients with rectal cancer. This review summarizes the changes in tumor immunity, including immune cells and immune components, after receiving RT and chemotherapy. The authors looked for clues to the proper strategy of combined RT, chemotherapy and other novel agents to magnify antitumor immunity based on these changes. In addition, it emphasizes the RT regimens implicated in distinct immune alterations, which might help improve the efficacy of RT in clinical applications.

The effect of water source on cognitive functioning in Chinese adults: A cross-sectional and follow-up study.

The effect of water source on cognitive functioning is poorly understood. The present study explored the associations between water source and cognition in 9921 participants from the China Health and Retirement Longitudinal Study (CHARLS). Cognitive functioning was measured from three aspects: orientation and attention, episodic memory, and visuo-construction. Water sources included tap and non-tap water. Generalized linear models and multiple logistic regression models were conducted to investigate the associations of cognitive scores with water source among the whole population and different subgroups. Results from cross-sectional analysis reported that participants without access to tap water showed a lower cognitive score (ß = - 0.57; 95% CI: - 0.74, - 0.39) than those with tap water as a water source; and this phenomenon was pronounced for both sexes and across all residences. During 4-years' follow-up, a greater decline of cognitive score was associated with no tap water use in the lowest quartile of baseline cognitive scores (ß = - 0.67; 95% CI: - 1.26, - 0.08). Additionally, the utilization rate of tap water was lower in rural areas compared to urban areas. The lowest utilization rates were observed in urban areas of the Anhui province (0.38 in 2011 and 0.55 in 2015) and in rural areas of Inner Mongolia (0.09 in 2011 and 0.20 in 2015). These findings suggest that having no tap water may be a risk factor for cognition impairment, particularly for those with a low basic cognition score. Additionally, our results support the need to expand tap water use in China.

UVRAG Promotes Tumor Progression through Regulating SP1 in Colorectal Cancer.

Colorectal cancer (CRC) is the third most common type of cancer. The ultraviolet radiation resistance-associated gene (UVRAG) plays a role in autophagy and has been implicated in tumor progression and prognosis. However, the role of UVRAG expression in CRC has remained elusive. In this study, the prognosis was analyzed via immunohistochemistry, and the genetic changes were compared between the high UVRAG expression group and the low UVRAG expression group using RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) data, and genetic changes were then identified by in vitro experiments. It was found that UVRAG could enhance tumor migration, drug resistance, and CC motif chemokine ligand 2 (CCL2) expression to recruit macrophages by upregulating SP1 expression, resulting in poor prognosis of CRC patients. In addition, UVRAG could upregulate the expression of programmed death-ligand 1 (PD-L1). In summary, the relationship between UVRAG expression and the prognosis of CRC patients as well as the potential mechanisms in CRC were explored, providing evidence for the treatment of CRC.

Design, Synthesis, and Biological Evaluation of Proteolysis-Targeting Chimeras as Highly Selective and Efficient Degraders of Extracellular Signal-Regulated Kinase 5.

Extracellular signal-regulated kinase 5 (ERK5) is recognized as a key member of the mitogen-activated protein kinase family and is involved in tumor growth, migration, and angiogenesis. However, the results of ERK5 inhibition in multiple studies are controversial, and a highly specific ERK5-targeting agent is required to confirm physiological functions. Using proteolysis-targeting chimera technology, we designed the selective ERK5 degrader PPM-3 and examined its biological effect on cancer cells. Interestingly, the selective degradation of ERK5 with PPM-3 did not influence tumor cell growth directly. Based on proteomics analysis, the ERK5 deletion may be associated with tumor immunity. PPM-3 influences tumor development by affecting the differentiation of macrophages. Therefore, PPM-3 is an effective small-molecule tool for studying ERK5 and a promising immunotherapy drug candidate.

Association Between Tea Drinking and Cognitive Disorders in Older Adults: A Meta-Analysis of Observational Studies.

Introduction: Previous research has shown that tea drinking has a bearing on Cognitive Disorders, but the conclusions are inconsistent. The purpose of this research was to systematically assess the published evidence pertaining to tea drinking and the risk of cognitive disorders in older adults using a meta-analysis, and to concurrently evaluate the dose-response association. Design: A meta-analysis. Setting and Participants: We used the PubMed and Web of Science databases for a literature search until 30 May 2021. We initially retrieved 20,908 studies (14,884 from PubMed and 6,024 from the Web of Science), Thirty-six studies met the inclusion criteria (7 case-control, 16 cohort, and 13 cross-sectional studies), involved 224,980 participants. Methods: Pooled odd ratios (ORs) with their corresponding 95% confidence intervals (CIs) were used to evaluate the strength of the association under a fixed- or random-effect model according to heterogeneity test results. Results: The results showed that drinking tea was negatively associated with cognitive disorders (OR: 0.76, 95% CI: 0.70-0.82). Moreover, dose-response associations were found between tea drinking and cognitive disorders (1 time/day: OR, 0.81; 95% CI, 0.70-0.95; 1 cup/day: OR, 0.86; 95% CI, 0.78-0.94). In addition, subgroup analyses were performed according to study designs, study population, types of tea drinking, outcomes and methods used to assess outcomes. Most of the results in the subgroup analyses were consistent with the main results. Conclusion: The results of the present study provided abundant evidence that tea drinking is inversely proportional with the occurrence of cognitive disorders in older adults. A linear dose-response association between tea drinking and decreased prevalence of cognitive disorders was found.

Co-interventions with Clostridium butyricum and soluble dietary fiber targeting the gut microbiota improve MAFLD via the Acly/Nrf2/NF-κB signaling pathway.

Purpose: The pathogenesis of metabolic associated fatty liver disease (MAFLD) is complex. Lipid metabolic disorder, chronic inflammation, and oxidative stress are the core events for MAFLD. Dietary intervention is an important treatment strategy for preventing the onset and progression of MAFLD. Clostridium butyricum (CB) and soluble dietary fiber (SDF) are often considered beneficial for health. We explored how two microbiota-targeted interventions (SDF and CB) influence the hepatic immune system, oxidative stress, and lipid metabolism in MAFLD mice. Methods: To explore the role of SDF and CB in MAFLD, we generated MAFLD mouse models by feeding C57BL/6 mice with a high-fat diet (HFD). After 8 weeks of intervention, we measured immune cell function, lipid metabolism, and oxidative stress levels in the livers of mice. Results: Single intervention with SDF or CB was not effective in improving MAFLD; however, co-interventions with SDF and CB increased microbiota diversity and decreased inflammation, oxidative stress, and lipid synthesis. Moreover, we determined that co-intervention with SDF and CB mediated fatty acid oxidation by activating the Acly/Nrf2/NF-κB signaling pathway. Most importantly, co-intervention exerted anti-inflammatory effects by inhibiting the differentiation of macrophages into pro-inflammatory M1 macrophages. Conclusion: This study show that co-intervention with SDF and CB can improve MAFLD, and co-intervention with  SDF and CB are suggested to be potential gut microbiota modulators and therapeutic substances for MAFLD.

Meta-analysis of sugar-sweetened beverage intake and the risk of cognitive disorders.

BACKGROUND: Previous epidemiological studies revealed inconsistent associations between sugar-sweetened beverage (SSB) consumption and cognitive disorders, but there have been no meta-analyses of the pooled results. Thus, a meta-analysis was performed to determine the association between SSB consumption and cognitive disorders. METHODS: A systematic search of the literature prior to May 20, 2022 was performed using the PubMed and Web of Science databases. Random effects models were used to calculate and combine odds ratios (ORs) depending on the degree of heterogeneity. RESULTS: 13 studies met the inclusion criteria. A total of 242,014 participants (2752 in three cross-sectional studies and 239,262 in ten cohort studies) were included. A random effects meta-analysis, according to the comprehensive analysis of SSB consumption, was associated with a greater prevalence of cognitive disorders (OR = 1.17, 95 % CI = 1.05-1.29; I2 = 90.1 %). Subgroup analyses of study design, type of SSB, or cognitive disorders outcome was performed. In subgroup analyses, we found that SSB intake was associated with a higher prevalence of cognitive disorders in cohort studies, middle-aged and elderly population, and participants with sugar-sweetened soft drinks. However, no significant association was found in other subgroups. CONCLUSION: Our results indicate that SSB intake is positively associated with the prevalence of cognitive disorders. Therefore, attention should be paid to reducing SSB intake as an early intervention for cognitive disorders.

Fruit and Vegetable Consumption and Cognitive Disorders in Older Adults: A Meta-Analysis of Observational Studies.

Objectives: The aim of this meta-analysis was to assess the quantitative associations between fruit and vegetable intake and cognitive disorders in older adults. Design: A meta-analysis. Setting and Participants: We used the PubMed, Web of Science and Scopus databases for a literature search to 12 April 2022. We preliminarily retrieved 11,759 studies, 16 of which met the inclusion criteria including six cross-sectional studies, nine cohort studies and one case-control study, incorporating 64,348 participants and 9,879 cases. Methods: Using the three databases, we identified observational studies exploring the association. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Results: Sixteen studies were included in the meta-analysis, and the results showed that increased fruit and vegetable consumption in older adults was associated with a decline in the prevalence of cognitive disorders (OR: 0.79, 95% CI: 0.76-0.83). Moreover, intake of fruits (OR: 0.83, 95% CI: 0.77-0.89) and vegetables (OR: 0.75, 95% CI: 0.70-0.80) alone were both associated with a lower prevalence of cognitive disorders. Subgroup analyses indicated that the intake of fruits and vegetables was associated with the prevalence of cognitive impairment (OR: 0.72, 95% CI: 0.76-0.80) and dementia (OR: 0.84, 95% CI: 0.78-0.91) but not Alzheimer's disease (OR: 0.88, 95% CI: 0.76-1.01). Conclusion and Implications: Our meta-analysis provides evidence that the intake of fruits and vegetables is inversely proportional and linearly associated with the prevalence of cognitive disorders in older adults. Future research is required to further investigate the preventive effects of the frequency, quantity, and duration of eating vegetables and fruits on cognitive disorders in older adults.

Bidirectional Longitudinal Study of Frailty and Depressive Symptoms Among Older Chinese Adults.

OBJECTIVE: Frailty and depression, as two common conditions among older adults in China, have been shown to be closely related to each other. The aim of this study was to investigate the bidirectional effects between frailty and depressive symptoms in Chinese population. METHODS: The bidirectional effect of frailty with depressive symptoms was analyzed among 5,303 adults ≥ 60 years of age from the China Health and Retirement Longitudinal Study (CHARLS). Phenotype and a frailty index were used to measure frailty. Depressive symptoms were evaluated using the Epidemiological Studies Depression Scale (CES-D). Logistic regression and Cox proportional hazard regression models were used to determine the bidirectional effects of frailty and depressive symptoms in cross-sectional and cohort studies, respectively. Subgroup and sensitivity analyses were further used to further verify the associations. RESULTS: In the cross-sectional study, the multivariate-adjusted ORs (95% CIs) for depressive symptoms among pre-frail and frail adults, as defined by the frailty index and phenotype, were 3.05 (2.68-3.49), and 9.78 (8.02-12.03), respectively. Depressed participants showed higher risks of pre-frailty and frailty [frailty index, 3.07 (2.69-3.50); and phenotypic frailty, 9.95 (8.15-12.24)]. During follow-up, the multivariate-adjusted HRs (95% CIs) for depressive symptoms among pre-frail and frail participants, as defined by the frailty index and phenotype, were 1.38 (1.22-1.57), and 1.30 (1.14-1.48), respectively. No significant relationship existed between baseline depressive symptoms and the incidence of frailty. Moreover, the results from subgroup and sensitivity analyses were consistent with the main results. CONCLUSION: Although a cross-sectional bidirectional association between depressive symptom and frailty has been observed in older (≥60 years old) Chinese adults, frailty may be an independent predictor for subsequent depression. Moreover, no effect of depressive symptoms on subsequent frailty was detected. Additional bidirectional studies are warranted in China.

Association between blood selenium levels and gestational diabetes mellitus: A systematic review and meta-analysis.

Introduction: The association between blood (serum or plasma) selenium concentrations and gestational diabetes mellitus (GDM) has been evaluated in some studies. However, the reported findings are debatable, and only case-control and cross-sectional studies were included. Objective: This research aimed to assess the association between blood selenium levels and GDM by analyzing existing literature. To provide a reference for the prevention and treatment of GDM, we included prospective studies which are not included in previous studies to collate more high-quality evidence and better test the etiological hypothesis between blood Se concentrations and GDM. Methods: The PubMed, EMBASE, and Web of Science databases were retrieved for literature up to September 2022, and relevant references were manually searched. Raw data from relevant studies were extracted, and a random effect model was adopted for meta-analysis. The total effects were reported as weighted mean differences. All data were analyzed using Stata 16.0 software. Results: Fourteen studies involving 890 pregnant women with GDM and 1618 healthy pregnant women were incorporated in the meta-analysis. Pregnancies with GDM had significantly lower blood selenium levels than those with normal glucose tolerance (weighted mean difference = -8.11; 95% confidence interval: -12.68 to -3.54, P = 0.001). Subgroup analyses showed that the association between blood selenium levels and GDM was consistent in the residents of Asia and Africa, but not in European. This trend was significant in the second and third trimester subgroups, but not in the first trimester subgroup. Articles published in 2006-2015 also showed this trend, but those published before 2005 and 2016-2019 did not show significant results. This difference was evident in non-prospective studies, but not significant in prospective studies. Studies using the Carpenter and Coustan diagnostic criteria were consistent with this trend, whereas studies using other diagnostic criteria found no differences. In addition, in terms of blood selenium measurement methods, atomic absorption spectrometry showed more significant differences than other methods. In the subgroup analysis based on the sample size of included studies and the quality of the studies, each subgroup showed statistical differences. Conclusion: Lower blood selenium concentrations are associated with GDM as shown in our study. Therefore, supplementing an appropriate amount of selenium may be helpful for GDM prevention and treatment.

Influences of Air-Voids on the Performance of 3D Printing Cementitious Materials.

This paper focuses on inspecting the influences of anti-foaming agent (AFA) on the performance of 3D printing cementitious materials (3DPC). The mini-slump, spreading diameter, yield stress, and strength of 3DPC were evaluated. Additionally, the air-void content, air-void morphology, and air-void size distribution of mortar with and without 0.05% AFA were assessed through image analysis. The mechanical performance and air-void structure of 3D printed samples were also investigated and compared to that of conventionally mould cast samples. Test results show that an optimal AFA content enables 3DPC to achieve favorable workability and mechanical performance. The addition of AFA exhibits lower air-void content in 3DPC than that of the sample without the AFA addition. This reduction in air-void content is further strengthened by the results of strength analysis. Electron microscope analysis shows that the use of AFA results in the suppressed formation of large air-voids during the process of fresh 3DPC. Moreover, the air-void morphology substantially influenced the mechanical performance of hardened 3DPC.

Association of Atrial Fibrillation With Incidence of Extracranial Systemic Embolic Events: The ARIC Study.

Background Atrial fibrillation (AF) increases the risk of stroke and extracranial systemic embolic events (SEEs), but little is known about the magnitude of the association of AF with SEE. Methods and Results This analysis included 14 941 participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age, 54.2±5.8, 55% women, 74% White) without AF at baseline (1987-1989) followed through 2017. AF was identified from study ECGs, hospital discharges, and death certificates, while SEEs were ascertained from hospital discharges. CHA2DS2-VASc was calculated at the time of AF diagnosis. Cox regression was used to estimate associations of incident AF with SEE risk in the entire cohort, and between CHA2DS2-VASc score and SEE risk in those with AF. Among eligible participants, 3114 participants developed AF and 270 had an SEE (59 events in AF). Incident AF was associated with increased risk of SEE (hazard ratio [HR], 3.58; 95% CI, 2.57-5.00), after adjusting for covariates. The association of incident AF with SEE was stronger in women (HR, 5.26; 95% CI, 3.28-8.44) than in men (HR, 2.68; 95% CI, 1.66-4.32). In those with AF, higher CHA2DS2-VASc score was associated with increased SEE risk (HR per 1-point increase, 1.24; 95% CI, 1.05-1.47). Conclusions AF is associated with more than a tripling of the risk of SEE, with a stronger association in women than in men. CHA2DS2-VASc is associated with SEE risk in AF patients, highlighting the value of the score to predict adverse outcomes and guide treatment decisions in people with AF.

An open label, single-armed, exploratory study of apatinib (a novel VEGFR-2 tyrosine kinase inhibitor) in patients with relapsed or refractory non-Hodgkin lymphoma.

BACKGROUND: Apatinib, a novel small molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, have shown remarkable efficacy in many solid cancers. But evidence of antitumor activity in patients with lymphoma is still limited. We conducted an open-label, single-armed, exploratory study in relapse or refractory non-Hodgkin lymphoma patients for the efficacy and safety of apatinib. EXPERIMENTAL DESIGN: Patients with relapse or refractory non-Hodgkin patients meet the criteria were eligible for enrollment. Treatment comprised of oral apatinib 500 mg once daily with 21 days as a treatment cycle. The primary end point was response rate. Secondary end points included progression-free survival (PFS) and overall survival (OS). RESULTS: Between February 2016 and December 2016, 21 patients were enrolled. The ORR (CR plus PR) was 47.6% (10 of 21 patients) included 9.5% CRs and 38.1% PRs. 23.8% patients achieved stable disease made the DCR 71.4% (15/21). The median OS was 7.3 months (95% CI, 7.1 to 7.9) and the median PFS was 7.1 months (95% CI, 4.2 to 7.3). Most patients suffered from grade 1 to grade 2 treatment-related adverse events and the most common nonhematologic adverse events were proteinuria (47.6%), hypertension (42.9%) and hand-foot syndrome (33.3%), respectively. CONCLUSIONS: In our study, the results we presented showed apatinib might have a rapid, safe and high efficacy on relapsed or refractory non-Hodgkin lymphoma patients. Based on the data more clinic trials are expected to be taken to identification the efficacy of apatinib on lymphoma further.

[Advances in diagnosis and treatment of Meniere's disease].

Meniere's disease (MD), a kind of common disease of otology, is based on the endolymphatic hydrops. The clinical features of MD are intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus and ear fullness. With the in-depth exploration of the disease, the diagnosis and treatment of MD has made a series of research results. In this paper, the related literature and research reports in recent years were reviewed.

[Transformation of full-length gene of mouse/human chimeric antibody against Hantaan virus into Arabidopsis thaliana].

AIM: To construct the transgenic Arabidopsis thaliana containing full-length gene of mouse/human chimeric antibody(3G1MH) against Hantaan virus. METHODS: The recombinant plasmid 3G1MH-pCAMBIA2301 was transformed into Agrobacterium tumefaciens GV3101 by TSS freeze-thaw method, and then the recombinant was transferred into wild Arabidopsis thaliana by vacuum-transgenic method. The regenerated transgenic plants were selected with kanamycin, and confirmed by PCR and Northern blot. RESULTS: PCR result showed stable integration of the 3G1MH gene IN Arabidopsis thaliana genome in 7 stains of the transformed plants. Northern blot analyses confirmed the transcription of heavy and light chains in the transgenic plants. CONCLUSION: The successful establishment of 3G1MH transgenic Arabidopsis thaliana plants pave the way for further research on expressing therapeutic antibody in transgenic plants.

[Expression and genetic immunization of hantaan virus G2 recombinant adenovirus].

AIM: To express hantaan virus(HTNV) envelope glycoprotein G(2) recombinant adenovirus(Adeno-G(2)) in vero E6 cells and explore its property of inducing immune response. METHODS: Vero E6 cells were infected with the HTNV Adeno-G(2) (100 MOI). The expression of Adeno-G(2) in the infected Vero E6 cells was detected by IFA. BALB/c mice were immunized with HTNV Adeno-G(2), then the immune response to Adeno-G(2) was tested by ELISA, microcell-culture neutralizing experiment and lymphocyte proliferation test (MTT colorimetry). RESULTS: IFA detection showed the expression of Adeno-G(2) in the infected Vero E6 cells. The titer of specific antibody was 1:40; The low-titer neutralization antibody was also detected. But the lymphocyte proliferation reaction was not notable. CONCLUSION: The HTNV Adeno-G(2) can stimulate BALB/c mice to develop specific humoral immune response instead of specific cell-mediated immunity. This study provides the experimental basis for the development of gene engineering vaccine of HFRS.