The TRIF-RIPK1-Caspase-8 signalling in the regulation of TLR4-driven gene expression.

The inflammatory response is tightly regulated to eliminate invading pathogens and avoid excessive production of inflammatory mediators and tissue damage. Caspase-8 is a cysteine protease that is involved in programmed cell death. Here we show the TRIF-RIPK1-Caspase-8 is required for LPS-induced CYLD degradation in macrophages. TRIF functions in the upstream of RIPK1. The homotypic interaction motif of TRIF and the death domain of RIPK1 are essential for Caspase-8 activation. Caspase-8 cleaves CYLD and the D235A mutant is resistant to the protease activity of Caspase-8. TRIF and RIPK1 serve as substrates of Capase-8 in vitro. cFLIP interacts with Caspase-8 to modulate its protease activity on CYLD and cell death. Deficiency in TRIF, Caspase-8 or CYLD can lead to a decrease or increase in the expression of genes encoding inflammatory cytokines. Together, the TRIF-Caspase-8 and CYLD play opposite roles in the regulation of TLR4 signalling.

ZNF131 facilitates the growth of hepatocellular carcinoma by acting as a transcriptional activator of SMC4 expression.

ZNF131 is a Zinc finger protein that acts as a transcription factor with oncogenic effects in multiple cancers. In this study, we aimed to explore the alternative splicing profile of ZNF131 in hepatocellular carcinoma (HCC), its regulatory effects on cell-cycle progression, and the downstream effectors. ZNF131 transcriptional profile and HCC survival analysis were conducted using data from the Cancer Genome Atlas (TCGA)-Liver Hepatocellular Cancer (LIHC) dataset. Chromatin immunoprecipitation (ChIP)-qPCR and dual-luciferase reporter assays were utilized to explore transcriptional regulation. CCK-8, colony formation and xenograft tumor models were used to study HCC tumor growth. Results showed that ZNF131 isoform 2 is upregulated in HCC tissues and its upregulation was associated with unfavorable overall survival (OS) and progression-free interval (PFI). Knockdown of endogenous ZNF131 inhibits HCC cell growth and induces G2/M cell-cycle arrest. ZNF131 binds to the SMC4 promoter by interacting with ZBTB33 and the ZBTB33 recognizing motif. ZNF131 transcriptionally activates SMC4 expression in HCC cells. The tumor-suppressive effects of ZNF131 shRNA could be partially reversed by enforced SMC4 overexpression. In summary, this study highlights the ZNF131/ZBTB33/SMC4 axis as a driver of pathological cell cycling and proliferation in HCC.

Revealing the pathogenesis of gastric intestinal metaplasia based on the mucosoid air-liquid interface.

BACKGROUND: Gastric intestinal metaplasia (GIM) is an essential precancerous lesion. Although the reversal of GIM is challenging, it potentially brings a state-to-art strategy for gastric cancer therapeutics (GC). The lack of the appropriate in vitro model limits studies of GIM pathogenesis, which is the issue this work aims to address for further studies. METHOD: The air-liquid interface (ALI) model was adopted for the long-term culture of GIM cells in the present work. This study conducted Immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR), transcriptomic sequencing, and mucoproteomic sequencing (MS) techniques to identify the pathways for differential expressed genes (DEGs) enrichment among different groups, furthermore, to verify novel biomarkers of GIM cells. RESULT: Our study suggests that GIM-ALI model is analog to the innate GIM cells, which thus can be used for mucus collection and drug screening. We found genes MUC17, CDA, TRIM15, TBX3, FLVCR2, ONECUT2, ACY3, NMUR2, and MAL2 were highly expressed in GIM cells, while GLDN, SLC5A5, MAL, and MALAT1 showed down-regulated, which can be used as potential biomarkers for GIM cells. In parallel, these genes that highly expressed in GIM samples were mainly involved in cancer-related pathways, such as the MAPK signal pathway and oxidative phosphorylation signal pathway. CONCLUSION: The ALI model is validated for the first time for the in vitro study of GIM. GIM-ALI model is a novel in vitro model that can mimic the tissue micro-environment in GIM patients and further provide an avenue for studying the characteristics of GIM mucus. Our study identified new markers of GIM as well as pathways associated with GIM, which provides outstanding insight for exploring GIM pathogenesis and potentially other related conditions.

Epigenetic Activation of Cytochrome P450 1A2 Sensitizes Hepatocellular Carcinoma Cells to Sorafenib.

Cytochrome P450 1A2 (CYP1A2) is a known tumor suppressor in hepatocellular carcinoma (HCC), but its expression is repressed in HCC and the underlying mechanism is unclear. In this study, we investigated the epigenetic mechanisms of CYP1A2 repression and potential therapeutic implications. In HCC tumor tissues, the methylation rates of CYP1A2 CpG island (CGI) and DNA methyltransferase (DNMT) 3A protein levels were significantly higher, and there was a clear negative correlation between DNMT3A and CYP1A2 protein expression. Knockdown of DNMT3A by siRNA significantly increased CYP1A2 expression in HCC cells. Additionally, treating HCC cells with decitabine (DAC) resulted in a dose-dependent upregulation of CYP1A2 expression by reducing the methylation level of CYP1A2 CGI. Furthermore, we observed a decreased enrichment of H3K27Ac in the promoter region of CYP1A2 in HCC tissues. Treatment with the trichostatin A (TSA) restored CYP1A2 expression in HCC cells by increasing H3K27Ac levels in the CYP1A2 promoter region. Importantly, combination treatment of sorafenib with DAC or TSA resulted in a leftward shift of the dose-response curve, lower IC50 values, and reduced colony numbers in HCC cells. Our findings suggest that hypermethylation of the CGI at the promoter, mediated by the high expression of DNMT3A, and hypoacetylation of H3K27 in the CYP1A2 promoter region, leads to CYP1A2 repression in HCC. Epigenetic drugs DAC and TSA increase HCC cell sensitivity to sorafenib by restoring CYP1A2 expression. Our study provides new insights into the epigenetic regulation of CYP1A2 in HCC and highlights the potential of epigenetic drugs as a therapeutic approach for HCC. SIGNIFICANCE STATEMENT: This study marks the first exploration of the epigenetic mechanisms underlying cytochrome P450 (CYP) 1A2 suppression in hepatocellular carcinoma (HCC). Our findings reveal that heightened DNA methyltransferase expression induces hypermethylation of the CpG island at the promoter, coupled with diminished H3K27Ac levels, resulting in the repression of CYP1A2 in HCC. The use of epigenetic drugs such as decitabine and trichostatin A emerges as a novel therapeutic avenue, demonstrating their potential to restore CYP1A2 expression and enhance sorafenib sensitivity in HCC cells.

Berberine Modulates Macrophage Activation by Inducing Glycolysis.

Classical activation of macrophage and monocyte differentiation induced by ß-glucan is accompanied with metabolic change in glucose. However, the role of the metabolic rewiring in monocyte/macrophage activation remains elusive. In this study, we show that berberine induces aerobic glycolysis by blocking the tricarboxylic acid cycle and modulates cytokine responses in bone marrow-derived macrophages (BMDMs) from mice and human PBMC. 13-Methyberberine had activities on glucose metabolism and BMDM activation similar to those of berberine, whereas other tested derivatives lost both activities. Glucose transporter (GLUT)1 expression and total cellular hexokinase activity increased gradually in BMDMs in the presence of berberine. In the contrast, LPS upregulated GLUT1 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) levels in 6 h. Extracellular glucose levels and replacing glucose with galactose in culture medium affected the cytokine secretion of BMDMs. Berberine alleviated enteritis of Salmonella typhimurium infection and protected mice against endotoxic shock. In mice i.p. injected with LPS, the increase of serum TNF-α and the drop of blood glucose were attenuated by berberine treatment. These data together demonstrated that macrophage activation was closely related with glucose metabolism.

Multiple coherent amplitude modes and exciton-phonon coupling in quasi-one-dimensional excitonic insulator Ta2NiSe5.

An excitonic insulator (EI) is an intriguing correlated electronic phase of condensed excitons. Ta2NiSe5 is a model material for investigating condensed excitonic states. Herein, femtosecond pump-probe spectroscopy is used to study the coherent phonon dynamics and associated exciton-phonon coupling in single-crystal Ta2NiSe5. The reflectivity time series consists of exponential decay due to hot carriers and damped oscillations due to the Ag phonon vibration. Given the in-plane anisotropic thermal conductivity of Ta2NiSe5, coherent phonon oscillations are stronger with perpendicular polarization to its quasi-one-dimensional chains. The 1-, 2-, and 4-THz vibration modes show coherent amplitude responses in the EI phase of Ta2NiSe5 with increasing temperature, totally different from those of normal coherent phonons (the 3- and 3.7-THz modes). The amplitude modes at higher frequencies decouple with the EI order parameter at lower temperatures, as supported by theoretical analysis with a model Hamiltonian of the exciton-phonon coupling system. Our work provides valuable insights into the character of the EI order parameter and its coupling to multiple coherent amplitude modes.

Treatment of ureteropelvic junction obstruction in patients with renal calculi via laparoscopic pyeloplasty and flexible vacuum-assisted ureteral access sheath ureteroscopy: a multicenter retrospective observational study.

BACKGROUND: Ureteropelvic junction obstruction (UPJO) is a common obstructive disease of the urinary tract. UPJO patients commonly exhibit coexistent renal calculi. The main aim of therapy is to relieve the obstruction and remove the stones at the same time. METHODS: This retrospective study included 110 patients diagnosed with UPJO coexisting with multiple renal calculi at Shanxi Bethune Hospital and the First Hospital of Shanxi Medical University between March 2016 and January 2022. Patients were divided according to the methods used for dealing with UPJO and renal calculi. In Group A, patients underwent traditional open pyeloplasty and pyelolithotomy. In Group B, patients underwent percutaneous nephrolithotomy first and then laparoscopic pyeloplasty. In Group C, patients underwent flexible cystoscopy to remove stones and then laparoscopic pyeloplasty. In Group D, patients underwent flexible vacuum-assisted ureteral access sheath (FV-UAS)assisted flexible ureteroscopy (f-URS) and underwent laparoscopic pyeloplasty. The stones were broken up using a holmium laser. The pyeloplasty success rate, stone clearance rate, operation time, bleeding amount, complication occurrence rate, postsurgical pain, length of stay, and hospitalization cost were compared between the groups. The follow-up period was at least 2 years. RESULTS: The use of f-URS and the FV-UAS, significantly increased the renal stone clearance rate and significantly reduced the complication incidence and operation time in UPJO patients with multiple coexisting renal calculi. CONCLUSIONS: Laparoscopic pyeloplasty combined with f-URS and FV-UAS is safe and effective for treating UPJO in patients complicated by renal caliceal stones. TRIAL REGISTRATION: Retrospectively registered.

Direct Observation of Trace Elements in Barium Titanate of Multilayer Ceramic Capacitors Using Atom Probe Tomography.

Accurately controlling trace additives in dielectric barium titanate (BaTiO3) layers is important for optimizing the performance of multilayer ceramic capacitors (MLCCs). However, characterizing the spatial distribution and local concentration of the additives, which strongly influence the MLCC performance, poses a significant challenge. Atom probe tomography (APT) is an ideal technique for obtaining this information, but the extremely low electrical conductivity and piezoelectricity of BaTiO3 render its analysis with existing sample preparation approaches difficult. In this study, we developed a new APT sample preparation method involving W coating and heat treatment to investigate the trace additives in the BaTiO3 layer of MLCCs. This method enables determination of the local concentration and distribution of all trace elements in the BaTiO3 layer, including additives and undesired impurities. The developed method is expected to pave the way for the further optimization and advancement of MLCC technology.

Glioma Single-Cell Biomechanical Analysis by Cyclic Conical Constricted Microfluidics.

Determining the grade of glioma is a critical step in choosing patients' treatment plans in clinical practices. The pathological diagnosis of patient's glioma samples requires extensive staining and imaging procedures, which are expensive and time-consuming. Current advanced uniform-width-constriction-channel-based microfluidics have proven to be effective in distinguishing cancer cells from normal tissues, such as breast cancer, ovarian cancer, prostate cancer, etc. However, the uniform-width-constriction channels can result in low yields on glioma cells with irregular morphologies and high heterogeneity. In this research, we presented an innovative cyclic conical constricted (CCC) microfluidic device to better differentiate glioma cells from normal glial cells. Compared with the widely used uniform-width-constriction microchannels, the new CCC configuration forces single cells to deform gradually and obtains the biophysical attributes from each deformation. The human-derived glioma cell lines U-87 and U-251, as well as the human-derived normal glial astrocyte cell line HA-1800 were selected as the proof of concept. The results showed that CCC channels can effectively obtain the biomechanical characteristics of different 12-25 µm glial cell lines. The patient glioma samples with WHO grades II, III, and IV were tested by CCC channels and compared between Elastic Net (ENet) and Lasso analysis. The results demonstrated that CCC channels and the ENet can successfully select critical biomechanical parameters to differentiate the grades of single-glioma cells. This CCC device can be potentially further applied to the extensive family of brain tumors at the single-cell level.

Resonance-enhanced excitation and relaxation dynamics of coherent phonons in Fe1.14Te.

Lattice dynamics plays a significant role in manipulating the unique physical properties of materials. In this work, femtosecond transient optical spectroscopy is used to investigate the generation mechanism and relaxation dynamics of coherent phonons in Fe1.14Te-a parent compound of chalcogenide superconductors. The reflectivity time series consist of the exponential decay component due to hot carriers and damped oscillations caused by the A1g phonon vibration. The vibrational frequency and dephasing time of the A1g phonons are obtained as a function of temperature. With increasing temperature, the phonon frequency decreases and can be well described with the anharmonicity model. Dephasing time is independent of temperature, indicating that the phonon dephasing is dominated by phonon-defect scattering. The impulsive stimulated Raman scattering mechanism is responsible for the coherent phonon generation. Owing to the resonance Raman effect, the maximum photosusceptibility of the A1g phonons occurs at 1.590 eV, corresponding to an electronic transition in Fe1.14Te.

The associations of ferritin, serum lipid and plasma glucose levels across pregnancy in women with gestational diabetes mellitus and newborn birth weight.

BACKGROUND: Women with gestational diabetes mellitus (GDM) are at greater risk of abnormal birth weight. Since the level of biochemical indicators could often affect the intrauterine growth and development of the fetus, it is of great practical significance to understand the changes of biochemical levels across pregnancy in women with GDM and to find out the indicators that play an important role in predicting birth weight. METHODS: The data source of this study was from the Xi'an Longitudinal Mother-Child Cohort study (XAMC), in which women with GDM with normal and high pre-pregnancy body mass index (BMI) and their newborns between January 1st and March 31st in 2018 were included. The data of ferritin, serum lipid profile and fasting plasma glucose (FPG) of mothers in the three trimesters of pregnancy, as well as birth weight of newborns were all collected from medical records. Multiple linear regression and multivariate logistic regression analyses were used to explore the association of the biochemical indexes and birth weight. A P value < 0.05 was considered statistically significant. RESULTS: A total of 782 mother-infant pairs were finally included and divided into normal weight group (NG) (n = 530, 67.8%) and overweight/obesity group (OG) (n = 252, 32.2%) according to maternal pre-pregnancy BMI. The level of ferritin in both NG and OG decreased during pregnancy (P for trend < 0.001 for all), whereas the levels of total cholesterol (TC), high density cholesterol (HDL-C), low density cholesterol (LDL-C) and triglycerides (TG) all showed an upward trend (P for trend < 0.05 for all). The levels of FPG in the two groups remained in a relatively stable during the whole pregnancy even though it was higher in OG during the 2nd and 3rd trimesters, whilst HbAlc levels in NG women increased (P for trend = 0.043) during pregnancy. Meanwhile, the risk of macrosomia and large-for-gestational-age (LGA) increased with the increase of FPG level (P for trend < 0.05). Multivariate logistic regression analyses results showed that only FPG level in the 3rd trimester was correlated with birth weight, with birth weight increased by 44.9 g for each SD increase in FPG level. CONCLUSION: Maternal FPG in the 3rd trimester is an independent predictor of newborn birth weight, and a higher level of that is associated with an increased risk of macrosomia and LGA.

Protective effect of intranasal insulin on postoperative cognitive dysfunction in elderly patients with metabolic syndrome undergoing noncardiac surgery: a randomized clinical trial.

BACKGROUND: Insulin plays a crucial and multifactorial role in cognitive activity, with insulin resistance appearing in neurodegenerative and metabolic diseases. Insulin resistance contributes to the pathobiology of postoperative cognitive dysfunction (POCD) in experimental models, which can be rescued by intranasal insulin administration. AIMS: To test the effect of intranasal insulin on the incidence of POCD in elderly patients with metabolic syndrome. METHODS: The study was designed as a randomized, double-blind, placebo-controlled clinical trial. 116 elderly participants were randomly assigned to receive either 40 IU insulin (n = 58) or placebo (n = 58) for 7 days. The primary outcome was the incidence of POCD at 7 days and 3 months after surgery. Secondary outcomes included the degree of peripheral insulin resistance postoperatively, changes in peripheral inflammation levels and the safety of interventions. RESULTS: The results showed that POCD occurred in the insulin group on the 7th postoperative day in 11 (20.8%) patients, which was fewer than the 23 (45.1%) patients in the placebo group (P = 0.008). The insulin group indicated better cognitive functional performance on language and memory test than the placebo group (P < 0.05). Mean peripheral plasma concentration of TNF-α (P < 0.05) and CRP (P < 0.001) in the insulin group was significantly declined compared with the placebo group on D3 and D7. CONCLUSIONS: Intranasal insulin administration reduced the incidence of POCD and alleviated peripheral inflammatory levels in elderly patients with metabolic syndrome. TRIAL REGISTRY: Chinese Clinical Trial Registry (ChiCTR1800015502).

Ultrafast Internal Exciton Dissociation through Edge States in MoS2 Nanosheets with Diffusion Blocking.

Edge states of two-dimensional transition-metal dichalcogenides (TMDCs) are crucial to quantum circuits and optoelectronics. However, their dynamics are pivotal but remain unclear due to the edge states being obscured by their bulk counterparts. Herein, we study the state-resolved transient absorption spectra of ball-milling-produced MoS2 nanosheets with 10 nm lateral size with highly exposed free edges. Electron energy loss spectroscopy and first-principles calculations confirm that the edge states are located in the range from 1.23 to 1.78 eV. Upon above bandgap excitations, excitons populate and diffuse toward the boundary, where the potential gradient blocks excitons and the edge states are formed through interband transitions within 400 fs. With below bandgap excitations, edge states are slowed down to 1.1 ps due to the weakened valence orbital coupling. These results shed light on the fundamental exciton dissociation processes on the boundary of functionalized TMDCs, enabling the ground work for applications in optoelectronics and light-harvesting.

Caesarean-section delivery and caries risk of 3-year-old Chinese children: a retrospective cohort study.

BACKGROUND: Caesarean-section (C-section) may influence children's long-term health by affecting bacterial colonization. However, few studies have focused on the association between C-section delivery (CSD) and dental caries, and previous conclusions have been conflicting. This study aimed to explore whether CSD would increase the risk of early childhood caries (ECC) in preschool children in China. METHODS: This study was a retrospective cohort study. Three-year-old children with full primary dentition were included through the medical records system. Children in the nonexposure group were vaginally delivered (VD), while children in the exposure group were delivered through C-section. The outcome was the occurrence of ECC. After agreeing to participate in this study, guardians of included children completed a structured questionnaire on maternal sociodemographic factors, children's oral hygiene and feeding habits. The chi-square test was used to determine differences in the prevalence and severity of ECC between the CSD and VD groups and to analyse the prevalence of ECC according to sample characteristics. Subsequently, potential risk factors for ECC were preliminarily identified through univariate analysis, and the adjusted odds ratios (ORs) were further calculated through multiple logistic regression analysis after controlling for confounding factors. RESULTS: The VD group included 2115 participants while CSD group included 2996 participants. The prevalence of ECC was higher in CSD children than in VD children (27.6% vs. 20.9%, P < 0.05), and the severity of ECC in CSD children was higher (mean number of decayed, missing, and filled teeth, dmft: 2.1 vs. 1.7, P < 0.05). CSD was a risk factor for ECC in 3-year-old children (OR = 1.43, 95% CI = 1.10-2.83). In addition, irregular tooth brushing and always prechewing children's food were risk factors for ECC (P < 0.05). Low maternal educational attainment (high school or below) or socioeconomic status (SES-5) may also increase the prevalence of ECC in preschool children and CSD children (P < 0.05). CONCLUSIONS: CSD would increase the risk of ECC in 3-year-old Chinese children. Paediatric dentists should devote more attention to the development of caries in CSD children. Obstetricians should also prevent excessive and unnecessary CSD.

CYP2E1 plays a suppressive role in hepatocellular carcinoma by regulating Wnt/Dvl2/ß-catenin signaling.

OBJECTIVE: Knowledge of the role of CYP2E1 in hepatocarcinogenesis is largely based on epidemiological and animal studies, with a primary focus on the role of CYP2E1 in metabolic activation of procarcinogens. Few studies have directly assessed the effects of CYP2E1 on HCC malignant phenotypes. METHODS: The expression of CYP2E1 in HCC tissues was determined by qRT-PCR, western blotting and immunohistochemistry. Overexpression of CYP2E1 in HCC cell was achieved by lentivirus transfection. The function of CYP2E1 were detected by CCK-8, wound healing, transwell assays, xenograft models and pulmonary metastasis model. TOP/FOPFlash reporter assay, western blotting, functional rescue experiments, Co-immunoprecipitation and reactive oxygen species detection were conducted to reveal the underlying mechanism of the tumor suppressive role of CYP2E1. RESULTS: CYP2E1 expression is down-regulated in HCC tissues, and this downregulation was associated with large tumor diameter, vascular invasion, poor differentiation, and shortened patient survival time. Ectopic expression of CYP2E1 inhibits the proliferation, invasion and migration and epithelial-to-mesenchymal transition of HCC cells in vitro, and inhibits tumor formation and lung metastasis in nude mice. Mechanistic investigations show that CYP2E1 overexpression significantly inhibited Wnt/ß-catenin signaling activity and decreased Dvl2 expression in HCC cells. An increase in Dvl2 expression restored the malignant phenotype of HCC cells. Notably, CYP2E1 promoted the ubiquitin-mediated degradation of Dvl2 by strengthening the interaction between Dvl2 and the E3 ubiquitin ligase KLHL12 in CYP2E1-stable HCC cells. CYP2E1-induced ROS accumulation was a critical upstream event in the Wnt/ß-Catenin pathway in CYP2E1-overexpressing HCC cells. CONCLUSIONS: These results provide novel insight into the role of CYP2E1 in HCC and the tumor suppressor role of CYP2E1 can be attributed to its ability to manipulate Wnt/Dvl2/ß-catenin pathway via inducing ROS accumulation, which provides a potential target for the prevention and treatment of HCC.

A randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in women at high risk in China.

BACKGROUND: Low-dose aspirin has been the most widely studied preventive drug for preeclampsia. However, guidelines differ considerably from country to country regarding the prophylactic use of aspirin for preeclampsia. There is limited evidence from large trials to determine the effect of 100 mg of aspirin for preeclampsia screening in women with high-risk pregnancies, based on maternal risk factors, and to guide the use of low-dose aspirin in preeclampsia prevention in China. OBJECTIVE: The Low-Dose Aspirin in the Prevention of Preeclampsia in China study was designed to evaluate the effect of 100 mg of aspirin in preventing preeclampsia among high-risk pregnant women screened with maternal risk factors in China, where preeclampsia is highly prevalent, and the status of low-dose aspirin supply is commonly suboptimal. STUDY DESIGN: We conducted a multicenter randomized controlled trial at 13 tertiary hospitals from 11 provinces in China between 2016 and 2019. We assumed that the relative reduction in the incidence of preeclampsia was at least 20%, from 20% in the control group to 16% in the aspirin group. Therefore, the targeted recruitment number was 1000 participants. Women were randomly assigned to the aspirin or control group in a 1:1 allocation ratio. Statistical analyses were performed according to an intention-to-treat basis. The primary outcome was the incidence of preeclampsia, diagnosed along with a systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg after 20 weeks of gestation, with a previously normal blood pressure (systolic blood pressure of <140 mm Hg and diastolic blood pressure of <90 mm Hg), and complicated by proteinuria. The secondary outcomes included maternal and neonatal outcomes. Logistic regression analysis was used to determine the significance of difference of preeclampsia incidence between the groups for both the primary and secondary outcomes. Interaction analysis was also performed. RESULTS: A total of 1000 eligible women were recruited between December 2016 and March 2019, of which the final 898 patients were analyzed (464 participants in the aspirin group, 434 participants in the control group) on an intention-to-treat basis. No significant difference was found in preeclampsia incidence between the aspirin group (16.8% [78/464]) and the control group (17.1% [74/434]; relative risk, 0.986; 95% confidence interval, 0.738-1.317; P=.924). Likewise, adverse maternal and neonatal outcomes did not differ significantly between the 2 groups. Meanwhile, the incidence of postpartum hemorrhage between the 2 groups was similar (6.5% [30/464] in the aspirin group and 5.3% [23/434] in the control group; relative risk, 1.220; 95% confidence interval, 0.720-2.066; P=.459). We did not find any significant differences in preeclampsia incidence between the 2 groups in the subgroup analysis of the different risk factors. CONCLUSION: A dosage of 100 mg of aspirin per day, initiated from 12 to 20 gestational weeks until 34 weeks of gestation, did not reduce the incidence of preeclampsia in pregnant women with high-risk factors in China.

Development of gestational diabetes mellitus in women with periodontitis in early pregnancy: A population-based clinical study.

AIM: This study aimed to determine whether periodontitis in early pregnancy and periodontal therapy during gestation affect the incidence of gestational diabetes mellitus (GDM) through a population-based clinical study. MATERIALS AND METHODS: Subjects without periodontitis at 1-4 weeks of gestation who met our inclusion criteria were enrolled in the non-periodontitis group. Periodontitis patients who agreed or refused to receive periodontal therapy during pregnancy were separately enrolled in the periodontitis treated or untreated group. At 12-16 weeks of gestation, gingival crevicular fluid (GCF) and venous blood were collected for analyses of bacterial species and serum inflammatory mediators, respectively. At 24-28 weeks of gestation, GDM patients were identified by oral glucose tolerance tests. The association tests were performed using Chi-squared statistics and regression analyses. RESULTS: The complete data of 3523 pregnant women were recorded during the study period. GDM incidence among the untreated periodontitis participants (84/749, 11.21%) was significantly higher than that among the non-periodontitis participants (108/2255, 4.79%) (p < .05), and periodontal treatment during gestation reduced the incidence from 11.21% (untreated group) to 7.32% (38/519, treated group) (p < .05). Based on multiple logistic regression analyses, it was found that periodontitis in early pregnancy was associated with GDM, and three-step regression analyses showed that Porphyromonas gingivalis (P. gingivalis) and the serum TNF-α and IL-8 levels played a role in the association between untreated periodontitis and GDM. Furthermore, Pearson's correlation test indicated that the existence of P. gingivalis in GCF was positively correlated with high serum levels of these two inflammatory mediators. CONCLUSIONS: This study establishes a connection between periodontitis in early pregnancy and GDM and demonstrates that the presence of P. gingivalis is associated with high levels of inflammatory mediators in serum, and thereby may contribute to the development of GDM. In-depth mechanistic studies are needed to further support these findings.

Effect of flavonoid intake on circulating levels of adiponectin and leptin: A systematic review and meta-analysis of randomized controlled clinical trials.

This meta-analysis of randomized controlled trials (RCTs) was conducted to explore the effects of flavonoid intake on adiponectin and leptin levels. The PubMed, EMBASE, and Cochrane Library databases were searched on March 1, 2021. Random-effects, subgroup, sensitivity, and meta-regression analyses were conducted on 40 publications. Flavonoid intake significantly increased circulating adiponectin (0.54 µg/ml, 95% CI [0.20, 0.88], p = .002; I2  = 86.4%) and significantly reduced leptin levels (weighted mean difference: -0.79 ng/ml, 95% CI [-1.33, -0.25], p = .004; I2  = 87.7%). Subgroup analysis demonstrated that flavonoid intervention produced a significant elevation in adiponectin levels only in studies that lasted more than 12 weeks, conducted in Asian regions, were parallel-designed, involved obese or overweight participants and participants with type 2 diabetes mellitus (T2DM) or cardiovascular diseases, used tea catechins, and used a dietary supplement intervention. A significantly negative effect on leptin levels was observed in studies conducted in Asian countries, with healthy participants and participants with T2DM, used whole food interventions, and involved participants with lower baseline leptin levels. In conclusion, flavonoid intake significantly increased circulating adiponectin and decreased leptin levels; however, study heterogeneity was very high. Future well-designed trials are required to address heterogeneous study designs and clarify the efficacy of plants in regulating adiponectin and leptin levels.

Immune infiltration profiling in gastric cancer and their clinical implications.

The abundance and type of immune cells in the tumor microenvironment (TME) significantly influence immunotherapy and tumor progression. However, the role of immune cells in the TME of gastric cancer (GC) is poorly understood. We studied the correlations, proportion, and infiltration of immune and stromal cells in GC tumors. Data analyses showed a significant association of infiltration levels of specific immune cells with the pathological characteristics and clinical outcomes of GC. Furthermore, based on the difference in infiltration levels of immune and stromal cells, GC patients were divided into two categories, those with "immunologically hot" (hot) tumors and those with "immunologically cold" (cold) tumors. The assay for transposase-accessible chromatin using sequencing and RNA sequencing analyses revealed that the hot and cold tumors had altered epigenomic and transcriptional profiles. Claudin-3 (CLDN3) was found to have high expression in the cold tumors and negatively correlated with CD8+ T cells in GC. Overexpression of CLDN3 in GC cells inhibited the expression of MHC-I and CXCL9. Finally, the differentially expressed genes between hot and cold tumors were utilized to generate a prognostic model, which predicted the overall survival of GC as well as patients with immunotherapy. Overall, we undertook a comprehensive analysis of the immune cell infiltration pattern in GC and provided an accurate model for predicting the prognosis of GC patients.

Establishment of a Systemic Inflammatory Response Syndrome Model and Evaluation of the Efficacy of Umbilical Cord Mesenchymal Stem Cell Transplantation.

Based on the characteristics of modern weapon injury, a repetitive model of traumatic systemic inflammatory response syndrome (SIRS) and an evaluation system were established. The models were treated with GFP-labeled tree shrew umbilical cord mesenchymal stem cells (UCMSCs). Forty out of 50 tree shrews were used to make a unilateral femoral comminuted fracture. Lipopolysaccharide was injected intravenously to create a traumatic SIRS model. The other 10 shrews were used as normal controls. After the model was established for 10 days, 20 tree shrews were injected intravenously with GFP-labeled UCMSCs, and 18 tree shrews were not injected as the model control group. The distribution of GFP-labeled cells in vivo was measured at 2 and 10 days after injection. Twenty days after treatment, the model group, the normal control group, and the treatment group were taken to observe the pathological changes in each tissue, and blood samples were taken for the changes in liver, renal, and heart function. Distribution of GFP-positive cells was observed in all tissues at 2 and 10 days after injection. After treatment, the HE staining results of the treatment group were close to those of the normal group, and the model group had a certain degree of lesions. The results of liver, renal, and heart function tests in the treatment group were returned to normal, and the results in the model group were abnormally increased. UCMSCs have a certain effect on the treatment of traumatic SIRS and provide a new technical solution for modern weapon trauma treatment.