Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases (TRICE trial): A randomized controlled trial.

BACKGROUND: It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. METHODS AND FINDINGS: This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. CONCLUSIONS: The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03493048.

Association between physical activity and allostatic load among pregnant women.

Allostatic load (AL) in pregnant women is associated with maternal and infant health outcomes. Whether physical activity (PA) is a modifiable factor associated with AL during pregnancy is unknown. In this cross-sectional study, including 725 pregnant women in 3 different trimesters, 8 biomarkers were included, and the high-risk quartile approach based on sample distribution was used to construct AL index (ALI). ALI <2 was defined as a low level and ≥2 as a high level. Student's t-test or Mann-Whitney U test and chi-squared test or Fisher exact test were used to compare differences in AL with different demographic characteristics among pregnant women. The relationship between PA and AL in pregnant women was analyzed using a binary logistic regression model. The results show that the detection rate of high-risk AL during pregnancy was 47.3%. In the adjusted model, sufficient PA was related to a lower AL than insufficient PA (OR = .693, 95%CI:.494,.971; p = .033). Compared with low- and high-intensity PAs, moderate-intensity PA was associated with lower AL (OR = .645, 95%CI:.447,.930; p = .019). The results suggest that PA is a modifiable factor related to AL, and intervention is recommended to be carried out in the first trimester to prevent the increased likelihood of high AL as pregnancy progresses. In addition, health care personnel should encourage pregnant women to participate in PA, especially moderate-intensity PA, in order to obtain lower AL and promote maternal and child health.

Exploring ALK fusion in colorectal cancer: a case series and comprehensive analysis.

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.

The Inhibitory Effects of Propofol on Colorectal Cancer Progression through the NF-κB/HIF-1α Signaling Pathway.

BACKGROUND AND OBJECTIVE: Colorectal cancer (CRC) is a neoplastic disease that gradually develops due to genetic variations and epigenetic changes. Surgical excision is the first-line treatment for CRC. Accumulating evidence has shown that total intravenous anesthesia has beneficial effects for CRC patients as it decreases the probability of tumor recurrence and metastasis. Propofol is one of the most frequently used intravenous anesthetics in clinical practice. However, it remains unknown whether it can reduce recurrence and metastasis after surgery in cancer patients. METHODS: CRC cell lines (HCT116 and SW480) were cultured in vitro, and different concentrations of propofol were added to the cell culture medium. The proliferation effect of propofol on CRC cell lines was evaluated by CCK-8 assay. The effect of propofol on the migration and invasion of CRC cells was evaluated by scratch healing and Transwell experiments. The inhibitory effects of propofol on NF-κB and HIF-1α expressions in CRC cell lines were determined by Western blotting and immunofluorescence assays to further clarify the regulatory effects of propofol on NF-κB and HIF-1α. RESULTS: Compared to the control, propofol significantly inhibited the proliferation, migration, and invasion abilities of CRC cells (HCT116 and SW480) (P < 0.0001). The expression levels of NF-κB and HIF-1α gradually decreased with increasing propofol concentration in both cell lines. After activation and inhibition of NF-κB, the expression of HIF-1α changed. Further studies showed that propofol inhibited LPS-activated NF-κB-induced expression of HIF-1α, similar to the NF-κB inhibitor Bay17083 (P < 0.0001). CONCLUSION: In vitro, propofol inhibited the proliferation, migration, and invasion of CRC cells (HCT116 and SW480) in a dose-dependent manner, possibly by participating in the regulation of the NF-κB/HIF-1α signaling pathway.

Association between allostatic load and depression in patients with sleep disorders: Evidence from national health and nutrition examination survey.

OBJECTIVE: Allostatic load (AL) is an indicator of cumulative wear and tear on the body's physiological systems that can predict the onset of a range of health problems. However, the relationship between AL and depression in patients with sleep disorders remains unclear. This study aimed to explore the association between AL and depression in patients with sleep disorders. METHODS: Using data from the 2015-2016 National Health and Nutrition Examination Survey, a total of 4618 adults aged 18 years and older in the United States were included in this cross-sectional analysis. AL was calculated using nine biological markers, with a score of ≥3 indicating a high level. Depression was assessed using the Patient Health Questionnaire-9, and a score of 10 or higher indicated a potential risk of depression. Logistic regression models were employed to analyze the relationship between AL and depression. RESULTS: Among the 1309 participants diagnosed with sleep disorders, 212 (16.2%) were identified as being at risk of depression. A total of 55.2% (n = 117) of the depressed persons had high AL levels. In the unadjusted model, AL levels were associated with depression in those with sleep disorders (OR:1.53, 95% CI = 1.14-2.05; P < .01). This relationship remained significant in the adjusted model (OR:1.52, 95% CI = 1.11-2.10, P < .05), after controlling for potential confounding factors. CONCLUSION: The findings showed that high AL levels in patients with sleep disorders were positively associated with depression, indicating that elevated AL may increase the risk of depression in this population, or alternatively, depression may increase the risk of AL.

The role of Testis-Specific Protein Y-encoded-Like 2 in kidney injury.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Recent findings suggest that Testis-Specific Protein Y-encoded-Like 2 (TSPYL2) plays a fibrogenic role in diabetes-associated renal injury. However, the role of TSPYL2 in IRI-induced kidney damage is not entirely clear. In this study, we found that the expression of TSPYL2 was upregulated in a mouse model of AKI and in the hypoxia/reoxygenation (H/R) cell model. Knockdown of TSPYL2 attenuated kidney injury after IRI. More specifically, the knockdown of TSPYL2 or aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) alleviated renal IRI-induced mitochondrial dysfunction and oxidative stress in vitro and in vivo. Further investigation showed that TSPYL2 regulated SREBP-2 acetylation by inhibiting SIRT1 and promoting p300 activity, thereby promoting the transcriptional activity of ACMSD. In conclusion, TSPYL2 was identified as a pivotal regulator of IRI-induced kidney damage by activating ACMSD, which may lead to NAD+ content and the damaging response in the kidney.

A mutation in CsGME encoding GDP-mannose 3,5-epimerase results in little and wrinkled leaf in cucumber.

KEY MESSAGE: Map-based cloning revealed that a mutation in a highly conserved amino acid of the CsGME gene encoding GDP-mannose 3,5-epimerase, causes the phenotype of little and wrinkled leaves in cucumbers. Leaf size is a critical determinant of plant architecture in cucumbers, yet only a few genes associated with this trait have been mapped or cloned. Here, we identified and characterized a mutant with little and wrinkled leaves, named lwl-1. Genetic analysis revealed that the phenotype of the lwl-1 was controlled by a single recessive gene. Through map-based cloning, the lwl-1 locus was narrowed down to a 12.22-kb region exclusively containing one fully annotated gene CsGME (CsaV3_2G004170). CsGME encodes GDP-mannose 3,5-epimerase, which is involved in the synthesis of ascorbic acid (ASA) and one of the components of pectin, RG-II. Whole-length sequencing of the 12.22 kb DNA fragment revealed the presence of only a non-synonymous mutation located in the sixth exon of CsGME in lwl-1, resulting in an amino acid alteration from Pro363 to Leu363. This mutation was unique among 118 inbred lines from cucumber natural populations. CsGME expression significantly reduced in various organs of lwl-1, accompanied by a significant decrease in ASA and pectin content in leaves. Both CsGME and Csgme proteins were localized to the cytoplasm. The mutant phenotype exhibited partial recovery after the application of exogenous boric acid. Silencing CsGME in cucumber through VIGS confirmed its role as the causal gene for lwl-1. Transcriptome profiling revealed that CsGME greatly affected the expression of genes related to the cell division process and cell plate formation. This study represents the first report to characterize and clone the CsGME in cucumber, indicating its crucial role in regulating leaf size and development.

mTOR signaling pathway regulation HIF-1 α effects on LPS induced intestinal mucosal epithelial model damage.

BACKGROUND: Sepsis-induced small-intestinal injury is associated with increased morbidity and mortality. Our previous study and other papers have shown that HIF-1α has a protective effect on intestinal mucosal injury in septic rats. The purpose of this study is to further verify the protective effect of HIF-1α on intestinal mucosa and its molecular mechanism in vitro experiments. METHODS: Caco-2 cells were selected and experiment was divided into 2 parts. Part I: HIF-1α activator and inhibitor were used to treat lipopolysacchrides (LPS)-stimulated Caco-2 cells respectively, to explore the effect of HIF-1α on LPS induced Caco-2 cell epithelial model; Part II: mTOR activator or inhibitor combined with or without HIF-1α activator, inhibitor to treat LPS-stimulated Caco-2 cells respectively, and then the molecular mechanism of HIF-1α reducing LPS induced Caco-2 cell epithelial model damage was detected. RESULTS: The results showed that HIF-1α activator decreased the permeability and up regulated tight junction (TJ) expression, while HIF-1α inhibitor had the opposite effect with the HIF-1α activator. mTOR activation increased, while mTOR inhibition decreased HIF-1α protein and expression of its downstream target molecules, which can be attenuated by HIF-1α activator or inhibitor. CONCLUSION: This study once again confirmed that HIF-1α alleviates LPS-induced mucosal epithelial model damage through P70S6K signalling pathway. It is of great value to explore whether HIF-2α plays crucial roles in the regulation of mucosal epithelial model functions in the future.

An improved method for isotopic and quantitative analysis of dissolved organic carbon in natural water samples.

A wet chemical oxidation (WCO) method has been widely used to obtain the dissolved organic carbon (DOC) content and carbon isotope (δ13CDOC) ratios. However, it is sometimes difficult to get high precision results because not enough CO2 was oxidized from the natural water samples with low DOC concentrations. This improvement primarily aims to increase the water sample volume, improve the removal rate of dissolved inorganic carbon (DIC), and minimize the blank DOC from the standard solution. Following the improved procedure, the δ13C ratios of standardized DOC solutions were consistent with their actual values, and their differences were less than 0.2‰. The improved method demonstrated good accuracy and stability when applied to natural water samples with DOC concentrations ≥0.5 mg L-1, with the precisions of DOC concentrations and δ13C ratios were better than 0.07 mg L-1 and 0.1‰, respectively. More importantly, this method saved much pre-treatment time and realized batch processing of water samples to obtain their DOC contents and isotope ratios.

Combined anti-PD-1, HDAC inhibitor and anti-VEGF for MSS/pMMR colorectal cancer: a randomized phase 2 trial.

Epigenetic modifications of chromatin, including histone acetylation, and tumor angiogenesis play pivotal roles in creating an immunosuppressive tumor microenvironment. In the randomized phase 2 CAPability-01 trial, we investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer. Forty-eight patients were randomly assigned to either the doublet arm (sintilimab and chidamide, n = 23) or the triplet arm (sintilimab, chidamide and bevacizumab, n = 25). The primary endpoint of progression-free survival (PFS) rate at 18 weeks (18wPFS rate) was met with a rate of 43.8% (21 of 48) for the entire study population. Secondary endpoint results include a median PFS of 3.7 months, an overall response rate of 29.2% (14 of 48), a disease control rate of 56.3% (27 of 48) and a median duration of response of 12.0 months. The secondary endpoint of median overall survival time was not mature. The triplet arm exhibited significantly improved outcomes compared to the doublet arm, with a greater 18wPFS rate (64.0% versus 21.7%, P = 0.003), higher overall response rate (44.0% versus 13.0%, P = 0.027) and longer median PFS rate (7.3 months versus 1.5 months, P = 0.006). The most common treatment-emergent adverse events observed in both the triplet and doublet arms included proteinuria, thrombocytopenia, neutropenia, anemia, leukopenia and diarrhea. There were two treatment-related fatalities (hepatic failure and pneumonitis). Analysis of bulk RNA sequencing data from the patients suggested that the triplet combination enhanced CD8+ T cell infiltration, resulting in a more immunologically active tumor microenvironment. Our study suggests that the combination of a PD-1 antibody, an HDACi, and a VEGF antibody could be a promising treatment regimen for patients with MSS/pMMR advanced colorectal cancer. ClinicalTrials.gov registration: NCT04724239 .

Methylated ctDNA predicts early recurrence risk in patients undergoing resection of initially unresectable colorectal cancer liver metastases.

Background: Patients with initially unresectable colorectal cancer liver metastases (IU-CRLM) might benefit from using an effective systemic treatment followed by resection of liver metastases but the curative success rate is quite low. Indeed, nearly one-third of patients exhibit early recurrence within the first 6 months after surgery, and these individuals often have poor overall survival. Objectives: This study aims to clarify the application value of serial circulating tumor DNA (ctDNA) analysis in predicting the clinical outcome of IU-CRLM patients following liver metastasectomy. Design: A retrospective study was conducted on a cohort of patients with IU-CRLM between February 2018 and April 2021. Methods: Plasma samples at different time points during CRLM treatment [baseline (BL), preoperation (PRE), postoperation (POST), end-of-treatment (EOT), and progressive disease (PD)] were retrospectively collected from patients with initially unresectable CRLM enrolled at the Sun Yat-sen University Cancer Center. Dynamic changes of SEPTIN 9 (SEPT9) and Neuropeptide Y (NPY) methylated circulating tumor DNA (MetctDNA) levels in serial plasma samples were detected using droplet-digital PCR (ddPCR). Results: SEPT9 and NPY genes were hypermethylated in colon cancer cell lines and tissues while no difference was observed between primary and metastatic tumors. Patients with MetctDNA positive at POST or EOT had significantly lower recurrence-free survival (RFS) compared to patients with MetctDNA negative at these time points [POST: Hazard ratio (HR) 9.44, 95% confidence interval (CI) 5.15-17.30, p < 0.001; EOT: HR 11.48, 95% CI 3.27-40.31, p < 0.001]. Multivariate analysis demonstrated that POST (OR 33.96, 95% CI 4.03-286.10, p = 0.001) and EOT (OR 18.36, 95% CI 1.14-295.71, p = 0.04) MetctDNA was an independent risk factor for early recurrence. Time-dependent receiver operating characteristic curve (T-ROC) analysis revealed that area under the curve (AUC) value was greatest at the relapse time point of 6 months post-intervention, with POST-AUC and EOT-AUC values of 0.74 (95% CI 0.66-0.81) and 0.73 (95% CI 0.53-0.94), respectively. Serial MetctDNA analysis showed that RFS was significantly lower in patients with no MetctDNA clearance compared with those with MetctDNA clearance (HR 26.05, 95% CI 4.92-137.81, p < 0.001). Conclusion: Our study confirmed that serial ctDNA analysis of NPY and SEPT9 gene methylation could effectively predict early recurrence in IU-CRLM patients, especially at POST and EOT.

Recent progress in hair follicle stem cell markers and their regulatory roles.

Hair follicle stem cells (HFSCs) in the bulge are a multipotent adult stem cell population. They can periodically give rise to new HFs and even regenerate the epidermis and sebaceous glands during wound healing. An increasing number of biomarkers have been used to isolate, label, and trace HFSCs in recent years. Considering more detailed data from single-cell transcriptomics technology, we mainly focus on the important HFSC molecular markers and their regulatory roles in this review.

Can digitalization effectively promote green energy efficiency? The linear and nonlinear relationship analysis.

In light of the integration of digitalization and the energy revolution, digitalization can be integrated into the energy industry to develop energy-saving technologies and improve resource allocation efficiency. On the basis of 2013-2019 Chinese provincial panel data, this paper measures the level of green energy efficiency based on the super-EBM-DEA model and analyzes the linear relationship, nonlinear relationship, and potential mechanism between digitalization and green energy efficiency. The findings indicate that (1) overall, both China's digitalization and green energy efficiency formed a steady upward trajectory during the sample period. Digitalization showed a spatial characteristic of extending and spreading from the eastern region to the central and western regions. Green energy efficiency was characterized by obvious regional heterogeneity. (2) Progress in digitalization has a significant driving effect on green energy efficiency. Subdimensional analysis shows that this driving effect mainly comes from digital development and digital transactions. (3) The impact of digitalization on green energy efficiency presents a threshold effect of economic agglomeration (with a threshold of 0.0257 and a marginally increasing, positive driving trend) and population agglomeration (with a threshold of 4.2750 and a marginally decreasing, positive driving trend). (4) Decomposing changes in green energy efficiency into scale efficiency and pure technical efficiency, this study shows that pure technical efficiency gains due to digitalization are the main driver of green energy efficiency improvements. Finally, some specific policy recommendations are proposed.

Chronic stress promotes gastric cancer progression via the adrenoceptor beta 2/PlexinA1 pathway.

Chronic stress is a common emotional disorder in cancer patients. Chronic stress promotes progression of gastric cancer (GC) and leads to poor outcomes. However, the underlying mechanisms remain not clear. Herein, we explored the possible mechanisms of chronic stress in GC progression. The Cancer Genome Atlas (TCGA) datasets were analyzed for differentially expressed genes. Clinical data of GC were evaluated for their association with PlexinA1 using TCGA and Kaplan-Meier-plotter databases. Chronic stress of GC patients was evaluated using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Chronic unpredictable mild stress (CUMS) was used to induce chronic stress in mice. Gastric xenograft tumor was constructed using the sewing method. Chronic stress-like behaviors were assessed using light/dark box and tail suspension tests. Protein expression was detected using immunohistochemistry and Western blot analysis. Analyses of TCGA and the Kaplan-Meier-plotter databases showed that patients with high levels of PlexinA1 in GC had worse overall survival than those with low levels of PlexinA1. A total of 36 GC patients were enrolled in the study, and about 33% of the patients had chronic stress. Compared with patients without chronic stress, higher expression levels of adrenoceptor beta 2 and PlexinA1 were observed in patients with chronic stress. The tumor size in mice under CUMS was significantly increased compared with the control mice. Adrenoceptor beta 2, PlexinA1, N-cadherin, and alpha-smooth muscle actin, as well as Ki67 were highly expressed in the tumors of CUMS group. However, E-cadherin was lowly expressed in the tumors of CUMS group. Importantly, chemical sympathectomy with 6-hydroxydopamine or treatment with a selective ß2 adrenergic receptor antagonist (ICI118,551) could reverse these effects. Our findings suggest that chronic stress plays an important role in GC progression and there is a potential for blocking the epinephrine-ß2AR/PlexinA1 pathway in the treatment of GC.

The impacts of water-sediment regulation on organic carbon in the Yellow River.

The Yellow River water-sediment regulation (WSR) is a unique hydraulic engineering project that involves the resuspension and rapid discharge of sediment downstream under the influence of density currents. This process leads to short-term high-intensity sediment scouring, which in turn increases the output of organic carbon. The impact of WSR on the biogeochemical cycling of organic carbon in rivers has not been adequately explored. In this study, we applied stable isotope and 3-D fluorescence analyses to investigate the impact of WSR at the Xiaolangdi (XLD) Reservoir on the sources and fluxes of dissolved organic carbon (DOC) and particulate organic carbon (POC) in the Yellow River. The POC and DOC fluxes during WSR (∼51 days) accounted for 95.5 % and 28.3 % of the annual fluxes. According to the Bayesian model used in the study, the fluxes of POC from sediment, terrestrial plants, and sewage increased by 23.2, 13.36, and 56.55 times, respectively, during the WSR period. On the other hand, the flux from various sources of DOC decreased by ∼0.7 times during the WSR process. The three-dimensional fluorescence index (specific UV absorbance [SUVA254], humification index [HIX], biological index [BIX], and fluorescence index [FI]) further reveals that in the WSR process, more DOC comes from sediment and upstream water. This study provides quantitative insights into the effects of WSR on river organic carbon export dynamics and the driving mechanisms behind them. It also has important implications for understanding the impact of anthropogenic disturbance on the global carbon cycle.

Lymphangiogenesis: A new strategy for heart disease treatment (Review).

Heart disease remains a global health challenge, contributing notably to morbidity and mortality. The lymphatic vasculature, an integral component of the cardiovascular system, plays a crucial role in regulating essential physiological processes, including fluid balance, transportation of extravasated proteins and immune cell trafficking, all of which are important for heart function. Through thorough scientometric analysis and extensive research, the present review identified lymphangiogenesis as a hotspot in cardiovascular disease research, and the mechanisms underlying impaired cardiac lymphangiogenesis and inadequate lymph drainage in various cardiovascular diseases are discussed. Furthermore, the way used to improve lymphangiogenesis to effectively regulate a variety of heart diseases and associated signaling pathways was investigated. Notably, the current review also highlights the impact of Traditional Chinese Medicine (TCM) on lymphangiogenesis, aiming to establish a clinical basis for the potential of TCM to improve cardiovascular diseases by promoting lymphangiogenesis.

Oxygen dynamic exchange and diffusion characteristics of ZnO nanorods from 17O MAS NMR.

Interactions of ZnO nanorods with water and the dynamic migration characteristic of surface oxygen species are important in controlling its structure and catalytic properties. Here, we apply 17O solid-state NMR spectroscopy to investigate the interactions, as well as oxygen ion diffusion properties of ZnO nanorods under different conditions.

PCDHGB7 hypermethylation-based Cervical cancer Methylation (CerMe) detection for the triage of high-risk human papillomavirus-positive women: a prospective cohort study.

BACKGROUND: Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. METHODS: A total of 3251 hrHPV-positive women aged 30-82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. RESULTS: CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 -) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). CONCLUSIONS: PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. TRIAL REGISTRATION: ChiCTR2100048972. Registered on 19 July 2021.

Effects of childhood maltreatment and major depressive disorder on functional connectivity in hippocampal subregions.

Major Depressive Disorder (MDD) with childhood maltreatment is a prevalent clinical phenotype. Prior studies have observed abnormal hippocampal activity in MDD patients, considering the hippocampus as a single nucleus. However, there is limited research investigating the static and dynamic changes in hippocampal subregion functional connectivity (FC) in MDD patients with childhood maltreatment. Therefore, we employed static and dynamic FC analyses using hippocampal subregions, including the anterior hippocampus and posterior hippocampus, as seed regions to investigate the neurobiological alterations associated with MDD resulting from childhood maltreatment. This study involved four groups: MDD with (n = 48) and without childhood maltreatment (n = 30), as well as healthy controls with (n = 57) and without (n = 46) childhood maltreatment. Compared to MDD patients without childhood maltreatment, those with childhood maltreatment exhibit altered FC between the hippocampal subregion and multiple brain regions, including the anterior cingulate gyrus, superior frontal gyrus, putamen, calcarine gyrus, superior temporal gyrus, angular gyrus, and supplementary motor area. Additionally, dynamic FC between the right medial-2 hippocampal head and the right calcarine gyrus shows a positive correlation with childhood maltreatment across all its subtypes. Moreover, dFC between the right hippocampal tail and the left angular gyrus moderates the relationship between childhood maltreatment and the depression severity. Our findings of distinct FC patterns within hippocampal subregions provide new clues for understanding the neurobiological basis of MDD with childhood maltreatment.