[Q-markers of Yuquan Capsules based on serum pharmacochemistry of Chinese medicine].

This study analyzed the quality markers(Q-markers) of Yuquan Capsules(YQC) based on serum pharmacochemistry of Chinese medicine and detected the components and metabolites of YQC absorbed into the blood by UPLC-Q-TOF-MS and UNIFI systems. As a result, 32 components of YQC were detected, including 17 prototype components and 15 metabolized components. Among them, 12 prototype components(ginsenoside Rh_2, genistein, formononetin, puerarin, daidzein, schizandrin A, schizandrin B, schizandrin C, schizandrol A, schizandrol B, gomisin D, and ononin) and 12 metabolized components(ginsenoside Rg_1, ginsenoside Rg_2, ginsenoside Rg_3, ginsenoside Ro, 3'-methoxypuerarin, daidzin, astragaloside Ⅱ, astragaloside Ⅳ, glycyrrhizic acid, liquiritigenin, isoliquiritin, and verbascoside) showed inhibitory effects and pharmacological activities against diabetes, and these 24 blood-entering components against diabetes were identified as Q-markers of YQC.

Association of mammographic density measures and breast cancer "intrinsic" molecular subtypes.

PURPOSE: We evaluated the association of percent mammographic density (PMD), absolute dense area (DA), and non-dense area (NDA) with risk of "intrinsic" molecular breast cancer (BC) subtypes. METHODS: We pooled 3492 invasive BC and 10,148 controls across six studies with density measures from prediagnostic, digitized film-screen mammograms. We classified BC tumors into subtypes [63% Luminal A, 21% Luminal B, 5% HER2 expressing, and 11% as triple negative (TN)] using information on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. We used polytomous logistic regression to calculate odds ratio (OR) and 95% confidence intervals (CI) for density measures (per SD) across the subtypes compared to controls, adjusting for age, body mass index and study, and examined differences by age group. RESULTS: All density measures were similarly associated with BC risk across subtypes. Significant interaction of PMD by age (P = 0.001) was observed for Luminal A tumors, with stronger effect sizes seen for younger women < 45 years (OR = 1.69 per SD PMD) relative to women of older ages (OR = 1.53, ages 65-74, OR = 1.44 ages 75 +). Similar but opposite trends were seen for NDA by age for risk of Luminal A: risk for women: < 45 years (OR = 0.71 per SD NDA) was lower than older women (OR = 0.83 and OR = 0.84 for ages 65-74 and 75 + , respectively) (P < 0.001). Although not significant, similar patterns of associations were seen by age for TN cancers. CONCLUSIONS: Mammographic density measures were associated with risk of all "intrinsic" molecular subtypes. However, findings of significant interactions between age and density measures may have implications for subtype-specific risk models.

Efficacy of berberine in treatment of rheumatoid arthritis: From multiple targets to therapeutic potential.

Rheumatoid arthritis is a systemic autoimmune disorder involved in persistent synovial inflammation. Berberine is a nature-derived alkaloid compound with multiple pharmacological activities in different pathologies, including RA. Recent experimental studies have clarified several determinant cellular and molecular targets of BBR in RA, and provided novel evidence supporting the promising therapeutic potential of BBR to combat RA. In this review, we recapitulate the therapeutic potential of BBR and its mechanism of action in ameliorating RA, and discuss the modulation of gut microbiota by BBR during RA. Collectively, BBR might be a promising lead drug with multi-functional activities for the therapeutic strategy of RA.

Automated volumetric breast density measures: differential change between breasts in women with and without breast cancer.

BACKGROUND: Given that breast cancer and normal dense fibroglandular tissue have similar radiographic attenuation, we examine whether automated volumetric density measures identify a differential change between breasts in women with cancer and compare to healthy controls. METHODS: Eligible cases (n = 1160) had unilateral invasive breast cancer and bilateral full-field digital mammograms (FFDMs) at two time points: within 2 months and 1-5 years before diagnosis. Controls (n = 2360) were matched to cases on age and date of FFDMs. Dense volume (DV) and volumetric percent density (VPD) for each breast were assessed using Volpara™. Differences in DV and VPD between mammograms (median 3 years apart) were calculated per breast separately for cases and controls and their difference evaluated by using the Wilcoxon signed-rank test. To simulate clinical practice where cancer laterality is unknown, we examined whether the absolute difference between breasts can discriminate cases from controls using area under the ROC curve (AUC) analysis, adjusting for age, BMI, and time. RESULTS: Among cases, the VPD and DV between mammograms of the cancerous breast decreased to a lesser degree (- 0.26% and - 2.10 cm3) than the normal breast (- 0.39% and - 2.74 cm3) for a difference of 0.13% (p value < 0.001) and 0.63 cm3 (p = 0.002), respectively. Among controls, the differences between breasts were nearly identical for VPD (- 0.02 [p = 0.92]) and DV (0.05 [p = 0.77]). The AUC for discriminating cases from controls using absolute difference between breasts was 0.54 (95% CI 0.52, 0.56) for VPD and 0.56 (95% CI, 0.54, 0.58) for DV. CONCLUSION: There is a small relative increase in volumetric density measures over time in the breast with cancer which is not found in the normal breast. However, the magnitude of this difference is small, and this measure alone does not appear to be a good discriminator between women with and without breast cancer.

Correction to: Isoliquiritigenin Provides Protection and Attenuates Oxidative Stress-Induced Injuries via the Nrf2-ARE Signaling Pathway After Traumatic Brain Injury.

The original version of this article unfortunately contained a mistake. The Fluorescence Immunoassays text written in Materials and Methods section and Fig. 1i, j is incorrect. In Fig. 1j, the images corresponding to Sham and TBI + ILG are incorrect. In Fig. 1i the figure caption "TBI + EDA" are incorrect. The corrected text and Fig. 1i, j are given below.

Early detection of cardiotoxicity by 3D speckle tracking imaging of area strain in breast cancer patients receiving chemotherapy.

Eighty-three breast cancer patients who underwent six cycles of EC chemotherapy regimen (epirubicin + cyclophosphamide) without symptoms and signs of heart disease were enrolled in the study. Three-dimensional speckle tracking imaging technique (3D-STI) was used to measure left ventricular global area strain (GAS), overall annular strain (GCS), overall longitudinal strain (GLS), and overall radial strain (GRS). Meanwhile, serum troponin T (Hs-cTnT) was measured. The clinical value of each index on cardiotoxicity after chemotherapy was analyzed using the receiver operating characteristic (ROC) curve. Hs-cTnT increased from the early stage to the end during chemotherapy, but it was still in the normal range. During the mid-chemotherapy and the end-chemotherapy, GAS, GLS, GCS, and E/A significantly reduced, while the changes in LVESV, LVEDV, LVEF, and GRS were not significant after chemotherapy. Pearson correlation analysis showed a significant negative correlation between GAS and anthracycline doses (r = -.772, P < .01); GAS and Hs-cTnT were significantly negatively correlated (P < .05). The area under the curve (AUC) of GAS, GLS, GCS, and GRS are 0.815, 0.683, 0.645, and 0.585, respectively. A GAS of -31.5% was used as the cutoff value for diagnosing left ventricular systolic dysfunction after receiving chemotherapy. The sensitivity of the previous parameters was 81.9%, and the specificity was 80.3%. Interobserver consistency analysis showed that 3D-STI strain parameter measurement has good repeatability. GAS has greater value in predicting early myocardial damage after anthracycline chemotherapy.

Automated and Clinical Breast Imaging Reporting and Data System Density Measures Predict Risk for Screen-Detected and Interval Cancers: A Case-Control Study.

Background: In 30 states, women who have had screening mammography are informed of their breast density on the basis of Breast Imaging Reporting and Data System (BI-RADS) density categories estimated subjectively by radiologists. Variation in these clinical categories across and within radiologists has led to discussion about whether automated BI-RADS density should be reported instead. Objective: To determine whether breast cancer risk and detection are similar for automated and clinical BI-RADS density measures. Design: Case-control. Setting: San Francisco Mammography Registry and Mayo Clinic. Participants: 1609 women with screen-detected cancer, 351 women with interval invasive cancer, and 4409 matched control participants. Measurements: Automated and clinical BI-RADS density assessed on digital mammography at 2 time points from September 2006 to October 2014, interval and screen-detected breast cancer risk, and mammography sensitivity. Results: Of women whose breast density was categorized by automated BI-RADS more than 6 months to 5 years before diagnosis, those with extremely dense breasts had a 5.65-fold higher interval cancer risk (95% CI, 3.33 to 9.60) and a 1.43-fold higher screen-detected risk (CI, 1.14 to 1.79) than those with scattered fibroglandular densities. Associations of interval and screen-detected cancer with clinical BI-RADS density were similar to those with automated BI-RADS density, regardless of whether density was measured more than 6 months to less than 2 years or 2 to 5 years before diagnosis. Automated and clinical BI-RADS density measures had similar discriminatory accuracy, which was higher for interval than screen-detected cancer (c-statistics: 0.70 vs. 0.62 [P < 0.001] and 0.72 vs. 0.62 [P < 0.001], respectively). Mammography sensitivity was similar for automated and clinical BI-RADS categories: fatty, 93% versus 92%; scattered fibroglandular densities, 90% versus 90%; heterogeneously dense, 82% versus 78%; and extremely dense, 63% versus 64%, respectively. Limitation: Neither automated nor clinical BI-RADS density was assessed on tomosynthesis, an emerging breast screening method. Conclusion: Automated and clinical BI-RADS density similarly predict interval and screen-detected cancer risk, suggesting that either measure may be used to inform women of their breast density. Primary Funding Source: National Cancer Institute.

Electrochemiluminescence Peptide-Based Biosensor with Hetero-Nanostructures as Coreaction Accelerator for the Ultrasensitive Determination of Tryptase.

In this work, a luminol-centric biosensor was constructed for the ultrasensitive detection of tryptase (TPS) combining dissolved O2 as the endogenous coreactant and Au-Ag-Pt heteronanostructures (AAPHNs) as coreaction accelerator. Dissolved O2 could rapidly generate superoxide anion radical (O2•-) with the catalysis of AAPHNs to in situ react with luminol anion radical (L•-) to generate excited-state species 3-aminophthalate (AP2-*) for emitting ECL signal, resulting in a remarkable "single on" state. In order to further improve the sensitivity of the sensor, we employed self-assembled DNA nanotubes (DNANTs) as a carrier to immobilize the luminophore of doxorubicin-luminol (Dox-Lu) complex. In this assay system, target tryptase could directly induce the cleavage of vasoactive intestinal peptide (VIP), which caused the ECL probe of DNANTs-Dox-Lu releasing from the electrode surface to obtain a significant "signal off" state. By changing the signal from "on" to "off", the proposed ECL peptide-based biosensor for TPS detection achieved a dynamic concentration range (2.5 pg/mL-200 ng/mL) with an extremely low detection limit of 0.81 pg/mL. This work presented a new signal amplification method for the construction of the sensor based on the luminol-dissolved O2 ECL system.

Does mammographic density mediate risk factor associations with breast cancer? An analysis by tumor characteristics.

BACKGROUND: Though mammographic density (MD) has been proposed as an intermediate marker of breast cancer risk, few studies have examined whether the associations between breast cancer risk factors and risk are mediated by MD, particularly by tumor characteristics. METHODS: Our study population included 3392 cases (1105 premenopausal) and 8882 (3192 premenopausal) controls from four case-control studies. For established risk factors, we estimated the percent of the total risk factor association with breast cancer that was mediated by percent MD (secondarily, by dense area and non-dense area) for invasive breast cancer as well as for subtypes defined by the estrogen receptor (ER+/ER-), progesterone receptor (PR+/PR-), and HER2 (HER2+/HER2-). Analyses were conducted separately in pre- and postmenopausal women. RESULTS: Positive associations between prior breast biopsy and risk of invasive breast cancer as well as all subtypes were partially mediated by percent MD in pre- and postmenopausal women (percent mediated = 11-27%, p ≤ 0.02). In postmenopausal women, nulliparity and hormone therapy use were positively associated with invasive, ER+ , PR+ , and HER2- breast cancer; percent MD partially mediated these associations (percent mediated ≥ 31%, p ≤ 0.02). Further, among postmenopausal women, percent MD partially mediated the positive association between later age at first birth and invasive as well as ER+ breast cancer (percent mediated = 16%, p ≤ 0.05). CONCLUSION: Percent MD partially mediated the associations between breast biopsy, nulliparity, age at first birth, and hormone therapy with risk of breast cancer, particularly among postmenopausal women, suggesting that these risk factors at least partially influence breast cancer risk through changes in breast tissue composition.

Isoliquiritigenin Provides Protection and Attenuates Oxidative Stress-Induced Injuries via the Nrf2-ARE Signaling Pathway After Traumatic Brain Injury.

Traumatic brain injury (TBI) is a serious public health and medical problem worldwide. Oxidative stress plays a vital role in the pathogenesis of TBI. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important factor in the cellular defense against oxidative stress, is activated following TBI. In this study, the protective effects of Isoliquiritigenin (ILG), a promising antioxidant stress drug, was evaluated as a protective agent against TBI. In a mouse model of controlled cortical impact Injury, we found that the ILG administration reduced the Garcia neuroscore, injury histopathology, brain water content, cerebral vascular permeability, the expression of cleaved caspase3, aquaporin-4, glial fibrillary acidic protein and the increased the expression of neurofilament light chain protein, indicating the protective effects against TBI in vivo. ILG treatment after TBI also restored the oxidative stress and promoted the Nrf2 protein transfer from the cytoplasm to the nucleus. We then used Nrf2-/- mice to test the protective effect of Nrf2 during ILG treatment of TBI. Our findings indicated that Nrf2-/- mice had greater brain injury and oxidative stress than wild-type (WT) mice and ILG was less effective at inhibiting oxidative stress and repairing the brain injury than in the WT mice. In vitro studies in SY5Y cells under oxygen glucose deprivation/re-oxygenation stimulation yielded results that were consistent with those obtained in vivo showing that ILG promotes Nrf2 protein transfer from the cytoplasm to the nucleus. Taken together, our findings demonstrate that Nrf2 is an important protective factor against TBI-induced injuries, which indicates that the protective effects of ILG are mediated by inhibiting oxidative stress after TBI via a mechanism that involves the promotion of Nrf2 protein transfer from the cytoplasm to the nucleus.

Comparison of Clinical and Automated Breast Density Measurements: Implications for Risk Prediction and Supplemental Screening.

Purpose To compare the classification of breast density with two automated methods, Volpara (version 1.5.0; Matakina Technology, Wellington, New Zealand) and Quantra (version 2.0; Hologic, Bedford, Mass), with clinical Breast Imaging Reporting and Data System (BI-RADS) density classifications and to examine associations of these measures with breast cancer risk. Materials and Methods In this study, 1911 patients with breast cancer and 4170 control subjects matched for age, race, examination date, and mammography machine were evaluated. Participants underwent mammography at Mayo Clinic or one of four sites within the San Francisco Mammography Registry between 2006 and 2012 and provided informed consent or a waiver for research, in compliance with HIPAA regulations and institutional review board approval. Digital mammograms were retrieved a mean of 2.1 years (range, 6 months to 6 years) before cancer diagnosis, with the corresponding clinical BI-RADS density classifications, and Volpara and Quantra density estimates were generated. Agreement was assessed with weighted κ statistics among control subjects. Breast cancer associations were evaluated with conditional logistic regression, adjusted for age and body mass index. Odds ratios, C statistics, and 95% confidence intervals (CIs) were estimated. Results Agreement between clinical BI-RADS density classifications and Volpara and Quantra BI-RADS estimates was moderate, with κ values of 0.57 (95% CI: 0.55, 0.59) and 0.46 (95% CI: 0.44, 0.47), respectively. Differences of up to 14% in dense tissue classification were found, with Volpara classifying 51% of women as having dense breasts, Quantra classifying 37%, and clinical BI-RADS assessment used to classify 43%. Clinical and automated measures showed similar breast cancer associations; odds ratios for extremely dense breasts versus scattered fibroglandular densities were 1.8 (95% CI: 1.5, 2.2), 1.9 (95% CI: 1.5, 2.5), and 2.3 (95% CI: 1.9, 2.8) for Volpara, Quantra, and BI-RADS classifications, respectively. Clinical BI-RADS assessment showed better discrimination of case status (C = 0.60; 95% CI: 0.58, 0.61) than did Volpara (C = 0.58; 95% CI: 0.56, 0.59) and Quantra (C = 0.56; 95% CI: 0.54, 0.58) BI-RADS classifications. Conclusion Automated and clinical assessments of breast density are similarly associated with breast cancer risk but differ up to 14% in the classification of women with dense breasts. This could have substantial effects on clinical practice patterns. (©) RSNA, 2015 Online supplemental material is available for this article.

Changed Synaptic Plasticity in Neural Circuits of Depressive-Like and Escitalopram-Treated Rats.

BACKGROUND: Although progress has been made in the detection and characterization of neural plasticity in depression, it has not been fully understood in individual synaptic changes in the neural circuits under chronic stress and antidepressant treatment. METHODS: Using electron microscopy and Western-blot analyses, the present study quantitatively examined the changes in the Gray's Type I synaptic ultrastructures and the expression of synapse-associated proteins in the key brain regions of rats' depressive-related neural circuit after chronic unpredicted mild stress and/or escitalopram administration. Meanwhile, their depressive behaviors were also determined by several tests. RESULTS: The Type I synapses underwent considerable remodeling after chronic unpredicted mild stress, which resulted in the changed width of the synaptic cleft, length of the active zone, postsynaptic density thickness, and/or synaptic curvature in the subregions of medial prefrontal cortex and hippocampus, as well as the basolateral amygdaloid nucleus of the amygdala, accompanied by changed expression of several synapse-associated proteins. Chronic escitalopram administration significantly changed the above alternations in the chronic unpredicted mild stress rats but had little effect on normal controls. Also, there was a positive correlation between the locomotor activity and the maximal synaptic postsynaptic density thickness in the stratum radiatum of the Cornu Ammonis 1 region and a negative correlation between the sucrose preference and the length of the active zone in the basolateral amygdaloid nucleus region in chronic unpredicted mild stress rats. CONCLUSION: These findings strongly indicate that chronic stress and escitalopram can alter synaptic plasticity in the neural circuits, and the remodeled synaptic ultrastructure was correlated with the rats' depressive behaviors, suggesting a therapeutic target for further exploration.

Research progress and challenges in stem cell therapy for diabetic foot: Bibliometric analysis and perspectives.

BACKGROUND: Stem cell therapy has shown great potential for treating diabetic foot (DF). AIM: To conduct a bibliometric analysis of studies on the use of stem cell therapy for DF over the past two decades, with the aim of depicting the current global research landscape, identifying the most influential research hotspots, and providing insights for future research directions. METHODS: We searched the Web of Science Core Collection database for all relevant studies on the use of stem cell therapy in DF. Bibliometric analysis was carried out using CiteSpace, VOSviewer, and R (4.3.1) to identify the most notable studies. RESULTS: A search was conducted to identify publications related to the use of stem cells for DF treatment. A total of 542 articles published from 2000 to 2023 were identified. The United States had published the most papers on this subject. In this field, Iran's Shahid Beheshti University Medical Sciences demonstrated the highest productivity. Furthermore, Dr. Bayat from the same university has been an outstanding researcher in this field. Stem Cell Research & Therapy is the journal with the highest number of publications in this field. The main keywords were "diabetic foot ulcers," "wound healing," and "angiogenesis." CONCLUSION: This study systematically illustrated the advances in the use of stem cell therapy to treat DF over the past 23 years. Current research findings suggested that the hotspots in this field include stem cell dressings, exosomes, wound healing, and adipose-derived stem cells. Future research should also focus on the clinical translation of stem cell therapies for DF.

Safety and efficacy of symptom-driven CT decision rule in fully conscious paediatric patients with symptoms after mild closed head trauma.

OBJECTS: The aim of the authors is to derive a safe, effective and feasible symptom-driven CT rule in fully conscious children ≥3 years with symptoms after head trauma, based on time-framed clinical course, radiological findings, outcome measures and prognosis of patients. METHODS: Fully conscious but symptomatic children ≥3 years after head injury (1997-2010) with CT performance ≤2 h since injury were included in the study. Additional exclusion criteria were set for patient selection. Evolution of clinical symptoms of patients in 24 h since injury was the focus in current study. Clinical data were extracted from standardised medical records on admission and observation charts. RESULTS: Data of 1897 eligible cases were retrospectively reviewed. Traumatic brain injury (TBI) was revealed radiologically in 73 cases (3.8%). Eight cases underwent surgery. Recursive partitioning analysis identified the following factors in the CT rule: any delayed headache commenced between 4 and 10 h since injury; significantly worsening headaches present between 2 and 12 h since injury; vomiting between 6 and 12 h since injury; and headache without significant changes persisted ≥12 h since injury. It has a sensitivity of 100% (95% CI 95.0% to 100.0%) and specificity of 72.1% (95% CI 70.0% to 74.1%) to predict cases with TBI. CONCLUSIONS: A symptom-driven CT rule has been derived to identify cases at high risk of having TBI in fully conscious, but symptomatic children with mild closed head injury. To be practical, an additional observation rule is added.

Preparation and characterization of mussel-inspired hydrogels based on methacrylated catechol-chitosan and dopamine methacrylamide.

A novel mussel-inspired adhesive hydrogel with enhanced adhesion based on methacrylated catechol-chitosan (MCCS) and dopamine methacrylate (DMA) was prepared via photopolymerization. The structure and morphology of the MCCS/DMA adhesive hydrogel were investigated by using FTIR, NMR, XRD, TG, and SEM. The rheological and texture properties, swelling and degradation characteristics, as well as the adhesion mechanism of the hydrogels were also examined. These results revealed that the MCCS/DMA hydrogels have a dense double cross-linking network structure with porous internal microstructures, and exhibited controllable swelling and degradation properties, good thermostability, and stable rheological characteristics. Furthermore, the adhesive mechanism of MCCS/DMA hydrogel has been confirmed by the FTIR and 2D correlation FTIR spectroscopy. Additionally, the results of in vitro cytotoxicity assessment indicated that the resulting hydrogels have good cytocompatibility. Overall, the MCCS/DMA adhesive hydrogel may have potential applications in medical bioadhesives.

The influence of mammogram acquisition on the mammographic density and breast cancer association in the Mayo Mammography Health Study cohort.

INTRODUCTION: Mammographic density is a strong risk factor for breast cancer. Image acquisition technique varies across mammograms to limit radiation and produce a clinically useful image. We examined whether acquisition technique parameters at the time of mammography were associated with mammographic density and whether the acquisition parameters confounded the density and breast cancer association. METHODS: We examined this question within the Mayo Mammography Health Study (MMHS) cohort, comprised of 19,924 women (51.2% of eligible) seen in the Mayo Clinic mammography screening practice from 2003 to 2006. A case-cohort design, comprising 318 incident breast cancers diagnosed through December 2009 and a random subcohort of 2,259, was used to examine potential confounding of mammogram acquisition technique parameters (x-ray tube voltage peak (kVp), milliampere-seconds (mAs), thickness and compression force) on the density and breast cancer association. The Breast Imaging Reporting and Data System four-category tissue composition measure (BI-RADS) and percent density (PD) (Cumulus program) were estimated from screen-film mammograms at time of enrollment. Spearman correlation coefficients (r) and means (standard deviations) were used to examine the relationship of density measures with acquisition parameters. Hazard ratios (HR) and C-statistics were estimated using Cox proportional hazards regression, adjusting for age, menopausal status, body mass index and postmenopausal hormones. A change in the HR of at least 15% indicated confounding. RESULTS: Adjusted PD and BI-RADS density were associated with breast cancer (p-trends < 0.001), with a 3 to 4-fold increased risk in the extremely dense vs. fatty BI-RADS categories (HR: 3.0, 95% CI, 1.7 - 5.1) and the ≥ 25% vs. ≤ 5% PD categories (HR: 3.8, 95% CI, 2.5 - 5.9). Of the acquisition parameters, kVp was not correlated with PD (r = 0.04, p = 0.07). Although thickness (r = -0.27, p < 0.001), compression force (r = -0.16, p < 0.001), and mAs (r = -0.06, p = 0.008) were inversely correlated with PD, they did not confound the PD or BI-RADS associations with breast cancer and their inclusion did not improve discriminatory accuracy. Results were similar for associations of dense and non-dense area with breast cancer. CONCLUSIONS: We confirmed a strong association between mammographic density and breast cancer risk that was not confounded by mammogram acquisition technique.

No evidence for association of inherited variation in genes involved in mitosis and percent mammographic density.

INTRODUCTION: Increased mammographic breast density is one of the strongest risk factors for breast cancer. While two-thirds of the variation in mammographic density appears to be genetically influenced, few variants have been identified. We examined the association of inherited variation in genes from pathways that mediate cell division with percent mammographic density (PMD) adjusted for age, body mass index (BMI) and postmenopausal hormones, in two studies of healthy postmenopausal women. METHODS: We investigated 2,058 single nucleotide polymorphisms (SNPs) in 378 genes involved in regulation of mitosis for associations with adjusted PMD among 484 unaffected postmenopausal controls (without breast cancer) from the Mayo Clinic Breast Cancer Study (MCBCS) and replicated the findings in postmenopausal controls (n = 726) from the Singapore and Sweden Breast Cancer Study (SASBAC) study. PMD was assessed in both studies by a computer-thresholding method (Cumulus) and linear regression approaches were used to assess the association of SNPs and PMD, adjusted for age, BMI and postmenopausal hormones. A P-value threshold of 4.2 × 10-5 based on a Bonferroni correction of effective number of independent tests was used for statistical significance. Further, a pathway-level analysis was conducted of all 378 genes using the self-contained gene-set analysis method GLOSSI. RESULTS: A variant in PRPF4, rs10733604, was significantly associated with adjusted PMD in the MCBCS (P = 2.7 × 10-7), otherwise, no single SNP was associated with PMD. Additionally, the pathway analysis provided no evidence of enrichment in the number of associations observed between SNPs in the mitotic genes and PMD (P = 0.60). We evaluated rs10733604 (PRPF4), and 73 other SNPs at P < 0.05 from 51 genes in the SASBAC study. There was no evidence of an association of rs10733604 (PRPF4) with adjusted PMD in SASBAC (P = 0.23). There were, however, consistent associations (P < 0.05) of variants at the putative locus, LOC375190, Aurora B kinase (AURKB), and Mini-chromosome maintenance complex component 3 (MCM3) with adjusted PMD, although these were not statistically significant. CONCLUSIONS: Our findings do not support a role of inherited variation in genes involved in regulation of cell division and adjusted percent mammographic density in postmenopausal women.

Alterations in the Gut Microbiota and Their Metabolites in Colorectal Cancer: Recent Progress and Future Prospects.

Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. The etiology and pathogenesis of CRC remain unclear. A growing body of evidence suggests dysbiosis of gut bacteria can contribute to the occurrence and development of CRC by generating harmful metabolites and changing host physiological processes. Metabolomics, a systems biology method, will systematically study the changes in metabolites in the physiological processes of the body, eventually playing a significant role in the detection of metabolic biomarkers and improving disease diagnosis and treatment. Metabolomics, in particular, has been highly beneficial in tracking microbially derived metabolites, which has substantially advanced our comprehension of host-microbiota metabolic interactions in CRC. This paper has briefly compiled recent research progress of the alterations of intestinal flora and its metabolites associated with CRC and the application of association analysis of metabolomics and gut microbiome in the diagnosis, prevention, and treatment of CRC; furthermore, we discuss the prospects for the problems and development direction of this association analysis in the study of CRC. Gut microbiota and their metabolites influence the progression and causation of CRC, and the association analysis of metabolomics and gut microbiome will provide novel strategies for the prevention, diagnosis, and therapy of CRC.

Diagnostic test accuracy of PCR by saliva specimen for cytomegalovirus infection in newborn: A protocol for systematic review and meta-analysis.

BACKGROUND: This study aimed to assess the diagnostic accuracy of polymerase-chain-reaction by saliva. METHOD: We searched Pubmed, EMBASE, Cochrane Library and Web of Science. A case-control or cohort study designed to explore the saliva specimens for diagnosing the cytomegalovirus infection was eligible for this study. Sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR), and summary receiver operating characteristic curves were calculated. RESULTS: Nine articles were selected for the meta-analysis. For assessing saliva PCR with urine culture, the SEN, SPE, and DOR were 0.97 [95% confidential interval (CI):0.61,1.00] 1.00 [95%CI:0.99, 1.00] 15672 [95%CI:558, 440325], respectively; for assessing saliva PCR with urine PCR, the SEN, SPE, and DOR were 0.87 [95%CI:0.79, 0.92] 1.00 [95%CI:1.00, 1.00] 15637 [95%CI:5946, 41126], respectively; for total assessment, the SEN, SPE, and DOR were0.91 [95%CI:0.70, 0.98] 1.00 [95%CI:1.00, 1.00] 8493 [95%CI:1429, 50487], respectively. CONCLUSION: We reported that saliva PCR performed well in the diagnosis of cytomegalovirus infection.

Effect of acupressure combined with Yinzhihuang granules on neonatal jaundice: a systematic review and meta-analysis of randomized controlled trials.

Background: With the improvement of living standards in recent years, people are paying increasing attention to neonatal jaundice. Yinzhihuang granule is a common Chinese herbal drug for the treatment of neonatal jaundice. The aim of this paper was to study the efficacy of acupressure-assisted Yinzhihuang granule in the treatment of neonatal jaundice by meta-analysis. Methods: We performed a search in the databases of PubMed, Embase, Cochrane Library, Chinese Journal Full-text Database (CNKI), VIP, Wanfang Science and Technology Journal Full-text Database, and Chinese Biomedical Literature Search Database (CBM) for articles on the therapeutic effect of acupressure-assisted Yinzhihuang granule on neonatal jaundice from database establishment to October 2021. The software Endnote X9 was used to check and eliminate the articles, screen the articles according to the required inclusion and exclusion criteria, extract the data, and perform quality evaluation according to the risk of bias tool of Cochrane Collaboration. The software Stata 15.1 and RevMan 5.3 were used to record the data, and a meta-analysis was performed on the effective rate of acupressure-assisted Yinzhihuang granule in the treatment of neonatal jaundice, according to serum total bilirubin values after treatment and duration of jaundice. And show the efficacy of Yinzhihuang particles through these results. The reliability of the results was assessed by sensitivity analysis. Funnel plots were used to test the publication bias of the articles. Results: A total of 3 articles were included. The results of meta-analysis showed that when acupressure-assisted Yinzhihuang granule was used to treat neonatal jaundice, the effective rate of the test group was not significantly different from that in the control group; the serum total bilirubin level in the test group was significantly lower than that in the control group after treatment; the duration of jaundice in the test group was significantly shorter than that in the control group. Discussion: Acupressure combined with Yinzhihuang granule is effective in treating neonatal jaundice, which has a positive effect on reducing the level of serum total bilirubin and reducing the duration of jaundice.