Epimedin A inhibits the PI3K/AKT/NF-κB signalling axis and osteoclast differentiation by negatively regulating TRAF6 expression.

BACKGROUND: Epimedin A (EA) has been shown to suppress extensive osteoclastogenesis and bone resorption, but the effects of EA remain incompletely understood. The aim of our study was to investigate the effects of EA on osteoclastogenesis and bone resorption to explore the corresponding signalling pathways. METHODS: Rats were randomly assigned to the sham operation or ovariectomy group, and alendronate was used for the positive control group. The therapeutic effect of EA on osteoporosis was systematically analysed by measuring bone mineral density and bone biomechanical properties. In vitro, RAW264.7 cells were treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) to induce osteoclast differentiation. Cell viability assays, tartrate-resistant acid phosphatase (TRAP) staining, and immunofluorescence were used to elucidate the effects of EA on osteoclastogenesis. In addition, the expression of bone differentiation-related proteins or genes was evaluated using Western blot analysis or quantitative polymerase chain reaction (PCR), respectively. RESULTS: After 3 months of oral EA intervention, ovariectomized rats exhibited increased bone density, relative bone volume, trabecular thickness, and trabecular number, as well as reduced trabecular separation. EA dose-dependently normalized bone density and trabecular microarchitecture in the ovariectomized rats. Additionally, EA inhibited the expression of TRAP and NFATc1 in the ovariectomized rats. Moreover, the in vitro results indicated that EA inhibits osteoclast differentiation by suppressing the TRAF6/PI3K/AKT/NF-κB pathway. Further studies revealed that the effect on osteoclast differentiation, which was originally inhibited by EA, was reversed when the TRAF6 gene was overexpressed. CONCLUSIONS: The findings indicated that EA can negatively regulate osteoclastogenesis by inhibiting the TRAF6/PI3K/AKT/NF-κB axis and that ameliorating ovariectomy-induced osteoporosis in rats with EA may be a promising potential therapeutic strategy for the treatment of osteoporosis.

Analysis of postoperative recurrence-free survival in non-small cell lung cancer patients based on consensus clustering.

AIMS: This study aims to assess whether consensus clustering, based on computed tomography (CT) radiomics from both intratumoral and peritumoral regions, can effectively stratify the risk of non-small cell lung cancer (NSCLC) patients and predict their postoperative recurrence-free survival (RFS). MATERIALS AND METHODS: A retrospective analysis was conducted on the data of surgical patients diagnosed with NSCLC between December 2014 and April 2020. After preprocessing CT images, radiomic features were extracted from a 9-mm region encompassing both the tumor and its peritumoral area. Consensus clustering was utilized to analyze the radiomics features and categorize patients into distinct clusters. A comparison of the differences in clinical pathological characteristics was conducted among the clusters. Kaplan-Meier survival analysis was employed to investigate differences in survival among the clusters. RESULTS: A total of 266 patients were included in this study, and consensus clustering identified three clusters (Cluster 1: n=111, Cluster 2: n=61, Cluster 3: n=94). Multiple clinical risk factors, including pathological TNM staging, programmed cell death ligand 1 (PD-L1), and epidermal growth factor receptor (EGFR) expression status exhibit significant differences among the three clusters. Kaplan-Meier survival analysis demonstrated significant variations in RFS across the clusters (P<0.001). The 3-year cumulative recurrence-free survival rates were 76.5% (95% CI: 68.6-84.4) for Cluster 1, 45.9% (95% CI: 33.4-58.4) for Cluster 2, and 41.5% (95% CI: 31.6-51.5) for Cluster 3. CONCLUSIONS: Consensus clustering of CT radiomics based on intratumoral and peritumoral regions can stratify the risk of postoperative recurrence in patients with NSCLC.

Prediction of programmed death-1 expression status in non-small cell lung cancer based on intratumoural and peritumoral computed tomography (CT) radiomics nomogram.

AIMS: This study aimed to predict the expression of programmed death-1 (PD-1) in non-small cell lung cancer (NSCLC) using intratumoral and peritumoral computed tomography (CT) radiomics nomogram. MATERIALS AND METHODS: Two hundred patients pathologically diagnosed with NSCLC from two hospitals were retrospectively analyzed. Of these, 159 NSCLC patients from our hospital were randomly divided into a training cohort (n=96) and an internal validation cohort (n=63) at a ratio of 6:4, while 41 NSCLC patients from another medical institution served as the external validation cohort. The radiomic features of the gross tumor volume (GTV) and peritumoral volume (PTV) were extracted from the CT images. Optimal radiomics features were selected using least absolute shrinkage and selection operator regression analysis. Finally, a CT radiomics nomogram of clinically independent predictors combined with the best rad-score was constructed. RESULTS: Compared with the 'GTV' and 'PTV' radiomics models, the combined 'GTV + PTV' radiomics model showed better predictive performance, and its area under the curve (AUC) values in the training, internal validation, and external validation cohorts were 0.90 (95% confidence interval [CI]: 0.83-0.97), 0.85 (95% CI: 0.74-0.96) and 0.78 (95% CI: 0.63-0.92). The nomogram constructed by the rad-score of the 'GTV + PTV' radiomics model combined with clinical independent predictors (prealbumin and monocyte) had the best performance, with AUC values in each cohort being 0.92 (95% CI: 0.85-0.98), 0.88 (95% CI: 0.78-0.97), and 0.80 (95% CI: 0.66-0.94), respectively. CONCLUSION: The intratumoral and peritumoral CT radiomics nomogram may facilitate individualized prediction of PD-1 expression status in patients with NSCLC.

[Epidemiological and clinical characteristics of human ocular helaziasis in China from 2011 to 2022 based on bibliometrics].

OBJECTIVE: To understand the clinical and epidemiological characteristics of human ocular thelaziasis patients in China. METHODS: Case reports regarding human ocular thelaziasis cases in China were retrieved in international and national electronic databases, including CNKI, VIP, CBM, Traditional Chinese Medical Literature Analysis and Retrieval System, Wanfang Database, PubMed and Web of Science from 2011 to 2022. Patients' gender, age, clinical symptoms, treatment, recurrence, site of infections, time of onset, affected eye, affected sites, number of infected Thelazia callipaeda, sex of T. callipaeda and source of infections were extracted for descriptive analyses. RESULTS: A total of 85 eligible publications were included, covering 101 cases of human ocular thelaziasis, including 57 males (56.44%) and 44 females (43.56%) and aged from 3 months to 85 years. The main clinical manifestations included foreign body sensation (56 case-times, 22.49%), eye itching (38 case-times, 15.26%), abnormal or increased secretions (36 case-times, 14.46%), tears (28 case-times, 11.24%) and eye redness (28 case-times, 11.24%), and conjunctival congestion (50 case-times, 41.67%) was the most common clinical sign. The most common main treatment (99/101, 98.02%) was removal of parasites from eyes using ophthalmic forceps, followed by administration with ofloxacin and pranoprofen. In publications presenting thelaziasis recurrence, there were 90 cases without recurrence (97.83%) and 2 cases with recurrence (2.17%). Of all cases, 51.96% were reported in four provinces of Hubei, Shandong, Sichuan, Hebei and Henan, and ocular thelaziasis predominantly occurred in summer (42.19%) and autumn (42.19%). In addition, 56.45% (35/62) had a contact with dogs. CONCLUSIONS: The human thelaziasis cases mainly occur in the continental monsoon and subtropical monsoon climate areas such as the Yellow River and the Yangtze River basin, and people of all ages and genders have the disease, with complex clinical symptoms and signs. Personal hygiene is required during the contact with dogs, cats and other animals, and individual protection is required during outdoor activities to prevent thelaziasis.

[Enamel developmental defects: environmental factors and clinical management].

Enamel formation is a complex physiological process that depends on the coordinated regulation of multiple mechanisms. This process is quite sensitive to various local and systemic interference factors. Therefore, during the long period from the embryonic stage to adolescence or even adulthood, various interference factors may lead to enamel developmental defects. Among them, early life is the most sensitive stage to environmental factors exposure, while it is also the critical period of enamel development of deciduous and permanent teeth. Environmental factors exposure during this period often leads to varying degrees of enamel development defects. In this review, we generalize the research progress of environmental factors affecting enamel developmental defects, summarize the potential mechanisms of environmental factors leading to enamel developmental defects, and conclude the clinical management strategies based on tertiary prevention. This work hopes to provide a theoretical basis for preventing abnormal teeth development from the critical time window of early life, propose eugenics health consultation and promote children 's oral health management.

Clinical Relevance of Plaque Distribution for Basilar Artery Stenosis.

BACKGROUND AND PURPOSE: There is no clear association between plaque distribution and postoperative complications in patients with basilar artery atherosclerotic stenosis. The aim of this study was to determine whether plaque distribution and postoperative complications after endovascular treatment for basilar artery stenosis are related. MATERIALS AND METHODS: Our study enrolled patients with severe basilar artery stenosis who were scanned with high-resolution MR imaging and followed by DSA before the intervention. According to high-resolution MR imaging, plaques can be classified as ventral, lateral, dorsal, or involved in 2 quadrants. Plaques affecting the proximal, distal, or junctional segments of the basilar artery were classified according to DSA. An experienced independent team assessed ischemic events after the intervention using MR imaging. Further analysis was conducted to determine the relationship between plaque distribution and postoperative complications. RESULTS: A total of 140 eligible patients were included in the study, with a postoperative complication rate of 11.4%. These patients were an average age of 61.9 (SD, 7.7) years. Dorsal wall plaques accounted for 34.3% of all plaques, and plaques distal to the anterior-inferior cerebellar artery accounted for 60.7%. Postoperative complications of endovascular treatment were associated with plaques located at the lateral wall (OR = 4.00; 95% CI, 1.21-13.23; P = .023), junctional segment (OR = 8.75; 95% CI, 1.16-66.22; P = .036), and plaque burden (OR = 1.03; 95% CI, 1.01-1.06; P = .042). CONCLUSIONS: Plaques with a large burden located at the junctional segment and lateral wall of the basilar artery may increase the likelihood of postoperative complications following endovascular therapy. A larger sample size is needed for future studies.

[Effects of prenatal nicotine exposure on enamel formation of offspring mice].

Objective: To investigate the effects of nicotine on the morphology, structure of offspring's dental germ, enamel organ and other dental tissues and the further potential epigenetic mechanisms by establishing prenatal nicotine exposure mouse model. Methods: Ten C57BL/6 pregnant mice were randomly divided into control group (physiological saline subcutaneous injection) and prenatal nicotine exposure (PNE) group (nicotine subcutaneous injection) by using a random number table. Postnatal day 0 (P0), postnatal day 14 (P14) and postnatal day 25 (P25) offspring mice were collected for subsequent experiments. The offspring mice were divided into offspring control group and offspring PNE group according to the maternal group respectively. Weights of P0 and P25 offspring mice were recorded. Micro-CT, scanning electron microscope (SEM) and Vickers hardness test were performed to analyze the related parameters of hard tissues including alveolar bones and mandibular incisors. Total RNAs were extracted from mandible tissues and the third generation of dental epithelial stem cells (DESC) in P25 mice. The relative expression levels of osteogenic and ameloblastic differentiation related genes were measured by real-time quantitative PCR (RT-qPCR). Immunohistochemical stainings of paraffin sections were then performed to observe the distribution and expression level of proliferating cell nuclear antigen (Pcna), amelogenin (Amelx), histone H3 trimethylated at lysine 27 (H3K27me3) and enhancer of zeste homolog 2 (Ezh2). Cell counting kit-8 (CCK-8) assays were used to detect the cell viabilities of DESCs after administrations of different concentrations of nicotine (0.01, 0.1, 1 mmol/L) and GSK126 (an inhibitor of histone methyltransferase Ezh2). Results: Compared with the control group, pregnant mice in PNE group were more likely to have adverse pregnancy outcomes, such as significantly lower offspring body weight [P0: offspring control (1.20±0.04) g, offspring PNE (0.99±0.02) g, P<0.001; P25: offspring control (15.26±1.70) g, offspring PNE (9.65±1.32) g, P<0.001] and increased stillbirths rate [offspring control (0), offspring PNE (46.40±9.30) %, P<0.001]. At P14 and P25, the distance parameters between the enamel mineralized deposits of mandibular incisors and the mesial surface of the first molar in offspring PNE group [P14: (-1 349±45) µm; P25: (-1 192±147) µm] was significantly decreased compared with the control group [P14: (-506±380) µm, P25: (504±198) µm] (P<0.05, P<0.001). The enamel column and enamel column stroma of incisors in offspring PNE group were blurred, arranged loosely and disorderly than those in the control group, while the microhardness of incisor enamel in offspring PNE group [(245.7±18.4) MPa] was significantly lower compared to the control group [(371.9±28.7) MPa] (P<0.001). HE staining showed disordered pre-ameloblast (Pre-Am) arrangement and delayed mineralization deposition point in offspring PNE group compared with the control group, while the length of transit-amplifying cell (TA) and Pre-Am region were prolonged as well. Immunohistochemical staining results displayed that the overall Pcna (P<0.05), H3K27me3 (P<0.01), Ezh2 (P<0.01) expression of labial cervical loop (LaCL) in PNE group were increased, while the positive signal of Amelx in ameloblast cytoplasm was impaired. In vitro, the addition of 1 mmol/L nicotine could significantly upregulate the expression level of Pcna (P<0.01) and downregulate the expression levels of B lymphoma Mo-MLV insertion region 1 (P<0.05), leucine rich repeats and immunoglobulin like domains 1 (P<0.05), Amelx (P<0.01). In addition, 1 mmol/L nicotine could also significantly enhance the proliferation activity of DESCs (P<0.001). Addition of 10 µmol/L GSK126, could rescue the proliferation activation effect of 1 mmol/L nicotine on DESCs. Conclusions: PNE may delay the process of enamel formation and lineage differentiation, leading to the abnormal proliferation of DESCs and changes of epigenetic modification state in H3K27me3, which affect the development of enamel in offspring mice,suggesting PNE might be one of risk environmental factor for tooth development.

Association of residential greenness with the risk of metabolic syndrome in Chinese older adults: a longitudinal cohort study.

AIMS: We aimed to investigate the association between residential greenness and MetS in older Chinese adults. METHODS: Longitudinal data on sociodemographic characteristics and lifestyle were collected from the Shenzhen Healthy Ageing Research (SHARE) cohort. Greenness exposure was assessed through satellite-derived Normalized Difference Vegetation Index (NDVI) values in the 250-m, 500-m, and 1250-m radius around the residential address for each participant. MetS was defined by standard guidelines for the Chinese population. RESULTS: A total of 49,893 older Chinese adults with a mean age of 70.96 (SD = 5.26) years were included in the study. In the fully adjusted models, participants who lived in the highest quartile of NDVI250-m, NDVI500-m, and NDVI1250-m had a 15% (odds ratio, OR = 0.85, 95% confidence interval, CI: 0.80-0.90), 12% (OR = 0.88, 95% CI: 0.83-0.93), and 11% (OR = 0.89, 95% CI: 0.85-0.95) lower incidence of MetS, respectively, than those living in the lowest quartile (all p-trend < 0.01). Interactions and subgroup analyses showed that age, sex, smoking status, and drinking status were significant effect modifiers (p-interaction for all NDVI < 0.05). CONCLUSIONS: Residential greenness is associated with a lower risk of MetS in Chinese older adults, especially for young older adults, females, non-smokers, and non-drinkers.

Thrombectomy Using the EmboTrap Clot-Retrieving Device for the Treatment of Acute Ischemic Stroke: A Glimpse of Clinical Evidence.

BACKGROUND: The EmboTrap Recanalization Device is a novel stent retriever for thrombectomy in the setting of acute ischemic stroke due to large-vessel occlusion. PURPOSE: Our aim was to summarize the safety and efficacy of the EmboTrap Recanalization Device in acute ischemic stroke-large-vessel occlusion through a systematic review and meta-analysis. DATA SOURCES: Medline, EMBASE, the Cochrane Library, Web of Science, and Google Scholar were searched up to April 2022. STUDY SELECTION: Nine observational studies using the EmboTrap Recanalization Device were selected. DATA ANALYSIS: We adapted effect size with 95% CIs for dichotomous data. P value <.05 was statistically significant. DATA SYNTHESIS: The estimated rate of successful recanalization (modified TICI 2b-3) was 90% (95% CI, 86%-95%; I 2 = 82.4%); 90-day favorable outcome (mRS 0-2), 53% (95% CI, 42%-63%; I 2 = 88.6%); modified first-pass effect, 43% (95% CI, 35%-51%; I 2 = 63.7%); and first-pass effect, 36% (95% CI, 29%-46%; I 2 = 10.7%). The rate of any intracerebral hemorrhage was 19% (95% CI, 16%-22%; I 2 = 0.0%); symptomatic intracerebral hemorrhage, 5% (95% CI, 1%-8%; I 2 = 84.6%); and 90-day mortality, 14% (95% CI, 9%-19%; I 2 = 79.3%). Subgroup analysis showed higher rates of complete recanalization for EmboTrap II than for the EmboTrap System. LIMITATIONS: The included studies are single-arm without direct comparison with other stent retrievers. Some of the studies recruited had a small sample size and were limited by the retrospective study design. In addition, the uncertain heterogeneity among studies was high. CONCLUSIONS: The EmboTrap Recanalization Device is safe and efficient in treating acute ischemic stroke due to large-vessel occlusion.

Impact of Thyroid Tissue Status on the Cut-Off Value of Lymph Node Fine-Needle Aspiration Thyroglobulin Measurements in Papillary Thyroid Cancer.

Objective: To study the optimal cut-off value of thyroglobulin measurement in a fine-needle aspiration (FNA-Tg) in diagnosing malignant lymph nodes and benign lymph nodes (LNs) according to the thyroid tissue status. Methods: A total of 517 LNs were aspirated: 401 preoperative LNs, 42 LNs after subtotal thyroidectomy and 74 suspected LNs after total thyroidectomy. The cut-off value of FNA-Tg was obtained from receiver operating characteristic (ROC) analysis. The cut-off value with the best diagnostic performance was then obtained by comparing different cut-off values from other studies. Results: LN FNA-Tg levels differed between preoperative and total thyroid disease (p < 0.001) and subtotal thyroidectomy and total thyroidectomy (p = 0.03), but not between preoperative and subtotal thyroidectomy (p = 1.00). Accordingly, those 443 LNs with preoperative and subtotal thyroidectomy were compared to those 74 without thyroid tissue. The optimal cut-off value in thyroid tissue group was 19.4 ng/ml and the area under the ROC curve (AUC) was 0.95 (95% CI 0.92-0.97). The optimal cut-off value in thyroid tissue absence group was 1.2 ng/ml and the AUC was 0.93 (0.85-0.98). After the analysis and comparison of multiple cut-off values, the optimal diagnostic performance was still found to be 19.4 ng/ml and 1.2 ng/ml. Conclusion: The influential factors of FNA-Tg are still controversial, and the optimal cut-off value of FNA-Tg can be determined based on the presence or absence of thyroid tissue. FNA-Tg can be used as an important auxiliary method for diagnosing cervical metastatic LNs of thyroid cancer.

Percutaneous Sacroplasty with or without Radiofrequency Ablation for Treatment of Painful Sacral Metastases.

BACKGROUND AND PURPOSE: Percutaneous sacroplasty is a variation of percutaneous vertebroplasty that has gained attention as a therapeutic option for patients with painful sacral insufficiency fractures due to osteoporosis or metastases. Additionally, percutaneous sacroplasty can also be used to treat painful sacral metastases without a pathologic fracture. The purpose of this retrospective study was to compare the efficacy and safety of fluoroscopy-guided percutaneous sacroplasty alone versus percutaneous sacroplasty plus radiofrequency ablation for the treatment of painful sacral metastases. MATERIALS AND METHODS: For this retrospective study, 126 patients (with a total of 162 painful sacral metastases) were enrolled from October 2012 to February 2021 and assigned to receive either percutaneous sacroplasty plus radiofrequency ablation (n = 51, group A) or percutaneous sacroplasty alone (n = 75, group B). Four different approaches were used for percutaneous sacroplasty: transiliac, interpedicular, anterior-oblique, and posterior. The Visual Analog Scale, Oswestry Disability Index, and Karnofsky Performance Scale were used to evaluate outcomes. RESULTS: The Visual Analog Scale, Oswestry Disability Index, and Karnofsky Performance Scale scores showed significant improvement in both groups after treatment (P < .05). The overall pain relief rate was significantly better in group A than in group B (90% versus 76%, P = .032). There were no significant differences in the incidence of polymethylmethacrylate leakage between the 2 groups or among the 4 different approaches (P > .05). CONCLUSIONS: Both percutaneous sacroplasty alone and the combination of percutaneous sacroplasty and radiofrequency ablation are safe and effective for treatment of painful sacral metastases. The combination of percutaneous sacroplasty and radiofrequency ablation appears to be more effective than percutaneous sacroplasty alone.

Relationship of resting heart rate and blood pressure with all-cause and cardiovascular disease mortality.

OBJECTIVES: This study aimed to investigate associations of resting heart rate (RHR) and blood pressure (BP) with all-cause and cardiovascular disease (CVD) mortality. STUDY DESIGN: A retrospective cohort study. METHODS: A total of 67,028 Chinese participants aged ≥60 years were included in the analysis. RHR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were evaluated according to quartiles ([41-69, 70-74, 75-79, 80-127 beats/min], [80-119, 120-129, 130-139, 140-238 mm Hg], and [40-70, 71-79, 80-84, 85-133 mm Hg]). Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause and CVD mortality with RHR, SBP, and DBP. Restricted cubic splines were used to evaluate the dose-response association. RESULTS: During the 361,975 person-year follow-up, 9326 deaths were recorded, of which 5039 deaths were due to CVD. The risk of all-cause mortality was increased by 25% with the quartiles four vs quartile one of RHR (HR [95% CI]:1.25 [1.17-1.33]), and CVD mortality was increased by 32% (HR [95% CI]: 1.32 [1.22-1.44]). Similar results were observed when comparing the quartiles four vs quartile one of SBP with the risk of all-cause and CVD mortality (HRs [95% CIs]: 1.14 [1.07, 1.22] and 1.23 [1.12. 1.34]) and DBP with the risk of all-cause and CVD mortality (HRs [95% CIs]: 1.17 [1.11. 1.24] and 1.36 [1.26. 1.47]). We found linear associations of RHR, SBP, and DBP with all-cause and CVD mortality (Pnon-linearity >0.05), except for the approximately J-shaped association between DBP and all-cause mortality (Pnon-linearity = 0.008). There was a significant interaction of RHR and SBP with all-cause and CVD mortality (Pinteraction <0.05). CONCLUSIONS: RHR and BP increased the risk of all-cause and CVD mortality, especially fast RHR combined with high SBP.

[Estradiol regulates the expression of plasma membrane Ca2+-ATPase isoform 2 in inner ear of rats].

Objective: To observe the effects of estradiol on expression of plasma membrane Ca2+-ATPase isoform 2 in inner ear of rats. Methods: Twenty-five Three-months-old female Sprague-Dawley rats were randomly and equally divided into five groups by random number table mathod,with five rats in each group. Animals in Sham group were sham-operated while others were bilateral ovariactmized. One month after modeling, the OVX groups were supplemented with estradiol (E2 group), progesterone (P group), estradiol and progesterone (E2+P group)and vehicle sesame oil (Veh group), while the Sham operation group (Sham group) was supplemented with vehicle sesame oil.All rats were sacrificed and otocysts were obtained immediately. Enzyme-linked immunosorbent assay was used to detect the changes in serum estradiol and progesterone levels of each group of rats before operation, before treatment and before sacrifice. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of total PMCA2 protein and mRNA in the inner ear of each group. Results: There was no significant difference in serum estradiol and progesterone levels among the five groups before operated(P>0.05). Before treatment, the serum estradiol and progesterone levels of rats in each group were significantly lower than those in Sham group (P<0.05). The serum estradiol level in E2 group and E2+P group was not significantly different from that in Sham group (P>0.05), while the serum estradiol level in P group and Veh group was significantly different from that in Sham group (P<0.05). The level of progesterone in P group and E2+P group was higher than that in Sham group (P<0.05), while the level of progesterone in Veh group and E2 group was lower than that in Sham group (P<0.05). Protein and mRNA expression of PMCA2 in P and Veh groups were significantly decreased compared with that of Sham group (P<0.05) while the expression levels underwent no significantly change in E2 and E2+P groups (P<0.05). Conclusion: The decrease of serum estradiol level can reduce the expression of otolith regulatory protein PMCA2 in rats, and then affect otolith metabolism, which may be an important link of estrogen affecting otolith metabolism.

Overall survival and progression-free survival with cyclin-dependent kinase 4/6 inhibitors plus endocrine therapy in breast cancer: an updated meta-analysis of randomized controlled trials.

OBJECTIVE: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) have been recommended as standard therapeutic strategies for hormone receptor-positive (HR+), human epidermal growth factor receptor type 2-negative (Her2-) advanced breast cancer (ABC). While the benefits to progression-free survival (PFS) rates have been confirmed, whether the combination of CDK4/6i and ET leads to overall survival (OS) rate improvements remains controversial. This study aimed to assess the long-term efficacy and safety of CDK4/6i in HR+, Her2- ABC patients and identify a population suitable for treatment with CDK4/6i by subgroup analysis. MATERIALS AND METHODS: Electronic literature databases (MEDLINE, EMBASE and the Cochrane Library) were searched for relevant randomized controlled trials (rcts) published from Jan 2014 to Jan 2020. In addition, abstracts and presentations from all major conference proceedings were reviewed. All rcts that compared the efficacy and safety of CDK4/6i plus ET with ET alone in HR+, Her2- ABC patients were selected. The pooled analyses of hazard ratios (hrs) for PFS and OS, and risk ratios (rrs) for the objective response rate (ORR) and adverse events (aes) were obtained with the random-effects model. RESULTS: A total of 6 rcts and 3421 HR+, Her2- ABC patients were enrolled for OS outcome analysis, while all 8 trials and 4580 patients were included for PFS outcome analysis. The pooled hrs for the OS and PFS were 0.76 (95% CI: 0.67-0.84) and 0.55 (95% CI: 0.50-0.59), respectively, and were consistent in the subgroup analysis. Moreover, CDK4/6i meaningfully improved the ORR in both the intention-to-treat population (RR=1.47; 95% CI: 1.29-1.67) and patients with measurable disease (RR=1.47; 95% CI: 1.30-1.67); however, CDK4/6i increased the incidence of grade 3/4 aes (RR=2.69; 95% CI: 2.43-2.97). CONCLUSIONS: The combination of CDK4/6i and ET was superior to ET alone in terms of OS and PFS regardless of the drugs administered, the treatment line, age distribution, race, PR status, menopausal status, metastasis site and endocrine resistance status.

[Effects of eye exercises on axial eye elongation in junior students].

Objective: To evaluate the association between the eye exercises and one-year axial eye elongation in grade 7 students in Beijing. Methods: Sampling was performed using a multistage random cluster approach, and 1 443 students of grade 7 were selected from 9 middle schools in 6 districts for the baseline survey. Data were collected by questionnaires and axial length measurement. Multiple linear regression analysis was used to evaluate the association between eye exercises and excessive axial eye elongation. Results: Among 1 197 (82.95%) students with complete information, the median (QR) age was 12.00 (1.00) years old, girls accounted for 44.28%, and the median (QR) axial eye elongation was 0.22 (0.18) mm. In the multiple linear regression analysis, the frequency of eye exercises was significantly correlated with excessive axial eye elongation in boys (ß=-0.135, 95%CI:-0.253--0.018) but not in girls (ß=-0.075, 95%CI:-0.207- 0.058) after adjusting for sex, age, body height, the number of myopic parents, time spent outdoors and time spent on reading and writing outside class; while the seriousness of eye exercises was not significantly associated with axial eye elongation in boys (ß=-0.028, 95%CI: -0.114-0.058) and girls (ß=-0.035, 95%CI: -0.134-0.064). Conclusion: The increased frequency of eye exercises is beneficial to control the axial eye elongation in boys in Beijing.

[Identification of potential regulatory genes for embryonic stem cell self-renewal and pluripotency by random forest].

OBJECTIVE: To identify novel genes associated with self-renewal and pluripotency of mouse embryonic stem cells(mESCs)by integrating multiomics data based on machine learning methods. METHODS: We integrated multiomics information of mESCs involving transcriptome, histone modifications, chromatin accessibility, transcription factor binding and architectural protein binding, and compared the signal differences between known stem cell self-renewal and pluripotency genes and other genes.By integrating these multiomics data, we established prediction models based on several machine learning classifiers including random forests and performed 5-fold cross validations.The model was trained using the training dataset containing two thirds of the input samples, and the remaining one third of the input samples were used as the test dataset to assess the performance of the model in independent tests.Finally, the results predicted by the model were validated through gene function annotation and cell function experiments including cell viability assay, colony formation assay and cell cycle analysis. RESULTS: Compared with the random genes, the genes known to be associated with self-renewal and pluripotency of mESCs in the multiomics data showed significantly different features.Random forest outperformed the other machine learning algorithms tested on these multiomics data, with an area under the curve (AUC) of 0.883±0.018 for cross validation and an AUC of 0.880±0.028 for independent test.Based on this model, we identified 893 potential regulatory genes associated wwith self-renewal and pluripotency of mESCs, which were similar to the known genes in functional annotation.Known-down of the predicted novel regulator gene Cct6a resulted in significant decreases in the cell viability of mESCs (P < 0.0001) and the number of cell clones (P < 0.01), significantly increased the number of cells in G1 phase (P < 0.01) and decreasedthe number of S phase cells (P < 0.05).Knockdown of Cct6a also led to failure of positive alkaline phosphatase staining of the mESCs. CONCLUSION: Machine learning model based on multiomics data can be used to predict potential self-renewal and pluripotency regulators with high performance.By using this model, we predicted potential self-renewal and pluripotency regulatory genes including Cct6a and applied experimental validation.This model provides new insights into the regulatory mechanism of mESCs and contribute to stem cell research.

Evaluation of Ultrafast Wave-Controlled Aliasing in Parallel Imaging 3D-FLAIR in the Visualization and Volumetric Estimation of Cerebral White Matter Lesions.

BACKGROUND AND PURPOSE: Our aim was to evaluate an ultrafast 3D-FLAIR sequence using Wave-controlled aliasing in parallel imaging encoding (Wave-FLAIR) compared with standard 3D-FLAIR in the visualization and volumetric estimation of cerebral white matter lesions in a clinical setting. MATERIALS AND METHODS: Forty-two consecutive patients underwent 3T brain MR imaging, including standard 3D-FLAIR (acceleration factor = 2, scan time = 7 minutes 50 seconds) and resolution-matched ultrafast Wave-FLAIR sequences (acceleration factor = 6, scan time = 2 minutes 45 seconds for the 20-channel coil; acceleration factor = 9, scan time = 1 minute 50 seconds for the 32-channel coil) as part of clinical evaluation for demyelinating disease. Automated segmentation of cerebral white matter lesions was performed using the Lesion Segmentation Tool in SPM. Student t tests, intraclass correlation coefficients, relative lesion volume difference, and Dice similarity coefficients were used to compare volumetric measurements among sequences. Two blinded neuroradiologists evaluated the visualization of white matter lesions, artifacts, and overall diagnostic quality using a predefined 5-point scale. RESULTS: Standard and Wave-FLAIR sequences showed excellent agreement of lesion volumes with an intraclass correlation coefficient of 0.99 and mean Dice similarity coefficient of 0.97 (SD, 0.05) (range, 0.84-0.99). Wave-FLAIR was noninferior to standard FLAIR for visualization of lesions and motion. The diagnostic quality for Wave-FLAIR was slightly greater than for standard FLAIR for infratentorial lesions (P < .001), and there were fewer pulsation artifacts on Wave-FLAIR compared with standard FLAIR (P < .001). CONCLUSIONS: Ultrafast Wave-FLAIR provides superior visualization of infratentorial lesions while preserving overall diagnostic quality and yields white matter lesion volumes comparable with those estimated using standard FLAIR. The availability of ultrafast Wave-FLAIR may facilitate the greater use of 3D-FLAIR sequences in the evaluation of patients with suspected demyelinating disease.

[Pilot study of genetic counseling and prenatal diagnosis in androgen insensitivity syndrome: with 3 families reports].

Objective: To explore genetic counseling and prenatal diagnosis strategies for women who have androgen insensitivity syndrome (AIS) family history or pregnancy history of AIS proband. Methods: Three families of complete AIS (CAIS) were retrospectively reported and summarized. The subsequent pregnancies and processes of prenatal diagnosis were followed up. Results: Among three CAIS families, one family had androgen receptors (AR) gene mutation diagnosis; the other two families were diagnosed clinically without gene diagnosis. All three mothers of CAIS probands were in pregnant again when they sought counseling, with gestational weeks between 7－13 weeks. They underwent chorionic villi sampling or amniocentesis in their second trimester (at 12, 16, 17 weeks respectively). Chromosome gender of all three fetuses were 46,XY, which was inconsistent with the ultrasonographic phenotype of external genitalia. All patients chose selective abortion in their second trimester. The external genitalia of all aborted fetuses were female phenotype, which supported the diagnosis of CAIS. Conclusion: Genetic counseling and prenatal diagnosis should be provided to high-risk patients with family history of AIS or proband pregnancy history, so as to achieve the goal of good childbearing and sound childrearing.