Genomic and transcriptomic profiling of combined small-cell lung cancer through microdissection: unveiling the transformational pathway of mixed subtype.

BACKGROUND: Combined small-cell lung carcinoma (cSCLC) represents a rare subtype of SCLC, the mechanisms governing the evolution of cancer genomes and their impact on the tumor immune microenvironment (TIME) within distinct components of cSCLC remain elusive. METHODS: Here, we conducted whole-exome and RNA sequencing on 32 samples from 16 cSCLC cases. RESULTS: We found striking similarities between two components of cSCLC-LCC/LCNEC (SCLC combined with large-cell carcinoma/neuroendocrine) in terms of tumor mutation burden (TMB), tumor neoantigen burden (TNB), clonality structure, chromosomal instability (CIN), and low levels of immune cell infiltration. In contrast, the two components of cSCLC-ADC/SCC (SCLC combined with adenocarcinoma/squamous-cell carcinoma) exhibited a high level of tumor heterogeneity. Our investigation revealed that cSCLC originated from a monoclonal source, with two potential transformation modes: from SCLC to SCC (mode 1) and from ADC to SCLC (mode 2). Therefore, cSCLC might represent an intermediate state, potentially evolving into another histological tumor morphology through interactions between tumor and TIME surrounding it. Intriguingly, RB1 inactivation emerged as a factor influencing TIME heterogeneity in cSCLC, possibly through neoantigen depletion. CONCLUSIONS: Together, these findings delved into the clonal origin and TIME heterogeneity of different components in cSCLC, shedding new light on the evolutionary processes underlying this enigmatic subtype.

Infection pattern and immunological characteristics of Epstein-Barr virus latent infection in cervical squamous cell carcinoma.

Previous studies reported the association between Epstein-Barr virus (EBV) and cervical squamous cell carcinoma (CSCC), but its infection pattern and clinical significance unclear. This study aimed to comprehensively investigate the infection pattern, clinicopathology, outcomes, and immunology of this entity in central China. We evaluated a total of 104 untreated CSCC tumor tissue specimens using in situ hybridization for EBV-encoded small RNAs (EBERs), and by employing flowcytometry fluorescence hybridization for human papillomavirus (HPV) genotyping. The expression of EBV latency proteins and immune biomarkers was evaluated and quantified by immunohistochemistry. EBERs transcripts were detected in 21 (20.2%) cases overall (in malignant epithelial cells of 13 cases and in lymphocytes of 8 cases). EBV belonged to latency type I infection in CSCC. The high-risk (HR)-HPV was detected in all of EBV-positive CSCC, and the difference of detection rate of HR-HPV was significant when compared with EBV-negative CSCC (p = 0.001). The specific clinicopathology with increased frequency of advanced clinical stages, tumor-positive lymph nodes, neural invasion, and increased infiltration depth (all p value < 0.05) were observed in cases with EBV. However, EBV infection was found to have no impact on prognosis of patients with CSCC. Increased densities of forkhead box P3 (FoxP3)+-tumor infiltrating lymphocytes (TILs) (p = 0.005) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)+-TILs (p = 0.017) and higher expression of programmed cell death-1 (PD-1) (p = 0.002) and programmed cell death-1 ligand 1 (PD-L1) (p = 0.040) were associated with EBV latent infection in CSCC, and these immunological changes were more likely to be associated with the infection in lymphocytes rather than tumor cells. Moreover, in patients with HPV-positive CSCC, similar significant differences were still found. In conclusions, EBV-positive CSCC may have specific infection pattern and clinicopathology and can exhibit an immunosuppressive microenvironment dominated by Treg cells aggregation and immune checkpoint activation.

Tunable dual quasi-bound states in continuum and electromagnetically induced transparency enabled by the broken material symmetry in all-dielectric compound gratings.

Dual quasi-bound states in continuum (quasi-BICs) enabled by the broken geometric symmetry offer an effective way to design high-quality photonic devices, yet challenged by tunable functionalities. Here we employ the material asymmetry originating from the tunable material property of phase-change materials to design quasi-BICs in all-dielectric compound gratings. We find the even and odd quasi-BICs are modulated by the geometric and material asymmetries, respectively, and this effect is ensured by two different types of structural symmetries in the compound structure. Particularly, tunable electromagnetically induced transparency (EIT) can be achieved by modulating the material asymmetry. Furthermore, we systematically design the compound gratings consisting of the phase-change material of Sb2Se3 to demonstrate tunable dual quasi-BICs and EITs. Analytical calculations and numerical simulations are performed to verify these findings. Our work provides a promising way to enhance the flexibility of realizing quasi-BICs, which may boost tunable applications in nanodevices assisted by quasi-BICs.

Controlling the directional excitation of surface plasmon polaritons using tunable non-Hermitian metasurfaces.

In this work, we propose an efficient approach to controlling the directional excitation of surface plasmon polaritons (SPPs) by dynamically modulating the real-part perturbation in a passive parity-time symmetric metasurface. This non-Hermitian system can experience two exceptional points that can induce two unidirectional excitation states of SPPs along opposite directions. Empowered by its superior modulation depth, the energy ratio and energy intensities of two excited SPP states can be effectively manipulated by this non-Hermitian metasurface. To demonstrate these findings, we design and numerically verify non-Hermitian metasurfaces integrated with an Sb2Se3 phase-change material. Our work provides a promising platform for the controllable engineering of SPP excitations, holding significant potential for the development of new plasmonic devices, including on-chip SPP sources, routers and sorters, and integrated optical circuits.

Dynamin-Related Protein 1 Binding Partners MiD49 and MiD51 Increased Mitochondrial Fission In Vitro and Atherosclerosis in High-Fat-Diet-Fed ApoE-/- Mice.

Novel components of the mitochondrial fission machinery, mitochondrial dynamics proteins of 49 kDa (MiD49) and 51 kDa (MiD51), have been recently described, and their potential therapeutic targets for treating cardiovascular disease have been shown, including acute myocardial infarction (AMI), anthracycline cardiomyopathy and pulmonary arterial hypertension (PAH). Here, we examined the role of MiD49 and MiD51 in atherosclerosis. MiD49/51 expression was increased in the aortic valve endothelial cells (ECs) of high-fat diet-induced atherosclerosis in ApoE-/-mice and IL-8-induced human umbilical vein endothelial cells (HUVECs), which accelerated dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Silencing MiD49/51 reduced atherosclerotic plaque size, increased collagen content, and decreased the IL-8-induced adhesion and proliferation of HUVECs. MiD51 upregulation resulted from decreased microRNA (miR)-107 expression and increased hypoxia-inducible factor-1a (HIF-1a) expression. Treatment with miR-107 mimics decreased atherosclerotic plaque size by reducing HIF-1α and MiD51 production. Both MiD49 and MiD51 were involved in atherosclerotic plaque formation through Drp1-mediated mitochondrial fission, and the involvement of MiD51 in this process was the result of decreased miR-107 expression and increased HIF-1α expression. The miR-107-HIF-1α-MiD51 pathway might provide new therapeutic targets for atherosclerosis.

Comparison of aprepitant versus desloratadine for EGFR-TKI-induced pruritus: A randomized phase 2 clinical trial.

BACKGROUND: Pruritus is one of the most common and challenging side effects of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and has impaired patients' quality of life and treatment compliance. Our study evaluated the efficacy and safety of aprepitant in managing EGFR-TKIs-related pruritus. METHODS: This randomized, double-blind, placebo-controlled study was conducted between December 2016 and August 2020 in China. Patients were eligible if they were 18 years or older and had histologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) with first onset of moderate to severe pruritus during EGFR-TKI treatment. RESULTS: A total of 130 eligible patients were randomly assigned to aprepitant (n = 65) or desloratadine (n = 65) groups. The median (interquartile range [Q1, Q3]) age was 63 (54, 70) years, and 79 (60.8%) were women. Mean visual analog scale scores at baseline were 6.35 (95% confidence interval [CI], 5.89-6.82) in the aprepitant group and 5.94 (95% CI, 5.56-6.32) in the desloratadine group. After 1 week of treatment, 33 (53.2%) patients responded to aprepitant, which was significantly higher than that of 14 (23.7%) patients responded to desloratadine (p = .001). Moreover, patients in the aprepitant group had a significantly shorter response time than patients in the desloratadine group (mean [days], 13.39 [95% CI, 11.08-15.70] vs. 16.67 [95% CI, 14.19-19.13], p = .04). The most frequent drug-related adverse events in aprepitant group and desloratadine were constipation and dry mouth, and all adverse events were grade 1-2. CONCLUSIONS: To the authors' knowledge, this is the first study to prospectively present that aprepitant elicited a better and faster response and mild toxicity for managing EGFR-TKI induced pruritus than desloratadine. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02646020.

Bufalin inhibits peritoneal dissemination of gastric cancer through endothelial nitric oxide synthase-mitogen-activated protein kinases signaling pathway.

Peritoneal dissemination threatens the survival of patients with gastric cancer (GC). Bufalin is an extract of traditional Chinese medicine, which has been proved to have anticancer effect. The target of bufalin in suppressing gastric cancer peritoneal dissemination (GCPD) and the underlying mechanism are still unclear. In this research, GC cell line MGC-803 and high-potential peritoneal dissemination cell line MKN-45P were treated with bufalin or L-NAME. Malignant biological behavior and protein level of GC cell lines were detected with MTT, wound healing, transwell, adhesion, and western blotting. Bioinformatics analysis and patient tissues were used to verify the role of endothelial nitric oxide synthase (NOS3) in GC. Mice model was used to assess the effect of bufalin and role of NOS3 in vivo. We found that bufalin inhibited the proliferation, invasion, and migration in GC cell lines. NOS3, which was an independent prognostic factor of GC patients, was predicted to be a potential target of bufalin. Further experiments proved that bufalin reduced the phosphorylation of NOS3, thereby inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway, and ultimately suppressed GCPD by inhibiting EMT process. In conclusion, NOS3 was a potential therapeutic target and prognostic biomarker of GC. Bufalin could suppress GCPD through NOS3-MAPK signaling pathway, which provided more evidence support for intraperitoneal perfusion of bufalin to treat GCPD.

Development and validation of self-management scale for tuberculosis patients.

BACKGROUND: Tuberculosis remains a major threat to global public health. Regarding its control, directly observed therapy is not suitable as a global strategy for all tuberculosis patients. Self-management may be an important patient-centered tuberculosis case management supplement to directly observed therapy. However, there is currently no well-established instrument for measuring the self-management of tuberculosis patients. This study aimed to develop and validate a self-management scale for tuberculosis patients. METHODS: We developed an initial scale based on the tuberculosis health promotion indicators framework developed by our research group. After item analysis and two rounds of exploratory factor analysis, a final version of the scale was developed. A survey of 462 tuberculosis patients was conducted to develop and validate this scale. Cronbach's α and intraclass correlation coefficients were used to assess reliability, and Pearson's correlation coefficients were used to evaluate content validity. Fit indices, convergent validity, and discriminant validity were evaluated using confirmatory factor analysis to determine the construct validity of the scale. RESULTS: The scale was composed of 17 items in three dimensions ("adherence to treatment behavior," "transmission prevention behavior," and "supportive therapy behavior"). These three dimensions explained 76.60% of the variance. Cronbach's α of the scale was 0.905, and the intraclass correlation coefficient was 0.897. Additionally, Pearson's correlation analysis showed that each item was strongly correlated with the dimension to which it belonged (r = 0.849-0.915, p < 0.01). Most fit indices (Comparative Fit Index, Normed Fit Index, Incremental Fit Index, Goodness of fit index) reached the recommended threshold, and the average variance extracted values of the three dimensions were higher than 0.5. The values of the square root of the average variance extracted within each dimension were greater than the correlation between dimensions, and all heterotrait-monotrait values were below 0.85. CONCLUSIONS: The self-management scale for tuberculosis patient demonstrated good reliability and validity and could be used as an instrument to evaluate the self-management of patients. Additionally, it could be used to develop evidence-based self-management interventions and evaluate those interventions.

Factors predicting self-report adherence (SRA) behaviours among DS-TB patients under the "Integrated model": a survey in Southwest China.

BACKGROUND: China is one of 30 countries with a high tuberculosis (TB) burden, and poor adherence to TB treatment is one of the biggest challenges for TB control. We aimed to explore the barriers and facilitators of treatment adherence among drug-sensitive tuberculosis (DS-TB) patients under the "Integrated model" in Western China, to provide evidence-based treatment and control regimens for DS-TB patients to improve adherence behaviours. METHODS: Both qualitative and quantitative research methods were used to explore the factors associated with self-reported adherence (SRA) behaviours. Questionnaire surveys with DS-TB patients and in-depth interviews with leaders from the Centers for Disease Control and Prevention (CDC) and community health sectors (CHCs), healthcare workers (HCWs) from CHCs, and DS-TB patients were conducted. RESULTS: A total of 459 eligible patients were included in the quantitative survey, and two patients and 13 healthcare providers were included in the in-depth interviews. The percentage of patients who experienced a missed dose, lack of follow-up sputum examination, and interrupted treatment were 19.0%, 11.3%, and 9.2%, respectively. Patients aged 20-39 had a higher risk of missed dose [OR (95% CI): 2.302 (1.001-5.305)] and a lower risk of interrupted treatment [OR (95% CI): 0.278 (0.077-0.982)] than patients more than 60 years. Patients who were of Han ethnicity (OR [95% CI]: 0.524 [0.301-0.912]) received psychological support (OR [95% CI]: 0.379 [0.144-0.998]) from their family and had a lower risk of missed doses. Patients who had drug side effects had a higher risk of interrupted treatment (OR [95% CI]: 2.587 [1.237-5.412]). Patients who possessed higher knowledge had a lower risk of lack of follow-up sputum examination [OR (95% CI): 0.817 (0.673-0.991)]. The results of the qualitative study also reported that patients' poor TB knowledge was the main reason for their non-SRA behaviours. CONCLUSIONS: Patient-centred strategies should be implemented to improve health literacy and strengthen psychological support. More effective case management should be designed and implemented based on different patient characteristics to improve adherence behaviours in further studies.

miR-1290 promotes IL-8-mediated vascular endothelial cell adhesion by targeting GSK-3ß.

BACKGROUND: MicroRNA-1290 (miR-1290) has been reported to be involved in many diseases and play a key role during the development process. However, the role of miR-1290 in atherosclerosis (AS) is still unclear. METHODS AND RESULTS: The current study showed that the expressions of miR-1290 were high in serum of patients with hyperlipidemia. The functional role of miR-1290 were then investigated in human umbilical vein endothelial cells (HUVECs). Here, we found that miR-1290 expressions were notably enhanced in HUVECs mediated by IL-8. miR-1290 inhibitor repressed monocytic THP-1 cells adhesion to HUVECs by regulating ICAM-1 and VCAM-1, inhibited proliferation through regulating cyclinD1 and PCNA, and inhibited inflammatory response by regulating IL-1ß. Mechanistically, we verified that miR-1290 mimic was able to directly target the 3'-UTR of GSK-3ß mRNA using luciferase reporter assay. Knockdown of GSK-3ß (si-GSK-3ß) promoted HUVECs adhesion and the expression of IL-1ß, and partially restore the depression effect of miR-1290 inhibitor on HUVECs adhesion and inflammation. In contrast, si-GSK-3ß inhibited the proliferation of HUVECs and the expression of cyclinD1 and PCNA. CONCLUSIONS: In summary, our study revealed that miR-1290 promotes IL-8-mediated the adhesion of HUVECs by targeting GSK-3ß. However, GSK-3ß is not the target protein for miR-1290 to regulate the proliferation of HUVECs. Our findings may provide potential target in atherosclerosis treatment.

Analysis of Muscular Electrical Activity and Blood Perfusion of Upper Extremity in Patients with Hemiplegic Shoulder Pain: A Pilot Study.

Background: Hemiplegic shoulder pain (HSP) is a common symptom for post-stroke patients, which has a severely adverse impact on their rehabilitation outcomes. However, the cause of HSP has not been clearly identified due to its complicated multifactorial etiologies. As possible causes of HSP, the abnormality of both muscular electrical activity and blood perfusion remains lack of investigations. Objective: This study aimed to analyze the alteration of muscular electrical activity and blood perfusion of upper extremity in patients with HSP by using surface electromyography (sEMG) and laser speckle contrast imaging (LSCI) measurement techniques, which may provide some insight into the etiology of HSP. Methods: In this observational and cross-sectional study, three groups of participants were recruited. They were hemiplegic patients with shoulder pain (HSP group), hemiplegic patients without shoulder pain (HNSP group), and healthy participants (Healthy group). The sEMG data and blood perfusion data were collected from all the subjects and used to compute three different physiological measures, the root-mean-square (RMS) and median-frequency (MDF) parameters of sEMG recordings, and the perfusion unit (PU) parameter of blood perfusion imaging. Results: The RMS parameter of sEMG showed significant difference (p < 0.05) in the affected side between HSP, HNSP, and Healthy groups. The MDF parameter of sEMG and PU parameter of blood perfusion showed no significant difference in both sides among the three groups (p > 0.05). The RMS parameter of sEMG showed a statistically significant correlation with the pain intensity (r = -0.691, p =0.012). Conclusion: This study indicated that the muscular electrical activity of upper extremity had a correlation with the presence of HSP, and the blood perfusion seemed to be no such correlation. The findings of the study suggested an alternative way to explore the mechanism and treatment of HSP.

Interfacial Super-Assembly of T-Mode Janus Porous Heterochannels from Layered Graphene and Aluminum Oxide Array for Smart Oriented Ion Transportation.

Salinity gradient energy existing in seawater and river water is a sustainable and environmentally energy resource that has drawn significant attention of researchers in the background of energy crisis. Nanochannel membrane with a unique nano-confinement effect has been widely applied to harvest the salinity gradient energy. Here, Janus porous heterochannels constructed from 2D graphene oxide modified with polyamide (PA-GO) and oxide array (anodic aluminum oxide, AAO) are prepared through an interfacial super-assembly method, which can achieve oriented ion transportation. Compared with traditional nanochannels, the PA-GO/AAO heterochannels with asymmetric charge distribution and T-mode geometrical nanochannel structure shows directional ionic rectification features and outstanding cation selectivity. The resulting heterochannel membrane can achieve a high-power density of up to 3.73 W m-2 between artificial seawater and river water. Furthermore, high energy conversion efficiency of 30.3% even in high salinity gradient can be obtained. These achievable results indicate that the PA-GO/AAO heterochannels has significant potential application in salinity gradient energy harvesting.

Extraordinary wave modes in purely imaginary metamaterials beyond the critical angle.

When waves are incident from a high-index medium to a low one, total reflection occurs commonly for the incidence beyond the critical angle. However, this common sense is broken by a purely imaginary metamaterial (PIM), which also supports a real refraction index yet with pure loss and gain elements in their permittivity and permeability. We find that even beyond the critical angle of a lower-index PIM slab, some extraordinary wave modes including laser, anti-laser, perfect attenuator and perfect amplifier can appear. The general conditions of these wave modes are theoretically given out and the underlying mechanisms are revealed. Also, we study the influence of incident polarizations, geometric thickness and the parameters of the PIM slab on these extraordinary wave modes, with more wave propagation behaviors discovered.

Distributed refractive index sensing based on bending-induced multimodal interference and Rayleigh backscattering spectrum.

A distributed refractive index (RI) sensor based on high-performance optical frequency domain reflectometry was developed by bending a piece of standard single-mode fiber to excite sets of higher-order modes that penetrate the surrounding medium. External variations in RI modifies the profiles of the sets of excited higher-order modes, which are then partially coupled back into the fiber core and interfere with the fundamental mode. Accordingly, the fundamental mode carries the outer varied RI information, and RI sensing can be achieved by monitoring the wavelength shift of the local Rayleigh backscattered spectra. In the experiment, an RI sensitivity of 39.08 nm/RIU was achieved by bending a single-mode fiber to a radius of 4 mm. Additionally, the proposed sensor maintains its buffer coating intact, which boosts its practicability and application adaptability.

Enhanced and unidirectional photonic spin Hall effect in a plasmonic metasurface with S4 symmetry.

In this Letter, we report the significant enhancement of the photonic spin Hall effect (SHE) in a plasmonic metasurface with ${\rm S}_4$ symmetry. We find that an enhanced SHE of reflected light can occur in both horizontally and vertically polarized incident beams, and the maximum transverse displacement can approach half of the beam waist. Such a large displacement is caused by the non-resonant and near-zero pseudo-Brewster angles in the plasmonic metasurface. Owing to ${\rm S}_4$ symmetry, a unidirectional SHE is obtained in the metasurface, i.e., large and tiny transverse displacements are realized for a linearly polarized beam incident from the opposite side. This Letter provides a new, to the best of our knowledge, way to achieve an enhanced photonic SHE and offers more opportunities for designing spin-based nanophotonic devices.

Multi-Modal Adaptive Fusion Transformer Network for the Estimation of Depression Level.

Depression is a severe psychological condition that affects millions of people worldwide. As depression has received more attention in recent years, it has become imperative to develop automatic methods for detecting depression. Although numerous machine learning methods have been proposed for estimating the levels of depression via audio, visual, and audiovisual emotion sensing, several challenges still exist. For example, it is difficult to extract long-term temporal context information from long sequences of audio and visual data, and it is also difficult to select and fuse useful multi-modal information or features effectively. In addition, how to include other information or tasks to enhance the estimation accuracy is also one of the challenges. In this study, we propose a multi-modal adaptive fusion transformer network for estimating the levels of depression. Transformer-based models have achieved state-of-the-art performance in language understanding and sequence modeling. Thus, the proposed transformer-based network is utilized to extract long-term temporal context information from uni-modal audio and visual data in our work. This is the first transformer-based approach for depression detection. We also propose an adaptive fusion method for adaptively fusing useful multi-modal features. Furthermore, inspired by current multi-task learning work, we also incorporate an auxiliary task (depression classification) to enhance the main task of depression level regression (estimation). The effectiveness of the proposed method has been validated on a public dataset (AVEC 2019 Detecting Depression with AI Sub-challenge) in terms of the PHQ-8 scores. Experimental results indicate that the proposed method achieves better performance compared with currently state-of-the-art methods. Our proposed method achieves a concordance correlation coefficient (CCC) of 0.733 on AVEC 2019 which is 6.2% higher than the accuracy (CCC = 0.696) of the state-of-the-art method.

The genetic sequence, origin, and diagnosis of SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new infectious disease that first emerged in Hubei province, China, in December 2019, which was found to be associated with a large seafood and animal market in Wuhan. Airway epithelial cells from infected patients were used to isolate a novel coronavirus, named the SARS-CoV-2, on January 12, 2020, which is the seventh member of the coronavirus family to infect humans. Phylogenetic analysis of full-length genome sequences obtained from infected patients showed that SARS-CoV-2 is similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as SARS-CoV. The possible person-to-person disease rapidly spread to many provinces in China as well as other countries. Without a therapeutic vaccine or specific antiviral drugs, early detection and isolation become essential against novel Coronavirus. In this review, we introduced current diagnostic methods and criteria for the SARS-CoV-2 in China and discuss the advantages and limitations of the current diagnostic methods, including chest imaging and laboratory detection.

Cause-specific death assessment of patients with stage I small-cell lung cancer: a competing risk analysis.

Aim: Stage I small-cell lung cancer (SCLC) is a potentially curable disease that needs timely and multidisciplinary management. The aim of this study was to evaluate the probability of cause-specific mortality for patients with stage I SCLC. Material & methods: We identified patients in the SEER database and constructed a proportional subdistribution hazard model to evaluate cancer-specific mortality. A nomogram was built based on Fine and Gray competing risk regression model. Results: A total of 864 stage I SCLC patients were identified. The 5-year cumulative incidence of SCLC-specific mortality was 56.2%, while that for other causes of death was 17.3%. The c-index for the prognostic prediction model was 0.66. Besides, the nomogram was well calibrated. Conclusion: Our nomogram might serve as a reference for clinicians when evaluating the prognosis of stage I SCLC.

Association between glycosylated hemoglobin A1c and bone biochemical markers in type 2 diabetic postmenopausal women: a cross-sectional study.

BACKGROUND: type 2 diabetes mellitus (T2DM) is a complicated disease that can affect bone health, but the change in bone biochemical markers caused by T2DM was controversial, so the aim of this study was to investigate whether there was a discrepancy in the levels of bone biochemical markers between postmenopausal women with T2DM and non-diabetic women and to explore the relationship between the level of glycosylated hemoglobin A1c (HbA1c) and bone biochemical markers in these subjects. METHODS: A total of 237 type 2 diabetic postmenopausal women visiting the First Affiliated Hospital of Anhui Medical University from January 2017 to October 2018 and 93 healthy postmenopausal women were retrospectively enrolled. The differences in the levels of bone biochemical markers between patients and controls were analyzed by one-way ANOVA or chi-square test. The relationship between HbA1c and bone biochemical markers was analyzed by multivariate regression, forest plot and fitted curve. RESULTS: Bone formation markers including N-MID osteocalcin and procollagen type 1 amino-terminal pro-peptide (PINP) were decreased in postmenopausal women with T2DM compared to controls (17.42 ± 9.50 vs 23.67 ± 7.58, p < 0.001; 48.47 ± 27.27 vs 65.86 ± 21.06, p < 0.001, respectively), but the bone resorption markers ß-crossLaps (ß-CTX) was no difference between the two groups (0.57 ± 0.28 vs 0.55 ± 0.21, p = 0.868). Multivariate regression showed that HbA1c was inversely associated with N-MID osteocalcin and PINP after adjusting for age, BMI, menopause's years, diabetic duration, TC, TG, HDL-c, LDL-c, creatinine, UA and eGFR. The adjusted coefficients for N-MID osteocalcin and PINP per 1% HbA1c decrease were - 0.71 (- 1.19, - 0.22) and - 1.79 (- 3.30, - 0.28), respectively. A segmentation effect was seen in the fitted curve between HbA1c and ß-CTX with an inflection point at 7.4% of HbA1c, the highest quartile of ß-CTX (> = 0.74 ng/ml) showed a significantly negative with HbA1c. No significant association was seen between HbA1c and other biochemical markers. CONCLUSIONS: Our study found that bone formation was inhibited in postmenopausal women with T2DM, but bone resorption was not affected, and poor glycemic control was related to lower levels of bone formation, may increase the risk of bone fracture in postmenopausal women with T2DM.

[Preventive effects of lutein on liver toxicity in mice induced by arsenic].

OBJECTIVE: To explore the intervention effects of lutein on liver toxicity in mice induced by arsenic trioxide (As2O3) and to evaluate the preventive effect and the antioxidant mechanism of lutein. METHODS: A total of 84 healthy KM mice were randomly divided into eight groups. There were 35 d control group, 70 d control group, 35 d lutein group, 70 d lutein group, arsenic exposure group, lutein treatment group and lutein prevention group. The activity and level of AST, ALT, T-AOC, MDA, GSH, SOD, NO in liver tissue were measured by kits. Compares the difference between each group of the single factor analysis of variance. RESULTS: The activity of ALT, AST and the contents of MDA of 70 d control group were significantly lower than that arsenic exposure group. The contents of GSH, T-AOC, NO and the activity of SOD of 70 d control group were increased significantly than arsenic exposure group. The activity of ALT, AST and the contents of MDA of lutein prevention group were significantly lower than that lutein treatment group. The contents of GSH, T-AOC, NO and the activity of SOD of lutein prevention group were increased significantly than lutein treatment group. The differences were statistically significant (P < 0.05). CONCLUSION: Lutein can improve antioxidation function and has protective effect on liver injury of mice induced by arsenic.