Assessment of macular choroidal and retinal thickness: a cohort study in Tibetan healthy children.

This research investigates the distribution, progressive changes, and contributing factors of macular choroidal and retinal thickness in Tibetan children utilizing swept-source optical coherence tomography (SS-OCT). The Lhasa childhood study recruited 1632 students from seven primary schools in Lhasa. These participants underwent OCT and ophthalmological evaluations, encompassing retinal and choroidal thickness measurements, refractive error, axial length (AL), and systemic examinations. The median age of the scholars was 8.57 ± 0.50 years with a median spherical equivalent (SE) of 0.19 ± 1.28D. Multivariate regression analysis revealed that thinner macular choroid thickness was correlated with lower value of SE, worse best-corrected visual acuity, higher mean arterial blood pressure (MABP) and boys, while retinal thickness was associated with better image quality and lower value of SE. The choroid and retina were significantly thinner in myopic children. SE was positively related to the thickness of all choroidal and full retinal subregions. In comparison to baseline data from 20 months prior, most regions of the full retina had significantly thinned. Choroidal thickness of Tibetan children is thinner than that of same-age children from other regions. Thinning of retina, the outer-sector GCC and GCIPL may be specified as a follow-up and prognostic indicator for myopia.

Integrated treatment guided by RNA-seq-based endometrial receptivity assessment for infertility complicated by MEN1.

Background: Preimplantation genetic testing (PGT) serves as a tool to avoid genetic disorders in patients with known genetic conditions. However, once a selected embryo is transferred, implantation success is attained independent of embryo quality. Using PGT alone is unable to tackle implantation failure caused by endometrial receptivity (ER) abnormalities in these patients. Methods: We validated our newly developed RNA-seq-based ER test (rsERT) in a retrospective cohort study including 511 PGT cycles and reported experience in treating an infertile female patient complicated by multiple endocrine neoplasia type 1 (MEN1). Results: Significant improvement in the clinical pregnancy rate was found in the performed personalized embryo transfer (pET) group (CR, 69.7%; P = 0.035). In the rare MEN1 case, pET was done according to the prediction of the optimal time of window of implantation after unaffected blastocysts were obtained by PGT-M, which ultimately led to a healthy live birth. However, none of the mRNA variants identified in the patient showed a strong association with the MEN1 gene. Conclusions: Applying the new rsERT along with PGT improved ART outcomes and brought awareness of the importance of the ER examination in MEN1 infertile female patients. MEN1-induced endocrine disorder rather than MEN1 mutation contributes to the ER abnormality. Trial Registration: Reproductive Medicine Ethics Committee of Xiangya Hospital Registry No.: 2022010.

A Markov model-based cost-effectiveness analysis comparing zanubrutinib to ibrutinib for treating relapsed and refractory chronic lymphocytic leukemia.

OBJECTIVE: This article examined the cost-effectiveness of zanubrutinib and ibrutinib for managing relapsed and refractory chronic lymphocytic leukemia from the viewpoint of payers in China and the US. METHODS: Markov models were employed to conduct comparisons. Baseline characteristics and clinical data were extracted from the ALPINE study. The cost-effectiveness outcome indicators encompassed cost, quality-adjusted life years, and the incremental cost-effectiveness ratio. RESULTS: The Markov model analysis revealed that the zanubrutinib group incurred an incremental cost per patient of $-24,586.53 compared to the ibrutinib group. The zanubrutinib group exhibited an incremental utility per capita of 0.28 quality-adjusted life years, resulting in an incremental cost-effectiveness ratio of $-88,068.16 per quality-adjusted life year, which is lower than the payment threshold in China. The willingness-to-pay value in China for 2022 was three times the country's gross domestic product per capita. In the US, patients in the zanubrutinib group experienced per capita incremental costs of $-79,421.56, per capita incremental utility of 0.28 quality-adjusted life years, and an incremental cost-effectiveness ratio of $-284,485.45 per quality-adjusted life year. CONCLUSION: For Chinese payers, zanubrutinib exhibited superior cost-effectiveness compared to ibrutinib. Zanubrutinib proved to be a more affordable option for US payers when considering the payment threshold.

Mortality-to-Incidence Ratio for Nasopharyngeal Carcinoma Is Associated with Health Expenditure.

Geographic and gender-specific disparity can be observed in nasopharyngeal carcinoma (NPC). While screening and more effective therapies, such as induction chemotherapy, could improve survival rates, they are costly. This study aims to explore the correlation between healthcare expenditure and the mortality-to-incidence ratio (MIR) in NPC. Data were obtained from the World Health Organization and the Global Cancer Observatory. The correlation was evaluated by Spearman's rank correlation coefficient. Most new cases and deaths occur in Asia, and more males are affected than females. Our study shows that countries with higher MIRs have lower levels of health expenditure regardless of the NPC's gender-specific incidence. Correspondingly, MIRs are all significantly negatively associated with current health expenditure (CHE) per capita and CHE as a percentage of gross domestic product (CHE/GDP) in both genders. CHE per capita and CHE/GDP have a significant impact on NPC outcomes. Moreover, economic status is a potential major factor in MIR differences between countries.

Monoterpene-flavonoid conjugates from Sarcandra glabra and their autophagy modulating activities.

Fourteen new monoterpene-flavonoid conjugates including four monoterpene-conjugated chalcones (glabratins A-D, 1-4), seven monoterpene-conjugated dihydrochalcones (glabratins E-K, 5-11), and three monoterpene-conjugated flavanones (glabratins L-N, 12-14), together with four known analogues (15-18) were isolated from the aerial parts of Sarcandra glabra. The structures and the absolute configurations of these compounds were elucidated by the spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1, 4-6, 9-14, and 18 showed obvious cell autophagy-inducing activities at 25 µM in HEK293 cells. Furthermore, the bioassay results also showed that 18 induced cell autophagy in a dose dependent manner. Our findings revealed a rare class of monoterpene-flavonoid conjugates in nature and firstly reported their autophagy-inducing activities.

Ecological risk assessment of wetland vegetation under projected climate scenarios in the Sanjiang Plain, China.

Wetland ecosystems have comprehensive ecological functions and are sensitive to climate change. Under climate change, wetlands plant community productivity and diversity may be affected. In previous studies of wetlands, the effects of climate change have been primarily investigated using field observations, factor-controlled experiments, and mechanism analyses. However, the ecological risks to wetland communities under potential long-term climate change on a regional scale remain uncertain. The Sanjiang Plain is the largest area of natural marsh wetlands and the national ecological functions in China. In this study, the changes in plant productivity and diversity of wetland ecosystems in the Sanjiang Plain were simulated under different climate change scenarios (i.e., Representative Concentration Pathways, RCP 2.6, RCP4.5, RCP6.0, and RCP8.5), and the rank of spatiotemporal risk on a regional scale was estimated using a pressure-state-response model. Temperature and precipitation had average rates of increase of 0.44 °C/10a and 12.13 mm/10a, respectively, under different climate change scenarios to 2050. The fluctuation range in climatic factors was largest under the RCP8.5 scenario. On a long-term scale, compared with the base year of 2010, vegetation productivity increased significantly under the RCP2.6 scenario, remained almost constant under RCP4.5 and RCP6.0 scenarios, and decreased under the RCP8.5 scenario. In contrast to productivity, plant diversity increased under all four scenarios, but the range of increase gradually decreased with the increase in scenarios. Spatially, a fluctuation range change in precipitation was one of the important factors that caused high risks to regional wetlands. In the northwest of the Sanjiang Plain, most wetlands were assessed as high risk at level-3. In the other regions, the risks were lower with the values below level-2, and only a few places were assessed at risk level-3. In national wetland nature reserves, the northeast of the Qixing River, Xingkai Lake, and the Dongfanghong Marsh wetland area were ranked as high risk at level-3. These findings suggest that wetland protection and management should be focus on hydrological allocation and the potential ecological risks to national wetland nature reserves. However, a joint risk assessment of climate change and human activity should be conducted to provide a comprehensive reference for the protection and development of natural marsh wetlands.

An Assessment of Chinese Pathways to Implement the UN Sustainable Development Goal-11 (SDG-11)-A Case Study of the Yangtze River Delta Urban Agglomeration.

Urban sustainability is a crucial part of the United Nations (UN) Sustainable Development Goals (SDGs) and one of the core objectives of China's national strategy to promote new urbanization and achieve integration in the Yangtze River Delta (YRD). This paper mainly focused on the 11th SDG, which is a universal call to make cities and human settlements inclusive, safe, resilient and sustainable. The full permutation polygon synthetic indicator (FPPSI) method was applied to synthetically evaluate the sustainable level of 26 cities in the YRD urban agglomeration from 2007 to 2016. The results showed that: (1) the synthesis indicators were increasing year by year, which implied that the sustainable development of the YRD has shown obvious progress in recent years. However, each city faced its own challenges to achieving the sustainable development goals. The sustainability level for the majority of cities was restricted by obstacles such as the per capita green area, air quality and commercial housing sales area; (2) Among the 26 cities, small and medium-sized cities were subject to the traditional strong sustainability indicators while large and mega cities were more affected by weak sustainability indicators; (3) Spatial differences were found for the overall sustainable development level of the YRD. The diffusion and assembly effect among cities had not yet been formed; however, the strong spillover effect of developed cities might influence the ability of other cities to achieve sustainable development goals in many aspects of the environment, economy and society. The results suggest the need for a stronger focus on improving regional developing patterns and strengthening coordination in the process of achieving the sustainable development goal of urban agglomeration in the YRD. Furthermore, according to the conditions of different cities, integrated policies are required to address all aspects of sustainability and to avoid unintended consequences.

Assessment of the effect of methyl-triclosan and its mixture with triclosan on developing zebrafish (Danio rerio) embryos using mass spectrometry-based metabolomics.

Methyl-triclosan (MTCS), as a biodegradation product from antibacterial triclosan (TCS), has been detected in water catchments, and it has also been verified to accumulate in biota due to its hydrophobicity. There is a lack, however, of toxicity studies on MTCS and its effects on organisms in conjunction with TCS. In this study, exposure experiments were conducted to assess the toxicity to embryonic zebrafish of selected concentrations of MTCS (from 1 ng/L to 400 µg/L) and MTCS/TCS mixtures (from 1 µg/L TCS and 100 ng/L MTCS to 300 µg/L TCS and 30 µg/L MTCS). Specimens were extracted using acetonitrile: isopropanol: water (3:3:2; v/v/v) and then analyzed using Gas chromatography-mass spectrometry (GC-MS) to identify the metabolites based on the Fiehn library database. The results showed that MTCS exposure led to the alterations of the metabolomes of the zebrafish embryos, including level changes of l-valine, d-mannose, d-glucose, and other metabolites. Multivariate analysis (PCA, PLS-DA, sPLS-DA) and univariate analysis (one-way ANOVA) indicated differences between the control and exposure groups of the metabolites, indicating that biological pathways, such as amino acid synthesis, pentose phosphate pathway (PPP), starch and sucrose metabolism were influenced. Moreover, when the embryos were exposed to a mix of TCS and MTCS, TCS dominated the mixture's effect on biological pathways because the concentration ratio within the mixture, which mimics environmental ratio of 10 TCS : 1 MTCS, leads to high bioavailability of TCS.

A decision tree-based prediction model for fluorescence in situ hybridization HER2 gene status in HER2 immunohistochemistry-2+ breast cancers: a 2538-case multicenter study on consecutive surgical specimens.

Objective: To investigate the proportion of HER2 gene amplifications and the association between the HER2-IHC-staining pattern and gene status in IHC-2+ breast cancers according to 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Methods: We retrospectively analyzed and re-evaluated the IHC-staining pattern of 2538 IHC-2+ surgical specimens of breast cancer from November 2014 to October 2015 in 12 institutions. All cases used for building a prediction model of HER2 gene amplification according to the IHC-staining pattern and were randomly divided into a training set (n = 1914) or validation set (n = 624). Results: The overall HER2 fluorescence in situ hybridization (FISH) amplification, non-amplification and equivocation rates in HER2 IHC-2+ cases were 17.8%, 76.2% and 6.0%, respectively. In the training set, cases that had ≤ 10% of cells with intense, complete and circumferential membrane staining or had > 85% of cells with complete membrane staining of any staining intensity tended to be HER2 gene amplified (77.0% and 60.5%, respectively). And cases with weak and incomplete membrane staining had the lowest amplification rate of 6.1%. The prediction model was constructed based on IHC-staining pattern in the training set and validated using a validation set. The positive and negative prediction values were 51.6% and 79.2%, respectively, in the validation set. Moreover, the HER2 copy number per cell was much higher in cases with amplification-associated staining patterns (7.84 and 8.75) than in cases with non-amplification-associated staining patterns (2.97 to 4.41, P < 0.05). Conclusions: In HER2 IHC-2+ breast cancers, the staining pattern is associated with the HER2 gene status. This finding is compatible with recommendations of 2013 ASCO/CAP guidelines.

Comparison of the Efficacy, Side Effects, and Cost of Modafinil and Intranasal Mometasone Furoate in Obstructive Sleep Apnea-Hypopnea Syndrome: A Preliminary Clinical Study.

BACKGROUND Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by repeated episodes of reduction in airflow due to the collapse of the upper airway during sleep. The aim of this study was to compare clinical outcome, side effects, and cost of treatment between modafinil and intranasal mometasone furoate in patients with OSAHS. MATERIAL AND METHODS Patients with OSAHS (N=250) were divided into two groups: the modafinil group (MG) (N=125) were treated with 100 mg modafinil twice a day; the intranasal mometasone furoate group (IMFG) (N=125) were treated with 100 µg of intranasal mometasone furoate in the evening. Quality of life, grading of OSAHS, plain-film radiography, the adenoidal-nasopharyngeal ratio (AN ratio), side effects, cost of treatment, and beneficial effects after discontinuation of treatment were evaluated for all patients. RESULTS Duration of sleep apnea was significantly reduced in the IMFG compared with the MG (p=0.0145, q=9.262). Modafinil and intranasal mometasone furoate both had moderate effects on improvement of the OSAHS score. The IMFG showed a significantly greater beneficial effect on the AN ratio when compared with the MG (p=0.0001, q=6.584). No adverse events of treatment with modafinil and intranasal mometasone furoate were reported. Cost of treatment and beneficial effect after discontinuation were both significantly greater for the IMFG compared with the MG. CONCLUSIONS The findings of this preliminary clinical study were that for patients diagnosed with OSAHS, night-time treatment with intranasal mometasone furoate was more effective than modafinil.

Nanoscale focused ion beam tomography of single bacterial cells for assessment of antibiotic effects.

Antibiotic resistance is a major risk to human health, and to provide valuable insights into mechanisms of resistance, innovative methods are needed to examine the cellular responses to antibiotic treatment. Focused ion beam tomography is proposed to image and assess the detailed three-dimensional (3D) ultrastructure of single bacterial cells. By iteratively removing slices of thickness in the order of 10 nm, high magnification 2D images can be acquired by scanning electron microscopy at single-digit nanometer resolution. In this study, Klebsiella pneumoniae was treated with polymyxin B, and 3D models of both cell envelope and cytoplasm regions containing the nucleoid and ribosomes were reconstructed. The 3D volume containing the nucleoid and ribosomes was significantly smaller, and the cell length along the longitudinal axis was extended by 40% in the treated cells, implying stress responses to the drug treatment. More than a 200% increase in protrusions per unit surface area on the cell envelope was observed in the curvature analysis after treatment. Experiments by conventional transmission electron microscopy and atomic force microscopy were also performed, followed by comparison and discussions. In conclusion, the proposed 3D imaging method and associated analysis provide a unique tool for the assessment of antibiotic effects on multidrug-resistant bacteria at nanometer resolution.

Low-cost silicone imaging casts for zebrafish embryos and larvae.

Due to their size and optical clarity, zebrafish embryos have long been appreciated for their usefulness in time-lapse confocal microscopy. Current methods of mounting zebrafish embryos and larvae for imaging consist mainly of mounting in low percentage, low melting temperature agarose in a Petri dish. Whereas imaging methods have advanced greatly over the last two decades, the methods for mounting embryos have not changed significantly. In this article, we describe the development and use of 3D printed plastic molds. These molds can be used to create silicone casts and allow embryos and larvae to be mounted with a consistent and reproducible angle, and position in X, Y, and Z. These molds are made on a 3D printer and can be easily and cheaply reproduced by anyone with access to a 3D printer, making this method accessible to the entire zebrafish community. Molds can be reused to create additional casts, which can be reused after imaging. These casts are compatible with any upright microscope and can be adapted for use on an inverted microscope, taking the working distance of the objective used into account. This technique should prove to be useful to any researcher imaging zebrafish embryos.