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Spectacle-based interventions for myopia control are appealing to parents and children due to their non-invasive nature. However, long-term efficacy results remain modest and do not account for high-risk children with early-onset myopia and fast progression. This paper presents the protocol of a trial designed to evaluate the efficacy of the new-generation Defocus Incorporated Multiple Segments (DIMS) spectacle lenses in slowing the progression of myopia in children with early-onset and fast myopia progression. This is a prospective, double-masked, active-controlled, randomised trial (ClinicalTrials.gov identifiers: NCT05888792 and NCT05888805). Participants are Chinese schoolchildren aged 4-12 years with myopia of at least -0.75 diopter (D) in both eyes and with fast progression (≥ 0.50 D per year) or fast axial growth (≥ 0.27 mm per year) in either or both eyes. They are age-stratified and randomly assigned to an experimental arm, a control arm or an auxiliary arm in a 1:1:1 ratio. The experimental arm receives new-generation DIMS spectacle lenses, while the control arm receives single-vision spectacle lenses. The control subjects will crossover to experimental lenses at the end of the first year, and all subjects will continue wearing experimental lenses in the second year. The auxiliary arm receives marketed DIMS spectacle lenses for two years. The primary and secondary outcome measures are the changes in cycloplegic objective refraction and axial length at 12 months from baseline. Peripheral refraction and choroidal thickness will also be monitored, and their relationships with myopia control efficacy will be explored. This study will provide insights into the efficacy of a new generation of DIMS technology for controlling myopia in children with early-onset and fast myopia progression, offering evidence-based practice for myopia management. ClinicalTrials.gov identifiers: NCT05888792 and NCT05888805.

The dynamics of phytoplankton biomass in the vertically mixed south-eastern part of the Bisan Strait, in the Seto Inland Sea of Japan, may be considered to be strongly dependent not only on nutrients but also on light status. This was investigated by examining variations in chlorophyll-a (Chl-a), nutrients, and Secchi-disc depth through high-frequency sampling (a mean of once every 1.7 days) at the same station from April to October 2019. Precipitation during the Japanese rainy season (East Asian monsoon rains) was associated with a decrease in salinity from 32 to 31 in late July. The highest concentration of dissolved inorganic nitrogen (DIN), the most deficient nutrient, also was recorded in late July in association with seasonal precipitation. However, the measured Chl-a peak (max. 4 μg l−1) in early August was not as high as expected, possibly due to low water clarity. A relatively small but substantial peak of DIN (max. 4 μM) was recorded in mid-August, which coincided with the passing of a typhoon. The small peak of DIN coupled with higher water clarity thereafter was followed by a phytoplankton bloom from mid-August to early September, at which the highest Chl-a (7 μg l−1) occurred. It is suggested that increased light penetration enhanced the efficiency of nutrient assimilation and thereby triggered the late-summer phytoplankton bloom. In contrast to the adjacent stratified areas, light rather than nutrient status appears to be the key determinant for the onset of phytoplankton blooms in the Bisan Strait.

AimsTo determine myopia progression in children who continued to wear the defocus incorporated multiple segments (DIMS) lenses or switched from single vision (SV) to DIMS lenses for a 1-year period following a 2-year myopia control trial.Methods128 children participated in this study. The children who had worn DIMS lenses continued to wear DIMS lenses (DIMS group), and children who had worn SV lenses switched to wear DIMS lenses (Control-to-DIMS group). Cycloplegic spherical equivalent refraction (SER) and axial length (AL) were measured at 6-month interval. Historical controls were age matched to the DIMS group at 24 months and used for comparing the third-year changes.ResultsOver 3 years, SER and AL changes in the DIMS group (n=65) were −0.52±0.69D and 0.31±0.26 mm; these changes were not statistically significant over time (repeated measures analysis of variance, p>0.05).SER (−0.04±0. 38D) and AL (0.08±0.12 mm) changes in the Control-to-DIMS group (n=55) in the third year were less compared with the first (mean difference=0.45 ± 0.30D, 0.21±0.11 mm, p<0.001) and second (0.34±0.30D, 0.12±0.10 mm, p<0.001) years.Changes in SER and AL in both groups over that period were significantly less than in the historical control group (DIMS vs historical control: mean difference=−0.18±0.42D, p=0.012; 0.08±0.15 mm, p=0.001; Control-to-DIMS versus historical control: adjusted mean differences=−0.30±0.42D, p<0.001; 0.12±0.16 mm, p<0.001).ConclusionsMyopia control effect was sustained in the third year in children who had used the DIMS spectacles in the previous 2 years and was also shown in the children switching from SV to DIMS lenses.

AimTo determine if ‘Defocus Incorporated Multiple Segments’ (DIMS) spectacle lenses slow childhood myopia progression.MethodsA 2-year double-masked randomised controlled trial was carried out in 183 Chinese children aged 8–13 years, with myopia between −1.00 and −5.00 D and astigmatism ≤1.50 D. Children were randomly assigned to wear DIMS (n=93) or single vision (SV) spectacle lenses (n=90). DIMS lens incorporated multiple segments with myopic defocus of +3.50 D. Refractive error (cycloplegic autorefraction) and axial length were measured at 6month intervals.Results160 children completed the study, n=79 in the DIMS group and n=81 in the SV group. Average (SE) myopic progressions over 2 years were −0.41±0.06 D in the DIMS group and −0.85±0.08 D in the SV group. Mean (SE) axial elongation was 0.21±0.02 mm and 0.55±0.02 mm in the DIMS and SV groups, respectively. Myopia progressed 52% more slowly for children in the DIMS group compared with those in the SV group (mean difference −0.44±0.09 D, 95% CI −0.73 to −0.37, p<0.0001). Likewise, children in the DIMS group had less axial elongation by 62% than those in the SV group (mean difference 0.34±0.04 mm, 95% CI 0.22 to 0.37, p<0.0001). 21.5% children who wore DIMS lenses had no myopia progression over 2 years, but only 7.4% for those who wore SV lenses.ConclusionsDaily wear of the DIMS lens significantly retarded myopia progression and axial elongation in myopic children. Our results demonstrated simultaneous clear vision with constant myopic defocus can slow myopia progression.Trial registration number NCT02206217.

The extracellular environment regulates the dynamic behaviors of cells. However, the effects of hydrostatic pressure (HP) on cell fate determination of mesenchymal stem cells (MSCs) are not clearly understood. Here, we established a cell culture chamber to control HP. Using this system, we found that the promotion of osteogenic differentiation by HP is depend on bone morphogenetic protein 2 (BMP2) expression regulated by Piezo type mechanosensitive ion channel component 1 (PIEZO1) in MSCs. The PIEZO1 was expressed and induced after HP loading in primary MSCs and MSC lines, UE7T-13 and SDP11. HP and Yoda1, an activator of PIEZO1, promoted BMP2 expression and osteoblast differentiation, whereas inhibits adipocyte differentiation. Conversely, PIEZO1 inhibition reduced osteoblast differentiation and BMP2 expression. Furthermore, Blocking of BMP2 function by noggin inhibits HP induced osteogenic maker genes expression. In addition, in an in vivo model of medaka with HP loading, HP promoted caudal fin ray development whereas inhibition of piezo1 using GsMTx4 suppressed its development. Thus, our results suggested that PIEZO1 is responsible for HP and could functions as a factor for cell fate determination of MSCs by regulating BMP2 expression.

Signal transmission from the mechanical forces to the various intracellular activities is a fundamental process during tissue development. Despite their critical role, the mechanism of mechanical forces in the biological process is poorly understood. In this study, we demonstrated that in the response to hydrostatic pressure (HP), the piezo type mechanosensitive ion channel component 1 (PIEZO1) is a primary mechanosensing receptor for odontoblast differentiation through coordination of the WNT expression and ciliogenesis. In stem cells from human exfoliated deciduous teeth (SHED), HP significantly promoted calcium deposition as well as the expression of odontogenic marker genes, PANX3 and DSPP , and WNT related-genes including WNT5b and WNT16 , whereas HP inhibited cell proliferation and enhanced primary cilia expression. WNT signaling inhibitor XAV939 and primary cilia inhibitor chloral hydrate blocked the HP-induced calcium deposition. The PIEZO1 activator Yoda1 inhibited cell proliferation but induced ciliogenesis and WNT16 expression. Interestingly, HP and Yoda1 promoted nuclear translocation of RUNX2, whereas siRNA-mediated silencing of PIEZO1 decreased HP-induced nuclear translocation of RUNX2. Taken together, these results suggest that PIEZO1 functions as a mechanotransducer that connects HP signal to the intracellular signalings during odontoblast differentiation.

Combined chemoradiotherapy (CRT) and programmed cell death‐ligand 1 (PD‐L1) blockade is a new care standard for unresectable stage III non‐small‐cell lung cancer (NSCLC). Although this consolidation therapy has improved the overall survival of patients with NSCLC, the synergistic action mechanisms of CRT and immunotherapy on T cells remain unclear. In addition, there is a paucity of reliable biomarkers to predict clinical responses to therapy. In this study, we analyzed T‐cell receptor (TCR) sequences in the peripheral blood of five patients with NSCLC. T‐cell receptor analysis was undertaken before treatment, after CRT, and after PD‐L1 blockade. Notably, we observed the expansion and alteration of the dominant T‐cell clonotypes in all cases with a complete response. In contrast, neither expansion nor alteration of the TCR repertoire was observed in cases with progressive disease. T cell expansion was initiated after CRT and was further enhanced after PD‐L1 blockade. Our findings suggest the systemic effect of CRT on circulating T cells in addition to the curative effect on limited tumor sites. Dynamic changes in circulating T‐cell clonotypes could have a prognostic significance for combined CRT and PD‐L1 blockade. This study analyzed TCR sequences in the peripheral blood of patients with NSCLC before and after combined chemoradiotherapy and PD‐L1 blockade. The analysis found the expansion of the dominant T‐cell clonotypes in the cases with a complete response. These findings suggest the systemic effect of CRT on circulating T cells, which may have a prognostic significance.

Background Although laparoscopic hepatectomy has increasingly been used to treat cancers in the liver, the accuracy of intraoperative diagnosis may be inferior to that of open surgery because the ability to visualize and palpate the liver surface during laparoscopy is relatively limited. Fluorescence imaging has the potential to provide a simple compensatory diagnostic tool for identification of cancers in the liver during laparoscopic hepatectomy. Methods In 17 patients who were to undergo laparoscopic hepatectomy, 0.5 mg/kg body weight of indocyanine green (ICG) was administered intravenously within the 2 weeks prior to surgery. Intraoperatively, a laparoscopic fluorescence imaging system obtained fluorescence images of its surfaces during mobilization of the liver. Results In all, 16 hepatocellular carcinomas (HCCs) and 16 liver metastases (LMs) were resected. Of these, laparoscopic ICG fluorescence imaging identified 12 HCCs (75 %) and 11 LMs (69 %) on the liver surfaces distributed over Couinaud’s segments 1–8, including the 17 tumors that had not been identified by visual inspections of normal color images. The 23 tumors that were identified by fluorescence imaging were located closer to the liver surfaces than another nine tumors that were not identified by fluorescence imaging (median [range] depth 1 [0–5] vs. 11 [8–30] mm; p  < 0.001). Conclusions Like palpation during open hepatectomy, laparoscopic ICG fluorescence imaging enables real-time identification of subcapsular liver cancers, thus facilitating estimation of the required extent of hepatic mobilization and determination of the location of an appropriate hepatic transection line.

Orthostatic intolerance (OI) is a key symptom of long COVID; however, the pathophysiology remains unknown. Among 688 long COVID patients who visited our clinic during the period from February 2021 to April 2023, 86 patients who were suspected of having OI and who underwent an active standing test (ST) were investigated to elucidate the clinical characteristics of OI in patients with long COVID. Of the 86 patients, 33 patients (38%) were ST-positive. Nausea and tachycardia in daily life were frequent complaints in the ST-positive group. The increase in heart rate (HR) during the ST was significantly greater during a 10-min period after standing in the ST-positive group (+ 30 bpm) than in the ST-negative group (+ 16 bpm). The initial increase in diastolic blood pressure (DBP) just after standing was significantly greater in the ST-positive group (+ 14 mmHg) than in the ST-negative group (+ 9 mmHg). Serum cortisol levels in the ST-positive patients aged over 20 years were higher and growth hormone levels in the patients under 20 years of age were lower than those in the ST-negative group. Autonomous nervous symptoms, transient DBP rise with increasing HR after standing, and endocrine dysfunctions are helpful for detecting OI related to long COVID.