Knockdown of EIF2AK2-OAS1 axis reduces ATP production inducing AMPK phosphorylation to inhibit the malignant behavior of gastric cancer cells.

Energy metabolism has always been a hot topic in cancer progression and targeted therapy, and exploring the role of genes in energy metabolic pathways in cancer cells has become key to address this issue. Eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) plays regulatory roles in cancer and disorders of energy metabolism. Indeed, the role of EIF2AK2 in energy metabolism has been underestimated. The aim of this study is to reveal the expression specificity of EIF2AK2 in gastric cancer (GC) progression and metastasis, and to demonstrate the role of EIF2AK2 in energy metabolism, cytoskeleton, proliferation, death and metastasis pathways in GC cells. Mechanistically, EIF2AK2 overexpression promoted cytoskeleton remodeling and ATP production, mediated cell proliferation and metastasis, upregulated OAS1 expression, decreases p-AMPK expression and inhibited apoptosis in GC cells. Conversely, knockdown of EIF2AK2 resulted in the opposite effect. However, overexpression of OAS1 mediated the upregulation of mitochondrial membrane potential and promoted ATP production and NAD+/NADH ratio, but knockdown of OAS1 inhibited the above effects. In addition, knockdown of OAS1 had no effect on EIF2AK2 expression, but inhibited AMPK and upregulated p-AMPK expression. In conclusion, our study identified EIF2AK2 and OAS1 as previously undescribed regulators of energy metabolism in GC cells. We hypothesized that EIF2AK2-OAS1 axis may regulate energy metabolism and inhibit cellular malignant behavior in cancer cells by affecting ATP production to induce AMPK phosphorylation, suggesting EIF2AK2 as a potential therapeutic target for cancer cell progression.

Hydromassage of macular hole edges for large and persistent full-thickness macular holes.

AIM: To introduce the macular hole (MH) hydromassage technique as a potentially beneficial approach for the treatment of large or persistent MH. METHODS: This retrospective observational case series comprised 16 consecutive patients (17 eyes) diagnosed with MH. Inclusion criteria involved a hole aperture diameter larger than 600 µm or the presence of an unclosed MH larger than 600 µm following the previous vitrectomy. Standard MH repair procedures were administered in all cases, involving the manipulation and aspiration of the hole margin through the application of water flow with a soft-tip flute needle. A comprehensive assessment was conducted for each case before and after surgery, and optical coherence tomography (OCT) images were captured at every follow-up point. RESULTS: The mean preoperative aperture diameter was 747±156 µm (range 611-1180 µm), with a mean base diameter of 1390±435 µm (range 578-2220 µm). Following surgery, all cases achieved complete anatomical closure of MH, with 13 cases (76.5%) exhibiting type 1 closure and 4 cases (23.5%) demonstrating type 2 closure. No significant differences were observed in the preoperative OCT variables between the two closure types. Eyes with type 1 closure showed a significantly improved visual acuity (0.70±0.10, range 0.50-0.80) compared to those with type 2 closure (0.90±0.12, range 0.80-1.00, P=0.014). CONCLUSION: The MH hydromassage technique demonstrates promising results, achieving acceptable closure rates in cases of large or persistent MH. This technique may serve as an effective adjunctive maneuver during challenging MH surgery.

A Review of Weak Gel Fracturing Fluids for Deep Shale Gas Reservoirs.

Low-viscosity slickwater fracturing fluids are a crucial technology for the commercial development of shallow shale gas. However, in deep shale gas formations with high pressure, a higher sand concentration is required to support fractures. Linear gel fracturing fluids and crosslinked gel fracturing fluids have a strong sand-carrying capacity, but the drag reduction effect is poor, and it needs to be pre-prepared to decrease the fracturing cost. Slick water fracturing fluids have a strong drag reduction effect and low cost, but their sand-carrying capacity is poor and the fracturing fluid sand ratio is low. The research and development of viscous slick water fracturing fluids solves this problem. It can be switched on-line between a low-viscosity slick water fracturing fluid and high-viscosity weak gel fracturing fluid, which significantly reduces the cost of single-well fracturing. A polyacrylamide drag reducer is the core additive of slick water fracturing fluids. By adjusting its concentration, the control of the on-line viscosity of fracturing fluid can be realized, that is, 'low viscosity for drag reduction, high viscosity for sand-carrying'. Therefore, this article introduces the research and application status of a linear gel fracturing fluid, crosslinked gel fracturing fluid, and slick water fracturing fluid for deep shale gas reservoirs, and focuses on the research status of a viscous slick water fracturing fluid and viscosity-controllable polyacrylamide drag reducer, with the aim of providing valuable insights for the research on water-based fracturing fluids in the stimulation of deep shale gas reservoirs.

Chronic restraint stress-induced hyperalgesia is modulated by the periaqueductal gray neurons projecting to the rostral ventromedial medulla in mice.

Stress-induced hyperalgesia (SIH) is induced by repeated or chronic exposure to stressful or uncomfortable environments. However, the neural mechanisms involved in the modulatory effects of the periaqueductal gray (PAG) and its associated loops on SIH development hav e not been elucidated. In the present study, we used chronic restraint stress (CRS)-induced hyperalgesia as a SIH model and manipulated neuronal activity via a pharmacogenetic approach to investigate the neural mechanism underlying the effects of descending pain-modulatory pathways on SIH. We found that activation of PAG neurons alleviates CRS-induced hyperalgesia; on the other hand, PAG neurons inhibition facilitates CRS-induced hyperalgesia. Moreover, this modulatory effect is achieved by the neurons which projecting to the rostral ventromedial medulla (RVM). Our data thus reveal the functional role of the PAG-RVM circuit in SIH and provide analgesic targets in the brain for clinical SIH treatment.

Sarcomatoid hepatocellular carcinoma: A case report and review of the literature.

RATIONALE: Sarcomatoid hepatocellular carcinoma (SHC) is a rare malignant tumor composed of both carcinoma and sarcoma components. It has atypical clinical symptoms and a high degree of malignancy, with rapid progression and a poor prognosis. PATIENT CONCERNS: A 63-year-old female patient was admitted to our hospital with a chief complaint of fatigue present for more than 1 month and fever for 10 days. DIAGNOSES: This patient underwent an upper abdominal MRI plain scan and enhanced scan showed a solid tumor in the right lobe of the liver, with a size of approximately 4.7 cm × 4.0 cm × 6.5 cm, present as low signal on T1WI, slightly high signal on T2WI, and heterogeneous high signal on DWI. Multi-phase dynamic contrast-enhanced MR scan showed significant enhancement in the arterial phase and low enhancement in the portal and delayed phases. The pathology showed the tumor cells to be positive for cytokeratin (CK), Vimentin, EMA, CD34, cyclinD1, negative for CK8, CK19, CK20, SMA, Desmin, S-100, CD117, Dog-1, Hepar-1, SOX-10 and ALK, and Ki-67 approximately 50%, which confirmed the diagnosis of SHC. INTERVENTIONS: Laparoscopic right posterior lobe of liver resection was conducted, and the postoperative pathology revealed the presence of SHC. OUTCOMES: The patient was discharged 9 days after the surgery without any complications. There has been no evidence of recurrence at the 1 month, however bilateral pleural metastases appeared during the follow-up 3 months after surgery. LESSONS: SHC is a rare and aggressive liver cancer. So far, there is still a lack of effective therapeutic strategy, and the prognosis was dismal even though patients received radical surgical resection.

The Impact of Vergence Dysfunction on Myopia Control in Children Wearing Defocus Spectacle Lenses.

Purpose: To investigate the impact of vergence dysfunction on myopia progression in children with Defocus incorporated multiple segments (DIMS) spectacle lenses. Patients and Methods: We retrospectively enrolled children prescribed DIMS spectacle lenses to slow myopic progression. Baseline vergence dysfunction was determined according to phoria at distance and near. Axial length (AL) measurement and cycloplegic subjective refraction were performed before fitting the lenses and at six-month and one-year follow-ups. The six-month and one-year AL and spherical equivalent (SE) change from baseline were calculated and compared in subgroups stratified with the type of vergence dysfunction. Results: Two hundred and ninety-two myopic children were included. Significant AL elongation and SE progression were observed at six months and one year (P < 0.05 for all comparisons). Multiple regression demonstrated that AL elongation at six months (P < 0.001) and one year (P < 0.001) was negatively correlated with age, and SE progression at six months was associated with age (P = 0.002). The AL elongation at six months in children with convergence excess was significantly greater than in normal myopic subjects (P = 0.011) and subjects with convergence insufficiency (P = 0.008), divergence excess (P = 0.007), divergence insufficiency (P = 0.024) and basic esophoria (P = 0.048) at six months. Conclusion: The present research demonstrated that vergence dysfunction influences myopia progression for myopic children with DIMS, and the children with convergence excess suffer from the greatest myopia progression among different types of vergence dysfunction.

High-throughput 3D microfluidic chip for generation of concentration gradients and mixture combinations.

Concentration gradient generation and mixed combinations of multiple solutions are of great value in the field of biomedical research. However, existing concentration gradient generators for single or two-drug solutions cannot simultaneously achieve multiple concentration gradient formations and mixed solution combinations. Furthermore, the whole system was huge, and required expensive auxiliary equipment, which may lead to complex operations. To address this problem, we devised a novel 3D microchannel network design, which is capable of creating all the desired mixture combinations and concentration gradients of given small amounts of the input solutions. As a proof of concept, the device we presented was verified by both colorimetric and fluorescence detection methods to test the efficiency. This can enable the implementation of one to three solutions with no driving pump and facilitate unique multiple types of more concentration gradients and mixture combinations in a single operation. We envision that this will be a promising candidate for the development of simplified methods for screening of the appropriate concentration and combination, such as various drug screening applications.

Comparison of the long-term effects of atropine in combination with Orthokeratology and defocus incorporated multiple segment lenses for myopia control in Chinese children and adolescents.

PURPOSE: The aim of this study was to evaluate the efficacy of Orthokeratology (Ortho-K), defocus incorporated multiple segment (DIMS) lens, combined Ortho-K/atropine, and combined DIMS/atropine for myopia control in children. METHODS: A retrospective study included 167 myopic children aged 6-14 years with a spherical equivalent refraction (SER) of -0.75 to -4.00 diopter treated with Ortho-K (OK, n = 41), combined Ortho-K/atropine (OKA, n = 43), DIMS (n = 41), or combined DIMS/atropine (DIMSA, n = 42). Axial length (AL) was measured at baseline and at 3, 6, 9 and 12 months. Axial elongation over time and between groups were analysed. RESULTS: After 12 months, the AL change was 0.20 ± 0.12 mm, 0.12 ± 0.14 mm, 0.22 ± 0.14 mm, and 0.15 ± 0.15 mm in the OK, OKA, DIMS, and DIMSA, respectively. There was no significant difference in AL change between OK and DIMS. OKA and DIMSA significantly slowed axial elongation compared to OK and DIMS monotherapy. After stratification by age, in the subgroup aged 6-10 years, there was significant difference in AL change between OKA and DIMS (p = 0.013), and no difference between other groups, while in the subgroup aged 10-14 years, the difference between OKA and DIMS became insignificant (p = 0.237), and the difference between OK and OKA, OK and DIMSA, DIMS and DIMSA became significant. CONCLUSIONS: Ortho-K and DIMS lenses show similar reductions in myopia progression among children with low initial myopia. Atropine can significantly improve the efficacy of myopia control of both Ortho-K and DIMS lenses, and this add-on effect is better in older children.

Development of Novel Silicon Quantum Dots and Their Potential in Improving the Enhanced Oil Recovery of HPAM.

Hydrolyzed polyacrylamide (HPAM) is commonly used in polymer flooding, however, it is prone to viscosity reduction at high temperatures and high salinities, weakening its ability to improve oil recovery. In this work, sulfonated modified silicon quantum dots (S-SiQDs) were synthesized and then added to HPAM to study the improvement of rheological properties and enhanced oil recovery performance of HPAM at high temperatures and salinities. It is found that the S-SiQDs with a concentration of only 0.1 wt % can significantly increase the viscosity of HPAM from 28.5 to 39.6 mPa·s at 60 °C and 10,000 mg/L NaCl. Meanwhile, the HPAM/S-SiQDs hybrid solution always possessed higher viscosity and viscoelastic moduli than HPAM, attributed to the hydrogen bonding between HPAM and S-SiQDs. Notably, HPAM/S-SiQDs still maintained elastic behavior at harsh conditions, indicating that they formed a strong network structure. Through oil displacement experiments, it was found that the oil recovery of HPAM/S-SiQDs was higher (28.3%), while that of HPAM was only 17.2%. Thereafter, the utilization sequence of oil during the displacement process was studied with nuclear magnetic resonance experiments. Ultimately, the oil displacement mechanism of HPAM/S-SiQDs was deeply analyzed, including viscosity thickening and wetting reversal.

Detection of Retinal Microvascular Changes with Optical Coherence Tomography Angiography in Patients with Acute Leukemia Without Retinopathy.

INTRODUCTION: Acute leukemia often affects microcirculation perfusion. This study aimed to investigate retinal microvascular changes in patients with acute leukemia without retinopathy during clinical remission using optical coherence tomography angiography (OCTA) and to determine the correlation of these changes with systemic laboratory values. METHODS: Thirty-eight patients in remission from acute leukemia with no retinopathy (NLR group) and 36 age-matched healthy individuals (control group) were included in this cross-sectional study. OCTA parameters, including the central foveal thickness (CFT), foveal avascular zone (FAZ) area, FAZ perimeter, acircularity index (AI), foveal density (FD300), and the vessel densities (VDs) of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris were analyzed in a 6 × 6 mm2 macular scan. Correlation and multiple linear regression analyses were conducted to identify potential systemic characteristics associated with these OCTA metrics. RESULTS: AI (P = 0.034) and FD300 (P < 0.001) differed significantly between the NLR and control groups. The VD of SCP in the parafovea (P = 0.001) and of DCP in both the parafovea (P = 0.011) and perifovea (P = 0.001) were significantly lower in the NLR group than in the control group. In a multiple linear regression analysis, the reduced VD of the perifoveal DCP was significantly correlated with the increased international normalized ratio (standardized beta [STD ß] = - 0.356; P = 0.047). CONCLUSIONS: Macular microvascular changes can be observed during remission from acute leukemia antecedent to clinically visible retinal lesions. Hematological disturbances may be associated with microvascular impairments in preclinical leukemic retinopathy.

Endophthalmitis in silicone oil-filled eye: A case report.

BACKGROUND: Endophthalmitis occurring in silicone oil-filled eyes is a very rare occurrence, with reported incidence rates ranging between 0.07% and 0.039%. Traditional methods of management of infectious endophthalmitis include the removal of silicone oil, washout of the vitreous cavity, administration of intravitreal antibiotics, and re-injection of silicone oil. CASE SUMMARY: Herein, we report the case of a 39-year-old man with unilateral endophthalmitis after pars plana vitrectomy and silicone oil tamponade. Intravitreal injections of full-dose antibiotics and anterior chamber washout were used to treat the patient. No signs of retinal toxicity were observed during the follow-up period. CONCLUSION: Intravitreal full-dose antibiotic injections and anterior chamber washout are promising alternatives to traditional therapies for endophthalmitis in silicone oil-filled eyes.

Clinical and genetic characteristics of maturity-onset diabetes of the young type 13: A systematic review of the literature.

OBJECTIVE: Maturity-onset diabetes of the young type 13 (MODY13), a rare type of monogenic diabetes, is often misdiagnosed as type 1 or type 2 diabetes. To improve early diagnosis and precise treatment, we performed a systematic review and analysis of the literature about MODY13. METHODS: PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI), Chinese BioMedical (CBM) Literature Database, and Wanfang Database were searched using the following search terms: "MODY13," "KCNJ11 maturity-onset diabetes of the young," "KCNJ11-MODY," "maturity-onset diabetes of the young type 13," and "neonatal diabetes mellitus KCNJ11." The demography, clinical characteristics, and gene mutations of patients were expressed with descriptive statistical methods. RESULTS: A total of 33 reports were included in this study, including 75 patients and 28 types of mutations. Thirty-six patients were male. The mean onset age was 25.20 ± 15.26 years. The averages of recorded body mass index, glycated hemoglobin (HbA1c), and fasting C-peptide were 23.45 ± 4.56kg/m2 , 10.07 ± 1.96%, and 0.31 ± 0.23nmol/L, respectively. Most of the mutation sites were located in the cytosolic region of N- and C-terminal domains of Kir6.2. Seven patients were reported to have diabetic chronic complications. CONCLUSION: MODY13 was diagnosed later than other types of MODY and was associated with low fasting C-peptide. Mutation sites of MODY13 were mostly concentrated in N- and C-terminal intracellular domains. The majority of KCNJ11 gene mutations causing MODY 13 were from G to A. The incidence rates of chronic complications were lower than type 1 and type 2 diabetes.

Development and Validation of Data-Level Innovation Data-Balancing Machine Learning Models for Predicting Optimal Implantable Collamer Lens Size and Postoperative Vault.

INTRODUCTION: There are only four sizes of implantable collamer lens (ICL) available for selection, which cannot completely fit all patients as a result of the discontinuity of ICL sizes. Sizing an optimal ICL and predicting postoperative vault are still unresolved problems. This study aimed to develop and validate innovative data-level data-balancing machine learning-based models for predicting ICL size and postoperative vault. METHODS: The patients were randomly assigned to training and internal validation sets in a 4:1 ratio. Feature selection was performed using analysis of variance (ANOVA) and Kruskal-Wallis feature importance methods. Traditional linear regression model and machine learning-based models were used. The accuracy of models was assessed using the area under the curve (AUC) and confusion matrix. RESULTS: A total of 564 patients (1127 eyes) were eligible for this study, consisting of 808 eyes in the training set, 202 eyes in the internal validation set, and 117 eyes in the external validation set. Compared with the traditional linear regression method, the machine learning model bagging tree showed the best performance for ICL size selection, with an accuracy of 84.5% (95% confidence interval (CI) 83.2-85.8%), and the AUC ranged from 0.88 to 0.99; the prediction accuracy of 12.1 mm and 13.7 mm ICL sizes was improved by 49% and 59%, respectively. The bagging tree model achieved the best accuracy [90.2%, (95% CI 88.9-91.5%)] for predicting the postoperative vault, and the AUC ranged from 0.90 to 0.94. The prediction accuracies of internal and external validation dataset for ICL sizing were 82.2% (95% CI 81.1-83.3%) and 82.1% (95% CI 81.1-83.1%), respectively. CONCLUSIONS: The innovative data-level data balancing-based machine learning model can be used to predict ICL size and postoperative vault more accurately, which can assist surgeons in choosing optimal ICL size, thus reducing risks of postoperative complications and secondary surgery.

Efficacy comparison of anti-vascular endothelial growth factor drugs for the treatment of type 1 retinopathy of prematurity: A network meta-analysis of randomised controlled trials.

PURPOSE: To compare the efficacy of different anti-vascular endothelial growth factor (VEGF) agents for the treatment of retinopathy of prematurity (ROP) in preterm infants. METHODS: Seven databases were searched for eligible literature up to February 22, 2023. Studies were included if they were randomised controlled trials (RCTs) investigating the efficacy of anti-VEGF agents for ROP in infants. A network meta-analysis (NMA) was performed. We also conducted subgroup analyses to determine the efficacy ranking of regimens used in different regions. The odds ratio (OR), standardised mean difference (SMD), and surface under the cumulative ranking curve (SUCRA) were calculated for each outcome. RESULTS: Thirteen RCTs of 10 different regimens, involving 1196 infants (2388 eyes), were identified. Bevacizumab (0.625 mg; OR = 0.16, 95% confidence interval [CI] 0.06-0.40, SUCRA = 80.6%) and conbercept (0.15 mg; OR = 0.08, 95% CI 0.02-0.30, SUCRA = 96.0%) were the most effective regimens in reducing the risk of ROP recurrence requiring retreatment in Western countries and China, respectively. Compared with laser therapy, bevacizumab (0.625 mg; SMD = 1.54, 95% CI 0.06-3.02) achieved significantly longer intervals between treatment and recurrence. No significant difference in the risk of retinal detachment was detected between any anti-VEGF agent and laser (p > 0.05). CONCLUSIONS: Bevacizumab (0.625 mg) and conbercept (0.15 mg) appeared to be the most effective therapies for ROP in Western countries and China, respectively. More high-quality RCTs are warranted to evaluate the efficacy and long-term safety of anti-VEGF drugs for the management of ROP.

Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

INTRODUCTION: This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. RESULTS: A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes was - 1.1 letters (95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. CONCLUSIONS: QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

Axial length to corneal radius of curvature ratio and refractive error in Chinese preschoolers aged 4-6 years: a retrospective cross-sectional study.

OBJECTIVE: This study aims to investigate the associations of axial length to corneal radius of curvature (AL/CRC) ratio with refractive error and to determine the effect of AL/CRC ratio on hyperopia reserve and myopia assessment among Chinese preschoolers. METHODS: This was a retrospective cross-sectional study that evaluated subjects aged 4-6 years. AL and CRC were obtained using a non-contact ocular biometer. Correlation analysis was performed to explore the associations of AL/CRC ratio with spherical equivalent refractive error (SER). The accuracy of AL/CRC ratio for hyperopia reserve and myopia assessment was analysed using cycloplegic refraction by drawing receiver operating characteristic (ROC) curves. RESULTS: The analysis included 1024 participants (537 boys, 52.4%). The mean AL/CRC ratios in hyperopes, emmetropes and myopes were 2.90±0.06, 2.95±0.05 and 3.08±0.07, respectively. The SER was found to be more strongly correlated with AL/CRC ratio (ρ=-0.66, p<0.001) than either AL or CRC alone (ρ=-0.52, p<0.001; ρ=-0.03, p=0.33, respectively). AL/CRC was correlated with SER in hyperopes (ρ=-0.54, p<0.001), emmetropes (ρ=-0.33, p<0.001) and myopes (r=-0.67, p<0.001). For low hyperopia reserve assessment, the area under the ROC curves of AL/CRC ratio was 0.861 (95% CI 0.829 to 0.892), the optimal cut-off value of the AL/CRC ratio was ≥2.955. For myopia assessment, the area under the ROC curves of AL/CRC ratio was 0.954 (95% CI 0.925 to 0.982), the optimal cut-off value of the AL/CRC ratio was ≥2.975. CONCLUSIONS: The SER showed a better correlation with AL/CRC ratio than either AL or CRC alone, especially in myopes, among children aged 4-6 years. These findings indicate that when cycloplegic refraction is unavailable, AL/CRC ratio could be used as an alternative indicator for identifying low hyperopia reserve and myopia among preschoolers, helping clinicians and parents screen children with low hyperopia reserve before primary school in a timely manner.

Efficacy of small back optic zone design on myopia control for corneal refractive therapy (CRT): a one-year prospective cohort study.

BACKGROUND: To investigate the control effect on the axial length elongation using corneal refractive therapy (CRT) with different optical zone diameters (BOZDs). We also sought to compare the difference in higher-order aberrations (HOAs), treatment zone (TZ) size and Zernike defocus coefficient with different BOZDs and seek the optimal parameter for predicting axial elongation. METHODS: This prospective cohort study included 7- to 14-year-olds fitted with orthokeratology (ortho-K) lenses of 5-mm (5-mm group) or 6-mm BOZD (6-mm group). Axial length (AL), corneal topography, HOAs and Zernike defocus coefficient were obtained at baseline, and 1, 3, 6, 9 and 12 months follow-up visits. Multivariate regression analyses were used to explore the association between AL change and ocular biometric parameters. Receiver operating characteristic (ROC) curve analysis was used to determine the best diagnostic value for AL change in ocular biometric parameters. RESULTS: In total, 301 participants completed the one-year follow-up. The mean AL change in the 5-mm group (0.13 ± 0.18 mm) was less than that in the 6-mm group (0.27 ± 0.15 mm) at the 12 months visit. The TZ size and decentration were smaller, while the Zernike defocus coefficient and HOAs were higher in the 5-mm group (all P < 0.05). Older age and smaller TZ size were protective factors against AL elongation in multiple regression. In predicting AL elongation, TZ diameter yielded an area under the ROC curve of 0.684 with a cut-off value of 3.82 mm. CONCLUSION: The 5-mm group showed 0.14 mm (51.8%) less axial elongation than the 6-mm group. The 5-mm BOZD produced a smaller TZ size, higher Zernike defocus coefficient and higher HOA after reshaping of the cornea. TZ size was the best predictor of AL elongation. TZ diameter less than 3.82 mm may lead to AL elongation less than 0.2 mm in one year.

Stem cell therapy for inherited retinal diseases: a systematic review and meta-analysis.

PURPOSE: Stem cell therapy is a promising therapeutic approach for inherited retinal diseases (IRDs). This study aims to quantitatively examine the effectiveness and safety of stem cell therapy for patients with IRDs, including retinitis pigmentosa and Stargardt disease (STGD). METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library databases, and the ClinicalTrials.gov website. The latest retrieval time was August 20, 2023. The primary outcomes were rates and mean difference (MD) of best-corrected visual acuity (BCVA) improvement. Subgroup analyses were conducted according to administration routes and stem cell types. This study was registered with PROSPERO (CRD42022349271). RESULTS: Twenty-one prospective studies, involving 496 eyes (404 RP and 92 STGD) of 382 patients (306 RP and 76 STGD), were included in this study. For RP, the rate of BCVA improvement was 49% and 30% at 6 months and 12 months, respectively, and the BCVA was significantly improved in the operative eyes at 6 months post-treatment (MD = - 0.12 logMAR, 95% CI .17 to - 0.06 logMAR; P < 0.001), while there was no significant difference at 12 months post-treatment (MD = -0.06 logMAR; 95% CI - 0.13 to 0.01 logMAR; P = 0.10). For STGD, the rate of BCVA improvement was 60% and 55% at 6 months and 12 months, respectively, and the BCVA was significantly improved in the operative eyes at 6 months (MD = - 0.14 logMAR, 95% CI - 0.22 to - 0.07 logMAR; P = 0.0002) and 12 months (MD = - 0.17 logMAR, 95% CI - 0.29 to - 0.04 logMAR; P = 0.01). Subgroup analyses showed suprachoroidal space injection of stem cells may be more efficient for RP. Eleven treated-related ocular adverse events from three studies and no related systemic adverse events were reported. CONCLUSIONS: This study suggests stem cell therapy may be effective and safe for patients with RP or STGD. The long-term vision improvement may be limited for RP patients. Suprachoroidal space injection of stem cells may be a promising administration route for RP patients. Limited by the low grade of evidence, large sample size randomized clinical trials are required in the future.

Nanocomposite Hydrogel Engineered Janus Membrane for Membrane Distillation with Robust Fouling, Wetting, and Scaling Resistance.

Membrane distillation (MD) is considered to be rather promising for high-salinity wastewater reclamation. However, its practical viability is seriously challenged by membrane wetting, fouling, and scaling issues arising from the complex components of hypersaline wastewater. It remains extremely difficult to overcome all three challenges at the same time. Herein, a nanocomposite hydrogel engineered Janus membrane has been facilely constructed for desired wetting/fouling/scaling-free properties, where a cellulose nanocrystal (CNC) composite hydrogel layer is formed in situ atop a microporous hydrophobic polytetrafluoroethylene (PTFE) substrate intermediated by an adhesive layer. By the synergies of the elevated membrane liquid entry pressure, inhibited surfactant diffusion, and highly hydratable surface imparted by the hydrogel/CNC (HC) layer, the resultant HC-PTFE membrane exhibits robust resistance to surfactant-induced wetting and oil fouling during 120 h of MD operation. Meanwhile, owing to the dense and hydroxyl-abundant surface, it is capable of mitigating gypsum scaling and scaling-induced wetting, resulting in a high normalized flux and low distillate conductivity at a concentration factor of 5.2. Importantly, the HC-PTFE membrane enables direct desalination of real hypersaline wastewater containing broad-spectrum foulants with stable vapor flux and robust salt rejection (99.90%) during long-term operation, demonstrating its great potential for wastewater management in industrial scenarios.

CRISPR/SaCas9-based gene editing rescues photoreceptor degeneration throughout a rhodopsin-associated autosomal dominant retinitis pigmentosa mouse model.

Rhodopsin (Rho) gene mutation was considered the highest prevalent mutation in autosomal dominant retinitis pigmentosa (ADRP); however, effective therapeutics for ADRP have not been developed. The process of gene editing via the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system offers the potentiality to provide cures for dominantly inherited disorders. Herein, we generated a CRISPR/SaCas9-mediated gene reduction system to inactivate the Rho mutant, while replacing normal rhodopsin in a rhodopsin mutation mouse model. When Rho-P23H knock-in mice were administered a subretinal injection of the "reduction and replacement" system, the expression of mutant rhodopsin was reduced, and retinal function was improved. Therefore, we concluded that CRISPR/SaCas9-based "reduction and replacement" gene therapy could provide structural and functional benefits for Rho mutant ADRP, as well as new directions for future clinical research on the treatment of such gain-of-function genetic diseases.