Overexpression of TRPV1 activates autophagy in human lens epithelial cells under hyperosmotic stress through Ca2+-dependent AMPK/mTOR pathway.

AIM: To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells (LECs) under hyperosmotic stress. METHODS: LECs were treated with hyperosmotic stress at the concentration of 270, 300, 400, 500, or 600 mOsm for 6, 12, 18, 24h in vitro. Polymerase chain reaction (PCR) was employed for the mRNA expression of autophagy-related genes, while Western blotting detected the targeted protein expression. The transfection of stub-RFP-sens-GFP-LC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux. Scanning electron microscopy was used to detect the existence of autolysosome. Short interfering RNA of autophagy-related gene (ATG) 7, transient receptor potential vanilloid (TRPV) 1 overexpression plasmid, related agonists and inhibitors were employed to their influence on autophagy related pathway. Flow cytometry was employed to test the apoptosis and intracellular Ca2+ level. Mitochondrial membrane potential was measured by JC-1 staining. The cell counting kit-8 assay was used to calculate the cellular viability. The wound healing assay was used to evaluate the wound closure rate. GraphPad 6.0 software was utilized to evaluate the data. RESULTS: The hyperosmotic stress activated autophagy in a pressure- and time-dependent manner in LECs. Beclin 1 protein expression and conversion of LC3B II to LC3B I increased, whereas sequestosome-1 (SQSTM1) protein expression decreased. Transient Ca2+ influx was stimulated caused by hyperosmotic stress, levels of mammalian target of rapamycin (mTOR) phosphorylation decreased, and the level of AMP-activated protein kinase (AMPK) phosphorylation increased in the early stage. Based on this evidence, autophagy activation through the Ca2+-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress. Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased. Inhibition of autophagy by ATG7 knockdown had similar results. TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress. CONCLUSION: A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.

Clinical observation of a modified technique for intrascleral fixation of flanged three-piece foldable intraocular lenses through a Hoffman pocket.

Purpose: To present the outcomes of a new technique for intrascleral fixation of a flanged three-piece foldable intraocular lens (IOL) without a conjunctival incision. Materials and methods: We retrospectively reviewed a consecutive series of 12 eyes of 12 patients who underwent scleral IOL fixation using this technique. Results: The follow-up period ranged 3-12 months. There was a significant improvement in best-corrected visual acuity, from 0.8 (1.6) logarithm of the minimum angle of resolution (logMAR) preoperatively to 0.45 (0.8) logMAR at the final postoperative follow-up (p = 0.012). Notable complications included one case of pupillary IOL capture and increased intraocular pressure. Conclusion: Our novel technique is a viable solution for managing secondary IOL fixation, enabling the use of a wider variety of IOLs and simplifying the reposition process for dislocated three-piece IOLs. This approach has the potential to lower complication rates and enhance patients' recovery.

Improving Accuracy of In-The-Bag Intraocular Lens Power Calculation in Adult Eyes with Unilateral Subluxated Lenses by Using the Anterior Chamber Depth of the Unaffected Eye.

INTRODUCTION: This study aimed to determine the interchangeability of bilateral anterior chamber depth (ACD) in intraocular lens (IOL) power calculations for cataractous eyes and refractive outcomes using the unaffected fellow eye's ACD in subluxated crystalline lenses. METHODS: The predicted postoperative spherical equivalent (SE) calculated using the Kane formula with and without fellow eye's ACD in 202 cataract patients was compared. Refractive outcomes of the newer formulas (the Kane, Barrett Universal II [BUII], and Pearl-DGS formulas) with affected eye's ACD and with unaffected fellow eye's ACD were compared in 33 eyes with lens subluxation (the affected eye) undergoing in-the-bag IOL implantation. The SD of the prediction error (PE) was assessed using the heteroscedastic method. RESULTS: In 202 paired cataractous eyes, no marked ACD difference was found bilaterally; the predicted SE obtained without the fellow eye's ACD was comparable with that calculated with the fellow eye one (p = 0.90), with a mean absolute difference of 0.03 ± 0.03 D. With the affected eye AL, keratometry, and ACD, the median absolute error (MedAE) was 0.38-0.64 D, and the percentage of PE within ±0.50 D was 30.30-57.58%. The unaffected eye's ACD improved the results (MedAE, 0.35-0.49 D; the percentage of PE within ±0.50 D, 54.55-63.64%). The SDs of the BUII (0.82 D) and Pearl-DGS formulas (0.87 D) with the affected eye's ACD were significantly larger than those of the Kane and Pearl-DGS formulas (both 0.69 D) with the unaffected eye's ACD. CONCLUSION: Bilateral ACD was interchangeable in IOL power calculation for cataractous eyes when using the Kane formula. Unaffected eye's ACD in lieu of affected eye's ACD can enhance the accuracy of newer formulas in patients with unilateral subluxated lenses undergoing in-the-bag IOL implantation.

HO-1-Mediated Autophagic Restoration Protects Lens Epithelial Cells Against Oxidative Stress and Cellular Senescence.

Purpose: Oxidative stress and cellular senescence are risk factors for age-related cataract. Heme oxygenase 1 (HO-1) is a critical antioxidant enzyme and related to autophagy. Here, we investigate the crosstalk among HO-1, oxidative stress, and cellular senescence in mouse lens epithelial cells (LECs). Methods: The gene expression of HO-1, p21, LC3, and p62 was measured in human samples. The protective properties of HO-1 were examined in hydrogen peroxide (H2O2)-damaged LECs. Autophagic flux was examined by Western blot and mRFP-GFP-LC3 assay. Western blotting and lysotracker staining were used to analyze lysosomal function. Flow cytometry was used to detect intracellular reactive oxygen species and analyze cell cycle. Senescence-associated ß-galactosidase assay was used to determine cellular senescence. The crosstalk between HO-1 and transcription factor EB (TFEB) was further observed in TFEB-knockdown cells. The TFEB binding site in the promoter region of Hmox1 was predicted by the Jasper website and was confirmed by chromatin immunoprecipitation assay. Results: HO-1 gene expression decreased in LECs of patients with age-related nuclear cataract, whereas mRNA expression levels of p21, LC3, and p62 increased. Upon H2O2-induced oxidative stress, LECs showed the characteristics of autophagic flux blockade, lysosomal dysfunction, and premature senescence. Interestingly, HO-1 significantly restored the impaired autophagic flux and lysosomal function and delayed cellular senescence. TFEB gene silencing greatly reduced the HO-1-mediated autophagic restoration, leading to a failure to prevent LECs from oxidative stress and premature senescence. Conclusions: We demonstrated HO-1 effects on restoring autophagic flux and delaying cellular senescence under oxidative stress in LECs, which are dependent on TFEB.

Effect of beinaglutide combined with metformin versus aspart 30 with metformin on metabolic profiles and antidrug antibodies in patients with type 2 diabetes: a randomized clinical trial.

Objective: This prospective study aimed to evaluate the effect of beinaglutide combined with metformin versus aspart 30 with metformin on metabolic profiles and antidrug antibodies (ADAs) in patients with type 2 diabetes (T2D). Methods: A total of 134 eligible participants were randomly assigned to the test group and the control group. Patients in the test group were treated with beinaglutide and metformin, whereas patients in the control group were randomly treated with aspart 30 and metformin, with a follow-up period of 6 months. The metabolic profiles and ADAs over 6 months were evaluated. Results: After 6 months, 101 (75.37%) patients completed the study. Compared with the control group, the beinaglutide group had significant reductions in 2-h postprandial blood glucose (2hBG) and low blood glucose index (LBGI). Glycated hemoglobin (HbA1c) decreased in both groups relative to baseline. In the test group, one had treatment-emergent beinaglutide ADAs. Significant reductions in triglycerides (TG), non-fasting TG, weight, waist circumference (WC), and body mass index (BMI) were observed. The values of insulin sensitivity index (HOMA-IR) were decreased to a statistically higher degree with beinaglutide treatment. Conclusion: Beinaglutide reduces metabolic dysfunction, LBGI, and weight in patients of T2D with a low risk of ADAs. Beinaglutide may offer the potential for a disease-modifying intervention in cardiovascular disease (CVD). Clinical trial registration: www.chictr.org.cn, identifier ChiCTR2200061003.

Telemedicine-assisted structured self-monitoring of blood glucose in management of T2DM results of a randomized clinical trial.

BACKGROUND: This prospective study aimed to compare telemedicine-assisted structured self-monitoring of blood glucose(SMBG) with a traditional blood glucose meter (BGM) in adults of type 2 diabetes mellitus (T2DM). METHODS: Adult participants with T2DM were assigned to an intervention group or a control group. The patients in the intervention group received a connected BGM with real-time data submission as well as individual needs-based tele-coaching to address and improve motivation and daily diabetes self-management. The patients in the control group received a traditional BGM. Changes in glycated hemoglobin(HbA1c), low blood glucose index(LBGI), and diabetes self-management behaviors were analyzed. RESULTS: The study demonstrated the superiority of the telemedicine-assisted structured SMBG versus the traditional BGM for improving HbA1c. Additionally, the telemedicine-assisted SMBG reduced the risk of hypoglycemia and enhanced diabetes self-management behaviors, as differences in the LBGI and the Diabetes Self-Management Questionnaire(DSMQ) results between the groups after 6 months were found to be significant. CONCLUSIONS: Telemedicine-assisted structured SMBG helps physicians and patients to achieve a specific level of glycemic control and reduce hypoglycemia. The use of coaching applications and telemedicine-assisted SMBG indicated beneficial effects for T2DM self-management, which may help limit disease progression. TRIAL REGISTRATION: Chinese Clinical Trail Registry No: ChiCTR2300072356 on 12/06/2023. Retrospectively registered.

Effect of Benaglutide on Gut Microbiota and Fecal Metabolites in Patients with Type 2 Diabetes Mellitus.

Objective: Benaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) that has been approved in the treatment of type 2 diabetes mellitus (T2DM). It is known to lead to significant weight loss, and it is hypothesized that changes in gut microbiota may play a significant role in such weight loss. However, it is unclear how gut microbiota and metabolites change as a result of benaglutide treatment. Methods: Healthy participants and patients with T2DM were included in this study. They received differentiated treatments, and stool specimens were collected separately. These stool specimens were subjected to 16S ribosomal RNA amplicon and metagenomic sequencing to create fecal metabolomic profiles. The diversity of gut microbiota and metabolic products in the stools of each participant was analyzed. Results: The data showed that Faecalibacterium prausnitzii was abundant in the gut microbiota of the control group, which was entirely made up of healthy individuals; however, it showed a statistically significant decrease in patients with T2DM treated with metformin alone, while no significant decrease was observed in patients treated with metformin combined with benaglutide. A metagenomic analysis revealed that benaglutide could improve the fecal microbiota diversity in patients with T2DM. Furthermore, there was a statistically significant correlation between the changes in the metabolites of patients with T2DM and the changes in their gut microbiota (including F. prausnitzii) after treatment with metformin and benaglutide. Conclusion: These findings suggest that the weight-reducing effect of benaglutide is attributed to its ability to normalize the gut microbiota of patients with T2DM, particularly by increasing the abundance of F. prausnitzii.

Exogenous Insulin Antibody Syndrome in Patients with Type 2 Diabetes.

Background: Exogenous insulin antibody syndrome (EIAS) is an immunological disorder caused by circulating insulin antibodies (IAs), featuring hypersensitivity to exogenous insulin and insulin resistance. With the wide use of recombinant human insulin and insulin analogs, there has been a significant proliferation of EIAS. Case Report: We describe two cases of diabetes mellitus (DM) with hyperinsulinemia and high serum levels of IAs. They had never been exposed to methimazole, glutathione, lipoic acid, and other sulfhydryl drugs, but they all received insulin treatment. The patient in case 1 had recurrent hypoglycemia before hospitalization. A prolonged oral glucose tolerance test (OGTT) showed hypoglycemia with inappropriately high insulin levels. The patient in case 2 was hospitalized for diabetic ketosis. An OGTT indicated hyperglycemia with hyperinsulinemia and low levels of C-peptide. IAs induced by exogenous insulin in the two patients with DM were positive at high titers, prompting a diagnosis of another condition-EIAS. Conclusion: We discussed the differences between these two cases of EIAS in clinical manifestations and treatment and summarized all patients of EIAS treated in our department to date.

Luteolin inhibits subretinal fibrosis and epithelial-mesenchymal transition in laser-induced mouse model via suppression of Smad2/3 and YAP signaling.

BACKGROUND: Subretinal fibrosis (SF) accounts for vision loss in patients with neovascular age-related macular degeneration (nAMD) even treated with adequate intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs. Currently, there is no treatment available to prevent or treat SF caused by nAMD. PURPOSE: This study aims to investigate the potential effects of luteolin on SF and epithelial-mesenchymal transition (EMT) as well as the underlying molecular pathways both in vivo and in vitro. METHODS: Seven-week-old male C57BL/6J mice were employed to establish laser-induced choroidal neovascularization (CNV) and SF. One day after the laser induction, luteolin was administered intravitreally. SF and CNV were assessed with the immunolabeling of collagen type I (collagen I) and isolectin B4 (IB4), respectively. RPE65 and α-SMA colocalization in the lesions was used to evaluate the extent of EMT in retinal pigment epithelial (RPE) cells by using immunofluorescence. In vitro, luteolin was administered to TGFß1-treated primary human RPE (phRPE) cells. RT-qPCR, Western blot and immunofluorescence were employed to evaluate the change of EMT-related molecules, epithelial markers, and relevant signaling pathways. The functional changes associated with EMT were investigated using the scratch assay, Transwell migration assay, and collagen gel contraction assay. CCK-8 was used to determine the cell viability of phRPE cells. RESULTS: On day 7 and 14 after laser induction in mice, intravitreal injection of luteolin dramatically decreased the immunolabeled sizes of both collagen I and IB4, as well as the amount of colocalized double immunostaining of α-SMA and RPE65 in laser-induced SF lesions. In vitro, TGFß1-treated phRPE cells demonstrated increased cell migration and contraction capacity, accompanied with considerable overexpression of fibronectin, α-SMA, N-cadherin and vimentin, as well as downregulation of E-cadherin and ZO-1. The above changes were largely inhibited by luteolin co-incubation. Mechanistically, luteolin could evidently decrease the phosphorylation of Smad2/3, whereas increase the phosphorylation of YAP in TGFß1-treated phRPE cells. CONCLUSION: This study demonstrates that luteolin exhibits the anti-fibrotic effect in a laser-induced mouse model by inhibiting EMT of RPE cells via deactivating Smad2/3 and YAP signaling, which provides a potential natural compound for the prevention and treatment of SF and fibrosis-related diseases.

Flapless and Conjunctiva-Sparing Technique for Transscleral Fixation of Intraocular Lens to Correct Refractive Errors in Eyes without Adequate Capsular Support.

Purpose: To evaluate refractive outcomes, intraocular lens (IOL) power calculation, and IOL position following a novel conjunctiva-sparing transscleral fixation technique. Methods: Forty-one eyes of 40 patients managed with a flapless transscleral-sutured technique were included. Preoperative and postoperative refractive errors (spherical equivalents, SE) were compared. IOL position was assessed on the Scheimpflug images. IOL power was calculated by SRK/T, Holladay 1, and Hoffer Q formulas. Results: The mean age was 57.39 ± 14.83 years (range: 26 to 79 years), and the mean follow-up was 7.46 ± 6.42 months (range: 1 to 24 months). Surgical indications were aphakia (n = 14), subluxated lenses (n = 3), and IOL dislocation (n = 24). The SE was 4.50 ± 6.38 diopter (D) (range: -3.75 to 13.75 D) preoperatively and -1.68 ± 1.57 D (range: -5.50 to 1.13 D) postoperatively (P < 0.001). The mean tilt angle and decentration were 2.90° ± 1.93° (range: 0.39° to 9.10°) and 0.23 ± 0.19 mm (range: 0.02 to 0.94 mm) vertically, and 1.75° ± 1.41° (range: 0.24° to 7.65°) and 0.18 ± 0.19 mm (range: 0.02 to 1.06 mm) horizontally, which were clinically insignificant. All three IOL formulas produced myopic errors (range: -0.29 to -0.50 D). The SRK/T had the lowest median absolute error (0.55 D), followed by the Holladay 1 (0.70 D) and the Hoffer Q (0.74 D). The three formulas had the same percentage of prediction errors (PEs) within ±0.5 D (43.48%), while the Hoffer Q had the highest percentage of PEs within ±1.0 D (82.61%). Conclusion: The present technique can serve as an alternative approach for transscleral IOL fixation and refractive correction in eyes with compromised capsular support, ensuring the stability of IOLs and reasonable IOL power calculation accuracy.

Cardiac Computed Tomography to Guide the Selection of Better Display Angle of Cardiac Right Ventricular Pacing Electrode in Radiography.

BACKGROUND: Traditional radiography angles do not adequately reveal the shape and position of the right ventricular pacing electrode. OBJECTIVE: This study aimed to explore better radiography angles with the help of cardiac computed tomography (CT). METHODS: We analyzed the cardiac CT images of consecutive outpatients from 2018 to 2019. The right anterior oblique (RAO) 30° and the left anterior oblique (LAO) 40° were found to sufficiently display the shape and position of the right ventricular pacing electrode. RESULTS: A total of 214 consecutive outpatients were enrolled, whose average age was 55.0 ± 13.0 years, and 151 were male (70.6%). Through analyzing the cardiac CT images, the α angle (33.7° ± 6.1) and the γ angle (38.8° ± 8.0) were determined. Furthermore, we verified these angles in 48 patients after pacemaker implantation. The results showed that the ratio of the length of right ventricular electrode using the RAO α angle (≈30°) to the posterior-anterior position (PA position) was 1.099 ± 0.157 vs. 1.053 ± 0.182 (the ratio using the traditional RAO 45°) (P < 0.001). We observed that the relationship between the right ventricular active electrode and the ventricular septum was better identified using the LAO γ angle (≈40°) than the traditional 60° angle. CONCLUSION: With the help of cardiac CT, we found that RAO 30° could better show the shape and length of the right ventricular pacing electrode, and LAO 40° could better show the positional relationship between the pacing electrode and the ventricular septum.

Retinal Vascular Geometry in Hypertension: cSLO-Based Method.

INTRODUCTION: We aim to introduce a method using confocal scanning laser ophthalmoscopy (cSLO) images for measuring retinal vascular geometry, including vessel branch angle (BA), vessel diameter, vessel tortuosity, and fractal dimension (Df), and to elucidate the relationship between hypertension and these metrics. METHODS: A total of 119 participants (119 eyes) were enrolled, among which 72 were normotensive and 47 were hypertensive. Infrared cSLO images were extracted from the circular scan around the optics disc using a commercial cSLO + optical coherence tomography instrument. Preprocessed cSLO images were further analyzed using the appropriate tool/macro/plugin of ImageJ. RESULTS: Intraclass correlation coefficients of selected methods used for conducting the cSLO-based geometric analyses were all higher than 0.80. Arterial/arteriolar BA, arteriolar vessel diameter, and total Df in normotensive subjects were 85.80 ± 7.79°, 116.80 ± 12.58 µm, and 1.430 ± 0.037, respectively, significantly higher than those of hypertensive subjects (82.13 ± 10.83°, 108.2 ± 11.12 µm, and 1.361 ± 0.044, all P < 0.05). The aforementioned metrics remained negatively correlated with hypertension even after adjusting for age alone or age and gender (P < 0.05). However, the difference between arteriolar tortuosity and all studied venous/venular geometric parameters in both subjects was insignificant (all P > 0.05). CONCLUSION: Proposed cSLO-based methods for assessing various vascular geometric parameters were highly repeatable and reproducible. Arterial/arteriolar BA, arteriolar vessel diameter, and total Df were retinal vascular parameters significantly correlated with hypertension in a negative manner.

Intrascleral sewing-machine technique: A Grooveless/flapless cyclopexy technique for large traumatic Cyclodialysis cleft repairs in pars plana vitrectomy.

PURPOSE: To describe a minimally invasive technique for the repair of large traumatic cyclodialysis clefts using intrascleral sewing machine suture and overhand friction knot techniques in pars plana vitrectomy. METHODS: This prospective, noncomparative, interventional case series included seven eyes of seven patients with a large traumatic cyclodialysis cleft. The sewing machine technique was modified by an intrascleral approach. The procedure was transconjunctival or subconjunctival performed without scleral flaps/grooves. An overhand friction knot was used to lead the cutting ends of the suture buried in the scleral tunnel. RESULTS: The closure of the cyclodialysis cleft was achieved in seven eyes. The mean follow-up duration was 49.1 ± 15.6 weeks (range, 30-70 weeks). The intraocular pressure increased from 7.3 ± 2.1 mm Hg (range, 5-11 mmHg) preoperatively to 13.6 ± 2.4 mm Hg (range, 10-17 mmHg) postoperatively ( P < 0.01). The best-corrected visual acuity improved from a mean of 2.76 ± 2.77 logarithm of the minimum angle of resolution preoperatively to 0.63 ± 0.82 logarithm of the minimum angle of resolution at the final follow-up ( P < 0.01). CONCLUSION: In conclusion, the present technique is safe and effective in the treatment of large traumatic cyclodialysis clefts with minimal surgical trauma and a decreased surgical duration.

Intrascleral Fixation of Flanged Polypropylene Suture(s) for Iridodialysis Repair.

PURPOSE: We will describe a minimally invasive technique for the repair of iridodialysis, without conjunctival dissections, using intrasceral fixation of a 6-0 polypropylene suture with a flanged tip. METHODS: A flange was created at the end of the suture with thermoplasticity. An ab interno passing of the needle attached to the suture was performed through the peripheral part of the iris and was further passed out from the eye 1.5 mm to 2 mm behind the limbus. Intrascleral fixation of the exterior suture was performed with the aid of the attached needle. After adjusting the tension of the iris relocation, the externalized end of the suture was cut flush to the sclera with scissors. For a wide dialysis, the same manipulations were repeated until the repair was completed. RESULTS: The technique was used in three eyes of three patients. No visual impairments of monocular diplopia and glare were observed after surgery. Postoperatively, the irises remained well positioned, with no suture erosion, suture loosening, hypotony, scleral atrophy, or chronic inflammation being observed within the follow-up period. Mild postoperative hyphema was observed in one eye of blunt trauma. CONCLUSION: The present technique provides minimal surgical invasion for the repair of iridodialysis without creations of scleral flap/groove/pocket and conjunctival dissection.

Comparison of anterior corneal aberrations measured by Scheimpflug and Placido Disc System for myopes.

BACKGROUND: To ascertain the agreement of corneal aberrations obtained from the Pentacam and the KR-1W in myopic populations and to investigate the influence of the level of myopia as well as the laterality on the agreement. METHODS: In this observational study, a rotating Scheimpflug camera (Pentacam AXL) and a Hartmann-Shack wavefront analyzer with Placido-disc topographer (KR-1W) were used to measure the aberrations of myopes in the anterior corneal surface by one experienced operator. All examinations were computed across a 6 mm diameter. Six subgroups were generated according to the degree of myopia (mild, moderate, and severe myopia) and the laterality of eyes (right and left eyes). RESULTS: The study included 245 eyes of 170 participants. For certain anterior corneal aberrations, statistically significant differences existed between the Pentacam and the KR-1W (all P < .05). The values of Zernike (Z)(2,0), Z(2,2), Z(3,1), and Z(4,0) varied in all levels of myopia regardless of the laterality, with the values of the Pentacam constantly larger than the KR-1W in the measurement of Z(2,0), Z(2,2), and Z(4,0). For 2nd to 6th aberrations, both instruments correlated poorly to moderately. The width of limits of agreement between the two instruments was clinically too wide (> 0.1 µm) for aberrations closely correlated with visual quality, including Z(3, ± 3), Z(3, ± 1), and Z(4,0), and almost all aberrations, indicating poor agreement. CONCLUSIONS: In clinical practice, the Pentacam based on Scheimpflug technology and the KR-1W based on Placido Disc System are not interchangeable in measuring anterior corneal aberration for myopes regardless of myopia degree and the laterality, suggesting that a consistent instrument should be selected for surgical design as well as follow-up.

Exclusive breastfeeding rate and related factors among mothers within maternal health WeChat groups in Jiaxing, Zhejiang province, China: a cross-sectional survey.

BACKGROUND: The health workers in Jiaxing of China have established maternal health WeChat groups for maternal health education and management since 2019. Pregnant women in Jiaxing are invited to join the WeChat groups and a health worker as the group manager provides health education and individual counselling for women within the group. This study aimed to investigate the exclusive breastfeeding (EBF) status up to six months and its associated factors among the mothers of infants aged 7-12 months within the WeChat groups. METHODS: This was a cross-sectional survey on healthy mothers with infants aged 7-12 months from seven maternal health WeChat groups in October 2021 in Jiaxing, China. EBF was defined as breastfeeding infants exclusively up to six months. Data including breastfeeding practice from birth to six months, maternal sociodemographic and obstetric characteristics, hospitalization information, work related factors and reasons for non-EBF up to six months were collected using an online self-administered questionnaire. A multivariable logistic regression analysis was performed to identify the factors independently associated with EBF up to 6 months. RESULTS: A total of 822 mothers were included in this study. Among them, 586 mothers (71.3%) exclusively breastfed infants up to six months. Multivariable logistic regression analysis showed that older maternal age (adjusted odds ratio [AOR] 0.956; 95% confidence interval [CI] 0.917, 0.997) and perceived insufficient breast milk (AOR 0.104; 95% CI 0.072, 0.149) were associated with lower odds of EBF up to six months. The five of common reasons for non-EBF up to six months were no or insufficient breast milk (59.8%), return to work (23.9%), no flexible nursing breaks at work (18.2 %), infant crying or feeling tired or troubled with breastfeeding (9.7%), and nipple and breast problems (9.3%). CONCLUSION: About 71.3% of infants were exclusively breastfed until six months of age in our WeChat groups. Perceived insufficient breast milk and work related factors are the main barriers to EBF up to six months in this setting. However, further comparative study is needed to confirm the effect of WeChat groups on breastfeeding.

Two-dimensional ultrathin Ti3C2 MXene nanosheets coated intraocular lens for synergistic photothermal and NIR-controllable rapamycin releasing therapy against posterior capsule opacification.

Posterior capsule opacification (PCO) is one of the most frequent late-onset complications after cataract surgery. Several kinds of drug-eluting intraocular lenses (IOL) were designed for sustainable drug release to suppress ocular inflammation, the proliferation of lens epithelial cells (LECs) and the development of PCO after cataract surgery. Despite previous advances in this field, the drug-loaded IOLs were limited in ocular toxicity, insufficient drug-loading capacity, and short release time. To prevent PCO and to address these drawbacks, a novel drug-loaded IOL (Rapa@Ti3C2-IOL), prepared from two-dimensional ultrathin Ti3C2 MXene nanosheets and rapamycin (Rapa), was fabricated with a two-step spin coating method in this study. Rapa@Ti3C2 was prepared via electrostatic self-assembly of Ti3C2 and Rapa, with a loading capacity of Rapa at 92%. Ti3C2 was used as a drug delivery reservoir of Rapa. Rapa@Ti3C2-IOL was designed to have the synergistic photothermal and near infrared (NIR)-controllable drug release property. As a result, Rapa@Ti3C2-IOL exhibited the advantages of simple preparation, high light transmittance, excellent photothermal conversion capacity, and NIR-controllable drug release behavior. The Rapa@Ti3C2 coating effectively eliminated the LECs around Rapa@Ti3C2-IOL under a mild 808-nm NIR laser irradiation (1.0 W/cm-2). Moreover, NIR-controllable Rapa release inhibited the migration of LECs and suppressed the inflammatory response after photothermal therapy in vitro. Then, Rapa@Ti3C2-IOL was implanted into chinchilla rabbit eyes, and the effectiveness and biocompatibility to prevent PCO were evaluated for 4 weeks. The Rapa@Ti3C2-IOL implant exhibited excellent PCO prevention ability with the assistance of NIR irradiation and no obvious pathological damage was observed in surrounding healthy tissues. In summary, the present study offers a promising strategy for preventing PCO via ultrathin Ti3C2 MXene nanosheet-based IOLs with synergistic photothermal and NIR-controllable Rapa release properties.

Biliverdin Reductase A Protects Lens Epithelial Cells against Oxidative Damage and Cellular Senescence in Age-Related Cataract.

Age-related cataract (ARC) is the common cause of blindness globally. Reactive oxygen species (ROS), one of the greatest contributors to aging process, leads to oxidative damage and senescence of lens epithelial cells (LECs), which are involved in the pathogenesis of ARC. Biliverdin reductase A (BVRA) has ROS-scavenging ability by converting biliverdin (BV) into bilirubin (BR). However, little is known about the protective effect of BVRA against ARC. In the present study, we measured the expression level of BVRA and BR generation in human samples. Then, the antioxidative property of BVRA was compared between the young and senescent LECs upon stress condition. In addition, we evaluated the effect of BVRA on attenuating H2O2-induced premature senescence in LECs. The results showed that the mRNA expression level of BVRA and BR concentration were decreased in both LECs and lens cortex of age-related nuclear cataract. Using the RNA interference technique, we found that BVRA defends LECs against oxidative stress via (i) restoring mitochondrial dysfunction in a BR-dependent manner, (ii) inducing heme oxygenase-1 (HO-1) expression directly, and (iii) promoting phosphorylation of ERK1/2 and nuclear delivery of nuclear factor erythroid 2-related factor 2 (Nrf2). Intriguingly, the antioxidative effect of BVRA was diminished along with the reduced BR concentration and repressed nuclear translocation of BVRA and Nrf2 in senescent LECs, which would be resulted from the decreased BVRA activity and impaired nucleocytoplasmic trafficking. Eventually, we confirmed that BVRA accelerates the G1 phase transition and prevents against H2O2-induced premature senescence in LECs. In summary, BVRA protects LECs against oxidative stress and cellular senescence in ARC by converting BV into BR, inducing HO-1 expression, and activating the ERK/Nrf2 pathway. This trial is registered with ChiCTR2000036059.