Lens regeneration using endogenous stem cells with gain of visual function.

The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells.

Mental health status of medical students during postgraduate entrance examination.

BACKGROUND: The postgraduate entrance examination can be a milestone for many medical students to advance their careers. An increasing number of students are competing for limited postgraduate offers available, and failure to enter postgraduate studies can have adverse mental health consequences. In this paper, we aim to investigate the mental health status of medical students during the postgraduate application entrance examination and to provide a targeted basis for mental health education and psychological counselling. METHODS: Using the Symptom Checklist-90 scale (SCL-90) questionnaire, the mental health status of 613 students who passed two rounds of the Postgraduate Entrance Examination in 2019 to enroll in Guangzhou Medical University in China was evaluated and followed up for retesting 6 months later. We used SPSS 20.0 statistical software for comparative analysis, including One-Sample T-Test, Independent-Samples T-Test, Paired Samples T-Test and Chi-square Test. RESULTS: Our data showed that 12.10% of students had mental health problems during the postgraduate entrance examination, and it decreased significantly to 4.40% at the 6-month follow-up after the examination period finished (P < 0.01). Somatization was the most significant symptom of the students both during and after the postgraduate entrance examination stages. All SCL-90 factors were scored significantly lower both in and after the postgraduate entrance examination stages than the 2008 national college student norm score (P < 0.01). Excluding psychiatric factors, all other SCL-90 factors in the postgraduate entrance examination stage scored higher than the graduate stage (P < 0.05), and the total score of SCL-90 in female medical students was higher compared to male students (P < 0.05). CONCLUSION: The postgraduate entrance examination event has a significant negative influence on students' mental health. The mental health of college and graduate students as an important part of their higher education experience should be systematically studied, and psychological counselling or help should be provided to them throughout their studies, specifically during the examination period. Educating applicants about mental health should be implemented during the postgraduate entrance examination curriculum.

Association of Early Increase in Body Temperature with Symptomatic Intracranial Hemorrhage and Unfavorable Outcome Following Endovascular Therapy in Patients with Large Vessel Occlusion Stroke.

INTRODUCTION: The aim of this study was to investigate for possible associations between an early increase in body temperature within 24 hours of endovascular therapy (EVT) for large vessel occlusion stroke and the presence of symptomatic intracranial hemorrhage (sICH) and other clinical outcomes. METHODS: This was a retrospective study of consecutive patients with large vessel occlusion stroke who were treated with EVT from August 2018 to June 2021. Patients were divided into two groups based on the presence of fever, as defined by a Peak Body Temperature (PBT) of ≥37.3 °C. The presence of sICH and other clinical outcomes were compared between the two groups. RESULTS: The median NIHSS admission score (IQR) was 16.0 (12.0, 21.0), with higher NIHSS scores in the PBT ≥37.3 °C group than in the PBT <37.3 °C group (18 vs 14, respectively; p = 0.002). There were no differences in clinical outcomes at 3 months between patients with PBT <37.3 °C and patients with PBT between 37.3 °C and 38 °C. However, patients with PBT ≥38 °C had an increased risk of sICH (adjusted odds ratio (OR) = 8.8, 95% confidence interval (95% CI): 1.7-46.0; p = 0.01), increased inpatient death or hospice discharge (OR = 10.5, 95% CI: 2.0-53.9; p = 0.005), poorer clinical outcome (OR = 25.6, 95% CI: 5.2-126.8; p < 0.001), and increased 3-month mortality (OR = 6.6, 95% CI: 1.8-24.6; p = 0.01). CONCLUSIONS: Elevated PBT (≥38 °C) within 24 hours of EVT was significantly associated with an increased incidence of symptomatic intracranial hemorrhage, discharge to hospice or inpatient death, poorer clinical outcome and 3-month mortality, and with less functional independence. Further large-scale, prospective and multicenter trials are needed to confirm these findings.

Apathy symptoms increase the risk of dementia conversion: a case-matching cohort study on patients with post-stroke mild cognitive impairment in China.

BACKGROUND: Apathy is a neuropsychiatric symptom frequently observed in patients with cognitive impairment. It has been found to be a predictor of conversion from mild cognitive impairment (MCI) to dementia of Alzheimer disease type. However, this association between apathy and dementia conversion has not yet been confirmed in vascular MCI, especially post-stroke MCI. The aim of this study was to evaluate whether apathy would increase the risk of dementia conversion in patients with post-stroke MCI after 6 months. METHOD: A prospective multi-centre cohort study was performed in 14 clinics in seven provinces and cities of China. A total of 989 subjects were included 2 weeks to 6 months after stroke, and met the diagnostic criteria of International Working Group for MCI. Symptoms of apathy were assessed using the apathy subscale of Geriatric Depression Scale. Subjects were divided into an apathy group (n = 128) and a non-apathy group (n = 861). The primary outcome was the dementia conversion after 6 months. To eliminate potential biases, subjects were chosen from 861 non-apathy patients with similarity in seven potential predictors of cognitive impairment to match with the apathy group (n = 128) at a 1:1 ratio, as a matched non-apathy group (n = 128). The dementia conversion rate was compared between the apathy group (n = 128) and its correspondingly matched non-apathy group (n = 128), and the relative risk (RR) was calculated. RESULTS: The prevalence of apathy in post-stroke MCI was 12.9%. After 6 months, 5.2% of patients with post-stroke MCI converted to dementia. The dementia conversion rate of the apathy group was significantly higher than that of the non-apathy group before case-matching (17.2% vs 3.4%, P < 0.001), and also after case-matching (17.2% vs 6.3%, P < 0.001). Symptoms of apathy increased the risk of conversion from MCI to dementia (RR 2.75, 95% CI 1.272-5.947, P < 0.001). CONCLUSIONS: For patients with post-stroke MCI, apathy symptoms increase the risk of conversion from MCI to dementia.

Autophagy Induced by Oxygen-Glucose Deprivation Mediates the Injury to the Neurovascular Unit.

BACKGROUND Autophagy is characterized by the degradation of cellular components in autophagosomes. It plays a significant role in cerebral ischemic injury and has a complex functional connection with apoptosis. The neurovascular unit (NVU) is a structural and functional unit of the nervous system presented as a therapeutic target of stroke. This study aimed to investigate the effect of autophagy induced by ischemic damage on NVUs. MATERIAL AND METHODS SH-SY5Y cells, C6 cells, and rat brain microvascular endothelial cells were cultured with oxygen-glucose deprivation (OGD) exposure for different time durations, and 3-methyladenine (3-MA) was added as an autophagy inhibitor. In all 3 cell lines, lactate dehydrogenase (LDH) release was measured. Furthermore, apoptosis was detected using Annexin V-fluorescein isothiocyanate/propidium iodide labeling and immunofluorescence staining. Autophagosomes were observed through AO/MDC (acridine orange/monodansycadaverine) double staining. LC3-II expression levels were evaluated by western blot analysis. RESULTS In the OGD groups of 3 cell lines, LDH leakage, and apoptotic rates were obviously increased. Remarkable increase in LC3-II expression was found in the OGD groups of SH-SY5Y cells and C6 cells. However, 3-MA decreased the LC3-II expression to varying degrees. CONCLUSIONS OGD could induce the over-activation of autophagy and augment the apoptotic activity in neurons and glial cells of NVUs.

Diabetes and vascular mild cognitive impairment among Chinese ≥50 years: A cross-sectional study with 2020 participants.

BACKGROUND: With the decline of cognitive function in vascular cognitive impairment, the burden on the family and society will increase. Therefore, early identification of vascular mild cognitive impairment (VaMCI) is crucial. The focus of early identification of VaMCI is on the attention of risk factors. Therefore, this study aimed to investigate the relationship between diabetes and VaMCI among the Chinese, hoping to predict the risk of VaMCI by diabetes and to move the identification of vascular cognitive impairment forward. METHODS: We collected data from seven clinical centers and nine communities in China. All participants were over 50 years of age and had cognitive complaints. We collected basic information of the participants, and cognitive function was professionally assessed by the Montreal Cognitive Assessment scale. Finally, logistic regression analysis was used to analyze the correlation between each factor and VaMCI. RESULTS: A total of 2020 participants were included, including 1140 participants with VaMCI and 880 participants with normal cognition. In univariate logistic regression analysis, age, heavy smoking, and diabetes had a positive correlation with VaMCI. At the same time, being married, high education, and light smoking had a negative correlation with VaMCI. After correction, only diabetes (OR = 1.04, 95% CI: 1.01-1.09, p = 0.05) had a positive correlation with VaMCI, and high education (OR = 0.60, 95% CI:.45-.81, p = 0.001) had a negative correlation with VaMCI. CONCLUSION: In our study, we found that diabetes had a positive correlation with VaMCI, and high education had a negative correlation with VaMCI. Therefore, early identification and timely intervention of diabetes may reduce the risk of VaMCI and achieve early prevention of VaMCI.

How Can China's New Health Care Reform Promote the Balance of Interest Game?-Based on Game Evolution and Simulation Analysis.

Purpose: The new round of medical reform is a significant exploration of reform in the public service sector in China. Health insurance regulatory departments, medical institutions, and patients, as critical stakeholders in China's medical reform, play a crucial role in the success of the reform through their strategic interactions. Patients and Methods: Starting from the perspective of bounded rationality, applies evolutionary game theory to establish an evolutionary game model for the collaborative governance of health insurance regulatory departments, medical institutions, and patients and analyzes the stability of each party's strategy and the sensitivity of parameters in the tripartite game system. Results: The study shows that an equilibrium point will be formed when medical institutions provide reasonable treatment, patients choose to accept treatment, and health insurance regulatory departments adopt a lenient regulatory strategy, maximizing the interests of all parties involved in the game. Factors such as the benefits of unreasonable treatment by medical institutions, fines, and regulatory costs impact the decision-making of health insurance regulatory departments. To maximize social welfare, health insurance regulatory departments should reform payment methods, adjust medical service behaviors of medical institutions, and guide the rational allocation of medical resources; the government should increase subsidies for the operation of medical institutions and the intensity of penalties; regulatory departments should reduce regulatory costs and introduce third-party forces to strengthen health insurance supervision further. Conclusion: The research findings of this paper will provide valuable insights into some countries' medical and health reform.

Lanosterol Synthase Prevents EMT During Lens Epithelial Fibrosis Via Regulating SREBP1.

Purpose: Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is a predominant pathological process underlying fibrotic cataracts. Here we investigated the role and mechanism of lanosterol synthase (LSS), a key rate-limiting enzyme in sterol biosynthesis, in EMT of LECs. Methods: Human lens epithelial explants, primary rabbit LECs, and whole rat lenses were treated with TGFß2. RNA-sequencing was conducted to explore genetic changes during fibrosis of human lens epithelial explants. Loss- and gain-of-function studies were performed in primary LECs to investigate roles and mechanisms of LSS, lanosterol and sterol regulatory element binding transcription protein 1 (SREBP1) in EMT. Rat lenses were applied to evaluate the potential effect of lanosterol on lens fibrosis. Expression of LSS, SREBP1, EMT-related regulators, and markers were analyzed by Western blot, qRT-PCR, or immunofluorescent staining. Results: LSS and steroid biosynthesis were downregulated in TGFß2-induced lens fibrosis. LSS inhibition directly triggered EMT by inducing Smad2/3 phosphorylation and nucleus translocation, an overexpression of LSS protected LECs from EMT by inhibiting Smad2/3 activation. Moreover, LSS inhibition decreased the expression of SREBP1, which regulated EMT via intervening TGFß2/Smad2/3 transduction. Furthermore, lanosterol protected LECs from EMT caused by both TGFß2 treatment and LSS inhibition via suppressing Smad2/3 activation and maintained lens transparency by preventing fibrotic plaques formation. Conclusions: We first identified that LSS protected LECs from EMT and played an antifibrotic role to maintain lens transparency. Additionally, lanosterol and sterol biosynthesis regulation might be promising strategies for preventing and treating fibrotic cataracts.

Antiepileptic therapy in a patient with star fruit intoxication: A case report.

RATIONALE: It is rare for uremia patients to have epileptic seizures after eating star fruit, only a dozen cases are reported worldwide. Such patients usually have poor prognoses. Few patients had good prognoses, all of them were treated with expensive renal replacement therapy. At present, there is no report on the addition of drug therapy to these patients based on the initial renal replacement therapy. PATIENT CONCERNS: A 67-year-old male patient with star fruit intoxication who had a history of diabetic nephropathy, hypertension, polycystic kidney, and chronic kidney disease in the uremic phase, and regular hemodialysis 3 times a week for 2 years. Initial clinical manifestations include hiccups, vomiting, speech disturbances, delayed reactions, and dizziness, which gradually progress to hearing and visual impairment, seizures, confusion, and coma. DIAGNOSES: This patient was diagnosed with seizures caused by star fruit intoxication. The experience of eating star fruit and the electroencephalograms can prove our diagnosis. INTERVENTIONS: We performed intensive renal replacement therapy according to the recommendations in the literature. However, his symptoms did not improve significantly until he received an extra dose of levetiracetam and resumed his previous dialysis schedule. OUTCOMES: The patient was discharged after 21 days without neurologic sequelae. Five months after discharge, he was readmitted due to poor seizure control. LESSONS: To improve the prognosis of these patients and to reduce their financial burden, the use of antiepileptic drugs should be emphasized.

The Impact of COVID-19 Pandemic Lockdown on Emergency Department Visits in a Tertiary Hospital.

Purpose: This study aimed to highlight the impact of the COVID-19 pandemic lockdown on emergency department (ED) visits of non-COVID-19 patients in a tertiary hospital and evaluate protocol development during this period. Patients and Methods: Clinical data of patients who visited the ED of Foshan Hospital of Traditional Chinese Medicine during the first-level response in Foshan, Guangdong province in 2020 (from January 23 to February 24) and the same period in 2019 and 2021 were collected. A retrospective cross-sectional analysis was performed to understand the characteristics of critically ill patients and compare the proportion of hospitalizations, deaths, and emergency ambulance calls (EACs). Results: The number of patients presenting to the ED was significantly decreased, with a 37.75% reduction in 2020 (6196) compared to the same period in 2019 (9954). A rise in patient ED presentations was observed in the same period in 2021 (10,503). This decline was mostly in the 15-45 age group. In 2019, 2020, and 2021, critically ill patients treated by the ED totaled 568 (5.706%), 339 (5.495%), and 590 (5.617%), respectively. Compared to the same period in 2019 and 2021, the proportion of critically ill patients with respiratory system involvement, severe trauma, and poisoning decreased most significantly in 2020 (P<0.05). In contrast, the rates of EACs, hospitalizations, and deaths increased significantly (P<0.05). Conclusion: The number of ED visits to hospitals was decreased during the 2020 lockdown, while the rates of EACs, hospitalizations, and deaths increased significantly though there were no documented COVID-19 cases. Optimizing emergency medical resources and ensuring the safety of healthcare providers and patients were essential to provide efficient emergency diagnosis and treatment during the lockdown.

Protective effect and possible mechanisms of geniposide for ischemia-reperfusion injury: A systematic review with meta-analysis and network pharmacology of preclinical evidence.

Background: Geniposide, as a pharmacologically bioactive component, is derived from a classic and common Chinese herb, Gardenia jasminoides Ellis. Geniposide has been shown to be effective for treating I/R injury in recent studies. Current effectively pharmaceutical treatments are scarce, and treatment based on geniposide may become a novel option. As far as we know, this research is the initial systematic evaluation of the protective effects of geniposide in I/R injury. Aim of the study: This study is engrossed in evaluating the mechanism of action of geniposide in I/R injury through a preclinical systematic review with meta-analysis and network pharmacology. Materials and methods: We built a systematic review which provided a view of effect and mechanism of geniposide for I/R injury. Based on seven databases, an open-ended search from their inception to August 31st, 2022, was conducted. Animal studies on the effects of geniposide in I/R injury were considered. The data was analyzed using Review Manager 5.3, and bias was assessed using the CAMARADES 10-item scale. 13 articles including 279 animals were selected finally. And network pharmacology was joined to elucidate the mechanism. Results: According to the meta-analysis, in I/R injury, geniposide can attenuate cardiomyocytes viability and the size of MI, decrease the volume of cerebral infraction and neurological score, decrease serum ALT and AST activity, and downregulated serum Cr and BUN. The review found that geniposide protects against I/R injury by inhibiting apoptosis, oxidation, inflammation and improvement of autophagy and mitochondrial respiration, which is consistent with the results of the network pharmacology screening. Conclusion: This preclinical systematic review including meta-analysis and network pharmacology, which was the first one summarizing the relationship between geniposide and ischemia diseases, shows a novel therapy for I/R injury and appears an enticing implication of geniposide in I/R injury, and further research is looked forward. Given the restricted quantity of included researches and the unclear risk of bias of the studies, we should interpret the results with caution.

A serum metabolomics study of vascular cognitive impairment patients based on Traditional Chinese medicine syndrome differentiation.

Objective: Vascular cognitive impairment (VCI) accounts for approximately 50%-70% of all dementia cases and poses a significant burden on existing medical systems. Identifying an optimal strategy for preventing VCI and developing efficient symptomatic treatments remains a significant challenge. Syndrome differentiation represents a fundamental approach for personalized diagnosis and treatment in Traditional Chinese Medicine (TCM) and aligns with the principles of precision medicine. The objective of this study was to elucidate the metabolic characteristics of VCI based on TCM syndrome differentiation, thus providing novel insights into the diagnosis and treatment of VCI. Methods: A 2-year cross-sectional cognitive survey was conducted in four communities in Beijing between September 2020 and November 2022. The syndrome differentiation of participants was based on the Kidney-Yang Deficiency Syndrome Scale (KYDSS), which was originally developed by Delphi expert consultation. The identification of serum metabolites was performed by Ultra performance liquid chromatography (UPLC) analysis coupled with an electrospray ionization quadruple time-of-flight mass spectrometer (ESI-QTOF MS). Multivariate, univariate, and pathway analyses were used to investigate metabolic changes. Logistic regression models were also used to construct metabolite panels that were capable of discerning distinct groups. Phospholipase A2 (PLA2) levels were measured by a commercial ELISA kit. Results: A total of 2,337 residents completed the survey, and the prevalence of VCI was 9.84%. Of the patients with VCI, those with Kidney-Yang deficiency syndrome (VCIS) accounted for 70.87% of cases and exhibited more severe cognitive impairments. A total of 80 participants were included in metabolomics study, including 30 with VCIS, 20 without Kidney-Yang deficiency syndrome (VCINS), and 30 healthy control participants (C). Ultimately, 45 differential metabolites were identified when comparing the VCIS group with group C, 65 differential metabolites between the VCINS group and group C, and 27 differential metabolites between the VCIS group and the VCINS group. The downregulation of phosphatidylethanolamine (PE), and phosphatidylcholine (PC) along with the upregulation of lysophosphatidylethanolamine (LPE), lysophosphatidylcholine (LPC), phosphatidic acid (PA) and phospholipase A2 (PLA2) can be considered as the general metabolic characteristics associated with VCI. Dysfunction of glycerophospholipids, particularly LPEs and PCs, was identified as a key metabolic characteristic of VCIS. In particular Glycerophospho-N-Arachidonoyl Ethanolamine (GP-NArE) was discovered for the first time in VCI patients and is considered to represent a potential biomarker for VCIS. The upregulation of PLA2 expression was implicated in the induction of alterations in glycerophospholipid metabolism in both VCIS and VCINS. Moreover, robust diagnostic models were established based on these metabolites, achieving high AUC values of 0.9322, 0.9550, and 0.9450, respectively. Conclusion: These findings contribute valuable information relating to the intricate relationship between metabolic disorders in VCI, neurodegeneration and vascular/neuroinflammation. Our findings also provide a TCM perspective for the precise diagnosis and treatment of VCI in the context of precision medicine.

The Rule of Law for the Exercise of Marriage and Reproductive Rights for Women with Intellectual Disabilities in China.

Women with intellectual disabilities (WIDs) are entitled to the rights to marriage and reproduction under Chinese law. However, Chinese marriage and reproduction regimes have imposed restrictions on their right to marry that limit the exercise of their reproductive rights. Marrying WIDs has become a popular choice for men in rural areas. Although in China's Civil Code, the legislature has repealed the prior requirement of a medical examination for marriage registration, the exercise of rights to marriage and reproduction by WIDs is still restricted. China has not fully implemented equal rights for persons with disabilities under the United Nations Convention on the Rights of Persons with Disabilities. China needs to set legal procedural requirements for the exercise of these rights for different types of WIDs, systematically constructing them at three levels: legal basis, legislative implementation, and institutional support.

Regulating the product quality of COVID-19 antigen testing reagents: A tripartite evolutionary game analysis under China's legal framework.

Personal purchases of novel coronavirus antigen detection reagents (ADRs) for self-detection have contributed to the optimization of medical resources and containment of the COVID-19 pandemic. The recurring occurrence of false testing results in China has generated concerns regarding the quality of ADRs and the testing mechanism for medical devices. Academic viewpoints and remarks on the sensitivity, application possibilities, and product innovation of ADRs may be found in the extant scientific literature. However, the current research does not explore the microscopic product quality concerns that emerge throughout the production and marketing of ADRs. To explore strategic equilibrium circumstances and behavioral evolution processes, an evolutionary game model was developed to include ADR manufacturers, third-party medical device inspection agencies, and regulatory authorities. The results reveal that the quantity of illegal incentives, the cost of regulation, and the loss of government credibility have a major impact on the decisions of regulatory authorities and determine three potential systemic equilibrium states. To maximize social welfare, ADRs should be incorporated into China's medication price monitoring system in order to manage market prices. To cut regulatory expenses, the government should employ blockchain technology for traceable network regulation of ADR product quality. The government should also protect the people's right to free speech and encourage online reporting of adverse incidents caused by ADRs. The conclusions of this article can provide many developing nations with important insights for regulating the quality of ADR products.

Multinucleated Retinal Pigment Epithelial Cells Adapt to Vision and Exhibit Increased DNA Damage Response.

Multinucleated retinal pigment epithelium (RPE) cells have been reported in humans and other mammals. Rodents have an extremely high percentage of multinucleated cells (more than 80%). Both mouse and human multinucleated RPE cells exhibit specific regional distributions that are potentially correlated with photoreceptor density. However, detailed investigations of multinucleated RPE in different species and their behavior after DNA damage are missing. Here, we compared the composition of multinucleated RPE cells in nocturnal and diurnal animals that possess distinct rod and cone proportions. We further investigated the reactive oxygen species (ROS) production and DNA damage response in mouse mononucleated and multinucleated RPE cells and determined the effect of p53 dosage on the DNA damage response in these cells. Our results revealed an unrealized association between multinucleated RPE cells and nocturnal vision. In addition, we found multinucleated RPE cells exhibited increased ROS production and DNA damage after X-ray irradiation. Furthermore, haploinsufficiency of p53 led to increased DNA damage frequency after irradiation, and mononucleated RPE cells were more sensitive to a change in p53 dosage. In conclusion, this study provides novel information on in vivo PRE topography and the DNA damage response, which may reflect specific requirements for vision adaption and macular function.

TFEB-Mediated Lysosomal Restoration Alleviates High Glucose-Induced Cataracts Via Attenuating Oxidative Stress.

Purpose: Diabetic cataract (DC) is a visual disorder arising from diabetes mellitus (DM). Autophagy, a prosurvival intracellular process through lysosomal fusion and degradation, has been implicated in multiple diabetic complications. Herein, we performed in vivo and in vitro assays to explore the specific roles of the autophagy-lysosome pathway in DC. Methods: Streptozotocin-induced DM and incubation in high glucose (HG) led to rat lens opacification. Protein Simple Wes, Western blot, and immunoassay were utilized to investigate autophagic changes in lens epithelial cells (LECs) and lens fiber cells (LFCs). RNA-sequencing (RNA-seq) was performed to explore genetic changes in the lenses of diabetic rats. Moreover, autophagy-lysosomal functions were examined using lysotracker, Western blot, and immunofluorescence analyses in HG-cultured primary rabbit LECs. Results: First, DM and HG culture led to fibrotic LECs, swelling LFCs, and eventually cataracts. Further analysis showed aberrant autophagic degradation in LECs and LFCs during cataract formation. RNA-seq data revealed that the differentially expressed genes (DEGs) were enriched in the lysosome pathway. In primary LECs, HG treatment resulted in decreased transcription factor EB (TFEB) and cathepsin B (CTSB) activity, and increased lysosomal size and pH values. Moreover, TFEB-mediated dysfunctional lysosomes resulted from excessive oxidative stress in LECs under HG conditions. Furthermore, TFEB activation by curcumin analog C1 alleviated HG-induced cataracts through enhancing lysosome biogenesis and activating protective autophagy, thereby attenuating HG-mediated oxidative damage. Conclusions: In summary, we first identified that ROS-TFEB-dependent lysosomal dysfunction contributed to autophagy blockage in HG-induced cataracts. Additionally, TFEB-mediated lysosomal restoration might be a promising therapeutic method for preventing and treating DC through mitigating oxidative stress.

Cognitive recovery in patients with post-stroke subjective cognitive complaints.

Background and purpose: The objective cognitive trajectory in patients with post-stroke subjective cognitive complaints (SCC) over time remained unknown. We investigated cognitive outcomes in patients with SCC within 1 year after stroke, and determined factors associated with cognitive recovery. Methods: This study included 599 patients with a clinical diagnosis of post-stroke SCC and evidence of cognitive deficits including Clinical Dementia Rating Scale (CDR) = 0.5, Montreal Cognitive Assessment (MoCA) score <26, and Mini-Mental State Examination score >17 (illiterate) or >20 (primary school) or >24 (junior school or above). Neuropsychological assessment was performed at baseline (2 weeks to 6 months after stroke) and 6-month follow-up visit. Cognitive recovery was operationalized as unimpaired cognition (MoCA score ≥26 and CDR = 0) after 6 months. Factors associated with recovery were defined through logistic regression analysis. Results: After 6 months, 583 patients completed the follow-up with 80 (13.72%) presenting cognitive recovery, among which, 22 (9.48%) cases reported SCC within 2 weeks after stroke, six (10%) at 15-30 days, 13 (15.12%) at 31-60 days, 10 (16.13%) at 61-90 days, five (10.42%) at 91-120 days, nine (23.08%) at 121-150 days, and 15 (26.79%) at 151-180 days. Compared to those reported cognitive complaints at 151-180 days after stroke, patients with early post-stroke SCC had poorer cognitive recovery, which was only significant in individuals with high level of education. Male sex, higher baseline MoCA scores, coffee intake and thalamus lesions were independently associated with high chance of cognitive recovery. Conclusions: Although post-stroke SCC contributes to persisting objective cognitive deficits, some patients presented cognitive recovery within 1 year after stroke. Patients with a high education level reporting SCC at earlier stage after stroke had poorer cognitive recovery. Male, higher baseline MoCA scores, coffee intake and thalamus lesions appear to independently predict cognitive recovery.

Long Non-Coding RNA H19 Prevents Lens Fibrosis through Maintaining Lens Epithelial Cell Phenotypes.

The integrity of lens epithelial cells (LECs) lays the foundation for lens function and transparency. By contrast, epithelial-mesenchymal transition (EMT) of LECs leads to lens fibrosis, such as anterior subcapsular cataracts (ASC) and fibrotic forms of posterior capsule opacification (PCO). However, the underlying mechanisms remain unclear. Here, we aimed to explore the role of long non-coding RNA (lncRNA) H19 in regulating TGF-ß2-induced EMT during lens fibrosis, revealing a novel lncRNA-based regulatory mechanism. In this work, we identified that lncRNA H19 was highly expressed in LECs, but downregulated by exposure to TGF-ß2. In both human lens epithelial explants and SRA01/04 cells, knockdown of H19 aggravated TGF-ß2-induced EMT, while overexpressing H19 partially reversed EMT and restored lens epithelial phenotypes. Semi-in vivo whole lens culture and H19 knockout mice demonstrated the indispensable role of H19 in sustaining lens clarity through maintaining LEC features. Bioinformatic analyses further implied a potential H19-centered regulatory mechanism via Smad-dependent pathways, confirmed by in vitro experiments. In conclusion, we uncovered a novel role of H19 in inhibiting TGF-ß2-induced EMT of the lens by suppressing Smad-dependent signaling, providing potential therapeutic targets for treating lens fibrosis.

Autophagy inhibition attenuates TGF-ß2-induced epithelial-mesenchymal transition in lens epithelial cells.

AIMS: Autophagy has been reported to play an essential role in fibrotic disorders. Known as fibrotic cataract, posterior capsular opacification (PCO) result from pathological epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). This study aims to identify the role and potential mechanism of autophagy in TGF-ß2-induced EMT in LECs. MAIN METHODS: Primary rabbit LECs were treated with TGF-ß2 to induce EMT as a model of fibrotic cataract in vitro. 3-methyladenine, chloroquine, bafilomycin A1, and gene silencing of autophagy-related protein 7 (ATG7) were treated in LECs for autophagy inhibition, while rapamycin was utilized for autophagy activation. The expression levels of EMT/autophagy-associated markers were analyzed by qRT-PCR, western blotting, immunofluorescence and transmission electron microscopy. We additionally examined cell migration ability with transwell migration assay and wound healing assay. KEY FINDINGS: TGF-ß2 promoted autophagy flux during EMT progression of LECs in a time-dependent manner. Autophagy activation by rapamycin enhanced TGF-ß2-triggered fibrogenic responses and cell migration in LECs, whereas pharmacological inhibition of autophagy alleviated TGF-ß2-induced increases of EMT markers and cell migration of LECs. In addition, the phosphorylation of Smad2/3 induced by TGF-ß2 was suppressed through autophagy inhibition, while it was promoted upon autophagy activation, indicating that TGF-ß2/Smad signaling was involved in the modulation of autophagy on EMT in LECs. Furthermore, ATG7-silenced LECs exerted anti-fibrosis effect induced by TGF-ß2 through downregulation of autophagy. SIGNIFICANCE: Intervention/inhibition of autophagy could attenuate TGF-ß2-induced EMT in LECs, which provides autophagy-related insights on preventing and treating the fibrotic cataract or other fibrotic diseases.