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Abstract Background Coronary artery disease (CAD) is a major global cardiovascular health threat and the leading cause of death in many countries. The disease has a significant impact in China, where it has become the leading cause of death. There is an urgent need to develop non-invasive, rapid, cost-effective, and reliable techniques for the early detection of CAD using machine learning (ML). Methods Six hundred eight participants were divided into three groups: healthy, hypertensive, and CAD. The raw data of pulse wave from those participants was collected. The data were de-noised, normalized, and analyzed using several applications. Seven ML classifiers were used to model the processed data, including Decision Tree (DT), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), Extra Trees (ET), Extreme Gradient Boosting (XGBoost), Light Gradient Boosting (LightGBM), and Unbiased Boosting with Categorical Features (CatBoost). Results The Extra Trees classifier demonstrated the best classification performance. After tunning, the results performance evaluation on test set are: 0.8579 accuracy, 0.9361 AUC, 0.8561 recall, 0.8581 precision, 0.8571 F1 score, 0.7859 kappa coefficient, and 0.7867 MCC. The top 10 feature importances of ET model are w/t 1, t 3/t max , t max , t 3/t 1, As, h f/3, t f/3/t max , t f/5, w and t f/3/t 1. Conclusion Radial artery pulse wave can be used to identify healthy, hypertensive and CAD participants by using Extra Trees Classifier. This method provides a potential pathway to recognize CAD patients by using a simple, non-invasive, and cost-effective technique.

Abstract The association between obstructive sleep apnea (OSA) and proteinuria is undetermined, with few studies on hypertension, a high-risk group for renal impairment. Therefore, we aimed to explore whether OSA is an independent risk factor for proteinuria in patients with hypertension. We investigated the cross-sectional association between OSA and proteinuria. Participants were divided into groups by apnea hypopnea index (AHI) category. Multivariable Logistic regression analysis was used to evaluate the association between OSA severity, objectively measured sleep dimensions, and proteinuria which is mainly defined by 24-h urine protein quantification > 300 mg/24 h. Sensitivity analyses were performed by excluding those with comorbidities (primary aldosteronism and homocysteine ≥ 15 μmol/L). Of the 2106 participants, the mean age was 47.57 ± 10.50 years, 67.2% were men, and 75.9% were OSA patients. In total participants, compared with those without OSA, patients with mild OSA, moderate OSA, and severe OSA showed 1.09 (95% CI 0.80–1.40), 1.24 (95% CI 0.89–1.74) and 1.47 (95% CI 1.04–2.08) fold risk for proteinuria with a trend test P trend

Abstract Background Warburg-Cinotti syndrome is a rare syndrome caused by de novo or inherited variants in discoding domain receptor tyrosine kinase 2 (DDR2). Only six cases have been reported worldwide and our knowledge of this disease remained sparse especially from an ophthalmological perspective, since previous literature mostly focused on systemic malformations or genetics. Case presentation A seven-year-old boy developed a gelatinous vascularized conjunctiva-like mass secondary to trauma. The mass enlarged and gradually invaded the cornea. With each surgical intervention, the mass recurred and grew even larger rapidly. The patient ended up with the mass covering the entire cornea along with symblepharon formation. Whole exome sequencing revealed a hemizygous variant in the DDR2 gene, which is consistent with Warburg-Cinotti syndrome. Conclusions Considering Warburg-Cinotti syndrome, we should be vigilant of patients exhibiting progressive conjunctival invasion of the cornea, even those without systemic manifestations or a positive family history.

Abstract Introduction The aim of this work was to compare the prognosis and characteristics of patients with Cytomegalovirus (CMV) infection (CMV+) with those of patients without virus infection (Virus–) undergoing repeat keratoplasty. Methods This prospective propensity score-matched cohort study enrolled patients who underwent repeat keratoplasty for graft failure at the Peking University Third Hospital between January 2016 and May 2022. Patients with prior viral keratitis before the first keratoplasty were excluded. The primary outcome measure was the graft failure rate. The secondary outcome measures included the anterior segment characteristics, intraocular pressure (IOP), and endothelial cell density. Results Ninety-four matched patient pairs were included. The graft failure rate in the CMV+ group (71%) was higher than that in the Virus– group (29%) (P

Abstract Background Aldosterone plays important parts in development of cardio-metabolic diseases as end product of renin-angiotensin-aldosterone system. However, factors elevating circulating aldosterone are not clear, and lifestyle-related factors are suggested to be involved, whereas less studied. Therefore, we aimed to explore the association of lifestyle factors with plasma aldosterone concentration (PAC) in community population. Methods In this cross-sectional study, we recruited participants using multistage random sampling from Emin China in 2019, and collected data and fasting blood samples. The considered lifestyle factors included obesity parameters (neck circumference, abdominal circumference), alcohol consumption, blood pressure (BP), physical activity, sleep duration, sleep quality, mental state (depression and anxiety), fasting blood glucose (FBG), and lipid profiles (total cholesterol and triglyceride). PAC was measured using radioimmunoassay. We performed sex-stratified linear and logistic regressions to explore associated factors of PAC. Component analysis was further performed to identify the main factors affecting PAC. Results Twenty-seven thousand four hundred thirty-six participants with 47.1% men were included. Obesity parameters (neck circumference, abdominal circumference), glucose metabolism (FBG), psychological status (anxiety status in men and women, depression status in men), BP, liver function (in men), lipid metabolism (TC and TG in men), sleep parameters (sleep quality in women), and renal function (in women) are the main factors associated with elevated PAC. Conclusion lower physical activity, alcohol consumption, higher BP, fat accumulation, dyslipidemia, higher fasting blood glucose, and presence of depression and anxiety were the main factors associated with eleveated PAC.

Abstract Purpose To summarize the outcomes of corneal sight rehabilitating surgery in Stevens-Johnson syndrome (SJS). Methods This is a retrospective analysis of a consecutive case series. Twenty-four eyes of 18 SJS patients were included in this study. The ocular parameters, surgical procedures, postoperative complications, and additional treatments of the cases were reviewed. Results A total of 29 corneal sight rehabilitating surgeries, which consists of 9 keratoplasties, 8 Keratolimbal allograft (KLAL) and 12 combined surgeries (keratoplasty and KLAL simultaneously) were performed on the 24 eyes. All patients were treated with glucocorticoid eyedrops and tacrolimus eyedrops for anti-rejection treatment without combining systemic immunosuppression, except two patients who were prescribed prednisone tablets for the management of systemic conditions. The mean follow-up period was 50.6 ± 28.1 months. The optimal visual acuity (VA) (0.74 ± 0.60 logarithm of the minimum angle of resolution [logMAR]) and endpoint VA (1.06 ± 0.82 logMAR) were both significantly better than the preoperative VA (1.96 ± 0.43 logMAR) (95% CI, p = 0.000). 57.1% patients (8/14) were no longer in the low vision spectrum, and 88.9% patients (8/9) were no longer blind. The mean epithelialization time was 7.1 ± 7.6 weeks. The success rate was 86.7%. Additional treatments for improving epithelialization included administration of serum eyedrops (n = 10), contact lens (n = 15), amniotic membrane transplantation (n = 6), and tarsorrhaphy (n = 8). Complications included delayed epithelialization (n = 4, over 12 weeks), glaucoma (n = 11), and severe allograft opacity (n = 4). Only one graft rejection was observed. Conclusions Keratoplasty and KLAL can remarkably enhance VA and improve low vision or even eliminate blindness for ocular complications of SJS. The outcome of the surgeries was correlated with the preoperative ocular situation and choice of operative methods.

Abstract Purpose To use artificial intelligence to establish an automatic diagnosis system for corneal endothelium diseases (CEDs). Methods We develop an automatic system for detecting multiple common CEDs involving an enhanced compact convolutional transformer (ECCT). Specifically, we introduce a cross-head relative position encoding scheme into a standard self-attention module to capture contextual information among different regions and employ a token-attention feed-forward network to place greater focus on valuable abnormal regions. Results A total of 2723 images from CED patients are used to train our system. It achieves an accuracy of 89.53%, and the area under the receiver operating characteristic curve (AUC) is 0.958 (95% CI 0.943–0.971) on images from multiple centres. Conclusions Our system is the first artificial intelligence-based system for diagnosing CEDs worldwide. Images can be uploaded to a specified website, and automatic diagnoses can be obtained; this system can be particularly helpful under pandemic conditions, such as those seen during the recent COVID-19 pandemic.

ABSTRACTUsing a sample of Chinese listed firms over 2011–2020, this study examines the impact of digital finance on accounting information transparency. Our findings reveal an inverted U-shaped relationship between digital finance and accounting information transparency, suggesting that digital finance within certain limits increases accounting information transparency by optimising information acquisition and processing, but excessive digital finance leads to information overload and impairs accounting information transparency. Our findings are robust to a variety of sensitivity tests and are still valid after using two-stage “shift-share” instrumental variable procedures, propensity score matching method and firm-level fixed effect regression to control for the endogeneity issue. Lastly, MD&A and annual reporting disclosure timeliness are two influential channels by which digital finance affects accounting information transparency, and further the inverted U-shaped relationship is more pronounced for firms in provinces with lower marketisation indexes (CEO-chairman duality) than for their counterparts.

ObjectiveTo explore the link between plasma aldosterone concentration (PAC) and the prevalence of metabolic dysfunction-related fatty liver disease (MAFLD) in hypertensive patients.MethodsWe analyzed data from 41,131 hospitalized patients from January 1, 2014, to December 31, 2023. Multivariate logistic regression models tested associations, with threshold, subgroup, and sensitivity analyses conducted to validate findings.ResultsFor each 5-unit increase in PAC, the risk of MAFLD rose by 1.57 times, consistent even in the fully adjusted model. The odds ratios for the Q2, Q3, and Q4 groups compared to Q1 were 1.21, 2.12, and 3.14, respectively. A threshold effect was observed at 14 ng/dL, with subgroup and sensitivity analyses supporting these results.ConclusionsThis study reveals a significant positive association between elevated PAC levels and the prevalence of MAFLD in hypertensive patients. These findings underscore the imperative for further large-scale, prospective studies to validate and expand upon this correlation.

PurposeOur study utilizes Mendelian Randomization (MR) to explore the causal relationships between a range of risk factors and preeclampsia, a major contributor to maternal and perinatal morbidity and mortality.MethodsEmploying the Inverse Variance Weighting (IVW) approach, we conducted a comprehensive multi-exposure MR study analyzing genetic variants linked to 25 risk factors including metabolic disorders, circulating lipid levels, immune and inflammatory responses, lifestyle choices, and bone metabolism. We applied rigorous statistical techniques such as sensitivity analyses, Cochran’s Q test, MR Egger regression, funnel plots, and leave-one-out sensitivity analysis to address potential biases like pleiotropy and population stratification.ResultsOur analysis included 267,242 individuals, focusing on European ancestries and involving 2,355 patients with preeclampsia. We identified strong genetic associations linking increased preeclampsia risk with factors such as hyperthyroidism, BMI, type 2 diabetes, and elevated serum uric acid levels. Conversely, no significant causal links were found with gestational diabetes, total cholesterol, sleep duration, and bone mineral density, suggesting areas for further investigation. A notable finding was the causal relationship between systemic lupus erythematosus and increased preeclampsia risk, highlighting the significant role of immune and inflammatory responses.ConclusionThis extensive MR study sheds light on the complex etiology of preeclampsia, underscoring the causal impact of specific metabolic, lipid, immune, lifestyle, and bone metabolism factors. Our findings advocate for a multidimensional approach to better understand and manage preeclampsia, paving the way for future research to develop targeted preventive and therapeutic strategies.

In the dynamics of grid-connected operation of brushless doubly fed generators (BDFG), when the grid voltage dips, it is equivalent to adding a reverse voltage source at the parallel node suddenly. By deriving the expressions of the transient current of power winding (PW), control winding (CW), and rotor winding (RW) of BDFG in the complex frequency domain under natural state, it is concluded that the overshoot and oscillation time are affected by the generator parameters, the drop degree and phase of the grid voltage, and the rotor speed. Then, a state feedback control strategy is proposed, and a state model with PW, CW, and RW current as state variables is constructed. State variables are added to the input through the feedback matrix, the parameters of system matrix of the generator are changed, that is, the equivalent parameters of the generator are changed. The pole distribution diagram shows that under the state feedback strategy, the poles shift significantly to the left compared with the poles with traditional control, so it could make the system accelerate convergence, reduce the amplitude. Finally, the feasibility of the state feedback algorithm was verified using tests on an experimental platform.

Summary: Background: Pregnant women with hepatitis C virus (HCV) infection represent a special population in which treatment access remains limited despite its increasing prevalence. A reliable estimate of the burden and clinical outcomes of pregnant women with HCV infection is crucial for HCV elimination. We aimed to determine the prevalence, maternal-to-child transmission (MTCT), maternal and fetal complication rates, and direct acting antivirals (DAA) treatment outcomes of chronic HCV infection in pregnant women. Methods: We searched PubMed, EMBASE, Scopus, Web of Science from inception until March 1, 2024, for studies reporting on the prevalence, MTCT, complications of HCV infection, and treatment outcomes of DAA in pregnant women. Study quality was assessed using the Newcastle–Ottawa Scale. We performed subgroup analysis based on 9 variables to explore the source of heterogeneity in HCV prevalence. The PROSPERO registration number is CRD42024500023. Findings: From a total of 311,905,738 pregnant women from 333 studies, the pooled global seroprevalence of HCV in pregnant women was 2.6% (95% CI: 2.0–3.2, I2 = 100%) which increased in patients with intravenous drug use and HIV. Majority of the HCV cases in pregnant women (75%) are diagnosed through universal screening. The pooled MTCT rate was 9.0% (95% CI: 6.6–11.7, I2 = 79%), which was higher with HIV co-infection (OR: 3.1, 95% CI: 2.1–4.6, I2 = 10%), but was not influenced by the mode of delivery or breastfeeding. Pregnant women with HCV infection had more maternal complications, including intrahepatic cholestasis, preterm delivery, and antepartum hemorrhage. Neonates of mothers with HCV had higher odds of being small for gestational age. The pooled rate of sustained virologic response (SVR12) among the 74 women treated with DAA during pregnancy was 98.4%, with no serious adverse events reported. Interpretation: HCV prevalence in pregnant women varies by geographic region and patient population, while MTCT occurs in almost one in ten viremic mothers. The incidence of both maternal and neonatal complications is significantly higher in patients with HCV infection. Limited data suggest that DAA are safe in pregnant women with HCV infection. Funding: None.

Based on the ecological environmental statistics and monitoring datas of municipal wastewater treatment plants in China， the empirical sludge yield coefficient（YQ） and the sludge yield coefficient（YCOD） calculated based on the sludge proliferation caused by the removal of COD in municipal wastewater treatment plants in China were analyzed，and the response relationships between single factor such as influent COD，design treatment scale，treatment process，regional distribution and sludge yield coefficient，as well as response relationships between multiple factors and sludge yield coefficient were studied. The results showed that the average of YQ of municipal wastewater treatment plants in China was 1.33×10-4 t/m3 and the average of YCOD was 0.81 kg/kg. YQ and YCOD showed positive skewed distribution in general. The average of YQ was positively correlated with COD in influent and design treatment scale，meanwhile the average of YCOD was negatively correlated with COD in influent and design treatment scale. The COD range corresponding to the average values of YQ and YCOD was 150-250 mg/L. YQ and YCOD for wastewater treatment plants with design treatment scale of 1×104-1×105 m3/d were the closest to the overall national average，with relative deviations of 2.8% and -4.3% respectively. YQ and YCOD of A2/O process，oxidation ditch type，ordinary activated sludge method and A/O process were close to the overall national average，with relative deviations ranging from -1.8%-1.9% and -2.3%-5.8% respectively. YQ of East China and Central China，YCOD of East China and Southwest China were basically the same as the national average. The COD in influent was the most significant influencing factor for YQ and YCOD through using multifactor analysis of variance.

Abstract Objective Recently, the stress hyperglycemia ratio (SHR) has been introduced as a metric to signify relative hyperglycemia. This study aimed to investigate the relationship between SHR and in-hospital mortality and length of stay occurring during hospitalization in stroke patients. Methods The retrospective cohort study comprised a total of 4,018 patients diagnosed with acute stroke. The SHR is expressed by the formula: SHR = ABG (mmol/L) / [1.59 × HbA1c (%) − 2.59]. Outcomes included in-hospital mortality and length of stay. Multivariable logistic and linear regression analyses were conducted. Receiver operating characteristic (ROC) analysis was performed to distinguish between the variables, and the area under the ROC curve (AUC) was compared. Results In this analysis, a total of 4,018 individuals participated, including 2,814 male patients, accounting for 70.0%. Overall, in-hospital mortality and length of stay tended to rise as SHR increased. A higher prevalence of in-hospital mortality was observed with each standard deviation (SD) increase of the SHR (odds ratio [OR]: 1.26, 95% confidence interval [CI]: 1.05–1.52). Moreover, after considering the confounders, a significant positive association between SHR levels and length of stay was observed (β = 0.70, 95% CI: 0.40-1.00). ROC analysis showed that among stroke patients, SHR (AUC = 0.693) was more effective than admission blood glucose (ABG) (AUC = 0.646) and glycosylated hemoglobin (HbA1c) (AUC = 0.523), which were more predictive of in-hospital mortality. Conclusions Elevated SHR levels are associated with increased in-hospital mortality and prolonged length of stay in stroke patients.

Abstract Purpose Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a relatively rare subtype of DLBCL. Herein, we report a case of a patient with EBV-positive iris DLBCL after undergoing penetrating keratoplasty and discuss its possible pathogenesis. Methods A 72-year-old male patient presented to our hospital with progressive blurring of vision in the left eye for the past 4 months. Small white nodular lesions were observed on the iris and retinal surface of the left eye, with a white cloud-like opacity in the vitreous cavity. Results The patient was eventually diagnosed with EBV-positive iris DLBCL after undergoing pathological and metagenomic tests. After injecting methotrexate in the left vitreous cavity and administering systemic and local antiviral treatments, the ocular lesions disappeared. Conclusion EBV infection, drug immunosuppression, and aging-related immune deterioration may play significant roles in the pathogenesis of EBV-positive iris DLBCL. Synopsis Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a new subtype of DLBCL, which rarely occurs. Herein, we report a case of a patient with EBV-positive iris DLBCL after undergoing penetrating keratoplasty and discuss its possible pathogenesis.

Abstract The purpose of this study was to determine the long-term pattern of plasma aldosterone concentration (PAC) trajectories and to explore the relationship between PAC trajectory patterns and cardiovascular disease (CVD) risk in patients with hypertension. Participants were surveyed three times between 2010 and 2016, and latent mixed modeling was employed to determine the trajectory of PAC over the exposure period (2010–2016). A Cox regression analysis was used to examine the association between PAC trajectory patterns and the risk of CVD (stroke and myocardial infarction). Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated and reported. During a median follow-up of 4.10 (3.37–4.50) years, 82 incident CVD cases (33 myocardial infarction cases and 49 stroke cases) were identified. Among all three PAC models, the high-stability PAC pattern exhibited the highest risk of CVD. After full adjustment for all covariables, HRs were 2.19 (95% CI 1.59–3.01) for the moderate-stable pattern and 2.56 (95% CI 1.68–3.91) for the high-stable pattern in comparison to the low-stable pattern. Subgroup and sensitivity analyses verified this association. The presence of a high-stable PAC trajectory pattern is associated with an elevated risk of CVD in hypertensive patients. Nevertheless, more studies are warranted to confirm these findings.

AIM: To compare the surgical outcomes of glaucoma drainage device implantation (GDI) and trans-scleral neodymium:YAG cyclophotocoagulation (CPC) in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty (DSAEK). METHODS: This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery (15 with GDI and 14 with CPC). The main outcome measures were intraocular pressure (IOP), glaucoma surgery success rate (defined as IOP of 6–21 mm Hg without additional anti-glaucoma operation), number of glaucoma medications, endothelial graft status, and best-corrected visual acuity (BCVA). RESULTS: The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries, both for the GDI and CPC groups. Both groups showed significant IOP reduction after glaucoma surgery. The GDI group presented a significantly higher success rate in IOP control than the CPC group (60% vs 21.4%, P=0.03). Both procedures significantly decreased the number of glaucoma medications (P=0.03). Forty percent and 57% of cases in the GDI and the CPC group, respectively, experienced endothelial graft failure during follow-up (P=0.36). Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group. CONCLUSION: Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK. GDI is preferable to CPC in refractory glaucoma cases after DSAEK, as it manifests a significantly higher success rate for IOP control, similar endothelial graft failure rate, and relatively preserves BCVA than CPC.

BackgroundPrior research has highlighted the association between uric acid (UA) and the activation of the renin-angiotensin-aldosterone system (RAAS). However, the specific relationship between aldosterone, the RAAS’s end product, and UA-related diseases remains poorly understood. This study aims to clarify the impact of aldosterone on the development and progression of hyperuricemia and gout in hypertensive patients.MethodsOur study involved 34534 hypertensive participants, assessing plasma aldosterone concentration (PAC)’s role in UA-related diseases, mainly hyperuricemia and gout. We applied multiple logistic regression to investigate the impact of PAC and used restricted cubic splines (RCS) for examining the dose-response relationship between PAC and these diseases. To gain deeper insights, we conducted threshold analyses, further clarifying the nature of this relationship. Finally, we undertook subgroup analyses to evaluate PAC’s effects across diverse conditions and among different subgroups.ResultsMultivariate logistic regression analysis revealed a significant correlation between the occurrence of hyperuricemia and gout and the elevation of PAC levels. Compared to the first quartile (Q1) group, groups Q2, Q3, and Q4 all exhibited a significantly increased risk of occurrence. Moreover, the conducted RCS analysis demonstrated a significant nonlinear dose-response relationship, especially when PAC was greater than 14 ng/dL, with a further increased risk of hyperuricemia and gout. Finally, comprehensive subgroup analyses consistently reinforced these findings.ConclusionThis study demonstrates a close association between elevated PAC levels and the development of UA-related diseases, namely hyperuricemia and gout, in hypertensive patients. Further prospective studies are warranted to confirm and validate this relationship.

Corneal opacity is one of the leading causes of severe vision impairment. Corneal transplantation is the dominant therapy for irreversible corneal blindness. However, there is a worldwide shortage of donor grafts and consequently an urgent demand for alternatives. Three-dimensional (3D) bioprinting is an innovative additive manufacturing technology for high-resolution distribution of bioink to construct human tissues. The technology has shown great promise in the field of bone, cartilage and skin tissue construction. 3D bioprinting allows precise structural construction and functional cell printing, which makes it possible to print personalized full-thickness or lamellar corneal layers. Seed cells play an important role in producing corneal biological functions. And stem cells are potential seed cells for corneal tissue construction. In this review, the basic anatomy and physiology of the natural human cornea and the grafts for keratoplasties are introduced. Then, the applications of 3D bioprinting techniques and bioinks for corneal tissue construction and their interaction with seed cells are reviewed, and both the application and promising future of stem cells in corneal tissue engineering is discussed. Finally, the development trends requirements and challenges of using stem cells as seed cells in corneal graft construction are summarized, and future development directions are suggested.

BackgroundDespite observational links between serum uric acid (SUA), sex hormone-related phenotypes, and female infertility, the causality behind these associations remains uncertain.ObjectiveThis study utilizes Bidirectional Two-Sample and Mediation Mendelian Randomization to explore the causal relationships and mediation effects of sex hormone-binding globulin (SHBG), total testosterone (TT), and estradiol on these associations.MethodsWe analyzed single-nucleotide polymorphisms (SNPs) associated with SUA and sex hormone levels using data from large-scale GWAS of European populations. Female infertility data were sourced from 6,481 cases and 75,450 controls in the FinnGen Consortium. We employed methods including Inverse Variance Weighted (IVW), Weighted Median, and MR-Egger regression to assess causality.ResultsWe found that elevated SUA levels causally increase the risk of female infertility (IVW OR: 1.13, P=0.047). Elevated SUA levels significantly decrease SHBG levels (β=-0.261; P=2.177e-04), with SHBG mediating 27.93% of the effect of SUA on infertility (OR=0.854; 95%CI, 0.793–0.920; P=2.853e-05). Additionally, elevated TT levels, which were associated with decreased SUA levels (β=-0.127), showed an indirect effect on infertility mediated by SUA (β=-0.0187; 95% CI, -0.041 to -0.003; P=0.046).ConclusionOur findings demonstrate causal links between high SUA and increased risk of female infertility mediated by hormonal factors such as SHBG and TT. These insights suggest new avenues for infertility treatment and highlight the need for further research into these mechanisms.

BackgroundPrevious studies have suggested that aldosterone may play a major role in calcium-phosphorus homeostasis and bone metabolism. However, the relationship between plasma aldosterone concentrations (PAC) and bone mineral density (BMD) in middle-aged and elderly hypertensive patients remains unclear. Therefore, this study sought to investigate the relationship between PAC levels and BMD and explore PAC’s potential impact on osteoporosis and future fracture risk in hypertensive patients.MethodsOur study included a total of 1430 participants. Associations are tested using multiple linear and logistic regression models. Nonlinearity was investigated using the restricted cubic spline (RCS). We also performed mediating analyses to assess mediating factors mediating the relationship between PAC and osteoporosis.ResultsThe multiple linear regression showed a negative correlation between PAC and BMD and was generally positively associated with FRAX scores. Meanwhile, logistic regression analyses indicated that osteoporosis was highly correlated with PAC levels. In addition, a clear non-linear dose-response relationship was also shown in the constructed RCS model. Finally, mediation analyses showed that serum potassium played an important role in the development of osteoporosis.ConclusionThis study demonstrates that elevated PAC levels are strongly associated with decreased BMD, increased prevalence of osteoporosis, and the risk of future fractures in middle-aged and elderly hypertensive patients. Further studies are needed to confirm this relationship and reveal its underlying mechanisms.

Abstract Background The structural features have an impact on the surgical prognosis for congenital corneal opacity (CCO). The structural classification system of CCO, however, is lacking. Based on data from ultrasound biomicroscopy (UBM) findings in infants and toddlers with CCO, this research proposed a classification system for the anterior segment structure severity. Methods Medical records, preoperative UBM images and slit-lamp photographs of infants and toddlers diagnosed with CCO at University Third Hospital between December 2018 and June 2022 were reviewed. According to the anterior segment structural features observed in UBM images, eyes were classified as follows: U1, opaque cornea only; U2, central anterior synechia; U3, peripheral anterior synechia combined with angle closure; and U4, aniridia or lens anomaly. The opacity appearance and corneal vascularization density observed in slit-lamp photographs were assigned grades according to previous studies. The extent of vascularization was also recorded. The corresponding intraocular anomaly classifications and ocular surface lesion severity were analysed. Results Among 81 eyes (65 patients), 41 (50.6%) were right eyes, and 40 (49.4%) were left eyes. The median age at examination was 6.91 months (n = 81, 1.00, 34.00). Two (2.5%) of the 81 eyes were classified as U1, 20 (24.7%) as U2, 22 (27.2%) as U3a, 11 (13.6%) as U3b and 26 (32.1%) as U4. Bilateral CCO eyes had more severe UBM classifications (P = 0.019), more severe dysgenesis (P = 0.012) and a larger angle closure (P = 0.009). Eyes with more severe UBM classifications had higher opacity grades (P = 0.003) and vascularization grades (P = 0.014) and a larger vascularization extent (P = 0.001). Eyes with dysgenesis had higher haze grades (P = 0.012) and more severe vascularization (P = 0.003 for density; P = 0.008 for extent), while the angle closure range was related to haze grade (P = 0.013) and vascularization extent (P = 0.003). Conclusions This classification method based on UBM and slit-lamp photography findings in the eyes of CCO infants and toddlers can truly reflect the degree of abnormality of the ocular surface and anterior segment and is correlated with the severity of ocular surface anomalies. This method might provide meaningful guidance for surgical procedure design and prognostic determinations for keratoplasty in CCO eyes.

Abstract Introduction Neurotrophic keratopathy (NK) is a rare degenerative ocular disease that can be difficult to treat. There were no effective resolutive treatments for severe NK caused by ocular graft-versus-host disease (oGVHD) along with virus infection. To address this question, we designed a prospective cohort study to evaluate the efficacy and safety of topical recombinant human nerve growth factor (rhNGF) in patients with recalcitrant NK of oGVHD and viral infection. Methods This prospective cohort study enrolled patients with recalcitrant NK diagnosed with oGVHD and treated with rhNGF. Clinical evaluations included the range of epithelial defects, best corrected visual acuity, intraocular pressure, slit-lamp examination, and corneal fluorescein staining. Examinations of the central corneal thickness, corneal sensitivity, and nerve fiber regeneration were performed at each visit at 4, 8, 12, 20 weeks and 6 months, respectively, after initiating rhNGF treatment. Results All enrolled patients were diagnosed with NK at stage 2 (7 eyes, 63.6%) or stage 3 (4 eyes, 36.4%) and responded to rhNGF treatment. Five of 11 (45.5%) and 9 of 11 eyes (81.8%) achieved complete corneal epithelial healing after 4 and 8 weeks, respectively. All 11 eyes (100%) achieved complete corneal healing after 12 weeks. There was also a significant reduction in the corneal ulcer area during each visit (P

Abstract Nitrogen has five valence electrons and can form a maximum of three shared electron-pair bonds to complete its octet, which suggests that its maximum bond order is three. With a joint anion photoelectron spectroscopy and quantum chemistry investigation, we report herein that nitrogen presents a quadruple bonding interaction with thorium in ThN. The quadruple Th≣N bond consists of two electron-sharing Th-N π bonds formed between the Th-6d xz/6d yz and N 2p x/2p y orbitals, one dative Th←N σ bond and one weak Th←N σ bonding interaction formed between Th-6d z 2 and N 2s/2p z orbitals. The ThC molecule has also been investigated and proven to have a similar bonding pattern as ThN. Nonetheless, due to one singly occupied σ-bond, ThC is assigned a bond order of 3.5. Moreover, ThC has a longer bond length as well as a lower vibrational frequency in comparison with ThN.

Abstract Background Deep anterior lamellar keratoplasty (DALK) has gained popularity in cases of corneal thinning and leaking descemetocele. In this study, we introduced an intralamellar tectonic patch graft in addition to conventional DALK procedures to treat frank cornea perforation. Methods This retrospective case series included 13 patients (13 eyes) with frank corneal perforations who underwent DALK combined with intralamellar tectonic patch graft between December 2015 and December 2021. In addition to the standard DALK procedure, the perforation site was repaired with an extra intralamellar tectonic patch graft. The collected data included patient demographics, aetiology, size and location of the corneal perforation, visual acuity, surgical details, and postoperative complications. Results Seven patients underwent autologous intralamellar patch grafts, whereas six received allogeneic ones. Anatomical success was achieved in all patients. The mean postoperative follow-up was 33.31 ± 25.96 months (6–73 months). The postoperative visual acuity (0.90 ± 0.65 logMAR) was significantly improved (P = 0.003) compared to the preoperative score (1.74 ± 0.83 logMAR). Best corrected visual acuity (BCVA) improved in 12 eyes (92.3%). The mean endothelial cell density was 2028 ± 463 cells/mm2, 6–12 months postoperatively. There was no recurrence of perforation, and the anterior lamellar graft remained transparent in 12 patients (92.3%). Postoperative complications included epithelial defects (23.1%), ocular hypertension (15.4%), and cataract (7.7%). Conclusions DALK combined with intralamellar tectonic patch graft may serve as a secure and effective alternative in treating frank corneal perforation, with reduced complications compared to conventional penetrating keratoplasty.

Abstract Background The goal of this study is to develop a fully automated segmentation and morphometric parameter estimation system for assessing abnormal corneal endothelial cells (CECs) from LASER in vivo confocal microscopy (IVCM) images. Methods First, we developed a fully automated deep learning system for assessing abnormal CECs using a previous development set composed of normal images and a newly constructed development set composed of abnormal images. Second, two testing sets, one with 169 normal images and the other with 211 abnormal images, were used to evaluate the clinical validity and effectiveness of the proposed system on LASER IVCM images with different corneal endothelial conditions, particularly on abnormal images. Third, the automatically calculated endothelial cell density (ECD) and the manually calculated ECD were compared using both the previous and proposed systems. Results The automated morphometric parameter estimations of the average number of cells, ECD, coefficient of variation in cell area and percentage of hexagonal cells were 257 cells, 2648 ± 511 cells/mm2, 32.18 ± 6.70% and 56.23 ± 8.69% for the normal CEC testing set and 83 cells, 1450 ± 656 cells/mm2, 34.87 ± 10.53% and 42.55 ± 20.64% for the abnormal CEC testing set. Furthermore, for the abnormal CEC testing set, Pearson’s correlation coefficient between the automatically and manually calculated ECDs was 0.9447; the 95% limits of agreement between the manually and automatically calculated ECDs were between 329.0 and − 579.5 (concordance correlation coefficient = 0.93). Conclusions This is the first report to count and analyze the morphology of abnormal CECs in LASER IVCM images using deep learning. Deep learning produces highly objective evaluation indicators for LASER IVCM corneal endothelium images and greatly expands the range of applications for LASER IVCM.

Demodex is one of the most common parasites in the human body. It can be classified into demodex folliculorum and demodex brevis based on the parasitic sites. It is an opportunistic pathogenic microorganism, and clinical symptoms may not appear in part of infected people, but the parasite can cause multiple common ocular diseases represented by blepharitis. Its typical symptoms include dry eyes, foreign body sensation in eyes, secretion attached to eyelashes, and ocular surface irritation. The diagnosis of demodex blepharitis should be based on the clinical manifestations and the results of etiological tests. The treatment is related to many kinds of drugs including plant essential oil and physical therapy. At present, diagnosing and treating demodex blepharitis is increasingly sophisticated, but the relationship between demodex infection and its pathogenicity remains unclear. This paper summarizes the current characteristics of demodex and the clinical manifestation, diagnosis, treatment, and existing issues of demodex blepharitis, hoping to provide a reference for future studies in demodex.

Visceral leishmaniasis (VL) is the most severe type of leishmaniasis which is caused by infection of Leishmania donovani complex. In the BALB/c mouse model of VL, multinucleated giant cells (MGCs) with heavy parasite infection consist of the largest population of hemophagocytes in the spleen of L. donovani-infected mice, indicating that MGCs provide the parasites a circumstance beneficial for their survival. Although ATP6V0D2 is a demonstrated factor inducing the formation of hemophagocytic MGCs during L. donovani infection, functions of this protein in shaping the infection outcome in macrophages remain unclear. Here we evaluated the influence of upregulated ATP6V0D2 on intracellular survival of the parasites. L. donovani infection-induced hemophagocytosis of normal erythrocytes by macrophages was suppressed by RNAi-based knockdown of Atp6v0d2. The knockdown of Atp6v0d2 did not improve the survival of amastigotes within macrophages when the cells were cultured in the absence of erythrocytes. On the other hand, reduced intracellular survival of amastigotes in macrophages by the knockdown was observed when macrophages were supplemented with antibody-opsonized erythrocytes before infection. There, increase in cytosolic labile iron pool was observed in the L. donovani-infected knocked-down macrophages. It suggests that ATP6V0D2 plays roles not only in upregulation of hemophagocytosis but also in iron trafficking within L. donovani-infected macrophages. Superior access to iron in macrophages may be how the upregulated expression of the molecule brings benefit to Leishmania for their intracellular survival in the presence of erythrocytes.

Wire electrical discharge machining (WEDM) is highly suitable for processing the hard-brittle materials like metallic glasses (MGs). However, the electro-thermal energy conversion involved in the WEDM process inevitably introduces some surface defects including bulges, discharge craters, and recast materials on the WEDMed MG surface, which significantly impedes its practical application. Here, an emerging automated polishing technology, laser polishing (LP), was performed in the nitrogen-rich environment to simultaneously improve the surface quality and hardness of the WEDMed Zr-based MG surface. The detailed effects of LP parameters on the surface roughness and morphology were systematically investigated. The morphology evolution and temperature distribution of the molten pool during LP were analyzed by simulation analysis. The experimental results indicated that after single LP of four representative WEDMed Zr-based MG surfaces using the optimized laser parameters, the surface roughness (Sa) was remarkably reduced from 1.27, 2.10, 3.49, and 4.58 μm to 0.09, 0.14, 0.17, and 0.21 μm, respectively, accompanied by an increase in surface hardness from 6.30 GPa to 7.39, 7.67, 8.51 and 8.99 GPa. This study demonstrated that LP could effectively achieve simultaneous enhancement of the quality and hardness of WEDMed MG surfaces, which would contribute to expanding the application prospects of MGs.

BackgroundPrevious studies have yielded conflicting findings regarding the association between circulating lipids and lipid-lowering drugs with urinary stones, and the causal relationship between the two remains inconclusive.ObjectiveThis study aimed to assess the causal relationship between circulating lipids (Triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], apolipoprotein A [APOA], apolipoprotein B [APOB] and Pure hypercholesterolaemia), lipid-lowering drugs (HMGCR [HMG-CoA reductase] inhibitors and PCSK9[Proprotein Convertase Subtilisin/Kexin Type 9] inhibitors) and the risk of urinary stones, using genetic data.MethodsGenetic instrumental variables (GIVs) for circulating lipids and lipid-lowering drugs were obtained from the UK Biobank and existing literature. Outcome data were extracted from a genetic association database with 3,625 urinary stone cases and 459,308 controls. Two-sample MR analysis, employing the TwoSampleMR software package in R 4.2.3, was conducted to assess the associations between multiple exposures. The primary outcome was determined using the inverse variance weighted (IVW) method for the causal relationship between exposure and outcome, while additional methods such as MR-Egger, weighted median, simple mode, and weighted mode were utilized as supplementary analyses. Robustness of the Mendelian Randomization (MR) analysis results was assessed through leave-one-out analysis and funnel plots.ResultsThe MR analysis revealed a significant association between elevated TG levels per 1 standard deviation and the occurrence of urinary stones (odds ratio [OR]: 1.002, 95% confidence interval [CI]: 1.000-1.003, P = 0.010). However, no significant association was observed between factors other than TG exposure and the risk of urinary stone occurrence across all methods(LDL-C: [OR], 1.001; 95% [CI], 1.000-1.003, P=0.132;HDL-C: [OR], 0.999; 95% [CI], 0.998-1.000, P=0.151;APOA:[OR] being 1.000 (95% [CI], 0.999-1.001, P=0.721;APOB: [OR] of 1.001 (95% [CI], 1.000-1.002, P=0.058;Pure hypercholesterolaemia: [OR] of 1.015 (95% [CI], 0.976-1.055, P=0.455) and lipid-lowering drugs (HMGCR inhibitors: [OR], 0.997; 95% [CI], 0.990-1.003, P=0.301 and PCSK9 inhibitors:[OR], 1.002; 95% [CI], 1.000-1.005, P=0.099).ConclusionOur findings provide conclusive evidence supporting a causal relationship between an increased risk of urinary stones and elevated serum TG levels. However, we did not find a significant association between urinary stone occurrence and the levels of LDL-C, HDL-C, APOA, APOB, Pure hypercholesterolaemia and lipid-lowering drugs.

ABSTRACTHuman papillomavirus (HPV) has a great impact on world health. Vaccination is among the most important methods of preventing HPV infection. This study investigated Chinese male college students’ knowledge of, attitude toward, and acceptance of the 9vHPV vaccine and the independent predictors. An online cross-sectional study was conducted among male college students at Chinese colleges and universities from March 12 to March 23, 2022. Based on a literature review of similar studies, a self-questionnaire was designed to investigate the students’ knowledge of, attitude toward, and acceptance of the 9vHPV vaccine. Multivariate logistic regression analysis was performed to identify factors influencing their willingness to be vaccinated. In addition, the structural equation model was constructed. A total of 1,547 male college students completed the survey. Of all the students, 54.95% were unwilling to receive a 9vHPV vaccination, while only 45.05% expressed willingness. Multivariate logistic regression analysis revealed that the male college students willing to receive the vaccine included medical students, those in a romantic relationship, those whose relatives and friends had cervical cancer, those whose relatives and friends had received the 9vHPV vaccine, those supportive of promoting the vaccine for men, and those who would recommend the vaccine to their relatives and friends. Male college students exhibited high hesitancy toward the 9vHPV vaccine. Acceptance of the 9vHPV vaccine by male college students can be improved by deepening their accurate understanding of the vaccine and enhancing their positive attitude toward it.

Background Obesity, especially visceral obesity, plays an important role in the progression of cardiovascular disease (CVD). The body roundness index (BRI) is a new measure of obesity that is considered to reflect visceral obesity more comprehensively than other measures. This study aims to evaluate the relationship between BRI and CVD risk in hypertensive patients with obstructive sleep apnea (OSA) and explore its superiority in predicting CVD. Methods The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD. The area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to assess which measures of obesity had the best predictive value for CVD risk. Results During a median follow-up period of 6.8 years, 324 participants suffered a CVD event. After multivariable adjustment, compared with the reference group (the first tertile), the HRs (95% CI) of CVD were 1.25 (95% CI, 0.93–1.70) and 1.74 (95% CI, 1.30–2.33) for subjects in the tertile 2 and tertile 3 groups, respectively. Compared with other measurement indicators, BRI has the highest predictive value for CVD risk [AUC: 0.627, 95% CI: 0.593–0.661]. The addition of the BRI to the fully adjusted multivariate model improved the predictive power for CVD, which was validated in the continuous NRI and the IDI (all P

BackgroundDuring cataract phacoemulsification surgery, the Alcon Centurion with Active Sentry can achieve a more stable anterior chamber, which allows a lower intraocular pressure (IOP) setting than the gravity fluidics system. In this randomized controlled trial, we compared these two systems’ damage to the cornea under different IOP settings.MethodsSeventy-eight eyes of 53 patients with corneal endothelial cell density (ECD) of 500∼1500/mm2 were enrolled and randomly divided into the active fluidics system (AFS) group using an Active Sentry handpiece with 30 mmHg IOP setting (40 eyes) and the gravity fluidics system (GFS) group using an Ozil handpiece with 80 cmH2O IOP setting (38 eyes). Intraoperative parameters, visual acuity, corneal edema ratio, central corneal thickness (CCT) changes as well as loss rate of ECD were analyzed.ResultsWe observed no significant differences in best corrected visual acuity (BCVA), cumulative dissipated energy (CDE), total case time, estimated fluidics usage (EFU) and ophthalmic viscoelastic devices (OVDs) usage between the two groups. The enrolled eyes were further divided into soft nucleus (27 eyes) and hard nucleus (51 eyes) subgroups. And we found less pain complaint during surgeries, lower corneal edema ratio at 1-day and 1-week visit, smaller CCT changes at 1-day visit and lower ECD loss rate at 1-month visit (p < 0.05) in both subgroups of the AFS group than in the GFS group, implying higher intraoperative comfort levels and less corneal damage of the AFS group with a low IOP setting.ConclusionOwing to a lower IOP setting, Centurion® Vision System with Active Sentry handpiece causes less corneal damage and pain perception during phacoemulsification for patients with low pre-operative ECD.Clinical Trial Registrationhttps://www.chictr.org.cn, identifier ChiCTR2300077865.

Abstract Introduction This purpose of this work is to give a detailed description of a surgical technique for frameless robot-assisted asleep deep brain stimulation (DBS) of the centromedian thalamic nucleus (CMT) in drug-resistant epilepsy (DRE). Methods Ten consecutively enrolled patients who underwent CMT-DBS were included in the study. The FreeSurfer "Thalamic Kernel Segmentation" module and experience target coordinates were used for locating the CMT, and quantitative susceptibility mapping (QSM) images were used to check the target. The patient's head was secured with a head clip, and electrode implantation was performed with the assistance of the neurosurgical robot Sinovation®. After opening the dura, the burr hole was continuously flushed with physiological saline to stop air from entering the skull. All procedures were performed under general anesthesia without intraoperative microelectrode recording (MER). Results The mean age of the patients at surgery and onset of seizures was 22 years (range 11–41 years) and 11 years (range 1–21 years), respectively. The median duration of seizures before CMT-DBS surgery was 10 years (2–26 years). CMT was successfully segmented, and its position was verified by experience target coordinates and QSM images in all ten patients. The mean surgical time for bilateral CMT-DBS in this cohort was 165 ± 18 min. The mean pneumocephalus volume was 2 cm3. The median absolute errors in the x-, y-, and z-axes were 0.7 mm, 0.5 mm, and 0.9 mm, respectively. The median Euclidean distance (ED) and radial error (RE) was 1.3 ± 0.5 mm and 1.0 ± 0.3 mm, respectively. No significant difference was found between right- and left-sided electrodes regarding the RE nor the ED. After a mean 12-month follow-up, the average reduction in seizures was 61%, and six patients experienced a ≥ 50% reduction in seizures, including one patient who had no seizures after the operation. All patients tolerated the anesthesia operation, and no permanent or serious complications were reported. Conclusions Frameless robot-assisted asleep surgery is a precise and safe approach for placing CMT electrodes in patients with DRE, shortening the surgery time. The segmentation of the thalamic nuclei enables the precise location of the CMT, and the flow of physiological saline to seal the burr holes is a good way to reduce the influx of air. CMT-DBS is an effective method to reduce seizures.

Abstract Objective The Coronavirus Disease 2019 (COVID-19) has brought severe damage to global health and socioeconomics. In China, traditional Chinese medicine (TCM) is the most important complementary and alternative medicine (CAM) and it has shown a beneficial role in the prevention and treatment of COVID-19. However, it is unknown whether patients are willing to accept TCM treatment. The objective of our study is to investigate the acceptance, attitude, and independent predictors of TCM among asymptomatic COVID-19 patients admitted to Shanghai fangcang hospital during the outbreak of the COVID-19 pandemic in Shanghai in 2022. Methods A cross-sectional study was conducted on asymptomatic COVID-19 patients in the largest fangcang hospital in Shanghai, China, from April 22, 2022, to May 25, 2022. Based on the literature review of previous similar studies, a self-report questionnaire was developed to assess the patients’ attitude and acceptance of TCM, and a multivariate logistic regression analysis was conducted to determine the independent predictors of TCM acceptance. Results A total of 1,121 patients completed the survey, of whom 91.35% were willing to accept CAM treatment whereas 8.65% of participants showed no willingness. Multivariate logistic regression analysis revealed that the patients who have received two doses of COVID-19 vaccine (OR = 2.069, 95%CI: 1.029–4.162, P = 0.041 vs. not received), understood the culture of TCM (OR = 2.293, 95%CI: 1.029–4.162, P = 0.014 vs. not understood), thought the TCM treatment is safe (OR = 2.856, 95%CI: 1.334–6.112, P = 0.007 vs. not thought), thought the TCM treatment is effective (OR = 2.724, 95%CI: 1.249–5.940, P = 0.012 vs. not thought), and those who informed their attending physician if using TCM for treatment (OR = 3.455, 95%CI:1.867–6.392, P

Background: The accurate identification and diagnosis of secondary hypertension is critical,especially while cardiovascular heart disease continues to be the leading cause of death. To develop a big data intelligence platform for secondary hypertension using electronic medical records to contribute to future basic and clinical research. Methods: Using hospital data, the platform, named Hypertension DATAbase at Urumchi (UHDATA), included patients diagnosed with hypertension at the People’s Hospital of Xinjiang Uygur Autonomous Region since December 2004. The electronic data acquisition system, the database synchronization technology, and data warehouse technology (extract–transform–load, ETL) for the scientific research big data platform were used to synchronize and extract the data from each business system in the hospital. Standard data elements were established for the platform, including demographic and medical information. To facilitate the research, the database was also linked to the sample database system, which includes blood samples, urine specimens, and tissue specimens. Results: From December 17, 2004, to August 31, 2022, a total of 295,297 hypertensive patients were added to the platform, with 53.76% being males, with a mean age of 59 years, and 14% with secondary hypertension. However, 75,802 patients visited the Hypertension Center at our hospital, with 43% (32,595 patients) being successfully diagnosed with secondary hypertension. The database contains 1458 elements, with an average fill rate of 90%. The database can continuously include the data for new hypertensive patients and add new data for existing hypertensive patients, including post-discharge follow-up information, and the database updates every 2 weeks. Presently, some studies that are based on the platform have been published. Conclusions: Using computer information technology, we developed and implemented a big database of dynamically updating electronic medical records for patients with hypertension, which is helpful in promoting future research on secondary hypertension.

PurposeTo verify the International Chronic Ocular Graft-Versus-Host Disease (ICCGVHD) Group diagnostic criteria and establish an easy-to-use and reliable diagnosis model for quick identification of chronic oGVHD.MethodsThis study included 180 patients (355 eyes) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and visited the Peking University Third Hospital Cornea and Ocular Surface Disease Specialist Clinic from July 2020 to February 2021. The proportion of chronic oGVHD was 76.06% (279/355).ResultsFive complaints, including eye dryness, photophobia, foreign body sensation, eye redness, and burning sensation; six ophthalmic examinations, including Ocular Surface Disease Index (OSDI) score, corneal fluorescein staining (CFS), tear break-up time (TBUT), Schirmer’s test score without anesthesia, conjunctival score, tear meniscus height, and non-ocular GVHD-involved organs were significantly different between patients with chronic oGVHD and control group (p

PurposeThe purpose of this study was to investigate the in vivo morphologic features of the cornea in patients with unilateral posterior interstitial keratitis.MethodsSeven eyes of 7 patients with unilateral posterior interstitial keratitis were examined by slit-lamp biomicroscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy (IVCM). The imaging features of the cornea were evaluated and analyzed.ResultsBy slit-lamp examination, the posterior corneal stromal opacities were observed in all 7 eyes, and deep neovascularization in 4 eyes. The posterior stromal opacities showed higher reflectivity with an intact overlying epithelium by AS-OCT and did not invade the Bowman’s layer in all cases. IVCM revealed highly reflective dispersed microdots, needle-shaped bodies, and increased reflectivity of keratocytes in the lesion site in all patients. Active Langerhans cells and an attenuated subbasal nerve plexus were observed in 5 eyes. After treatment, the active Langerhans cells disappeared; however, highly reflective microdots and needle-shaped bodies remained.ConclusionThe three-dimensional evaluation of slit-lamp biomicroscopy, AS-OCT, and IVCM may help in the early diagnosis of patients with posterior interstitial keratitis.

AIM: To investigate corneal graft survival rate and endothelial cell density (ECD) loss after keratoplasty in cytomegalovirus (CMV) positive patients. METHODS: This was a retrospective cohort study. We analyzed the clinical data of patients who underwent viral DNA detection in aqueous humor/corneal tissue collected during keratoplasty from March 2015 to December 2018 at the Peking University Third Hospital, Beijing, China. To further evaluate the effect of CMV on graft survival rate and ECD loss, patients were divided into three groups: 1) CMV DNA positive (CMV+) group; 2) viral DNA negative (virus-) group, comprising virus- group eyes pairwise matched to eyes in the CMV+ group according to ocular comorbidities; 3) control group, comprising virus- group eyes without ocular comorbidities. The follow-up indicators including graft survival rate, ECD, ECD loss, and central corneal thickness (CCT), were analyzed by Tukey honestly significant difference (HSD) test. RESULTS: Each group included 29 cases. The graft survival rate in CMV+ group were lowest among the three groups (P=0.000). No significant difference in donor graft ECD was found among three groups (P=0.54). ECD in the CMV+ group was lower than the virus- group at 12 (P=0.009), and 24mo (P=0.002) after keratoplasties. Furthermore, ECD loss was higher in the CMV+ group than in the virus- group in the middle stage (6-12mo) post-keratoplasty (P=0.017), and significantly higher in the early stage (0-6mo) in the virus- group than in the control group (P=0.000). CONCLUSION: CMV reduces the graft survival rate and exerts persistent detrimental effects on the ECD after keratoplasty. The graft ECD loss associate with CMV infection mainly occurrs in the middle stage (6-12mo postoperatively), while ocular comorbidities mainly affects ECD in the early stage (0-6mo postoperatively).

Abstract Background Axenfeld-Rieger syndrome (ARS) is a rare kind of anterior segment dysgenesis (ASD). The most common ocular features of ARS are posterior embryotoxon and iris hypoplasia, while some patients may manifest as corneal opacity and edema. However, the current understanding of how ARS affects the cornea is still incomplete. This study reports a novel histopathological finding of ARS, complicating corneal abnormalities, including congenital corneal opacity and irreversible endothelial decompensation. Methods This retrospective study included 6 eyes of 3 ARS patients, 5 of which underwent keratoplasty for irreversible endothelial decompensation from May 2016 to January 2019. No eye had a history of surgery. We reviewed the data of epidemiology, clinical manifestations and histopathologic examinations. Results Five eyes developed irreversible endothelial decompensation, among which 4 were born with corneal opacity. One eye exhibited transparent cornea but showed a continuous loss of endothelial cells in the absence of surgery and elevated intraocular pressure thereafter. Anterior segment optical coherence tomography photographs showed that anterior synechia existed in the area with corneal opacities, where we found the interlayer splitting of the Descemet membrane inserted by hypoplastic iris and a basement membrane-like structure under a light microscope. Conclusion Anterior synechia might be associated with corneal abnormalities in ARS patients. The novel histopathologic finding revealed the internal relation between anterior segment dysgenesis and would help explore the inner mechanism of corneal abnormalities in ARS.

Abstract Background Regulatory T cells (Tregs) play a neuroprotective role by suppressing microglia and macrophage-mediated inflammation and modulating adaptive immune reactions. We previously documented that Treg immunomodulatory mechanisms are compromised in Alzheimer’s disease (AD). Ex vivo expansion of Tregs restores and amplifies their immunosuppressive functions in vitro. A key question is whether adoptive transfer of ex vivo expanded human Tregs can suppress neuroinflammation and amyloid pathology in a preclinical mouse model. Methods An immunodeficient mouse model of AD was generated by backcrossing the 5xFAD onto Rag2 knockout mice (5xFAD-Rag2KO). Human Tregs were expanded ex vivo for 24 days and administered to 5xFAD-Rag2KO. Changes in amyloid burden, microglia characteristics and reactive astrocytes were evaluated using ELISA and confocal microscopy. NanoString Mouse AD multiplex gene expression analysis was applied to explore the impact of ex vivo expanded Tregs on the neuroinflammation transcriptome. Results Elimination of mature B and T lymphocytes and natural killer cells in 5xFAD-Rag2KO mice was associated with upregulation of 95 inflammation genes and amplified number of reactive microglia within the dentate gyrus. Administration of ex vivo expanded Tregs reduced amyloid burden and reactive glial cells in the dentate gyrus and frontal cortex of 5xFAD-Rag2KO mice. Interrogation of inflammation gene expression documented down-regulation of pro-inflammatory cytokines (IL1A&B, IL6), complement cascade (C1qa, C1qb, C1qc, C4a/b), toll-like receptors (Tlr3, Tlr4 and Tlr7) and microglial activations markers (CD14, Tyrobp,Trem2) following Treg administration. Conclusions Ex vivo expanded Tregs with amplified immunomodulatory function, suppressed neuroinflammation and alleviated AD pathology in vivo. Our results provide preclinical evidences for Treg cell therapy as a potential treatment strategy in AD.

Abstract Background Adolescent obesity has been reported to have deleterious consequences but is considered a promising modifiable risk factor. We aimed to investigate the optimal intervention for obese and overweight children and adolescents. Methods We searched the Medline (PubMed, 1946–December 2020), PsycINFO (Ovid, 1927–December 2020), Cochrane library (1966–December 2020), Web of Science (1900–December 2020), Embase (1974–December 2020), CINAHL (1937–December 2020), Chinese Biomedical Literature (1978–December 2020), and ClinicalTrials.gov (December 2020) databases. We included randomized controlled trials (RCTs) reporting the association between various interventions and obese/overweight children and adolescents. The quality of the included studies was judged by two independent reviewers using the Cochrane Collaboration Risk of Bias Tool. A Bayesian network meta-analysis was conducted to summarize the comparative effectiveness of interventions based on several outcomes. Results We included 118 RCTs comprising 71,064 participants in our analyses. Based on the outcome of the body mass index (BMI), face-to-face physical activity (FTF PA) combined with dietary intervention (DI) (mean difference [MD] = − 0.98; 95% credible interval [CrI] − 1.19, − 0.77), FTF multi-lifestyle intervention (MLI) (MD = − 0.95; 95% CrI − 1.14, − 0.75), and mobile health (MH)-delivered MLI (MD = − 0.87; 95% CrI − 1.63, − 0.09) showed significant benefits over the named control group (NCG). For the outcome of BMI z-score, FTF PA+DI (MD = − 0.10; 95% CrI − 0.15, − 0.04) and MH-delivered PA+DI (MD = − 0.09; 95% CrI − 0.14, − 0.04) were more effective than the NCG. Sensitivity analyses revealed similar findings after exclusion of studies with

Abstract Background This study was performed to investigate the association between symptoms and signs in patients with meibomian gland dysfunction (MGD). Methods Data were obtained from 122 MGD patients who were recruited for intense pulsed light therapy from November 2017 to April 2018 and the severity of their symptoms and signs at baseline were observed and recorded. Spearman correlation analyses were performed to analyze the relationships between SPEED score and signs. Subjects were divided into different subgroups based on possible influencing factors, and the differences in symptoms and signs were compared between different subgroups. Then influencing factors were controlled by regression analysis to explore the relationship between symptoms and signs and the strong factors affecting symptoms and signs. Results Analysis of baseline data showed that SPEED scores were not correlated with TBUT, CFSS, MGYSS or any index of eyelid margin abnormality (p > 0.05). In addition, abnormalities of lid margins, including hyperemia, thickening, rounding, hyperkeratinization, and telangiectasia around orifices, were more likely to occur in older patients, menopausal patients, and patients living in northern China. Multiple linear regression analysis indicated that there was still no correlation between symptoms and signs (p > 0.05) after adjusting for influencing factors. Further analysis suggested that each influencing factor has different effects on symptoms and signs, among which menopause affects the SPEED score (R = -4.112, p = 0.025), and age and region have significant effects on eyelid margin abnormalities. Conclusions In conclusion, the results demonstrated a poor correlation between symptoms and signs in MGD patients. Age, hormone, and a dry environment may influence the disease, which suggests that the severity of the disease needs to be comprehensively assessed.

PurposeIridocorneal endothelial (ICE) syndrome is a progressive anterior segment disorder that can be tricky to treat. Keratoplasty is commonly used to treat corneal edema in ICE syndrome. However, glaucoma is an important risk factor affecting graft survival. To address this question, we designed a retrospective cohort study to evaluate the effect of Spokewise Iridotomy (SI) on Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) Grafts in Iridocorneal Endothelial (ICE) Syndrome.MethodsThis was a retrospective cohort study. A total of 29 patients were included; 31 eyes with ICE syndrome underwent DSAEK at Peking University Third Hospital between June 2015 and June 2022, including 11 eyes with combined SI during DSAEK. The aim was to explore the effect of SI on vision, glaucoma control, complications, peripheral anterior synechiae recurrence, endothelial cell count, and graft survival.ResultsThe median follow-up time was 30.83 months (mo.) in the SI+Endothelial Keratoplasty (EK) group and 6.17 mo in the EK group. The 2-year cumulative survival rate of grafts in the SI+EK group was 100%, compared with the 6-month and 1-year cumulative survival rates of 80.2 and 63.2%, respectively, in the EK group (p = 0.043). The SI+EK group had a lower incidence of immediate postoperative complications (p = 0.005), fewer postoperative anti-glaucoma medications (AGMs) (p = 0.029), smaller peripheral anterior synechiae recurrence (p = 0.001), and significant visual acuity improvement (p < 0.05). More AGMs were used in failed grafts (p = 0.002).ConclusionSI can help control intraocular pressure, improve visual acuity, and increase graft survival after DSAEK in ICE syndrome patients.

A Sorghum flour (SF) is a leading and prominent food source for humans in African countries. Recently extensive studies have been conducted on Sorghum bread (SB) or sorghum composite bread (SCB), covering various aspects. However, there are many technical challenges in the formation of SF and sorghum composite flour (SCF) that impact the quality of the bread and fail to meet the consumer’s desires and expectations. This review primarily focuses on the characteristics of SF, SCF, SB, and SCB, with discussions encompassing the rheological and morphological properties of the dough, improvement strategies, and bread quality. Moreover, a comprehensive analysis has been conducted to investigate the behavior of SF and SCF along with a discussion of the challenges affecting bread quality and the strategies applied for improvement. The significant demand for nutrients-rich and gluten-free bread indicates that sorghum will become one of the most vital crops worldwide. However, further comprehensive research is highly demanded and necessary for an in-depth understanding of the key features of SF and the resulting bread quality. Such understanding is vital to optimize the utilization of sorghum grain in large-scale bread production.

Corneal transplantation is the only treatment for corneal endothelial blindness. However, there is an urgent need to find substitutes for corneal endothelium grafts due to the global shortage of donor corneas. An emerging research field focuses on the construction of scaffold-based corneal endothelium tissue engineering (CETE). Long-term success in CETE transplantation may be achieved by selecting the appropriate biomaterials as scaffolds of corneal endothelial cells and adding bioactive materials to promote cell activity. This article reviews the research progress of CETE biomaterials in the past 20 years, describes the key characteristics required for corneal endothelial scaffolds, and summarizes the types of materials that have been reported. Based on these, we list feasible improvement strategies for biomaterials innovation. In addition, we describe the improved techniques for the scaffolds’ surface topography and drug delivery system. Some promising technologies for constructing CETE are proposed. However, some questions have not been answered yet, and clinical trials and industrialization should be carried out with caution.

Abstract The impact of renin on kidney remain unclear among hypertensives with glucose metabolic disorders (GMD). We aimed to evaluate the association between plasma renin activity (PRA) and kidney damage in hypertensive patients with GMD. Overall, 2033 inpatients with hypertension and GMD free of chronic kidney disease (CKD) at baseline were included. CKD was defined using estimated glomerular filtration rate (eGFR) and urine protein. PRA was treated as continuous variable, and also dichotomized as high (≥0.65) or low (