Arginine Biosynthesis Mediates Wulingzhi Extract Resistance to Busulfan-Induced Male Reproductive Toxicity.

Busulfan, an indispensable medicine in cancer treatment, can cause serious reproductive system damage to males as a side effect of its otherwise excellent therapeutic results. Its widespread use has also caused its accumulation in the environment and subsequent ecotoxicology effects. As a Chinese medicine, Wulingzhi (WLZ) has the effects of promoting blood circulation and improving female reproductive function. However, the potential effects of WLZ in male reproduction and in counteracting busulfan-induced testis damage, as well as its probable mechanisms, are still ambiguous. In this study, busulfan was introduced in a mouse model to evaluate its production of the testicular damage. The components of different WLZ extracts were compared using an untargeted metabolome to select extracts with greater efficacy, which were further confirmed in vivo. Here, we demonstrate abnormal spermatogenesis and low sperm quality in busulfan-injured testes. The WLZ extracts showed a strong potential to rehabilitate the male reproductive system; this effect was more prominent in room-temperature extracts. Additionally, both water and ethanol WLZ extracts at room temperature alleviated various busulfan-induced adverse effects. In particular, WLZ recovered spermatogenesis, re-activated arginine biosynthesis, and alleviated the increased oxidative stress and inflammation in the testis, ultimately reversing the busulfan-induced testicular injury. Collectively, these results suggest a promising approach to protecting the male reproductive system from busulfan-induced adverse side effects, as well as those of other similar anti-cancer drugs.

A phase separation-fortified bi-specific adaptor for conditional tumor killing.

A common approach in therapeutic protein development involves employing synthetic ligands with multivalency, enabling sophisticated control of signal transduction. Leveraging the emerging concept of liquid-liquid phase separation (LLPS) and its ability to organize cell surface receptors into functional compartments, we herein have designed modular ligands with phase-separation modalities to engineer programmable interreceptor communications and precise control of signal pathways, thus inducing the rapid, potent, and specific apoptosis of tumor cells. Despite their simplicity, these "triggers", named phase-separated Tumor Killers (hereafter referred to as psTK), are sufficient to yield interreceptor clustering of death receptors (represented by DR5) and tumor-associated receptors, with notable features: LLPS-mediated robust high-order organization, well-choreographed conditional activation, and broad-spectrum capacity to potently induce apoptosis in tumor cells. The development of novel therapeutic proteins with phase-separation modalities showcases the power of spatially reorganizing signal transduction. This approach facilitates the diversification of cell fate and holds promising potential for targeted therapies against challenging tumors.

Gallic Acid-Modified Polyethylenimine-Polypropylene Carbonate-Polyethylenimine Nanoparticles: Synthesis, Characterization, and Anti-Periodontitis Evaluation.

The aim of the research was to develop novel gallic acid (GA)-modified amphiphilic nanoparticles of polyethylenimine (PEI)-polypropylene carbonate (PPC)-PEI (PEPE) and comprehensively assess its properties as an antiperiodontitis nanoparticle targeting the Toll-like receptor (TLR). The first step is to evaluate the binding potential of GA to the core trigger receptors TLR2 and TLR4/MD2 for periodontitis using molecular docking techniques. Following this, we conducted NMR, transmission electron microscopy, and dynamic light scattering analyses on the synthesized PEPE nanoparticles. As the final step, we investigated the synthetic results and in vitro antiperiodontitis properties of GA-PEPE nanoparticles. The investigation revealed that GA exhibits potential for targeted binding to TLR2 and the TLR4/MD2 complex. Furthermore, we successfully developed 91.19 nm positively charged PEPE nanoparticles. Spectroscopic analysis indicated the successful synthesis of GA-modified PEPE. Additionally, CCK8 results demonstrated that GA modification significantly reduced the biotoxicity of PEPE. The in vitro antiperiodontitis properties assessment illustrated that 6.25 µM of GA-PEPE nanoparticles significantly reduced the expression of pro-inflammatory factors TNF-α, IL-1ß, and IL-6. The GA-PEPE nanoparticles, with their targeted TLR binding capabilities, were found to possess excellent biocompatibility and antiperiodontitis properties. GA-PEPE nanoparticles will provide highly innovative input into the development of anti- periodontitis nanoparticles.

Elevated aerobic glycolysis driven by p62-mTOR axis promotes arsenic-induced oncogenic phenotypes in human mammary epithelial cells.

Chronic arsenic exposure is considered to increase the risk of breast cancer. p62 is a multifunctional adaptor protein that controls myriad cellular processes and is overexpressed in breast cancer tissues. Although previous studies have indicated the involvement of p62 accumulation in arsenic tumorigenesis, the underlying mechanism remains obscure. Here, we found that 0.1 µM or 0.5 µM arsenite exposure for 24 weeks induced oncogenic phenotypes in human mammary epithelial cells. Elevated aerobic glycolysis, cell proliferation capacity, and activation of p62-mTOR pathway, as indicated by increased protein levels of p62, phosphorylated-mTOR (p-mTOR) and hypoxia-inducible factor 1α (HIF1α), were observed in chronically arsenite-exposed cells, and of note in advance of the onset of oncogenic phenotypes. Moreover, p62 silencing inhibited acquisition of oncogenic phenotypes in arsenite-exposed cells. The protein levels of p-mTOR and HIF1α, as well as aerobic glycolysis and cell proliferation, were suppressed by p62 knockdown. In addition, re-activation of p­mTOR reversed the inhibitory effects of p62 knockdown. Collectively, our data suggest that p62 exerts an oncogenic role via mTORC1 activation and acts as a key player in glucose metabolism during arsenite-induced malignant transformation, which provides a new mechanistic clue for the arsenite carcinogenesis.

The urinary level of 2,4,5-trichlorophenol was positively associated with both all-cause and cause-specific mortalities in general adult residents of United States.

Chlorophenols are widespread environmental organic pollutants with harmful effects on human beings. Although relationships between chlorophenols and various dysfunctions/diseases have been reported, the contribution of chlorophenols exposure to mortalities is underdetermined. In this cohort study, we included 4 types of urinary chlorophenols, aiming to estimate associations of chlorophenols exposure with all-cause and cause-specific mortalities. Urinary chlorophenols were examined at baseline of National Health and Nutrition Examination Survey (NHANES) 2003-2010, and adjusted for the urinary creatinine level. Associations between chlorophenols and mortalities were estimated using COX regression analyses, results were shown as hazard ratio (HR) and 95% confidence interval (95% CI). By dividing participants into four subgroups based on quartiles of urinary levels of chlorophenols, associations between mortalities and categorical variables of chlorophenols were estimated. Furthermore, the quantile g-computation analysis was used to estimate the joint effects of 4 chlorophenols on mortalities. Among 5817 adults (2863 men), 1034 were deceased during the follow-up. After adjusted for confounders, 2,4,5-trichlorophenol (2,4,5-TCP) was found to be positively associated with both all-cause (HR = 1.46; 95% CI: 1.16, 1.84) and cardiovascular disease (CVD) mortalities (HR = 1.60; 95% CI: 1.00, 2.55). Compared to the subgroup of the lowest level of chlorophenols, participants in subgroups of higher 2,4,5-TCP levels showed higher risk of all-cause mortality (P-value for trend = 0.003). For CVD mortality, HRs in subgroups of higher levels of 2,4-dichlorophenol (2,4-DCP) and 2,4,6-trichlorophenol (2,4,6-TCP) were statistically significant (P-values for trend were 0.017 for 2,4-DCP and 0.049 for 2,4,6-TCP). The HRs (95% CI) of joint effects of 4 chlorophenols were 1.11 (1.01, 1.21) and 1.32 (1.10, 1.57) for all-cause and CVD-specific mortalities, and 2,4,5-TCP showed the highest weight in joint effects. All of these findings implied that among 4 urinary chlorophenols we included, 2,4,5-TCP might be a sensitive one in associations with mortalities among general populations.

Protective and immunomodulatory effects of mesenchymal stem cells on multiorgan injury in male rats with heatstroke.

Heatstroke (HS) causes multiple organ dysfunction syndrome (MODS) with a mortality rate of 60% after hospitalization. Currently, there is no effective and targeted approach for the treatment of HS. Despite growing evidence that mesenchymal stem cells (MSCs) may reduce multiorgan damage and improve survival through immunomodulatory effects in several diseases, no one has tested whether MSCs have immunomodulatory effects in heatstroke. The present study focused on pathological changes and levels of the cytokines and immunoglobulins to investigate the mechanisms underlying the protective effect and the anti-inflammatory effects of MSCs. We found that MSCs treatment significantly reduced the 28-day mortality rate (P < 0.05), the levels of hepatic and renal function markers on day 1 (P < 0.01) and the pathological lesion scores of multiple organs in HS rats. The levels of IgG1, IgM, and IgA of the HS + MSC group was significantly higher than that in HS group on days 3 and 28(P < 0.05). In conclusion, MSCs contribute to protecting against multiorgan injury, reducing pro-inflammatory cytokines, stabilizing immunoglobulins, and reducing the mortality rate of HS rats.

Anti-inflammatory effect and mechanism of catalpol in various inflammatory diseases.

Catalpol is a kind of iridoid glucoside, widely found in a variety of plants, mostly extracted from the rhizome of the traditional medicinal herb rehmanniae. It has various biological activities such as anti-inflammatory, antioxidant, and antitumor. The anti-inflammatory effects of catalpol have been demonstrated in a variety of diseases, such as neurological diseases, atherosclerosis, renal diseases, respiratory diseases, digestive diseases, bone and joint diseases, eye diseases, and periodontitis. The purpose of this review is to summarize the existing literature on the anti-inflammatory effects of catalpol in a variety of inflammatory diseases over the last decade and to focus on the anti-inflammatory mechanisms of catalpol.

Drug-drug interaction potential of SH-1028, a third-generation EGFR-TKI: in vitro and clinical trials.

SH-1028 is an irreversible third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). Considering the possibility of combination therapy in patients with NSCLC, we investigated the drug-drug interaction (DDI) potential of SH-1028 both in vitro and in clinical trials. The in vitro studies were conducted to determine the potential of SH-1028 as a substrate, inducer, or inhibitor of cytochrome P450 (CYP) subtypes. A phase I drug-drug interaction study in healthy volunteers was performed to evaluate the impact of co-administering rifampicin (a strong CYP3A4 inducer) and itraconazole (a strong CYP3A4 inhibitor) on the pharmacokinetics of SH-1028. The in vitro experiments showed that SH-1028 was mainly metabolized by CYP3A4. The activities of CYP1A2, 2B6, 2C19, 2D6 and 3A4 enzymes were slightly inhibited in vitro with SH-1028. SH-1028 has no obvious induction effect on CYP1A2 and CYP2B6 activities, but has potential induction effect on CYP3A4 mRNA expression. However, SH-1028 may not induce or inhibit human CYPs significantly at the clinically expected dose (200 mg). The geometric mean ratios of pharmacokinetic parameters and their corresponding 90% confidence intervals for SH-1028 in combination and alone did not fall within the range of 80-125%. It is speculated that itraconazole and rifampicin affect the metabolism of SH-1028. In the clinical application of SH-1028, special attention should be paid to the interaction between SH-1028 and drugs or foods that affect the activity of CYP3A4. (Clinical trial registration number: CTR20210558).

Alginate-oil gelator composite foam for effective oil spill treatment.

Oil spills threaten ecosystem and health seriously. Porous foams have been proved as ideal candidates for oil absorbents, however, many with poor oil retention (re-bleeding). Here, we creatively developed a composite foam oil absorbent capable of oil absorption and oil gelation, based on porous alginate foam and hydroxyl aluminum stearate oil gelator. The microstructure of alginate foam can be adjusted by the addition of t-butanol in the solvent, and long alkyl chains of gelator endow foam skeleton with good hydrophobicity, avoiding secondary pollution from traditional hydrophobic chemical modification. Interconnected skeleton decorated by oleophilic gelators contributes to high oil absorption. Oleophilic gelator can self-assemble into 3D network to entrap oils to form gels, giving rise to effective oil retention, realizing the integration of high oil absorption and oil retention. The natural abundant, low-cost composite foam would be promising for tackling oil spills.

Applications of Titanium Dioxide Nanostructure in Stomatology.

Breakthroughs in the field of nanotechnology, especially in nanochemistry and nanofabrication technologies, have been attracting much attention, and various nanomaterials have recently been developed for biomedical applications. Among these nanomaterials, nanoscale titanium dioxide (nano-TiO2) has been widely valued in stomatology due to the fact of its excellent biocompatibility, antibacterial activity, and photocatalytic activity as well as its potential use for applications such as dental implant surface modification, tissue engineering and regenerative medicine, drug delivery carrier, dental material additives, and oral tumor diagnosis and treatment. However, the biosafety of nano-TiO2 is controversial and has become a key constraint in the development of nano-TiO2 applications in stomatology. Therefore, in this review, we summarize recent research regarding the applications of nano-TiO2 in stomatology, with an emphasis on its performance characteristics in different fields, and evaluations of the biological security of nano-TiO2 applications. In addition, we discuss the challenges, prospects, and future research directions regarding applications of nano-TiO2 in stomatology that are significant and worthy of further exploration.

Loratadine-associated cystoid macular edema: A case report.

Purpose: To report the first known case of bilateral cystoid macular edema in a patient undergoing long-term loratadine treatment. Observations: A 49-year-old Chinese woman who had been undergoing treatment with loratadine for the past 6 years presented with decreased visual acuity and bilateral cystoid macular edema (CME). Upon cessation of loratadine, macular edema partially resolved, and visual acuity markedly improved. Fundus autofluorescence (FAF), optical coherence tomography (OCT), and fluorescence fundus angiography (FFA) were used to document the severity of CME and its subsequent resolution after cessation of loratadine therapy. Conclusions and Importance: Long-term use of loratadine might cause CME that partially resolves with discontinuation of the drug. The pathophysiology of drug-induced CME without leakage remains unclear. Dysfunction of histamine receptor1-expressed retinal neurons and the associated signal transduction, toxicity to Müller cells or RPE cells with subsequent intracellular fluid accumulation, and subclinical damage to the blood-retina barrier leading to leakage of extracellular fluid, have been proposed.

The Study on the Regulation of Th Cells by Mesenchymal Stem Cells Through the JAK-STAT Signaling Pathway to Protect Naturally Aged Sepsis Model Rats.

Sepsis is the leading cause of death among patients, especially elderly patients, in intensive care units worldwide. In this study, we established a sepsis model using naturally aged rats and injected 5×106 umbilical cord-derived MSCs via the tail vein. Each group of rats was analyzed for survival, examined for biochemical parameters, stained for organ histology, and analyzed for the Th cell subpopulation ratio and inflammatory cytokine levels by flow cytometry. Western blotting was performed to detect the activity of the JAK-STAT signaling pathway. We designed the vitro experiments to confirm the regulatory role of MSCs, and verified the possible mechanism using JAK/STAT inhibitors. It was revealed from the experiments that the 72 h survival rate of sepsis rats treated with MSCs was significantly increased, organ damage and inflammatory infiltration were reduced, the levels of organ damage indicators were decreased, the ratios of Th1/Th2 and Th17/Treg in peripheral blood and spleen were significantly decreased, the levels of pro-inflammatory cytokines such as IL-6 were decreased, the levels of anti-inflammatory cytokines such as IL-10 were increased, and the levels of STAT1 and STAT3 phosphorylation were reduced. These results were validated in in vitro experiments. Therefore, this study confirms that MSCs can control the inflammatory response induced by sepsis by regulating Th cells and inflammatory factors, and that this leads to the reduction of tissue damage, protection of organ functions and ultimately the improvement of survival in aged sepsis model rats. Inhibition of the JAK-STAT signaling pathway was surmised that it may be an important mechanism for their action.

Modified Yamane technique with a 26-gauge needle: single corneal incision and simplified haptic insertion.

A modified Yamane technique with a 26-gauge needle for aphakia correction is described. Single corneal or corneoscleral incision is set at 12 o'clock. The 26-gauge needles are used to make 2 angled incisions parallel to the limbus to fix the haptics of a 3-piece intraocular lens. The modifications provide an easier and safer way of haptic insertion into the needle tip and decreases the possibility of bending or breaking the haptic.

Mesenchymal stem cells regulate activation of microglia cells to improve hippocampal injury of heat stroke rats.

Heat stroke is a severe systemic inflammatory response disease caused by high fever, mainly with nervous system damage. Mesenchymal stem cells (MSCs) are currently believed to have anti-inflammation and immunomodulatory effects. Therefore, we aimed to explore the protective effect and mechanism of MSCs on heat stroke-induced excessive inflammation and neurological dysfunction. We established a heat stroke model in rats under conditions of continuous high temperature and high humidity. After modeling, rats were randomly divided into heat stroke model group, MSCs treatment group and normal temperature control group without any treatment. We performed survival analysis, neurological deficit score, histological staining of hippocampus and cerebellum, immunofluorescence staining of microglia, detection of inflammatory and chemokine levels in the hippocampus and cerebellum in each group. We found that MSCs treatment not only significantly reduced early (day 3) and late (day 28) mortality, but also prominently reduced nerve injury in heat stroke rats, and improved pathology and neuronal cell damage in the hippocampus and cerebellum. In addition, MSCs treatment can significantly inhibit the over-activation of hippocampal microglia in heat stroke rats and the levels of pro-inflammatory factors and chemokines in the hippocampus. Early treatment of MSCs can greatly promote the activation of cerebellar microglia in heat stroke rats. Meanwhile, MSCs treatment has an inhibitory effect on the level of chemokine in the cerebellum of rats in the early stage of heat stroke. In conclusion, the application of MSCs in the treatment of heat stroke in rats can significantly reduce mortality and neurological deficits and improve hippocampal damage, possibly by inhibiting the excessive activation of hippocampal microglia in heat stroke rats.

Heterogeneous miRNA-mRNA Regulatory Networks of Visceral and Subcutaneous Adipose Tissue in the Relationship Between Obesity and Renal Clear Cell Carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most lethal urologic cancer. Associations of both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with ccRCC have been reported, and underlying mechanisms of VAT perhaps distinguished from SAT, considering their different structures and functions. We performed this study to disclose different miRNA-mRNA networks of obesity-related ccRCC in VAT and SAT using datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA); and find out different RNAs correlated with the prognosis of ccRCC in VAT and SAT. Methods: We screened out different expressed (DE) mRNAs and miRNAs of obesity, in both VAT and SAT from GEO datasets, and constructed miRNA-mRNA networks of obesity-related ccRCC. To evaluate the sensitivity and specificity of RNAs in networks of obesity-related ccRCC in both VAT and SAT, Receiver Operating Characteristic (ROC) analyses were conducted using TCGA datasets. Spearman correlation analyses were then performed to find out RNA pairs with inverse correlations. We also performed Cox regression analyses to estimate the association of all DE RNAs of obesity with the overall survival. Results: 136 and 185 DE mRNAs of obesity in VAT and SAT were found out. Combined with selected DE miRNAs, miRNA-mRNA networks of obesity-related ccRCC were constructed. By performing ROC analyses, RNAs with same trend as shown in networks and statistically significant ORs were selected to be paired. Three pairs were finally remained in Spearman correlation analyses, including hsa-miR-182&ATP2B2, hsa-miR-532&CDH2 in VAT, and hsa-miR-425&TFAP2B in SAT. Multivariable Cox regression analyses showed that several RNAs with statistically significant adjusted HRs remained consistent trends as shown in DE analyses of obesity. Risk score analyses using selected RNAs showed that the overall survival time of patients in the low-risk group was significantly longer than that in the high-risk group regardless of risk score models. Conclusions: We found out different miRNA-mRNA regulatory networks of obesity-related ccRCC for both VAT and SAT; and several DE RNAs of obesity-related ccRCC were found to remain consistent performance in terms of ccRCC prognosis. Our findings could provide valuable evidence on the targeted therapy of obesity-related ccRCC.

Regulation of Inflammatory Cytokine Storms by Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have been widely used in preclinical and clinical trials for various diseases and have shown great potential in the treatment of sepsis and coronavirus disease (COVID-19). Inflammatory factors play vital roles in the pathogenesis of diseases. The interaction between inflammatory factors is extremely complex. Once the dynamics of inflammatory factors are unbalanced, inflammatory responses and cytokine storm syndrome develop, leading to disease exacerbation and even death. Stem cells have become ideal candidates for the treatment of such diseases due to their immunosuppressive and anti-inflammatory properties. However, the mechanisms by which stem cells affect inflammation and immune regulation are still unclear. This article discusses the therapeutic mechanism and potential value of MSCs in the treatment of sepsis and the novel COVID-19, outlines how MSCs mediate innate and acquired immunity at both the cellular and molecular levels, and described the anti-inflammatory mechanisms and related molecular pathways. Finally, we review the safety and efficacy of stem cell therapy in these two diseases at the preclinical and clinical levels.

A Comparison of Adverse Events Among Radiofrequency Ablation, Conventional Transarterial Chemoembolization (TACE) and Drug-Eluting Bead TACE in Treating Hepatocellular Carcinoma Patients.

BACKGROUND: There has been very limited investigation regarding the comparison of adverse events (AEs) among radiofrequency ablation (RFA), conventional transarterial chemoembolization (cTACE), and drug-eluting bead TACE (DEB-TACE) in treating HCC patients; therefore, the present study aimed to resolve this issue. METHODS: Two-hundred and forty-six HCC patients (with a total of 267 procedures [treatment times]) treated with RFA (73 patients with 79 procedures), cTACE (86 patients with 94 procedures), or DEB-TACE (87 patients with 94 procedures) were included. Demographic and clinical data were collected. The information on AEs was also retrieved and analyzed. RESULTS: Total AEs incidence was notably different among the RFA group, cTACE group, and DEB-TACE group and was the highest in cTACE group (86.2%), then in DEB-TACE group (76.6%), and the lowest in RFA group (63.3%). Regarding specific AEs incidence, the incidences of fever, fatigue, and nausea were distinctive among the three groups, while no distinctiveness was found in incidence of other AEs. Furthermore, multivariate logistic regression revealed that cTACE (versus RFA) was independently correlated with increased risk of total AEs, fatigue, and nausea/vomiting; however, the interventional therapies were not independently correlated with the risk of pain, fever or constipation. Other independent predictive factors for total AEs risk were male gender, bronchial asthma, and disease duration. CONCLUSION: cTACE resulted in the highest AEs incidence compared with RFA and DEB-TACE in treating HCC patients.

ZSCAN16-AS1 expedites hepatocellular carcinoma progression via modulating the miR-181c-5p/SPAG9 axis to activate the JNK pathway.

Hepatocellular carcinoma (HCC) is generally known as one of the most common cancers in the world. Nowadays, interventional therapies such as transcatheter arterial chemoembolization (TACE) have emerged as an efficient therapy for HCC patients. Accumulating evidence has unveiled that long non-coding RNAs (lncRNAs) are crucial regulators in HCC progression. Nonetheless, the biological function of lncRNA zinc finger and SCAN domain containing 16 antisense RNA 1 (ZSCAN16-AS1) in HCC has not been systematically clarified. RT-qPCR was used to test ZSCAN16-AS1 expression in HCC cells. The biological functions of RP11-757 G1.5 on HCC cell proliferation, migration, invasion and apoptosis were investigated by colony formation, EdU, CCK-8 and transwell assays, as well as flow cytometry analysis. RNA immunoprecipitation (RIP), RNA pull-down and luciferase reporter assays were utilized to explore the specific mechanism of ZSCAN16-AS1. ZSCAN16-AS1 was significantly up-regulated in HCC cells. ZSCAN16-AS1 silence inhibited HCC cell proliferation, migration and invasion, while it accelerated HCC cell apoptosis. ZSCAN16-AS1 worked as a competing endogenous RNA (ceRNA) to regulate sperm associated antigen 9 (SPAG9) expression through sponging miR-181 c-5p. Moreover, SPAG9 could activate the c-Jun-N-terminal kinase (JNK) pathway. Taken together, our study elucidated that ZSCAN16-AS1 expedited HCC progression via modulating the miR-181 c-5p/SPAG9 axis to activate the JNK pathway, which might be a highly potential HCC therapy and treatment target.

Characteristics of fixation patterns and their relationship with visual function of patients with idiopathic macular holes after vitrectomy.

To analyze the relationships between the fixation location and the visual function of idiopathic macular hole (IMH) patients with macular integrity assessment (MAIA) examination preoperatively and 3 months postoperatively. This was a retrospective case analysis. Forty-three eyes of 43 patients diagnosed with IMH were included in this study. The best corrected visual acuity (BCVA) assessments, optical coherence tomography (OCT) and MAIA examinations were performed before surgery and 1 week, 1 month and 3 months after surgery. The relationships between MAIA parameters and visual acuity were assessed by correlation analysis. Grouping by fixation location with the foveola (2°) as the centre, the locations could be divided into five groups, including foveolar, temporal, nasal, inferior and superior fixation. The mean macular sensitivity (MMS) of the macular area was correlated with the BCVA in the IMH patients before and 3 months after surgery (before surgery P = 0.00, after surgery P = 0.00). The MMS could be used as a good indicator for evaluating visual function in IMH patients. There was a significant difference in fixation location before and after the operation (P = 0.01). The preoperative fixation location of IMH patients was mainly in the superior area, while postoperatively moved to the foveola and nasal areas. Paying attention to the changes of fixation locations in IMH patients may provide new clues for further improving postoperative visual function.

Surgery at early versus late for intermittent exotropia: a Meta-analysis and systematic review.

AIM: To compare the outcomes between early surgery and late surgery for intermittent exotropia (IXT) with a Meta-analysis. METHODS: Scientific databases including PubMed, Embase, Web of Science, Cochrane and China National Knowledge Infrastructure were searched prior to December 16, 2019. From this broad database search, we performed some Meta-analysis including eleven independent studies, to further evaluate the outcome(s) when comparing early versus late surgery for IXT. The boundaries between early and late surgery and the surgery methods were not inconsistent, so subgroup analyses were conducted by different boundaries of age at surgery and different surgical approaches. The pooled odds ratios (ORs) and the 95% confidence interval (CI) were estimated according to the random-effects model for high heterogeneity between studies. RESULTS: Eleven retrospective studies were included in this Meta-analysis. No significant difference between early and late surgery was observed for IXT patients (ORFirst follow-up=0.88, 95%CI 0.53-1.44, P=0.61; ORFinal follow-up=1.48, 95%CI 0.94-2.31, P=0.09). However, sensitivity analysis performed by sequentially omitting individual studies showed that the final follow-up result was not stable. Subgroup analyses revealed that an earlier surgical procedure could lead to a better outcome in the 4-year boundary subgroup as well as the bilateral lateral rectus recession (BLR) subgroup for the final follow-up (OR4y=2.64, 95%CI 1.57-4.44, P=0.00; ORBLR=2.25, 95%CI 1.36-3.74, P=0.00). CONCLUSION: Early surgery for IXT provides a better long term follow-up outcome when patients are younger than 4 years old or choose the BLR surgical method.