Malignant myopericytoma originating from the colon: A case report.

BACKGROUND: Myopericytoma is a benign tumor that typically occurs within subcutaneous tissue and most often involves the distal extremities, followed by the proximal extremities, neck, thoracic vertebrae and oral cavity. Complete resection is often curative. Malignant myopericytoma is extremely rare and has a poor prognosis. Here, we report for the first time a case of malignant myopericytoma originating from the colon. CASE SUMMARY: A 69-year-old male was admitted to our hospital with right upper quadrant pain for five days. Imaging suggested a liver mass with hemorrhage. A malignant hepatic tumor was the initial diagnosis. Surgical resection was performed after a complete preoperative work up. Initial postoperative pathology suggested that the mass was a malignant myoblastoma unrelated to the liver. Four months after the first surgery, an enhanced computed tomography (CT) scan revealed a recurrence of the tumor. The diagnosis of malignant myopericytoma derived from the colon was confirmed on histopathological examination of the specimen from the second surgery. The patient did not return to the hospital regularly for surveillance. The first postoperative abdominal CT examination six months after the second surgery demonstrated multiple liver metastases. Survival time between the diagnosis of the tumor to death was approximately one year. CONCLUSION: Malignant myopericytoma is a rare cancer. Preoperative diagnosis may be difficult. Due to a lack of treatment options, prognosis is poor.

Cationic-motif-modified exosomes for mRNA delivery to retinal photoreceptors.

Topical treatment of vitreoretinal diseases remains a challenge due to slow corneal uptake and systemic clearance. Exosomes are emerging nanocarriers for drug delivery due to biocompatibility and cellular targeting properties. To apply them for retinal targeting via the topical route, exosomes must traverse various ocular barriers including the cornea, lens, vitreous humor (VH), and the retina itself. Here we engineered high-purity milk-derived exosomes by anchoring arginine-rich cationic motifs via PEG2000 lipid insertion on their surface. Modification enabled exosomes to use weak-reversible electrostatic interactions with anionic glycosaminoglycan (GAG) and water content of the tissue to enhance their transport rate and retention. Addition of cationic motifs neutralized the anionic surface charge of exosomes (-24 to -2 mV) without impacting size or morphology. Cationic-motif-modified exosomes exhibited two-fold faster steady state diffusivity through bovine corneas compared to unmodified exosomes. Fluorescence recovery after photobleaching confirmed that cationic-motif-modified exosomes can diffuse through VH without steric hindrance. In healthy VH, cationic-motif-modified exosomes demonstrated stronger binding resulting in three-fold lower average diffusivity that enhanced by six-fold in 50% GAG-depleted VH recapitulating advanced liquefaction. Cationic-motif-modified exosomes penetrated through the full-thickness of porcine retinal explants resulting in ten-fold higher uptake in photoreceptors and three-fold greater transfection with encapsulated eGFP mRNA compared to unmodified exosomes. Cationic-motif-modified exosomes are safe to use as they did not adversely affect the mechanical swelling properties of the cornea or lens nor impact retinal cell viability. Cationic-motif-modified exosomes, therefore, offer themselves as a cell-free nanocarrier platform for gene delivery to retinal photoreceptors potentially via the topical route.

Characteristics of optic disc hemorrhage and optic nerve changes following acute primary angle closure.

Introduction: Acute primary angle closure (APAC) is an emergency ophthalmic presentation and a major cause of irreversible blindness in China. However, only a few studies have focused on the characteristics of optic disc hemorrhage (ODH) during an APAC attack, including its shape, depth, location, scope, and duration after intraocular pressure (IOP) control, along with changes in the optic nerve. This study aimed to analyze the characteristics of ODH and optic nerve changes in patients during their first APAC episode. Methods: This retrospective study involved 32 eyes from 32 patients with APAC who received sequential treatment and analyzed the following parameters: the highest IOP and its duration, ODH, retinal nerve fiber layer thickness (RNFLT), and mean deviation (MD). We compared parameters obtained from the affected eye (ODH group) and contralateral unaffected eye (control group), as well as intragroup comparisons. Results: The mean IOP in the ODH group was 64.28 ± 10.36 mmHg, with a duration of 4.44 ± 2.35 days. Flame and splinter shapes accounted for 84.38% of the ODH. The mean ODH duration was 4.81 ± 3.25 weeks. ODH during APAC was isolated to one sector in 59.38% of cases, mostly occurring in the temporal superior and temporal inferior (each accounting for 21.88% of the cases). There was a positive correlation between the extent of hemorrhage and the highest IOP duration (p < 0.001). RNFLT was significantly thickened within 72 h post-IOP control but was thinned by 2 weeks. By 6 months, the thinning stabilized, and there was no difference noted between the ODH and control groups at 12 months. MD partly improved at 6 months post-IOP control, and ODH scope significantly affected the MD (p < 0.001). The duration of high IOP was positively correlated to the ODH scope and MD damage. Discussion: Timely and effective IOP management is essential for recovering visual function following an APAC attack.

Efficacy and Safety of Surgical Peripheral Iridectomy, Goniosynechialysis, and Goniotomy for Advanced Primary Angle-closure Glaucoma without Cataract: One-year Results of a Multicenter Study.

PRCIS: The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle-closure glaucoma without cataract. PURPOSE: To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle-closure glaucoma (PACG) eyes without cataract. PATIENTS AND METHODS: A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6-18 mm Hg with at least a 20% reduction compared to baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression. RESULTS: A total of 61 eyes of 50 advanced PACG were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8 mm Hg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P=0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P=0.036) reduced success rate. CONCLUSIONS: The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients.

Genetic and inflammatory factors underlying gestational diabetes mellitus: a review.

Gestational diabetes mellitus (GDM) poses a significant global health concern, impacting both maternal and fetal well-being. Early detection and treatment are imperative to mitigate adverse outcomes during pregnancy. This review delves into the pivotal role of insulin function and the influence of genetic variants, including SLC30A8, CDKAL1, TCF7L2, IRS1, and GCK, in GDM development. These genetic variations affect beta-cell function and insulin activity in crucial tissues, such as muscle, disrupting glucose regulation during pregnancy. We propose a hypothesis that this variation may disrupt zinc transport, consequently impairing insulin production and secretion, thereby contributing to GDM onset. Furthermore, we discussed the involvement of inflammatory pathways, such as TNF-alpha and IL-6, in predisposing individuals to GDM. Genetic modulation of these pathways may exacerbate glucose metabolism dysregulation observed in GDM patients. We also discussed how GDM affects cardiovascular disease (CVD) through a direct correlation between pregnancy and cardiometabolic function, increasing atherosclerosis, decreased vascular function, dyslipidemia, and hypertension in women with GDM history. However, further research is imperative to unravel the intricate interplay between inflammatory pathways, genetics, and GDM. This understanding is pivotal for devising targeted gene therapies and pharmacological interventions to rectify genetic variations in SLC30A8, CDKAL1, TCF7L2, IRS1, GCK, and other pertinent genes. Ultimately, this review offers insights into the pathophysiological mechanisms of GDM, providing a foundation for developing strategies to mitigate its impact.

Charge-Reversed Exosomes for Targeted Gene Delivery to Cartilage for Osteoarthritis Treatment.

Gene therapy has the potential to facilitate targeted expression of therapeutic proteins to promote cartilage regeneration in osteoarthritis (OA). The dense, avascular, aggrecan-glycosaminoglycan (GAG) rich negatively charged cartilage, however, hinders their transport to reach chondrocytes in effective doses. While viral vector mediated gene delivery has shown promise, concerns over immunogenicity and tumorigenic side-effects persist. To address these issues, this study develops surface-modified cartilage-targeting exosomes as non-viral carriers for gene therapy. Charge-reversed cationic exosomes are engineered for mRNA delivery by anchoring cartilage targeting optimally charged arginine-rich cationic motifs into the anionic exosome bilayer by using buffer pH as a charge-reversal switch. Cationic exosomes penetrated through the full-thickness of early-stage arthritic human cartilage owing to weak-reversible ionic binding with GAGs and efficiently delivered the encapsulated eGFP mRNA to chondrocytes residing in tissue deep layers, while unmodified anionic exosomes do not. When intra-articularly injected into destabilized medial meniscus mice knees with early-stage OA, mRNA loaded charge-reversed exosomes overcame joint clearance and rapidly penetrated into cartilage, creating an intra-tissue depot and efficiently expressing eGFP; native exosomes remained unsuccessful. Cationic exosomes thus hold strong translational potential as a platform technology for cartilage-targeted non-viral delivery of any relevant mRNA targets for OA treatment.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

Efficacy of Morning Versus Evening Latanoprost/Timolol Fixed Combination for Open-Angle Glaucoma and Ocular Hypertension: A Randomized Clinical Trial.

Purpose: To compare the efficacy of morning and evening latanoprost/timolol fixed-combination (LTFC) dosing in patients with primary open-angle glaucoma (POAG) and ocular hypertension. Methods: In this double-blind, randomized clinical trial, 63 untreated Chinese patients with POAG and ocular hypertension were enrolled. All patients received LTFC and were randomized (1:1) to group 1, morning (8 AM) dosing, or group 2, evening (8 PM) dosing. Vehicle drops were used in the morning or evening, accordingly, to preserve masking. Patients were treated for 4 weeks. Outcomes included mean reduction of the 24-hour intraocular pressure (IOP) and IOP fluctuation from baseline after a 4-week treatment. Results: Fifty-six patients were included in the final analysis. In both groups, the posttreatment IOP values were significantly lower than those at baseline at each 24-hour measuring time point. A significant difference between the groups in IOP reduction from baseline was observed at the 9:30 AM time point (4.01 ± 2.62 vs. 2.42 ± 3.23 mm Hg, evening dosing versus morning dosing group; P = 0.048). Both groups showed decreased IOP fluctuation after treatment. However, the morning dosing group had a significantly greater decrease in diurnal IOP fluctuation than that of the evening dosing group (2.04 ± 2.32 mm Hg vs. 0.50 ± 1.70 mm Hg, respectively; P = 0.012). Conclusions: Both morning and evening LTFC dosing can effectively reduce 24-hour IOP and IOP fluctuation. Morning dosing is more likely to effectively control diurnal IOP fluctuations. Translational Relevance: This multicenter, double-blind, randomized clinical trial generates robust evidence on the optimal LTFC dosing regimen to help clinical decision-making in the treatment of raised IOP.

Milk exosomes anchored with hydrophilic and zwitterionic motifs enhance mucus permeability for applications in oral gene delivery.

Exosomes have emerged as a promising tool for the delivery of drugs and genetic materials, owing to their biocompatibility and non-immunogenic nature. However, challenges persist in achieving successful oral delivery due to their susceptibility to degradation in the harsh gastrointestinal (GI) environment and impeded transport across the mucus-epithelium barrier. To overcome these challenges, we have developed high-purity bovine milk exosomes (mExo) as a scalable and efficient oral drug delivery system, which can be customized by incorporating hydrophilic and zwitterionic motifs on their surface. In our study, we observed significantly improved transport rates by 2.5-4.5-fold in native porcine intestinal mucus after the introduction of hydrophilic and zwitterionic surface modifications, as demonstrated by transwell setup and fluorescence recovery after photobleaching (FRAP) analysis. Remarkably, mExo functionalized by a block peptide (BP), consisting of cationic and anionic amino acids arranged in blocks at the two ends, demonstrated superior tolerability in the acidic gastric environment (with a protein recovery rate of 84.8 ± 7.7%) and exhibited a 2.5-fold increase in uptake by intestinal epithelial cells. Furthermore, both mExo and mExo-BP demonstrated successful intracellular delivery of functional siRNA, resulting in up to 65% suppression of the target green fluorescence protein (GFP) gene expression at a low dose of siRNA (5 pmol) without causing significant toxicity. These findings highlight the immense potential of modifying mExo with hydrophilic and zwitterionic motifs for effective oral delivery of siRNA therapies.

Value of q waves in lateral and left precordial leads in patients with left bundle branch block to predict the response to cardiac resynchronization therapy.

BACKGROUND: The cardiac resynchronization therapy (CRT) non-response rate can reach 30% in heart failure (HF) patients with left bundle branch block (LBBB). This study aimed to evaluate the value of baseline q waves in leads I, V5, or V6 in predicting response to CRT in patients with HF and LBBB. METHODS: Patients with HF (left ventricular ejection fraction ≤35%) and LBBB receiving CRT implantation were retrospectively enrolled. Baseline characteristics and electrocardiogram parameters, including lateral and left precordial q waves were evaluated. Non-response to CRT was defined as the improvement of left ventricular ejection fraction (LVEF) < 5% at a 6-month follow-up. RESULTS: A total of 132 patients (mean age 63.0 ± 10.4 years, 94 [71.2%] male) were included. Among them, 32 patients with q waves in leads I, V5, or V6 were classified into the qLBBB (+) group, and the rest without q waves in these leads were defined as the qLBBB (-) group. The CRT non-response rate in the qLBBB (+) group was markedly higher than that in the qLBBB (-) group (68.8% vs. 33.3%, p < .001). Multivariable logistic regression analysis revealed that the presence of baseline q waves in leads I, V5, or V6 remained significantly associated with a higher rate of CRT non-response in patients with HF and LBBB (odds ratio: 4.8, 95% confidence interval: 1.5-15.0, p = .007). CONCLUSION: Any q wave in leads I, V5, or V6 was an independent predictive factor for CRT non-response in patients with HF and LBBB.

Safety and Efficacy of Goniotomy following Failed Surgery for Glaucoma.

PRCIS: Goniotomy (GT) is an alternative surgery for patients with prior failed surgery for glaucoma. PURPOSE: To evaluate the efficacy and safety of GT in patients with prior failed surgery for glaucoma. MATERIALS AND METHODS: A prospective, observational multicentered study was performed for patients who underwent GT with prior single or multiple surgery for glaucoma. Outcome measures included intraocular pressure (IOP) change, best-corrected visual acuity change, ocular hypotensive medication use, and occurrence of adverse events through 12 months. Complete success was defined as a postoperative IOP within 6-18 mmHg and a 20% reduction from baseline without ocular hypotensive medications. Qualified success was the same as the definition of complete success, except for postoperative use of medication. Logistic regression models were used to investigate the potential factors for surgical success. RESULTS: A total of 38 eyes of 34 patients were included. Twenty-three eyes had only 1 prior surgery, 13 eyes had 2 prior surgeries, 1 eye had 3 prior surgeries, and 1 eye had 4 prior surgeries. At month 12, there was complete success in 42.1% of the eyes and qualified success in 78.9% of the eyes. Preoperatively, the mean IOP was 29.4±6.9 mmHg and the median number of glaucoma medications used was 3.0 (2.0, 4.0); this decreased to 16.7±3.6 mmHg (43.2% reduction; P <0.001) and 2.0 (0.0, 3.0) ( P <0.001) at month 12, respectively. The most common complications included hyphema (13.2%), IOP spike (7.9%), and corneal edema (5.2%). Older age significantly contributed to surgical success. CONCLUSIONS: GT seems to be a safe and effective procedure for patients with prior failed surgery for glaucoma.

Influence of Goniotomy Size on Treatment Safety and Efficacy for Primary Open-Angle Glaucoma: A Multicenter Study.

PURPOSE: To compare the efficacy and safety of 120-, 240-, and 360-degree goniotomy (GT) with or without phacoemulsification with intraocular lens implantation (PEI) for patients with primary open-angle glaucoma (POAG). DESIGN: Multicenter, retrospective, comparative, nonrandomized interventional study. METHODS: Patients diagnosed with POAG who underwent GT with or without PEI were included, and divided into 6 groups: 1) standalone 120-degree GT (120GT); 2) standalone 240-degree GT (240GT); 3) standalone 360-degree GT (360GT); 4) PEI + 120GT; 5) PEI + 240GT; and 6) PEI + 360GT. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. Success was defined as a postoperative IOP within the range of 6 to 18 mm Hg and a 20% reduction from baseline without further glaucoma surgery. Complete success and qualified success were defined as the above without and with ocular hypotensive medications, respectively. RESULTS: Three hundred eight eyes of 231 patients were included with a mean follow-up of 14.4 ± 8.6 months (6.0-48.0 months). There were no significant differences in the reductions in IOP and number of medications and cumulative survival probability for complete and qualified success rates among the 3 groups of standalone GT and PEI + GT. The 360GT group had the highest proportion of hyphema with or without PEI. CONCLUSIONS: 120GT, 240GT, and 360GT with or without PEI showed similar efficacy in reducing IOP and medications used in POAG. 360GT with or without PEI was more likely to cause hyphema compared with 120GT or 240GT. 120GT with or without PEI was sufficient for treating POAG with or without cataract..

One-Year Results of a Multicenter Study: Intraocular Pressure-Lowering Effect of Combined Phacoemulsification, Goniosynechialysis, and Goniotomy for Cases of Advanced Primary Angle-Closure Glaucoma With Cataract.

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering effect of the combination of phacoemulsification with intraocular lens implantation (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes of advanced primary angle-closure glaucoma (PACG) with cataract. DESIGN: Multicenter observational study. METHODS: We enrolled 83 eyes of 83 patients with advanced PACG who received combined PEI+GSL+GT at 8 ophthalmic institutes. Each patient was assessed before treatment and at 1, 7 days, 1, 3, 6, and 12 months postsurgery. The criteria for complete success were IOP within 6 to 18 mm Hg and at least 20% of reduction in IOP from baseline without ocular hypotensive medications or reoperation. The definition of qualified success was similar to that of complete success, except for the need for ocular hypotensive medications. The potential prognostic factors for surgical success were investigated using a multivariate logistic model. RESULTS: All participants completed 1 year of follow-up. Complete and qualified success were achieved in 74 (89.1%) and 79 (95.2%) of 83 eyes, respectively. The mean preoperative and postsurgical IOPs were 27.4±7.3 and 14.2±2.6 mm Hg, respectively. Participants used an average of 2.0 and 0.3 types of ocular hypotensive medications before and after surgery, respectively. The chief complications included hyphema (n=9), IOP spike (n=9), and corneal edema (n=8). None of the eyes required reoperation or developed vision-threatening complications. Multivariate analysis showed that older age was associated with a higher probability of complete success (odds ratio=1.13; 95% CI: 1.02-1.25; P=0.020). CONCLUSIONS: The 1-year results of combination of PEI+GSL+GT in treating advanced PACG cases with cataract appear to be safe and effective. Further large-scale multination and multicenter studies are warranted.

Minimally Invasive Glaucoma Surgery in Primary Angle-Closure Glaucoma.

Primary angle-closure glaucoma (PACG) is responsible for half of the glaucoma-related blindness worldwide. Cataract surgery with or without trabeculectomy has been considered to be the first-line treatment in eyes with medically uncontrolled PACG. While minimally invasive glaucoma surgery has become an important surgical approach for primary open-angle glaucoma, its indications and benefits in PACG are less clear. This review summarizes the efficacy and safety profile of minimally invasive glaucoma surgery in PACG to unfold new insights into the surgical management of PACG.

Repeated bacteremia and hepatic cyst infection lasting 3 years following pancreatoduodenectomy: A case report.

BACKGROUND: Simple hepatic cysts are commonly occurring lesions that are usually asymptomatic and require no treatment. Hepatic cyst infection, however, is considered a severe complication. We report a case of hepatic cyst infection following pancreatoduodenectomy with repeated fever lasting for almost 3 years, and two cysts were infected successively. CASE SUMMARY: A 72-year-old woman diagnosed with adenocarcinoma of duodenal papilla underwent pancreatoduodenectomy with Child reconstruction. She then suffered repeated occurrences of bacteremia and hepatic cyst infection for 3 years. Blood cultures were positive for Klebsiella pneumoniae and Escherichia coli a total of 7 times and 4 times, respectively. During the early stage, we suspected that postoperative reflux cholangitis was the cause of fever and bacteremia. Multiple cysts were observed, so it was difficult to determine which cyst was infected. Through repeat examination, we found the focus of infection, and we treated the patient with antimicrobials and performed percutaneous cyst drainage. The patient did not experience another cyst infection for more than 4 years. CONCLUSION: Biliary reconstruction inducing hepatic cyst infection is easily misdiagnosed as biliary reflux infection, Repeated imaging examination is a method for identifying the infected focus.

Role of Estrogen Receptor-Positive/Negative Ratios in Regulating Breast Cancer.

The alpha estrogen receptor (ERα) contributes to breast cancer progression and recent guidelines define ER positivity as ≥1% stained cells, and a few tumor tissues show no ERα expression at all or are at 100%. Although ER and aromatase inhibitors are widely used to treat hormone receptor-positive (HR+) breast cancer, their effect on tumor activity at different ERα levels remains unclear. Therefore, we investigated the role of ERα+/ERα- ratios in determining the ERα level. We used ERα stably transfected and wild-type MDA-MB-231 cells (MDA-MB-231Trans-ER and MDA-MB-231WT, respectively) as represented ER+ and ER- cells, respectively, and MCF-7 cells were the positive control. MDA-MB-231Trans-ER and MDA-MB-231WT cells were mixed and cocultured at a ratio of 0%, 20%, 40%, 70%, and 100%. Migration and invasion functions at different cell ratios were evaluated in vitro using the Transwell and scratch test. In a xenograft mouse model, the polarization of the tumor-associated (M2) macrophage and the expression of breast cancer gene 1 (BRCA1), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF)-α were measured. The results showed that the cell invasion and migration were significantly higher at 40% and 70% than they were at other ratios. Additionally, in vivo, the 70% ERα+/ERα-ratio was a critical indicator of cell activity and cytokine expression. The highest M2 level and expression of VEGR, TNF-α, BRCA1, and HER2 were shown at a ratio of 70%. Moreover, the effects of ERα were not linear in breast cancer, indicating that the ERα status requires continuous monitoring during long-term endocrine treatment. These results indicate that during HR+ breast cancer treatment, the ERα+/ERα- ratio may be a useful predictor and should be evaluated further.

Screening for Atrial Fibrillation by Village Doctors in Rural Areas of China: The Jiangsu Province Rural Community AF Project.

China has a large population of elderly in rural areas. Village doctors are acting as health-care gatekeepers for the rural elderly in China and are encouraged to provide more long-term care for patients with chronic diseases such as atrial fibrillation (AF). The data of AF registries from the rural elderly are limited. The present registry aims to provide contemporary data on the current AF-related health status of the rural elderly and the gaps in management of AF by village doctors. This study has two phases. The first phase is a cross-sectional study of AF screening in two rural towns of eastern China. All the residents aged ≥65 years are eligible and will be invited to attend a government-led health examination or an in-house AF screening program. The AF detection rate, the awareness of AF and the usage of oral anticoagulants and smartphones by AF patients, and the ability to diagnose and manage AF by village doctors will be assessed. Participants with AF detected in the first phase are eligible for the second phase. A variety of modes of intensified education will be provided to all AF patients and their family members to enrich their AF-related knowledge. Their village doctors will be offered a lecture-based training program focusing on Atrial fibrillation Better Care (ABC) pathway. Follow-up will be conducted for 1 year. The primary endpoint is the composite of all stroke and all-cause mortality. The first phase of AF screening was conducted between April 2019 and June 2019, and 18,712 participants with the mean age of 73.1±5.8 years were enrolled. The second phase that includes 810 patients with AF, started on 1 May 2019. This study will provide a perspective of primary care system and would indirectly reflect the current status of chronic disease care in rural China.

Efficacy and safety of trabeculectomy versus peripheral iridectomy plus goniotomy in advanced primary angle-closure glaucoma: study protocol for a multicentre, non-inferiority, randomised controlled trial (the TVG study).

INTRODUCTION: Primary angle-closure glaucoma (PACG) is a major subtype of glaucoma that accounts for most bilateral glaucoma-related blindness globally. Filtering surgery is a conventional strategy for PACG, yet it has a long learning curve and undesirable disastrous complications. Minimally invasive glaucoma surgery (MIGS) plays an increasing role in the management of glaucoma due to its safer and faster recovery profile; cataract surgery-based MIGS is the most commonly performed such procedure in PACG. However, for patients with a transparent lens or no indications for cataract extraction, incorporation of MIGS into PACG treatment has not yet been reported. Therefore, this multicentre, non-inferiority, randomised controlled clinical trial aims to compare the efficacy and safety of trabeculectomy versus peripheral iridectomy plus an ab interno goniotomy in advanced PACG with no or mild cataracts. METHODS AND ANALYSIS: This non-inferiority, multicentre, randomised controlled trial will be conducted at seven ophthalmic departments and institutes across China. Eighty-eight patients with no or mild cataracts and advanced PACG will be enrolled and randomised to undergo trabeculectomy or peripheral iridectomy plus ab interno goniotomy. Enrolled patients will undergo comprehensive ophthalmic examinations before and after surgery. The primary outcome is intraocular pressure (IOP) at 12 months postoperatively. The secondary outcomes are cumulative success rate of surgery, surgery-related complications and number of IOP-lowering medications. Participants will be followed up for 36 months postoperatively. ETHICS AND DISSEMINATION: The study protocol was approved by the ethical committees of the Zhongshan Ophthalmic Center, Sun Yat-sen University, China (ID: 2021KYPJ191) and of all subcentres. All participants will be required to provide written informed consent. The results will be published in peer-reviewed journals and disseminated in international academic meetings. TRIAL REGISTRATION NUMBER: NCT05163951.

Ocular Factors of Fractal Dimension and Blood Vessel Tortuosity Derived From OCTA in a Healthy Chinese Population.

Purpose: To identify the ocular factors of microvascular fractal dimension (FD) and blood vessel tortuosity (BVT) of macula measured with optical coherence tomography angiography (OCTA) in a healthy Chinese population. Methods: Healthy subjects without ocular disorders were recruited at Zhongshan Ophthalmic Center. The FD and BVT in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at the macula were obtained from OCTA images. The FD was calculated using the box-counting method, and the BVT was defined as the ratio of the actual distance between two points to the straight distance on the skeletonized image. Univariate and stepwise multivariate linear regression analyses were performed to identify the ocular factors of FD and BVT, and the results are presented as coefficients and 95% confidence intervals (CIs). Only the right eye of each subject was included. Results: A total of 2189 healthy individuals (2189 eyes) were included with a mean age of 49.9 ± 13.2 years; 54.4% were female. In the multivariate model, the FD in the SCP was significantly associated with higher intraocular pressure (IOP) (ß = 0.204; 95% CI, 0.073-0.335; P < 0.001), axial length (AL) (ß = -0.875; 95% CI, -1.197 to -0.552; P < 0.001; R2 = 0.26; root mean square error [RMSE] = 7.78). The FD in the DCP was significantly associated with best-corrected visual acuity (ß = -6.170; 95% CI, -10.175 to -2.166; P = 0.003) and anterior chamber depth (ß = -0.348; 95% CI, -0.673 to -0.023; P = 0.036; R2 = 0.10; RMSE = 2.58). Superficial BVT was independently associated with IOP (ß = -0.044; 95% CI, -0.079 to -0.009; P = 0.012) and AL (ß = 0.097; 95% CI, 0.014-0.181; P = 0.022; R2 = 0.15; RMSE = 2.02). Deep BVT was independently associated with IOP (ß = -0.004; 95% CI, -0.009 to -0.0005; P = 0.028) and lens thickness (ß = 0.036, 95% CI, 0.003-0.060; P = 0.028; R2 = 0.07, RMSE = 0.25). Conclusions: The IOP and AL were dependent ocular parameters variables of FD and BVT in the SCP in this healthy population. The FD in the DCP was also influenced by visual acuity and anterior chamber depth. These factors should be considered when microvascular geometrics are used in the future studies. Translational Relevance: This work discovered the influence factors of OCTA geometrics parameters for further establishment of diagnostic model or method for glaucoma and other microvasculature-related ocular diseases.