Morphine and morphine-6-glucuronide (M6G) produce central nervous system (CNS) effects by activating mu-opioid receptors, while naloxone is used mainly for the reversal of opioid overdose, specifically for the fatal complication of respiratory depression, but also for alleviating opioid-induced side effects. In this study we developed a physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD) model to simultaneously predict pharmacokinetics and CNS effects (miosis, respiratory depression and analgesia) of morphine as well as antagonistic effects of naloxone against morphine. The pharmacokinetic and pharmacodynamic parameters were obtained from in vitro data, in silico, or animals. Pharmacokinetic and pharmacodynamic simulations were conducted using 39 and 36 clinical reports, respectively. The pharmacokinetics of morphine and M6G following oral or intravenous administration were simulated, and the PBPK-PD model was validated using clinical observations. The Emax model correlated CNS effects with free concentrations of morphine and M6G in brain parenchyma. The predicted CNS effects were compared with observations. Most clinical observations fell within the 5th-95th percentiles of simulations based on 1000 virtual individuals. Most of the simulated area under the concentration-time curve or peak concentrations also fell within 0.5-2-fold of observations. The contribution of morphine to CNS effects following intravenous or oral administration was larger than that of M6G. Pharmacokinetics and antagonistic effects of naloxone on CNS effects were also successfully predicted using the developed PBPK-PD model. In conclusion, the pharmacokinetics and pharmacodynamics of morphine and M6G, antagonistic effects of naloxone against morphine-induced CNS effects may be successfully predicted using the developed PBPK-PD model based on the parameters derived from in vitro, in silico, or animal studies.

Successful fertilization and early embryonic development heavily depend on the quality of the oocytes. Carbendazim (CBZ), a broad-spectrum fungicide, is widely available in the environment and has adverse effects on organisms. The present study focused on exploring the potential reproductive toxicity of CBZ exposure by investigating its effects on the maturation of mouse oocytes. The results demonstrated that although no disruptions were observed in the G2/M stage transition for meiosis resumption, CBZ did hinder the polar body extrusion (PBE) occurring during oocyte maturation. Cell cycle distribution analysis revealed that CBZ exposure interfered with the meiotic process, causing oocytes to be arrested at the metaphase I (MI) stage. The subsequent investigation highlighted that CBZ exposure impeded the spindle assembly and chromosomal alignment, which was linked to a decline in the level of p-MAPK. Additionally, CBZ exposure adversely affected the kinetochore-microtubule (K-MT) attachment, leading to the persistent activation of the spindle-assembly checkpoint (SAC). The study further noticed a substantial rise in the acetylation of α-tubulin and a reduction in spindle microtubule stability in CBZ-treated oocytes. In addition, the distribution pattern of estrogen receptor alpha (ERα) was altered in oocytes treated with CBZ, with abnormal aggregation on the spindles. CBZ exposure also resulted in altered histone modifications. A notable finding from this research was that the meiotic maturation of some oocytes remained unaffected even after CBZ treatment. However, during the ensuing metaphase II (MII) stage, these oocytes displayed anomalies in their spindle morphology and chromosome arrangement and diminished ability to bind to the sperm. The observations made in this study underscore the potential for CBZ to disrupt the meiotic maturation of oocytes, leading to a decline in the overall quality of oocytes.

OBJECTIVE: The purpose of the study was to investigate the changes of choroidal blood perfusion in different layers and quadrants and its possible related factors after 1 h visual task by augmented reality (AR) device in two-dimensional (2D) and three-dimensional (3D) mode, respectively.
METHODS: Thirty healthy subjects aged 22-37 years watched the same video source in 2D and 3D mode separately using AR glasses for 1 h with a one-week interval. Swept-source optical coherence tomography angiography (SS-OCTA) was performed before and immediately after watching to acquire choroidal thickness (ChT), three-dimensional choroidal vascularity index (CVI) of large- and middle-sized choroidal vessels and choriocapillaris flow voids (FV%) at macular and peripapillary area. Near point of accommodation (NPA) and accommodative facility (AF) were examined to evaluate the accommodative ability. Pupil diameters by infrared-automated pupillometer under scotopic, mesopic and photopic condition were also obtained.
RESULTS: Compared with pre-visual task, the subfoveal CVI decreased from 0.406 ± 0.097 to 0.360 ± 0.102 after 2D watching (p < 0.001) and to 0.368 ± 0.102 after 3D watching (p = 0.002). Pupil sizes under different illuminance conditions became smaller after both 2D and 3D watching (all p < 0.001). AF increased after both 2D and 3D watching (both p < 0.05). NPA receded in post-3D watching (p = 0.017) while a not significant tendency was observed in post-2D.
CONCLUSIONS: A reduction in subfoveal choroidal blood flow accompanied with pupil constriction was observed immediately after 1 h visual task using AR glasses in 2D and 3D mode. Accommodative facility improved after 2D and 3D watching with AR glasses, whereas decrease in the maximum accommodation power was only found in 3D mode.

To evaluate the effect of miosis and laser peripheral iridotomy (LPI) on intraocular lens (IOL) power prediction and ocular biometry in eyes with primary angle closure disease (PACD).
In this prospective observational study, primary angle closure suspects (PACS), and subjects classified with primary angle closure (PAC)/primary angle-closure glaucoma (PACG) undergoing LPI were enrolled. Ocular biometric parameters were measured with IOLMaster700 at baseline (T0), one week after pilocarpine instillation (T1), and another week post LPI (T2). Biometric changes and the IOL power predicted for emmetropia using Barrett Universal II, Haigis, Holladay2, Hoffer Q and SRK/T formulae were analysed and compared among different time points.
100 eyes of 50 PACS and 50 PAC/PACG patients were enrolled. Following pilocarpine-induced miosis, lens thickness (LT) increased and anterior chamber depth (ACD) decreased (all groups p < 0.01), while white-to-white diameter decreased and central corneal thickness increased significantly only in the PACS cohort (both p < 0.01). Compared to baseline, LPI induced an increase of ACD and a slight decrease of LT in PACS (both p < 0.01), whereas only axial length changed significantly (p = 0.012) in the PAC/PACG cohort. Regardless of the formula used, no significant difference to the predicted IOL power for emmetropia existed among the three time points in each group (all p > 0.1).
We report the changes of anterior segment parameters induced by miosis and LPI in PACD. These interventions do not significantly affect the IOL power calculation predicted for emmetropia in Chinese eyes when common third-, fourth-and new generation IOL formulae are used.

Lower response of aqueous outflow pathway structures after pilocarpine could be observed in primary open angle glaucoma (POAG) patients, which is likely to be helpful for understanding intraocular pressure (IOP) evaluation in glaucoma.
To evaluate the morphologic changes in the trabecular meshwork (TM), Schlemm canal (SC), scleral spur (SS), and ciliary muscle after miosis in patients with POAG and healthy individuals.
A total of 30 patients with POAG and 26 healthy controls were recruited. All participants underwent complete ophthalmologic examinations, including IOP and swept-source optical coherence tomography (OCT), before and 1 hour after the local administration of pilocarpine (2%). OCT measurements included TM thickness and width, SC diameter and area, SS length, ciliary muscle thickness, and ciliary muscle angle (CMA).
Pilocarpine administration induced a decline in IOP (15.6±2.3-14.6±2.2 mm Hg), decrease in nasal SS length (196.31±47.75-171.52±33.93 μm), decrease in TM thickness (90.18±16.43-83.02±13.74 μm), and increase in SC diameter (134.84±32.28-162.08±48.67 μm) and SC area (3851.37±1455.07-4801.39±1762.37 μm 2 ) among healthy controls. In contrast, no significant changes in IOP and OCT measurements were found in patients with POAG. At baseline, CMA was independently correlated with IOP in normal eyes. After miosis, the change in TM thickness was independently correlated with changes in IOP in normal eyes; in eyes with POAG, changes in SS length and CMA were independently associated with changes in IOP.
Topical pilocarpine-induced morphologic changes to outflow pathway structures in healthy individuals without significant changes in POAG. The lower response observed in patients with glaucoma may be relevant to understanding IOP changes.

BACKGROUND: Congenital anomalies of the pupil are quite varied, including abnormal size, shape, color, response to stimulus, and function. We are here reporting an unusual case presented with the absence of pupillary opening with folds of iris tissue at the center. Only an extremely small pupil (diameter < 0.5 mm) could be observed during the operation.
METHODS: A 15-year-old male patient visited our outpatient clinic due to vision difficulty in his right eye for more than ten years. The best-corrected visual acuity was 2.0 logMAR and 0 logMAR for the right and left eye, respectively. There were amblyopia, astigmatism and constant exotropia in his right eye. Ophthalmic examination of the right eye showed flat iris root, minimal iris pigmentation, and the pupil area was entirely covered by iris tissue. Lens status and fundus evaluation could not be commented. The left eye was found to be within normal limit. Based on ophthalmic examination, the admission diagnosis was given as acorea. Pupilloplasty was performed on the right eye due to the situation that the iris tissue blocked the visual axis, which led to visual impairment and stimulus deprivation amblyopia. However, an extremely small pupil at the center of his pupillary area was observed during the operation. The postoperative course was favorable, and a normal pupil was secured. Hospital discharge diagnosis was given as microcoria, and amblyopia treatment was followed.
CONCLUSIONS: We report a rare case of congenital pupillary abnormality. The further diagnosis was given as microcoria, which should be differentiated from acorea. For this kind of pupil disorder which blocks the visual axis, early diagnosis and treatment can help prevent the development of stimulus deprivation amblyopia.

OBJECTIVE: To compare 6 methods for intraoperative pupil dilatation in eyes with insufficient pupil size during phacoemulsification.
METHODS: This was a prospective case-control study. 99 microcoria cataract patients (120 eyes) were collected and were divided into 6 groups(20 eyes each group), and their pupils were dilated by bimanual stretching pupil (group I), pupil radial cut open(group II), mechanical pupil dilatation with iris-retractor hooks (group III), OASIS iris expander (group IV), and Malyguin-ring (Microsurgical company, America) (group V), B-HEX Pupil Expander (Med Invent Devics, India)(group VI),respectively. 3.0 mm clear corneal incision were used in phacoemulsification. All cases were followed up at 1 week and 1, 3, 6 months after the surgery. The best corrected visual acuity (BCVA), intraocular pressure(IOP), corneal endothelium cell density(ECD), pupil diameter(PD) of before and after surgery were compared.
RESULTS: One same doctor finished all cataract surgeries successfully. The eyes\' condition before surgery and at 6 months after surgery were compared. There were no significant statistical differences for the conditions of the eyes before surgery among six groups. The ECDs were better at 6 months postoperatively in group III and V, median values: 2114/mm2, 1961/mm2. PD was largest in group II (median value: 5.5 mm), which was significantly larger than other groups (Padjusted < 0.05).
CONCLUSIONS: All 6 methods used in this study were effective for the mechanical dilatation of small pupils and didn\'t affect the postoperative visual acuity and intraocular pressure in microcoria cataract phacoemulsification. Iris-retractor hooks and the Malyugin Ring can reduce intraoperative corneal endothelium cell loss. Postoperative PD is larger when the iris was cut open radially.

An application of the XpandNT iris speculum in eyes with small pupils during secondary intraocular lens (IOL) implantation in congenital cataract patients is described. The iris speculum was first positioned in the eye to expand the pupil. A 30-gauge needle was used to separate the adhesion of the iris tissue and the capsular rim. Vitrectomy was used to clean Soemmerring\'s ring near the capsular rim. The iris expander was retracted with the Williamson XpandNT Manipulator. The IOL was then implanted. Fourteen aphakic eyes from 10 consecutive patients were studied retrospectively; pupil expansion was achieved in all 14 eyes intraoperatively without serious intraoperative or postoperative complications. The iris speculum was a safe and excellent tool for removing Soemmerring\'s ring and solving small pupil problems during secondary IOL implantation in pediatric cataract surgery patients.

Objective: To analyze the epidemiological characteristics and response process of an acute poisoning event caused by carbofuran in buttered tea and provide scientific evidence for the investigation of similar events in the future. Methods: Field epidemiological survey, animal experiments and laboratory tests were conducted for an acute poisoning event occurred in Suopo township of Danba county of Sichuan province in 2018. Descriptive epidemiological method was used to analyze the epidemiological characteristics of the acute poisoning event. Results: A total of 26 poisoning cases occurred in 3 villages. The total attack rate was 41.27%. No death cases were reported. The 26 cases occurred in a few minutes after drinking buttered tea, the main symptoms were vomit, dizziness, miosis and nausea. A dog showed the same symptoms after drinking a sample of buttered tea. Carbofuran was detected in buttered tea, vomitus and zanba samples. Conclusions: The acute poisoning was caused by carbofuran in buttered tea, the transmission mode was point source spread. Effective epidemiological investigation and simple animal experiment can provide evidence for the rapid sample detection and clinical treatment of cases in emergency response. Timely case treatment and strict poisoning source control are the key measures to reduce casualty and prevent the spread of poisoning.
目的： 分析一起由呋喃丹引起的酥油茶急性中毒事件的流行特征和处置过程，为今后类似事件的调查处置提供科学依据。 方法： 对2018年丹巴县梭坡乡发生的一起急性中毒事件开展现场流行病学调查、动物实验和实验室检测，采用描述性流行病学方法对该起疫情资料进行分析。 结果： 本次疫情共有病例26例，涉及3个村的村民，总罹患率为41.27%，无死亡病例。26例病例均于饮用酥油茶后数分钟发病，主要临床表现为呕吐、头晕、瞳孔缩小、恶心等。现场1只犬饮用样品酥油茶后发病。实验室在所采集的样品酥油茶、呕吐物、糌粑中同时检出呋喃丹。 结论： 本起疫情是呋喃丹引起的急性中毒事件，为点源传播模式。应急处置中有效流行病学调查，简易的动物实验可为快速采样检测、病例救治提供方向；病例及时送医救治，严格落实源头控制措施是降低伤亡，防止事件扩大的关键环节。.

To evaluate post-miosis changes in the anterior chamber structures in various angle-closure glaucomas (ACG). Totally 14 eyes of primary chronic angle-closure glaucoma (PCACG), 12 eyes of lens-induced secondary chronic angle-closure glaucoma (LSACG) and 14 healthy eyes were recruited. After miosis, for PCACG group, intraocular pressure (IOP) and anterior chamber depth (ACD) changed not significantly, while anterior chamber angle widened significantly. LSACG group showed a significant increase in IOP, decrease in ACD, and narrowing in anterior chamber angle. Healthy eyes showed significant decreases in IOP and anterior chamber parameters. Thus, miosis could widen the anterior chamber angle of patients with PCACG, while increase the narrowing of anterior chamber angle and IOP of patients with LSACG. We should pay attention to the distinction between PCACG and LSACG patients and the proper administration of pilocarpine in the treatment of patients with chronic ACG.