Objective To evaluate the effect of multifocal visual evoked potential(mfVEP)on the detection of glaucomatous field defects. Design Case-controlled study. Participants 20 healthy individuals and 20 patients with primary glaucoma accepted mfVEP test. Methods 20 healthy individuals and 20 patients with primary glaucoma were tested with RETIscan multifocal VEP System 3.20 and OCTOPUS 101 automated perimetry G2 test program. Amplitudes were measured and interocular response asymmetry coefficient (RAC) was calculated for each site from all participants. The abnormal areas from mfVEP test were compared with field defects from automated perimetry. Main Outcome Measures Amplitude, RAC. Results 90% of suffered eyes showed at least 3 adjacent points had an amplitude decrease or RAC outside 2 standard deviations (SD) from healthy individual database, in which 63% showed at least 3 adjacent points had an amplitude decrease outside 2 SD from normal database while 70% showed at least 3 adjacent points had a RAC outside 2 SD from normal database. 2 patients (2 eyes) had field defects in mfVEP though automated perimetry showed normal field. None of the healthy showd field defects in mfVEP test. Conclusions mfVEP could be used to detect field defects of glaucoma.

Objective To compare the effect of electrode positions o n multifocal visual evoked potential(mf-VEP). Methods Ten healt hy individuals were tested with RETIscan multifocal VEP system 3.20, each indiv idual was tested with four electrode positions: the active and reference electro de were placed 2.0 cm above and below the inion in Ch1;3.0 cm above and 4.5 cm below the inion in Ch2;2.0 cm on both right and left side of the inion in C h3 and 4.0 cm on both right and left side of the inion in Ch4. The summed ampli tudes of hemifield mf-VEP were analyzed and compared according to different ele ctrode positions. Results The difference among summed amplitud es of the upper or lower hemifield mf-VEP recorded with Ch1、Ch2、Ch3 and Ch4 w as statistically significant;and the difference between Ch2 and the other chann els was statistically significant too. The difference among summed amplitudes of the horizontal sites whose amplitudes were small when recorded with Ch2 and sum med amplitudes of the corresponding sites recorded with Ch3 and Ch4 were statist ically significant;and the difference between Ch4 and the other channels was st atistically significant too. Conclusions compared to Ch1、Ch3 and Ch4, Ch2 can make a better recording of mf-VEP. As for some sites, especi ally those along horizontal line, horizontal electrodes could improve the amplit udes of mf-VEP recorded with vertical electrodes,and Ch4 could do better to im prove the mf-VEP recorded with Ch2 than Ch3.

Objective: To investigate the influence of lidocaine on systemic inflammation in the perioperative ventricular septal defect (VSD). Methods: Twenty patients, scheduled for ventricular septal defect were randomly divided into 2 groups: lidocaine and control groups. Before rebeat lidocaine 1 mg/kg was given.The venous blood samples were obtained from the central venous at the following points: after induction of anesthesia and before cardiopulmonary bypass(CPB,T1),1 h after CPB(T2),2 h after CPB(T3), and 4 h after CPB(T4). IL-6 and IL-8 were determined by radio-immunoassay. Results: Compared with those at T1, the levels of white blood cells,polymorphonuclear neutrophils,IL-6 and IL-8 increased significantly from T2 to T4 in both groups. IL-6 and IL-8 levels reached the peak at T2. Compared with those in control groups, IL-6 level decreased obviously in lidocaine group from T2 to T4, but IL-8 level remained unchanged significantly. Conclusion: Under CPB and VSD repair the systemic inflammation is obvious, reaches the peak 30 min after CPB and persists to 4 h after CPB. Perioperative administration of lidocaine is effective against the inflammation.

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OBJECTIVETo improve the oral bioavailability of patchoulic alcohol in rats by using self-microemulsifying drug delivery systems (SMEDDS).

METHODPatchoulic alcohol was separated and purified from patchoulic oil, and the SMEDDSs including patchoulic alcohol or patchoulic oil were optimized by pseudo-ternary phase diagrams via central composite design-response surface methodology. Pharmacokinetics of both SMEDDSs and patchoulic alcohol itself in rats were investigated.

RESULTThe patchoulic alcohol SMEDDS (Cremophor EL-Tween 80-PEG 400-isopropyl myristate-patchoulic alcohol, 2:2:0.8:1.95:0.65) was considered as the optimized formulation. The mean drop size of the system was 30. 1 nm after diluted 100 folds in water. The average self-microemulsifying time was 142 s. Patchoulic alcohol SMEDDS and patchoulic oil SMEDDS showed no signficant difference in Tmax compared with patchoulic alcohol with around 60 minutes, while the AUCs of both SMEDDSs (2001 745.6 +/- 329 663.6) and (1594 005.6 +/- 280 150.3) microg x min x L(-1) were significantly higher than that of patchoulic alcohol (1 163 153.3 +/- 232 324.3) microg x min x L(-1).

CONCLUSIONSMEDDS can effectively improve the oral bioavailability of patchoulic alcohol in rats.

Administration, Oral ; Animals ; Biological Availability ; Chemistry, Pharmaceutical ; Drug Delivery Systems ; methods ; Drug Stability ; Emulsifying Agents ; chemistry ; Ethanol ; chemistry ; Female ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Self Administration ; Sesquiterpenes ; chemistry ; Solubility

Objective:To observe the clinical and imaging features of infiltrative optic neuropathy (ION) secondary to extraocular malignant tumors.Methods:A retrospective case study. From January 2017 to October 2022, 26 eyes of 20 patients with ION secondary to extraocular malignancies and 32 eyes of 16 patients with early papilloedema (EP) secondary to intracranial metastatic carcinoma were included in the study. All eyes underwent best corrected visual acuity (BCVA), fundus color photography, orbital and/or craniocerebral magnetic resonance imaging (MRI). A total of 54 eyes were examined by visual field examination, among which ION and EP were 22 and 32 eyes, respectively. Clinical and imaging features of the affected eye were retrospectively analyzed.Results:Among 26 eyes of 20 ION patients, there were 13 males and 7 females, with the mean age of (52.8±16.9) years. There were 10 patients of hematologic malignancy, 7 patients of periorbital malignancy, 2 patients of lung cancer, 1 patient of gastric cancer, 1 patient of breast cancer and 1 patient of prostate cancer. Two patients of nasal lymphoma were recorded as hematologic malignancies and periorbital malignancies. Sixteen patients had a history of systemic or periorbital malignancy, among which 4 patients reported that they had been "clinically cured". Optic neuritis was diagnosed in 15 patients. Among the 16 patients with EP, 5 were males and 11 were females, with the mean age of (47.9±12.3) years. The primary malignant tumors were lung cancer, breast cancer, leukemia, gastric cancer, ovarian cancer, colon cancer and rectal cancer in 7, 2, 2, 2, 1, 1, 1, respectively. In 26 eyes of ION, 20 eyes complained of blurred vision or peripheral vision occlusion and progressive aggravation; no obvious visual symptoms in 6 eyes. BCVA was light sensing to 1.0 with a median of 0.3, including light sensing and light sensing in 4 eyes. Optic disc edema was observed in 19 eyes; no obvious abnormality in 7 eyes. Visual field examination showed that in 22 eyes, normal or mild enlargement of blind spot in 3 eyes, arcuate scotoma in 4 eyes, annular scotoma in 6 eyes, tubular visual field or concentric contraction of visual field in 6 eyes, and diffuse depression in 3 eyes. MRI showed optic nerve enlargement with sheath enhancement in all ION eyes. Among 32 eyes of EP, 28 eyes showed recurrent transient amaurosis, and the other 4 eyes showed horizontal diplopia. BCVA ranged from 0.8 to 1.5, with a median of 1.0. All EP patients showed different degrees of optic disc hyperemia and edema by fundus examination. The visual field examination showed normal or mild enlargement of the physiological blind spot. MRI showed thickening of the optic nerve and widening of the intrathecal space, but no obvious enhancement of the optic nerve and its intrathecal membrane, and obviously enhanced space-occupying lesions in the brain parenchyma, accompanied by compression and edema of the surrounding brain tissue and midline displacement.Conclusions:ION secondary to extrocular malignant tumors mainly manifested as mild visual symptoms and obvious optic disc edema. MRI showed thickened optic nerve and strengthened sheath, and no obvious abnormality in optic nerve parenchyma.

OBJECTIVETo investigate the apoptosis inducing effects of ponicidin (PON) on leukemic K562 cells and its mechanisms of action.

METHODK562 cells in culture medium in vitro were given different concentrations of PON (10-50 micromol x L(-1)) for 24, 48 and 72 h. The inhibitory rate of the cells was measured by MTT assay, cell apoptotic rates were detected by flow cytometry (FCM) using Annexin V staining after K562 cells were treated with different concentrations of PON for 72 hours, and cell morphology was observed by Wright-Giemsa staining. Western blot was used to detect caspase-3 and poly(ADP-ribose) polymerase (PARP) expression, and the protein levels in mitogen-activated protein kinase signaling pathways (MAPKs, p-P38, p-ERK and p-JNK) as well as p-AKT and p-P85 in PI3K/AKT signaling pathways were also detected.

RESULTPON (over 30 micromol x L(-1)) could inhibit the growth of K562 cells in both time- and dose-dependent manner. FCM analysis revealed that apoptotic cells were gradually increased in a dose-dependent manner after treatment for 72 hours, and that marked morphological changes of cell apoptosis such as condensation of chromatin was clearly observed by Wright-Giemsa staining after treatment by 50 micromol x L(-1) PON. Western blot showed cleavage of the caspase-3 zymogen protein (32 kD), with the appearance of its 17 kD subunit, and a cleaved 89 kD fragment of 116 kD PARP was also found. Furthermore, Western blotting also showed that expression of p-AKT and p-P85 in PI3K/AKT signaling pathways was downregulated dramatically whereas the expression of p-P38 as well as p-ERK and p-JNK remained unchanged after the cells were treated by PON for 48 h.

CONCLUSIONThe results demonstrate that PON exhibits in vitro anti-leukemia effect by induction of apoptosis in K562 cells, and that PON induced apoptosis in K562 cells mainly related to activation of caspase-3 as well as inactivation of PI3K/AKT signaling pathway via down regulation of the expression of p-AKT and p-P85 protein levels. These results provide strong laboratory evidence for further anti-leukemia trials of PON.

Apoptosis ; drug effects ; Blotting, Western ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Diterpenes ; pharmacology ; Humans ; Poly(ADP-ribose) Polymerases ; metabolism ; Signal Transduction ; drug effects

Objective:To observe the changes in blood flow density of radial retinal peripapillary capillary (RPC) around the optic disc in patients with non-arteritic anterior ischemic optic neuropathy (NAION) at different stages of the continuous course of the disease.Methods:A prospective cohort study. From January to December 2020, 29 cases of 29 eyes of NAION patients diagnosed in the Eye Center of the Second Affiliated Hospital of Zhejiang University School of Medicine were included in the study. Among them, there were 18 males with 18 eyes and 11 females with 11 eyes. The average age was 53.62±6.67 years old. The affected eye underwent routine eye examination and visual field, optic cohenrence tomography angiography (OCTA) examination. Visual field inspection was performed to obtain the average visual mean defect (MD) value. OCTA was used to measure the thickness of the peripapillary retinal nerve flayer (pRNFL) around the optic disc, the whole en face image vessel density (wiVD), intro disc vessel density (diVD), RPC blood flow density around the optic disc, and macular ganglion cell complex (GCC). The course of disease ≤3 weeks was defined as the acute phase; 4-12 weeks was defined as the subacute phase; >12 weeks was defined as the chronic phase. The changes of visual field MD, optic disc RPC blood flow density, pRNFL thickness and macular GCC thickness were observed in the acute, subacute and chronic phases (12-24, >24 weeks). A completely randomized design of variance analysis was used to compare the differences in visual field MD, RPC blood flow density, GCC, and pRNFL thickness in different courses. Pearson correlation analysis was used to analyze the correlation between pRNFL thickness, macular GCC thickness, visual field MD changes and RPC blood flow density around the optic disc sex.Results:The wiVD of the eyes in the acute phase, subacute phase, and chronic phase (12-24 weeks, >24 weeks) were (44.96±2.76)%, (41.50±3.49)%, (39.08±5.43)%, (38.56±6.48)%. There was a statistically significant difference in wiVD of eyes with different disease courses ( F=8.939, P<0.001). The average difference of wiVD between 12-24 weeks and >24 weeks in the chronic phase was -0.984, and the difference was not statistically significant ( P>0.05). There was no statistically significant difference in diVD of patients with different courses of disease ( F=1.079, P=0.365). The blood flow density of RPC around the optic disc of the affected eye, except for the lower part, the blood flow density of the nasal side, the temporal side, and the upper quadrant, decreased significantly with the progression of the disease, and the difference was statistically significant ( F=8.816, 6.069, 8.943; P<0.05). In the chronic phase, the average difference of blood flow density between the nasal, temporal, and upper sides of the eyes between 12-24 weeks and more than 24 weeks in the chronic phase was -0.984, -0.230, -0.198, and the difference was not statistically significant ( P>0.05). There was no statistically significant difference in the visual field MD of patients with different courses of disease ( F=0.277, P=0.842); the overall pRNFL thickness and average macular GCC thickness were compared with statistical significance ( F=47.122, 14.954; P<0.001, <0.001), all became significantly thinner with the progression of the disease. The results of Pearson correlation analysis showed that the blood flow density of the entire optic disc wiVD, the blood flow density of RPC in the temporal quadrant around the optic disc and the visual field MD ( r=-0.225, -0.268; P<0.05), and the average thickness of GCC ( r=0.480, 0.436; P<0.01) were all related. Conclusion:The blood flow density of RPC in the entire optic disc and around the optic disc (except the lower quadrant) of NAION eyes gradually decrease with the progression of the disease, and stabilize after 12 weeks of the disease.

Objective:To observe the clinical features and visual prognostic factors of ethambutol-induced optic neuropathy (EON).Methods:A cohort study. Twenty-four inpatients (46 eyes) identified as EON in Neuro-Ophthalmology Department of Chinese PLA General Hospital from January 2014 to December 2017 were enrolled, including 14 males (26 eyes) and 10 females (20 eyes) with a ratio of 1.4/1 male/female. The average age was 42.79±15.12 years and the average weight was 62.46±12.31 kg. The average time duration between oral administration of ethambutol and occurrence of EON was 9.94±16.49 months. The average time of ethambutol duration was 7.06±11.68 months, with an average accumulative dose of 156.7±1 779.0 g and the average daily dose of 15.07±8.95 mg/(kg·d). All patients were tested with visual acuity, fundus photos, colour vision, OCT, visual field, VEP, orbital MRI and the gene of OPA1 and mitochondrial deoxyribonucleic acid(mtDNA). All the patients accepted drug withdrawal immediately after diagnosis, and were given the treatment of systemic nerve nutrition and improvement of microcirculation for 2 weeks. The time of follow-up was more than 12 months. According to whether the visual acuity (VA) in any of eyes was over than 0.1 at the last follow- up, all the patients were divided into two groups: the bad VA group (VA less than or equal to 0.1) and the better VA group (VA over than 0.1) group. The χ2 test and Fisher's exact probabilistic method test were used to compare the counting data between groups, and the Wlincox rank sum test was used to compare the measurement data. Multiple factors of VA outcome between the patients with bad or better va were analyzed by logistic regression. Results:Thirty eyes (65.2%) had VA less than or equal to 0.1 and 5 eyes (10.9%) had VA over than 0.5 at EON onset. The VA of the rest 11 eyes (23.9%) was higher than 0.1 and lower than 0.5. At the last follow- up, 20 eyes (43.5%) had VA less than or equal to 0.1 and 9 eyes (19.6%) had VA over than 0.5, the VA of the rest 17 eyes (36.9%) was higher than 0.1 and lower than 0.5. Fundus examination revealed 7 eyes (15.3%) with optic disc edema. OCT revealed significant loss of the retinal nerve fiber layer (RNFL) in the affected eyes, mainly in the temporal RNFL of the optic disc. All patients had dyschromasia, mainly in distinguishing the color of red and green. The types of visual field defect was as following: central dark spot (52.2%), diffuse visual acuity decreased (30.4%), temporal hemianopsia (17.4%). Orbital MRI revealed that 12/24 (50.0%) patients had T2 lesions with T1 enhancement in 6/24 patients (25.0%). Genetic test showed that 4 patients (16.7%) had gene mutation. Among them, there were 2 patients with OPA1 mutation, 1 with mtDNA 14340 point mutation and 1 with the mtDNA 11778 point mutation. Thirteen patients showed better VA outcomes (over than 0.1) while 11 showed bad VA outcomes after discontinuation of ethambutol. Between the better VA group and the bad VA group, there were statistically significant differences in the daily dose of ethambutol and gene mutation( P=0.031, 0.023). The daily dose was related to visual prognosis of EON while only the daily dose of more than 18 mg/(kg·d) may lead to bad VA outcomes according to the logistic analysis (95% CI 0.007-0.736, OR=0.069, P=0.027). Conclusions:EON may have OPA1 and mtDNA mutation with more bilateral eyes involved and less optic edema, which about 43.5% of the patients showed irreversible visual impact. The daily dose of ethambutol is related to the vision recovery.

Methods:Two thousand standard sections images werre collected from 2 000 clinical retrospective pediatric hip ultrasound videos from January 2019 to January 2021. All standard sections were annotated by the annotation team through the self-designed software based on Python 3.6 environment for image cross-media data annotation and manual review standardization process with unified standards. Among them, 1 753 were randomly selected for training the deep learning system, and the remaining 247 were used for testing the system. Further, 200 standard sections were randomly selected from the test set, and 8 clinicians independently completed the film reading annotation. The 8 independent results were then compared with the AI results.Results:The testing set consists of 247 patients. Compared with the clinician's measurements, the area under the receiver operating characteristic curve (AUC) of diagnosing hip joint maturity was 0.865, the sensitivity was 76.19%, and the specificity was 96.9%. The AUC of AI system interpretation under Graf detailed typing was 0.575, the sensitivity was 25.90%, the specificity was 89.10%. The 95% LoA of α-angle determined by Bland-Altman method, of -4.7051° to 6.5948° ( Bias -0.94, P<0.001), compared with clinicians' measurements. The 95% LoA of β-angle, of -7.7191 to 6.8777 ( Bias -0.42, P=0.077). Compared with those from 8 clinicians, the results of AI system interpretation were more stable, and the β-angle effect was more prominent. Conclusion:The AI system can quickly and accurately measure the Graf correlation index of standard DDH ultrasonic standard diagnosis plane.