Orbital liposarcoma: a retrospective, single-center study of thirteen patients.

AIM: To explore the clinical and pathological characteristics of thirteen patients with orbital liposarcoma. METHODS: The clinical history data of thirteen patients diagnosed as orbital liposarcoma at Beijing Tongren Hospital, from 2006 to 2021 were collected and analyzed. The data includes age, gender, affected orbital side, course of disease, status of disease (primary or recurrent), clinical manifestations, preoperative visual acuity, operative treatment, the relations between liposarcoma and surrounding tissue, longest diameter of liposarcoma, histological subtype, immunohistochemical indicators, follow-up treatment and prognosis. RESULTS: The initial symptoms are diverse. Proptosis is the most frequent chief complaint and the others included vision loss, epiphora, diplopia, and eyelid palpable mass. Results of imaging examination [computed tomography (CT) or magnetic resonance imaging (MRI)] showed orbital mass. In terms of treatment, 10 patients received tumor resection, and the mean longest diameter of the tumor was 3.39±1.36 cm. The other 3 patients had optic nerve invaded, so they received orbital exenteration. Pathological examination results confirmed the diagnose of liposarcoma for 13 patients. Six patients displayed as myxoid type, and three patients in each type of dedifferentiated and well-differentiated type. One patient was verified as pleomorphic, which was a rare type of liposarcoma. All of the patients showed Vimentin positive, and most showed CD34 and S-100 positive. Besides, four patients showed smooth muscle actin positive. All thirteen patients were alive. CONCLUSION: Orbital liposarcoma is a rare disease and it has no specific clinical manifestation. The diagnosis of liposarcoma should be considered when proptosis and orbital mass occurred in orbit. It is recommended to perform pathological examination to achieve early detection and early treatment.

Analysis of clinical and pathological features of ciliary body medulloepithelioma.

AIM: To analyze and summarize the clinical and pathological features of ciliary body medulloepithelioma. METHODS: The clinical and pathological data of 11 patients (11 eyes) who were diagnosed with ciliary body medulloepithelioma at Beijing Tongren Hospital, Capital Medical University, from 2007 to 2021 were retrospectively analyzed. RESULTS: The initial symptoms of 11 patients included vision loss (6 eyes), atrophia bulbi (1 eye), proptosis (2 eyes), and leukocoria (2 eyes). Most patients suffered with corneal opacity, anterior chamber flare and hyphema. Iris neovascularization and synechia, complicated cataract, and secondary glaucoma occurred in several cases. Three patients even had lens subluxation and retinal detachment. B-scan ultrasonography showed vitreous opacity and a medium-high uneven echo mass in the eyeball. Ultrasound biomicroscopy examination showed a spherical or hemispherical ciliary body mass with uneven internal echoes and irregular cystic spaces. All of the 11 patients were diagnosed with malignant ciliary body medulloepithelioma by pathological evidence. In this study, 6 patients had enucleation (2 patients had systemic chemotherapy after surgery), and the other 5 patients had local tumor resection (1 patient had plaque radiotherapy after surgery). CONCLUSION: Ciliary body medulloepithelioma is a rare intraocular tumor and may be easily confused with retinoblastoma. Analyzing the clinical and pathological features of ciliary body medulloepithelioma is useful to further understand ciliary body medulloepithelioma, and can make an accurate diagnosis and better treatment.

Synthesis and Biological Activity Evaluation of 2-Cyanopyrrole Derivatives as Potential Tyrosinase Inhibitors.

In order to find potential inhibitors of tyrosinase, two series of pyrrole derivatives A (1-17) and B (1-8) were synthesized and screened for their inhibitory activities on tyrosinase. Most of the 2-cyanopyrrole derivatives exhibited effective inhibitory activities. In particular, A12 exhibited the strongest inhibitory activities, with the IC50 values of 0.97 µM, which is ∼30 times stronger than the reference inhibitor kojic acid (IC50: 28.72 µM). The inhibitory mechanism analysis results revealed that A12 was a reversible and mixed-type inhibitor. Molecular docking experiments clarified the interaction between A12 with tyrosinase. Furthermore, A12 (100 µM) presented effective inhibitory effect on tyrosinase in B16 melanoma cells with inhibition of 33.48%, which was equivalent to that of Kojic acid (39.81%). Accordingly, compound A12 may serve as the lead structure for the further design of potent tyrosinase inhibitors. Molecular docking studies confirmed the interaction between the compound and tyrosinase.

Association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects in offspring: a prospective cohort study. / å­•æœŸé‡é‡‘å±žå ƒç´ å’Œå¾®é‡å ƒç´ æ°´å¹³ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— ç›¸å ³æ€§çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To study the association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects (CHD) in offspring, and to establish a model for predicting the probability of CHD based on the levels of heavy metals and trace elements during pregnancy. METHODS: Based on the prospective birth cohort study in Gansu Provincial Maternal and Child Health Hospital in 2010-2012, a nested case-control study was conducted for the follow-up observation of 14 359 pregnant women. Among the pregnant women, 97 pregnant women whose offspring were diagnosed with CHD during follow-up were enrolled as the CHD group, and 194 pregnant women whose offspring had no CHD were selected as the control group. Inductively coupled plasma mass spectrometry was used to measure the levels of heavy metals and trace elements in maternal blood samples and fetal umbilical cord blood samples. A multivariate logistic regression analysis was used to evaluate the association between heavy metal and trace elements and CHD in offspring. A nomogram model for predicting the probability of CHD in offspring was established based on the levels of heavy metals and trace elements during pregnancy. RESULTS: Compared with the control group, the CHD group had significantly higher levels of aluminum (Al), natrium (Na), calcium (Ca), titanium (Ti), selenium (Se), strontium (Sr), stannum (Sn), stibium (Sb), barium (Ba), and thorium (Th) in maternal blood samples (P<0.05), as well as significantly higher levels of Al, zinc (Zn), magnesium (Mg), kalium (K), Ca, Ti, chromium (Cr), copper (Cu), arsenic (As), Se, Sr, argentum (Ag), cadmium (Cd), Sn, and plumbum (Pb) in umbilical cord blood (P<0.05). The multivariate logistic regression analysis showed that the increase in the Sb level in maternal blood was associated with the increase in the risk of CHD in offspring [adjusted odds ratio (aOR)=4.81, 95% confidence interval (CI): 1.65-14.07, P=0.004], while in umbilical cord blood, the high levels of Al (aOR=4.22, 95%CI: 1.35-13.16, P=0.013), Mg (aOR=8.00, 95%CI: 1.52-42.08, P=0.014), and Pb (aOR=3.82, 95%CI: 0.96-15.23, P=0.049) were significantly associated with the risk of CHD in offspring. The levels of Al, Th, and Sb in maternal blood and levels of Al, Mg, and Pb in umbilical cord blood were included in the predictive model for CHD in offspring based on the levels of heavy metals and trace elements during pregnancy, and the calibration curve of the nomogram predictive model was close to the ideal curve. CONCLUSIONS: Increases in the levels of Al, Th, Sb, Mg, and Pb during pregnancy may indicate the increase in the risk of CHD in offspring, and the nomogram predictive model based on these indices can be used to predict the probability of CHD in offspring.

Effects of perioperative managements on ocular surface microbiota in intravitreal injection patients.

AIM: To investigate the effects of on ocular surface microbiota in patients who received intravitreal injections. METHODS: Samples of ocular surface microbiota were obtained from 41 eyes of 41 patients who visited the Department of Ophthalmology. Patients were separated for three groups. Group A did not receive perioperative managements or intravitreal injection. Group B1 received only once and B2 received more than twice. In operating room, the samples were collected on the ocular surface. Operating taxonomic units (OTUs) clustering and alpha/beta diversity analysis was performed. The microbial 16S rRNA from samples were analyzed using the HiSeq 2500 platform. RESULTS: Alpha diversity did not differ in each group, and beta diversity differed in the B2 group. Beta diversity showed a significant difference between Group A and B2 (P=0.048). With the perioperative managements before intravitreal injection, the composition and relative abundance were altered. Top 10 microbiota on phylum and genus level, and then microbiota notably changed at genus level were listed. Gram-negative bacteria were varied more. Furthermore, Proteus was not found in Groups A and B1, but it was appeared after the patients received perioperative management and intravitreal injections in Group B2. CONCLUSION: With the perioperative managements, the balance of microbiota on the ocular surface is destroyed, and relative composition and abundance of microbiota on the ocular surface is obviously altered. The clinical doctors should pay more attention on the consequence of perioperative managements before intravitreal injection.

Systematic review and meta-analysis of vitamin D deficiency in different pregnancy on preterm birth: Deficiency in middle pregnancy might be at risk.

BACKGROUND: Current studies suggest that vitamin D deficiency during pregnancy can produce a certain effect for preterm birth (PTB), but there is no research showing whether vitamin D deficiency has a consistent effect in different pregnancies; thus, we conducted a systematic review and meta-analysis of 24 observational studies, grouping them according to the gestational age at the time of serum sampling, to investigate whether vitamin D deficiency in different periods of gestation has different effects on PTB and to provide an evidence-based basis for pregnant women to measure and supplement vitamin D. METHODS: The databases PubMed-Medline, EMBASE, the Cochrane Library, Web of Science, EBSCO, CBM, and CNKI were searched until February 2020. Two researchers independently assessed the eligibility and quality of studies, and STATA 12.0 software was used for meta-analysis. RESULT: Seven cohort studies, 13 case-control studies, and 4 cross-sectional studies were included from 2500 articles by inclusion and exclusion criteria. After adjusting for age, race, and other confounding factors, meta-analysis results showed that vitamin D deficiency in the first trimester, the second trimester, and the third trimester did not increase the risk of PTB (odds ratio (OR) = 1.01, 95% confidence interval (CI) (0.88, 1.16), P = .867; OR = 1.12, 95%CI (0.92, 1.37), P = .249; OR = 1.05, 95%CI (0.87, 1.27), P = .602). However, there was moderate heterogeneity in the study of vitamin D deficiency in the second trimester, and subgroup analysis suggested that vitamin D deficiency in the second trimester may increase the risk of PTB (OR = 1.33, 95%CI (1.15, 1.54), P = .000). A sensitivity analysis of the second trimester showed that excluding any 1 study did not significantly change the results. CONCLUSIONS: Vitamin D deficiency in early and late pregnancy may not be associated with PTB, while vitamin D deficiency in middle pregnancy is likely to have an important effect on PTB. Vitamin D levels should be measured in the second trimester of pregnancy, and vitamin D supplements should be provided if necessary.

Efficacy of wet-lab training versus surgical-simulator training on performance of ophthalmology residents during chopping in cataract surgery.

AIM: To analyze whether wet-lab training (WLT) or surgical-simulator training (SST) is better for ophthalmology residents to master the chopping technique. METHODS: Sixty ophthalmology residents (in their second year) and three cataract surgeons participated in the study. The residents were randomly separated into two groups, WLT group and SST group. The residents in WLT group were asked to perform 10 trials of chopping using pig eyes and scored by the surgeons, and then they performed and scored using simulator for one time. The residents in SST group underwent 10 trials of chopping using simulator, and the simulator scored each trail. Then, this group were asked to perform the chopping using pig eyes and scored by the surgeons. At last, we investigated the residents' satisfaction about the training. RESULTS: The demographic characteristics had no significant differences between the two groups. Recorded by the simulator, the residents in SST group got significantly higher overall score (83.90±1.31) than WLT group (78.73±1.92, P=0.03). And the residents in SST group got less corner area injured, and they spend less time than WLT group (P<0.05). Moreover, the residents in WLT group used more ultrasonic energy value than SST group (P=0.03). However, scored by the surgeons, the residents in two groups got nearly the same overall score. The residents in WLT group performed better on the frequencies of posterior capsule torn and incisional stress (P=0.03, 0.008, respectively). In the survey, the residents in two groups held the same opinion that the training was helpful and they strongly recommended this training. And all of them enjoyed the training, and enjoyed being randomized in their own group. However, with respect to the realistic character, the residents thought that WLT was better than SST (P<0.001). CONCLUSION: Both of the Eyesi surgical-stimulator and the wet-lab improve the residents' chopping ability and each has its own advantages. The combination of the two training ways could be considered to be a part of the training curriculum for new residents.

LncRNA AK148321 alleviates neuroinflammation in LPS-stimulated BV2 microglial cell through regulating microRNA-1199-5p/HSPA5 axis.

AIMS: Dysregulated long non-coding RNA (lncRNA) expression is closely related to neuroinflammation, leading to multiple neurodegenerative diseases. In this study, we investigated the function and regulation of lncRNA AK148321 in neuroinflammation using an in vitro lipopolysaccharide (LPS)-stimulated BV2 microglial cell system. METHODS: Expression of AK148321 was analyzed by qPCR. Inflammatory cytokine expression levels were determined by ELISA assay. The interaction between AK148321, microRNA (miRNA), and its target gene was validated by luciferase reporter assay and RNA immunoprecipitation (RIP). Cell apoptosis was analyzed by Annexin V/PI staining. RESULTS: LPS treatment suppressed AK148321 expression in BV2 cells. Overexpression of AK148321 inhibited LPS-induced BV2 microglial cell activation and decreased the expression of inflammatory cytokine TNF-α and IL-1ß. AK148321 function as a competing endogenous RNA (ceRNA) by sponging microRNA-1199-5p (MiR-1199-5p). In LPS-stimulated BV2 cells, AK148321 exerted its inhibitory function via negatively modulating miR-1199-5p expression. Moreover, we identified that Heat Shock Protein Family A Member 5 (HSPA5) was a direct target of miR-1199-5p. RIP assay using the anti-Ago2 antibody further validated the relationship among AK148321, miR-1199-5p and HSPA5. The AK148321/miR-1199-5p/HSPA5 axis regulated the neuroinflammation in LPS-induced BV2 microglial cells. Microglial cell culture supernatant from LPS-stimulated, AK148321-overexpressing BV2 cells suppressed the cell apoptosis of mouse hippocampal neuronal cell HT22, while HSPA5 knockdown abrogated the suppression effect. CONCLUSION: Our findings suggest that AK148321 alleviates neuroinflammation in LPS-stimulated BV2 microglial cells through miR-1199-5p/HSPA5 axis.

The role of diagnostic magnetic resonance hysterosalpingography in the evaluation of fallopian tubal occlusion of female infertility: A meta-analysis.

OBJECTIVE: To evaluate the diagnostic performance of magnetic resonance hysterosalpingography for fallopian tubal occlusion in the context of female infertility when compared to the diagnostic performance of conditional X-ray hysterosalpingography. METHODS: PubMed, EMBASE, Web of Science, EBSCO, Cochrane Library database, Scopus were searched for studies in which magnetic resonance hysterosalpingography and X-ray hysterosalpingography were used as diagnostic tools for tubal occlusion assessment; databases were searched through April 2020. Two researchers conducted study inclusion assessment, data extraction, a systematic review, and pooled meta-analysis independently. Stata 15.1 software was used to analyze the pooled sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratios, and the area under the summary receiver-operating characteristic curve of magnetic resonance hysterosalpingography. RESULTS: A total of five studies involving 101 patients and 198 fallopian tubes were finally included. Compared with the conditional X-ray hysterosalpingography (the imaging gold standard), the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve of magnetic resonance hysterosalpingography for tubal occlusion were 0.91 (95% CI: 0.48-0.99), 1.00 (95% CI: 0.87-1.00), 230.47 (95% CI: 6.79-7824.72), 0.09 (95% CI: 0.01-0.80), 2676.10 (95% CI: 61.35-120,000), and 1.00 (95% CI: 0.99-1.00), respectively. Subgroup analyses revealed that viscosity of contrast agent (P = 0.024) and test order (P = 0.036) affected the accuracy of MR-HSG to evaluate tubal occlusion. CONCLUSIONS: Our meta-analysis indicated magnetic resonance hysterosalpingography may serve as an alternative for further evaluation of fallopian tubal occlusion of female infertility.

Vitrectomy with air tamponade for surgical repair of rhegmatogenous retinal detachment by eye position guided fluid-air exchange.

AIM: To observe the efficacy and safety of pars plana vitrectomy (PPV) with eye position guided fluid-air exchange (FAX) and air tamponade in the treatment of rhegmatogenous retinal detachment (RRD). METHODS: RRD patients without severe proliferative vitreoretinopathy (PVR) C1 or more were enrolled. All patients underwent PPV combining with air tamponade. During operation, the primary retinal break(s) were placed at lower site and subretinal fluid was aspirated through the break(s) at the same time when eye position guided FAX was proceeding. Sufficient laser spots were made to seal the retinal break(s) after FAX, and filtered air was left in vitreous cavity as tamponade agent finally. The main outcomes were primary and final success rates, best corrected visual acuity (BCVA), and the secondary outcomes were rate of postoperative cataract surgery and high intraocular pressure. RESULTS: A total of 37 eyes (20 males and 17 females) with a follow-up time of ≥6mo were included. The range of RRD was 5.6±1.8h, and the number of retinal breaks was 1.9±1.2. The breaks located at inferior quadrants (between 3:00 and 9:00) in 5 cases (13.5%), and both superior and inferior breaks were found in 3 cases (8.1%). A total of 25 cases (67.6%) with macular detached involvement, 9 cases (24.3%) with intraocular lens, and 8 patients (21.6%) were treated with phacoemulsification and intraocular lens implantation together. The success rate of primary retinal reattachment was 100% (37/37). At 6mo postoperatively, BCVA (logMAR) was increased from 1.13±1.07 to 0.23±0.15 (P<0.001). Phacoemulsification combined with intraocular lens implantation was performed in 2 patients (5.4%), and one of them underwent macular epiretinal membrane peeling in addition (2.7%). Furthermore, high intraocular pressure was found in 4 cases (10.8%). CONCLUSION: PPV with air tamponade by eye position guided FAX can achieve a high reattachment success rate in the management of patients with RRD, and it has the advantages of short postoperative prone time and fewer operative complications.

AQ-4, a deuterium-containing molecule, acts as a microtubule-targeting agent for cancer treatment.

The important physiological function of microtubules makes them an indispensable and clinically effective target of anti-tumor agents. Herein, we sought to design, synthesize, and evaluate a novel 4-anilinoquinazoline derivative and identify its anti-tumor activity in vitro and in vivo. The novel compound, N-(4-methoxyphenyl)-N-methyl-2-(methyl-d3)quinazolin-4-amine (AQ-4), was identified as a representative scaffold and potent microtubule-targeting agent. As a promising antimitotic agent, AQ-4 displayed remarkable anti-tumor activity with an average IC50 value of 19 nM across a panel of 14 human cancer cell lines. AQ-4 also exhibited nearly identical potent activities against drug-resistant cells, with no evidence of toxicity towards normal cells. A further target verification study revealed that AQ-4 targets the tubulin-microtubule system by significantly inhibiting tubulin polymerization and disrupting the intracellular microtubule spindle dynamics. According to the results of mechanism study, AQ-4 induced cell cycle arrest in the G2/M phase, promoting evident apoptosis and a collapses of mitochondrial membrane potential. The superior anti-tumor effect of AQ-4 in vivo suggests that it should be further investigated to validate its use for cancer therapy.