[Changes of serum calcium and bone turnover markers in maintenance hemodialysis patients treated with denosumab].

A total of 20 patients (8 males and 12 females) aged (64.8±13.9) years who underwent regular hemodialysis and had bone loss or osteoporosis in Peking University People's Hospital from July to December 2021 were recruited. Sixty milligrams of denosumab were given subcutaneously. The average serum calcium decreased by 0.31 mmol/L and 40% (8/20) of the patients had hypocalcemia one month after treatment. The markers of bone turnover began to decrease 3 days after treatment, and continued to decrease until 5 months after denosumab medication. Multivariate logistic regression analysis failed to detect any independent risk factor for hypocalcemia (R2=0.516, P=0.021). Therefore, denosumab can significantly inhibit bone turnover in hemodialysis patients, however, patients with denosumab medication are more prone to hypocalcemia.

[Observation of microstructure and vessel density changes in the superficial retinal layer in buried optic disc drusen patients].

Objective: To investigate the changes of the microstructure and vascular density in the superficial retinal layer of buried optic disc drusen (ODD) patients. Methods: Retrospective case-control study. A total of 36 ODD eyes (20 patients) and 26 normal control eyes were recruited in Beijing Union Medical College Hospital from January 2018 to July 2020. Measurement of best corrected visual acuity (BCVA), intraocular pressure, slit lamp, fundus examination and visual field examination were performed. The images and data of spectral domain-optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA) were analyzed and summarized. The differences of nasal retinal nerve fiber layer (RNFL), ganglion cell complex (GCC) thickness and macular superficial vascular density (VD) between ODD patients and normal controls were compared by independent sample t-test or Mann Whitney U test (the right eye was selected in bilateral ODD patients). Results: The 20 ODD patients and 26 normal controls were all female. There was no significant difference in age between the two groups (P>0.05). The BCVA and visual field examination was normal in all ODD patients. The SD-OCT examination showed an oval low signal shadow under the nasal outer nuclear layer of the optic disc, or local accumulation like a medium signal shadow with a clear boundary, and a high signal capsule in ODD patients. The RNFL in the upper nasal side of the ODD group was significantly different from the normal control group [(102.6±19.1) µm vs. (119.0±13.8) µm; t=-2.81; P<0.01]. Compared with normal control group [101.0 (100.0, 102.0) µm], the average GCC thickness in the ODD group [97.0 (89.3, 99.8) µm] was significantly different (U=48.50; P<0.01). The OCTA en-face scan showed that the vascular network in the macular area of the affected eyes was sparser than that of the control eyes. There was significant difference in superficial macular VD beteeen the ODD group (48.5%±2.8%) and the control group (51.0%±2.3%) (t=-2.63; P<0.05). Conclusions: There is thinning in the RNFL upper nasal side and GCC layer of the macular region in buried ODD patients, and the superficial VD of the macular region in buried ODD patients is lower than that in the normal controls.

[GPCR48 promotes invasion and metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma cells].

Objective: To observe the G protein-coupled receptor 48 (GPCR48) expression in hepatocellular carcinoma (HCC) cell lines with different metastatic potential and its characteristics effect on the invasion and metastasis of Huh7 hepatoma cells via epithelial-mesenchymal transition (EMT). Methods: Western blot was used to detect the protein expression level of GPCR48 in HCC cells with different metastatic potential. The lentivirus vector expressing GPCR48 gene was constructed. GPCR48 was overexpressed in Huh7 hepatoma cells. The GPCR48 overexpression level was detected by real-time PCR and Western blot. Transwell invasion and migration assay was used to detect the Huh7 hepatoma cells invasion and migration ability in the Control, Mock and GPCR48 overexpression group. Real-time PCR and Western blot were used to detect Huh7 hepatoma cells mRNA and protein expression levels of the EMT related markers (E-cadherin, N-cadherin, vimentin, and γ catenin) in the Control, Mock and GPCR48 overexpression groups, respectively. Analysis of variance was used to compare the differences between data sets. Results: GPCR48 protein expression level in metastatic HCC cell lines was significantly higher than non-metastatic HCC cell lines (P < 0.05). The lentivirus vector expressing the GPCR48 gene had effectively transfected the Huh7 hepatoma cells and stably expressed the GPCR48mRNA and protein. Compared with the Mock and the Control group, Huh7 hepatoma cells invasion and migration ability in the GPCR48 overexpression group was significantly enhanced (F≥5.54, P < 0.05), and the mRNA and protein expression levels of epithelial phenotypic markers E-cadherin and γ-catenin were decreased (P < 0.05). The mRNA and protein expression levels of the mesenchymal phenotypic markers N-cadherin and Vimentin were increased (P < 0.05), indicating that EMT changes occurred in Huh7 hepatoma cells had overexpressed GPCR48. Conclusion: GPCR48 expression level is positively correlated with the metastatic potential of HCC cells. GPCR48 overexpression can down-regulate the expression of epithelial phenotypic markers and up-regulate the expression of mesenchymal phenotypic markers, and induce EMT changes in HCC cells, thus promoting HCC cells invasion and migration.

[Veracity of using a visual chart with a testing distance of 2.5 meters for measurement of distance visual acuity in teenagers].

Objective: To compare the results of visual acuity testing for teenagers with visual acuity charts designed at 2.5-meter and 5-meter distances, and to investigate the accuracy of the 2.5-meter visual acuity chart. Methods: It was a self-control study. A total of 227 teenagers (454 eyes) with ametropia who came to the ophthalmic clinic of Peking Union Medical College Hospital from March 2019 to September 2019 were included. There were 123 males and 104 females aged (11.74±3.26) years. The vision examiners were trained in the same testing environment and passed the consistency test. Distance visual acuity of all participants was tested with charts designed at 2.5 meters and 5 meters in a 10-minute interval. According to the age (7-9, 10-12, 13-15 and 16-18 years old) and visual acuity (1.00-0.52, 0.40-0.30 and 0.22-0.10), the results of two kinds of visual acuity charts were compared. The testing order of the two visual charts was randomly determined. The visual acuity results were converted into logMAR values and compared. Paried t-student test was used to compare the difference between two charts, and Pearson correlation test was used to explore the correlation between the results of two charts. Results: The visual acuity of the right eye was 0.37±0.24 (logMAR) at 2.5 meters and 0.50±0.26 (logMAR) at 5 meters. The distance visual acuity measured with the 2.5-meter visual acuity chart was better (t=16.19, P<0.01). The visual acuity of the left eye was 0.36±0.23 (logMAR) at 2.5 meters and 0.45±0.23 (logMAR) at 5 meters (t=11.71, P<0.01). The differences between two charts were larger among teenagers with lower visual acuity (r=0.387,P<0.01). Conclusion: Under the same test conditions, the distance visual acuity measured with a 2.5-meter chart was significantly better than a 5-meter chart. The visual acuity chart designed at 2.5 meters was not an appropriate tool to measure distance vision in adolescents. (Chin J Ophthalmol, 2021, 57: 122-125).

[Peripapillary and macular vessel density in eyes with different phases of thyroid-associated ophthalmopathy].

Objective: To analyze the characteristics of vessel density in the optic disc and macular area of patients with different phases of thyroid-associated ophthalmopathy (TAO) and their correlation with visual function. Methods: This case-control study was conducted at the Department of Ophthalmology of Peking Union Medical College Hospital between June 2019 and September 2019. TAO patients and healthy volunteers were included in the study. Patients with a clinical activity score greater than or equal to 3 points were categorized as active TAO. Dysthyroid optic neuropathy (DON) patients with a course less than 6 months were categorized as acute phase of DON, and those more than 6 months were in the chronic group. Healthy volunteers were in the control group. Each group included 12 subjects, with right eyes for analysis. There were 6 males and 6 females in each group. All participants underwent comprehensive ophthalmic examination including best corrected visual acuity and visual field examination for the mean defect (MD). Best corrected visual acuity was subsequently converted to logarithm of minimum angle of resolution (logMAR). Optical coherence tomography was used to measure the thickness of the retinal nerve fiber layer (RNFL) and retinal ganglion cell complex (GCC). Optical coherence tomography angiography was used to the peripapillary and macular vessel density. The differences in the vessel densities in the optic disc and macular area between groups and their correlation with different factors were analyzed. Analysis of variance, non-parametric Mann-Whitney U test and Spearman coefficient were conducted for statistical analysis. Results: There was no significant difference in age among the four groups (P>0.05). The logMAR of the acute DON group was 0.1 (0.0, 0.2), worse than the control group, which was 0.0 (0.0, 0.0) (U=114.000, P<0.05). The overall vessel densities of the optic disc in acute DON and chronic DON were significantly lower than the control group (54.70%±2.31% and 54.31%±3.65% vs. 57.54%±2.17%; t=3.104, 2.636; both P<0.05). The overall superficial vessel densities of the macular area in active TAO, acute DON and chronic DON were significantly lower than the control group (46.07%±3.06% and 42.26%±5.05% and 45.63%±3.87% vs. 49.34%±3.08%), and the differences were statistically significant (t=2.614, 4.147, 2.603; all P<0.05). There was no statistically significant difference in the size of the foveal avascular zone or the density of deep blood vessels in the macular area among the four groups (all P>0.05). In the active TAO period, there was no correlation between the MD value, RNFL thickness, GCC thickness and the vessel densities of the optic disc and macular area (all P>0.05). The vascular density of the whole layer of the optic disc in acute DON was negatively correlated with the MD value (r=-0.591, P<0.05) and positively correlated with the RNFL thickness and GCC thickness (r=0.595, 0.693; both P<0.05). In chronic DON, the overall capillary density of the optic disc was negatively correlated with the MD value (r=-0.673, P<0.05); the superficial overall blood vessel density of the macular area was positively correlated with the thickness of RNFL and GCC (r=0.732, 0.712;both P<0.01). Conclusions: In active TAO, only the blood supply to the superficial layer of the macular area is decreased. In the acute and chronic phases of DON, the blood supply to the superficial layer of the macular area and the optic disc is both reduced; the smaller the blood vessel density, the more severe the visual field defect, and the thinner the RNFL and GCC. (Chin J Ophthalmol, 2020, 56:824-831).

[Optic nerve morphology and vessel density in eyes with different phases of non-arteritic anterior ischemic optic neuropathy].

Objective: To compare the blood flow around the optic disc and related factors in patients with acute and chronic non-arteritic anterior ischemic optic neuropathy (NAION) and healthy volunteers with small disc cups under the same anatomical structure. Methods: This was a prospective case-control study. NAION patients with unilateral onset and healthy volunteers of the same phase were included in the study conducted at the Department of Ophthalmology of Peking Union Medical College Hospital between February 2017 and September 2018. Patients with a course of ≤ 3 months were categorized in the acute phase of NAION, and those with a course of >3 months were in the chronic phase of NAION. Healthy volunteers were in the control group. All subjects underwent the examination of best corrected visual acuity converted to logarithm of the minimum angle of resolution (LogMAR), measurement of non-contact intraocular pressure, slit lamp examination, small pupil fundus examination, and axial measurement. Optical coherence tomography was used to measure the thickness of retinal nerve fiber layers (RNFL) and retinal ganglion cell complex (GCC). Optical coherence tomography angiography was used to measure the vessel density around the optic disc. NAION patients underwent the visual field examination. Analysis of variance, non-parametric Mann-Whitney U test and Spearman coefficient was used for statistical analysis. Results: This study included 16 patients with acute phase of NAION, aged (57±9) years, 6 males and 10 females. There were 17 patients with chronic disease, aged (56±10) years, 7 males and 10 females. There were 15 healthy controls, aged (57±10) years old, 6 males and 9 females. There were no significant differences in age and gender between the groups (both P>0.05). The RNFL and the GCC in the NAION chronic phase group were significantly thinner than those in the acute phase group [(78±38) µm vs. (191±99) µm, (75±19) µm vs. (98±28) µm; t=4.389, 2.758; both P<0.05]. The cup/disc area ratio, cup/disc vertical diameter ratio and cup/disc horizontal diameter ratio in the chronic phase group were larger than those in the acute phase group [0.18 (0.11, 0.31) vs. 0.05 (0.01, 0.18), 0.45 (0.39, 0.56) vs. 0.22 (0.11, 0.41), 0.39 (0.28, 0.54) vs. 0.20 (0.07, 0.42)], and the difference was statistically significant (U=212.000, 208.000, 205.000; all P<0.05). Compared with the optic disc vessel density in the control group (53%±6%), there was a significant decrease in the acute phase group and the chronic phase group (45%±7%, 41%±8%; t=3.705, 4.940; both P<0.01). The blood vessel density in the nasal inferior of the chronic phase group was significantly lower than that in the acute phase group (36%±8% vs. 42%±7%, P=0.039), other sections didn't have significant difference (all P>0.05). There were tortuous capillaries in 8/16 of the acute phase cases, with a low blood flow density and visual field defect in relative positions. Correlation analysis showed that the whole density and peripapillary density in the NAION patients were negatively correlated with LogMAR, mean visual field defect, cup/disc area ratio, focal loss of volume of GCC and general loss of volume of GCC (r=-0.510, -0.733, -0.372, -0.532, -0.648; all P<0.01), but positively correlated with GCC and RNFL thickness (r=0.604, 0.508; both P<0.01). Conclusions: The optic disc vessel density in the acute phase and chronic phase of NAION is significantly reduced. The vessel density in the nasal area of the chronic phase is significantly reduced compared with the acute phase. The vessel density is correlated with visual acuity, visual field defect, disc indexes, thickness of RNFL and GCC. (Chin J Ophthalmol, 2019, 55: 677-686).

[The correlation of ganglion cell layer thickness with visual field defect in non-functional pituitary adenoma with chiasm compression].

Objective: To investigate the consequences of the thickness of ganglion cell layer (GCL) and visual field defect of non-functional pituitary adenoma with chiasm compression. Methods: A case control study. The study included 40 (80 eyes) non-functional pituitary adenoma patients in Peking Union Medical College Hospital from March 2015 to February 2017. Twenty patients (no visual field defect group, 40 eyes) of them were detected to be chiasm compressed or touched by the adenoma with no visual field defect detected, and the other 20 patients (visual field defect group, 40 eyes) were the sex-and-age matched pituitary adenoma patients with bitemporal heminopsia. This study also included 20 (control group, 40 eyes) sex-and-age matched healthy controls. The para-papillary retinal nerve fiber layer (RNFL) thickness in 6 quadrants including nasal, temporal, nasal superior, temporal superior, nasal inferior and temporal inferior as well as the macular GCL thickness and ganglion cell-inner plexiform layer (GCIPL) thickness in 4 quadrants including nasal superior, nasal inferior, temporal superior and temporal inferior were measured. The non-parametric test was used to compare the RNFL, GCL and GCIPL thickness among the three groups. Results: The mean age among the three groups was (46±10) years and the difference among the three groups was not significant (P=0.88). The sex ratio of the three groups was 9∶11 (male∶female) and the difference among the three groups was not significant. The mean axial length among the three groups was (23.22±0.90) mm and the difference among the three groups was not significant (P=0.51). The thickness of para-papillary RNFL of temporal superior, temporal, nasal superior, nasal, nasal inferior quadrants and whole circumference was significantly thinner in the visual field defect group than the control group [(129.88±28.64) µm, (63.63±26.84) µm, (88.08±32.16) µm, (50.68±19.99) µm, (92.48±25.06) µm, and (85.00±20.65) µm vs. (141.10±18.95) µm, (79.12±16.78) µm, (113.68±21.28) µm, (69.67±14.23) µm, (117.80±31.32) µm, and (102.80±9.68) µm, t=2.26, 3.06, 4.14, 4.84, 4.25, 4.88, all P<0.05]. In the nasal quadrant, the para-papillary RNFL of the no visual field defect group was significantly thinner compared with the control group [(61.45±9.83) µm vs. (69.67±14.23) µm, t=2.97, P<0.05]. The total GCL thickness was (30.48±5.42) µm in the visual field defect group, (31.35±2.77) µm in the no visual field defect group, thinner than that in the control group [(33.32±2.92) µm, t=2.92, 3.62; both P<0.05]. The total GCIPL thickness showed no significant difference among the three groups (P=0.07). In the superior and inferior temporal quadrants, the GCL and GCIPL thickness showed no significant difference among the three groups (all P>0.05). In the superior and inferior nasal quadrants, the GCL thickness was (29.41±5.97) µm, and (28.47±5.13) µm in the visual field defect group, (31.15±3.27) µm and (30.61±2.96) µm in the no visual field defect group, and (34.23±3.16) µm and (32.97±2.78) µm in the control group. The GCL thickness in the nasal quadrant was thinner in the visual field defect group (t=4.45, 4.82)and the no visual field defect group(t=4.23, 3.63) than in the control group (all P<0.01). However, no significant difference in GCL thickness was detected between the visual field defect group and the no visual field defect group (both P>0.05). In the superior and inferior nasal quadrants, the GCIPL thickness was (54.06±10.50) µm and (51.77±9.18) µm in the visual field defect group, (58.03±4.00) µm and (56.23±5.37) µm in the no visual field defect group, and (62.26±7.11) µm and (59.39±6.64) µm in the control group. The GCIPL thickness was thinner in the nasal quadrant in the visual field defect group than in the control group (t=3.95, 4.20, both P<0.01). Only in the Superior nasal quadrant, the GCIPL was significantly thinner in the no visual field defect group than the control group (t=3.25, P<0.01). Conclusion: The optic GCL may get thinner in pituitary nonfunctional adenoma with chiasm compression patients without the RNFL layer thinning and visual field defect. (Chin J Ophthalmol, 2019, 55: 186-194).

Emergence of topological nodal loops in alkaline-earth hexaborides XB6 (X = Ca, Sr, and Ba) under pressure.

Based on first-principles calculations, we report that external pressure can induce a topological phase transition in alkaline-earth hexaborides, XB6 (X = Ca, Sr, and Ba). It was revealed that XB6 are transformed from trivial semiconductors to topological node-line semimetals under moderate pressure when the spin-orbit coupling (SOC) is ignored. The band inversion between the B p-orbitals at the X point is responsible for the formation of node-line semimetals. Three node-line rings around the X point are protected by the combination of the time-reversal and spatial inversion symmetries, and drumhead surface bands are obtained in the interiors of the projected node-line rings. When the SOC is included, tiny gaps (<4.8 meV) open at the crossing lines and the XB6 become strong topological insulators with Z2 indices (1 : 111). As the SOC-induced gap opening is negligible, our findings thus suggest ideal real systems for experimental exploration of the fundamental physics of topological node-line semimetals.