Age-related macular degeneration (AMD) has become one of the leading causes of irreversible blindness worldwide.With the advancement of stem cell technology,tissue engineering and biomaterials,cell-based therapy has been inspiring for many degenerative diseases.For its unique advantages,AMD has become one of the most promising fields for cell-based therapy,which involve retinal pigment epithelium(RPE)cells,induced differentiation of neural retina cells and related cytokine regulations.RPE cells can be derived from human embryonic stem cells (hESC) or Induced pluripotent stem cells (iPS).Recently hESC-derived RPE cells have been applied to patients with dry AMD with initial success in clinical trials.In terms of tissue engineering,studies are focused on factors affecting the long-term survival of transplanted cells,including tissue scaffolds,soluble hybrid materials and scaffold anchoring.This article briefly reviews the RPE differentiation,neural retina differentiation and related cytokines of cell-based therapy and scaffolds,materials,and cell-scaffolds interactions of tissue engineering in AMD treatment.

Objective To review the ophthalmic features of granulomatosis with polyangiitis (GPA).Methods Clinical data of 164 GPA patients diagnosed in Peking Union Medical College Hospital during the past 10 years were retrospectively reviewed.Results Among 164 patients,48 (29.3％) had ocular involvement with a male to female ratio of 1.4:1 and an average age of (45 ± 15) years.Nine patients (5.5％) were first diagnosed at the ophthalmology department.Scleritis (15.9％,26/164),orbit lesions (13.4％,22/164) and peripheral corneal ulcer (9.1％,15/164) were the three most common ophthalmic complications.Twenty-two patients (13.4％) had positive findings in the orbit imaging.Six patients (3.7％,6/164) lost their vision due to GPA.Conclusion The ocular manifestations of GPA are diverse and complicated.GPA may affect every component of the eye,sclera,orbit and cornea are the most frequently affected sites of the eye.

Objective To investigate the expression and clinical significance of COX-2 and telomerase activity in esophageal carcinoma tissues(ECT)and resection margin of the esophagus(RME),and to analyze their diagnostic and prognostic value for esophageal carcinoma.Methods The expression of COX-2 and telomerase activity in ECT and RME was examined in 82 patients with esophageal carcinoma and 40 normal esophageal epithelium tissues(NEET) by tissue array with EnVision imimunohistochemistry.Their correlations with the clinicopathologic factors were analyzed statistically.Results The positive expression rates of COX-2 and telomerase in ECT and RME were significantly higher than those in NEET(82.9 ％,29.3 ％vs 12.5 ％;and 87.8 ％,18.3 ％vs 5.0 ％;respectively;all P ＜ 0.05).The expression of COX-2 and telomerase in ECT and RME was correlated to TNM stage,tumor cell differentiation and lymph node metastasis (all P ＜0.01),while both expression in RME was closely related to anastomotic recurrence following resection of esophageal carcinoma (P＜0.01).The survival rate in esophageal carcinoma patients with the positive expression of COX-2 and telomerase in RME could be much lower than those with negative expression of COX-2 and telomerase in RME (P=0.000,Log-rank test).COX-2 expression was positively correlated to telomerase in ECT and RME (r=0.786,0.218,P＜0.05).Conclusion COX-2 and telomerase might be important biological markers for malignant transformation and invasion and metastasis of esophageal carcinoma.The activity of COX-2 and telomerase in RME could prognosticate anastomotic recurrence,and could be potential biomarkers evaluate the surgical treatment and prognosis of esophageal carcinoma.

Objective To evaluate the optical coherence tomograghy (OCT) morphological parameters for predicting anatomical outcomes and postoperative visual acuity in idiopathic macular hole (IMH) after pars plana vitrectomy (PPV).Methods A retrospective study.A total of 26 eyes in 23 IMH patients underwent PPV,internal limiting membrane (ILM) peeling and gas filling surgery were included in this study.The patients included 8 eyes of 7 males and 18 eyes of 16 females,with the mean age of (63.9 ± 9.4).All patients received the best corrected visual acuity (BCVA),slit lamp microscope,indirect ophthalmoscopy and three-dimensional optical coherence tomography (3D OCT) examinations.The BCVA was measured using the international standard visual acuity chart,and the results were converted to the logarithm of the minimum angle of resolution visual acuity.According to the standard classification system of International Vitreomacular Traction Study (IVTS) Group,8 eyes were medium full-thickness macular hole (FTMH) and 18 eyes were large FTMH,none of which were with vitreomacular traction (VMT).The minimum diameter (MIN),base diameter (BASE),height (H),left and right arm length (LAL and RAL),diameter of ellipsoid zone absence (DEZA) were measured.Macular hole index (MHI),hole form factor (HFF),tractional hole index (THI),diameter hole index (DHI) were calculated.The average follow-up period were (9.2 ± 9.7) months.The postoperative DEZA were measure at the last time.Anatomical outcomes were divided into 3 groups.The multiple factors related with predicting anatomical outcome and visual acuity were analyzed.Results In the 26 eyes,the hole was closed in 16 eyes of type 1,7 eyes of type 2,3 eyes of type 3.The mean pre-and post-operative logMAR BCVA were 0.9 ± 0.3,0.7 ± 0.3 respectively.The MIN,BASE,H were (533 ± 176),(1 035 ±270),(462 ± 138) μm respectively.The MHI,HFF,THI,DHI were 0.46 ±0.15,0.72 ±0.19,0.95 ±0.37,0.52 ±0.11 respectively.The mean preand post-operative DEZA were (1 775 ± 486),(960 ± 138) μm respectively.Postoperative logMAR BCVA were correlated significantly with MHI,THI (all P ≤ 0.01),correlated weakly with MIN,BASE,HFF (all P ≤ 0.05),but not correlated with age,sex,DHI,pre-and post-operative DEZA (all P ＞ 0.05).Anatomical prognosis types were significantly correlated with MHI,HFF,THI (all P ≤ 0.01),weakly correlated with MIN,DHI (all P ≤ 0.05),but not correlated with age,sex,BASE,pre-and post-operative DEZA (all P ＞ 0.05).Conclusions For medium and large FTMH in IVTS classification system,MHI,THI have the best correlation with postoperative BCVA and can be considered as key indicators for predicting postoperative BCVA.MHI,HFF,THI have the best correlation with anatomical outcomes and can be considered as key indicators for predicting anatomical outcomes of IMH.

Objective To analyze the results of diagnostic pars plana vitrectomy (PPV) in patients with uveitis of unknown cause.Methods This is a retrospective case series study.Sixty-five patients (67 eyes) with uveitis of unknown cause were enrolled in this study.There were 31 males (32 eyes) and 34 females (35 eyes).The ages were from 6 to 84 years,with the mean age of (55.00± 18.56) years.All eyes were received PPV.Examination of vitreous samples consisted of microbial stains and culture,microbial DNA and antibody detection,cytokine measurement,cytology,flow cytometry and gene rearrangement detection.Results Vitreous analysis was positive in 40 of 67 eyes (59.7％).Positive results indicated bacterial endophthalmitis in 20 of 40 eyes (50.0％),lymphoma in 11 eyes (27.5％),viral IgM and IgG increased significantly in 3 eyes (7.5％),fungal endophthalmitis in 3 eyes (7.5％),IgG of toxocara increased significantly in 2 eyes (5.0％),IgG of toxoplasma Gondii increased significantly in 1 eye (2.5％).Conclusion The diagnostic yield of vitreous samples in uveitis eyes of unknown cause is 59.7％.

Covalent organic nanospheres(CONs)were explored as a fiber coating for solid-phase microextraction of genotoxic impurities(GTIs)from active ingredients(AIs).CONs were synthesized by an easy solution-phase procedure at 25℃.The obtained nanospheres exhibited a high specific surface area,good ther-mostability,high acid and alkali resistance,and favorable crystallinity and porosity.Two types of GTIs,alkyl halides(1-iodooctane,1-chlorobenzene,1-bromododecane,1,2-dichlorobenzene,1-bromooctane,1-chlorohexane,and 1,8-dibromooctane)and sulfonate esters(methyl p-toluenesulfonate and ethyl p-toluenesulfonate),were chosen as target molecules for assessing the performance of the coating.The prepared coating achieved high enhancement factors(5097-9799)for the selected GTIs.The strong affinity between CONs and GTIs was tentatively attributed to T-T and hydrophobicity interactions,large surface area of the CONs,and size-matching of the materials.Combined with gas chromatography-mass spectrometry(GC-MS),the established analytical method detected the GTIs in capecitabine and imatinib mesylate samples over a wide linear range(0.2-200 ng/g)with a low detection limit(0.04-2.0 ng/g),satisfactory recovery(80.03％-109.5％),and high repeatability(6.20％-14.8％)and reproducibility(6.20％-14.1％).Therefore,the CON-coated fibers are promising alternatives for the sensitive detection of GTIs in AI samples.

OBJECTIVE: To investigate the clinical manifestations, biochemical abnormalities and pathogenic variants among children with Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency detected by neonatal screening. METHODS: A total of 2 730 852 newborns were screened from January 2016 to December 2021 with liquid chromatography tandem mass spectrometry. Suspected SBCAD deficiency patients were diagnosed by urine organic acid analysis and high-throughput gene sequencing analysis. The clinical, biochemical and genetic changes of the confirmed cases were analyzed, in addition with guidance for diet and life management, L-carnitine supplement, and survey of growth and intellectual development. RESULTS: Twelve cases of SBCAD deficiency were diagnosed, which yielded a prevalence of 1/227 571. The lsovaleryl carnitine (C5) of primary screening blood samples was between 0.6 and 2.1 µmol/L, all exceeded the normal range. C5/acety1 carnitine (C2) was between 0.02 and 0.12, with 6 cases exceeding the normal range. C5/propionyl carnitine (C3) was between 0.1 and 1.16, with 5 cases exceeding the normal range. Free carnitine (C0) was between 18.89 and 58.12 µmol, with 1 case exceeding the normal range. Three neonates with abnormal screening results were recommended to have appropriate restriction for protein intake and two were given L-carnitine. During follow-up, their C5 has ranged from 0.22 to 2.32 µmol/L, C5/C2 has ranged from 0.01 to 0.31, C5/C3 has ranged from 0.14 to 1.7. C5 or C5/C2 and C5/C3 were transiently normal in all patients except for case 8 during the neonatal screening and follow-up. C0 was 17.42 ∼ 76.83 µmol/L Urine organic acid analysis was carried out in 9 of the 12 cases, and 2-methylbutyroglycine was elevated in 8 cases. Urine organic acid analysis was carried out in 9 cases, and 2-methylbutyrylglycine was increased in 8 cases. Genetic analysis was carried out for 11 children, and in total 6 ACADSB gene variants were identified, which included 4 missense variants (c.655G>A, c.923G>A, c.461G>A, c.1165A>G), 1 frameshift variant (c.746del) and 1 nonsense variant (c.275C>G). Among these, the C.461G>A variant was unreported previously. The most common variants were c.1165A>G (40.9%) and C.275C>G (22.7%). The patients were followed up for 18 days to 55 months. Only one patient had mental retardation, with the remainders having normal physical and mental development. CONCLUSION SBCAD deficiency is a rare disease. The detection rate of newborn screening in this study was 1/227 571. Early intervention can be attained in most asymptomatic patients through neonatal screening. In this study, the common gene variants are c.1165A>G and c.275C>G.
Humans ; Infant, Newborn ; Amino Acid Metabolism, Inborn Errors/genetics* ; Carnitine ; Neonatal Screening/methods*

Considering the surgical risk stratification for patients with severe calcific aortic stenosis (AS), transcatheter aortic valve replacement (TAVR) is a reliable alternative to surgical aortic valve replacement (SAVR) (Fan et al., 2020, 2021; Lee et al., 2021). Despite the favorable clinical benefits of TAVR, stroke remains a dreaded perioperative complication (Auffret et al., 2016; Kapadia et al., 2016; Kleiman et al., 2016; Huded et al., 2019). Ischemic overt stroke, identified in 1.4% to 4.3% of patients in TAVR clinical practice, has been associated with prolonged disability and increased mortality (Auffret et al., 2016; Kapadia et al., 2016; Levi et al., 2022). The prevalence of hyperintensity cerebral ischemic lesions detected by diffusion-weighted magnetic resonance imaging (DW-MRI) was reported to be about 80%, which is associated with impaired neurocognitive function and vascular dementia (Vermeer et al., 2003; Barber et al., 2008; Kahlert et al., 2010).
Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve Insufficiency ; Diffusion Magnetic Resonance Imaging ; Aortic Valve Stenosis ; Stroke

Objective To understand the distribution characteristics of death causes and potential life loss of residents in Pudong New Area from 2009 to 2018, assess the disease burden caused by different diseases, and provide a basis for formulating regional prevention and control strategies. Methods The mortality data of residents in Pudong New Area of Shanghai from 2009 to 2018 were collected. The death causes were classified by International Classification of Diseases (ICD-10). The crude mortality rate, standardized mortality rate, potential years of life lost (PYLL), potential years of life lost rate (PYLLR), and average years of life lost (AYLL) were calculated. Results The crude mortality and standardized mortality of residents in Pudong New Area between 2009 and 2018 were 7.55‰ and 3.65‰, respectively. The top five causes of death in Pudong New Area residents were circulatory system diseases, tumors, respiratory diseases, endocrine nutrition and metabolic diseases, and injury and poisoning, accounting for 87.85% of the total deaths. The PYLL was 687 729 person-years, the PYLLR was 24.11‰ and the AYLL was 3.19 years per person. The top 5 causes of life loss of residents in Pudong New Area was tumor, circulatory system disease, injury and poisoning, endocrine nutrition and metabolism illness, and congenital anomalies, accounting for 82.08% of total life loss of residents. Conclusion Chronic non-infectious diseases, including circulatory diseases, tumors, and endocrine nutritional metabolism diseases, were the main causes of death of residents in Pudong New Area, and caused a heavy disease burden, which should be the focus of prevention and control in the future. Comprehensive preventive and control measures should be taken to protect the residents from the harm due to chronic non-communicable diseases and improve the health condition of the residents in Pudong New Area.

Objective To explore the epidemiological characteristics and the potential years of life lost of gynecological malignant tumors among female residents in Pudong New Area of Shanghai between 2002 and 2019. Methods Crude mortality rate (CMR), age-standardized mortality rate (SMR), potential years of life lost (PYLL), average years of life lost (AYLL) and annual percent change (APC) of the cervical cancer，uterine cancer and ovarian cancer deaths were calculated to analyze the mortality situation of gynecological malignant tumors among female residents in Pudong New Area. Results The crude mortality rate were 2.65/100 000, 2.44/100 000 , 4.55/100 000, and age-standardized mortality rate were 1.33/100 000, 1.06/100 000, 2.26/100 000, respectively, among female residents in Pudong New Area during 2002 to 2019. In the study period, both the crude mortality rate and the age-standardized mortality rate of cervical cancer rose over the years; Both the crude mortality rate and the age-standardized mortality rate of uterine cancer kept stable; The crude mortality rate of ovarian cancer showed an upward trend, and the age-standardized mortality rate kept stable. The PYLL of cervical cancer was 7335 years, the PYLL rate was 0.30‰, and the AYLL was 11.20 years per person; The PYLL of uterine cancer was 3556 years, the PYLL rate was 0.14‰, and the AYLL was 5.90 years per person; The PYLL of uterine cancer was 10017 years, the PYLL rate was 0.41‰, and the AYLL was 8.91 years per person. Conclusion The mortality rate of cervical cancer and ovarian cancer rose over years, and the mortality of uterine cancer kept stable among female residents in Pudong New Area during 2002 to 2019. The gynecological malignant tumors caused severe disease burden.