Expression of TRIP4 and DDIT4 in Glioma Tissue and Their Relationship with Clinical Pathological Parameters and Prognosis / 现代检验医学杂志

Objective To study the expression of thyroid hormone receptor binding protein 4(TRIP4)and DNA damage inducing transcription factor 4(DDIT4)in glioma tissue and their relationship with clinical pathological characteristics and prognosis.Methods 94 glioma patients admitted to the First Hospital of Hebei Medical University from February 2018 to February 2019 were selected as the research subjects.The expression of TRIP4,DDIT4 proteins in tissues were detected by immunohistochemistry.The relationship between the expression of TRIP4,DDIT4 proteins in glioma tissues and clinical pathological characteristics were compared.The differences in survival prognosis of glioma patients with different levels of TRIP4,DDIT4 protein expression were analyzed by Kaplan-Meier survival curve.Univariate and multivariate COX regression analysis was conducted to analyze the factors affecting the survival prognosis of glioma patients.Results The positive rates of TRIP4(68.09%),DDIT4(65.96%)proteins in glioma tissues were higher than those in adjacent tissues(13.83%,10.64%),with statistically significant differences(χ2=57.212,60.866,all P<0.05).There was a significant positive correlation between TRIP4 and DDIT4 protein expression in glioma tissues(r=0.722,P<0.05).The positive rates of TRIP4(83.64%vs 46.15%,80.00%vs 51.28%)and DDIT4(80.00%vs 46.15%,76.36%vs 51.28%)proteins in glioma tissues with tumor diameter≥3cm,WHO grade Ⅲ were significantly higher than those in tissues with tumor diameter＜3cm,WHO grade Ⅰ～Ⅱ(χ2=6.393～14.754,P<0.05).The 3-year overall survival rates of the TRIP4 positive and negative expression groups were 37.50%(24/64)and 66.67%(20/30),respectively.The 3-year cumulative survival of the TRIP4 positive expression group was significantly lower than that in the TRIP4 negative expression group(Log-rank χ2=5.949,P=0.015).The 3-year overall survival rate of DDIT4 positive and negative expression group was 37.10%(23/62)and 70.00%(21/30),respectively.The 3-year cumulative survival of the DDIT4 positive expression group was significantly lower than that in the DDIT4 negative expression group(Log-rank χ2=7.642,P=0.006).Tumor diameter≥3cm(HR=1.614,P=0.000),WHO grade Ⅲ(HR=1.790,P=0.000),positive TRIP4(HR=1.665,P=0.000)and positive DDIT4(HR=1.476,P=0.000)were independent risk factors affecting the survival prognosis of glioma patients.Conclusion The expression of TRIP4 and DDIT4 protein in glioma tissue was increased.Both of them were related to tumor diameter and WHO grade,and are potential tumor markers for survival prognosis of glioma.

Analysis of the interaction of fasting blood glucose and serum uric acid on di-abetic retinopathy / 眼科新进展

Objective To investigate the impact of the interaction of fasting blood glucose(FBG)and serum uric acid(SUA)on diabetic retinopathy(DR).Methods A total of 306 diabetes mellitus(DM)patients diagnosed and re-ceived comprehensive ophthalmic examination in the First Affiliated Hospital of Gannan Medical University from January 2019 to January 2021 were selected.According to the presence or absence of DR,these patients were divided into the DR group(178 patients)and the non-DR(NDR)group(128 patients).The general clinical data of patients in the two groups were compared.The least absolute shrinkage and selection operator(LASSO)regression method and multivariate Logistic regression analysis were used to screen the independent influencing factors of DR in DM patients,and the odds ratio of risk factors was calculated.The sensitivity analysis of the results was performed using the E-value method.The interaction of FBG and SUA on DR in DM patients was analyzed by an additive interaction model.The Nomogram model to predict DR in DM patients was constructed and verified internally.The receiver operating characteristic curve(ROC)was used to evalu-ate the effects of FBG,SUA and both FBG and SUA on DR in DM patients.Results Compared with the NDR group,the course of DM in the DR group was significantly longer,the proportion of patients with history of oral medication was signif-icantly lower,the proportion of patients with history of insulin therapy was significantly higher,and the levels of total cho-lesterol,triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,blood urea nitrogen,serum creatinine,SUA and FBG were significantly higher(all P＜0.05).The history of insulin therapy,course of DM≥9.66 years,TG≥2.07 mmol·L-1,SUA ≥ 297.73 μmol·L-1 and FBG ≥8.92 mmol·L-1 were the risk factors for DR in DM pa-tients,while the history of oral medication was the protective factor for DR in DM patients.The Nomogram model based on the above independent risk factors was accurate in predicting the occurrence of DR in DM patients.SUA and FBG had inter-active effects on DR in DM patients.The value of SUA-FBG interaction in the diagnosis of DR was greater than that of both alone.Conclusion SUA≥ 297.73 μmol·L-1 and FBG ≥8.92 mmol·L-1 are the risk factors for DR in DM patients.The value of interaction of FBG and SUA in the diagnosis of DM accompanied by DR is greater than that of both alone.

Synergistic Functionality of Dopants and Defects in Co-Phthalocyanine/B-CN Z-Scheme Photocatalysts for Promoting Photocatalytic CO2 Reduction Reactions.

The realization of solar-light-driven CO2  reduction reactions (CO2 RR) is essential for the commercial development of renewable energy modules and the reduction of global CO2 emissions. Combining experimental measurements and theoretical calculations, to introduce boron dopants and nitrogen defects in graphitic carbon nitride (g-C3 N4 ), sodium borohydride is simply calcined with the mixture of g-C3 N4 (CN), followed by the introduction of ultrathin Co phthalocyanine through phosphate groups. By strengthening H-bonding interactions, the resultant CoPc/P-BNDCN nanocomposite showed excellent photocatalytic CO2 reduction activity, releasing 197.76 and 130.32 µmol h-1  g-1 CO and CH4 , respectively, and conveying an unprecedented 10-26-time improvement under visible-light irradiation. The substantial tuning is performed towards the conduction and valance band locations by B-dopants and N-defects to modulate the band structure for significantly accelerated CO2 RR. Through the use of ultrathin metal phthalocyanine assemblies that have a lot of single-atom sites, this work demonstrates a sustainable approach for achieving effective photocatalytic CO2 activation. More importantly, the excellent photoactivity is attributed to the fast charge separation via Z-scheme transfer mechanism formed by the universally facile strategy of dimension-matched ultrathin (≈4 nm) metal phthalocyanine-assisted nanocomposites.

High Fischer ratio peptide of hemp seed: Preparation and anti-fatigue evaluation in vivo and in vitro.

The high Fischer (F) ratio hemp peptide (HFHP) was prepared by enrichment using activated carbon adsorption, ultrafiltration, and Sephadex G-25 gel filtration chromatography. The OD220/OD280 ratio reached 47.1 with a molecular weight distribution from 180 to 980 Da, a peptide yield up to 21.7 %, and the F value was 31.5. HFHP had high scavenging ability of DPPH, hydroxyl free radicals, and superoxide. Mice experiments showed that the HFHP increased the activity of superoxide dismutase and glutathione peroxidase. The HFHP had no effect on the body weight of mice, but prolonged their weight-bearing swimming time. The lactic acid, serum urea nitrogen, and malondialdehyde of the mice after swimming was reduced, and the liver glycogen increased. The correlation analysis indicated that the HFHP had significant anti-oxidation and anti-fatigue properties.

Immune Thrombocytopenia Induced by Sintilimab in Lung Cancer: A Case Report and Literature Review / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) show unique advantages in the treatment of lung cancer, making the treatment of lung cancer enter the era of immunotherapy, but ICIs will also have adverse reactions, and the incidence of immune-induced hematological toxicity is not very high. Immunotherapy-induced thrombocytopenia is a rare adverse event.We report one case of thrombocytopenia induced by ICIs and review the literature on thrombocytopenia associated with ICIs and discuss the clinical features, possible mechanisms, and optimal treatment. 
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Bioinformatics and Computer Simulation Approaches to the Discovery and Analysis of Bioactive Peptides.

The traditional process of separating and purifying bioactive peptides is laborious and time-consuming. Using a traditional process to identify is difficult, and there is a lack of fast and accurate activity evaluation methods. How to extract bioactive peptides quickly and efficiently is still the focus of bioactive peptides research. In order to improve the present situation of the research, bioinformatics techniques and peptidome methods are widely used in this field. At the same time, bioactive peptides have their own specific pharmacokinetic characteristics, so computer simulation methods have incomparable advantages in studying the pharmacokinetics and pharmacokineticpharmacodynamic correlation models of bioactive peptides. The purpose of this review is to summarize the combined applications of bioinformatics and computer simulation methods in the study of bioactive peptides, concentrating on the role of bioinformatics in simulating the selection of enzymatic hydrolysis and precursor proteins, activity prediction, molecular docking, physicochemical properties, and molecular dynamics. Our review shows that new bioactive peptide molecular sequences with high activity can be obtained by computer-aided design. The significance of the pharmacokinetic-pharmacodynamic correlation model in the study of bioactive peptides is emphasized. Finally, some problems and future development potential of bioactive peptides binding new technologies are being prospected.

Mental retardation autosomal dominant 35 caused by de novo missense variants in PPP2R5D gene: a case report and literature review / 中华神经科杂志

Objective:To enhance understanding of mental retardation autosomal dominant 35 (MRD35) by analyzing the clinical and genetic characteristics of the disease.Methods:Clinical and genetic data of 1 case of MRD35 in Beijing Children′s Hospital in July 2018 were reported, and literature review was conducted.Results:The male proband, 1 year and 3 months old, was admitted with the clinical manifestations including mental retardation, low-grade fever, a large forehead, flat nose, open mouth, and hypomyotonia. The brain magnetic resonance imaging showed enlarged lateral ventricles, cavum septum, cavum verge and cavum velum interpositum cyst. The whole exome sequencing test showed that the proband carried a missense mutation c.1258 G>A, (p.E420K) in the PPP2R5D gene, and the mutation was de novo confirmed by Sanger sequencing. There were ten literatures reported, including a total number of 31 cases. Counting on this case, totally 32 cases were included. Among the 32 patients, 32 cases (100.0%) had mental retardation, 26 cases (81.3%) with motor retardation, 26 cases (81.3%) with macrocephaly, 8 cases (25.0%) with epilepsy. Facial dysmorphic features, ocular abnormalities, skeletal abnormalities, and cardiac malformations were also reported. All reported individuals had missense mutations of PPP2R5D gene and were autosomal dominantly inherited. Conclusions:The main clinical manifestations of MRD35 include growth retardation/mental retardation, severe speech impairment, macrocephaly, hypomyotonia, seizures and dysmorphic facial features. A novel missense mutation in the PPP2R5D gene is the cause of MRD35.

CHINA PH ARMACY Volume 33，Number 6，March 30，2022 Semimonthly Table of Contents Guideline for the evaluation of medicine list in Chinese med ical instituti ons / 中国药房

In order to improve the management level of medicine list of medical institutions in China ，and help medical institutions build a medicine list of medical institutions with reasonable drug use structure ，standardized adjustment procedures ， convenient operation and application and scientific evaluation methods ，so as to meet the needs of clinical rational drug use to the greatest extent ，with the support of the Pharmaceutical Care Professional Committee of the Chinese Pharmaceutical Association ， China-Japan Friendship Hospital and the First Affiliated Hospital of University of Science and Technology of China （Anhui Provincial Hospital ）jointly initiate and complete Guideline for the Evaluation of Medicine List in Chinese Medical Institutions jointly with a number of medical institutions. In strict accordance with the methodological requirements of World Health Organization standard guidelines ，based on the Delphi method ，the guideline formulation working group has constructed the quality evaluation index system and quantitative scoring table of medicine list management in medical institutions from the 5 dimensions of organization and management ，structure，adjustment，application and e valuation of the list. It is used to help medical institutions evaluate the quality of their medicine list management ，so asto play a positive role in the fine management of medicine list in medical institutions.

Penetration enhancer for pharmacy prepared compound terbinafine ointment / 药学实践杂志

Objective To screen and identify the penetration enhancer in pharmacy prepared compound terbinafine ointment. Methods In vitro percutaneous penetration test was conducted with vertical Franz diffusion pool. The SD rat's abdomen skin was used for permeable membrane and 60% polyethylene glycol 400-40% saline for receiving liquid to analyze different osmotic promoters. Results The permeability of compound terbinafine ointment was significantly higher with 10% propylene glycol than 15% propylene glycol. The compound terbinafine ointment with 10% propylene glycol was also better than 3% azone in permeability. Conclusion 10% propylene glycol was selected to be the penetration promoter for pharmacy prepared compound terbinafine ointment, which improved the solubility of the drug in the skin.

Progress of ascites in diagnosis and treatment of ovarian cancer / 肿瘤研究与临床

Owing to its insidious onset, the diagnosis of ovarian cancer is usually delayed and followed with ascites, which results in a poor prognosis compared to other gynecological malignant tumors. Ascites, a pathological accumulation of fluid in the abdominal cavity, contains a variety of cellular and non-cellular components, which promotes tumor metastasis, leads to chemotherapy resistance, and seriously affects the quality of life and prognosis of patients. In this article, the basic characteristics and the recent progress of ascites in ovarian cancer are reviewed, so as to provide references for further research.

Generation of developmentally competent oocytes and fertile mice from parthenogenetic embryonic stem cells

Parthenogenetic embryos, created by activation and diploidization of oocytes, arrest at mid-gestation for defective paternal imprints, which impair placental development. Also, viable offspring has not been obtained without genetic manipulation from parthenogenetic embryonic stem cells (pESCs) derived from parthenogenetic embryos, presumably attributable to their aberrant imprinting. We show that an unlimited number of oocytes can be derived from pESCs and produce healthy offspring. Moreover, normal expression of imprinted genes is found in the germ cells and the mice. pESCs exhibited imprinting consistent with exclusively maternal lineage, and higher X-chromosome activation compared to female ESCs derived from the same mouse genetic background. pESCs differentiated into primordial germ cell-like cells (PGCLCs) and formed oocytes following in vivo transplantation into kidney capsule that produced fertile pups and reconstituted ovarian endocrine function. The transcriptome and methylation of imprinted and X-linked genes in pESC-PGCLCs closely resembled those of in vivo produced PGCs, consistent with efficient reprogramming of methylation and genomic imprinting. These results demonstrate that amplification of germ cells through parthenogenesis faithfully maintains maternal imprinting, offering a promising route for deriving functional oocytes and having potential in rebuilding ovarian endocrine function.

The assay of voriconazole in plasma from patients with hepatic insufficiency by UPLC-MS/MS / 药学实践杂志

Objective To establish an UPLC-MS/MS method of voriconazole assay in human plasma for clinical therapeutic drug monitoring. Methods The plasma samples were treated with methanol to precipitate protein and the supernatants were assayed by UPLC-MS/MS. The chromatographic column was InertSustain C18 HP (3.0 mm×100 mm, 3 μm) with the mobile phase of water and acetonitrile solution (15:85) at 35 ℃ and 0.3 ml/min flow rate. ESI was used for Mass Spectrum in positive ion MRM mode with target ions m/z: 350.9/282.2(voriconazole) and m/z: 307.0/238.0(fluconazole). Results The linear range of voriconazole was 0.1–20 μg/ml (r=0.999 5）. The lower limit of quantitation was 0.1 μg/ml. The extraction recovery was higher than 90%. RSDs of inter-day and intra-day were all lower than 10%. The plasma concentrations measured by this method were in the range of 0.97 to 18.7 μg/ml from 10 patients with hepatic insufficiency who were treated with voriconazole. Conclusion The established method was fast, accurate and sensitive。It can be applied for the therapeutic drug monitoring of voriconazole，and provided a good base for rationalized medication treatment in patients with hepatic insufficiency.

Analysis of spatial clustering of dogs infected with Leishmania in Wenxian and Diebu counties of Gansu Province / 中华地方病学杂志

Objective:To analyze the spatial distribution characteristics of dogs infected with Leishmania in Wenxian and Diebu counties of Gansu Province, and provide a scientific basis for implementation of precise prevention and control measures. Methods:In 2019, blood samples were collected from all dogs in visceral leishmaniasis endemic areas Xinglong Village, Wenxian County and Luoda Village, Diebu County, Gansu Province, by cluster sampling method. The primer RV1-RV2 which was commonly used to diagnose visceral leishmaniasis, was used for PCR amplification of dog blood samples. SaTScan V9.5 software was used to analyze the spatial clustering of dogs infected with Leishmania. Results:A total of 537 dogs were investigated, and the number of positive infection was 221, with a positive rate of 41.2%. Among them, the positive rates of dogs infected with Leishmania in Wenxian and Diebu counties were 64.6% (95/147) and 32.3% (126/390), respectively. The results of SaTScan analysis showed that the spatial clustering of dogs infected with Leishmania in Wenxian and Diebu counties were not statistically significant ( P > 0.05). Conclusions:There are no spatial clustering of dogs infected with Leishmania in Wenxian and Diebu counties, but the positive rate of dogs infected with Leishmania is higher, and there is a higher risk of epidemic. It is recommended to strengthen health education in local area, strictly drive out lacewings, detect and kill diseased dogs, and reduce the risk of visceral leishmaniasis transmission.

Survey on Leishmania infection in dogs in Wenxian County and Diebu County of Gansu Province in 2019 / 中华地方病学杂志

Objective:To investigate the Leishmania infection status in dogs in canine-derived visceral leishmaniasis endemic areas in Wenxian County and Diebu County of Gansu Province, to provide basis for formulating effective prevention and treatment measures for visceral leishmaniasis. Methods:In 2019, household survey method was used to collect dog basic information (such as gender and age) in villages with higher incidence of previous cases in Wenxian County and Diebu County of Gansu Province; and venous blood of dog was collected, PCR method was used to detect microloop DNA of Leishmania. Results:A total of 537 dogs were investigated, the positive rate of Leishmania detected by PCR was 41.15% (221/537); the positive rates of PCR detection were 64.63% (95/147) and 32.31% (126/390) in Wenxian County and Diebu County, respectively, and the positive rate in Wenxian County was higher than that in Diebu County (χ 2=46.044, P < 0.05). In 35 dogs with clinical symptoms of visceral leishmaniasis, the positive rate of PCR detection was 74.29% (26/35); the positive rates of PCR detection in symptomatically infected dogs were 84.62% (22/26) and 4/9 in Wenxian County and Diebu County, respectively, the positive rate in Wenxian County was higher than that in Diebu County ( P < 0.05). The positive rate of PCR detection was 38.84% (195/502) in 502 asymptomatic dogs; the positive rates of PCR detection were 60.33% (73/121) and 32.02% (122/381) in Wenxian County and Diebu County, respectively, the positive rate in Wenxian County was higher than that in Diebu County (χ 2=39.982, P < 0.05). Conclusions:The infection rates of Leishmania in dogs are high in Wenxian County and Diebu County of Gansu Province, the positive rate of PCR detection in asymptomatic dogs infected with Leishmania is high. This indicates that local residents and dogs are at high risk of infection with Leishmania. It is recommended that relevant departments should enhance residents' awareness of active protection and strengthen efforts to control the Leishmania infection of dogs.

Abnormal Upregulation of Cardiovascular Disease Biomarker PLA2G7 Induced by Proinflammatory Macrophages in COVID-19 patients

BACKGROUNDCoronavirus disease 2019 (COVID-19) triggers distinct patterns of pneumonia progression with multiorgan disease, calling for cell- and/or tissue-type specific host injury markers. METHODSAn integrated hypothesis-free single biomarker analysis framework was performed on nasal swabs (n = 484) from patients with COVID-19 in GSE152075. The origin of candidate biomarker was assessed in single-cell RNA data (GSE145926). The candidate biomarker was validated in a cross-sectional cohort (n = 564) at both nucleotide and protein levels. RESULTSPhospholipase A2 group VII (PLA2G7) was identified as a candidate biomarker in COVID-19. PLA2G7 was predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, PLA2G7 was found in patients with COVID-19 and pneumonia, especially in severe pneumonia, rather than patients suffered mild H1N1 influenza infection. Up to 100% positive rates of PLA2G7 were positively correlated with not only viral loads in patients with COVID-19 but also severity of pneumonia in non-COVID-19 patients. Although Ct values of PLA2G7 in severe pneumonia was significantly lower than that in moderate pneumonia (P = 7.2e-11), no differences were observed in moderate pneumonia with COVID-19 between severe pneumonia without COVID-19 (P = 0.81). Serum protein levels of PLA2G7, also known as lipoprotein-associated phospholipase A2 (Lp-PLA2), were further found to be elevated and beyond the upper limit of normal in patients with COVID-19, especially among the re-positive patients. CONCLUSIONSWe firstly identified and validated PLA2G7, a biomarker for cardiovascular diseases (CVDs), was abnormally enhanced in COVID-19 patients at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in COVID-19 patients. PLA2G7 could be a hallmark of COVID-19 for monitoring disease progress and therapeutic response. FUNDINGThis study was supported by grants from China Mega-Projects for Infectious Disease (2018ZX10711001), National Natural Science Foundation of China (82041023).

Genome-wide data inferring the evolution and population demography of the novel pneumonia coronavirus (SARS-CoV-2)

As the highly risk and infectious diseases, the outbreak of coronavirus disease 2019 (COVID-19) poses unprecedent challenges to global health. Up to March 3, 2020, SARS-CoV-2 has infected more than 89,000 people in China and other 66 countries across six continents. In this study, we used 10 new sequenced genomes of SARS-CoV-2 and combined 136 genomes from GISAID database to investigate the genetic variation and population demography through different analysis approaches (e.g. Network, EBSP, Mismatch, and neutrality tests). The results showed that 80 haplotypes had 183 substitution sites, including 27 parsimony-informative and 156 singletons. Sliding window analyses of genetic diversity suggested a certain mutations abundance in the genomes of SARS-CoV-2, which may be explaining the existing widespread. Phylogenetic analysis showed that, compared with the coronavirus carried by pangolins (Pangolin-CoV), the virus carried by bats (bat-RaTG13-CoV) has a closer relationship with SARS-CoV-2. The network results showed that SARS-CoV-2 had diverse haplotypes around the world by February 11. Additionally, 16 genomes, collected from Huanan seafood market assigned to 10 haplotypes, indicated a circulating infection within the market in a short term. The EBSP results showed that the first estimated expansion date of SARS-CoV-2 began from 7 December 2019.

The effect of inspiratory muscle training on pulmonary function and diaphragm movement after stroke / 中华物理医学与康复杂志

Objective:To investigate the effect of inspiratory muscle training on the lung function and diaphragm movement of stroke survivors.Methods:Twenty-four stroke survivors were randomly divided into a control group and an experimental group. Both groups were given routine rehabilitation therapy, while the experimental group was additionally provided with 20 minutes of inspiratory muscle training, 5 times per week for 4 weeks. Before and after the treatment, the forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) expressed as percentages of the predicted values were used to assess ventilation. The maximum inspiratory pressure (MIP) and peak inspiratory flow (PIF) were used to assess inspiratory muscle function. Diaphragm mobility, as well as the diaphragm′s thickness at the end of expiration (DTee) and inspiration (DTei) and the diaphragm thickening fraction (DTF) were measured using ultrasonography. Any pulmonary infection was also recorded.Results:There was no significant difference between the two groups in any of the measurements before treatment. After the intervention the average FVC, FEV1, MIP, PIF, diaphragm mobility, DTei and DTF of the experimental group were all significantly better than before treatment and significantly better than the control group′s averages. However, no significant difference was found in the average PEF or DTee, nor in the rate of pulmonary infection between the two groups.Conclusion:Inspiratory muscle training can effectively improve ventilation, inspiratory muscle function, diaphragm mobility and diaphragm thickness at the end of inspiration among stroke survivors.

Correction to: Characterization of oogonia stem cells in mice by Fragilis

In the original publication the labelling on Fig. 2A and B were incorrectly published as E7.5. The correct labelling of Fig. 2A and B should be read as E17.5 which is provided in this correction.

Correction to: Characterization of oogonia stem cells in mice by Fragilis

In the original publication the labelling of Figure 1D, Y-axis is incorrectly published. The correct labeling should be read as Fragilis+/SSEA1+ and the correct figure is provided in this correction.

Correction to: Characterization of oogonia stem cells in mice by Fragilis

In the original publication the labelling of Figure 1D, Y-axis is incorrectly published. The correct labeling should be read as Fragilis+/SSEA1+ and the correct figure is provided in this correction.