The Validation of Deep Learning-Based Grading Model for Diabetic Retinopathy.

Purpose: To evaluate the performance of a deep learning (DL)-based artificial intelligence (AI) hierarchical diagnosis software, EyeWisdom V1 for diabetic retinopathy (DR). Materials and Methods: The prospective study was a multicenter, double-blind, and self-controlled clinical trial. Non-dilated posterior pole fundus images were evaluated by ophthalmologists and EyeWisdom V1, respectively. The diagnosis of manual grading was considered as the gold standard. Primary evaluation index (sensitivity and specificity) and secondary evaluation index like positive predictive values (PPV), negative predictive values (NPV), etc., were calculated to evaluate the performance of EyeWisdom V1. Results: A total of 1,089 fundus images from 630 patients were included, with a mean age of (56.52 ± 11.13) years. For any DR, the sensitivity, specificity, PPV, and NPV were 98.23% (95% CI 96.93-99.08%), 74.45% (95% CI 69.95-78.60%), 86.38% (95% CI 83.76-88.72%), and 96.23% (95% CI 93.50-98.04%), respectively; For sight-threatening DR (STDR, severe non-proliferative DR or worse), the above indicators were 80.47% (95% CI 75.07-85.14%), 97.96% (95% CI 96.75-98.81%), 92.38% (95% CI 88.07-95.50%), and 94.23% (95% CI 92.46-95.68%); For referral DR (moderate non-proliferative DR or worse), the sensitivity and specificity were 92.96% (95% CI 90.66-94.84%) and 93.32% (95% CI 90.65-95.42%), with the PPV of 94.93% (95% CI 92.89-96.53%) and the NPV of 90.78% (95% CI 87.81-93.22%). The kappa score of EyeWisdom V1 was 0.860 (0.827-0.890) with the AUC of 0.958 for referral DR. Conclusion: The EyeWisdom V1 could provide reliable DR grading and referral recommendation based on the fundus images of diabetics.

Enhanced ionic conductivity and lithium dendrite suppression of polymer solid electrolytes by alumina nanorods and interfacial graphite modification.

Poor room-temperature ionic conductivity and lithium dendrite formation are the main issues of solid electrolytes. In this work, rod-shaped alumina incorporation and graphite coating were simultaneously applied to poly (propylene carbonate) (PPC)-based polymer solid electrolytes (Wang et al., 2018). The obtained alumina modified solid electrolyte membrane (Al-SE) achieves a high ionic conductivity of 3.48 × 10-4 S/cm at room temperature with a wide electrochemical window of 4.6 V. The assembled NCM622/Al-SE/Li solid-state battery exhibits initial discharge capacities of 198.2 mAh/g and 177.5 mAh/g at the current density of 0.1 C and 0.5 C, with the remaining capacities of 165.8 mAh/g and 161.3 mAh/g after 100 cycles respectively. The rod-shaped structure of Al2O3 provides fast transport channels for lithium ions and its Lewis acidity promotes the dissociation of lithium salts and release of free lithium ions. The lithiophilic Al2O3 and Graphite form intimate contact with metallic Li and create fast Li+ conductive layers of Li-Al-O layer and LiC6 layer, thus facilitating the uniform deposition of Li and inhibiting Li dendrite formation during long-term cycling. This kind of composite Al-SE is expected to provide a promising alternative for practical application in solid electrolytes.

HNF-1 binding point mutation of the AFP gene promotes cirrhosis in post-menopausal women.

OBJECTIVE: α-fetoprotein (AFP) expression is activated during the embryonic stage or hepatocellular carcinogenesis, so it is presumed that AFP is a key endogenous molecule to promote cell proliferation or differentiation. We carried out gene screening in an unknown family with hyper-alpha-fetoproteinemia and some sporadic menopausal women, and discussed the relationship between AFP expression and liver cirrhosis. METHODS: Peripheral blood samples from family members, patients with malignant liver tumors, and normal controls were collected. Full-length sequence of AFP was amplified and directly sequenced, and compared with normal controls. HNF-1α and HNF-1ß in plasma levels of family members, patients with liver cancer, newborns, pregnant women, and normal subjects were detected by ELISA, and the relationship between HNF-1 and AFP mutation or high expression was evaluated. RESULTS: There was a mutation in AFP promoter region at c.-200 C>T, which was located at the binding site of AFP hepatocyte nuclear factor 1 (HNF-1). AFP was higher than 4000 ng/L in all members carrying the mutation, but liver cancer was excluded in the family with hyper-alpha-fetoprotein. However, cirrhosis occurred in post-menopausal women. The cases reviewed showed that unknown hyper-alpha-fetoprotein was closely related to HNF-1 binding point of AFP in post-menopausal women with cirrhosis (7/11), while the plasma levels of HNF-1α and HNF-1ß were not significantly different. CONCLUSION: The mutation of the HNF-1 binding point of AFP may lead to an abnormal high expression of AFP by altering the binding of HNF transcription factors, which is closely related to cirrhosis in menopausal women.

Remote modulation of network excitability during deep brain stimulation for epilepsy.

Deep brain stimulation (DBS) has become a well-accepted medical therapy in the treatment of movement disorders such as Parkinson's disease, and is currently under investigation as a treatment for other disorders, including epilepsy. Although DBS is widely used, its therapeutic mechanisms remain poorly understood. Recent research shows that seizures are network-level phenomena, but the incomplete knowledge of neural circuit function has left a gap in our understanding of how disruption at a molecular or cellular level generates epilepsy. In addition, DBS may potentially provide the opportunity to selectively modulate targeted brain regions and related networks. Therefore, a better understanding of the relationship between normal neural networks and epileptogenic networks, as well as the role of DBS in the modulation of neural networks will help us to find the optimal stimulation targets and parameters to achieve a better therapeutic effect. This review will outline the most recent advances in the relationship between normal brain networks and epileptogenic networks, and the modulation of DBS on the excitability of epileptogenic networks. We will then discuss how to optimize DBS stimulation targets and parameters by taking into consideration the concept of network modulation in order to improve treatment of epilepsy in the future.

Antitumor effect of photodynamic therapy with a novel targeted photosensitizer on cervical carcinoma.

The antitumor effect of photodynamic therapy (PDT) mediated by a novel photosensitizer I (Ps I; {γ-[N-poly(ethyleneglycol)]folic acid}-5,10,15-tris(3-hydroxyphenyl)-20-(4-carboxyphenyl)chlorin), in which chlorin was used as a photoactive unit, folic acid as a tumor­targeting warhead, and polyethylene glycol as a linker, on cervical carcinoma was studied in vitro and in vivo. Ps I exhibited a considerably higher cellular uptake by HeLa cells than folic acid-free analogue Ps A (tert-butyl N-poly(ethyleneglycol)ethylcarbamate-5,10,15-tris(3-hydroxyphenyl)-20-(4-carboxyphenyl)chlorin), and the cellular uptake by HeLa cells of Ps I could be competitively inhibited by excess folic acid. Moreover, at different time points after the intravenous (i.v.) injection of Ps I and A, Ps I produced a >2-fold higher tumor to normal tissue ratio in tumor-bearing nude mice as compared to Ps A. MTT assay indicated that the HeLa cell proliferation inhibition ratio was increased 34% after Ps I-PDT compared with Ps A-PDT with a photosensitizer concentration of 15.2 µmol/l. Administration of Ps I (7 mg/kg, i.v.) followed by light exposure (80 J/cm2) markedly suppressed the growth of xenograft tumors, and the tumor volume was 10-fold smaller than that of the control group. Tumor growth inhibition in vitro and in vivo had an obvious dependency on the Ps I concentration and irradiation dose. The mode of cell death post-Ps I-PDT was analyzed by flow cytometry, confocal laser scanning microscopy, and electron microscope, and the results suggested that apoptosis was the primary mode of HeLa cell death induced by Ps I-PDT. The results also demonstrated that tumor targeting of Ps I was clearly improved because of the endocytosis mediated by the folate receptor. As a result, Ps I-PDT exhibited higher antitumor activity than Ps A-PDT and has potential as an alternative treatment modality for cervical cancer.

[Effects of UV-radiation on biological characteristics of different body-color biotypes of Sitobion avenae (Fab.)].

UV-radiation exerts strong selection stress on the evolution of aphid populations, and thus, leads to their genetic differentiation. However, the effects of UV-radiation on different body-color biotypes of aphids are still ambiguous. In this study, new-born nymphae of red and green biotypes of Sitobion avenae were placed on two wheat varieties (Xiaoyan-22 and Astron), bred in an artificial bioclimatic chamber under strict controlled conditions (at 15 degrees C, 20 degrees C, and 25 degrees C, and treated with 30 W lamp of UV-B for 30 min per day for 5 days), and their development duration, mass, and mean relative growth rate were measured. The results showed that at lower temperature, UV-radiation delayed the growth of green biotype aphid on Xiaoyan-22 and Astron significantly; while at higher temperature, UV-radiation significantly delayed the growth of red biotype aphid on Xiaoyan-22, but had lesser effects on the growth of the two biotypes on Astron, illustrating that different biotypes of aphids had different responses to UV-radiation, and the responses were correlated to temperature and wheat varieties.

[Expression of fms-like tyrosine kinase receptor 1 in placenta of pre-eclampsia].

OBJECTIVE: To investigate the expression of fms-like tyrosine kinase receptor 1 (Flt-1) in placentas of pre-eclampsia. METHODS: The expression of Flt-1 mRNA in the placentas from 20 pre-eclampsia patients and 20 pregnant women with normal blood pressure was detected by semi-quantitative reverse transcription-polymerase chain reaction. The protein expression of Flt-1 was analyzed using western blot in 18 pre-eclampsia patients and 18 normotensive pregnant women. RESULTS: Placental Flt-1 mRNA level in pre-eclampsia was 2.25 +/- 0.19 (intensity ratios of Flt-1 mRNA to beta-actin mRNA), significantly higher than in normotensive pregnant women 1.23 +/- 0.29 (P < 0.05). Western blot showed that Flt-1 protein level in pre-eclamptic placenta was 2.67 +/- 1.19 [western blot signal intensity ratios of Flt-1 to glyceraldehyde-3-phosphate dehydrogenase (GAPDH)], significantly higher than in pregnant women with normal blood pressure 0.94 +/- 0.51 (P < 0.05). CONCLUSION: Increased Flt-1 expression in pre-eclamptic placenta may be involved in pathogenesis of pre-eclampsia.

[Alteration and potential role of soluble fms-like tyrosine kinase receptor 1 in preeclampsia].

OBJECTIVE: To investigate the alteration of serum soluble fms-like tyrosine kinase receptor 1 (sFlt-1) and the possible source in preeclampsia, and the relationship between sFlt-1 and the pathogenesis of preeclampsia. METHODS: (1) Semi-quantitative RT-PCR was carried out to detect the level of sFlt-1 mRNA in placental tissue of 10 preeclampsia (preeclampsia group) and 10 normotensive pregnancies (normotensive pregnancy group). (2) Enzyme linked immunosorbent assay (ELISA) was used to detect the serum level of sFlt-1 in peripheral venous blood in preeclampsia group 1 (n = 35) and normotensive pregnancies group 1 (n = 35); the serum level of sFlt-1 of uterine vein blood in preeclampsia group 2 (n = 20) and normotensive pregnancies group 2 (n = 20); and the volume of peripheral venous blood sFlt-1 in 10 early (early pregnancy group) and 10 middle pregnancies (middle pregnancy group). RESULTS: (1) sFlt-1 mRNA of placental tissue was significantly higher in preeclampsia group (0.95 +/- 0.04) than that in normal pregnancy group (0.64 +/- 0.15). (2) The serum level of sFlt-1 of peripheral vein in preeclampsia group 1 (5640 +/- 3191) ng/L was higher than that in normal pregnancy group 1 (2194 +/- 635) ng/L. (3) The serum sFlt-1 of uterine vein in preeclampsia group 2 (7673 +/- 2296) ng/L was higher than that in normotensive pregnancy group 2 (3057 +/- 785) ng/L, indicating that the volume of sFlt-1 of uterine vein blood was significantly higher than that of peripheral venous blood (P < 0.01). (4) The serum levels of sFlt-1 in early and middle pregnancy groups were (32 +/- 20) ng/L and (994 +/- 302) ng/L, respectively, showing that the level of sFlt-1 in peripheral venous blood increasingly elevated with the development of pregnancy. CONCLUSIONS: (1) The placenta may be the major source of elevated sFlt-1. (2) The serum level of sFlt-1 is related with the development of pregnancy. The alteration of sFlt-1 may contribute to the pathogenesis of preeclampsia.

[The differential expression of hypoxia-inducible factor-1alpha in placenta tissues from pregnancy induced hypertension and normal pregnancy].

AIM: To explore the differential expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in placenta tissues from pregnancy induced hypertension and normal pregnancy. METHODS: The expression of HIF-1alpha protein and mRNA was detected by Western blot and real-time PCR, respectively. RESULTS: As compared with the expression levels of HIF-1alpha protein and mRNA in placenta tissues from normal pregnancy, those from pregnancy induced hypertension increased notably (P<0.05). CONCLUSION: The high expression of HIF-1alpha in the placenta tissues pregnancy induced may relate with pathogenesis and pathophysiological process of hypertension.

[Expression of hypoxia inducible factor-1alpha in placenta of pregnancy induced hypertension].

OBJECTIVE: To investigate the expression of hypoxia inducible factor-1alpha (HIF-1alpha) in placentas of pregnancy induced hypertension (PIH). METHODS: Placentas of 49 PIH pregnancies (PIH group 1) and 26 normotensive pregnancies (control group 1) were investigated for HIF-1alpha protein expression using microarray and immunohistochemistry. The expression of HIF-1alpha mRNA in placentas of 12 PIH pregnancies (PIH group 2) and 12 normal pregnancies(control group 2) was respectively detected by RT-PCR. RESULTS: (1) There was significant difference in the positive and slight-moderate-positive spot proportions of HIF-1alpha protein between the PIH group 1 (63.1%, 23.3%) and the control group 1 (20.9%, 7.0%, P < 0.01). (2) The level of HIF-1alpha mRNA between PIH group 2 and control group 2 (0.96 +/- 0.37 vs 0.95 +/- 0.20, P > 0.05) was not statistically different. CONCLUSIONS: (1) There was no significant difference in HIF-1alpha mRNA level between the PIH and normal placentas, but there was a remarkable difference in protein level between the two groups. (2) HIF-1alpha regulate the pathological and physiological progress of PIH at protein level rather than at transcription level.