[Safety and efficacy of donor-derived chimeric antigen receptor T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People's Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events. Results: A total of 81.82% (n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546-1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% (n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients (n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion: Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

Dietary supplementation of proteases on growth performance, nutrient digestibility, blood characteristics and gut microbiota of growing pigs fed sorghum-based diets.

Low-tannin sorghum is an excellent energy source in pig diets. However, sorghum contains several anti-nutritional factors that may have negative effects on nutrient digestibility. The impacts of proteases on growth performance, nutrient digestibility, blood parameters, and gut microbiota of growing pigs fed sorghum-based diets were studied in this study. Ninety-six pigs (20.66 ± 0.65 kg BW) were allocated into three groups (eight pens/group, four pigs/pen): (1) CON (control diet, sorghum-based diet included 66.98% sorghum), (2) PRO1 (CON + 200 mg/kg proteases), (3) PRO2 (CON + 400 mg/kg proteases) for 28 d. No differences were observed in growth performance and apparent total tract digestibility (ATTD) of nutrients between CON and PRO1 groups. Pigs fed PRO2 diet had increased (P < 0.05) BW on d 21 and 28, and increased (P < 0.05) average daily gain during d 14-21 and the overall period compared with pigs fed CON diet. In addition, pigs fed PRO2 diet had improved (P < 0.05) ATTD of gross energy, CP, and DM compared with pigs fed CON and PRO1 diets. Pigs fed PRO2 diet had lower (P < 0.05) plasma globulin (GLB) level and higher (P < 0.05) plasma glucose, albumin (ALB) and immunoglobulin G levels, and ALB/GLB ratio than pigs fed CON and PRO1 diets. Furthermore, pigs fed PRO2 diet had decreased (P < 0.05) the relative abundance of Acidobacteriota at the phylum level and increased (P < 0.05) the relative abundance of Prevotella_9 at the genus level. The linear discriminant analysis effect size analysis also showed that pigs fed PRO2 diet had significantly enriched short-chain fatty acid-producing bacteria, such as Subdoligranulum and Parabacteroides. In conclusion, protease supplementation at 400 mg/kg improved the growth performance of growing pigs fed sorghum-based diets, which may be attributed to the improvement of nutrient digestibility, host metabolism, immune status and associated with the altered gut microbiota profiles.

Effects of dietary methionine supplementation from different sources on growth performance and meat quality of barrows and gilts.

Methionine is indispensable for growth and meat formation in pigs. However, it is still unclear that increasing dietary sulphur-containing amino acid (SAA) levels using different methionine sources affects the growth performance and meat quality of barrows and gilts. To investigate this, 144 pigs (half barrows and half gilts) were fed the control (100% SAA, CON), DL-Methionine (125% SAA, DL-Met)-supplemented, or OH-Methionine (125% SAA, OH-Met)-supplemented diets during the 11-110 kg period. The results showed that plasma methionine levels varied among treatments during the experimental phase, with increased plasma methionine levels observed following increased SAA consumption during the 25-45 kg period. In contrast, pigs fed the DL-Met diet had lower plasma methionine levels than those fed the CON diet (95-110 kg). Additionally, gilts fed the DL-Met or OH-Met diets showed decreased drip loss in longissimus lumborum muscle (LM) compared to CON-fed gilts. OH-Met-fed gilts had higher pH45min values than those fed the CON or DL-Met diets, whereas OH-Met-fed barrows had higher L45min values than those fed the CON or DL-Met diets. Moreover, increased consumption of SAA, regardless of the methionine source, tended to decrease the shear force of the LM in pigs. In conclusion, this study indicates that increasing dietary levels of SAA (+25%) appeared to improve the meat quality of gilts by decreasing drip loss and increasing meat tenderness.

[The application potential and direction of artificial intelligence in the prevention and treatment of glaucoma].

The rapid iteration of artificial intelligence (AI) technology has driven the development of intelligent ophthalmology, with enormous potential for application in the regional screening, precise diagnosis, and disease progression prediction of intractable blinding diseases, particularly glaucoma. Aiming to encourage collaborative discussions among ophthalmologists, this article elucidates the application potential and direction of AI in the prevention and treatment of glaucoma from the aspects of enhancing glaucoma screening and diagnosis levels through AI, promoting initiatives for the application of AI, and exploring the prospects of AI.

[Analysis of disease composition and primary surgical procedures in pediatric secondary glaucoma inpatients: a single-center study].

Objective: To analyze the disease composition and primary surgical procedures in pediatric inpatients with secondary glaucoma. Methods: A retrospective case series study was conducted. Clinical data of children aged≤16 years with secondary glaucoma who were admitted to the Zhongshan Ophthalmic Center, Sun Yat-sen University, between January 1, 2017, and December 31, 2021, were included. The patients were classified according to the Childhood Glaucoma Research Network (CGRN) classification system, and their diagnoses, underlying factors, gender, age of onset, affected eye(s), age and type of initial surgery, and ophthalmic examination data were analyzed. Statistical analysis was performed using Kruskal-Wallis rank sum test and χ2 test. Results: A total of 540 patients (744 eyes) were included in this study, comprising 319 males (59.1%) and 221 females (40.9%). Unilateral disease was observed in 336 cases (62.2%), while bilateral involvement was present in 204 cases (37.8%). The age of onset was 4.0 (0.0, 9.0) years, and the median age of the first anti-glaucoma surgery was 5.0 (0.7, 10.0) years. Among them, there were 195 cases (36.1%) of secondary glaucoma associated with non-acquired ocular anomalies (SCG-O), with a median age of onset of 0.0 (0.0, 4.0) years, and 97 of these cases (49.7%) were male. secondary glaucoma associated with non-acquired systemic disease or syndrome (SCG-S) were observed in 68 cases (12.6%), with a median age of glaucoma onset of 0.1 (0.0, 4.0) years, and 47 of these cases (69.1%) were male. Secondary glaucoma associated with acquired conditions (SCG-A) accounted for 192 cases (35.6%), with a median age of onset of 9.0 (5.0, 13.0) years, and 125 of these cases (65.1%) were male. There were 85 cases (15.7%) of secondary glaucoma following cataract surgery (SCG-C), with a median age of onset of 3.0 (0.8, 7.0) years, and 50 of these cases (58.8%) were male. Male patients were predominant in SCG-S and SCG-A, with 47 cases (69.1%) and 125 cases (65.1%), respectively (χ2=9.94, 17.52; P=0.002,<0.001). Except for SCG-O, all other types of pediatric secondary glaucoma predominantly affected only one eye: SCG-S in 52 cases (76.5%), SCG-A in 128 cases (66.7%), and SCG-C in 54 cases (63.5%) (χ2=19.06, 21.33, 6.22; all P<0.05). The highest proportion of SCG-O was attributed to congenital ectropion uveae (46 cases, 23.6%). Sturge-Weber syndrome was the most common SCG-S (45 cases, 66.3%), while SCG-A mostly resulted from trauma (59 cases, 30.8%) and corticosteroid use (56 cases, 29.2%). Trabeculectomy (211 eyes, 30.8%) and glaucoma drainage device implantation (197 eyes, 28.7%) were the most frequently performed primary surgical procedures. Conclusions: SCG-O and SCG-A were found to be common types of pediatric secondary glaucoma. The age of onset and the choice of primary anti-glaucoma surgical procedures varied among different types of pediatric secondary glaucoma. However, overall, trabeculectomy and glaucoma drainage device implantation were the primary surgical procedures predominantly employed.

[Splicing abnormalities caused by a novel mutation in the PHKA2 gene in children with glycogen storage disease type IX].

Objective: Glycogen storage disease type IX (GSD-IX) is a rare primary glucose metabolism abnormality caused by phosphorylase kinase deficiency and a series of pathogenic gene mutations. The clinical characteristics, gene analysis, and functional verification of a mutation in a child with hepatomegaly are summarized here to clarify the pathogenic cause of the disease. Methods: The clinical data of a child with GSD-IX was collected. Peripheral blood from the child and his parents was collected for genomic DNA extraction. The patient's gene diagnosis was performed by second-generation sequencing. The suspected mutations were verified by Sanger sequencing and bioinformatics analysis. The suspected splicing mutations were verified in vivo by RT-PCR and first-generation sequencing. Results: Hepatomegaly, transaminitis, and hypertriglyceridemia were present in children. Liver biopsy pathological examination results indicated glycogen storage disease. Gene sequencing revealed that the child had a c.285 + 2_285 + 5delTAGG hemizygous mutation in the PHKA2 gene. Sanger sequencing verification showed that the mother of the child was heterozygous and the father of the child was of the wild type. Software such as HSF3.1 and ESEfinder predicted that the gene mutation affected splicing. RT-PCR of peripheral blood from children and his mother confirmed that the mutation had caused the skipping of exon 3 during the constitutive splicing of the PHKA2 gene. Conclusion: The hemizygous mutation in the PHKA2 gene (c.285 + 2_285 + 5delTAGG) is the pathogenic cause of the patient's disease. The detection of the novel mutation site enriches the mutation spectrum of the PHKA2 gene and serves as a basis for the family's genetic counseling.

[Research progress on the epidemiology and risk factors of dry eye in children].

The prevalence of dry eye in children is increasing with changes in the environment and the widespread use of electronic products. However, due to poor ability to express themselves and hidden symptoms of children, lack of understanding of dry eye in children, children with dry eye are likely to be misdiagnosed. Dry eye can seriously affect the quality of children's learning, life, vision and visual development. Therefore, it is urgent to raise awareness of clinical workers about dry eye in children, prevent the occurrence of related complications of dry eye, and avoid permanent visual damage to children. This review discusses and summarizes the epidemiology and common risk factors of children with dry eye, with the aim of improving doctors' understanding of dry eye in children.

Sodium MRI at 7T for Early Response Evaluation of Intracranial Tumors following Stereotactic Radiotherapy Using the CyberKnife.

BACKGROUND AND PURPOSE: Conventionally, early treatment response to stereotactic radiotherapy in intracranial tumors is often determined by structural MR imaging. Tissue sodium concentration is altered by cellular integrity and energy status in cells. In this study, we aimed to investigate the feasibility of sodium MR imaging at 7T for the preliminary evaluation of radiotherapeutic efficacy for intracranial tumors. MATERIALS AND METHODS: Data were collected from 16 patients (12 men and 4 women, 24-75 years of age) with 22 intracranial tumors who were treated with stereotactic radiation therapy using CyberKnife at our institution between December 1, 2016, and August 15, 2019. Sodium MR imaging was performed at 7T before and 48 hours, 1 week, and 1 month after CyberKnife radiation therapy. Tissue sodium concentration (TSC) was calculated and analyzed based on manually labeled regions of tumors. RESULTS: Ultra-high-field sodium MR imaging clearly showed the intratumoral signal, which is significantly higher than that of normal tissue (t = 5.250, P <.001)., but the edema zone has some influence. The average TSC ratios of tumor to CSF in the 22 tumors, contralateral normal tissues, edema zones, frontal cortex, and frontal white matter were 0.66 (range, 0.23-1.5), 0.30 (range, 0.15-0.43), 0.58 (range, 0.25-1.21), 0.25 (range, 0.17-0.42), and 0.30 (range, 0.19-0.49), respectively. A total of 12 tumors in 8 patients were scanned at 48 hours, 1 week, and 1 month after treatment. The average TSC at 48 hours after treatment was 0.06 higher than that before treatment and began to decrease at 1 week. The TSC ratios of 10 continued to decline and 2 tumors increased at 1 month, respectively. Tumor volume decreased by 2.4%-99% after 3 months. CONCLUSIONS: Changes in the TSC can be quantified by sodium MR imaging at 7T and used to detect radiobiologic alterations in intracranial tumors at early time points after CyberKnife radiation therapy.

[Research advances in the pathogenesis of exfoliative glaucoma].

Exfoliative glaucoma is a type of glaucoma secondary to pseudoexfoliation syndrome. In recent years, great progress has been made in the research of pathogenesis and risk factors of exfoliative glaucoma. A variety of risk genes, abnormal growth factors and cytokines, changes in the anterior and posterior segments have been found. Based on the systematic summary of these achievements, this article points out the problems that need to be further studied, so as to provide a reference for future research in this field.

[The effects and mechanism of baicalin in a mouse acute hypertensive glaucoma model].

Objective: To explore the potential neuroprotection effects and associated mechanism of baicalin in a rodent acute hypertensive glaucoma model and oxygen-glucose deprivation/reperfusion (OGD/R) induced retinal ganglion cell (RGC) injury. Methods: Experiment research. A rapid and substantial elevation of intraocular pressure was performed to establish an acute hypertensive glaucoma model, and retinal thickness was assessed at 1, 3, 5, and 7 days. The mice were then randomly divided into three groups: normal control group, hypertension group, and baicalin (50 mg/kg) for hypertension group. The effects of baicalin on the RGCs were evaluated by retrograde transporting of Fluoro-Gold. The mRNA levels of tumor necrosis factor-α, interleukine-1ß (IL-1ß), and inducible nitric oxide synthase were detected by real-time PCR, and the protein levels were measured by Western blot in the retina tissue of acute hypertensive glaucoma model. Purified primary RGC survival under OGD/R stress was measured by flow cytometry, which was also performed to measure the survival rate of RGCs pretreated by different doses of baicalin (2.5 µmol/L, 5.0 µmol/L, and 10.0 µmol/L). The effects of baicalin on primary RGCs co-cultured with mouse microglia cell line BV2 were evaluated by flow cytometry. The cytokine IL-1ß in the culture supernatant was measured by immunochemical analyses. Statistical analysis was performed using analysis of variance. Results: Retinal tissue injuries and RGC loss were observed both in vivo and in vitro. Retinal thickness was decreased to 87.32%±0.94% at 3 days (t=6.73, P<0.01), 74.86%±2.43% at 5 days (t=13.40, P<0.01), and 63.53%±2.15% at 7 days (t=19.46, P<0.01). Treatment of 50 mg/kg baicalin significantly promoted the RGC survival from 61.32%±5.94% to 89.93%±10.08% (t=4.84, P<0.01). Baicalin alleviated the retinal damages by suppressing the expression of inflammatory cytokines as revealed by Western blot and real-time PCR. In vitro the RGC survival under OGD/R stress was increased from 51.53%±1.36% to 69.37%±7.09% and 66.23%±4.25% with 5.0, 10.0 µmol/L baicalin administration (t=5.50, 4.53; both P<0.01). BV2 under OGD/R stress did extra damage to RGCs, and baicalin could reverse the damages and increase the survival from 69.37%±7.09% to 73.00%±5.20% (t=2.82, P=0.048) by reducing the release of IL-1ß [(39.97±8.76) pg/ml vs. (61.33±5.78) pg/ml, t=4.19, P=0.010]. Conclusion: Baicalin could alleviate retina tissue injury directly and promote the survival of RGCs by downregulating the expression of inflammatory cytokines and protecting RGCs from ischemia reperfusion injury. (Chin J Ophthalmol, 2020, 56: 376-382).

LncRNA TTTY15 regulates hypoxia-induced vascular endothelial cell injury via targeting miR-186-5p in cardiovascular disease.

OBJECTIVE: Dysfunction of vascular endothelial cells was associated with diverse human diseases, including cardiovascular disease. Long noncoding RNAs (LncRNAs) were involved in the regulation of cell injury. We aimed to investigate the role of lncRNA testis-specific transcript, Y-linked 15 (TTTY15) in hypoxia-induced cell injury in human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: Cell counting kit-8 (CCK8) assay was used to check cell viability. Lactate dehydrogenase (LDH) assay kit and flow cytometry were utilized to evaluate the leakage rate of LDH and cell apoptosis, respectively. The protein levels of Cyclin D1 and B-cell lymphoma-2-Associated X (Bax) in hypoxia-induced HUVECs were measured by Western blot. Quantitative Real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression levels of TTTY15 and miR-186-5p in hypoxia-induced HUVECs. The starBase was utilized to predict the binding sites between TTTY15 and miR-186-5p and the dual-luciferase reporter assay was performed to verify the interaction. RESULTS: Hypoxia inhibited cell viability and promoted the release of LDH and cell apoptosis in HUVECs. Besides, hypoxia significantly decreased the protein level of Cyclin D1 and increased the protein level of Bax in HUVECs. In addition, the expression level of TTTY15 was obviously upregulated in hypoxia-induced HUVECs, opposite to the level of miR-186-5p. Meanwhile, knockdown of TTTY15 or upregulation of miR-186-5p mitigated hypoxia-induced cell injury in HUVECs. Further studies suggested that TTTY15 targeted miR-186-5p and regulated hypoxia-induced cell injury via interacting with miR-186-5p in HUVECs. CONCLUSIONS: Downregulation of TTTY15 ameliorated hypoxia-induced cell injury by targeting miR-186-5p in HUVECs.

The Discriminative Efficacy of Retinal Characteristics on Two Traditional Chinese Syndromes in Association with Ischemic Stroke.

We aimed to investigate the efficacy of an objective method using AI-based retinal characteristic analysis to automatically differentiate between two traditional Chinese syndromes that are associated with ischemic stroke. Inpatient clinical and retinal data were retrospectively retrieved from the archive of our hospital. Patients diagnosed with cerebral infarction in the department of acupuncture and moxibustion between 2014 and 2018 were examined. Of these, the patients with Qi deficiency blood stasis syndrome (QDBS) and phlegm stasis in channels (PSIC) syndrome were selected. Those without retinal photos were excluded. To measure and analyze the patients' retinal vessel characteristics, we applied a patented AI-assisted automated retinal image analysis system developed by the Chinese University of Hong Kong. The demographic, clinical, and retinal information was compared between the QDBS and PSIC patients. The t-test and chi-squared test were used to analyze continuous data and categorical data, respectively. All the selected clinical information and retinal vessel measures were used to develop different discriminative models for QDBS and PSIC using logistic regression. Discriminative efficacy and model performances were evaluated by plotting a receiver operating characteristic curve. As compared to QDBS, the PSIC patients had a lower incidence of insomnia problems (46% versus 29% respectively, p=0.023) and a higher tortuosity index (0.45 ± 0.07 versus 0.47 ± 0.07, p=0.027). Moreover, the area under the curve of the logistic model showed that its discriminative efficacy based on both retinal and clinical characteristics was 86.7%, which was better than the model that employed retinal or clinical characteristics individually. Thus, the discriminative model using AI-assisted retinal characteristic analysis showed statistically significantly better performance in QDBS and PSIC syndrome differentiation among stroke patients. Therefore, we concluded that retinal characteristics added value to the clinical differentiation between QDBS and PSIC.

[Mechanism of microglia promoting retinal ganglion cell death in vitro].

Objective: To investigate the role and mechanism of microglial activation in the process of retinal ganglion cell (RGC) death in the oxygen-glucose deprivation/reperfusion (OGD/R) model which mimicked retinal ischemia/reperfusion injury in vitro. Methods: Experimental study. Primary RGCs from C57BL/6 mice and BV2 microglia were co-cultured or cultured alone. The OGD/R model was established in vitro (reoxygenation time was set to 6 h, 24 h, 36 h, 48 h). BV2 microglial activation was assessed by immunofluorescence staining of ionized calcium binding adapter molecule 1 (iba1), and the survival rate of RGCs was detected by the Cell Counting Kit-8. The apoptosis rate of RGC was detected by using apoptosis detection kit. The levels of Toll-like receptor-4 (TLR4) and Nod-like receptor family pyrin domain containing protein 3 (NLRP3) in BV2 cells were detected by PCR, Western-blot and immunofluorescence staining. The activity of caspase-8 in BV2 cells was detected by the CaspGLOW Kit, and the content of interleukine-1ß (IL-1ß) in the supernatant was detected by enzyme linked immunosorbent assay. After the corresponding pathways were blocked by TLR4 small interfering RNA (siRNA) transfection or caspase-8 inhibitor, the expression changes of TLR4 and NLRP3, the activity of caspase-8, and the difference of IL-1ß content could be observed as well as the activity of RGCs co-cultured with BV2. Statistical analysis was performed using analysis of variance. Results: Under co-culture of RGC and BV2 cells, cellular immunofluorescence detection showed that the expression of iba1 in BV2 cells increased, which indicated BV2 cells were activated significantly in the OGD/R model. In the OGD/R model, the apoptosis rate of RGC co-cultured with BV2 cells (71.1%±3.2%) was significantly higher than that of RGC cultured alone (35.1%±1.8%) (t=10.10, P<0.01). Cellular immunofluorescence detection showed that the expression of TLR4 and NLRP3 in BV2 cells in the OGD/R model increased significantly when BV2 cells were cultured alone, and their mRNA levels increased significantly with prolongation of reoxygenation time (F=64.45, 72.74; P<0.01), and peaked at OGD/R 24 h (TLR4 mRNA, relative ratio to control was 2.83±0.23; NLRP3 mRNA, relative ratio to control was 3.12±0.27). Caspase-8 activity also increased with prolonged reoxygenation time, the difference was statistically significant (F=93.57, P<0.01), and peaked at OGD/R 24 h (relative ratio to control was 2.92±0.31). After transfection of BV2 cells with TLR4 siRNA, its caspase-8 activity was significantly inhibited, but using caspase-8 inhibitor did not affect the up-regulation of TLR4 expression in BV2 cells. However, the mature IL-1ß secreted by BV2 cells exposed to OGD/R was significantly reduced by using caspase-8 inhibitor (from 3.52±0.55 to 1.39±0.37, t=7.19, P<0.01), meanwhile, the expression of NLRP3 was also significantly decreased after caspase-8 inhibitor pretreatment (from 2.79±0.23 to 1.37±0.19, t=9.37, P<0.01). In the OGD/R model, the activity of RGC cells co-cultured with TLR4 siRNA-transfected BV2 cells was 74.5%±1.2%, and the activity of RGC cells co-cultured with BV2 cells treated with caspase-8 inhibitor was 62.8%±1.5%, those were both higher than that of RGC cells co-cultured with untreated BV2 cells (36.7%±0.3%), and the difference was statistically significant (t=11.60, 6.83; both P<0.01). Conclusion: TLR4-caspase-8-NLRP3 inflammasome pathway is activated in microglia exposed to OGD/R, resulting in the production of IL-1ß, thereby contributing to the death of RGCs. (Chin J Ophthalmol, 2020, 56: 32-40).

Decreased Expression of MYPT1 Contributes to Tumor Angiogenesis and Poor Patient Prognosis in Human Prostate Cancer.

BACKGROUND: Our previous study demonstrated that Myosin Phosphatase Targeting subunit 1 (MYPT1) may function as a direct target of microRNA-30d, which promotes tumor angiogenesis and tumor growth of prostate cancer (PCa). Here, we aimed to investigate the clinical significance of MYPT1 expression and its functions in PCa. METHODS: Roles of MYPT1 deregulation in tumor angiogenesis of PCa was determined in vitro and in vivo experiments. Expression patterns of MYPT1 and CD31 proteins were examined by immunohistochemistry and immunofluorescence, respectively. Associations of MYPT1/CD31 combination with various clinicopathological features and patients' prognosis of PCa were also statistically evaluated. RESULTS: Through gain- and loss-of-function experiments, MYPT1 inhibited capillary tube formation of endothelial cells and in vivo tumor angiogenesis in a mouse model with the downregulation of VEGF and CD31 expression. In addition, MYPT1 expression was significantly decreased, while CD31 expression was dramatically increased in PCa tissues compared to benign prostate tissues. Notably, MYPT1 expression levels in PCa tissues were negatively correlated with that of CD31. Statistically, MYPT1-low/CD31- high expression was distinctly associated with high Gleason score, positive biochemical recurrence, and reduced overall survival of PCa patients. Moreover, PCa patients with MYPT1-low/CD31-high expression more frequently had shorter overall, biochemical recurrence-free and metastasis-free survivals. MYPT1/CD31 combination was identified as an independent factor to predict biochemical recurrence-free and metastasis-free survivals of PCa patients. CONCLUSIONS: Our findings indicate that MYPT1 may inhibit angiogenesis and contribute favorable prognosis in PCa patients, implying that MYPT1 might be a potential drug candidate in anticancer therapy.

[Research on the effect of biological glue on augmenting the viscosity of tissue engineering retinal nerve scaffolds].

Objective: To evaluate the adhesion effect of tissue engineering retinal nerve scaffolds modified with biological glue. Methods: Experimental study. To fabricate a biological glue by blending laminin, collagen Ⅳ, entactin and HSPG(2) with phosphate-buffered saline (PBS) buffer solution, scaffolds were then modified with the biological glue of various concentration levels (10 µl/cm(2), 20 µl/cm(2), 30 µl/cm(2) and 40 µl/cm(2)). The effects of various concentration levels glue on inducing scaffold adhesion were analyzed after 24 h. Cell count method and CCK-8 kit were used to assess the effects of biological glue on cell growth and toxicity. Then the scaffolds modified with or without glue were transplanted into rabbit's retina by 23 G pars plana vitrectomy. Intraocular pressure(IOP) and retina examination were assessed by ICare, fundus photograph and OCT. The adhesion effects of various concentration levels glue were analyzed by chi-square test. The cell adhesion rate of different scaffolds was analyzed by Mann-Whitney U test. One-Way ANOVA was used to compare the cell survival rate of different scaffolds. After transplantation, the IOP variance of rabbits was analyzed by repetitive measurement deviation analysis. Results: Compared with the control groups, the maximum adhesion rate of the biological glue was 91.7% (χ(2)=8.79, P<0.05) at 30µl/cm(2) concentration level. After 24h of cultivation, cell adhesion rate of glue-scaffold group (86.85%) was significantly higher than that of pure scaffold group (13.78%, U=0.01, P<0.05), while there was no significant difference between the cell survival rates of the two groups (F=7.235, P=0.11). There was no significant difference (F=79.16, P=0.07) between the IOP of viscosity modified group [(18.4+0.93) mmHg (1 mmHg=0.133 kPa)] and non- modified group [(17.1±0.04)mmHg]. The retina adhesion rate of viscosity modified scaffold was 80% at 7 days postoperatively, and the fundus examination showed no inflammatory response in retina and vitreous cavity. Conclusion: This study showed that the biological glue has favorable viscosity modifying effect on tissue engineering neural retina scaffolds, which is beneficial for the biological material transplantation. (Chin J Ophthalmol, 2018, 54: 277-282).

Nanoscale diffusive memristor crossbars as physical unclonable functions.

Physical unclonable functions have emerged as promising hardware security primitives for device authentication and key generation in the era of the Internet of Things. Herein, we report novel physical unclonable functions built upon the crossbars of nanoscale diffusive memristors that translate the stochastic distribution of Ag clusters in a SiO2 matrix into a random binary bitmap that serves as a device fingerprint. The random dispersion of Ag led to an uneven number of clusters at each cross-point, which in turn resulted in a stochastic ability to switch in the Ag:SiO2 diffusive memristors in an array. The randomness of the dispersion was a barrier to fingerprint cloning and the unique fingerprints of each device were persistent after fabrication. Using an optimized fabrication procedure, we maximized the randomness and achieved an inter-class Hamming distance of 50.68%. We also discovered that the bits were not flipping after over 104 s at 400 K, suggesting superior reliability of our physical unclonable functions. In addition, our diffusive memristor-based physical unclonable functions were easy to fabricate and did not require complicated post-processing for digitization and thus, provide new opportunities in hardware security applications.

Effects of maternal methyl donor on the pork characteristics of offspring pigs with prenatal exposure to bisphenol A.

To explore the effects of maternal nutrition on offspring muscle characteristics, a total of 56 sows were assigned to one of the four dietary groups during gestation: control (CON), or control diets supplemented with methyl donor (MET), bisphenol A (BPA), and combined BPA and MET (BPA+MET). Compared with CON offspring, MET offspring showed a higher meat redness value, but lower glycogen content in the longissimus thoracis (LT). Moreover, compared with CON offspring, MET offspring showed lower LT glycogen synthase (GS) mRNA levels at birth and the finishing stage, and increased methylation at the GS promoter. Prenatal BPA exposure reduced the pH and redness value of meat, but increased the lightness value, lactate content, glycolytic potential and lactate dehydrogenase (LDH) enzyme activity in the LT muscle. Prenatal BPA exposure increased LDH mRNA levels in the LT muscle at birth and the finishing stage, and reduced methylation at the LDH promoter. Thus, maternal MET affects muscle GS and LDH expression via DNA methylation, thereby resulting in persistent effects on pork quality.

Perdeuterated and 13C-enriched myo-inositol for DNP assisted monitoring of enzymatic phosphorylation by inositol-3-kinase.

The synthesis of perdeuterated and 13C enriched myo-inositol is presented. Myo-inositol and its derivatives are of interest as substrates for enzymes producing phosphorylated species with regulatory functions in many organisms. Its utility in monitoring real-time phosphorylation by myo-inositol-3-kinase is illustrated using dynamic nuclear polarization (DNP) to enhance NMR observation.

[Comparison of vacuum bag fixation and Orfit rack with thermoplastic membrane fixation for image-guided cervical cancer radiotherapy].

Objective: To compare the difference of displacement between the vacuum bag fixation and the Orfit rack with thermoplastic membrane fixation of the cervical cancer patients, and to explore the individual fixation of the patients. Methods: We retrospectively analyzed the clinical data of 66 patients diagnosed as cervical cancer in Zhangzhou Municipal Hospital of Fujian Province from December 2014 to April 2016. Among them, 33 patients were fixed with vacuum bag, 33 patients were fixed with the Orfit rack with thermoplastic membrane. The cone-beam computed tomography (CBCT) images were acquired daily for the first three times of the radiotherapy, followed by once every other day for a total of 15 times. The CBCT scan images were matched with the CT scan images, and the matching results were recorded and analyzed. Results: The absolute value of the displacement in the left and right directions of the vacuum bag group was (0.28±0.30) cm, significantly lower than (0.38±0.46) cm in the Orfit rack with thermoplastic membrane group(P<0.001). The absolute value of the displacement in the anteroposterior direction of the vacuum bag group was (0.28±0.32) cm, with no significant difference of (0.27±0.23) cm in the Orfit rack with thermoplastic membrane group (P=0.580). The absolute value of the displacement in the up and down directions was (0.33±0.60) cm, with no statistically significant difference of (0.27±0.48) cm in the Orfit rack with thermoplastic membrane group (P=0.150). During the three times of CBCT scans, the differences of displacement in the left and right directions of the vacuum bag group were negligible, while apparently varied in the anteroposterior and up and down directions, however, the differences were not statistically significant (P>0.05). The change of the displacement in the three-dimensional direction in the Orfit rack with thermoplastic membrane group was marginal, and all of the differences were not significant(all P>0.05). Conclusions: Both the vacuum bag fixation and the Orfit rack with thermoplastic membrane fixation are suitable for the cone-beam CT image-guided radiotherapy of cervical cancer patients. However, the displacement in the left and right directions of the vacuum bag fixation is smaller than the Orfit rack with thermoplastic membrane fixation. During the period of treatment, the mean value of the difference of displacement in the anterior and posterior directions of the Orfit rack with thermoplastic membrane fixation is mild, which can be used individually by the patients with a flexible body and good tolerance.

Mechanism of pingyangmycin-induced apoptosis of cultured human umbilical vein endothelial cells.

In this study, we investigated the effects of pingyangmycin (PYM) on the growth inhibition and apoptosis of human umbilical vein endothelial cells (HUVEC). In this study, we aimed to explore the optimal concentration of PYM to induce the apoptosis of HUVEC and to determine its mechanism of action. After treatment of HUVEC with different concentrations of PYM for 24 h, cell counting kit-8 (CCK-8) was used to detect growth inhibiting effects. Annexin V-FITC/propidium iodide stain was used to detect apoptosis, and western blot was used to detect the expression of glucose-related protein 78 (GPR78) and C/EBP homologous protein (CHOP) endoplasmic reticulum stress proteins. With increasing PYM concentration, the growth inhibition of HUVEC increased (P < 0.05), the apoptotic numbers of HUVEC increased (P < 0.05), with higher PYM concentrations inducing necrosis, and the protein expression of GRP78 and CHOP increased (P < 0.05). PYM could obviously inhibit the proliferation and promote the apoptosis of HUVEC. Necrotic cells were more prevalent than apoptotic cells at high PYM concentrations. This study helped to determine the proper concentration of PYM to induce more apoptosis than necrosis, which is critical to minimize inflammation, enhance the healing of the skin, and maintain safety for the patient. PYM might induce HUVEC apoptosis through the endoplasmic reticulum stress pathway.