APC mutations disrupt ß-catenin destruction complex condensates organized by Axin phase separation.

The Wnt/ß-catenin pathway is critical to maintaining cell fate decisions. Recent study showed that liquid-liquid-phase separation (LLPS) of Axin organized the ß-catenin destruction complex condensates in a normal cellular state. Mutations inactivating the APC gene are found in approximately 80% of all human colorectal cancer (CRC). However, the molecular mechanism of the formation of ß-catenin destruction complex condensates organized by Axin phase separation and how APC mutations impact the condensates are still unclear. Here, we report that the ß-catenin destruction complex, which is constructed by Axin, was assembled condensates via a phase separation process in CRC cells. The key role of wild-type APC is to stabilize destruction complex condensates. Surprisingly, truncated APC did not affect the formation of condensates, and GSK 3ß and CK1α were unsuccessfully recruited, preventing ß-catenin phosphorylation and resulting in accumulation in the cytoplasm of CRCs. Besides, we propose that the phase separation ability of Axin participates in the nucleus translocation of ß-catenin and be incorporated and concentrated into transcriptional condensates, affecting the transcriptional activity of Wnt signaling pathway.

Construction of blood quality monitoring indicator system in blood banks of Shandong / 中国输血杂志

【Objective】 To establish a blood quality monitoring indicator system, in order to continuously improve blood quality and standardized management. 【Methods】 Based on the research of literature and standards, and guided by the key control points of blood collection and supply process, the blood quality monitoring indicator system was developed. Through two rounds of Delphi expert consultation, the indicator content was further revised and improved according to expert opinions after six months of trial implementation. The indicator weight was calculated by questionnaire and analytic hierarchy process. 【Results】 A blood quality monitoring indicator system covering the whole process of blood collection and supply was constructed, including five primary indicators, namely blood donation service, blood component preparation, blood testing, blood supply and quality control, as well as 72 secondary indicators, including definitions, calculation formulas, etc. Two rounds of expert consultation and two rounds of feasibility study meeting were held to revise 17 items and the weight of each indicator was obtained through the analytic hierarchy process. After partial adjustments, a blood quality monitoring indicator system was formed. 【Conclusion】 A blood quality monitoring indicator system covering the whole process of blood collection and supply has been established for the first time, which can effectively evaluate the quality management level of blood banks and coordinate blood quality control activities of blood banks in Shandong like pieces in a chess game, thus improving the standardized management level

Application of quality monitoring indicators of blood testing in blood banks of Shandong province / 中国输血杂志

【Objective】 To objectively evaluate the quality control level of blood testing process in blood banks through quantitative monitoring and trend analysis, and to promote the homogenization level and standardized management of blood testing laboratories in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation service, blood component preparation, blood testing, blood supply and quality control was established. The questionnaire Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong province. Quality monitoring indicators of each blood bank from January to December 2022 were collected, and 31 indicators in terms of blood testing were analyzed using SPSS25.0 software. 【Results】 The proportion of unqualified serological tests in 17 blood bank laboratories was 55.84% for ALT, 13.63% for HBsAg, 5.08% for anti HCV, 5.62% for anti HIV, 18.18% for anti TP, and 1.65% for other factors (mainly sample quality). The detection unqualified rate and median were (1.23±0.57)% and 1.11%, respectively. The ALT unqualified rate and median were (0.74±0.53)% and 0.60%, respectively. The detection unqualified rate was positively correlated with ALT unqualified rate (r=0.974, P0.05), while the outrage rate was positively correlated with the usage rate (r=0.592, P<0.05). A total of 443 HBV DNA positive samples were detected in all blood banks, with an unqualified rate of 3.78/10 000; 15 HCV RNA positive samples were detected, with an unqualified rate of 0.13/10 000; 5 HIV RNA positive samples were detected, with an unqualified rate of 0.04/10 000. The unqualified rate of NAT was (0.72±0.04)‰, the single NAT reaction rate [(0.39±0.02)‰] was positively correlated with the single HBV DNA reaction rate [ (0.36±0.02) ‰] (r=0.886, P<0.05). There was a difference in the discriminated reactive rate by individual NAT among three blood bank laboratories (C, F, H) (P<0.05). The median resolution rate of 17 blood station laboratories by minipool test was 36.36%, the median rate of invalid batch of NAT was 0.67%, and the median rate of invalid result of NAT was 0.07‰. The consistency rate of ELISA dual reagent detection results was (99.63±0.24)%, and the median length of equipment failure was 14 days. The error rate of blood type testing in blood collection department was 0.14‰. 【Conclusion】 The quality monitoring indicator system for blood testing process in Shandong can monitor potential risks before, during and after the experiment, and has good applicability, feasibility, and effectiveness, and can facilitate the continuous improvement of laboratory quality control level. The application of blood testing quality monitoring indicators will promote the homogenization and standardization of blood quality management in Shandong, and lay the foundation for future comprehensive evaluations of blood banks.

Application of quality control indicator system in blood banks of Shandong / 中国输血杂志

【Objective】 To establish an effective quality monitoring indicator system for blood quality control in blood banks, in order to analyze the quality control indicators for blood collection and supply, and evaluate blood quality control process, thus promoting continuous improvement and standardizing management of blood quality control in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation services, component preparation, blood testing, blood supply and quality control was established. The Questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process was distributed to 17 blood banks in Shandong, which clarified the definition and calculation formula of indicators. The quality monitoring indicator data from January to December 2022 in each blood bank were collected, and 20 quality control indicators data were analyzed by SPSS25.0 software. 【Results】 The average pass rate of key equipment monitoring, environment monitoring, key material monitoring, and blood testing item monitoring of 17 blood banks were 99.47%, 99.51%, 99.95% and 98.99%, respectively. Significant difference was noticed in the pass rate of environment monitoring among blood banks of varied scales(P<0.05), and the Pearson correlation coefficient (r) between the total number of blood quality testing items and the total amount of blood component preparation was 0.645 (P<0.05). The average discarding rates of blood testing or non-blood testing were 1.14% and 3.36% respectively, showing significant difference among blood banks of varied scales (P<0.05). The average discarding rate of lipemic blood was 3.07%, which had a positive correlation with the discarding rate of non testing (r=0.981 3, P<0.05). There was a statistically significant difference in the discarding rate of lipemic blood between blood banks with lipemic blood control measures and those without (P<0.05). The average discarding rate of abnormal color, non-standard volume, blood bag damage, hemolysis, blood protein precipitation and blood clotting were 0.20%, 0.14%, 0.06%, 0.06%, 0.02% and 0.02% respectively, showing statistically significant differences among large, medium and small blood banks(P<0.05).The average discarding rates of expired blood, other factors, confidential unit exclusion and unqualified samples were 0.02%, 0.05%, 0.003% and 0.004%, respectively. The discarding rate of blood with air bubbles was 0.015%, while that of blood with foreign body and unqualified label were 0. 【Conclusion】 The quality control indicator system of blood banks in Shandong can monitor weak points in process management, with good applicability, feasibility, and effectiveness. It is conducive to evaluate different blood banks, continuously improve the quality control level of blood collection and supply, promote the homogenization and standardization of blood quality management, and lay the foundation for comprehensive evaluation of blood banks in Shandong.

Quality monitoring indicator system in blood banks of Shandong: applied in blood donation services, component preparation and blood supply process / 中国输血杂志

【Objective】 To establish an effective quality indicator monitoring system, scientifically and objectively evaluate the quality management level of blood banks, and achieve continuous improvement of quality management in blood bank. 【Methods】 A quality monitoring indicator system that covers the whole process of blood collection and supply was established, the questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong. Statistical analysis of 21 quality monitoring indicators in terms of blood donation service (10 indicators), blood component preparation (7 indicators ), and blood supply (4 indicators) from each blood bank from January to December 2022 were conducted using SPSS25.0 software The differences in quality monitoring indicators of blood banks of different scales were analyzed. 【Results】 The average values of quality monitoring indicators for blood donation service process of 17 blood banks were as follows: 44.66% (2 233/5 000) of regular donors proportion, 0.22% (11/50) of adverse reactions incidence, 0.46% (23/5 000) of non-standard whole blood collection rate, 0.052% (13/25 000) of missed HBsAg screening rate, 99.42% (4 971/5 000) of first, puncture successful rate, 86.49% (173/200) of double platelet collection rate, 66.50% (133/200) of 400 mL whole blood collection rate, 99.25% (397/400) of donor satisfaction rate, 82.68% (2 067/2 500) of use rate of whole blood collection bags with bypass system with sample tube, and 1 case of occupational exposure in blood collection.There was a strong positive correlation between the proportion of regular blood donors and the collection rate of 400 mL whole blood (P<0.05). The platelet collection rate, incidence of adverse reactions to blood donation, and non-standard whole blood collection rate in large blood banks were significantly lower than those in medium and small blood banks (P<0.05). The average quality monitoring indicators for blood component preparation process of 17 blood banks were as follows: the leakage rate of blood component preparation bags was 0.03% (3/10 000), the discarding rate of lipemic blood was 3.05% (61/2 000), the discarding rate of hemolysis blood was 0.13%(13/10 000). 0.06 case had labeling errors, 8 bags had blood catheter leaks, 2.76 bags had blood puncture/connection leaks, and 0.59 cases had non-conforming consumables. The discarding rate of hemolysis blood of large blood banks was significantly lower than that of medium and small blood banks (P<0.05), and the discarding rate of lipemic blood of large and medium blood banks was significantly lower than that of small blood banks (P<0.05). The average values of quality monitoring indicators for blood supply process of 17 blood banks were as follows: the discarding rate of expired blood was 0.023% (23/100 000), the leakage rate during storage and distribution was of 0.009%(9/100 000), the discarding rate of returned blood was 0.106% (53/50 000), the service satisfaction of hospitals was 99.16% (2 479/2 500). The leakage rate of blood components during storage and distribution was statistically different with that of blood component preparation bags between different blood banks (P<0.05). There were statistically significant differences in the proportion of regular blood donors, incidence of adverse reactions, non-standard whole blood collection rate, 400 mL whole blood collection rate, double platelet collection rate, the blood bag leakage rate during preparation process, the blood components leakage rate during storage and distribution as well as the discarding rate of lipemic blood, hemolysis blood, expired blood and returned blood among large, medium and small blood banks (all P<0.05). 【Conclusion】 The establishment of a quality monitoring indicator system for blood donation services, blood component preparation and blood supply processes in Shandong has good applicability, feasibility and effectiveness. It can objectively evaluate the quality management level, facilitate the continuous improvement of the quality management system, promote the homogenization of blood management in the province and lay the foundation for future comprehensive evaluation of blood banks.

Effects of Modified Yupingfeng Powder Medicated Serum on RLE-6TN Cells Inflammatory Reaction Based on NF-κB Signaling Pathway / 中国中医药信息杂志

Objective To investigate the effects of modified Yupingfeng Powder medicated serum on the inflammatory response of rat lung epithelial type Ⅱ cells RLE-6TN;To explore the mechanism based on nuclear factor(NF)-κB signaling pathway.Methods The inflammatory reaction of RLE-6TN cells was induced by lipopolysaccharide,and the cells were divided into control group,model group,dexamethasone medicated serum group,and 5%,10%and 20%TCM serum group,and the cell model was intervened with different serum.After 24 hours,the content of lactate dehydrogenase(LDH)in cell supernatant was detected by kit,and the content of reactive oxygen species(ROS)in cells were detected by fluorescence staining,Hoechst/PI double staining was used to observe cell apoptosis,and ELISA was used to detect tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β contents in cell supernatant,RT-qPCR was used to detect Toll like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and NF-κB inhibitory protein α(IκBα)mRNA expression,Western blot was used to detect protein expressions of TLR4,MyD88,NF-κBp65 and IκBα.Results Compared with the control group,the contents of LDH,TNF-α,IL-6,IL-1β in RLE-6TN cell supernatant and ROS content in cells of model group significantly increased(P<0.01),the cell apoptosis rate significantly increased(P<0.01),the expressions of TLR4 and MyD88 mRNA and protein significantly increased(P<0.01),the expression of IκBα mRNA significantly decreased(P<0.01),and the ratio of p-NF-κBp65/NF-κBp65 and p-IκBα/IκBα significantly increased(P<0.01).Compared with the model group,the content of LDH,TNF-α,IL-6,IL-1 in RLE-6TN cell supernatant and ROS content in cells significant decreased in the 20%TCM serum group and dexamethasone medicated serum group(P<0.01),the cell apoptosis rate significantly decreased(P<0.01),the expressions of TLR4 and MyD88 mRNA and protein significantly decreased(P<0.05,P<0.01),the expression of IκBα mRNA significantly increased(P<0.01),and the ratio of p-NF-κBp65/NF-κBp65 and p-IκBα/IκBα significantly decreased(P<0.05,P<0.01).Conclusion Modified Yupingfeng Powder medicated serum can reduce RLE-6TN cells inflammatory reaction,and its mechanism may be related to the regulation of NF-κB signaling pathway.

Relationship between lifestyle and the comorbidity of myopia and depressive symptoms among primary and secondary school students in Nanjing / 中国学校卫生

Objective@#To explore the relationship between lifestyle and myopia and depressive symptoms comorbidity among primary and secondary school students in Nanjing, so as to provide a scientific basis for developing effective prevention measures.@*Methods@#In October 2022, a stratified cluster random sampling method was used to select primary and secondary school students aged 9-19 years in 4 urban and 4 suburban districts in Nanjing as the research subjects. A total of 10 498 students were included for physical examination and questionnaire survey by using the student health condition and influencing factors questionnaire. Chisquare test was used for univariate analysis, and multifactor Logistic regression analysis was used to analyze the relationship between students lifestyle and the cooccurrence of myopia and depressive symptoms.@*Results@#The prevalence of comorbidity of screening positive myopia and depression among primary and secondary school students in Nanjing was 18.11%. The prevalence of comorbidity was higher in girls (20.97%) than in boys (15.47%), higher in boarding students (31.31%) than in nonboarding students (16.51%), and higher in high school students than in middle and primary school students (28.63%, 19.10%, 7.76%), with statistically significant differences (χ2=53.49, 149.31, 522.55, P<0.01). Multivariate Logistic regression results showed that smoking (OR=1.51), drinking (OR=2.36), looking at electronic screens in dim conditions (OR=2.40), screen time ≥2 h/d(OR=1.50), afterschool homework time ≥2 h/d(OR=1.48) were positively correlated with the prevalence of comorbidity of screening positive myopia and depressive symptoms, healthy diet (OR=0.67), outdoor activities during breaks (OR=0.80), sufficient sleep (OR=0.64), meeting physical activity standards (OR=0.74) and outdoor activity time ≥2 h/d(OR=0.84) were negatively correlated with the prevalence of comorbidity of screening positive of myopia and depressive symptoms (P<0.05).@*Conclusions@#The lifestyle of primary and secondary school students in Nanjing is related to the comorbidity of myopia and depressive symptoms. Schools and families should carry out relevant education and intervention measures to promote students to develop good living habits and jointly prevent the occurrence of myopia and depressive symptoms.

Effects of Astragaloside Ⅳ on High Glucose-Induced Pyroptosis and Invasive Migration of Human Chorionic Trophoblast Cells(HTR-8/SVneo) / 广州中医药大学学报

Objective To investigate the effect of astragaloside Ⅳ on high glucose-induced pyroptosis and invasive migration of human chorionic trophoblast cells(HTR-8/SVneo).Methods HTR-8/SVneo cells were divided into 4 groups:control group(untreated),high glucose group(high glucose stimulation)and astragaloside Ⅳ 50 and 100 μmol/L group(high glucose stimulation + astragaloside).Cell activity was detected by Cell Counting Kit 8(CCK-8),cell invasion and migration abilities were determined by Transwell assay and scratch assay,respectively,cell pyroptosis was assessed by Hoechst 33342/propidium iodide(PI)dual fluorescence staining.The protein expression levels of NOD-like receptor thermoprotein structural domain(NLRP3),cleaved-Caspase-1,GSDMD-NT,and IL-18 were detected by Western Blot.Results Compared with the control group,HTR-8/SVneo cell viability was significantly reduced in the high glucose group,the rate of cell migration was significantly reduced,the number of invasive cells was significantly reduced,the percentage of PI-positive cells was significantly increased,and the levels of NLRP3,cleaved-Caspase-1,GSDMD-NT and IL-18 protein expression levels were significantly increased(P<0.05 or P<0.01);compared with the high glucose group,cell viability was significantly higher in the astragaloside Ⅳ treated group,the rate of cell migration was significantly increased,the number of invasive cells was significantly increased,the percentage of PI-positive cells was significantly decreased,and the protein expressions of number of NLRP3,cleaved-Caspase-1,GSDMD-NT,IL-18 were significantly decreased(P<0.05 or P<0.01).Conclusion AstragalosideⅣcan inhibit high glucose-induced HTR-8/SVneo cell pyrolysis and improve cell invasion and migration ability.

A Functional Magnetic Resonance Imaging Study Using Dynamic Amplitude of Low-Frequency Fluctuation to Assess Brain Activity in Patients with Moyamoya Disease.

Introduction: The purpose of this study was to monitor and record the dynamic brain activity of patients with moyamoya disease (MMD), as well as to study the relationship between brain abnormalities and presenting clinical features. Methods: A total of 16 patients with MMD (2 males and 14 females) were invited to participate in the study, as were healthy controls (HCs) with the same number and sex ratio. In this study, the dynamic amplitude of low-frequency fluctuation (dALFF) was utilized to assess changes in spontaneous brain activity. Moreover, we also used correlation analysis to study the relationship among the measured mean of dALFF, behavioral performances, and the retinal nerve fiber layer and the Hospital Anxiety and Depression Scale (HADS) score to explore the potential relationship between MMD and anxiety and depression. Results: Our study reveals that in MMD, dALFF levels decreased in the left lingual gyrus, right insula, and occipital lobe. Discussion: In this study, we found and discussed the potential relationship between the abnormal activities in multiple brain regions and related functional network disorders in patients with MMD, as well as the damage to brain regions that process emotion and vision, in the hopes of providing more ideas for the clinical diagnosis and treatment of MMD.

IGF2BP3 promotes the progression of colorectal cancer and mediates cetuximab resistance by stabilizing EGFR mRNA in an m6A-dependent manner.

Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an RNA-binding protein, is associated with tumorigenesis and progression. However, the exact molecular mechanisms of IGF2BP3 in colorectal cancer (CRC) oncogenesis, progression, and drug resistance remain unclear. This study found that IGF2BP3 was upregulated in CRC tissues. Clinically, the elevated IGF2BP3 level is predictive of a poor prognosis. Functionally, IGF2BP3 enhances CRC tumorigenesis and progression both in vitro and in vivo. Mechanistically, IGF2BP3 promotes epidermal growth factor receptor (EGFR) mRNA stability and translation and further activates the EGFR pathway by serving as a reader in an N6-methyladenosine (m6A)-dependent manner by cooperating with METTL14. Furthermore, IGF2BP3 increases the drug resistance of CRC cells to the EGFR-targeted antibody cetuximab. Taken together, our results demonstrated that IGF2BP3 was a functional and clinical oncogene of CRC. Targeting IGF2BP3 and m6A modification may therefore offer rational therapeutic targets for patients with CRC.

Investigation of Altered Spontaneous Brain Activity Patterns in Herpes Zoster Keratitis Using the Percent Amplitude of Fluctuation Method: A Resting-State Functional Magnetic Resonance Imaging Study.

Purpose: The purpose of this study was to use the percent amplitude of fluctuation (PerAF) to study the changes in brain activity and nerve function of herpes zoster keratitis (HZK) patients. Methods: We recruited 20 HZK patients and 20 healthy controls (HCs). Each of these groups included ten males and ten females and were matched in weight and age. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). The percent amplitude of fluctuation (PerAF) method was used for analysis and detected differences between the two groups in the neurological function of brain areas. We also applied the receiver operating characteristic (ROC) curve to analyze the two groups and did a correlation analysis between the PerAF value, anxiety and depression score, and visual acuity. Results: The PerAF signal at the right putamen and right precentral gyrus was significantly higher in patients than in HCs. However, the PerAF value of the left inferior temporal was lower in patients than in HCs. In addition, the HZK patients' anxiety and depression score (HADS) and visual acuity (V.A.) Log MAR negatively correlated with the PerAF value at the left inferior temporal gyrus. Conclusion: HZK patients had some changes in brain regions, and the changes were also related to their mood and visual acuity. These findings might contribute to other studies on the potential pathological mechanism, disease development, prognosis, and brain function in HZK patients.

RNF43 inhibits PD-L1 expression via β-catenin in melanoma cells and promotes CD8 + T cell-mediated anti-tumor immune reaction / 国际肿瘤学杂志

Objective:To investigate the regulatory effects of ring finger protein 43 (RNF43) on CD8 + T cell-mediated anti-tumor immune reaction in melanoma. Methods:RNF43 gene was over-expressed and knockdown in mouse melanoma cells line B16-OVA by lentivirus infection; In vivo proliferation of mouse melanoma cells line B16-OVA in the Lv-Ctrl-OE, Lv-RNF43-OE, Lv-Ctrl-KD and Lv-RNF43-KD groups was detected by subcutaneous tumorigenesis assay in mice, and the expression levels of CD8 + T cells perforin and interferon γ (IFN-γ) in tumor immune microenvironment of melanoma were detected by flow cytometry; The expression levels of β-catenin and programmed death-ligand 1 (PD-L1) mRNA in cells were detected by quantitative real-time PCR assay; The effect of RNF43 on the transcriptional regulation of PD-L1 was detected by dual-luciferase reporter gene assay. Results:Stable RNF43 over-expressing and RNF43 knockdown mouse melanoma cells lines Lv-RNF43-OE and Lv-RNF43-KD were successfully constructed. The results of subcutaneous tumorigenesis experiment in mice showed that the tumor mass of the Lv-RNF43-OE group was (0.08±0.06) g, which was significantly smaller than that of the Lv-Ctrl-OE group [ (1.04±0.52) g], with a statistically significant difference ( t=3.71, P=0.032) ; The tumor mass of Lv-RNF43-KD group was (1.94±0.29) g, with no statistically significant difference ( t=-1.70, P=0.164) compared with that of the Lv-Ctrl-KD group (1.15±0.74) g. The flow cytometry results showed that the fluorescence intensity of CD8 + T cell perforin in the Lv-RNF43-OE group was 9 034 ± 2 628, which was significantly higher than that in the Lv-Ctrl-OE group (3 847 ±1 637), with a statistically significant difference ( t=-3.35, P=0.015) ; The fluorescence intensity of CD8 + T cell perforin in the Lv-RNF43-KD group was 966±247, which was significantly lower than that in the Lv-Ctrl-KD group (2 226±646), with a statistically significant difference ( t=3.16, P=0.034) ; The fluorescence intensity of IFN-γ of CD8 + T cell in the Lv-RNF43-OE group was 2 422±429, which was significantly higher than that of 1 688±324 in the Lv-Ctrl-OE group, with a statistically significant difference ( t=-2.73, P=0.034) ; The fluorescence intensity of IFN-γ of CD8 + T cell in the Lv-RNF43-KD group was 614 (454, 863), with a statistically significant difference ( Z=-1.96, P=0.050) compared with 1 159 (1 152, 2 068) in the Lv-Ctrl-KD group. The results of quantitative real-time PCR showed that the relative expression level of β-catenin mRNA in the Lv-RNF43-OE group was 0.67±0.16, which was significantly lower than that of 1.00±0.11 in the Lv-Ctrl-OE group, with a statistically significant difference ( t=2.98, P=0.041) ; The relative expression level of PD-L1 mRNA in the Lv-RNF43-OE group was 0.32±0.09, which was significantly lower than that of 1.00±0.09 in the Lv-Ctrl-OE group, with a statistically significant difference ( t=9.13, P=0.001). The results of the dual-luciferase reporter gene assay showed that the PD-L1 promoter luciferase activity in the pCMV6-NC, RNF43, RNF43+β-catenin and β-catenin groups were 1.00±0.00, 0.84±0.00, 1.49±0.00 and 1.57±0.03 ( F=2 218.33, P<0.001). Further pairwise comparison showed that compared with the pCMV6-NC group, PD-L1 promoter luciferase activity was significantly lower in the RNF43 group ( P<0.001) and significantly higher in the RNF43+β-catenin and β-catenin groups ( P<0.001; P=0.003) ; compared with the RNF43 group, PD-L1 promoter luciferase activity was significantly higher in the RNF43+β-catenin group ( P<0.001) . Conclusion:RNF43 may reduce the expression of PD-L1 mRNA in melanoma by inhibiting the expression of β-catenin and promote CD8 + T cell-mediated anti-tumor immune reaction.

Dihydrotanshinone I preconditions myocardium against ischemic injury via PKM2 glutathionylation sensitive to ROS

Ischemic preconditioning (IPC) is a potential intervention known to protect the heart against ischemia/reperfusion injury, but its role in the no-reflow phenomenon that follows reperfusion is unclear. Dihydrotanshinone I (DT) is a natural compound and this study illustrates its role in cardiac ischemic injury from the aspect of IPC. Pretreatment with DT induced modest ROS production and protected cardiomyocytes against oxygen and glucose deprivation (OGD), but the protection was prevented by a ROS scavenger. In addition, DT administration protected the heart against isoprenaline challenge. Mechanistically, PKM2 reacted to transient ROS via oxidization at Cys423/Cys424, leading to glutathionylation and nuclear translocation in dimer form. In the nucleus, PKM2 served as a co-factor to promote HIF-1α-dependent gene induction, contributing to adaptive responses. In mice subjected to permanent coronary ligation, cardiac-specific knockdown of Pkm2 blocked DT-mediated preconditioning protection, which was rescued by overexpression of wild-type Pkm2, rather than Cys423/424-mutated Pkm2. In conclusion, PKM2 is sensitive to oxidation, and subsequent glutathionylation promotes its nuclear translocation. Although IPC has been viewed as a protective means against reperfusion injury, our study reveals its potential role in protection of the heart from no-reflow ischemia.

Effect of deep muscle relaxation by rocuronium on oxygenation of jet ventilation during rigid bronchoscopy procedures / 中国内镜杂志

Objective To observe the effect of deep muscle relaxation by rocuronium on oxygenation of normal frequency jet ventilation during rigid bronchoscopy procedures.Methods From December 2021 to February 2023,60 patients with central airway diseases underwent rigid bronchoscopy under general anesthesia,they were randomly divided into deep muscle relaxation group(group D,n = 30)and moderate muscle relaxation group(group M,n = 30).After induction of general anesthesia,the patients were inserted rigid bronchoscopy for jet ventilation,muscle relaxant was rocuronium in induction and maintenance.Train of four(TOF)stimulation was used to measure the depth of muscle relaxation in group M,and the TOF count was maintained at 1 or 2;In Group D,the depth of muscle relaxation was measured by post tetanic count(PTC),and the PTC was maintained at 1 or 2.After operation,Sugammadex antagonized residual muscle relaxation.Results There was no significant difference in operation time,recovery time and extubation time between the two groups(P＞0.05).The total operation time,operation pause time and anesthesia time in group D were shorter than those in group M,the dosage of muscle relaxant in group D was more than that in group M,the incidence of hypoxemia during surgery in group D was less than that in group M,the operators'satisfaction in group D was better than that in group M,and the arterial partial pressure of oxygen(PaO2)in group D was higher than that in group M at 15 min(T1)and 30 min(T2)after jet ventilation,the number of patients with postoperative sore throat in group D was less than that in group M,the differences were statistically significant(P＜0.05).Conclusion The application of deep muscle relaxation by rocuronium in rigid bronchoscopy procedures can improve the oxygenation effect of normal frequency jet ventilation,reduce the operation pause time and anesthesia time,improve the satisfaction of operators,antagonizing residual muscle relaxation with Sugammadex can relieve the worry of delayed recovery from deep muscle relaxation.

Applications of genetic code expansion in the study of lysine acylation / 中国药科大学学报

@#Lysine acylation is a ubiquitous protein modification that controls various aspects of protein function. However, it can be challenging to decipher the biological function of site-specific acylation modifications in living cells.The recently developed genetic code expansion (GCE) technology has enabled site-specific incorporation of unnatural amino acids (UAAs) that are structurally consistent with the natural acylation modifications in vivo through orthogonal aminoacyl-tRNA synthetase/tRNA pairs, thus facilitating the study of physicochemical properties and biological behaviors of homogeneously acylated proteins.Besides, GCE technology allows for the targeted introduction of UAAs that mimic acylation modifications but cannot be recognized by deacylases, which improves the stability of lysine acylation modification products.Moreover, the insertion of photo-crosslinked UAAs at specific sites of the target protein has been used to elucidate the reciprocal proteome of acylated modified proteins.Based on the introduction of different structural and functional acylation modifications, we described the novel design of GCE technology combined with three types of UAAs, and their application in studying the functional effects of protein acylation modifications on the enzyme activity, protein stability, cellular localization, protein-DNA interactions and protein-protein interactions of target proteins, with a description of the limitations and prospects of GCE technology in studying protein acylation modification.

Corrigendum: Regional homogeneity in patients with mild cognitive impairment: A resting-state functional magnetic resonance imaging study.

[This corrects the article DOI: 10.3389/fnagi.2022.877281.].

The Predictive Value of CA-125 and Hb for Ocular Metastasis in Hepatocellular Carcinoma Patients.

Objective: To explore the risk factors of ocular metastasis (OM) in patients with hepatocellular carcinoma (HCC) by analyzing the demographic characteristics and serum markers. Methods: From July 2002 to December 2012, 1064 HCC patients were included in our study. The chi-squared test and Student's t-test were used to assess the difference between OM and any other metastasis (NOM). Receiver operating curve (ROC) was used to analyze the diagnostic value of serum biomarkers in HCC patients with OM. Results: The incidence of OM in HCC patients was 1.88% in our research. There are no significant differences in age, gender, or histopathology in the OM group and the group without any metastasis. Binary logistic regression analysis presented that compared with the patients without cancer metastasis, carbohydrate antigen 125 (CA-125) and hemoglobin (Hb) were risk factors in hepatocellular carcinoma patients with OM (P < 0.05). The ROC curve analysis showed that the areas under the CA-125, Hb, and CA125+Hb curves were 0.877, 0.554, and 0.431, and the cutoff values of CA-125 and Hb each were 115.78 u/mL and 120.50 g/L. Conclusion: Our data suggest that CA-125 and Hb are risk indicators in hepatocellular carcinoma patients with OM, and that CA-125+Hb has potentially greater utility in diagnosing hepatocellular carcinoma.

Retinal microvasculature alteration in patients with systemic sclerosis and chloroquine treatment.

Background: Retinal vascular abnormality is an important part of ocular systemic sclerosis (SSc), and long-term use of chloroquine can lead to retinal toxicity. This study was conducted to evaluate retinal microvascular changes using optical coherence tomography angiography (OCTA) in patients with SSc and SSc patients on long-term chloroquine treatment. Methods: Fifteen SSc patients without chloroquine (30 eyes), 15 SSc patients taking long-term chloroquine (30 eyes) and 15 healthy controls (30 eyes) were recruited to this cross-sectional study. OCTA was used to examine the superficial and deep retinal capillary plexus in the macular retina of each eye. The densities of microvessels (MIR), macrovessels (MAR) and total microvessels (TMI) in the superficial and deep retina of the three groups were calculated and compared. We used the hemisphere segmentation method [superior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)] and Early Treatment Diabetic Retinopathy Study (ETDRS) method [right (R), superior (S), left (L), and inferior (I)] to analyze changes in retinal microvascular density. Results: The superficial and deep retinal MIR density in SSc patients decreased (P<0.05) compared with the healthy control group. This significant difference was found in both superficial and deep layers in S, L, SR, SL and IL regions (P<0.05), and additionally in the R and I regions in the superficial layer (P<0.05). Similarly, compared with SSc patients who did not take chloroquine, the superficial and deep retinal MIR density of SSc patients on long-term chloroquine also decreased (P<0.05). This significant difference was found in both superficial and deep layers in R, I and IL regions (P<0.05), and additionally in the IR region in the superficial layer (P<0.05). Conclusions: The OCTA results suggest that retinal MIR density is decreased in SSc patients, and that long-term use of chloroquine will aggravate this damage, resulting in a further decrease in retinal MIR density.

AFP and CA-125 as an accurate risk factor to predict eye metastasis in hypertension patients with liver carcinoma: A STROBE-compliant article.

Purpose: In this study, we analyzed the differences between hypertension patients with ocular metastasis of liver cancer and those with metastases to other sites, the correlation between history of HBV and liver cancer metastasis, and independent risk factors for ocular metastasis. Methods: We used treatment records from 488 patients with metastases of primary liver cancer from August 2001 to May 2015, divided into two groups based on metastatic sites: OM (ocular metastasis) and NOM (non-ocular, other sites of metastasis) groups. The Student's t-test and Chi-square test were used to assess the significance of differences between the groups and define the relationship between history of HBV and ocular metastasis of liver cancer. Binary logistic regression analysis was used to identify indicators of ocular metastasis of liver cancer and receiver operating curve (ROC) analyses to estimate their diagnostic value. Results: No significant differences in sex, age, tumor stage, pathological type, or treatment were identified between the OM and NOM groups, while the prevalence of HBV was higher in the former than that in latter. Binary logistic regression demonstrated that AFP and CA-125 were independent indicators of liver metastasis (both p < 0.001). ROC curve analyses generated cut-off values for AFP and CA-125 of 957.2 ng/ml and 114.25 U/ml, respectively, with corresponding AUC values of 0.739 and 0.810. The specificity of the combination of AFP and CA-125 was higher than either factor separately. Discussion: To explore the diagnostic value of AFP and CA125 in predicting the development of ocular metastases of hypertensive patients with liver cancer, which will help us to diagnose the occurrence and development of the disease more accurately and make the best clinical diagnosis and treatment measures.

Potential factors of cytokeratin fragment 21-1 and cancer embryonic antigen for mediastinal lymph node metastasis in lung cancer.

Objective: Lung cancer is a common malignant tumor, characterized by being difficult to detect and lacking specific clinical manifestations. This study aimed to find out the risk factors of mediastinal lymph node metastasis and explore the correlation between serum tumor markers and mediastinal lymph node metastasis and lung cancer prognosis. Methods: A retrospective study of 3,042 lung cancer patients (330 patients with mediastinal lymph node metastasis and 2,712 patients without mediastinal lymph node metastasis) collected from the First Affiliated Hospital of Nanchang University from April 1999 to July 2020. The patients were divided into two groups, namely, mediastinal lymph node metastasis group and non-mediastinal lymph node metastasis group. Student's t test, non-parametric rank sum test and chi-square test were used to describe whether there is a significant difference between the two groups. We compared the serum biomarkers of the two groups of patients, including exploring serum alkaline phosphatase (ALP), calcium hemoglobin (HB), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA125, CA-199, CA -153, cytokeratin fragment 19 (CYFRA 21-1), total prostate specific antigen (TPSA), neuron-specific enolase (NSE) levels and the incidence and prognosis of lung cancer mediastinal lymph node metastasis. Binary logistic regression analysis was used to determine its risk factors, and receiver operating curve (ROC) analysis was used to evaluate its diagnostic value for mediastinal lymph node metastasis. Results: Binary logistic regression analysis showed that carcinoembryonic antigen and CYFRA 21-1 were independent risk factors for mediastinal lymph node metastasis in patients with lung cancer (p < 0.001 and p = 0.002, respectively). The sensitivity and specificity of CEA for the diagnosis of mediastinal lymph node metastasis were 90.2 and 7.6%, respectively; CYFRA 21-1 were 0.6 and 99.0%, respectively. Conclusion: Serum CEA and CYFRA 21-1 have predictive value in the diagnosis of mediastinal lymph node metastasis in patients with lung cancer.