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p38 MAPK inhibitor SB202190 suppresses ferroptosis in the glutamate-induced retinal excitotoxicity glaucoma model

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Neural Regeneration Research 2024年第10期19卷 2299-2309页

作者： Lemeng Feng Chao Wang Cheng Zhang Wulong Zhang Weiming Zhu Ye He Zhaohua Xia Weitao Song National clinical Research center for Geriatric Diseases Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Eye center of Xiangya Hospital Central South UniversityChangshaHunan ProvinceChina Hunan Key Laboratory of Ophthalmology ChangshaHunan ProvinceChina

Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

关键词： ferroptosis glaucoma glutamate excitotoxicity p38 MAPK retinal ganglion cell SB202190

Preoperative prognostic nutritional index predicts long-term outcomes of patients with ampullary adenocarcinoma after curative pancreatoduodenectomy

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1291-1300页

作者： Chong-Yuan Sun Xiao-Jie Zhang Zheng Li He Fei Ze-Feng Li Dong-Bing Zhao Department of Pancreatic and Gastric Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND The prognostic nutritional index(PNI),a marker of immune-nutrition balance,has predictive value for the survival and prognosis of patients with various *** To explore the clinical significance of the preoperative PNI on the prognosis of ampullary adenocarcinoma(AC)patients who underwent curative *** The data concerning 233 patients diagnosed with ACs were extracted and analyzed at our institution from January 1998 to December *** patients were categorized into low and high PNI groups based on the cutoff value determined by receiver operating characteristic curve *** compared disease-free survival(DFS)and overall survival(OS)between these groups and assessed prognostic factors through univariate and multivariate *** The optimal cutoff value for the PNI was established at *** with a PNI≥45.3 were categorized into the PNI-high group,while those with a PNI<45.3 were assigned to the PNI-low *** within the PNI-low group tended to be of advanced age and exhibited higher levels of aspartate transaminase and total bilirubin and a lower creatinine level than were those in the PNI-high *** 5-year OS rates for patients with a PNI≥45.3 and a PNI<45.3 were 61.8%and 43.4%,respectively,while the 5-year DFS rates were 53.5%and 38.3%,*** in the PNI-low group had shorter OS(P=0.006)and DFS(P=0.012).In addition,multivariate analysis revealed that the PNI,pathological T stage and pathological N stage were found to be independent prognostic factors for both OS and *** The PNI is a straightforward and valuable marker for predicting long-term survival after *** PNI should be incorporated into the standard assessment of patients with AC.

关键词： Ampullary carcinoma Prognostic nutritional index Prognosis Pancreaticoduodenectomy

Factors influencing willingness to participate in ophthalmic clinical trials and strategies for effective recruitment

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 157-163页

作者： Jia-En Liang Meng-Yin Liang En-En Zhang Yu-Ying Peng Ling-Ling Chen Jia-Yu Deng Ting Lin Jun Fu Jia-Ni Zhang Shao-Li Li Fei Li Hui-Ming Xaio Wen-Min Huang Yu-Hong Liu State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangdong Provincial Clinical Research Center for Ocular DiseasesGuangzhou 510060Guangdong ProvinceChina

AIM:To explore the factors influencing individuals’willingness to participate in ophthalmic clinical ***:A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic center,Sun Yat-sen University,in Guangzhou,*** survey gathered data on respondents’willingness,demographic and socioeconomic profiles,as well as their reasons and concerns regarding engagement in clinical ***:Of the 1078 residents surveyed(mean age 31.2±13.1y;65.8%females)in Guangzhou,749(69.5%)expressed a willingness to participate in future ophthalmic clinical *** characteristics associated with greater willingness included a younger age,lower annual income,higher education,prior participation experience,previous ophthalmic treatment,and a better understanding of clinical *** the exception of age,these characteristics were significantly linked to a higher *** primary barrier to participation,expressed by 64.8%of those willing and 54.4%of those unwilling,was“Uncertain efficacy”.In terms of motivations,the willing group ranked“Better therapeutic benefits”(35.0%),“Professional monitoring”(34.3%),and“Trust in healthcare professionals”(33.1%)as their top three reasons,whereas the unwilling participants indicated“Full comprehension of the protocol”(46.2%)as the key ***:This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic *** in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment ***,the need for and trust in healthcare professionals stand out as powerful motivations,underscoring the importance of enhancing physician-patient relationships,adopting patient-centered communication approaches,and addressing individualized needs to improve accrual rates.

关键词： participation willingness recruitment strategy ophthalmic clinical trial

Classification of congenital cataracts based on multidimensional phenotypes and its association with visual outcomes

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 473-479页

作者： Yuan Tan Ying-Shi Zou Ying-Lin Yu Le-Yi Hu Ting Zhang Hui Chen Ling Jin Duo-Ru Lin Yi-Zhi Liu Hao-Tian Lin Zhen-Zhen Liu State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangdong Provincial Clinical Research Center for Ocular DiseasesGuangzhou 510060Guangdong ProvinceChina

●AIM:To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes.●METHODS:Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were *** on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients’medical records.A hierarchical cluster analysis was *** main outcome measure was the identification of distinct clusters of eyes with congenital cataracts.●RESULTS:A total of 164 children(299 eyes)were divided into two clusters based on their ocular *** 1(96 eyes)had a shorter axial length(mean±SD,19.44±1.68 mm),a low prevalence of macular abnormalities(1.04%),and no retinal abnormalities or posterior *** 2(203 eyes)had a greater axial length(mean±SD,20.42±2.10 mm)and a higher prevalence of macular abnormalities(8.37%),retinal abnormalities(98.52%),and posterior cataracts(4.93%).Compared with the eyes in Cluster 2(57.14%),those in Cluster 1(71.88%)had a 2.2 times higher chance of good best-corrected visual acuity[<0.7 logMAR;OR(95%CI),2.20(1.25–3.81);P=0.006].●CONCLUSION:This retrospective study categorizes congenital cataracts into two distinct clusters,each associated with a different likelihood of visual *** innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit,thereby making strides toward precision medicine in the field of congenital cataracts.

关键词： classification congenital cataract phenotype visual acuity cluster analysis

Novel PLCZ1 mutation caused polyspermy during in vitro fertilization

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Asian Journal of Andrology 2024年第4期26卷 389-395页

作者： Ke-Ya Tong Wei-Wei Liu Li-Wei Sun Dong-Yun Liu Ye-Zhou Xiang Chong Li Lu-Wei Chai Ke Chen Guo-Ning Huang Jing-Yu Li Chongqing Key Laboratory of Human Embryo Engineering Center for Reproductive MedicineWomen and Children’s Hospital of Chongqing Medical UniversityChongqing 400012China Chongqing clinical Research center for Reproductive Medicine Center for Reproductive MedicineChongqing Health Center for Women and ChildrenChongqing 400012China.

Failure of oocyte activation,including polyspermy and defects in pronuclear(PN)formation,triggers early embryonic developmental *** studies have shown that phospholipase C zeta 1(PLCZ1)mutations cause failure of PN formation following intracytoplasmic sperm injection(ICSI);however,whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization(IVF)remains ***-exome sequencing(WES)was performed to identify candidate mutations in couples with primary *** sequencing was used to validate the *** PLCZ1-mutated sperm were injected into human and mouse oocytes to explore whether PN formation was *** oocyte activation(AOA)after ICSI was performed to overcome the failure of oocyte *** identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles,including a novel missense mutation c.1154C>T,*** formation failure was observed during the ICSI ***,injection of multiple PLCZ1-mutated sperm induced PN formation,suggesting that the Ca2+oscillations induced by the sperm exceeded the necessary threshold for PN *** after ICSI enabled normal fertilization,and all patients achieved successful *** findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking ***,this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.

关键词： AOA PLCZ1 polyspermy pronuclear formation

Effect of lens surgery on health-related quality of life in preschool children with congenital ectopia lentis

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 66-72页

作者： Yan-Qiao Huang Qian-Zhong Cao Yi-Yao Wang Yi-Jing Zhou Dan-Ying Zheng State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangdong Provincial Clinical Research Center for Ocular DiseasesGuangzhou 510060Guangdong ProvinceChina

AIM:To evaluate the effect of lens surgery on health-related quality of life(HRQoL)of preschool children with congenital ectopia lentis(CEL).METHODS:A prospective self-controlled study was conducted in Zhongshan Ophthalmic *** aged from 5 to 7y whom were diagnosed with CEL and underwent phacoemulsification with scleral-fixated posterior chamber intraocular lens implantation and their parents were enrolled in this *** of them completed the child and proxy(parental)PedsQL™4.0 before and after the *** preoperative scores were compared to their postoperative *** analyses were performed based on gender and preoperative bilateral presenting visual acuity of the ***:Thirty-two children with CEL successfully underwent surgery without any complications,among whom 8 had monocular surgery and 24 had binocular *** and postoperative questionnaires were completed by 32 child-parent *** intervention could significantly improve the vision of affected children(P<0.001).The medians of physical,psychosocial and total health scores self-reported by the children were 68.75(62.50,81.25),65.00(60.00,80.00)and 67.39(60.87,78.26)preoperatively and were 93.75(87.50,100.00),90.00(83.33,96.67)and 89.13(85.32,95.65)*** preoperative scores of the affected children were significantly lower in all scales than age-matched healthy children(P<0.001).All the postoperative scores were significantly higher than the preoperative scores in affected children and their parents(P<0.001).In the physical functioning evaluation,the preoperative score reported by parents of girls was higher than parents of boys(P=0.041),and the postoperative score of girls was higher than that of boys(P=0.036).CONCLUSION:CEL is associated with significantly worse quality of life in preschool *** intervention can significantly improve the HRQoL in affected children from both personal and family perspective.

关键词： congenital ectopia lentis surgical intervention health-related quality of life preschool children

The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes:findings from a prospective,nationwide,and multicenter registry

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Journal of Geriatric Cardiology 2024年第5期21卷 523-533页

作者： Rui FU Ying-Xuan ZHU Kong-Yong CUI Jin-Gang YANG Hai-Yan XU Dong YIN Wei-Hua SONG Hong-Jian WANG Cheng-Gang ZHU Lei FENG Wei WU Kai-HongCHEN Yan-Yan ZHAO Ye LU Ke-Fei DOU Yue-Jin YANG on behalf of the CAMI Registry Investigators Cardiometabolic Medicine center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Medical Research&Biometrics center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Coronary Heart Disease center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Cardiology Guangzhou Traditional Chinese Medical College First Affiliated HospitalGuangdong ProvinceChina Department of Cardiology Longyan Hospital First HospitalFujian ProvinceChina 不详

OBJECTIVES To evaluate the predictive value of fasting plasma glucose(FPG)for in-hospital mortality in patients with acute myocardial infarction(AMI)with different glucose metabolism *** We selected 5,308 participants with AMI from the prospective,nationwide,multicenter CAMI registry,of which 2,081 were diabetic and 3,227 were *** were divided into high FPG and low FPG groups according to the optim-al cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts,*** primary endpoint was in-hospital *** Overall,94 diabetic patients(4.5%)and 131 nondiabetic patients(4.1%)died during hospitalization,and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L,*** with individuals who had low FPG,those with high FPG were significantly associated with higher in-hospital mortality in diabet-ic cohort(10.1%vs.2.8%;odds ratio[OR]=3.862,95%confidence interval[CI]:2.542-5.869)and nondiabetic cohort(7.4%vs.1.7%;HR=4.542,95%CI:3.041-6.782).After adjusting the potential confounders,this significant association was not ***-more,FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic *** FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic *** This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mor-tality in AMI patients with and without *** might be useful to stratify patients with AMI.

关键词： patients fasting infarction

Leech Poecilobdella manillensis protein extract ameliorated hyperuricemia by restoring gut microbiota dysregulation and affecting serum metabolites

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World Journal of Gastroenterology 2024年第29期30卷 3488-3510页

作者： Xia Liu Xing-Qiu Liang Tian-Cai Lu Zhe Feng Min Zhang Nan-Qing Liao Feng-Lian Zhang Bo Wang Li-Sheng Wang Medical College Guangxi UniversityNanning 530004Guangxi Zhuang Autonomous RegionChina Department of Traditional Chinese Medicine HIV/AIDS Clinical Treatment Center of Guangxi(Nanning)The Fourth People’s Hospital of NanningNanning 530023Guangxi Zhuang Autonomous RegionChina Department of Science and Technology Ruikang Hospital Affiliated to Guangxi University of Chinese MedicineNanning 530011Guangxi Zhuang Autonomous RegionChina General Manager’s Office Guangxi Fuxinyi Biological Technology Co.Ltd.Pingnan 537300Guangxi Zhuang Autonomous RegionChina Department of Joint and Sports Medicine Ruikang Hospital Affiliated to Guangxi University of Chinese MedicineNanning 530011Guangxi Zhuang Autonomous RegionChina Department of Gerontology Nanning Social Welfare HospitalNanning 530004Guangxi Zhuang Autonomous RegionChina

BACKGROUND Hyperuricemia(HUA)is a public health concern that needs to be solved *** lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA;however,its underlying metabolic regulation remains *** To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host *** A mouse model of rapid HUA was established using a high-purine diet and potassium oxonate *** mice received oral drugs or ***,16S rRNA sequencing and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics were performed to identify changes in the microbiome and host metabolome,*** levels of uric acid transporters and epithelial tight junction proteins in the renal and intestinal tissues were analyzed using an enzyme-linked immunosorbent *** The protein extract of Poecilobdella manillensis lyophilized powder(49 mg/kg)showed an enhanced anti-trioxypurine ability than that of allopurinol(5 mg/kg)(P<0.05).A total of nine bacterial genera were identified to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which included the genera of Prevotella,Delftia,Dialister,Akkermansia,Lactococcus,Escherichia_Shigella,Enterococcus,and ***,22 metabolites in the serum were found to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which correlated to the Kyoto Encyclopedia of Genes and Genomes pathways of cysteine and methionine metabolism,sphingolipid metabolism,galactose metabolism,and phenylalanine,tyrosine,and tryptophan *** analysis found that changes in the gut microbiota were significantly related to these *** The proteins in Poecilobdella manillensis powder were effective for ***,they are associated with improvements in g

关键词： Gut microbiota Metabolism Multi-omics Poecilobdella manillensis Sphingolipid metabolism pathway Galactose metabolism pathway Hyperuricemia

UniBind:a novel artificial intelligence-based prediction model for SARS-CoV-2 infectivity and variant evolution

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Signal Transduction and Targeted Therapy 2024年第1期9卷 14-15页

作者： Qihong Yan Jincun Zhao State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina

In a recent study published in Nature Medicine,Wang et *** an excellent framework called UniBind based on artificial intelligence(AI),which enables accurately predicting infectivity of SARS-CoV-2 variants and evolutionary trends of future viral variants.1 This computational method holds the possibility to not only serve as a valuable early-warning tool for monitoring potential pathogenic SARS-CoV-2 variants but also facilitate fundamental research on protein-protein interactions(PPIs).

关键词： artificial Bind prediction