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

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

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Cancer profiles in China and comparisons with the USA:a comprehensive analysis in the incidence,mortality,survival,staging,and attribution to risk factors

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Science China(Life Sciences) 2024年第1期67卷 122-131页

作者： Siyi he Changfa xia he Li Maomao Cao Fan Yang Xinxin Yan Shaoli zhang Yi Teng Qianru Li Wanqing Chen Office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

China faces a disproportionate cancer burden to the population size and is undergoing a transition in the cancer spectrum.We extracted data in five aspects of cancer incidence,mortality,survival,staging distributions,and attribution to risk factors in China,the USA and worldwide from open-source databases.We conducted a comprehensive secondary analysis of cancer profiles in China in the above aspects,and compared cancer statistics between China and the USA.A total of 4,546,400 new cancer cases and 2,992,600 deaths occurred in China in 2020,accounting for 25.1%and 30.2%of global cases,respectively.Lifestyle-related cancers including lung cancer,colorectal cancer,and breast cancer showed an upward trend and have been the leading cancer types in China.41.6%of new cancer cases and 49.3%of cancer deaths occurred in digestive-system cancers in China,and the cancers of esophagus,nasopharynx,liver,and stomach in China accounted for over 40%of global cases.Infection-related cancers showed the highest population-attributable fractions among Chinese adults,and most cancers could be attributed to behavioral and metabolic factors.The proportions of stage I for most cancer types were much higher in the USA than in China,except for esophageal cancer(78.2%vs.41.1%).The 5-year relative survival rates in China have improved substantially during 2000–2014,whereas survival for most cancer types in the USA was significantly higher than in China,except for upper gastrointestinal cancers.Our findings suggest that although substantial progress has been made in cancer control,especially in digestive system cancers in China,there was still a considerable disparity in cancer burden between China and the USA.More robust policies on risk factors and standardized screening practices are urgently warranted to curb the cancer growth and improve the prognosis for cancer patients.

关键词： cancer burden survival rate neoplasm staging risk factors China

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Marginal zone lymphoma with severe rashes: A case report

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World Journal of Clinical Cases 2024年第3期12卷 565-574页

作者： Si-Jun Bai Ye Geng Yi-Nan Gao Cai-xia zhang Qian Mi Chen zhang Jia-Ling Yang Si-Jie he Zhen-YingYan Jian-xia he Department of hematology Shanxi Provincial People’s HospitalTaiyuan 030012Shanxi ProvinceChina

BACKGROUND Marginal zone lymphoma(MZL)is an indolent subtype of non-Hodgkin lymphoma(NHL),which is rare clinically with severe rashes as the initial symptom.CASE SUMMARY This study reports a case of MZL with generalized skin rashes accompanied by pruritus and purulent discharge.First-line treatment with rituximab combined with zanubrutinib had poor effects.However,after switching to obinutuzumab combined with zanubrutinib,the case was alleviated,and the rashes disappeared.CONCLUSION For patients with advanced stage MZL not benefiting from type I anti-CD20 monoclonal antibody(mAb)combination therapy,switching to a type II anti-CD20 mAb combination regimen may be considered.This approach may provide a new perspective in the treatment of MZL.

关键词： Marginal zone lymphoma Mucosa-associated lymphoid tissue Extranodal marginal zone lymphoma Primary cutaneous marginal zone lymphoma Rituximab,Obinutuzumab Zanubrutinib Case report

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Effect of Microstructural Characteristics on Fracture Toughness in Direct Energy Deposited Novel Ti-6Al-4V-1Mo Alloy

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Acta Metallurgica Sinica(English Letters) 2024年第1期37卷 119-131页

作者： Chao xia Kexin Zhao Xin Zhou Yuqi he Panpan Gao hengxin zhang Guangrui Gao Fengying zhang Hua Tan School of Material Science and Engineering Chang’an UniversityXi’an710064China Science and Technology on Plasma Dynamics Laboratory Air Force Engineering UniversityXi’an710038China State Key Laboratory of Solidification Processing Northwestern Polytechnical UniversityXi’an710072China Surface Material Protection Co. LtdXi’an710018China

Meeting the damage tolerance requirements for engineering-grade titanium alloys pose a significant challenge in achieving high fracture toughness in direct energy deposition(DED)titanium alloys.This work primarily investigated the relationship between the microstructure and the fracture toughness of DED new Ti-6Al-4V-1Mo alloy.Two types of microstructures were designed via two process strategies:high-line energy density(he)and low-line energy density(LE).Relative to LE samples,he samples possess larger-sized microstructural characteristics(coarser grain boundaryα(α_(GB)),largerαcolonies,and coarserαlaths).Lessα/βphase boundaries were formed by coarserαlaths in the he samples,increasing the movement of dislocations,resulting in tensile strength decreasing from 1007.1 MPa(LE)to 930.8 MPa(he)and elongation increasing from 10.8%(LE)to 15.7%(he).Also,he samples exhibited an excellent fracture toughness of 114.0 MPa m^(1/2),significantly higher than that of LE samples(76.8 MPa m^(1/2)).An analysis of crack propagation paths was conducted to investigate the factors contributing to toughening.The primary factor enhancing toughness is the frequent obstruction of cracks by coarseαGB and largeαcolonies in he samples.Particularly,the pretty large-angle deflections induced by the superposition effect of coarseαGB and largeαcolonies play a vital of significant role.These factors induced the long and tortuous high-energy pathways,which resulted in ultimately improved fracture toughness.The discovered microstructural toughening mechanisms can serve as a reference for future studies involving titanium alloys,offering insights on how to enhance fracture toughness by achieving similar characteristics.

关键词： Direct energy deposition Ti-6Al-4V-1Mo Tensile properties Fracture toughness Crack propagation

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Regulating the conductance of tungsten diselenide by oxygen plasma and improving its electrical stability by encapsulation

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Nano Research 2024年第4期17卷 3253-3260页

作者： Zhaofang Cheng Shaodan he Shimin zhang Shijun Duan Min Wang Ziyu Liu Rong zhang Wenya Qiang Xudong zhang Minggang xia MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter School of PhysicsXi’an Jiaotong UniversityXi’an 710049China Department of Applied Physics School of PhysicsXi’an Jiaotong UniversityXi’an 710049China Shaanxi Province Key Laboratory of Quantum Information and Optoelectronic Quantum Devices School of PhysicsXi’an Jiaotong UniversityXi’an 710049China

Two-dimensional(2D)tungsten selenide(WSe_(2))is promising candidate material for future electronic applications,owing to its potential for ultimate device scaling.For improving the electronic performance of WSe_(2)-based field-effect transistors(FETs),the modification of surface properties is essential.In this study,the seamless structural phase transition in WSe_(2) lattice is achieved by soft oxygen plasma,regulating the electrical conductance of WSe_(2)-based FETs.We found that during the soft oxygen plasma treatment with optimal processing time,the generated oxygen ions can substitute some selenium atoms and thus locally modify the bond length,inducing 2H→1T phase transition in WSe_(2) with seamless interfaces.The mosaic structures have been proven to tailor the electronic structure and increase the hole carrier concentration inside WSe_(2),significantly increasing the channel conductance of WSe_(2) FETs.With the further increase of the oxygen plasma treatment time,the creation of more selenium vacancy defects leads to the electronic doping,resulting in the reduction of conductance.Benefiting from the hexagonal boron nitride(h-BN)encapsulation to interrupt the partial structural relaxation from 1T to 2H phase,our WSe_(2) FET exhibits high electronic stability with conductance of 6.8×10^(-4) S,which is about four orders of magnitude higher than 2H WSe_(2)(5.8×10^(-8) S).This study could further broaden the WSe_(2) FETs in applications for functionalization and integration in electronics.

关键词： tungsten selenide(WSe2) structural phase transition oxygen plasma conductance hexagonal boron nitride(h-BN)encapsulation

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Cancer statistics for young adults aged 20 to 49 years in China from 2000 to 2017:a population-based registry study

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Science China(Life Sciences) 2024年第4期67卷 711-719页

作者： Yi Teng Changfa xia he Li Maomao Cao Fan Yang Xinxin Yan Siyi he Mengdi Cao Shaoli zhang Qianru Li Wanqing Chen Office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

An increasing cancer incidence among adults younger than 50 years has been reported for several types of cancer in multiple countries.We aimed to report cancer profiles and trends among young adults in China.Data from the China Cancer Registry Annual Report were used to estimate incidence and mortality among young adults(ages 20–49 years)in China in 2017,and an age-period-cohort model was employed to estimate the average annual percent change(AAPC)in incidence and mortality from 2000 to 2017.All 25 cancer types were grouped into obesity-or overweight-associated cancers(12 cancer types)and additional cancers(13 cancer types).In 2017,there were 681,178new cases and 214,591 cancer deaths among young adults in China.Among young adults,the most common cancers were thyroid,breast,cervical,liver,lung,and colorectal cancer,and the leading causes of cancer deaths were liver,lung,cervical,stomach,breast,and colorectal cancer.From 2000 to 2017,the cancer incidence increased for all cancers combined among young adults,with the highest AAPC(1.46%)for adults aged 20–24 years,while cancer mortality decreased,with the highest AAPC(-1.63%)for those aged 35–39 years.In conclusion,the cancer incidence in China has increased among young adults,while cancer mortality has decreased for nearly all ages.Cancer control measures,such as obesity control and appropriate screening,may contribute to reducing the increasing cancer burden among young adults.

关键词： young adults incidence mortality trends China

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SLC6A14 promotes ulcerative colitis progression by facilitating NLRP3 inflammasome-mediated pyroptosis

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World Journal of Gastroenterology 2024年第3期30卷 252-267页

作者： Qing Gu Huan xia Yue-Qiong Song Jun Duan Yun Chen You zhang he-Ping Chen Li zhang Department of Elderly Digestive Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalUniversity of Electronic Science and TechnologyChengdu 610072Sichuan ProvinceChina Geriatrics Research Institute Sichuan Provincial People’s HospitalChengdu 610072Sichuan ProvinceChina

BACKGROUND Ulcerative colitis(UC)is an inflammatory condition with frequent relapse and recurrence.Evidence suggests the involvement of SLC6A14 in UC pathogenesis,but the central regulator remains unknown.AIM To explore the role of SLC6A14 in UC-associated pyroptosis.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR),immunoblotting,and immunohistochemical were used to assess SLC6A14 in human UC tissues.Lipopolysaccharide(LPS)was used to induce inflammation in FHC and NCM460 cells and model enteritis,and SLC6A14 levels were assessed.Pyroptosis markers were quantified using enzyme-linked immunosorbent assay,Western blotting,and qRT-PCR,and EdU incubation,CCK-8 assays and flow cytometry were used to examine proliferation and apoptosis.Mouse models of UC were used for verification.RESULTS SLC6A14 was increased and correlated with NLRP3 in UC tissues.LPS-induced FHC and NCM460 cells showed increased SLC6A14 levels.Reducing SLC6A14 increased cell proliferation and suppressed apoptosis.Reducing SLC6A14 decreased pyroptosis-associated proteins(ASC,IL-1β,IL-18,NLRP3).NLRP3 overexpression counteracted the effects of sh-SLC6A14 on LPS-induced FHC and NCM460 cell pyroptosis.SLC6A14 improved the mucosa in mice with dextran sulfate sodium-induced colitis.CONCLUSION SLC6A14 promotes UC pyroptosis by regulating NLRP3,suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.

关键词： Ulcerative colitis SLC6A1 NLRP3 Pyroptosis Inflammasome

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Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19

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Genes & Diseases 2024年第3期11卷 220-231页

作者： Jilei zhang Yongguo zhang Yinglin xia Jun Sun Division of Gastroenterology and hepatology Department of MedicineUniversity of Ilinois ChicagoIL60612USA Uic Cancer Center Department of Microbiology and ImmunologyUniversity of Ilinois ChicagoChicagoIL60612USA Jesse Brown VA Medical Center ChicagoIL60612USA

Long CoVID,also known for post-acute sequelae of CovID-19,describes the people who have the signs and symptoms that continue or develop after the acute coviD-19 phase.Long CovID patients suffer from an inflammation or host responses towards the virus approx-imately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an unchar-acterized duration.Anyone infected with CovID-19 before could experience long-CcovID conditions,including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection early.People with long CoviD may experience health problems from different types and combinations of symptoms over time,such as fa-tigue,dyspnea,cognitive impairments,and gastrointestinal(Gl)symptoms(e.g.,nausea,vom-iting,diarrhea,decreased or loss of appetite,abdominal pain,and dysgeusia).The critical role of the microbiome in these Gl symptoms and long CovID were reported in clinical patients and experimental models.here,we provide an overall view of the critical role of the Gl tract and microbiome in the development of long COVID,including the clinical Gl symptoms in patients,dysbiosis,viral-microbiome interactions,barrier function,and inflammatory bowel disease patients with long CovID.We highlight the potential mechanisms and possible treatment based on Gl health and microbiome.Finally,we discuss challenges and future direction in the long CoVID clinic and research.

关键词： Gastrointestinal symptoms Gl tract Gut microbiome Inflammatorybowel diseases Intestinal barrier Long CoVID Metabolites Tight junctions

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Timing theory integrated nursing combined behavior change integrated theory of nursing on primiparous influence

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World Journal of Clinical Cases 2024年第2期12卷 293-301页

作者： Yan-xia he Yang Lv Ting-Ting Lan Fang Deng Yuan-Yuan zhang Department of Obstetrics and Gynecology Wuhan Children’s HospitalWuhan 430015Hubei ProvinceChina Center for Reproductive Medicine Department of Obstetrics and GynecologySichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610072Sichuan ProvinceChina

BACKGROUND The comprehension and utilization of timing theory and behavior change can offer a more extensive and individualized provision of support and treatment alternatives for primipara.This has the potential to enhance the psychological well-being and overall quality of life for primipara,while also furnishing healthcare providers with efficacious interventions to tackle the psychological and physiological obstacles encountered during the stages of pregnancy and postpartum.AIM To explore the effect of timing theory combined with behavior change on selfefficacy,negative emotions and quality of life in patients with primipara.METHODS A total of 80 primipara cases were selected and admitted to our hospital between August 2020 and May 2022.These cases were divided into two groups,namely the observation group and the control group,with 40 cases in each group.The nursing interventions differed between the two groups,with the control group receiving routine nursing and the observation group receiving integrated nursing based on the timing theory and behavior change.The study aimed to compare the pre-and post-nursing scores of Chinese Perceived Stress Scale(CPSS),Edinburgh Postpartum Depression Scale(EPDS),Self-rating Anxiety Scale(SAS),breast milk knowledge,self-efficacy,and SF-36 quality of life in both groups.RESULTS After nursing,the CPSS,EPDS,and SAS scores of the two groups was significantly lower than that before nursing,and the CPSS,EPDS,and SAS scores of the observation group was significantly lower than that of the control group(P=0.002,P=0.011,and P=0.001 respectively).After nursing,the breastfeeding knowledge mastery,selfefficacy,and SF-36 quality of life scores was significantly higher than that before nursing,and the breastfeeding knowledge mastery(P=0.013),self-efficacy(P=0.008),and SF-36 quality of life(P=0.011)scores of the observation group was significantly higher than that of the control group.CONCLUSION The integration of timing theory and behavior change integrated theory has been found to be a

关键词： Timing theory Behavior change Primipara Bad mood Quality of life

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Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis: A Multi-center, Double-Blinded and Randomized Controlled Trial

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Chinese Journal of Integrative Medicine 2024年第7期30卷 579-587页

作者： zhang Shao-yan QIU Lei zhang Shun-xian xiaO he-ping CHU Nai-hui zhang xia zhang Hui-qiang ZheNG Pei-yong zhang Hui-yong LU Zhen-hui Institute of Respiratory Diseases Longhua Hospital Shanghai University of Traditional Chinese Medicine Clinical Research Center Shanghai University of Traditional Chinese Medicine Department of Tuberculosis Shanghai Pulmonary HospitalTongji University Department of Tuberculosis Beijing Chest Hospital Capital Medical University Department of Tuberculosis the Second Hospital of Nanjing Department of Tuberculosis the First Hospital Affiliated to Xinxiang Medical College

Objective: To assess the efficacy and safety of Bufei Jiedu(BFJD) Granules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis(MDR-PTB). Methods: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups(1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months(6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life(QoL) of patients. Adverse reactions were monitored during and after the trial. Results: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo(58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion(5 months vs. 11 months). The cavity closure rate of the BFJD Granules group(50.6%, 43/85) was higher than that of the placebo group(32.1%, 26/81; P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group(all Phe death rates in the two groups were not significantly different; 5.1%(8/156) in the BFJD Granules group and 2.6%(4/156) in the placebo group. Conclusions: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rate, and rapidly improved QoL of patients with MDR-PTB(Registration No. ChiCTR-TRC-

关键词： alternative medicine Chinese herbal formula Bufei Jiedu Granules multidrug-resistant tuberculosis long-course chemotherapy regimen randomized controlled trial

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