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ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 341-353页

作者： Zhibin YAN ying shi Runling YANG Jijun XUE Caiyun FU Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine College of Life Sciences and MedicineZhejiang Sci-Tech UniversityHangzhou310018China State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical EngineeringLanzhou University Lanzhou 730000China Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical Sciences2019RU066Lanzhou UniversityLanzhou 730000China

Kidney fibrosis is an inevitable result of various chronic kidney diseases(CKDs)and significantly contributes to end-stage renal failure.Currently,there is no specific treatment available for renal fibrosis.ELA13(amino acid sequence:RRCMPLHSRVPFP)is a conserved region of ELABELA in all vertebrates;however,its biological activity has been very little studied.In the present study,we evaluated the therapeutic effect of ELA13 on transforming growth factor-β1(TGF-β1)-treated NRK-52E cells and unilateral ureteral occlusion(UUO)mice.Our results demonstrated that ELA13 could improve renal function by reducing creatinine and urea nitrogen content in serum,and reduce the expression of fibrosis biomarkers confirmed by Masson staining,immunohistochemistry,real-time polymerase chain reaction(RT-PCR),and western blot.Inflammation biomarkers were increased after UUO and decreased by administration of ELA13.Furthermore,we found that the levels of essential molecules in the mothers against decapentaplegic(Smad)and extracellular signal-regulated kinase(ERK)pathways were reduced by ELA13 treatment in vivo and in vitro.In conclusion,ELA13 protected against kidney fibrosis through inhibiting the Smad and ERK signaling pathways and could thus be a promising candidate for anti-renal fibrosis treatment.

关键词： ELA13 Kidney fibrosis Inflammation Smad Extracllular signal-regulated kinase(ERK)

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Development of small molecule drugs targeting immune checkpoints

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Cancer Biology & Medicine 2024年第5期21卷 382-399页

作者： Luoyi Chen Xinchen Zhao Xiaowei Liu Yujie Ouyang Chuan Xu ying shi Department of Oncology Sichuan Academy of Medical SciencesSichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610054China Institute for Breast Health Medicine State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Acupuncture and Massage College Chengdu University of Traditional Chinese MedicineChengdu 611137China

Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints.Thousands of small molecule drugs or biological materials,especially antibody-based ICIs,are actively being studied and antibodies are currently widely used.Limitations,such as anti-tumor efficacy,poor membrane permeability,and unneglected tolerance issues of antibody-based ICIs,remain evident but are thought to be overcome by small molecule drugs.Recent structural studies have broadened the scope of candidate immune checkpoint molecules,as well as innovative chemical inhibitors.By way of comparison,small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features.Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions,including immune regulation,anti-angiogenesis,and cell cycle regulation.In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins,which will lay the foundation for further exploration.

关键词： Immune checkpoints small molecule drugs programmed death protein 1 CD47 signal-regulatory proteinα

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SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 978-992页

作者： Ming-Yan shi Yarong Wang ying shi Ruofei Tian Xiaohong Chen Hai Zhang Ke Wang Zhinan Chen Ruo Chen National Translational Science Center for Molecular Medicine & Department of Cell Biology Fourth Military Medical UniversityXi'anShaanxi 710032China

Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor progression.CD147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism reprogramming.Nevertheless,the relationship between the PTMs of CD147 and apoptosis has not been reported.In our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent tissues.SETDB1 was identified as the methyltransferase catalyzing CD147 to generate CD147-K71me2.RNA-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)groups.Subsequently,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell apoptosis.In vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell apoptosis.Taken together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

关键词： CD147 di-methylation Cell apoptosis FOSB Non-small cell lung cancer SETDB1

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Omental fibroma combined with right indirect inguinal hernia masquerades as a scrotal tumor: A case report

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World Journal of Clinical Cases 2024年第5期12卷 988-994页

作者： Ping Zhou Chan-Hui Jin ying shi Guo-Qing Ma Wen-Hao Wu Yu Wang Kun Cai Wu-Feng Fan Tian-Bao Wang Department of Gastrointestinal Surgery South China Hospital of Shenzhen UniversityShenzhen 518000Guangdong ProvinceChina

BACKGROUND The most common causes of scrotal enlargement in patients include primary tumor of the scrotum,inflammation,hydrocele of the tunica vaginalis,and indirect inguinal hernia;scrotal enlargement caused by external tumors of the scrotum is rare.The patient had both a greater omentum tumor and an inguinal hernia,and the tumor protruded into the scrotum through the hernia sac,which is even rarer.Moreover,omental tumors are mostly metastatic,and primary omental fibroma is rare.CASE SUMMARY Here,we report a rare case of a 25-year-old young man with scrotal enlargement and pain for 3 months.Preoperative examination and multidisciplinary discu-ssions considered intra-abdominal tumor displacement and inguinal hernia,and intraoperative exploration confirmed that the greater omentum tumor protruded into the scrotum.Therefore,tumor resection and tension-free inguinal hernia repair were performed.The final diagnosis was benign fibroma of the greater omentum accompanied by an indirect inguinal hernia.CONCLUSION This unusual presentation of a common inguinal hernia disease illustrates the necessity of performing detailed history taking,physical examination,and imaging before surgery.

关键词： Hernia Indirect inguinal hernia Fibroma Omental tumor Scrotal tumor Greater omentum Case report

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Light at night and lung cancer risk:A worldwide interdisciplinary and time-series study

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 56-62页

作者： Runchen Wang Qixia Wang Jianfu Li Jianrong Zhang shixuan Lyu Wenhao Chi Zhiming Ye Xuanzhuang Lu ying shi Yubin Wang Xinjian Wu Ruiyu Hu Mónica Pérez-Ríos Jianxing He Wenhua Liang Department of Thoracic Surgery and Oncology The First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthGuangzhouGuangdong 510120China Department of Respiratory Disease China State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory DiseaseThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510120China Centre for Cancer Research&Department of General Practice Faculty of MedicineDentistry and Health SciencesUniversity of MelbourneVictorian Comprehensive Cancer CentreMelbourneVictoria 3010Australia Department of Civil Engineering University of BristolBristolBS81TRUK Academy of Mathematics and Systems Science Chinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Nanshan School Guangzhou Medical UniversityGuangzhouGuangdong 511436China State Key Laboratory of Information Engineering in Surveying Mapping and Remote Sensing Wuhan UniversityWuhanHubei 430079China GNSS Research Center Wuhan UniversityWuhanHubei 430079China First Clinical School Guangzhou Medical UniversityGuangzhouGuangdong 511436China Preventive Medicine and Public Health Department University of Santiago de CompostelaCIBER de Epidemiología y Salud Pública(CIBERESP)Health Research Institute of Santiago de Compostela(IDIS)Santiago de CompostelaGalicia 15782Spain Southern Medical University GuangzhouGuangdong 510515China

Background:Light at night(LAN)has become a concern in interdisciplinary research in recent years.This global interdisciplinary study aimed to explore the exposure-lag-response association between LAN exposure and lung cancer incidence.Methods:LAN data were obtained from the Defense Meteorological Satellite Program’s Operational Linescan System.Data of lung cancer incidence,socio-demographic index,and smoking prevalence of populations in 201 countries/territories from 1992 to 2018 were collected from the Global Burden of Disease Study.Spearman correlation tests and population-weighted linear regression analysis were used to evaluate the correlation between LAN exposure and lung cancer incidence.A distributed lag nonlinear model(DLNM)was used to assess the exposure-lag effects of LAN exposure on lung cancer incidence.Results:The Spearman correlation coefficients were 0.286-0.355 and the population-weighted linear regression correlation coefficients were 0.361-0.527.After adjustment for socio-demographic index and smoking preva-lence,the Spearman correlation coefficients were 0.264-0.357 and the population-weighted linear regression correlation coefficients were 0.346-0.497.In the DLNM,the maximum relative risk was 1.04(1.02-1.06)at LAN exposure of 8.6 with a 2.6-year lag time.After adjustment for socio-demographic index and smoking prevalence,the maximum relative risk was 1.05(1.02-1.07)at LAN exposure of 8.6 with a 2.4-year lag time.Conclusion:High LAN exposure was associated with increased lung cancer incidence,and this effect had a specific lag period.Compared with traditional individual-level studies,this group-level study provides a novel paradigm of effective,efficient,and scalable screening for risk factors.

关键词： Light at night Satellite imagery Lung cancer Distributed lag nonlinear model(DLNM) Melatonin

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Neighbor Product Distinguishing Total Coloring via Combinatorial Nullstellensatz

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Acta Mathematicae Applicatae Sinica 2024年

作者： Meng-ying shi Li ZHANG School of Mathematical Sciences Tongji University

Let G =(V, E) be a simple graph and φ : V(G) ∪ E(G) → {1, 2, · · ·, k} be a proper total-k-coloring of G. Let f(v) = φ(v)Π(uv∈E(G))φ(uv). The coloring φ is neighbor product distinguishing if f(u) ≠ f(v) for each edge uv ∈ E(G). The neighbor product distinguishing total chromatic number of G, denoted by χΠ’’(G),is the smallest integer k such that G admits a k-neighbor product distinguishing total coloring. Li et al. conjectured that χΠ’’(G) ≤ △(G) + 3 for any graph with at least two vertices and confirmed the conjecture for K4-minor free graph. In this paper, we prove that for a graph G with at least two vertices,(1) if mad(G) <(60)/(17),then χΠ’’(G) ≤ max{△ + 2, 8};(2) if mad(G) <8/3, then χΠ’’(G) ≤ max{△ + 2, 6}. Furthermore, by using the Combinatorial Nullstellensatz, we simplify their proof and show that χΠ’’(G) ≤ max{△(G) + 2, 6} for any K4-minor free graph.

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Value of multiple models of diffusion-weighted imaging to predict hepatic lymph node metastases in colorectal liver metastases patients

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World Journal of Gastroenterology 2024年第4期30卷 308-317页

作者： Hai-Bin Zhu Bo Zhao Xiao-Ting Li Xiao-Yan Zhang Qian Yao ying-shi Sun Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of RadiologyPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND About 10%-31% of colorectal liver metastases(CRLM)patients would concomitantly show hepatic lymph node metastases(LNM),which was considered as sign of poor biological behavior and a relative contraindication for liver resection.Up to now,there’s still lack of reliable preoperative methods to assess the status of hepatic lymph nodes in patients with CRLM,except for pathology examination of lymph node after resection.AIM To compare the ability of mono-exponential,bi-exponential,and stretchedexponential diffusion-weighted imaging(DWI)models in distinguishing between benign and malignant hepatic lymph nodes in patients with CRLM who received neoadjuvant chemotherapy prior to surgery.METHODS In this retrospective study,97 CRLM patients with pathologically confirmed hepatic lymph node status underwent magnetic resonance imaging,including DWI with ten b values before and after chemotherapy.Various parameters,such as the apparent diffusion coefficient from the mono-exponential model,and the true diffusion coefficient,the pseudo-diffusion coefficient,and the perfusion fraction derived from the intravoxel incoherent motion model,along with distributed diffusion coefficient(DDC)andαfrom the stretched-exponential model(SEM),were measured.The parameters before and after chemotherapy were compared between positive and negative hepatic lymph node groups.A nomogram was constructed to predict the hepatic lymph node status.The reliability and agreement of the measurements were assessed using the coefficient of variation and intraclass correlation coefficient.RESULTS Multivariate analysis revealed that the pre-treatment DDC value and the short diameter of the largest lymph node after treatment were independent predictors of metastatic hepatic lymph nodes.A nomogram combining these two factors demonstrated excellent performance in distinguishing between benign and malignant lymph nodes in CRLM patients,with an area under the curve of 0.873.Furthermore,parameters from SEM showed substantial repeatability.CONCLUSION The dev

关键词： Colorectal cancer Individualized treatment Diffusion magnetic resonance imaging Intravoxel incoherent motion Liver

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Successful management of severe hypoglycemia induced by total parenteral nutrition in patients with hepatocellular injury: Three cases reports

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World Journal of Clinical Cases 2024年第1期12卷 157-162页

作者： Ling-Zhi Fang Hui-Xin Jin Na Zhao Yu-Pei Wu ying-Qin shi Department of Pharmacy Hebei Key Laboratory of Clinical PharmacyHebei General HospitalShijiazhuang 050051Hebei ProvinceChina

BACKGROUND Glucose imbalance is common in total parenteral nutrition(TPN).Hypoglycemia seems to be less frequent than hyperglycemia,but it influences the clinical outcome to a greater extent.Therefore,it should be effectively prevented and treated.However,there is no relevant report on how to treat hypoglycemia caused by TPN in patients with liver cell injury.CASE SUMMARY We present three patients with liver cell injury who developed severe hypo-glycemia during or after TPN infusion.The causes of severe hypoglycemia and glucose-raising strategies were discussed.According to the physiological charac-teristics of the hepatocellular injury,the ratio of nutrition components prescribed in TPN was appropriately adjusted for the three cases.We simultaneously reduced the dose of insulin and fat emulsion,and increased the dose of glucose in TPN.The blood glucose level was restored to normal range and clinical symptoms were eliminated.CONCLUSION When hypoglycemia occurs during or after TPN in patients with hepatocellular injury,physicians need to simultaneously reduce insulin and fat emulsion,and increase glucose,and correct severe hypoglycemia in time to reduce its adverse consequences.

关键词： Total parenteral nutrition Hepatocellular injury Severe hypoglycemia Treatment Causes Case report

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Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China: A nationwide, multi-center, population-based cross-sectional study

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中华医学杂志(英文版) 2024年第11期137卷 2024 Apr 12页

作者： Zhang Weiyu Liu Huixin Liu Ming ying shi Yuan Renbin Zeng Hao Zhang Zhenting Han Sujun Si Zhannan Hu Bin Wen Simeng Xu Pengcheng Yu Weimin Chen Hui Wang Liang Lin Zhitao Dai Tao Lin Yunzhi Xu Tao Hospital Tianjin China Department of Urology Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China National Cancer Center Beijing China National Clinical Research Center for Cancer Beijing China Department of Urology Liaoning Cancer Hospital Shenyang Liaoning China Department of Urology The Second Hospital of Tianjin Medical University Tianjin China Tianjin Institute of Urology Tianjin Medical University Tianjin China Department of Urology Lu’an Affiliated Hospital of Anhui Medical University Lu’an Anhui China Department of Urology Renmin Hospital of Wuhan University Wuhan Hubei China Department of Urology Harbin Medical University Affiliated Cancer Hospital Harbin Heilongjiang China Department of Urology Peking University People’s Hospital Beijing China Department of Urology The Second Hospital of Dalian Medical University Dalian Liaoning China Department of Urology Surgery Fujian Cancer Hospital Fuzhou Fujian China Department of Urology Surgery Hunan Cancer Hospital Changsha Hunan China Department of Urology Surgery The First Affiliated Hospital of Fujian Medical University Fuzhou Fujian China Department of Clinical Epidemiology and Biostatistics Peking University People’s Hospital Beijing China Department of Urology Beijing Hospital National Center of Gerontology Beijing China Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing China Department of Urology Wuhan Union Hospital Huazhong University of Science &amp Technology Wuhan Hubei China Department of Urology The Third People’s Hospital of Chengdu Chengdu Sichuan China Department of Urology West China Hospital of Sichuan University Chengdu Sichuan China Department of Urologic Oncology Tianjin Medical University Cancer Institute &amp

Background: Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods: Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups.χ2 or Fisher’s exact test was used for comparison of categorical variables.Results: A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to

关键词： Prostate cancer Castration Cardiovascular disease Prevalence Cardiovascular risk

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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 recruited.Data 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 performed.The 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 features.Cluster 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 cataracts.Cluster 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 outcomes.This 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

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