Management of Adult Growth Hormone Deficiency at Peking Union Medical College Hospital:A Survey among Physicians

Objective To evaluate physicians' attitude and knowledge about the management of adult growth hormone deficiency(AGHD) at Peking Union Medical College Hospital and impact factors associated with better decision-making.Methods A 21-question anonymous survey was distributed and collected at Peking Union Medical College Hospital,a major teaching hospital in Chinese Academy of Medical Sciences.Data of physicians' educational background,clinical training,patient workload per year and continuing medical education in AGHD were collected.Factors associated with appropriate answers were further analyzed by multivariate regression models.Results One hundred and eighteen internal medicine residents,endocrine fellows,attending physicians and visiting physicians responded to the survey.Among them,44.9% thought that AGHD patients should accept recombinant human growth hormone replacement therapy.Moreover,56.8% selected insulin tolerance test and growth hormone-releasing hormone-arginine test for the diagnosis of AGHD.Logistic regression analysis of physician demographic data,educational background,and work experience found no consistent independent factors associated with better decision-making,other than continued medical education,that were associated with treatment choice.Conclusions The physicians' reported management of AGHD in this major academic healthcare center in Beijing was inconsistent with current evidence.High quality continued medical education is required to improve Chinese physician management of AGHD.

Positive Rate of Different Hepatitis B Virus Serological Markers in Peking Union Medical College Hospital,a General Tertiary Hospital in Beijing

Objectives To investigate the positive rate of different hepatitis B virus （HBV） serological markers, and the demographic factors related to HBV infection. Methods We enrolled all patients tested for HBV serological markers, such as HBV surface antigen （HBsAg）, HBV surface antibody （HBsAb）, hepatitis B e antigen （HBeAg）, hepatitis B e antibody （HBeAb）, HBV core antibody （HBcAb）, and HBV-DNA from July 2008 to July 2009 in Peking Union Medical College Hospital. The positive rate of each HBV serological marker was calculated according to gender, age, and department, respectively. The positive rates of HBV-DNA among patients with positive HBsAg were also analyzed. Results Among 27 409 samples included, 2681 （9.8%） were HBsAg positive. When patients were divided into 9 age groups, the age-specific positive rate of HBsAg was 1.2%, 9.6%, 12.3%, 10.9%, 10.3%, 9.7%, 8.0%, 5.8%, and 4.3%, respectively. The positive rate of HBsAg in non-surgical department, surgical department, and health examination center was 16.2%, 5.8%, and 4.7%, respectively. The positive rate of HBsAg of males （13.3%） was higher than that of females （7.3%, P=0.000）. Among the 2681 HBsAg （＋） patients, 1230 （45.9%） had HBV-DNA test, of whom 564 （45.9%） were positive. Patients with HBsAg （＋）, HBeAg （＋）, and HBcAg （＋） result usually had high positive rate of HBV-DNA results （71.8%, P=0.000）. Conclusions Among this group of patients in our hospital, the positive rate of HBsAg was relatively high. Age group of 20-29, males, and patients in non-surgical departments were factors associated with high positive rate of HBsAg.

Pregnancy Outcomes of Repeat Cesarean Section in Peking Union Medical College Hospital

Objective To evaluate the effect of elective repeat cesarean section on the maternal and neonatal outcomes. Methods A retrospective clinic- and hospital-based survey was designed for comparing the maternal and neonatal outcomes of elective repeat cesarean section [RCS group （one previous cesarean section） and MRCS group （two or more previous cesarean sections）] and primary cesarean section （FCS group） at Peking Union Medical College Hospital from January 1998 to December 2007. Results The incidence of repeat cesarean section increased from 1.26% to 7.32%. The mean gestational age at delivery in RCS group （38.1±1.8 weeks） and MRCS group （37.3±2.5 weeks） were significantly shorter than that in FCS group （38.9±2.1 weeks, all P〈0.01）. The incidence of complication was 33.8% and 33.3% in RCS group and MRCS group respectively, and was significantly higher than that in FCS group （7.9%, P〈0.05）. Dense adhesion （13.5% vs. 0.4%, OR=7.156, 95% CI： 1.7-30.7, P〈0.01） and uterine rupture （1.0% vs. O,P〈0.05） were commoner in RCS group compared with FCS group. Neonatal morbidity was similar among three groups （P〉0.05）. Conclusions Repeat cesarean section is associated with more complicated surgery technique and increased frequency of maternal morbidity. However, the incidence of neonatal morbidity is similar to primary cesarean section.

Prevalence and risk factors of chronic post-thoracotomy pain in Chinese patients from Peking Union Medical College Hospital

Background In clinical practice, the mechanisms underlying chronic post-surgical pain （CPSP） remain insufficiently understood. The primary goals of this study were to determine the incidence of chronic pain after thoracic surgery and to identify possible risk factors associated with the development of chronic post-thoracotomy pain in Chinese patients. The secondary goal was to determine whether the difference between pre- and post-operative white blood cell （WBC） counts could predict the prevalence of CPSP after thoracotomy. The impact of chronic pain on daily life was also investigated. Methods We contacted by phone 607 patients who had undergone thoracotomy at our hospital during the period February 2009 to May 2010. Statistical comparisons were made between patients with or without CPSP. Results Results were ultimately analyzed from 466 qualified patients. The overall incidence of CPSP was 64.5%. Difference between pre- and post-operative WBC counts differed significantly between patients with or without CPSP （P 〈0.001） and was considered as an independent risk factor for the development of CPSP following thoracotomy （P 〈0.001）. Other predictive factors for chronic pain included younger age （〈60 years, P 〈0.001）, diabetes mellitus （P=0.023）, acute post-operative pain （P=0.005） and the duration of chest tube drainage （P 〈0.001）. At the time of interviews, the pain resulted in at least moderate restriction of daily activities in 15% of the patients, of which only 16 patients had paid a visit to the doctor and only three of them were satisfied with the therapeutic effects, Conclusions Chronic pain is common after thoracotomy. WBC count may be a new independent risk factoring surgical patients during peri-operative period. Besides, age, diabetes mellitus, acute post-operative pain, and duration of chest tube drainage may also play a role in chronic post-surgical pain occurrence.

Treatment of respiratory failure in metastatic pulmonary choriocarcinoma： an experience at Peking Union Medical College Hospital, China

Background Respiratory failure caused by metastatic pulmonary choriocarcinoma usually develops rapidly and is associated with a high mortality. The clinical management strategy is important in choriocarcinoma patients with acute respiratory failure. The objective of this study was to evaluate the clinical characteristics, treatment outcome and potential risk factors in patients with acute respiratory failure from metastatic pulmonary choriocarcinoma. Methods Sixteen patients with acute respiratory failure from pulmonary metastases choriocarcinoma were enrolled and treated at Peking Union Medical College Hospital from 1995 to 2010. Clinical characteristics, causes of pulmonary failure, treatment profiles and outcomes were analyzed retrospectively. Results The presence of respiratory infection or hemorrhage was associated with acute respiratory failure in patients with metastatic choriocarcinoma. Fifteen （93.8%） patients presented with pulmonary infection, 8 （50.0%） patients with pulmonary hemorrhage. All patients were treated with face mask or mechanical ventilation. Fourteen （87.5%） patients received initial chemotherapy at a low dosage or with modified regimens, with a median of 2 cycles （range 1 to 4）. Seven patients achieved a complete remission （CR）, two had a partial remission. Six CR patients remained alive with a median follow-up of 59 months （range 16 to 120）. Seven patients developed progressive diseases and subsequently died. Conclusions Respiratory infection and hemorrhage were associated with acute respiratory failure in metastatic pulmonary choriocarcinoma. The initial administration of gentle chemotherapy regimens, accompanied with mechanical ventilation, is feasible and effective in attenuatina resDiratorv failure in patients with metastatic oulmonarv choriocarcinoma.

Transsphenoidal approach to pituitary adenoma： surgical technique of the Peking Union Medical College Hospital

Although presented over one hundred years ago, the transsphenoidal approach to pituitary adenoma is still the most suitable and safe route to pituitary adenoma, with a series of significant evolutional steps. The transsphenoidal approach to pituitary adenoma is still a non-universal approach used in different centers of different areas in our country. The transsphenoidal approach has a number of variations, including the endonasal rhinoseptoplastic, transnasal displacement,

Diagnosis and Clinical Management of Acute Severe Hepatitis of Unknown Origin: Operational Recommendation of Peking Union Medical College Hospital

Around 450 cases of acute severe hepatitis of unknown origin in children have been reported in 21 countries and region globally since April 2022,which has exceeded the past annual incidences of related regions,and has aroused wide concern.Affected patients were predominantly children under 16years of age,presented with symptoms of acute hepatitis with markedly elevated liver enzymes,and had been ruled out of common viral infections such as hepatitis A,B,C,D,and E.Similar cases have not been reported in China yet.However,considering that the severe acute hepatitis has involved worldwide areas,still with unknown origin,and incidences of severity is relatively high,we formulated this recommendation to standardize diagnosis and treatment of acute severe hepatitis of unknown origin in Peking Union Medical College Hospital,to get fully prepared to the possible public health events.

Bridging the translation gap and building the translation platform:translational medicine at Peking Union Medical College Hospital

Although there have been progressive advancements in the life sciences since the beginning of the 21st Century, basic medical sciences generally fail to be efficiently translated into clinical research and ultimately into clinical practice. Translational medicine has become a fashionable term de- scribing the inclination of basic science and clinical re- searchers to ultimately help patients through facilitating the incorporation of basic research findings into clinical prac- tice （Zerhouni, 2005）.

Clinical Characteristics of Patients Who Underwent Surgery for Genital Tract Malformations at Peking Union Medical College Hospital across 31 Years

Background：Female genital malformations represent miscellaneous deviations from normal anatomy.This study aimed to explore the clinical characteristics of patients who underwent surgery for genital tract malformations at Peking Union Medical College Hospital （PUMCH） during a 31-year period.Methods：We retrospectively reviewed surgical cases of congenital malformation of the female genital tract at PUMCH for a 31-year period,analyzed the clinical characteristics of 1634 hospitalized patients,and investigated their general condition,diagnosis,and treatment process.Results：The average patient age was 27.6 ± 9.9 years.The average ages of patients who underwent surgery for uterine malformation and vaginal malformation were 31.9 ± 8.8 years and 24.7 ± 9.0 years,respectively;these ages differed significantly （P 〈 0.01）.Among patients with genital tract malformation,the percentages of vaginal malformation,uterine malformation,vulva malformation,cervical malformation,and other malformations were 43.9%,43.5%,7.4%,2.3%,and 2.8%,respectively.Among patients with uterine malformation,34.5% underwent surgery for the genital tract malformation,whereas in patients with vaginal malformation,the proportion is 70.6%;the difference between the two groups was statistically significant （P 〈 0.01）.The percentage of complications of the urinary system in patients with vaginal malformations was 10.2%,which was statistically significantly higher than that （5.3%） in patients with uterine malformations （P 〈 0.01）.Conclusions：Compared to patients with uterine malformations,patients with vaginal malformations displayed more severe clinical symptoms,a younger surgical age,and a greater need for attention,early diagnosis,and treatment.Patients with genital tract malformations,particularly vaginal malformations,tend to have more complications of the urinary system and other malformations than patients with uterine malformations.

Germ-cell tumors of the central nervous system in Peking Union Medical College Hospital:A 20-year clinicopathologic review

To the Editor:Germ-cell tumors(GCTs)of the central nervous system(CNS),the morphologic,immunophenotypic,and(in some respects)genetic homologs of gonadal and other extraneuraxial germ-cell neoplasms,principally affect children and adolescents.[1]The diagnosis of GCT of the CNS is not difficult,and the major GCT types are germinoma,teratoma,yolk sac tumor(YST),embryonal carcinoma,and choriocarcinoma.Neoplasms harboringmultiple types are calledmixed GCT(MGCT).Peak incidence of GCT of the CNS occurs in patients aged 10 to 14 years,and a clear majority of cases of all histologic types involve males.GCT of the CNS seems to be more prevalent in eastern Asia than in Europe and the United States.[1-5]In Japan,70%of patients withGCT of CNS aged 10 to 24 years and 73%were males,[6]but there were limited Chinese patients’large-scale data,only two studies reportedmore than 100 cases.[7,8]Were the types and clinical characteristics of GCTs in the CNS in Chinese patients consistent with Japan’s?We reviewed all cases of GCTs in the CNS diagnosed by pathology in Peking Union Medical College Hospital from year 1999 to 2019.We retrospectively collected and analyzed all cases underwent optical microscopy and immunohistochemical staining examinations,aiming to summarize and analyze the clinicopathologic features of them.

Standard Operation Procedure of Percutaneous Endomyocardial Biopsy in Peking Union Medical College Hospital

Percutaneous endomyocardial biopsy (EMB) is a technique that biopsy samples are obtained using bioptome through peripheral blood vessel. This technique has been used and refined more than 50 years in clinical application. Now EMB has become an important diagnostic tool in the diagnosis of myocarditis and cardiomyopathy. Department of cardiology, Peking Union Medical College Hospital (PUMCH) has performed more than 500 cases of EMB and accumulated abundant practical experience. The clinical practice guideline of percutaneous EMB in PUMCH was also established, including indications, contradictions, operation key points, sample handling and processing, post-procedure monitoring, and treatment strategy for potential complications, etc. Due to the limitation of EMB, cardiologists should collaborate with experts in echocardiography, cardiac magnetic resonance and cardiac pathology to avoid missed diagnosis and misdiagnosis. Cardiologists should pay more attention to the value of EMB and actively perform EMB to improve the diagnosis level for myocarditis and cardiomyopathy in China.

Management of regional citrate anticoagulation for continuous renal replacement therapy:guideline recommendations from Chinese emergency medical doctor consensus

Continuous renal replacement therapy(CRRT)is widely used for treating critically-ill patients in the emergency department in China.Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT.Regional citrate anticoagulation(RCA)has been shown to potentially be safer and more effective,and is now recommended as the preferred anticoagulant method for CRRT.However,there is still a lack of unified standards for RCA management in the world,and there are many problems in using this method in clinical practice.The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association(CMDA)organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues,including the advantages and disadvantages of RCA in CRRT anticoagulation,the principle of RCA,parameter settings for RCA,monitoring of RCA(mainly metabolic acid-base disorders),and special issues during RCA.Based on the latest available research evidence as well as the paneled experts'clinical experience,considering the generalizability,suitability,and potential resource utilization,while also balancing clinical advantages and disadvantages,a total of 16 guideline recommendations were formed from the experts'consensus.

Advances in Medical Treatment of Primary Aldosteronism

Primary aldosteronism(PA)is the most common form of secondary hypertension,with its main manifestations including hypertension and hypokalemia.Early identification of PA is extremely important as PA patients can easily develop cardiovascular complications such as atrial fibrillation,stroke,and myocardial infarction.The past decade has witnessed the rapid advances in the genetics of PA,which has shed new light on PA treatment.While surgery is the first choice for unilateral diseases,bilateral lesions can be treated with mineralocorticoid receptor antagonists(MRAs).The next-generation non-steroidal MRAs are under investigations.New medications including calcium channel blockers,macrophage antibiotics,and aldosterone synthase inhibitors have provided a new perspective for the medical treatment of PA.

Text duplication of papers in four medical related fields

Purpose:To reveal the typical features of text duplication in papers from four medical fields:basic medicine,health management,pharmacology and pharmacy,and public health and preventive medicine.To analyze the reasons for duplication and provide suggestions for the management of medical academic misconduct.Design/methodology/approach:In total,2,469 representative Chinese journal papers were included in our research,which were submitted by researchers in 2020 and 2021.A plagiarism check was carried out using the Academic Misconduct Literature Check System(AMLC).We generated a corrected similarity index based on the AMLC general similarity index for further analysis.We compared the similarity indices of papers in four medical fields and revealed their trends over time;differences in similarity index between review and research articles were also analyzed according to the different fields.Further analysis of 143 papers suspected of plagiarism was also performed from the perspective of sections containing duplication and according to the field of research.Findings:Papers in the field of pharmacology and pharmacy had the highest similarity index(8.67±5.92%),which was significantly higher than that in other fields,except health management.The similarity index of review articles(9.77±10.28%)was significantly higher than that of research articles(7.41±6.26%).In total,143 papers were suspected of plagiarism(5.80%)with similarity indices≥15%;most were papers on health management(78,54.55%),followed by public health and preventive medicine(38,26.58%);90.21%of the 143 papers had duplication in multiple sections,while only 9.79%had duplication in a single section.The distribution of sections with duplication varied among different fields;papers in pharmacology and pharmacy were more likely to have duplication in the data/methods and introduction/background sections,however,papers in health management were more likely to contain duplication in the introduction/background or results/discussion sections.Different structures for papers in different fields may have caused these differences.Research limitations:There were three limitations to our research.Firstly,we observed that a small number of papers have been checked early.It is unknown who conducted the plagiarism check as this can be included in other evaluations,such as applications for Science and technology projects or awards.If the authors carried out the check,text with high similarity indices may have been excluded before submission,meaning the similarity index in our research may have been lower than the original value.Secondly,there were only four medical fields included in our research.Additional analysis on a wider scale is required in the future.Thirdly,only a general similarity index was calculated in our study;other similarity indices were not tested.Practical implications:A comprehensive analysis of similarity indices in four medical fields was performed.We made several recommendations for the supervision of medical academic misconduct and the formation of criteria for defining suspected plagiarism for medical papers,as well as for the improved accuracy of text duplication checks.Originality/value:We quantified the differences between the AMLC general similarity index and the corrected index,described the situation around text duplication and plagiarism in papers from four medical fields,and revealed differences in similarity indices between different article types.We also revealed differences in the sections containing duplication for papers with suspected plagiarism among different fields.

Long-term prognosis and its associated predictive factors in patients with eosinophilic gastroenteritis

BACKGROUND Eosinophilic gastroenteritis(EGE)is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract.Glucocorticoids remain the most common treatment method.However,disease relapse and glucocorticoid dependence remain notable problems.To date,few studies have illuminated the prognosis of EGE and risk factors for disease relapse.AIM To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up.METHODS This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022.Clinical records were collected and analyzed.Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival(RFS).RESULTS EGE showed a median onset age of 38 years and a slight female predominance(56.4%).The main clinical symptoms were abdominal pain(89.1%),diarrhea(61.8%),nausea(52.7%),distension(49.1%)and vomiting(47.3%).Forty-three(78.2%)patients received glucocorticoid treatment,and compared with patients without glucocorticoid treatments,they were more likely to have elevated serum immunoglobin E(IgE)(86.8%vs 50.0%,P=0.022)and descending duodenal involvement(62.8%vs 27.3%,P=0.046)at diagnosis.With a median follow-up of 67 mo,all patients survived,and 56.4%had at least one relapse.Six variables at baseline might have been associated with the overall RFS rate,including age at diagnosis<40 years[hazard ratio(HR)2.0408,95%confidence interval(CI):1.0082–4.1312,P=0.044],body mass index(BMI)>24 kg/m^(2)(HR 0.3922,95%CI:0.1916-0.8027,P=0.014),disease duration from symptom onset to diagnosis>3.5 mo(HR 2.4725,95%CI:1.220-5.0110,P=0.011),vomiting(HR 3.1259,95%CI:1.5246-6.4093,P=0.001),total serum IgE>300 KU/L at diagnosis(HR 0.2773,95%CI:0.1204-0.6384,P=0.022)and glucocorticoid treatment(HR 6.1434,95%CI:2.8446-13.2676,P=0.003).CONCLUSION In patients with EGE,younger onset age,longer disease course,vomiting and glucocorticoid treatment were risk factors for disease relapse,whereas higher BMI and total IgE level at baseline were protective.

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Notch信号通路——对健康和疾病的机械论观点

The Notch signaling pathway is evolutionarily conserved across metazoan species and plays key roles in many physiological processes.The Notch receptor is activated by two families of canonical ligands(Deltalike and Serrate/Jagged)where both ligands and receptors are single-pass transmembrane proteins usually with large extracellular domains,relative to their intracellular portions.Upon interaction of the core binding regions,presented on opposing cell surfaces,formation of the receptor/ligand complex initiates force-mediated proteolysis,ultimately releasing the transcriptionally-active Notch intracellular domain.This review focuses on structural features of the extracellular receptor/ligand complex,the role of posttranslational modifications in tuning this complex,the contribution of the cell membrane to ligand function,and insights from acquired and genetic diseases.

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Telomerase-related advances in hepatocellular carcinoma:A bibliometric and visual analysis

BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two decades.AIM To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase.METHODS The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were identified.We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences.VOSviewer was utilized to compile and visualize the bibliometric data.RESULTS A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in 2016.Up to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each paper.The United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and Japan.Among the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the University of Paris Cité,Public Assistance-Hospitals of Paris,and the National Institute of Health and Medical Research(INSERM)were the most prolific.As for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific authors.Kaneko S ranked first by H-index,G-index,and overall publication count,while Zucman-Rossi J ranked first in citation count.The five most popular journals were the World Journal of Gastroenterology,Hepatology,Journal of Hepatology,Oncotarget,and Oncogene,while Nature Genetics,Hepatology,and Nature Reviews Disease Primers had the most citations.We extracted 2293 keywords from the publications,120 of which appeared more than ten times.The most frequent were HCC,telomerase and human telomerase reverse transcriptase(hTERT).Keywords such as mutational landscape,TERT promoter mutations,landscape,risk,and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years.CONCLUSION Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.