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Abstract Background Sevoflurane (Sev) is a commonly used volatile anesthetic that might suppress the process of breast cancer. Also, circular RNAs (circRNAs) have been reported to partake in the pathogenesis of breast cancer. Accordingly, this research was designed to investigate the mechanism of hsa_circ_0005962 on Sev‐mediated breast cancer development. Methods Sev was applied to treat breast cancer cells. Cell proliferation ability, migration, invasion, and apoptosis were detected using Cell Counting Kit‐8 (CCK‐8), 5‐ethynyl‐2′‐deoxyuridine (EdU), Transwell, and flow cytometry assay. Proliferating cell nuclear antigen (PCNA), Matrix metallopeptidase 9 (MMP9), B‐cell lymphoma‐2 (Bcl‐2)‐associated X protein (Bax), and Epithelial stromal interaction 1 (EPSTI1) were assessed using western blot assay. circ_0000129, microRNA‐578 (miR‐578), and EPSTI1 levels were determined using real‐time quantitative polymerase chain reaction (RT‐qPCR). Using bioinformatics software (Circinteractome and Targetscan), the binding between miR‐578 and circ_0000129 or EPSTI1 were predicted, and proved using dual‐luciferase reporter and RNA pull‐down assay. The biological roles of circ_0000129 and Sevoflurane on tumor growth were analyzed using a xenograft tumor model in vivo. Results Sevoflurane blocked tumor cell proliferation, migration, invasion, and promoted apoptosis. Circ_0000129 and EPSTI1 expression were increased, and miR‐578 was decreased in breast cancer cells. Also, they presented an opposite trend in Sev‐treated tumor cells. Circ_0000129 upregulation might abolish Sev‐mediated tumor progression in vitro. Mechanically, circ_0000129 can affect EPSTI1 expression by sponging miR‐578. Sev might inhibit tumor growth by regulating circ_0000129 in vivo. Conclusion Circ_0000129 relieved Sev‐triggered suppression impacts on breast cancer development partly via the miR‐578/EPSTI1 axis, which provides a new mechanism for studying mediated therapy of breast cancer treatment.

Abstract Receptor‐interacting protein kinase 1 (RIPK1) mediates necroptosis and inflammation in various pathophysiologies, emerging as a pharmacological target for neurodegenerative and inflammatory indications. This phase I, first‐in‐human, placebo‐controlled study evaluated the safety, pharmacokinetics (PKs), and pharmacodynamics (PDs) of GFH312, an RIPK1 inhibitor, in healthy adults. Subjects received GFH312 as a single ascending dose up to 500 mg (part I) or once‐daily repeated doses up to 200 mg for 14 days (part II). PKs were assessed using plasma and cerebrospinal fluid (CSF); PDs were assessed by phospho‐RIPK1 levels. Seventy‐six subjects were enrolled between April 2021 and June 2022: 38 (part I) and 19 (part II) received GFH312; 14 and five received placebo, respectively. At least one treatment‐emergent adverse event (TEAE) occurred in 42.1% (part I) and 63.2% (part II) of subjects receiving GFH312, compared with 42.9% and 40.0% of subjects receiving placebo, respectively. The most common TEAE was headache (21.1%). Two treatment‐related TEAEs were reported in part I and four in part II. No serious TEAEs were reported. Systemic absorption was rapid; exposure (area under the concentration‐time curve from time zero to the last measurable concentration and maximum plasma concentration) increased with dose level. The GFH312 CSF concentration post 100 mg single dose was approximately fourfold higher than the half maximal inhibitory concentration of human monocyte‐derived macrophages necroptosis with expected central nervous system penetration. Subjects receiving GFH312 had decreased phospho‐RIPK1 levels in peripheral blood mononuclear cells postdose. In conclusion, GFH312 was well‐tolerated and demonstrated RIPK1 inhibition in healthy subjects. Ongoing studies will inform the use of GFH312 in potential indications.

Abstract Levetiracetam (LEV) is an anti‐epileptic drug approved for use in various populations. The pharmacokinetic (PK) behavior of LEV may be altered in the elderly and patients with renal and hepatic impairment. Thus, dosage adjustment is required. This study was conducted to investigate how the physiologically‐based PK (PBPK) model describes the PKs of LEV in adult and elderly populations, as well as to predict the PKs of LEV in patients with renal and hepatic impairment in both populations. The whole‐body PBPK models were developed using the reported physicochemical properties of LEV and clinical data. The models were validated using data from clinical studies with different dose ranges and different routes and intervals of administration. The fit performance of the models was assessed by comparing predicted and observed blood concentration data and PK parameters. It is recommended that the doses be reduced to ~70%, 60%, and 45% of the adult dose for the mild, moderate, and severe renal impairment populations and ~95%, 80%, and 57% of the adult dose for the Child Pugh‐A (CP‐A), Child Pugh‐B (CP‐B), and Child Pugh‐C (CP‐C) hepatic impairment populations, respectively. No dose adjustment is required for the healthy elderly population, but dose reduction is required for the elderly with organ dysfunction accordingly, on a scale similar to that of adults. A PBPK model of LEV was successfully developed to optimize dosing regimens for special populations.

Abstract Background The clinical effect of postoperative radiotherapy (PORT) in non‐malignant meningioma (NMM) has not been well explored. Methods A total of 8629 patients with NMM (surgery alone group: n = 7716, postoperative radiotherapy group: n = 913) were obtained from the Surveillance, Epidemiology, and End Results database. Patient profiles were matched by 1:1 propensity score matching (PSM). Logistic regression analysis was performed to identify factors associated with PORT versus surgery alone (SA). Univariate and multivariate Cox regression analyses determined prognostic variables with overall survival (OS) in NMM. Subgroup analyses were performed with Cox proportional hazards regression models. Results All the SA (n = 7716) and PORT (n = 913) groups were included. Women with PORT (66.3%) and SA (70.9%) were almost twice as likely as men, and tumors with benign behaviors in the SA group were almost seven times more frequent than those with malignant characteristics. We explored the demographic, clinical characteristics, and prognostic factors in NMM. Laterality, surgery, tumor size, diagnosis year, age, and tumor behavior were associated with PORT versus SA. Patients treated with PORT had better OS than those treated with SA (p = 0.03). After PSM, PORT remained comparable to SA (hazard ratio 0.56, 95% confidence interval 0.35–0.88, p = 0.013). In the subgroup analysis of PORT treatment, borderline malignant behavior increased the death risk by 23%, while other variables did not have a significant clinical benefit (p > 0.05). Conclusions Borderline malignant behavior should be considered seriously, and the PORT regimen should be actively implemented for patients with benign meningiomas.

Objective New vertebral compression fracture (NVCF) occurring after bone cement injection in middle‐aged and elderly patients with vertebral compression fracture is very common. Preoperative baseline characteristics and surgical treatment parameters have been widely studied as a risk factor, but the importance of the patients' laboratory indicators has not been thoroughly explored. We aimed to explore the relationship between laboratory indicators and NVCF, and attempt to construct a clinical prediction model of NVCF together with other risk factors. Methods Retrospective analysis was performed for 200 patients who underwent bone cement injection (percutaneous kyphoplasty or vertebroplasty) for vertebral compression fractures between January 2019 and January 2020. We consulted the relevant literature and collated the factors affecting the occurrence of NVCF. Feature selection of patients with NVCF was optimized using the least absolute shrinkage and selection operator regression model, which was used to conduct multivariable logistic regression analysis, to create a predictive model incorporating the selected features. The discrimination, calibration, and clinical feasibility of the predictive model were assessed using the concordance index (C‐index), calibration plots, and decision curve analysis. Internal validation was performed using Bootstrap resampling verification. Results Time from injury to surgery exceeding 7 days, low osteocalcin levels, elevated homocysteine levels, osteoporosis, mode of operation (percutaneous vertebroplasty), lack of postoperative anti‐osteoporosis treatment, and poor diffusion of bone cement were independent risk factors for NVCF in middle‐aged and elderly patients with vertebral compression fracture after bone cement injection. The C‐index of the nomogram constructed using these seven factors was 0.895, indicating good discriminatory ability. The calibration plot showed that the model was well calibrated. Bootstrap resampling verification yielded a significant C‐index of 0.866. Decision curve analysis demonstrated that the greatest clinical net benefit for predicting NVCF after bone cement injection could be achieved with a threshold of 1%–91%. Conclusion This nomogram can effectively predict NVCF incidence after bone cement injection in middle‐aged and elderly patients with vertebral compression fracture, thus aiding clinical decision‐making and postoperative management, promoting effective postoperative rehabilitation, and improving the quality of life.

Abstract Pesticide resistance relies on a myriad of mechanisms, ranging from single mutations to a complex and polygenic architecture, and it involves mechanisms such as target‐site insensitivity, metabolic detoxification, or a combination of these, with either additive or synergistic effects. Several resistance mechanisms against abamectin, a macrocyclic lactone widely used in crop protection, have been reported in the cosmopolitan pest Tetranychus urticae. However, it has been shown that a single mechanism cannot account for the high levels of abamectin resistance found across different mite populations. Here, we used experimental evolution combined with bulked segregant analyses to map quantitative trait loci (QTL) associated with abamectin resistance in two genetically unrelated populations of T. urticae. In these two independent QTL mapping experiments, three and four QTLs were identified, of which three were shared between experiments. Shared QTLs contained genes encoding subunits of the glutamate‐gated chloride channel (GluCl) and harboured previously reported mutations, including G314D in GluCl1 and G326E in GluCl3, but also novel resistance candidate loci, including DNA helicases and chemosensory receptors. Surprisingly, the fourth QTL, present only in only one of the experiments and thus unique for one resistant parental line, revealed a non‐functional variant of GluCl2, suggesting gene knock‐out as resistance mechanism. Our study uncovers the complex basis of abamectin resistance, and it highlights the intraspecific diversity of genetic mechanisms underlying resistance in a cosmopolitan pest.

Abstract Background To evaluate the surgical safety in myasthenia gravis (MG) patients aged 65 and over. Methods A total of 564 patients with MG who underwent surgery in the Department of Thoracic Surgery of Beijing Hospital from November 2011 to March 2022 were included in the study and divided into two groups taking the age of 65 as the boundary. Perioperative data of patients were recorded and statistically analyzed. Results Compared with young patients, FEV1, FEV1% and MVV in lung function of elderly MG patients were worse (p

Abstract Objective To study the influencing factors of myasthenic crisis in patients with myasthenia gravis during perioperative period. Methods A total of 564 myasthenia gravis (MG) patients who underwent standard expanded resection of thymoma/thymoma in the Department of Thoracic Surgery of Beijing Hospital from January 2011 to March 2022 were retrospectively included in the study. Clinical indicators such as gender, age, thymoma, American Society of Anesthesiologists (ASA) score, operation time, intraoperative blood loss, and some others were recorded. Results Osserman‐stages IIB + III + IV (odds ratio [OR] 16.091, 95% confidence interval [CI] 5.170–50.076, p value

Abstract Background The global Phase III IMpower132 study evaluating atezolizumab plus pemetrexed and carboplatin or cisplatin (APP) versus pemetrexed plus carboplatin or cisplatin (PP) for first‐line treatment of non‐squamous advanced non‐small cell lung cancer (NSCLC) met its co‐primary progression‐free survival (PFS) endpoint at the primary analysis in the intention‐to‐treat (ITT) population. Although the co‐primary overall survival (OS) endpoint was not met, numerical OS improvement favoring APP over PP was observed at the final analysis. We report primary results for Chinese patients in IMpower132. Methods Treatment‐naive Chinese patients with non‐squamous stage IV EGFR/ALK mutation‐negative NSCLC were randomized 1:1 to receive 4 or 6 cycles of APP or PP, followed by maintenance atezolizumab plus pemetrexed or pemetrexed. Co‐primary endpoints were investigator‐assessed PFS and OS. Results The ITT population included 163 Chinese patients (82 in the APP arm and 81 in the PP arm). At data cutoff (median follow‐up, 11.7 months), the median PFS in the APP and PP arms was 8.3 and 5.8 months, respectively; the unstratified hazard ratio (HR) was 0.73 (95% CI: 0.50, 1.08). At the interim OS analysis, median OS was not estimable in either arm; the unstratified HR was 0.70 (95% CI: 0.40, 1.24). No new safety signals were observed. Conclusion Among Chinese patients in IMpower132, PFS benefit was seen with APP versus PP. Though interim OS data were immature, there was a trend toward OS benefit favoring APP versus PP. The safety profile of the APP was consistent with the known risks of the individual treatment components. ClinicalTrials.gov: NCT02657434.

Abstract Background Myasthenia gravis (MG) patients are reported to have a high risk of other autoimmune diseases (ADs), and thymectomy may increase the risk further. A cohort of MG patients in which thymectomy was performed were investigated to analyze the prevalence, types and features of the new onset ADs. Methods Consecutive patients with MG who underwent thymectomy at Beijing Hospital between January 2012 and August 2021 were retrospectively enrolled. Patients with a postoperative follow‐up period shorter than a year or incomplete clinical records were excluded. Clinical and follow‐up data were collected. Statistical analyses were performed using SPSS version 22.0. Results A total of 445 patients were included in this study. The median follow‐up period was 72 months (range, 12–135 months). A total of 63 (14.2%) MG patients had concurrent ADs. The incidence rate was higher than the background prevalence of population (5%), and also higher than that of a former Chinese MG cohort (11.6%). A total of 47 patients (10.6%) were diagnosed with ADs before thymectomy, and 19 (4.3%) developed a new AD after thymectomy. The most common types of new onset ADs after thymectomy were Hashimoto's thyroiditis and rheumatoid arthritis (RA), which were different from those before thymectomy (hyperthyroidism and Hashimoto's thyroiditis). The incidence rate of new onset RA (1.35%) was higher than the frequency of RA before thymectomy (0.45%), and also higher than the incidence rate in a Chinese MG cohort (0.5%). There was a higher proportion of female patients (p = 0.026) with postoperative ADs. A younger age at operation may increase the risk of nonthymoma MG patients (p = 0.040) developing ADs. The postoperative treatment effect of MG was similar between patients with and without new onset ADs (p > 0.05). Conclusions We observed a higher incidence rate of autoimmune diseases, especially rheumatoid arthritis, in MG patients after thymectomy. The most common types of ADs after thymectomy were different from those before thymectomy. New onset ADs tended to occur in female and young nonthymoma MG patients. The postoperative effect of MG was not related with the new occurrence of ADs.

Abstract Background High fasting plasma glucose (HFPG) is the leading risk factor contributing to the increase of stroke burden in the past three decades. However, the global distribution of stroke burden specifically attributable to HFPG was not studied in depth. Therefore, we analyzed the HFPG‐attributable burden in stroke and its subtypes in 204 countries and territories from 1990 to 2019. Methods Detailed data on stroke burden attributable to HFPG were obtained from the Global Burden of Disease Study 2019. The numbers and age‐standardized rates of stroke disability‐adjusted life years (DALYs), deaths, years lived with disability, and years of life lost between 1990 and 2019 were estimated by age, sex, and region. Results In 2019, the age‐standardized rate of DALYs (ASDR) of HFPG‐attributable stroke was 354.95 per 100 000 population, among which 49.0% was from ischemic stroke, 44.3% from intracerebral hemorrhage, and 6.6% from subarachnoid hemorrhage. The ASDRs of HFPG‐attributable stroke in lower sociodemographic index (SDI) regions surpassed those in higher SDI regions in the past three decades. Generally, the population aged over 50 years old accounted for 92% of stroke DALYs attributable to HFPG, and males are more susceptible to HFPG‐attributable stroke than females across their lifetime. Conclusions Successful key population initiatives targeting HFPG may mitigate the stroke disease burden. Given the soaring population‐attributable fractions of HFPG for stroke burden worldwide, each country should assess its disease burden and determine targeted prevention and control strategies.

Abstract Background We examined attitudes toward the COVID‐19 vaccine, potential factors underlying these attitudes, and ways to increase vaccination willingness in autoimmune inflammatory rheumatic diseases (AIIRD) patients. Methods A multicenter, web‐based, observational survey using an online questionnaire was conducted among AIIRD patients aged ≥18 years from May 24, 2021, to June 3, 2021. Participants were 3104 AIIRD patients (2921 unvaccinated and 183 vaccinated). Results Of the unvaccinated patients, 32.9% were willing to receive the COVID‐19 vaccine, 45.0% were uncertain, and 14.8% were unwilling. When vaccination was recommended by physicians, patients' willingness increased to 93.8%. Participants' main concerns were that the vaccine may aggravate AIIRD disease (63.0%) and may cause vaccine‐related adverse events (19.9%). Female patients were less likely to be vaccinated. However, patients who had children aged ≤18 years were more willing to be vaccinated. In addition, vaccination willingness was higher in patients with trust in the safety and efficacy of the COVID‐19 vaccine. Notably, 183 (5.9%) patients were vaccinated. The major vaccination side effects were injection reaction, myalgia, and fatigue. At a median follow‐up of 88 (38, 131) days, patients' disease activities were stable. Conclusions The findings show that AIIRD patients were unwilling to receive the COVID‐19 vaccine because of fears of potential disease exacerbation and additional adverse events. Sociodemographic characteristics and concerns about COVID‐19 disease and vaccines had a significant effect on vaccination willingness.

Abstract Background Interleukin‐15 (IL‐15) is a promising immunotherapeutic agent owing to its powerful immune‐activating effects. However, the clinical benefits of these treatments are limited. Crosstalk between tumor cells and immune cells plays an important role in immune escape and immunotherapy drug resistance. Herein, this study aimed to obtain in‐depth understanding of crosstalk in the tumor microenvironment for providing potential therapeutic strategies to prevent tumor progression. Methods T‐cell killing assays and co‐culture models were developed to determine the role of crosstalk between macrophages and tumor cells in breast cancer resistant to IL‐15. Western blotting, histological analysis, CRISPR‐Cas9 knockout, multi‐parameter flow cytometry, and tumor cell‐macrophage co‐injection mouse models were developed to examine the mechanism by which IL‐15Rα+ tumor‐associated macrophages (TAMs) regulate breast cancer cell resistance to IL‐15. Results We found that macrophages contributed to the resistance of tumor cells to IL‐15, and tumor cells induced macrophages to express high levels of the α subunit of the IL‐15 receptor (IL‐15Rα). Further investigation showed that IL‐15Rα+ TAMs reduced the protein levels of chemokine CX3C chemokine ligand 1 (CX3CL1) in tumor cells to inhibit the recruitment of CD8+ T cells by releasing the IL‐15/IL‐15Rα complex (IL‐15Rc). Administration of an IL‐15Rc blocking peptide markedly suppressed breast tumor growth and overcame the resistance of cancer cells to anti‐ programmed cell death protein 1 (PD‐1) antibody immunotherapy. Interestingly, Granulocyte‐macrophage colony‐stimulating factor (GMCSF) induced γ chain (γc) expression to promote tumor cell‐macrophage crosstalk, which facilitated tumor resistance to IL‐15. Additionally, we observed that the non‐transcriptional regulatory function of hypoxia inducible factor‐1alpha (HIF‐1α) was essential for IL‐15Rc to regulate CX3CL1 expression in tumor cells. Conclusions The IL‐15Rc‐HIF‐1α‐CX3CL1 signaling pathway serves as a crosstalk between macrophages and tumor cells in the tumor microenvironment of breast cancer. Targeting this pathway may provide a potential therapeutic strategy for enhancing the efficacy of cancer immunotherapy.

Abstract Film dielectric capacitors have been widely used in high‐power electronic equipment. The design of microstructure and the choice of fillers play an important role in nanocomposites' energy storage density. Machine learning methods can classify and summarise the limited data and then explore the promising composite structure. In this work, a dataset has been established, which contained a large amount of data on the maximum energy storage density of nanocomposites. Though using processed visual image information to express the internal information of composite, the prediction accuracy of the prediction models built by three machine learning algorithms increase from 84.1% to 91.9%, 80.9% to 68.9%, 70.6% to 81.6%, respectively. By calculating the branch weight in the random forest prediction model, the influence degree of different descriptors on the energy storage performance of nanocomposites is analysed. A total of 10 groups of composites with different structure and filler amount were prepared in the laboratory, which were used to verify the reliability of prediction models. Finally, the effective filler's structure is explored by three prediction models and some suggestions for the interface design of filler are given.

Abstract The roles of oncogenic KRAS in tumor immune evasion remain poorly understood. Here, mutant KRAS is identified as a key driver of tumor immune evasion in colorectal cancer (CRC). In human CRC specimens, a significant reduction in cytotoxic CD8+ T‐cell tumor infiltration is found in patients with mutant versus wild type KRAS. This phenomenon is confirmed by preclinical models of CRC, and further study showed KRAS mutant tumors exhibited poor response to anti‐PD‐1 and adoptive T‐cell therapies. Mechanistic analysis revealed lactic acid derived from mutant KRAS‐expressing tumor cells sensitized tumor‐specific cytotoxic CD8+ T‐cells to activation‐induced cell death via NF‐κB inactivation; this may underlie the inverse association between intratumoral cytotoxic CD8+ T‐cells and KRAS mutation. Importantly, KRAS mutated tumor resistance to immunotherapies can be overcome by inhibiting KRAS or blocking lactic acid production. Together, this work suggests the KRAS‐mediated immune program is an exploitable therapeutic approach for the treatment of patients with KRAS mutant CRC.

Abstract Aim This study aimed to describe and visualize the current research state and collaborative networks in home care safety for older adults over the past 11 years to analyse the gaps of research and future research trends. Background The amount of research on safety in home care for older adults is increasing. It is necessary to understand the status of development and main research topics and identify the main contributors and their relationships. Methods A total of 2,631 publications were retrieved from the Web of Science. The external characteristics of the publications were summarized with the Web of Science and Histcite. Collaborative networks and keywords were analysed and visually displayed using analysis tools. Results The number of articles increased over the years. Articles were identified from 79 countries, 3,630 institutions, 647 journals and 11,691 authors, and complex cooperative relations among them and five research topics were identified. Conclusion Research on home care safety for older adults is developing steadily, and this field may be understood to a greater extent in the future. Countries, institutions and scholars need to cooperate more in this research field. Implications for Nursing Management This study contributes important information for understanding achievements in the research field of home care safety and provides insights into future research.

Background The detection rate of bilateral multiple pulmonary nodules (BMPNs) is increasing due to widespread use of chest computed tomography (CT) screening. However, there is no consensus on the treatment options for BMPNs and whether simultaneous bilateral pulmonary resection is safe remains controversial. The purpose of this study was to evaluate the feasibility and safety of simultaneous bilateral pulmonary resection for BMPNs. Methods A total of 16 consecutive patients with BMPNs who underwent simultaneous bilateral pulmonary resection in Beijing Hospital from June 2013 to July 2020 were enrolled in this study. Clinical characteristics, imaging and pathological features, and perioperative outcomes were retrospectively reviewed. Results There were 10 males and six females included in the study with a mean age of 61.9 (range: 39–78) years. A total of 35 nodules were resected in 16 patients including 12 patients with bilateral primary lung cancer, three patients with primary lung cancer on one side and a benign nodule on the contralateral side, and one patient with bilateral benign nodules. All patients underwent bilateral pulmonary resection via single‐utility port video‐assisted thoracoscopic surgery (VATS). Nine, four, two, and one patients underwent lobectomy with contralateral segmentectomy or wedge resection, segmentectomy with contralateral wedge resection, bilateral segmentectomy and bilateral wedge resection, respectively. All operations were accomplished successfully without intraoperative blood transfusion, conversion to thoracotomy, major complication and postoperative 90‐day death. The mean operation time was 220.1 ± 65.6 minutes, median thoracic drainage duration was four days (range: 2–8 days), mean pleural drainage was 1387.5 ± 694.7 mL, and median postoperative hospital stay was seven days (range: 5–18 days). There were three cases (18.8%) of minor complications, including one case of pulmonary air leakage, one case of atrial fibrillation, and one case of poor healing of surgical site. A total of 50% (8/16) of the patients had severe postoperative pain and required additional analgesia. Conclusions For selected patients, simultaneous bilateral pulmonary resection via single‐utility port VATS is a safe and feasible minimally invasive procedure for BMPNs. Adequate postoperative analgesia via a multimodal analgesia strategy should be used to prevent postoperative pain. Key points Significant findings of the study The incidence of major complication after minimally invasive bilateral pulmonary resection is low for patients with good pulmonary function, but there is a relatively high incidence of minor complications and pain at the surgical site. Adequate postoperative analgesia via multimodal analgesia strategy should be used to prevent postoperative pain. What this study adds For the treatment of bilateral multiple pulmonary nodules, simultaneous bilateral pulmonary resection via single‐utility port video‐assisted thoracoscopic surgery is safe and feasible for selected patients.

Abstract Introduction Stress‐related brain disorders can be associated with glucocorticoid disturbance and hippocampal alteration. However, it remains largely unknown how cortisol affects the structure and function of hippocampus. Cushing's disease (CD) provides a unique “hyperexpression model” to explore the effects of excessive cortisol on hippocampus as well as the relation between these effects and neuropsychological deficits. Methods We acquired high‐resolution T1‐weighted and resting‐state functional magnetic resonance imaging in 47 CD patients and 53 healthy controls. We obtained the volume and functional connectivity of the hippocampal rostral and caudal subregions in both groups. Relationships between hippocampal alterations, neuroendocrine, and neuropsychological assessments were identified. Results Relative to control subjects, the CD patients had smaller volumes of all four hippocampal subregions. Furthermore, whole brain resting‐state functional connectivity analyses with these four different hippocampal regions as seeds revealed altered hippocampal functional connectivity with high‐order networks, involving the DMN, frontoparietal, and limbic networks in CD patients. The intrinsic hippocampal functional connectivity was associated with the quality of life of the CD patients. Conclusions Our findings elucidate the cumulative effect of excess cortisol on the morphology and function of hippocampus and reinforce the need for effective interventions in stress‐related brain disease to halt potential hippocampal damage.

Abstract The aim of our study was to explore the value of the 8th edition TNM staging system on evaluating the prognosis of colorectal carcinoid. Colorectal carcinoid patients between 1988 and 2015 were selected in the Surveillance, Epidemiology, and End Results Program (SEER) database for analysis. About 4286 patients with colorectal carcinoid tumors were identified, of which were carcinoid tumor NOS (n = 1726), neuroendocrine carcinoma (NEC) (n = 1346) and other carcinoid tumor (OCT) (n = 591). Worsening 10‐year CSS rates with increasing N status, M status, and SEER historic stage were demonstrated across all three above groups (all P