A candidate super-Earth planet orbiting near the snow line of Barnard's star.

Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs1, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known2,3 and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging4-6, astrometry7,8 and direct imaging9, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.

Prediction of programmed death-1 expression status in non-small cell lung cancer based on intratumoural and peritumoral computed tomography (CT) radiomics nomogram.

AIMS: This study aimed to predict the expression of programmed death-1 (PD-1) in non-small cell lung cancer (NSCLC) using intratumoral and peritumoral computed tomography (CT) radiomics nomogram. MATERIALS AND METHODS: Two hundred patients pathologically diagnosed with NSCLC from two hospitals were retrospectively analyzed. Of these, 159 NSCLC patients from our hospital were randomly divided into a training cohort (n=96) and an internal validation cohort (n=63) at a ratio of 6:4, while 41 NSCLC patients from another medical institution served as the external validation cohort. The radiomic features of the gross tumor volume (GTV) and peritumoral volume (PTV) were extracted from the CT images. Optimal radiomics features were selected using least absolute shrinkage and selection operator regression analysis. Finally, a CT radiomics nomogram of clinically independent predictors combined with the best rad-score was constructed. RESULTS: Compared with the 'GTV' and 'PTV' radiomics models, the combined 'GTV + PTV' radiomics model showed better predictive performance, and its area under the curve (AUC) values in the training, internal validation, and external validation cohorts were 0.90 (95% confidence interval [CI]: 0.83-0.97), 0.85 (95% CI: 0.74-0.96) and 0.78 (95% CI: 0.63-0.92). The nomogram constructed by the rad-score of the 'GTV + PTV' radiomics model combined with clinical independent predictors (prealbumin and monocyte) had the best performance, with AUC values in each cohort being 0.92 (95% CI: 0.85-0.98), 0.88 (95% CI: 0.78-0.97), and 0.80 (95% CI: 0.66-0.94), respectively. CONCLUSION: The intratumoral and peritumoral CT radiomics nomogram may facilitate individualized prediction of PD-1 expression status in patients with NSCLC.

Fragmentomic analysis of circulating tumor DNA-targeted cancer panels.

BACKGROUND: The isolation of cell-free DNA (cfDNA) from the bloodstream can be used to detect and analyze somatic alterations in circulating tumor DNA (ctDNA), and multiple cfDNA-targeted sequencing panels are now commercially available for Food and Drug Administration (FDA)-approved biomarker indications to guide treatment. More recently, cfDNA fragmentation patterns have emerged as a tool to infer epigenomic and transcriptomic information. However, most of these analyses used whole-genome sequencing, which is insufficient to identify FDA-approved biomarker indications in a cost-effective manner. PATIENTS AND METHODS: We used machine learning models of fragmentation patterns at the first coding exon in standard targeted cancer gene cfDNA sequencing panels to distinguish between cancer and non-cancer patients, as well as the specific tumor type and subtype. We assessed this approach in two independent cohorts: a published cohort from GRAIL (breast, lung, and prostate cancers, non-cancer, n = 198) and an institutional cohort from the University of Wisconsin (UW; breast, lung, prostate, bladder cancers, n = 320). Each cohort was split 70%/30% into training and validation sets. RESULTS: In the UW cohort, training cross-validated accuracy was 82.1%, and accuracy in the independent validation cohort was 86.6% despite a median ctDNA fraction of only 0.06. In the GRAIL cohort, to assess how this approach performs in very low ctDNA fractions, training and independent validation were split based on ctDNA fraction. Training cross-validated accuracy was 80.6%, and accuracy in the independent validation cohort was 76.3%. In the validation cohort where the ctDNA fractions were all <0.05 and as low as 0.0003, the cancer versus non-cancer area under the curve was 0.99. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that sequencing from targeted cfDNA panels can be utilized to analyze fragmentation patterns to classify cancer types, dramatically expanding the potential capabilities of existing clinically used panels at minimal additional cost.

Transcriptomic and clinical heterogeneity of metastatic disease timing within metastatic castration-sensitive prostate cancer.

BACKGROUND: Metastatic castration-sensitive prostate cancer (mCSPC) is commonly classified into high- and low-volume subgroups which have demonstrated differential biology, prognosis, and response to therapy. Timing of metastasis has similarly demonstrated differences in clinical outcomes; however, less is known about any underlying biologic differences between these disease states. Herein, we aim to compare transcriptomic differences between synchronous and metachronous mCSPC and identify any differential responses to therapy. PATIENTS AND METHODS: We performed an international multi-institutional retrospective review of men with mCSPC who completed RNA expression profiling evaluation of their primary tumor. Patients were stratified according to disease timing (synchronous versus metachronous). The primary endpoint was to identify differences in transcriptomic profiles between disease timing. The median transcriptomic scores between groups were compared with the Mann-Whitney U test. Secondary analyses included determining clinical and transcriptomic variables associated with overall survival (OS) from the time of metastasis. Survival analysis was carried out with the Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 252 patients were included with a median follow-up of 39.6 months. Patients with synchronous disease experienced worse 5-year OS (39% versus 79%; P < 0.01) and demonstrated lower median androgen receptor (AR) activity (11.78 versus 12.64; P < 0.01) and hallmark androgen response (HAR; 3.15 versus 3.32; P < 0.01). Multivariable Cox regression identified only high-volume disease [hazard ratio (HR) = 4.97, 95% confidence interval (CI) 2.71-9.10; P < 0.01] and HAR score (HR = 0.51, 95% CI 0.28-0.88; P = 0.02) significantly associated with OS. Finally, patients with synchronous (HR = 0.47, 95% CI 0.30-0.72; P < 0.01) but not metachronous (HR = 1.37, 95% CI 0.50-3.92; P = 0.56) disease were found to have better OS with AR and non-AR combination therapy as compared with monotherapy (P value for interaction = 0.05). CONCLUSIONS: We have demonstrated a potential biologic difference between metastatic timing of mCSPC. Specifically, for patients with low-volume disease, those with metachronous low-volume disease have a more hormone-dependent transcriptional profile and exhibit a better prognosis than synchronous low-volume disease.

Preparation and Evaluation of Bacterial Nanocellulose/Hyaluronic Acid Composite Artificial Cornea for Application of Corneal Transplantation.

The treatment for corneal damage requires donor corneal transplantation, but there is a serious scarcity of donor corneas worldwide. In this study, we aimed to design a new artificial cornea with good cytocompatibility, excellent optical properties and suture resistance, and great moisturizing properties. A new bacterial nanocellulose (BNC) membrane with anisotropic mechanical properties and high light transmission was produced in a horizontal rotary drum reactor. However, as a potential material for artificial keratoplasty, the transparency and mechanical properties of the new BNC membrane were not satisfactory. Thus, hyaluronic acid (HA) was introduced in the BNC to synthesize the BNC/HA composite membrane by using 1,4-butanediol diglycidyl ether (BDDE) as the chemical cross-linking agent. The micro-morphology, light transmittance, mechanical properties, water content, moisture retention ability, and cytocompatibility of the composite membranes were further evaluated. HA was fixed in the BNC network by the ether bond, and the composite membrane was found to have excellent light transmittance (up to 95.96%). The composite membrane showed excellent mechanical properties, for instance, its tensile strength exceeded the human normal intraocular pressure (IOP) (1.33-2.80 kPa), the maximum burst pressure was about 130 kPa, 46-97 times that of the normal IOP, and its suture force was close to that of the human amniotic membrane (0.1 N). Based on the three-dimensional network scaffold of BNC and the high water absorption characteristics of HA, the artificial cornea had high water content and high moisture retention ability. The rabbit corneal stromal cells cultured in vitro showed that the artificial cornea substitute had excellent cytocompatibility. BDDE is the most frequently used cross-linker in most HA products in the current cosmetic medicine industry owing to its long-term safety records for over 15 years. Therefore, the BNC/HA composite hydrogel cross-linked with BDDE has great potential in artificial keratoplasty or ocular surface repair.

Radiomics nomogram integrating intratumoural and peritumoural features to predict lymph node metastasis and prognosis in clinical stage IA non-small cell lung cancer: a two-centre study.

AIM: To investigate the value of a radiomics nomogram integrating intratumoural and peritumoural features in predicting lymph node metastasis and overall survival (OS) in patients with clinical stage IA non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This study retrospectively enrolled 199 patients (training cohort: 71 patients from Affiliated Tumour Hospital of Nantong University; internal validation cohort: 46 patients from Affiliated Tumour Hospital of Nantong University; external validation cohort: 82 patients from the public database). CT radiomics models were constructed based on four volumes of interest: gross tumour volume (GTV), gross and 3 mm peritumoural volume (GPTV3), gross and 6 mm peritumoural volume (GPTV6), and gross and 9 mm peritumoural volume (GPTV9). The optimal radiomics signature was further combined with independent clinical predictors to develop a nomogram. Univariable and multivariable Cox regression analysis were applied to determine the relationship between factors and OS. RESULTS: GPTV6 radiomics yielded better performance than GTV, GPTV3, and, GPTV9 radiomics in the training (area under the curve [AUC], 0.81), internal validation (AUC, 0.79), and external validation cohorts (AUC, 0.71), respectively. The nomogram integrating GPTV6 radiomics and spiculation improved predictive ability, with AUCs of 0.85, 0.80, and 0.74 in three cohorts, respectively. Pathological lymph node metastasis, nomogram-predicted lymph node metastasis, and pleural indentation were independent risk predictors of OS (p<0.05). CONCLUSIONS: The nomogram integrating GPTV6 radiomics features and independent clinical predictors performed well in predicting lymph node metastasis and prognosis in patients with clinical stage IA NSCLC.

CT-based radiomics nomogram for the preoperative prediction of microsatellite instability and clinical outcomes in colorectal cancer: a multicentre study.

AIM: To develop and validate a computed tomography (CT)-based radiomics nomogram for preoperative prediction of microsatellite instability (MSI) status and clinical outcomes in colorectal cancer (CRC) patients. MATERIALS AND METHODS: This retrospective study enrolled 497 CRC patients from three centres. Least absolute shrinkage and selection operator regression was utilised for feature selection and constructing the radiomics signature. Univariate and multivariate logistic regression analyses were employed to identify significant clinical variables. The radiomics nomogram was constructed by integrating the radiomics signature and the identified clinical variables. The performance of the nomogram was evaluated through receiver operating characteristic curves, calibration curves, and decision curve analysis. Kaplan-Meier analysis was performed to investigate the prognostic value of the nomogram. RESULTS: The radiomics signature comprised 10 radiomics features associated with MSI status. The nomogram, integrating the radiomics signature and independent predictors (age, location, and thickness), demonstrated favourable calibration and discrimination, achieving areas under the receiver operating characteristic (ROC) curves (AUCs) of 0.89 (95% confidence interval [CI]: 0.83-0.95), 0.87 (95% CI: 0.79-0.95), 0.88 (95% CI: 0.81-0.96), and 0.86 (95% CI: 0.78-0.93) in the training cohort, internal validation cohort, and two external validation cohorts, respectively. The nomogram exhibited superior performance compared to the clinical model (p<0.05). Additionally, survival analysis demonstrated that the nomogram successfully stratified stage II CRC patients based on prognosis (hazard ratio [HR]: 0.357, p=0.022). CONCLUSION: The radiomics nomogram demonstrated promising performance in predicting MSI status and stratifying the prognosis of patients with CRC.

Radiomics model and clinical scale for the preoperative diagnosis of silent corticotroph adenomas.

OBJECTIVE: Silent corticotroph adenomas (SCAs) are a subtype of nonfunctioning pituitary adenomas that exhibit more aggressive behavior. However, rapid and accurate preoperative diagnostic methods are currently lacking. DESIGN: The purpose of this study was to examine the differences between SCA and non-SCA features and to establish radiomics models and a clinical scale for rapid and accurate prediction. METHODS: A total of 260 patients (72 SCAs vs. 188 NSCAs) with nonfunctioning adenomas from Peking Union Medical College Hospital were enrolled in the study as the internal dataset. Thirty-five patients (6 SCAs vs. 29 NSCAs) from Fuzhou General Hospital were enrolled as the external dataset. Radiomics models and an SCA scale to preoperatively diagnose SCAs were established based on MR images and clinical features. RESULTS: There were more female patients (internal dataset: p < 0.001; external dataset: p = 0.028) and more multiple microcystic changes (internal dataset: p < 0.001; external dataset: p = 0.012) in the SCA group. MRI showed more invasiveness (higher Knosp grades, p ≤ 0.001). The radiomics model achieved AUCs of 0.931 and 0.937 in the internal and external datasets, respectively. The clinical scale achieved an AUC of 0.877 and a sensitivity of 0.952 in the internal dataset and an AUC of 0.899 and a sensitivity of 1.0 in the external dataset. CONCLUSIONS: Based on clinical information and imaging characteristics, the constructed radiomics model achieved high preoperative diagnostic ability. The SCA scale achieved the purpose of rapidity and practicality while ensuring sensitivity, which is conducive to simplifying clinical work.

In vitro and in vivo Inhibitory Activity of C-glycoside Flavonoid Extracts from Mung Bean Coat on Pancreatic Lipase and α-glucosidase.

Mung bean is a kind of legume commonly eaten by human. In the present study, a HPLC method for analyzing of two C-glycoside flavonoids, isovitexin and vitexin, in Mung bean was developed. Results showed that the flavonoids are mainly existed in Mung bean coat (MBC), while kernel contains very trace. The extraction of C-glycoside flavonoids from MBC was optimized. MBC extracts with isovitexin and vitexin contents of 29.0 ± 0.28% and 35.8 ± 0.19% were obtained with yield of 1.6 ± 0.21%. MBC extracts exhibited inhibitory activities on pancreatic lipase and α-glucosidase with IC50 values of 0.147 mg/ml and 0.226 mg/ml, respectively. The inhibitory kinetics revealed that MBC extracts showed mixed-type inhibition on these enzymes. Fluorescence quenching titration confirmed the binding of MBC extracts with the enzyme proteins. In vivo study revealed that pre-administration with MBC extracts significantly reduced the triglyceride absorption. Furthermore, it also improved postprandial hyperglycemia in rats through the inhibition of α-glucosidase.

Three Dose Levels of a Maternal Respiratory Syncytial Virus Vaccine Candidate Are Well Tolerated and Immunogenic in a Randomized Trial in Nonpregnant Women.

BACKGROUND: Respiratory syncytial virus (RSV) causes respiratory tract infections, which may require hospitalization especially in early infancy. Transplacental transfer of RSV antibodies could confer protection to infants in their first months of life. METHODS: In this first-in-human, placebo-controlled study, 502 healthy nonpregnant women were randomized 1:1:1:1 to receive a single dose of unadjuvanted vaccine containing 30/60/120 µg of RSV fusion (F) protein stabilized in the prefusion conformation (RSVPreF3) or placebo. RESULTS: Solicited local adverse events (AEs) were more frequently reported in the RSVPreF3 groups (4%-53.2%) versus placebo (0%-15.9%); most were mild/moderate. Unsolicited AEs were comparably reported among groups. Three serious AEs were reported; none was vaccination-related. Compared with prevaccination values, anti-RSV A neutralizing antibody geometric mean titers and anti-RSVPreF3 immunoglobulin G geometric mean concentrations increased 8- to 14-fold and 12- to 21-fold at day 8 and persisted 5- to 6-fold and 6- to 8-fold higher until day 91 in the RSVPreF3 groups versus 1-fold in placebo. Comparisons at day 8 and day 31 showed that the higher dose levels were significantly more immunogenic than the lowest one. CONCLUSIONS: The RSVPreF3 vaccine was well tolerated and immunogenic. The 60 and 120 µg dose levels were selected for further investigation in pregnant women. CLINICAL TRIALS REGISTRATION: NCT03674177.

A non-coding RNA balancing act: miR-346-induced DNA damage is limited by the long non-coding RNA NORAD in prostate cancer.

BACKGROUND: miR-346 was identified as an activator of Androgen Receptor (AR) signalling that associates with DNA damage response (DDR)-linked transcripts in prostate cancer (PC). We sought to delineate the impact of miR-346 on DNA damage, and its potential as a therapeutic agent. METHODS: RNA-IP, RNA-seq, RNA-ISH, DNA fibre assays, in vivo xenograft studies and bioinformatics approaches were used alongside a novel method for amplification-free, single nucleotide-resolution genome-wide mapping of DNA breaks (INDUCE-seq). RESULTS: miR-346 induces rapid and extensive DNA damage in PC cells - the first report of microRNA-induced DNA damage. Mechanistically, this is achieved through transcriptional hyperactivation, R-loop formation and replication stress, leading to checkpoint activation and cell cycle arrest. miR-346 also interacts with genome-protective lncRNA NORAD to disrupt its interaction with PUM2, leading to PUM2 stabilisation and its increased turnover of DNA damage response (DDR) transcripts. Confirming clinical relevance, NORAD expression and activity strongly correlate with poor PC clinical outcomes and increased DDR in biopsy RNA-seq studies. In contrast, miR-346 is associated with improved PC survival. INDUCE-seq reveals that miR-346-induced DSBs occur preferentially at binding sites of the most highly-transcriptionally active transcription factors in PC cells, including c-Myc, FOXA1, HOXB13, NKX3.1, and importantly, AR, resulting in target transcript downregulation. Further, RNA-seq reveals widespread miR-346 and shNORAD dysregulation of DNA damage, replication and cell cycle processes. NORAD drives target-directed miR decay (TDMD) of miR-346 as a novel genome protection mechanism: NORAD silencing increases mature miR-346 levels by several thousand-fold, and WT but not TDMD-mutant NORAD rescues miR-346-induced DNA damage. Importantly, miR-346 sensitises PC cells to DNA-damaging drugs including PARP inhibitor and chemotherapy, and induces tumour regression as a monotherapy in vivo, indicating that targeting miR-346:NORAD balance is a valid therapeutic strategy. CONCLUSIONS: A balancing act between miR-346 and NORAD regulates DNA damage and repair in PC. miR-346 may be particularly effective as a therapeutic in the context of decreased NORAD observed in advanced PC, and in transcriptionally-hyperactive cancer cells.

Prognostic predictors of non-small cell lung cancer treated with curative resection: the role of preoperative CT texture features, clinical features, and laboratory parameters.

AIM: To explore the value of preoperative contrast-enhanced computed tomography (CT) tumour texture characteristics, and clinical and laboratory parameters on the prognosis of curative resection for non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This retrospective study included 64 patients (34 men and 30 women) with NSCLC who underwent curative resection and were then followed up for 5 years or until death. Preoperative contrast-enhanced CT images, clinical features, and laboratory parameters were collected for these patients. CT texture features of the primary tumour before surgery were extracted from the contrast-enhanced CT images using ImageJ software. Based on the cut-off values determined by X-tile software, the preoperative CT texture features, clinical features, and laboratory parameters were divided into two groups. Kaplan-Meier survival curves and log-rank tests were used to compare the 5-year overall survival (OS) of patients. Multivariate Cox regression analysis was used to determine the independent factors influencing the prognosis. RESULTS: The mean survival was 51.5 months. Tumour volume, entropy, platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and albumin-to-globulin ratio (AGR) were shown to be significantly associated with 5-year OS (p<0.05). Multivariate Cox regression analysis revealed that entropy was the independent factor of prognosis (hazard ratio 4.375, 95% confidence interval [CI]: 1.646-11.620, p=0.003). CONCLUSION: Entropy is an important and potentially non-invasive imaging biomarker for predicting the prognosis of NSCLC undergoing curative resection.

Prediction and verification of survival in patients with non-small-cell lung cancer based on an integrated radiomics nomogram.

AIM: To develop and validate a nomogram to predict 1-, 2-, and 5-year survival in patients with non-small-cell lung cancer (NSCLC) by combining optimised radiomics features, clinicopathological factors, and conventional image features extracted from three-dimensional (3D) computed tomography (CT) images. MATERIALS AND METHODS: A total of 172 patients with NSCLC were selected to construct the model, and 74 and 72 patients were selected for internal validation and external testing, respectively. A total of 828 radiomics features were extracted from each patient's 3D CT images. Univariable Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to select features and generate a radiomics signature (radscore). The performance of the nomogram was evaluated by calibration curves, clinical practicability, and the c-index. Kaplan-Meier (KM) analysis was used to compare the overall survival (OS) between the two subgroups. RESULT: The radiomics features of the NSCLC patients correlated significantly with survival time. The c-indexes of the nomogram in the training cohort, internal validation cohort, and external test cohort were 0.670, 0.658, and 0.660, respectively. The calibration curves showed that the predicted survival time was close to the actual survival time. Decision curve analysis shows that the nomogram could be useful in the clinic. According to KM analysis, the 1-, 2- and 5-year survival rates of the low-risk group were higher than those of the high-risk group. CONCLUSION: The nomogram, combining the radscore, clinicopathological factors, and conventional CT parameters, can improve the accuracy of survival prediction in patients with NSCLC.

Bacteria-engineered porous sponge for hemostasis and vascularization.

BACKGROUND: Hemostasis and repair are two essential processes in wound healing, yet early hemostasis and following vascularization are challenging to address in an integrated manner. RESULTS: In this study, we constructed a hemostatic sponge OBNC-DFO by fermentation of Komagataeibacter xylinus combined with TEMPO oxidation to obtain oxidized bacterial nanocellulose (OBNC). Then angiogenetic drug desferrioxamine (DFO) was grafted through an amide bond, and it promoted clot formation and activated coagulation reaction by rapid blood absorption due to the high total pore area (approximately 42.429 m2/g measured by BET). The further release of DFO stimulated the secretion of HIF-1α and the reconstruction of blood flow, thus achieving rapid hemostasis and vascularization in damaged tissue. This new hemostatic sponge can absorb water at a rate of approximate 1.70 g/s, rapidly enhancing clot formation in the early stage of hemostasis. In vitro and in vivo coagulation experiments (in rat tail amputation model and liver trauma model) demonstrated superior pro-coagulation effects of OBNC and OBNC-DFO to clinically used collagen hemostatic sponges (COL). They promoted aggregation and activation of red blood cells and platelets with shorter whole blood clotting time, more robust activation of endogenous coagulation pathways and less blood loss. In vitro cellular assays showed that OBNC-DFO prevailed over OBNC by promoting the proliferation of human umbilical vein endothelial cells (HUVECs). In addition, the release of DFO enhanced the secretion of HIF-1α, further strengthening vascularization in damaged skin. In the rat skin injury model, 28 days after being treated with OBNC-DFO, skin appendages (e.g., hair follicles) became more intact, indicating the achievement of structural and functional regeneration of the skin. CONCLUSION: This hemostatic and vascularization-promoting oxidized bacterial nanocellulose hemostatic sponge, which rapidly activates coagulation pathways and enables skin regeneration, is a highly promising hemostatic and pro-regenerative repair biomaterial.

A study on serum pro-neurotensin (PNT), furin, and zinc alpha-2-glycoprotein (ZAG) levels in patients with acromegaly.

PURPOSE: Acromegaly caused by growth hormone cell adenoma is commonly associated with abnormal glucolipid metabolism, which may result from changes in adipocytokine secretion. This study aims to investigate serum adipokine levels, including pro-neurotensin (PNT), furin, and zinc alpha-2-glycoprotein (ZAG), in acromegalic patients and the correlation between the levels of these three adipokines and GH levels and glucolipid metabolism indices. METHODS: Sixty-eight acromegalic patients and 121 controls were included, and their clinical data were recorded from electronic medical record system. Serum PNT, furin and ZAG levels were measured by ELISA. RESULTS: Serum PNT levels in acromegalic patients were significantly higher than controls (66.60 ± 12.36 vs. 46.68 ± 20.54 pg/ml, P < 0.001), and acromegaly was an independent influencing factor of PNT levels (P < 0.001). Moreover, subjects with the highest tertile of PNT levels had a close correlation with acromegaly (OR = 22.200, 95% CI 7.156 ~ 68.875, P < 0.001), even in Model 1 adjusted for gender and age and Model 2 adjusted for gender, age and BMI. Additionally, serum PNT levels were positively correlated with BMI (r = 0.220, P = 0.002) and triglycerides (TGs, r = 0.295, P < 0.001), and TGs were an independent influencing factor of serum PNT levels in acromegalic subjects (P < 0.001). Furthermore, serum PNT levels in obese acromegalic patients were significantly higher than those with normal BMI (P < 0.05). However, serum furin levels were lower in acromegalic patients than controls (0.184 ± 0.036 vs. 0.204 ± 0.061 ng/ml, P < 0.001). CONCLUSION: This study is the first to demonstrate that acromegalic patients have increased serum PNT levels. Moreover, serum PNT plays a potential role in abnormal lipid metabolism of acromegalic patients.

[The influence of lung metastasis on prognosis of previously untreated gestational trophoblastic neoplasia patients].

Objective: To investigate the impact of lung metastases on the prognosis of patients with gestational trophoblastic neoplasia (GTN). Methods: Patients with International Federation of Gynaecology and Obstetrics (FIGO) stage Ⅰ-Ⅲ GTN receiving primary chemotherapy in Peking Union Medical College Hospital between July 2014 and December 2018 were retrospectively analyzed and divided into group 1 with lung metastasis and group 2 without lung metastasis. The baseline characteristics and treatment outcomes of the two groups were compared. The optimal cut-off values of the diameter of largest lung nodule associated with recurrence were identified by receiver operating characteristic (ROC) curves. Logistic regression analyses were performed to identify risk factors for prognosis. Survival analysis was performed by Kaplan-Meier method and Log rank test. Results: Of the 381 GTN patients enrolled (216 with lung metastases and 165 without lung metastases), the pretreatment ß human chorionic gonadotrophin [median: 12 572 IU/L (1 832-51 594 IU/L) vs. 5 614 IU/L (559-26 140 IU/L), P=0.001] and FIGO score [median: 3 (1-6) vs. 2 (1-4), P=0.038] were significantly higher in patients with lung metastases than those without lung metastases. In patients with FIGO score≥5, the emergence of resistance (26.76% vs. 10.26%, P=0.036) and median number of chemotherapy courses to achieve complete remission [6 (6-8) vs. 5 (4-6), P<0.001] were significantly higher than patients with lung metastases. In patients with FIGO score 0-4, no significant difference was found in the treatment outcomes between the two groups(P=0.833). Among all patients with lung metastases, the ROC curve showed a sensitivity and specificity of 62.5% and 78.8%, respectively, for predicting recurrence when the length of the largest lung nodule was 1.6 cm, with an area under the curve (AUC) of 0.711 (95% CI: 0.550, 0.871, P=0.044). Multivariate logistic regression analysis suggested a significantly higher recurrence rate when the largest lung nodule was ≥1.6 cm (OR=7.394, 95% CI: 1.003, 54.520, P=0.049). The 1-year disease-free survival rate was significantly lower in patients with the largest lung nodule ≥1.6 cm than in patients with the nodule <1.6 cm (98.2% vs. 82.4%, P=0.001). Conclusions: Lung metastasis is associated with increased first-line chemotherapy resistance in patients with FIGO scores≥5. The diameter of the largest lung metastatic nodule ≥1.6 cm is an effective factor for predicting recurrence.

[Prediction of platinum-based chemotherapy sensitivity for epithelial ovarian cancer by multi-sequence MRI-based radiomic nomogram].

Objective: To investigate a preoperative multi-sequence MRI-based radiomic nomogram for prediction of platinum-based chemotherapy sensitivity in patients with epithelial ovarian cancer (EOC). Methods: The complete data of 114 patients with EOC confirmed by surgery and pathology in Nantong Tumor Hospital of Nantong University from January 2015 to May 2020 were retrospectively analyzed, with an average age of 32-76 (57±8) years. All patients underwent platinum-based chemotherapy after maximal cytoreductive surgery. According to whether relapse occurred within 6 months, those patients were divided into platinum-resistant disease (PR, n=39) group and platinum-sensitive disease group (PS, n=75).All patients underwent MRI examination before treatment, and the 3-dimensional solid component of the tumor area of interest (ROI) on T2-weighted image (T2WI), diffusion weighted imaging (DWI) and T1-weighted image-enhanced image (T1CE) were manually delineated using Itk-snap software.Then AK software was imported for radiomics features extracting. They were randomly divided into training group (n=80) and validation group (n=34) in a ratio of 7∶3 (stratified sampling method). Firstly, the radiomics features were initially screened by the method of maximum correlation and minimum redundancy (mRMR), and features with the greatest predictive power were retained. Then, the LASSO regression analysis was performed to select the best features and construct the radiomics model. Univariate analysis was used to screen out clinical relevant factors, which combined with radiomic score (Radscore) was applied to develop a radiomics nomogram by multivariable logistic regression. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the predictive ability and clinical application value of radiomics model, clinical related factor model and radiomics nomogram. Results: Compared with the radiomics model (12 optimal radiomics features) and the clinical relevant factors model (residual disease, neutrophil count, carbohydrate antigen 199), the radiomics nomogram model demonstrated the best prediction performance: in the training groups, the AUC (Area Under the ROC Curve), accuracy, sensitivity, and specificity were 0.90 (95%CI:0.82-0.99), 90.0%, 89.0%, and 92.0%, respectively. In the validation groups, the AUC, accuracy, sensitivity, and specificity were 0.89 (95%CI:0.78-1.00), 85.0%, 87.0%, and 80.0%, respectively. DCA shows that the use of nomograms with a threshold in the range of 0.01 to 0.90 has a greater clinical application value in predicting the sensitivity of platinum chemotherapy in patients with EOC. Conclusion: The multi-sequence MRI-based radiomics nomogram has a high diagnostic value in predicting the sensitivity of platinum-based chemotherapy in patients with EOC.

[Analysis of disease progression rate and related factors in amyotrophic lateral sclerosis patients at initial visit].

Objective: To find out the relationship of the progression rate of amyotrophic lateral sclerosis (ALS) patients with relevant clinical indicators at initial visit so as to enrich the knowledge of ALS at its early stage. Methods: The clinical data of 282 patients diagnosed with ALS at Neurology Department of the First Medical Center, Chinese PLA General Hospital from June 2016 to March 2021 were collected in order to make a retrospective analysis of the dynamic change of the progression rate (ΔFS) and influencing factors, and thus a classification of the progression rate will be summarized. Results: Among 282 patients, 164 were males and 118 were females. The age of onset was (53±11) years old. The ΔFS had a negative exponential relationship with delay time of diagnosis no matter what kinds of onset the patients experienced (upper limb onset, lower limb onset or bulbar onset). The ΔFS for the limb function sub-group had a similar functional relationship with diagnostic delay in patients with either upper limb onset or lower limb onset. The statistical model indicated that the disease progression rate of ALS at initial visit can be classified into three types (high speed type: ΔFS≥1.0 score/month; moderate speed type: 0.5≤ΔFS<1.0 score/month; low speed type: ΔFS<0.5 score/month). The critical values of the three types in patients with upper limb onset were 8 and 20 months, while 9 and 24 months for lower limb onset patients, and 9 and 36 months for bulbar onset patients. At initial visit, there were significant statistical differences among these three types in age at onset (P=0.008), diagnostic delay (P<0.001), ALS functional rating scale-revised (ALSFRS-R) score (P<0.001) and onset site (P=0.006). The age at onset in moderate speed type was significantly greater than that of the slow speed type [(54.9±10.4) years vs (50.2±9.6) years, P=0.002]. The diagnostic delay in high speed type [6 (4, 10) months] was significantly shorter than that in moderate speed type [12 (8, 19) months, P<0.001] and low speed type [22 (14, 36) months, P<0.001], and the moderate speed type was shorter in comparison with low speed type (P<0.001). As for the ALSFRS-R score, the high speed type [36(32, 39)] was significantly lower than the moderate speed type [39 (36, 42), P<0.001] and low speed type [42 (39, 44), P<0.001], and the moderate speed type was lower in comparison with low speed type (P=0.002). The proportion of cases with upper limb onset in high speed type (20.3%) was significantly lower than that in low speed type (42.2%, P<0.001) and moderate speed type (37.5%, P=0.014). By contrast, the proportion of cases with lower limb onset in high speed type (39.2%) was significantly higher than that in low speed type (28.9%, P=0.023), however no difference was shown between the fast speed type and moderate speed type (32.0%, P=0.061). There was no difference among these three progression types in patients with bulbar onset. Conclusions: The disease progression rate of ALS at initial visit can be classified into three types including high speed, moderate speed and low speed. At early stage of ALS, ΔFS is affected by onset age, onset site, diagnostic delay and ALSFRS-R score.

[Relationship between white matter lesions and theresponse of cerebral spinal fluid tap test and clinical features in the patients with idiopathic normal pressure hydrocephalus].

Objective: To explore the relationship between white matter lesions and clinical features and response of cerebral spinal fluid (CSF) tap test in patients with idiopathic normal pressure hydrocephalus(iNPH). Methods: Possible iNPH patients were enrolled from outpatients and inpatients in Peking Union Medical College Hospital between 2014 and 2019. All patients underwent detailed neuropsychological and walking assessments, CSF tap test, as well as head magnetic resonance imaging. The Fazekas score of white matter lesions, the fractional anisotropy (FA)and mean diffusivity (MD) values of regions of interest by means ofdiffusion tensor imaging (DTI) were compared between CSF tap test positive and negative response groups. The correlation between DTI parameters and clinical characteristics was analyzed. Results: Forty-three patients (29 male and 14 female, age range: 52-79 years] wererecruited.Compared with the negative group, patients in the positive group tended to have higher Fazekas score of periventricular white matter(U=108.00, P=0.03), higher MD value of the region near anterior horn of left lateral ventricles[(1.14±0.27)×10-9mm2/s vs (0.85±0.08) ×10-9mm2/s, P=0.003], lower FA value of the region near anterior horn of the right lateral ventricles[(0.20±0.07)vs(0.27±0.09), P=0.058], and higher MD value near the posterior horn of right lateral ventricle [(1.17±0.34)×10-9mm2/s vs (0.95±0.01)×10-9mm2/s, P=0.003]. FA and MD were significantly correlated with motor function, cognitive and functional scores, and iNPH grading scale (iNPHGS) scores(all P<0.05). Conclusions: The white matter lesions might be one of the pathogeneses of lNPH and apathological changewhich can be reversed by CSF drainage. More white matter lesions should not be the contraindication of CSF drainage surgery.

[Efficacy and safety of combination therapy with chemotherapy, programmed death-1 inhibitor and anlotinib in the treatment of advanced dedifferentiated liposarcoma].

Objective: To investigate the efficacy and safety of the combination therapy with chemotherapy, programmed death-1 (PD-1) inhibitor and anlotinib in the treatment of advanced dedifferentiated liposarcoma (DDLPS). Methods: The clinical data of patients with dedifferentiated liposarcoma who received chemotherapy combined with PD-1 inhibitor and anlotinib in the Department of Medical Oncology, Zhongshan Hospital Affiliated to Fudan University from January 1, 2020 to November 30, 2021 were retrospectively analyzed. A total of 24 patients were included in this study, including 12 males and 12 females, with a median age of onset of 56 years (range, 31-69 years). Efficacy and safety in those patients were assessed. Results: All patients had unresectable or metastatic dedifferentiated liposarcoma with G2 (moderate differentiation) or G3 (differential differentiation) in a concise three-grade grading scheme of tumor pathology. Twelve patients received the regimen as the first-line treatment, while the other 7 taken the regimen as second-line treatment and 5 as third-line or above. The median follow-up time for overall survival (OS) was 7.7 months. The overall response rate (ORR) was 20.8% (5/24) and disease control rate (DCR) was 83.3% (20/24) with 5 partial response (PR), 15 stable disease (SD) and 4 progressive disease (PD). Overall, the median progression-free survival (PFS) was 4.9 months (95%CI: 3.4-16.2 months). The ORR of anthracycline-based, eribulin-based or gemcitabine-based regimens was 1/12, 2/6 and 2/6, respectively; and the median PFS was 7.7, 7.3 and 4.4 months, respectively. Waterfall plots showed notable tumor shrinkage of any degree in eribulin and gemcitabine-based regimens(3/6 and 2/6, respectively), while there were more patients presented with SD in anthracycline-based group(9/12). Common adverse reactions included myelosuppression, fatigue, anorexia, rash, pruritus, palpitate, hypothyroidism and hypertension. Conclusions: The combination regimen with chemotherapy, PD-1 inhibitor and anlotinib in the treatment of advanced DDLPS is effective and well tolerable. There are more responders in eribulin or gemcitabine-based regimens.