[The Efficacy and Safety of Venetoclax Combined with Azacitidine in the Treatment of Adult Patients with Acute Myeloid Leukemia Who Are Unfit for Intensive Chemotherapy].

OBJECTIVE: To observe the clinical efficacy and safety of venetoclax (VEN) combined with azacitidine (AZA) in the treatment of adult acute myeloid leukemia (AML) patients who are unfit for intensive chemotherapy. METHODS: The clinical data of 21 adult patients with unfit AML who were treated with VEN combined with AZA in the Second Hospital of Shanxi Medical University from January 2021 to May 2022 were collected, and the efficacy and safety were analyzed retrospectively. RESULTS: After one course of treatment with VEN and AZA, 16 out of 21 unfit AML patients reached complete remission (CR)/CR with incomplete hematologic recovery (CRi), 2 patients reached partial remission (PR), the overall response rate (ORR) was 85.7%. Among the 16 patients with CR/CRi, 13 achieved minimal residual disease (MRD) negativity. Among the 11 patients with adverse prognosis, 8 achieved CR/CRi. By the deadline of follow-up, the median overall suivival (OS) of the entire cohort was not reached, with 1-year OS rate of 61.7%. The main adverse events of VEN combined with AZA were myelosuppression, gastrointestinal reactions and infections. There were 13 cases of leukopenia, 7 cases of neutropenia, 7 cases of anemia, 4 cases of thrombocytopenia, and these hematologic adverse events were all grade 3-4. There were 11 cases with gastrointestinal reactions and 7 cases with infections. The above adverse events were controllable and tolerable. No tumor lysis syndrome or infection related death occurred. CONCLUSION: VEN combined with AZA can quickly achieve deep remission in adult patients with unfit AML, and it shows a good safety profile.

Assessing synchronous ovarian metastasis in gastric cancer patients using a clinical-radiomics nomogram based on baseline abdominal contrast-enhanced CT: a two-center study.

BACKGROUND: To build and validate a radiomics nomogram based on preoperative CT scans and clinical data for detecting synchronous ovarian metastasis (SOM) in female gastric cancer (GC) cases. METHODS: Pathologically confirmed GC cases in 2 cohorts were retrospectively enrolled. All cases had presurgical abdominal contrast-enhanced CT and pelvis contrast-enhanced MRI and pathological examinations for any suspicious ovarian lesions detected by MRI. Cohort 1 cases (n = 101) were included as the training set. Radiomics features were obtained to develop a radscore. A nomogram combining the radscore and clinical factors was built to detect SOM. The bootstrap method was carried out in cohort 1 as internal validation. External validation was carried out in cohort 2 (n = 46). Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA) and the confusion matrix were utilized to assess the performances of the radscore, nomogram and subjective evaluation model. RESULTS: The nomogram, which combined age and the radscore, displayed a higher AUC than the radscore and subjective evaluation (0.910 vs 0.827 vs 0.773) in the training cohort. In the external validation cohort, the nomogram also had a higher AUC than the radscore and subjective evaluation (0.850 vs 0.790 vs 0.675). DCA and the confusion matrix confirmed the nomogram was superior to the radscore in both cohorts. CONCLUSIONS: This pilot study showed that a nomogram model combining the radscore and clinical characteristics is useful in detecting SOM in female GC cases. It may be applied to improve clinical treatment and is superior to subjective evaluation or the radscore alone.

Simultaneous Ring Contraction and Expansion Reaction: Electrosynthesis of Heterocycle-Fused Fulleroids and Photovoltaic Application.

Simultaneous electrochemical ring contraction and expansion reactions remain unexplored to date. Herein, the reductive electrosynthesis of heterocycle-fused fulleroids from fullerotetrahydropyridazines and electrophiles in the presence of a trace amount of oxygen has been achieved with concurrent ring contraction and ring expansion. When trifluoroacetic acid and alkyl bromides are employed as electrophiles, heterocycle-fused fulleroids with a 1,1,2,6-configuration are regioselectively formed. In contrast, heterocycle-fused fulleroids with a 1,1,4,6-configuration are regioselectively produced as two separable stereoisomers if phthaloyl chloride is used as the electrophile. The reaction proceeds through multiple steps of electroreduction, heterocycle ring-opening, oxygen oxidation, heterocycle contraction, fullerene cage expansion, and nucleophilic addition. The structures of these fulleroids have been determined by spectroscopic data and single-crystal X-ray diffraction analyses. The observed high regioselectivities have been rationalized by theoretical calculations. Representative fulleroids have been applied in organic solar cells as the third component and exhibit good performance.

Oncological Safety of Diagnostic Hysteroscopy for Apparent Early-Stage Type II Endometrial Cancer: A Multicenter Retrospective Cohort Study.

Objective: To study the oncological safety of diagnostic hysteroscopy for women with apparent early-stage type II endometrial cancer. Patients and Methods: A total of 429 women with presumed early-stage type II endometrial cancer were included. The 5-year disease-free survival (DFS) and overall survival (OS) were estimated and compared using the Kaplan-Meier method and the log-rank test among patients diagnosed by Dilation & Curettage (D&C) or diagnostic hysteroscopy. The Cox proportional hazards regression model was employed to adjust for potential confounding factors. Results: 160 cases underwent D&C and 269 cases were diagnosed by diagnostic hysteroscopy. The 5-year DFS rate was 72.17% in the diagnostic hysteroscopy group and 76.16% in the D&C group, diagnostic hysteroscopy was not associated with deteriorated 5-year DFS rate (HR 1.25, 95% CI 0.84-1.86, P=0.281). The 5-year OS rate was 67.23% in the diagnostic hysteroscopy group and 70.71% in the D&C group, diagnostic hysteroscopy did not increase the risk of all-cause death (HR 1.11, 95% CI 0.78-1.57, P=0.573). Multivariable analysis showed that the method of endometrial sampling was not independently associated with DFS (aHR 1.38, 95% CI 0.92-2.07, P=0.122) and OS (aHR 1.23, 95% CI 0.85-1.77, P=0.272). Conclusion: For apparent early-stage type II endometrial cancer, endometrial sampling by diagnostic hysteroscopy was as safe as D&C.

[Proteomics of serum exosomes in children in the acute stage of Kawasaki disease: a prospective study]. / æ€¥æ€§æœŸå·å´Žç— æ‚£å„¿è¡€æ¸ å¤–æ³Œä½“è›‹ç™½è´¨ç»„å­¦çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the biological processes and functions of serum exosomes in children in the acute stage of Kawasaki disease (KD), so as to provide new biomarkers for the early diagnosis of KD. METHODS: In this prospective study, 13 children with KD who were treated in Children's Hospital of Soochow University from June 2019 to August 2020 were enrolled as the KD group, and 13 children who were hospitalized due to bacterial infection during the same period were enrolled as the control group. Whole blood was collected on the next morning after admission, serum samples were obtained by centrifugation, and exosomes were extracted through ultracentrifugation. Serum exosomes were analyzed by label-free quantitative proteomics, and differentially expressed proteins (DEPs) were screened out for functional enrichment analysis. A protein-protein interaction (PPI) network was plotted, and unique proteins were validated by targeted proteomics. RESULTS: A total of 131 DEPs were screened out for the two groups, among which 27 proteins were detected in both groups. There were 48 unique DEPs in the KD group, among which 23 were upregulated and 25 were downregulated, and these proteins acted on "complement and coagulation cascades" and "the MAPK signaling pathway". Validation by targeted proteomics showed that FGG, SERPING1, C1R, C1QA, IGHG4, and C1QC proteins were quantifiable in the KD group. A total of 29 proteins were only expressed in the control group, among which 12 were upregulated and 17 were downregulated. Four proteins were quantifiable based on targeted proteomics, i.e., VWF, ECM1, F13A1, and TTR. A PPI network was plotted for each group. In the KD group, FGG and C1QC had close interaction with other proteins, while in the control group, VWF had close interaction with other proteins. CONCLUSIONS: The serum exosomes FGG and C1QC in children in the acute stage of KD are expected to become the biomarkers for the early diagnosis of KD. For children with unexplained fever, detection of FGG, C1QC1, and VWF may help with etiological screening.

[Perinatal Outcomes of Using Ursodeoxycholic Acid to Treat Monochorionic and Dichorionic Twin Pregnancy Complicated by Intrahepatic Cholestasis of Pregnancy].

OBJECTIVE: To study the effect of using ursodeoxycholic acid (UDCA) to treat monochorionic and dichorionic twin pregnancies complicated by intrahepatic cholestasis of pregnancy (ICP) and to examine the differences in perinatal outcomes. METHODS: A total of 406 twin-carrying pregnant women who had ICP and received care at West China Second Hospital, Sichuan University between January 1, 2015 and November 1, 2018 were included in the study. The clinical data of monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twins with ICP were analyzed. Analysis was done to compare the treatment effect for lowering serum total bile acid (TBA) and the perinatal outcomes with simple UDCA medication or combination medication. RESULTS: There were no statistically significant differences in TBA levels, early-onset ICP, simple UDCA medication or combination medication, neonatal Apgar score, birth weight, length of hospital stay, C-section rate, and perinatal mortality between the MCDA and the DCDA twin groups with ICP. However, maternal age, BMI, scarred uterus, in vitro fertilization-embryo transfer, preeclampsia, twin comorbidity rate of the two groups showed statistical differences. Further comparison between twin pregnancies with mildly-elevated TBA and those with severely-elevated TBA showed significant difference in preterm birth rate ( P<0.05). CONCLUSION: Simple UDCA medication or combination medication may have the same therapeutic effect on MCDA and DCDA twin pregnancies with ICP. Monochorionic twin pregnancy, twin comorbidities and pregnancy complications were still important factors affecting pregnancy outcomes of twin pregnancies with ICP. Twin pregnancies with slightly elevated TBA have been managed as severe ICP, which may be associated with increased iatrogenic preterm births.

Retroperitoneum ganglioneuroma: imaging features and surgical outcomes of 35 cases at a Chinese Institution.

BACKGROUND: The preoperative evaluation is crucial for diagnosis and surgical plan of retroperitoneum ganglioneuroma (GN). In this study, we reviewed a relatively large series of histopathological proved retroperitoneum GN cases, summarized the imaging features and further depicted risk factors of increased surgical blood loss. METHODS: A total of 35 (18 male, 17 female) patients were retrospectively enrolled from January 2012 to June 2019 at our institution. Among them, 24 patients had undergone CT scans and 19 patients had undergone MR examination before treatment. The clinical and radiological features were analyzed and the relationships between image features and surgical blood loss were evaluated. RESULTS: The media age of the involved 35 patients was 40 years (range, 14-66 years). The histological tumor size was 10.12 ± 4.56 cm for average. Retroperitoneum GN was relatively low density on unenhanced CT images and showed delayed progressive enhancement on enhanced CT and MR images. The whorled sign could be seen in 14 patients. The vessel encasement sign could be found in 17 patients. Univariate analysis revealed maximal tumor size measured on axial image, maximal tumor size measured on coronal image, encasing one or both renal pedicles, encasing the aorta and/or vena cava and whorled sign on MRI showed significant difference between the blood loss ≥ 400 ml and blood loss < 400 ml group. Logistic regression further detected that maximal tumor size measured on axial images (OR: 1.12; 95% CI: 1.02-1.24; P = 0.023) and encasing one or both renal pedicles (OR: 22.39; 95% CI: 1.35-372.99; P = 0.030) were independently correlated with surgical blood loss. CONCLUSIONS: Preoperative CT and MR imaging analysis was valuable for both diagnosis and surgical risk prediction of retroperitoneum GN.

RETRACTED: Liposomal valinomycin mediated cellular K+ leak promoting apoptosis of liver cancer cells.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the corresponding author. It has been found that Fig 2B contains manipulated components, and Fig 5A partially overlaps with Fig 6 of a published paper authored by Mirza Muhammad Faran Ashraf Baig, et, al., The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors, J. Pharm. Anal. 11 (2021) 174-182, https://doi.org/10.1016/j.jpha.2020.10.003. The corresponding author indicated that they cannot guarantee the integrity of the images in the manuscript, as well as the conclusions of the paper. As a result, the Editor-in-Chief has decided to retract the paper. The corresponding author deeply regrets the circumstances and apologizes to the scientific community for not having detected this prior to publication.

Altered integrity of hepatocyte tight junctions in rats with triptolide-induced cholestasis.

Triptolide (TP), an active component of Tripterygium wilfordiiHook. f. (TWHF), has been widely used for centuries as a traditional Chinese medicine. However, the clinical application of TP has been restricted due to multitarget toxicity, such as hepatotoxicity. In this study, 28 days of oral TP administration (100, 200, or 400 µg·kg-1·d-1) induced the occurrence of cholestasis in female Wistar rats, as evidenced by increased serum levels of γ-glutamyl transpeptidase (γ-GGT), alkaline phosphatase (ALP) and hepatic total bile acids (TBAs). In addition, the heptocyte polarity associated with the strcture of tight junctions (TJs) was disrupted in both rats and sandwich-cultured primary hepatocytes. Immunoblotting revealed decreased expression of the TJ-associated proteins occludin, claudin-1, and zonula occludens protein (ZO-1), and downregulated mRNA levels of these TJs was also detected by real-time PCR. An immunofluorescence analysis showed abnormal subcellular localization of occludin, claudin-1 and ZO-1, which was also confirmed by transmission electron microscopy. Moreover, the concentration of FITC-dextran, a marker of paracellular penetration, was found to increase rapidly in bile increased rapidly (within 6 minutes) after treatment with TP, which indicated the functional impairment of TJs. Taken together, these results suggest that the administration of TP for 28 consecutive days to rats could induce cholestatic injury in the liver, and the increased paracellular permeability might play an important role in these pathological changes.

MRI-based radiomics approach for differentiation of hypovascular non-functional pancreatic neuroendocrine tumors and solid pseudopapillary neoplasms of the pancreas.

BACKGROUND: This study aims to investigate the value of radiomics parameters derived from contrast enhanced (CE) MRI in differentiation of hypovascular non-functional pancreatic neuroendocrine tumors (hypo-NF-pNETs) and solid pseudopapillary neoplasms of the pancreas (SPNs). METHODS: Fifty-seven SPN patients and twenty-two hypo-NF-pNET patients were enrolled. Radiomics features were extracted from T1WI, arterial, portal and delayed phase of MR images. The enrolled patients were divided into training cohort and validation cohort with the 7:3 ratio. We built four radiomics signatures for the four phases respectively and ROC analysis were used to select the best phase to discriminate SPNs from hypo-NF-pNETs. The chosen radiomics signature and clinical independent risk factors were integrated to construct a clinic-radiomics nomogram. RESULTS: SPNs occurred in younger age groups than hypo-NF-pNETs (P < 0.0001) and showed a clear preponderance in females (P = 0.0185). Age was a significant independent factor for the differentiation of SPNs and hypo-NF-pNETs revealed by logistic regression analysis. With AUC values above 0.900 in both training and validation cohort (0.978 [95% CI, 0.942-1.000] in the training set, 0.907 [95% CI, 0.765-1.000] in the validation set), the radiomics signature of the arterial phase was picked to build a clinic-radiomics nomogram. The nomogram, composed by age and radiomics signature of the arterial phase, showed sufficient performance for discriminating SPNs and hypo-NF-pNETs with AUC values of 0.965 (95% CI, 0.923-1.000) and 0.920 (95% CI, 0.796-1.000) in the training and validation cohorts, respectively. Delong Test did not demonstrate statistical significance between the AUC of the clinic-radiomics nomogram and radiomics signature of arterial phase. CONCLUSION: CE-MRI-based radiomics approach demonstrated great potential in the differentiation of hypo-NF-pNETs and SPNs.

Oncological safety of hysteroscopy in the diagnosis of stage I endometrial cancer: protocol for a systematic review and meta-analysis.

BACKGROUND: The oncological safety of diagnostic hysteroscopy in patients with stage Ⅰ endometrial cancer remains uncertain and conflicting. The aim of the proposed systematic review and meta-analysis is to summarise the available evidence examining the association between diagnostic hysteroscopy and the prognosis of stage Ⅰ endometrial cancer and to statistically synthesise the results of relevant studies. METHODS AND ANALYSIS: Systematic searches of PubMed/MEDLINE, Embase, Cochrane Library and Web of Science will be undertaken using prespecified search strategies. Two authors will independently conduct eligible studies selection process, perform data extraction and appraise the quality of included studies. Original case-control studies, cohort studies and randomised controlled trails published in English will be considered for inclusion. The outcomes of interest will be 5-year recurrence-free survival, disease-specific survival and overall survival. Meta-analyses will be performed to calculate pooled estimates. ETHICS AND DISSEMINATION: Our study will be based on published data, and thus there is no requirement for ethics approval. The results will be shared through publication in a peer-reviewed journal and presentations at academic conferences. PROSPERO REGISTRATION NUMBER: CRD42020193696.

The long noncoding RNA FTH1P3 promotes the proliferation and metastasis of cervical cancer through microRNA­145.

Emerging evidence has revealed that long noncoding RNAs (lncRNAs) play crucial roles in the development and progression of tumors. The present study aimed to examine the roles and illustrate the underlying mechanisms of lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) in cervical cancer. The expression of lncRNA FTH1P3 and microRNA­145 (miRNA­145 or miR­145) in human cervical cancer samples and cervical cancer cell lines was detected by qRT­PCR (reverse transcription­quantitative polymerase chain reaction). FTH1P3 overexpression, siRNA plasmid, hsa­miR­145 mimic or hsa­miR­145 inhibitor were transfected. The target of FTH1P3 was predicted by bioinformatics analysis and validated by luciferase assay. Statistical significance analysis was performed by SPSS software. The results revealed that FTH1P3 was significantly upregulated in cervical cancer tissues compared with normal tissues. Increased expression of FTH1P3 was revealed in human cervical cancer cell lines compared with cervical normal epithelial cells. Downregulation of FTH1P3 inhibited cell proliferation, invasion and migration, and promoted apoptosis in cervical cancer cells. miR­145 was predicted and validated as a direct target of FTH1P3. Moreover, FTH1P3 siRNA partially attenuated the effects of the miR­145 inhibitor on cell viability and mobility in cervical cancer cells. The present results demonstrated that lncRNA FTH1P3 functioned as a promoting factor in cervical cancer by targeting miR­145.

A DNA Nanodevice Simultaneously Activating the EGFR and Integrin for Enhancing Cytoskeletal Activity and Cancer Cell Treatment.

Cell-surface receptors (e.g., EGFR and integrin) and their interactions play determining roles in signal transduction and cytoskeletal activation, which affect cell attachment/detachment, invasion, motility, metastasis (intracellular), and cell-cell signaling. For instance, the interactions between the EGFR and integrin (α6ß4) may cause increased mechanical force and shear stress via enhanced cytoskeleton activation. Here, we design a DNA nanodevice (DNA-ND) that can simultaneously target the EGFR and integrin receptors on the caveolae. The piconewton (pN) forces in response to the EGFR-integrin coactivation can be sensed upon the unfolding of the DNA hairpin structure on the side arm of the device via changes of the fluorescence and plasmonic signals. We find that simultaneous activation of EGFR-integrin receptors causes enhanced signal transduction, contractions of the cells, and initiation of the biochemical pathways, thus resulting in a change of the cell division and endocytosis/exocytosis processes that affect the cell proliferation/apoptosis. The DNA-ND further enables us to visualize the cointernalization and degradation of the receptors by lysosomes, providing a novel approach toward bioimaging and mechano-pharmacology.

Specific cell capture and noninvasive release via moderate electrochemical oxidation of boronic ester linkage.

Early diagnosis and therapy of cancer metastasis are of great importance for disease outcome. Circulating tumor cells (CTCs) offer the ability for noninvasive tumor profiling in real time. However, simply capturing and counting tumor cells are inadequate to provide valuable information about tumor. Efficiently releasing the captured cells is necessary for the downstream characterization. Herein, we describe a mild electrochemical strategy to effectively isolate CTCs from the bloodstream and rapidly release the captured cells in 2 min for downstream molecular characterization, as realized on a conductive poly(aminophenylboronic acid) derivatized electrode. The boronic ester linkage between dopamine (DA) and boronic acids-functionalized electrode is stable, and only upon the application of a weak potential perturbation does the boronic ester dissociate and release cells without compromising cell viability. This platform is reusable after acid treatment and has the potential to be the next-generation platform for cell capture and release, realizing the clinical value of CTCs as biomarkers.

Nanochannel-Ion Channel Hybrid Device for Ultrasensitive Monitoring of Biomolecular Recognition Events.

We propose an in situ and label-free method for detection of biomolecular recognition events by use of a nanochannel-ion channel hybrid device integrated with an electrochemical detector. The aptamer is first immobilized on the outer surface of the nanochannel-ion channel hybrid. Its binding with target thrombin in solution considerably regulates the mass-transfer behavior of the device owing to the varied surface charge density and effective channel size. Via the electrochemical detector, the changed mass-transport property can be monitored in real time, which enables in situ and label-free detection of thrombin-aptamer recognition. The solution pH has a significant influence on detection sensitivity. Under optimal pH conditions, a detection limit as low as 0.22 fM thrombin can be achieved, which is much lower than most reported work. The present nanofluidic device provides a simple, ultrasensitive, and label-free platform for monitoring biomolecular recognition events, which would hold great potential in exploring the functions and reaction mechanisms of biomolecules in living systems.

Water as a Universal Infrared Probe for Bioanalysis in Aqueous Solution by Attenuated Total Reflection-Surface Enhanced Infrared Absorption Spectroscopy.

Monitoring the properties and reactions of biomolecules at their interface has attracted ever-growing interest. Here, we propose an approach of infrared analysis technique that utilizes water molecule as a universal probe for in situ and label free monitoring of interfacial bioevents in aqueous solution with high sensitivity. The strong infrared (IR) signal of O-H stretching vibrations from the repelled water is used to sensitively reveal the kinetics of interfacial bioevents at molecular level based on the steric displacement of water using an attenuated total reflection-surface enhanced infrared absorption spectroscopy. Using interfacial immuno-recognition and DNA hybridization as demonstrations, water IR probe offers 26 and 34 times higher sensitivity and even 200 and 86 times lower detection limit for immunosensing and DNA sensing, respectively, as compared to the traditional IR molecular fingerprints.

Plasmon Coupling Effect-Enhanced Imaging of Metal Ions in Living Cells Using DNAzyme Assembled Core-Satellite Structures.

We demonstrate a core-satellite plasmonic nanoprobe assembled via metal-ion-dependent DNA-cleaving DNAzyme linker for imaging intercellular metal ion based on plasmon coupling effect at a single-particle level. As metal ions are present in the system, the DNAzyme linker will be cleaved, and thus, disassembly of the core-satellite nanoprobes occurs, which results in distinct blue shift of the scattering spectra of Au core-satellite probes and naked color change of the scattering light. This change in scattering spectra has been supported by theoretical simulations. As a proof of concept, sensitive detection of Cu2+ with a limit of detection down to 67.2 pM has been demonstrated. The nanoprobes have been further utilized for intracellular Cu2+ imaging in living cells. The results demonstrate that the present strategy provides a promising platform for detection and imaging of metal ions in living cells and could be potentially applied to imaging other interesting target molecules simply by substituting the oligonucleotide sequence.