ABSTRACT
Although our knowledge of autism spectrum disorder (ASD) has been deepened, the accurate diagnosis of ASD from normal individuals is still left behind. In this study, we proposed to apply the spatial pattern of the network topology (SPN) to identify children with ASD from normal ones. Based on two independent batches of electroencephalogram datasets collected separately, the accurate recognition of ASD from normal children was achieved by applying the proposed SPN features. Since decreased long-range connectivity was identified for children with ASD, the SPN features extracted from the distinctive topological architecture between two groups in the first dataset were used to validate the capacity of SPN in classifying ASD, and the SPN features achieved the highest accuracy of 92.31%, which outperformed the other features e.g., power spectrum density (84.62%), network properties (76.92%), and sample entropy (73.08%). Moreover, within the second dataset, by using the model trained in the first dataset, the SPN also acquired the highest sensitivity in recognizing ASD, when compared to the other features. These results consistently illustrated that the functional brain network, especially the intrinsic spatial network topology, might be the potential biomarker for the diagnosis of ASD.
ABSTRACT
As a major concern shared by parents globally, COVID-19 vaccine safety is typically being messaged to the public in a negative frame in many countries. However, whether the COVID-19 vaccine safety framing have an effect on parents when vaccinating their children is unclear. Here we implement an online survey with a convenience sample of 3,861 parents living in mainland China, all over 18 years old and with at least one child under 18. The parents were randomly assigned to receive information about COVID-19 vaccine safety in either a negative frame (incidence of side effects) or a positive frame (the inverse incidence of side effects), to compare parental reactions to a range of questions about communication, risk perception, trust, involvement and behavioral intention. We found that parents were more likely to regard vaccine safety as relevant to policy support and as a higher priority for government when receiving positively framed information (p = 0.002). For some specific subgroups, parents in positive framing group showed lower risk perception and higher trust (p<0.05). This suggests that positive framing of COVID-19 vaccine safety messages show more effective performance than negative framing in terms of involvement, as well as trust and risk perception in specific subgroups, which may lead to a reflection on whether to adjust the current widespread use of negative framing. Our findings inform how governments and health care workers strategically choose the framing design of COVID-19 vaccine safety information, and have important implications for promoting COVID-19 vaccination in children in the future.
Subject(s)
COVID-19 Vaccines , COVID-19 , Child , Humans , Adolescent , COVID-19 Vaccines/adverse effects , Patient Acceptance of Health Care , COVID-19/prevention & control , Communication , Parents , Vaccination/adverse effectsABSTRACT
BACKGROUND: Previous neuroimaging and pathological studies have found myelin-related abnormalities in bipolar disorder (BD), which prompted the use of magnetic resonance (MR) imaging technology sensitive to neuropathological changes to explore its neuropathological basis. We holistically investigated alterations in myelin within BD patients by inhomogeneous magnetization transfer (ihMT), which is sensitive and specific to myelin content. METHODS: Thirty-one BD and 42 healthy controls (HC) were involved. Four MR metrics, i.e., ihMT ratio (ihMTR), pseudo-quantitative ihMT (qihMT), magnetization transfer ratio and pseudo-quantitative magnetization transfer (qMT), were compared between groups using analysis methods based on whole-brain voxel-level and white matter regions of interest (ROI), respectively. RESULTS: The voxel-wise analysis showed significantly inter-group differences of ihMTR and qihMT in the corpus callosum. The ROI-wise analysis showed that ihMTR, qihMT, and qMT values in BD group were significantly lower than that in HC group in the genu and body of corpus callosum, left anterior limb of the internal capsule, left anterior corona radiate, and bilateral cingulum (p < 0.001). And the qihMT in genu of corpus callosum and right cingulum were negatively correlated with depressive symptoms in BD group. LIMITATIONS: This study is based on cross-sectional data and the sample size is limited. CONCLUSION: These findings suggest the reduced myelin content of anterior midline structure in the bipolar patients, which might be a critical pathophysiological feature of BD.
Subject(s)
Bipolar Disorder , Magnetic Resonance Imaging , Myelin Sheath , Humans , Bipolar Disorder/diagnostic imaging , Bipolar Disorder/pathology , Female , Male , Adult , Myelin Sheath/pathology , Middle Aged , Corpus Callosum/diagnostic imaging , Corpus Callosum/pathology , White Matter/diagnostic imaging , White Matter/pathology , Case-Control Studies , Brain/diagnostic imaging , Brain/pathologyABSTRACT
Two-dimensional (2D) materials with superior properties exhibit tremendous potential in developing next-generation electronic and optoelectronic devices. Integrating various functions into one device is highly expected as that endows 2D materials great promise for more Moore and more-than-Moore device applications. Here, we construct a WSe2/Ta2NiSe5 heterostructure by stacking the p-type WSe2 and the n-type narrow gap Ta2NiSe5 with the aim to achieve a multifunction optoelectronic device. Owing to the large interface potential barrier, the heterostructure device reveals a prominent diode feature with a large rectify ratio (7.6 × 104) and a low dark current (10-12 A). Especially, gate voltage- and bias voltage-tunable staggered-gap to broken-gap transition is achieved on the heterostructure device, which enables gate voltage-tunable forward and reverse rectifying features. As results, the heterostructure device exhibits superior self-powered photodetection properties, including a high detectivity of 1.08 × 1010 Jones and a fast response time of 91 µs. Additionally, the intrinsic structural anisotropy of Ta2NiSe5 endows the heterostructure device with strong polarization-sensitive photodetection and high-resolution polarization imaging. Based on these characteristics, a multimode optoelectronic logic gate is realized on the heterostructure via synergistically modulating the light on/off, polarization angle, gate voltage, and bias voltage. This work shed light on the future development of constructing high-performance multifunctional optoelectronic devices.
ABSTRACT
Acute interstitial nephritis (AIN) is a significant contributor to acute kidney injury and can be attributed to a variety of factors, including but not limited to allergens or drugs, infections, autoimmune or systemic diseases, and idiopathic forms of the disease. In some cases, AIN requires a therapeutic action according to a single specific etiology by handling the offending agent and applying an immunosuppressant. Although AIN can be diagnosed through renal biopsy, it is not able to pinpoint the precise cause when multiple causes are suspected to be present simultaneously. Such situations arise when a patient suffering from infection develops AIN during antibiotic therapy, the exact causative factor of which becomes a challenge for the clinicians to determine. This is attributed to the different approaches employed in different etiologies, wherein clinicians are required to maintain the current antibiotic therapy or augment the dose in cases of infection as AIN etiology, without resorting to immunosuppressant therapy as the primary objective is infection killing. In contrast, antibiotics as an etiology for AIN require an alternative drug from the antibiotics group, along with an immunosuppressant. In the interim, delaying the identification of the precise cause may result in interstitial fibrosis and chronic kidney disease. This narrative review highlights certain findings that can be typical of infection-associated ATIN compared with antibiotic-associated ATIN based on clinical history and physical examination, clinical presentation of different antibiotic drug classes, histopathological features, classical and novel biomarkers, serum and urine cytokines and chemokines, cellular biomarkers, and genetic biomarkers. Although these findings cannot provide conclusive and clear recommendations that can be useful in the clinical practice, they can entice researchers to conduct original research on these features to discover clear recommendations.
Subject(s)
Clinical Trials as Topic , Humans , Female , Genital Neoplasms, Female/therapy , Consensus , ChinaABSTRACT
BACKGROUND: Cervical cancer patients with isolated para-aortic lymph nodes (PALN) recurrence were mainly associated with treatment failure. For these patients, radiotherapy, chemotherapy, surgery ± adjuvant therapy or chemoradiotherapy may be advised, however, no specific therapy has been proposed yet. This study aimed to explore factors influencing the prognosis of cervical cancer cases with isolated PALN recurrence and to find out an effective salvage therapy. METHODS: Cervical cancer cases with isolated PALN recurrence who received therapies in Zhejiang Cancer Hospital between January 2013 and June 2021 were analyzed retrospectively. RESULTS: Carcinoembryonic antigen (CEA) level > 10 ng/mL and positron emission tomography/computed tomography (PET/CT) imaging method used to detect the recurrence were found to be associated with the local control rate. PALN (positive), squamous-cell carcinoma-antigen (SCC-Ag) level (> 10 ng/mL) upon initial diagnosis, and CEA level (> 10 ng/mL), number of metastatic lymph nodes (several) at recurrence were associated with worse survival. Compared with surgery ± adjuvant therapy, chemotherapy (CT) alone or sequential chemoradiotherapy (SCRT) was associated with worse PFS or OS. Concurrent chemoradiotherapy (CCRT) after PALN recurrence could reduce the risk of the second recurrence. 3-year OS of cases after surgery ± adjuvant therapy was the highest (65%), followed by CCRT (45.7%), SCRT (38.9%), radiotherapy (RT) (33.3%), and CT (20.6%). CONCLUSION: In cervical cancer patients with isolated PALN recurrence, chemoradiotherapy or surgery ± adjuvant therapy may be preferred as the salvage treatment.
ABSTRACT
Suicidal behavior and non-suicidal self-injury (NSSI) are common in adolescent patients with major depressive disorder (MDD). Thus, delineating the unique characteristics of suicide attempters having adolescent MDD with NSSI is important for suicide prediction in the clinical setting. Here, we performed psychological and biochemical assessments of 130 youths having MDD with NSSI. Participants were divided into two groups according to the presence/absence of suicide attempts (SAs). Our results demonstrated that the age of suicide attempters is lower than that of non-attempters in participants having adolescent MDD with NSSI; suicide attempters had higher Barratt Impulsiveness Scale (BIS-11) impulsivity scores and lower serum CRP and cortisol levels than those having MDD with NSSI alone, suggesting levels of cortisol and CRP were inversely correlated with SAs in patients with adolescent MDD with NSSI. Furthermore, multivariate regression analysis revealed that NSSI frequency in the last month and CRP levels were suicidal ideation predictors in adolescent MDD with NSSI, which may indicate that the increased frequency of NSSI behavior is a potential risk factor for suicide. Additionally, we explored the correlation between psychological and blood biochemical indicators to distinguish suicide attempters among participants having adolescent MDD with NSSI and identified a unique correlation network that could serve as a marker for suicide attempters. Our research data further suggested a complex correlation between the psychological and behavioral indicators of impulsivity and anger. Therefore, our study findings may provide clues to identify good clinical warning signs for SA in patients with adolescent MDD with NSSI.
Subject(s)
Depressive Disorder, Major , Self-Injurious Behavior , Adolescent , Humans , Suicide, Attempted , Hydrocortisone , AngerABSTRACT
BACKGROUND: Depressed patients often suffer from sleep disturbance, which has been recognized to be responsible for glymphatic dysfunction. The purpose of this study was to investigate the coupling strength of global bloodoxygen-level-dependent (gBOLD) signals and cerebrospinal fluid (CSF) inflow dynamics, which is a biomarker for glymphatic function, in depressed patients and to explore its potential relationship with sleep disturbance by using resting-state functional MRI. METHODS: A total of 138 depressed patients (112 females, age: 34.70 ± 13.11 years) and 84 healthy controls (29 females, age: 36.6 ± 11.75 years) participated in this study. The gBOLD-CSF coupling strength was calculated to evaluate glymphatic function. Sleep disturbance was evaluated using the insomnia items (item 4 for insomnia-early, item 5 for insomnia-middle, and item 6 for insomnia-late) of The 17-item Hamilton Depression Rating Scale for depressed patients, which was correlated with the gBOLD-CSF coupling strength. RESULTS: The depressed patients exhibited weaker gBOLD-CSF coupling relative to healthy controls (p = 0.022), possibly due to impairment of the glymphatic system. Moreover, the gBOLD-CSF coupling strength correlated with insomnia-middle (r = 0.097, p = 0.008) in depressed patients. Limitations This study is a cross-sectional study. CONCLUSION: Our findings shed light on the pathophysiology of depression, indicating that cerebral waste clearance system deficits are correlated with poor sleep quality in depressed patients.
Subject(s)
Depressive Disorder , Glymphatic System , Sleep Initiation and Maintenance Disorders , Sleep Wake Disorders , Female , Humans , Young Adult , Adult , Middle Aged , Sleep Initiation and Maintenance Disorders/diagnostic imaging , Cross-Sectional Studies , Magnetic Resonance ImagingABSTRACT
BACKGROUND: This study investigated the effect of poly(ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy after first- and second-line chemotherapy on platinum sensitivity in patients with recurrent high-grade serous epithelial ovarian cancer (rHGSOC). METHODS: This study retrospectively analyzed 172 patients with rHGSOC treated at Zhejiang Cancer Hospital and Jiaxing Maternity and Child Health Care Hospital between January 2017 and December 2021. The 1st-PARPi group comprised patients who received a PARPi as maintenance therapy after first-line chemotherapy (n=23), and the 1st-control group comprised those who did not (n = 105). Similarly, the 2nd-PARPi group comprised patients not given a PARPi in their first-line treatment (n = 30), and the 2nd-control group comprised those who were given a PARPi (n = 89). RESULTS: Among the 23 patients in the 1st-PARPi group and the 105 patients in the 1st-control group, nine and 99 were platinum-sensitive, and 14 and six were platinum-resistant, respectively (hazard ratio [HR]: 14.46, P < 0.0001). Among the 30 patients in the 2nd-PARPi group and 89 patients in the 2nd-control group, 10 and 71 were platinum-sensitive, and 20 and 18 were platinumresistant, respectively (HR: 4.37, P < 0.0001). Age, stage, residual tumor, the courses of platinumbased chemotherapy, and breast cancer susceptibility gene mutations were not associated with platinum sensitivity when using a PARPi as maintenance therapy after first- and second-line chemotherapy. CONCLUSION: Patients with rHGSOC using a PARPi were more likely to be platinum-sensitive and develop platinum resistance independent of PARPi duration. Care should be taken when using a PARPi as maintenance therapy after first- and second-line chemotherapy.
Subject(s)
Carcinoma, Ovarian Epithelial , Drug Resistance, Neoplasm , Neoplasm Recurrence, Local , Ovarian Neoplasms , Poly(ADP-ribose) Polymerase Inhibitors , Humans , Female , Retrospective Studies , Middle Aged , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/pathology , Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Aged , Adult , Maintenance Chemotherapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Platinum/therapeutic use , Platinum/administration & dosage , Platinum/pharmacology , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/pathologyABSTRACT
BACKGROUND: Several studies have demonstrated that secondary cytoreductive surgery (SCS) for patients with recurrent uterine malignancies may improve the survival. However, the selection criteria for SCS remain to be defined. This study aimed to assess the outcome of SCS and to explore factors that may influence the prognosis. METHODS: Data of patients with recurrent uterine malignancies who received SCS in our hospital between January 2005 and January 2015 were retrospectively analyzed. Patients were assigned into endometrial carcinoma (EC) group and uterine sarcoma (US) group. RESULTS: 84 cases in total were involved in the study, including 47 cases with recurrent EC and 37 cases with recurrent US. The 5-year survival of cases with recurrent EC and recurrent US was 59.6% and 33.3%, respectively. Recurrent EC cases with a lower tumor grade (G1/G1-G2/G2), size of the largest tumor ≤ 6 cm, single recurrent tumor, a history of adjuvant therapy, as well as recurrent US cases with younger age, a longer disease-free interval (DFI) before SCS (≥ 12 months), no peritoneal dissemination, and a history of complete cytoreduction were associated with a longer survival. The number of recurrent tumors was found as an independent prognostic factor of SCS. CONCLUSION: Recurrent EC cases with a lower tumor grade, smaller tumor size, single tumor, a history of adjuvant therapy, as well as recurrent US cases with younger age, a longer DFI before SCS, no peritoneal dissemination, and a history of complete cytoreduction were more likely to benefit from SCS.
Subject(s)
Endometrial Neoplasms , Ovarian Neoplasms , Female , Humans , Infant , Ovarian Neoplasms/pathology , Prognosis , Cytoreduction Surgical Procedures , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Endometrial Neoplasms/surgery , Endometrial Neoplasms/pathologyABSTRACT
Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) typically manifests as rapidly progressive glomerulonephritis with crescent formation. In this report, we present a local case of myeloperoxidase (MPO)-AAV-associated acute interstitial nephritis (AIN), showing slight pauci-immune glomerulonephritis and positive MPO-ANCA. This case is characterized by foot process effacement of podocytes in the glomerulus, a favorable prognosis, and an absence of crescentic formation. To further understand this condition, we conducted a comprehensive literature search on Google Scholar and PubMed, employing both free text words and MeSH terms related to "AAV and AIN." This search yielded 24 cases, which we analyzed for their clinical features, laboratory findings, renal pathological characteristics, and therapeutic outcomes. AAV-associated interstitial nephritis predominantly affects elderly patients and is often associated with anemia, proteinuria, hematuria, and nonspecific manifestations, including fever, anorexia, fatigue, edema, and weight loss. Most of the cases in our review were MPO-ANCA-positive and exhibited isolated interstitial inflammation. These patients typically presented with relatively lower levels of serum creatinine, 24-h urine protein levels, and MPO-ANCA titers. All patients in our study received immunosuppressive therapy, including glucocorticoids, immunosuppressants, and rituximab, with the majority achieving clinical remission. Isolated AIN in the context of AAV is a rare occurrence, but it displays distinct clinical, laboratory, and pathological features. Patients with this presentation show a positive response to immunosuppressive treatment. Nevertheless, the establishment of definitive therapy guidelines for AAV-associated AIN remains uncertain and necessitates further investigation to develop comprehensive treatment guidelines. AIN, particularly when lacking typical glomerulus lesions, may represent a novel subgroup within MPO-AAV warranting additional research and clinical attention. Key Points ⢠This study contributes valuable scientific insights by highlighting that MPO-AAV-associated interstitial nephritis, even without crescentic formation, can exhibit podocyte foot process effacement and respond well to treatment. ⢠The presence of AIN, independent of crescentic glomerulonephritis, suggests the potential emergence of a new subclass within MPA-AAV. ⢠Notably, some cases of MPO-AAV-associated AIN may present with normal levels of Scr (Table 5, cases 5, 6, and 17). ⢠This observation highlights the importance of considering renal biopsy, diagnosis, and therapy in a timely manner to prevent the development of chronic kidney disease (CKD).
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Glomerulonephritis , Nephritis, Interstitial , Humans , Aged , Antibodies, Antineutrophil Cytoplasmic , Kidney/pathology , Glomerulonephritis/etiology , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Nephritis, Interstitial/pathology , Immunosuppressive Agents , PeroxidaseABSTRACT
Gray matter (GM) atrophy is well documented in patients with major depressive disorder (MDD), but its underlying mechanism remains unknown. This study aimed to examine the GM atrophy in MDD patients with diverse suicidal ideations (SIs) and to explore whether those alterations were driven by connections. GM volume was estimated in 163 patients with recurrent MDD (comprising 122 with SI [MDDSI] and 41 without SI [MDDNSI]) and 134 health controls (HCs). A two-sample t-test was used to identify GM volume abnormalities in MDD patients and their subgroups. Functional connectivity was computed between pairs of aberrant GM in both patients and HCs, which were further compared with the connectivity of random brain regions. A permutation test was performed to assess its significance. Propensity score matching (PSM) was further performed to validate the main results. Compared with HCs, the MDDNSI group exhibited GM atrophy in 24 regions, with the largest effect sizes found in the frontal and parietal lobes, while the MDDSI group exhibited more widespread GM atrophy involving 49 regions, with the largest effect sizes in the frontal lobe, parietal lobe, temporal lobe, and the limbic system. Furthermore, patients and HCs exhibited significantly increased functional connectivity between regions with GM atrophy compared with randomly selected regions (p < 0.05). PSM analysis presented similar results to the main analysis. MDD patients had diverse GM atrophy features according to their SI tendency. Moreover, connectome architecture modulates the GM atrophy in MDD patients, implying the possibility that connections drive these pathological changes.
Subject(s)
Atrophy , Brain , Connectome , Depressive Disorder, Major , Gray Matter , Magnetic Resonance Imaging , Suicidal Ideation , Humans , Depressive Disorder, Major/pathology , Depressive Disorder, Major/diagnostic imaging , Gray Matter/pathology , Gray Matter/diagnostic imaging , Male , Female , Connectome/methods , Magnetic Resonance Imaging/methods , Adult , Brain/pathology , Brain/diagnostic imaging , Middle Aged , Neural Pathways/pathology , Neural Pathways/diagnostic imagingABSTRACT
BACKGROUND: Up to the present time, there has remained a lack of strong evidence as to whether sentinel lymph node biopsy can replace lymphadenectomy for early endometrial cancer. The traditional surgery for endometrial cancer includes pelvic lymphadenectomy and paraaortic lymph node resection, but complications often seriously affect patients' quality of life. Two randomized controlled trials with large samples have proved that lymphadenectomy does not improve the overall recurrence rate and survival rate of patients. On the contrary, it increases the incidence of complications and even mortality. The current trial is designed to clarify whether sentinel lymph node biopsy can replace lymphadenectomy for early endometrial cancer patients with negative lymph nodes. METHODS: This study is a randomized, open-label, multicenter and non-inferiority controlled clinical trial in China. Potential participants will be patients with pathologically confirmed endometrial cancer at the Zhejiang Cancer Hospital, Jiaxing Maternity and Child Health Care Hospital, and the First Hospital of Jiaxing in China. The total sample size for this study is 722. Patients will be randomly assigned in a 1:1 ratio to two groups. Patients in one group will undergo sentinel lymph node biopsy + total hysterectomy + bilateral salpingo-oophorectomy ± paraaortic lymph node resection. Patients in the other group will undergo sentinel lymph node biopsy + total hysterectomy + bilateral salpingo-oophorectomy + pelvic lymphadenectomy ± paraaortic lymph node resection. The 3-year disease-free survival rate, overall survival rate, quality of life (use EORTC QLQ-C30 + QLQ-CX24), and perioperative related indexes of the two groups will be compared. RESULTS: We expect to find that for patients with early endometrial cancer, the 3-year disease-free survival rate following sentinel lymph node biopsy with indocyanine green combined with near-infrared fluorescence imaging is similar to that following lymphadenectomy. The operation time, as well as incidence of pelvic lymphocyst, lymphedema of lower limb, and edema of vulva in patients who only undergo sentinel lymph node biopsy are expected to be significantly lower than in patients who undergo lymphadenectomy. The quality of life of patients who undergo sentinel lymph node biopsy alone will be significantly better than that of patients who undergo lymph node dissection. CONCLUSION: This will prove that the prognosis of sentinel lymph node biopsy alone with indocyanine green combined with near-infrared fluorescence imaging is not inferior to that of sentinel lymph node biopsy plus lymphadenectomy for early stage endometrial cancer with negative nodal assessment intraoperatively. In addition, sentinel lymph node biopsy alone with indocyanine green combined with near-infrared fluorescence imaging results in fewer surgical complications and gives patients better quality of life. TRIAL REGISTRATION: chictr.org.cn, ChiCTR1900023161. Registered 14 May 2019, http://www.chictr.org.cn/edit.aspx?pid=38659&htm=4 .
Subject(s)
Endometrial Neoplasms , Sentinel Lymph Node , Pregnancy , Child , Humans , Female , Sentinel Lymph Node Biopsy/methods , Indocyanine Green , Quality of Life , Sentinel Lymph Node/surgery , Sentinel Lymph Node/pathology , Lymph Node Excision/adverse effects , Lymph Node Excision/methods , Lymph Nodes/surgery , Lymph Nodes/pathology , Endometrial Neoplasms/pathology , Randomized Controlled Trials as TopicABSTRACT
Gastric cancer (GC) remains a prevalent malignancy with high morbidity and mortality. CDKN1A interacting zinc finger protein 1 (CIZ1) has been demonstrated to have oncogenic functions in the development of cancers. We detected CIZ1 expression via quantitative real-time PCR (RT-qPCR). The protein level of CIZ1 was measured through Western blot. We noticed that CIZ1 expression was markedly enhanced in GC cells. Furthermore, functional experiments including colony formation assay, EdU staining assay, transwell assay, TUNEL staining assay and flow cytometry analysis uncovered that CIZ1 silencing attenuated cell malignant phenotypes in GC. Through bioinformatics tools and mechanism assays, we explored the up-stream mechanism of CIZ1 and determined that CIZ1 was modulated by FBXL19 antisense RNA 1 (FBXL19-AS1) and microRNA-339-3p (miR-339-3p). Additionally, miR-339-3p exerted a negative role on GC development in vitro, and FBXL19-AS1 depletion also had the inhibitory impacts on the progression of GC in vitro. Eventually, the finding that CIZ1 overexpression reversed the effects of FBXL19-AS1 silencing on GC development was validated by rescue assays. In a word, CIZ1 functioned as a tumor promoter in GC, indicating that CIZ1 might be a promising target for GC treatment.
ABSTRACT
BACKGROUND: Poly (ADP-ribose) polymerase (PARP) inhibitors are a new maintenance therapy option for patients with ovarian cancer (OC). OBJECTIVE: To evaluate the efficacy and influencing factors of the novel PARP inhibitor niraparib for maintenance treatment of Chinese patients with advanced OC. PATIENTS AND METHODS: In this retrospective multicenter real-world study patients with advanced OC from 15 hospitals throughout China were enrolled. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included the time to treatment discontinuation and safety. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to identify possible risk factors for PFS, after which a prediction model was established to evaluate the likelihood of achieving an 18-month PFS. The relationship between the dose of niraparib and PFS was also evaluated. RESULTS: The PFS rates of 199 patients at 6, 12, 18, 24, and 30 months were 87.4%, 75.9%, 63.6%, 56.1%, and 51.8%, respectively. LASSO regression model revealed that only age < 65 years (P = 0.011), BRCA mutations (P < 0.001), and R0 status after cytoreductive surgery (P = 0.01) were significant factors associated with prolonged PFS times. Based on the LASSO logistic regression analysis, a clinical prediction formula was developed: - 2.412 + 1.396Age≥65yr + 2.374BRCAwt + 1.387R1 + 0.793Interval≥12w + 0.178BMI>24kg/m2 which yielded a cut-off value of 0.091, an area under the curve (AUC) of 0.839 (0.763-0.916), a sensitivity of 94.3%, and an accuracy of 78.5%. A nomogram was then built to visualize the results. The major treatment-emergent adverse events of ≥ grade 3 included a platelet count decrease (19.1%), white blood cell count decrease (15.1%), neutrophil count decrease (13.1%), and anemia (18.6%). The 18-month PFS rates in patients treated with 200 mg niraparib were somewhat higher than in patients treated with 100 mg after 3-months of therapy. CONCLUSIONS: For Chinese OC patients, niraparib, particularly at a 200 mg individual starting dose, was an effective therapy with easily manageable safety.
Maintenance therapy with poly (ADP-ribose) polymerase inhibitors is a new option for patients with ovarian cancer (OC) after they have received platinum-based chemotherapy to reduce the recurrence or relapse rates, but it remains unclear whether there are any changes in efficacy and safety when different starting doses of niraparib are administrated to Chinese patients, who typically have a bodyweight < 77 kg. We found that niraparib exhibited satisfactory efficacy with tolerable safety during maintenance therapy for advanced OC whether administered at 100 mg or 200 mg doses. We believe these regimens can serve as a valuable addition to the previous results of randomized controlled trials.
Subject(s)
Ovarian Neoplasms , Humans , Female , Aged , Carcinoma, Ovarian Epithelial/drug therapy , Indazoles/pharmacology , Indazoles/therapeutic use , Piperidines/pharmacology , Piperidines/therapeutic useABSTRACT
Ischemic stroke is a disease with a very high incidence in the clinic, and hypertension is the most important variable risk factor of ischemic stroke. Studies have shown that intestinal microbes are involved in the occurrence and development of various diseases. This study aims to explore whether intestinal microbes play an important role in the pathogenesis of ischemic stroke in a hypertensive population. In this study, the inpatients in the Department of Neurology and Cardiology of the Second Affiliated Hospital of Shandong First Medical University in April 2021 were selected, including seven patients with hypertension complicated with ischemic stroke and only seven patients with hypertension. After collecting the stool samples of patients, the gene sequence of the samples was detected by 16S rRNA sequencing technology, and the double-ended 2 × 150 bp sequencing was carried out. After sequencing, the results were analyzed by diversity analysis, species difference analysis, species function difference analysis, and other bioinformatics tests. According to the test results, serum proteomics and biochemical blood tests were carried out to verify. There was no significant difference in α diversity and ß diversity between hypertension complicated with the cerebral infarction and hypertension groups. LEfSe analysis showed that at the genus level, compared with the hypertension group, Bacteroides, UCG_009, and Eisenbergiella had significantly increased relative abundance. The genera with relatively significantly reduced abundance are Ruminococcus_gnavus_group, Sutterellaceae, Burkholderia, and Prevotella and the LDA score of Prevotella is < - 4, which indicates that there are significant differences. Compared with the blood biochemical indexes, the results showed that the level of APOA1 in hypertensive patients with ischemic stroke was significantly higher than that in hypertensive patients (p < 0.05), but there was no significant difference in total cholesterol (CHOL), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein B (APOB), and free fatty acid (NEFA). Proteomic analysis showed that there were 89 up-regulated genes and 51 down-regulated genes in the serum of the two groups, and the expression of APOC2 and APOC3 in the cerebral infarction group with hypertension was significantly higher than that in the hypertension group (p < 0.05). The intestinal diversity of patients with hypertension complicated with stroke is similar to that of patients with hypertension, but there are differences in microbiota, among which Prevotella is the most significant. Prevotella could affect lipid metabolism so that APOC2 and APOC3 in the blood are significantly increased, leading to cerebral artery atherosclerosis and, finally, ischemic stroke. This provides a new idea for preventing and treating ischemic stroke in patients with hypertension, but the mechanism of Prevotella acting on apolipoprotein needs further verification by basic medical research.
Subject(s)
Hypertension , Ischemic Stroke , Microbiota , Stroke , Humans , Ischemic Stroke/complications , RNA, Ribosomal, 16S , Apolipoprotein C-II , Proteomics , Stroke/complications , Hypertension/complications , Cerebral InfarctionABSTRACT
Light and phytohormone are external and internal cues that regulate plant growth and development throughout their life cycle. BBXs (B-box domain proteins) are a group of zinc finger proteins that not only directly govern the transcription of target genes but also associate with other factors to create a meticulous regulatory network to precisely regulate numerous aspects of growth and developmental processes in plants. Recent studies demonstrate that BBXs play pivotal roles in light-controlled plant growth and development. Besides, BBXs have been documented to regulate phytohormone-mediated physiological procedures. In this review, we summarize and highlight the multi-faced role of BBXs, with a focus in photomorphogenesis, photoperiodic flowering, shade avoidance, abiotic stress, and phytohormone-mediated growth and development in plant.
ABSTRACT
BACKGROUND: Distinguishing bipolar disorder (BD) and unipolar disorder (UD) remains challenging. To identify the common and diagnosis-specific neuropathological alterations and their potential molecular mechanisms in patients with UD and BD (with a current depressive episode). METHODS: Resting-state functional magnetic resonance imaging was obtained from 279 participants (95 BD patients, 107 UD patients and 77 health controls). Connectome gradients analysis was performed to explore the shared and diagnosis-specific gradient alterations in BD and UD. The Allen Human Brain Atlas data was used to explore the potential gene mechanisms of the gradient alterations. RESULTS: BD and UD had shared hierarchical disorganisation, including downgrading and contraction from the unimodal sensory networks (vision and sensorimotor) to the transmodal cognitive networks (limbic, frontoparietal, dorsal attention, and default) (all P < 0.05, FDR corrected) in gradient 1 and gradient 2. The BD patients had specific connectome gradient dysfunction in the subcortical network. Moreover, the hierarchical disorganisation was closely correlated with profiles of gene expression specific to the neuroglial cells in the prefrontal cortex in BD and UD, while the most correlated gene ontology biological processes and function were concentrated in synaptic signalling, calcium ion binding, and transmembrane transporter activity. CONCLUSION: These findings reveal the shared and diagnosis-specific neurobiological mechanism underlying BD and UD patients, which advances our understanding of the neuromechanisms of these disorders.
Subject(s)
Bipolar Disorder , Connectome , Humans , Bipolar Disorder/diagnostic imaging , Bipolar Disorder/genetics , Neurobiology , Transcriptome , Brain/diagnostic imagingABSTRACT
Objectives: Physical activity (PA) is known to improve physical functioning and mental health and to reduce the incidence of dementia. However, studies of the effects of non-recreational PA on the incidence of dementia, especially in East Asian populations, remain limited. In this study, we evaluate the association of doing housework with the risk of dementia among participants in the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Methods: The analysis was conducted with data from 7,237 CLHLS participants age over 65 obtained in 2008/2009, 2011/2012, 2014, and 2018. The frequency of housework performance was classified into four groups. A Cox proportional-hazards model was used to examine the association of the baseline housework frequency with the incidence of dementia, with adjustment for demographic and socioeconomic characteristics and lifestyle and health conditions. Results: The adjusted multivariate model showed that the incidence of dementia was lower among participants who did housework almost every day than among those who rarely or never did housework (hazard ratio = 0.49; 95% confidence interval, 0.39-0.61). The subgroup and sensitivity analyses yielded similar results. Conclusion: A high frequency of housework performance was associated with a reduced incidence of dementia among older Chinese adults, especially those who did not exercise regularly. The encouragement of engagement in housework would be a cost-effective measure promoting healthy aging in the Chinese population.