Hepatoid adenocarcinoma in ureter with next-generation sequencing: A case report and literature review.

BACKGROUND: Hepatoid adenocarcinoma (HAC) is rare in the urinary system, with only 7 reported cases in upper urinary tract. This report aimed to explore the genetic characteristics of ureteral HAC for first time, and to describe the treatment prognosis of ureteral HAC. CASE PRESENTATION: We present a rare case of ureteral HAC in a 53-year-old female, showing elevated serum levels of AFP and CEA, prolonged chronic irritation may be an important cause of her ureteral HAC. Radical nephroureterectomy was performed, the serum levels of AFP and CEA decreased significantly, and metastasis in lymph nodes was found at 9 months after surgery, she had no related symptoms after 18 months postoperatively without adjuvant chemotherapy. Three driver somatic mutations in cancer were identified by NGS testing, including: TP53D281H, KMT2DL1211Ifs*2, KMT2DT1843Nfs*5, demonstrating that ureteral HAC has the similar mutational features to upper tract urothelial carcinoma. Homologous-recombination deficiency (HRD) was positive in this tumor with no mutations in HRD-related genes, which was possibly induced by the copy number deletion of SETD2 gene. CONCLUSIONS: We report a rare case of ureteral HAC with elevated serum levels of AFP and CEA. NGS testing demonstrated that ureteral HAC has the similar mutational features to upper tract urothelial carcinoma, which is an important guide for the diagnosis and treatment of ureteral HAC.

DLGAP5 triggers proliferation and metastasis of bladder cancer by stabilizing E2F1 via USP11.

Bladder cancer (BLCA) is one of the most widespread malignancies worldwide, and displays significant tumor heterogeneity. Understanding the molecular mechanisms exploitable for treating aggressive BLCA represents a crucial objective. Despite the involvement of DLGAP5 in tumors, its precise molecular role in BLCA remains unclear. BLCA tissues exhibit a substantial increase in DLGAP5 expression compared with normal bladder tissues. This heightened DLGAP5 expression positively correlated with the tumor's clinical stage and significantly affected prognosis negatively. Additionally, experiments conducted in vitro and in vivo revealed that alterations in DLGAP5 expression notably influence cell proliferation and migration. Mechanistically, the findings demonstrated that DLGAP5 was a direct binding partner of E2F1 and that DLGAP5 stabilized E2F1 by preventing the ubiquitination of E2F1 through USP11. Furthermore, as a pivotal transcription factor, E2F1 fosters the transcription of DLGAP5, establishing a positive feedback loop between DLGAP5 and E2F1 that accelerates BLCA development. In summary, this study identified DLGAP5 as an oncogene in BLCA. Our research unveils a novel oncogenic mechanism in BLCA and offers a potential target for both diagnosing and treating BLCA.

Effect of electromagnetic induction drying on the drying-incineration process of dyeing sludge: focus on migration and conversion of sulfur.

Secondary sulfur pollution in dyeing sludge (DS) during drying and incineration is a major environmental problem necessitating in-situ control. To robustly immobilise sulfur during drying-incineration, the authors introduce an electromagnetic induction (EMI) drying method and reveal the corresponding migration and conversion of sulfur in DS. The EMI-drying efficiency reached 10.69%/min, five times that of thermal drying. EMI drying increases the relative sulfoxide ratio from that of thermal drying. In a sludge-sulfur model, the proposed treatment promoted the oxidation and decomposition of organic sulfur without noticeably affecting the inorganic sulfur. The selective oxidation process during EMI drying promotes sulfur stabilisation in dried DS, decreasing the performance and stability of DS combustion. The sulfur-containing pollutants released during the incineration of DS mainly contain H2S, followed by CH3SH and SO2. EMI drying increases the outputs of SO2 and CH3SH but decreases the outputs H2S and total sulfur compared with the outputs of thermal drying. Under the sulfur-model conditions, EMI promoted the conversion of inorganic sulfur to sulfur-containing gases (especially H2S) during incineration. In contrast, the sulfur stabilised by partial oxidation of organic sulfur in the EMI-dried DS was not easily converted to gaseous sulfur during subsequent combustion. Overall, EMI inhibits the release of sulfur during the combined drying-incineration process of DS.

Functional and structural brain reorganization in patients with ischemic stroke: a multimodality MRI fusion study.

Understanding how structural and functional reorganization occurs is crucial for stroke diagnosis and prognosis. Previous magnetic resonance imaging (MRI) studies focused on the analyses of a single modality and demonstrated abnormalities in both lesion regions and their associated distal regions. However, the relationships of multimodality alterations and their associations with poststroke motor deficits are still unclear. In this study, 71 hemiplegia patients and 41 matched healthy controls (HCs) were recruited and underwent MRI examination at baseline and at 2-week follow-up sessions. A multimodal fusion approach (multimodal canonical correlation analysis + joint independent component analysis), with amplitude of low-frequency fluctuation (ALFF) and gray matter volume (GMV) as features, was used to extract the co-altered patterns of brain structure and function. Then compared the changes in patients' brain structure and function between baseline and follow-up sessions. Compared with HCs, the brain structure and function of stroke patients decreased synchronously in the local lesions and their associated distal regions. Damage to structure and function in the local lesion regions was associated with motor function. After 2 weeks, ALFF in the local lesion regions was increased, while GMV did not improve. Taken together, the brain structure and function in the local lesions and their associated distal regions were damaged synchronously after ischemic stroke, while during motor recovery, the 2 modalities were changed separately.

Acupuncture Alters Brain's Dynamic Functional Network Connectivity in Stroke Patients with Motor Dysfunction: A Randomised Controlled Neuroimaging Trial.

Objectives: Neuroimaging studies have confirmed that acupuncture can promote static functional reorganization in poststroke patients with motor dysfunction. But its effect on dynamic brain networks remains unclear. This study is aimed at investigating how acupuncture affected the brain's dynamic functional network connectivity (dFNC) after ischemic stroke. Methods: We conducted a single-center, randomised controlled neuroimaging study in ischemic stroke patients. A total of 53 patients were randomly divided into the true acupoint treatment group (TATG) and the sham acupoint treatment group (SATG) at a ratio of 2 : 1. Clinical assessments and magnetic resonance imaging (MRI) scans were performed on subjects before and after treatment. We used dFNC analysis to estimate distinct dynamic connectivity states. Then, the temporal properties and strength of functional connectivity (FC) matrix were compared within and between the two groups. The correlation analysis between dynamic characteristics and clinical scales was also calculated. Results: All functional network connectivity (FNC) matrices were clustered into 3 connectivity states. After treatment, the TATG group showed a reduced mean dwell time and found attenuated FC between the sensorimotor network (SMN) and the frontoparietal network (FPN) in state 3, which was a sparsely connected state. The FC between the dorsal attention network (DAN) and the default mode network (DMN) was higher after treatment in the TATG group in state 1, which was a relative segregated state. The SATG group preferred to increase the mean dwell time and FC within FPN in state 2, which displayed a local tightly connected state. In addition, we found that the FC value increased between DAN and right frontoparietal network (RFPN) in state 1 in the TATG group after treatment compared to the SATG group. Correlation analyses before treatment showed that the Fugl-Meyer Assessment (FMA) lower score was negatively correlated with the mean dwell time in state 3. FMA score showed positive correlation with FC in RFPN-SMN in state 3. FMA-lower score was positively correlated with FC in DAN-DMN and DAN-RFPN in state 1. Conclusions: Acupuncture has the potential to modulate abnormal temporal properties and promote the balance of separation and integration of brain function. True acupoint stimulation may have a more positive effect on regulating the brain's dynamic function. Clinical Trial Registration. This trial is registered with Chinese Clinical Trials Registry (ChiCTR1800016263).

Scalp acupuncture regulates functional connectivity of cerebral hemispheres in patients with hemiplegia after stroke.

Background: Stroke is a common cause of acquired disability on a global scale. Patients with motor dysfunction after a stroke have a reduced quality of life and suffer from an economic burden. Scalp acupuncture has been proven to be an effective treatment for motor recovery after a stroke. However, the neural mechanism of scalp acupuncture for motor function recovery remains to be researched. This study aimed to investigate functional connectivity (FC) changes in region of interest (ROI) and other brain regions to interpret the neural mechanism of scalp acupuncture. Methods: Twenty-one patients were included and randomly divided into patient control (PCs) and scalp acupuncture (SAs) groups with left hemiplegia due to ischemic stroke, and we also selected 20 matched healthy controls (HCs). The PCs were treated with conventional Western medicine, while the SAs were treated with scalp acupuncture (acupuncture at the right anterior oblique line of vertex temporal). All subjects received whole-brain resting-state functional magnetic resonance imaging (rs-fMRI) scan before treatment, and the patients received a second scan after 14 days of treatment. We use the National Institutes of Health Stroke Scale (NIHSS) scores and the analyses of resting-state functional connectivity (RSFC) as the observational indicators. Results: The contralateral and ipsilateral cortex of hemiplegic patients with cerebral infarction were associated with an abnormal increase and decrease in basal internode function. An abnormal increase in functional connectivity mainly exists in the ipsilateral hemisphere between the cortex and basal ganglia and reduces the abnormal functional connectivity in the cortex and contralateral basal ganglia. Increased RSFC was observed in the bilateral BA6 area and bilateral basal ganglia and the connectivity between bilateral basal ganglia nuclei improved. However, the RSFC of the conventional treatment group only improved in the unilateral basal ganglia and contralateral BA6 area. The RSFC in the left middle frontal gyrus, superior temporal gyrus, precuneus, and other healthy brain regions were enhanced in SAs after treatment. Conclusion: The changes in functional connectivity between the cerebral cortex and basal ganglia in patients with cerebral infarction showed a weakening of the bilateral hemispheres and the enhancement of the connections between the hemispheres. Scalp acupuncture has the function of bidirectional regulation, which makes the unbalanced abnormal brain function state restore balance.

Integrated analysis of the roles of oxidative stress related genes and prognostic value in clear cell renal cell carcinoma.

BACKGROUND: Patients with clear cell renal cell carcinoma (ccRCC), which is the most commonly diagnosed subtype of renal cell carcinoma, are at risk of tumor metastasis and recrudescence. Previous research has shown that oxidative stress can induce tumorigenesis in many cancers and can be a target of cancer treatment. Despite these findings, little progress has been made understanding in the association of oxidative stress-related genes (OSRGs) with ccRCC. METHODS: In vitro experiments were conducted with MTT survival assays, qRT‒PCR, apoptosis assays, cell cycle assays, ROS assays, and IHC staining. RESULTS: In our study, 12 differentially expressed oxidative stress-related genes (DEOSGs) and related transcription factors (TFs) that are relevant to overall survival (OS) were screened, and their mutual regulatory networks were constructed with data from the TCGA database. Moreover, we constructed a risk model of these OSRGs and performed clinical prognostic analysis and validation. Next, we performed protein-protein interaction (PPI) network analysis and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of MELK, PYCR1, and PML. A tissue microarray also verified the high expression of MELK and PYCR1 in ccRCC. Finally, in vitro cellular experiments demonstrated that knockdown of MELK or PYCR1 significantly inhibited ccRCC cell proliferation by causing cell apoptosis and inducing cell cycle arrest in the G1 phase. Intracellular ROS levels were elevated after these two genes were knocked down. CONCLUSION: Our results revealed the potential DEORGs to be used in ccRCC prognostic prediction and identified two biomarkers, named PYCR1 and MELK, which regulated the proliferation of ccRCC cells by affecting ROS levels. Furthermore, PYCR1 and MELK could be promising targets for predicting the progression and prognosis of ccRCC, thereby serving as new targets for medical treatments.

Aspartoacylase suppresses prostate cancer progression by blocking LYN activation.

BACKGROUND: Globally, despite prostate cancer (PCa) representing second most prevalent malignancy in male, the precise molecular mechanisms implicated in its pathogenesis remain unclear. Consequently, elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies, ultimately advancing the management of PCa. METHODS: A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University. The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa. The expression of aspartoacylase (ASPA) in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques. To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis, a comprehensive set of in vitro and in vivo assays were conducted, including orthotopic and tumor-bearing mouse models (n = 8 for each group). A combination of experimental approaches, such as Western blotting, luciferase assays, immunoprecipitation assays, mass spectrometry, glutathione S-transferase pull-down experiments, and rescue studies, were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa. The Student's t-test was employed to assess the statistical significance between two distinct groups, while one-way analysis of variance was utilized for comparisons involving more than two groups. A two-sided P value of less than 0.05 was deemed to indicate statistical significance. RESULTS: ASPA was identified as a novel inhibitor of PCa progression. The expression of ASPA was found to be significantly down-regulated in PCa tissue samples, and its decreased expression was independently associated with patients' prognosis (HR = 0.60, 95% CI 0.40-0.92, P = 0.018). Our experiments demonstrated that modulation of ASPA activity, either through gain- or loss-of-function, led to the suppression or enhancement of PCa cell proliferation, migration, and invasion, respectively. The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models. Mechanistically, ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets, JNK1/2 and C-Jun, in both PCa cells and mouse models, in an enzyme-independent manner. Importantly, the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models. Moreover, we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples, suggesting a potential regulatory role of ASPA in modulating LYN signaling. CONCLUSION: Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.

Neuroimaging mechanisms of acupuncture on functional reorganization for post-stroke motor improvement: a machine learning-based functional magnetic resonance imaging study.

Objective: Motor recovery is crucial in stroke rehabilitation, and acupuncture can influence recovery. Neuroimaging and machine learning approaches provide new research directions to explore the brain functional reorganization and acupuncture mechanisms after stroke. We applied machine learning to predict the classification of the minimal clinically important differences (MCID) for motor improvement and identify the neuroimaging features, in order to explore brain functional reorganization and acupuncture mechanisms for motor recovery after stroke. Methods: In this study, 49 patients with unilateral motor pathway injury (basal ganglia and/or corona radiata) after ischemic stroke were included and evaluated the motor function by Fugl-Meyer Assessment scores (FMA) at baseline and at 2-week follow-up sessions. Patients were divided by the difference between the twice FMA scores into one group showing minimal clinically important difference (MCID group, n = 28) and the other group with no minimal clinically important difference (N-MCID, n = 21). Machine learning was performed by PRoNTo software to predict the classification of the patients and identify the feature brain regions of interest (ROIs). In addition, a matched group of healthy controls (HC, n = 26) was enrolled. Patients and HC underwent magnetic resonance imaging examination in the resting state and in the acupuncture state (acupuncture at the Yanglingquan point on one side) to compare the differences in brain functional connectivity (FC) and acupuncture effects. Results: Through machine learning, we obtained a balance accuracy rate of 75.51% and eight feature ROIs. Compared to HC, we found that the stroke patients with lower FC between these feature ROIs with other brain regions, while patients in the MCID group exhibited a wider range of lower FC. When acupuncture was applied to Yanglingquan (GB 34), the abnormal FC of patients was decreased, with different targets of effects in different groups. Conclusion: Feature ROIs identified by machine learning can predict the classification of stroke patients with different motor improvements, and the FC between these ROIs with other brain regions is decreased. Acupuncture can modulate the bilateral cerebral hemispheres to restore abnormal FC via different targets, thereby promoting motor recovery after stroke. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=37359, ChiCTR1900022220.

The relationship between patient-family caregiver congruence/incongruence in acceptance of illness and family caregivers' anticipatory grief.

OBJECTIVE: Cancer is a family affair that negatively impacts the lives of patients and their family caregivers. This study takes a dyadic perspective to investigate the effect of patient-family caregiver illness acceptance congruence/incongruence on family caregivers' anticipatory grief (AG) and examine whether caregivers' resilience moderates the abovementioned relationship. METHODS: For the study, 304 dyads of advanced lung cancer patients and their family caregivers from three tertiary hospitals in Jinan, Shandong Province, China were recruited. The data were analyzed using polynomial regressions and response surface analyses. RESULTS: Family caregivers' AG was lower when patient-family caregiver illness acceptance was congruent rather than incongruent. Lower patient-caregiver illness acceptance congruence was associated with higher AG in family caregivers compared with higher illness acceptance congruence. Family caregivers reported significantly higher AG only if their illness acceptance was lower than that of their patients. In addition, caregivers' resilience moderated the effects of patient-caregiver illness acceptance congruence/incongruence on family caregivers' AG. CONCLUSIONS: Patient-family caregiver illness acceptance congruence was beneficial to family caregivers' AG; resilience can be a protective factor for buffering the impact of illness acceptance incongruence on family caregivers' AG.

Transrectal versus transperineal prostate biopsy in detection of prostate cancer: a retrospective study based on 452 patients.

BACKGROUND: Transrectal (TR) ultrasound guided prostate biopsy and transperineal (TP) ultrasound guided prostate biopsy are the two most commonly used methods to detect prostate cancer, the detection rate of the two biopsy approaches may differ in patients with different clinical characteristics. Here we aimed to compare the prostate cancer detection rate and positive rate of biopsy cores between TR and TP prostate biopsy in patients with different clinical characteristics. METHODS: We retrospectively analyzed and compared the clinical data of 452 patients underwent TR or TP prostate biopsy in our hospital from June 2017 to September 2021. And patients were stratified according to several clinical characteristic (serum PSA level, prostate volume, PSA density, T stage and ISUP grade), cancer detection rate and positive rate of biopsy cores were compared in different stratified groups. RESULTS: There was no significant difference in age, PSA level, prostate volume, and PSA density between the TR and TP groups. TR group had a higher overall cancer detection rate and positive rate of biopsy cores than TP group. Further subgroup analysis showed that TR group had a higher cancer detection rate in patients with prostate volumes 30-80 mL, and that the TR group had a higher positive rate of biopsy cores among the patients with T3-T4 stages, while TP group had a higher positive rates of biopsy cores among the patients with T1-T2 stages. There were no significant differences between the TR and TP groups for each subgroup when stratified by PSA level, PSA density and ISUP grade. CONCLUSIONS: TR approach may have advantage in patients with prostate volumes 30-80 mL and T3-T4 stages, while TP approach may have advantage in patients with T1-T2 stages.

Tai Chi increases functional connectivity and decreases chronic fatigue syndrome: A pilot intervention study with machine learning and fMRI analysis.

BACKGROUND: The latest guidance on chronic fatigue syndrome (CFS) recommends exercise therapy. Tai Chi, an exercise method in traditional Chinese medicine, is reportedly helpful for CFS. However, the mechanism remains unclear. The present longitudinal study aimed to detect the influence of Tai Chi on functional brain connectivity in CFS. METHODS: The study recruited 20 CFS patients and 20 healthy controls to receive eight sessions of Tai Chi exercise over a period of one month. Before the Tai Chi exercise, an abnormal functional brain connectivity for recognizing CFS was generated by a linear support vector model. The prediction ability of the structure was validated with a random forest classification under a permutation test. Then, the functional connections (FCs) of the structure were analyzed in the large-scale brain network after Tai Chi exercise while taking the changes in the Fatigue Scale-14, Pittsburgh Sleep Quality Index (PSQI), and the 36-item short-form health survey (SF-36) as clinical effectiveness evaluation. The registration number is ChiCTR2000032577 in the Chinese Clinical Trial Registry. RESULTS: 1) The score of the Fatigue Scale-14 decreased significantly in the CFS patients, and the scores of the PSQI and SF-36 changed significantly both in CFS patients and healthy controls. 2) Sixty FCs were considered significant to discriminate CFS (P = 0.000, best accuracy 90%), with 80.5% ± 9% average accuracy. 3) The FCs that were majorly related to the left frontoparietal network (FPN) and default mode network (DMN) significantly increased (P = 0.0032 and P = 0.001) in CFS patients after Tai Chi exercise. 4) The change of FCs in the left FPN and DMN were positively correlated (r = 0.40, P = 0.012). CONCLUSION: These results demonstrated that the 60 FCs we found using machine learning could be neural biomarkers to discriminate between CFS patients and healthy controls. Tai Chi exercise may improve CFS patients' fatigue syndrome, sleep quality, and body health statement by strengthening the functional connectivity of the left FPN and DMN under these FCs. The findings promote our understanding of Tai Chi exercise's value in treating CFS.

Using Haemocoagulase Agkistrodon in Patients Undergoing Transurethral Plasmakinetic Resection of the Prostate: A Pilot, Real-World, and Propensity Score-Matched Study.

Objectives: To compare the clinical outcomes of using different hemostatic agents after transurethral plasmakinetic resection of the prostate (TUPKP) in benign prostatic hyperplasia (BPH) patients. Methods: The patients were divided into 5 groups according to the hemostatic agents used after TUPKP, including the haemocoagulase agkistrodon for injection (HCA), hemocoagulase for injection (HC), hemocoagulase bothrops atrox for injection (HCB), ethylenediamine diaceturate injection (EDD), and tranexamic acid (TXA). Propensity score matching was performed based on age, body mass index, prostate volume, hypertension status, fasting blood glucose, smoking, and drinking history. The hospitalization time, bladder irrigation time, indwelling catheterization time, the patency of urine flow, and blood transfusion records were used as outcome indicators to compare the clinical effects of these five agents. Results: We finally matched 65 pairs receiving HCA or HC, 71 pairs receiving HCA or HCB, 38 pairs receiving HCA or TXA, and 29 pairs receiving HCA or EDD. Compared with HC, HCA given during the perioperative period significantly reduced the median hospitalization time [7.00 days (5.00, 8.00) vs. 9.00 days (8.00, 10.00); p < 0.001] and median catheterization time (109.00 hours [88.00, 129.00] vs. 164.00 hours [114.00, 189.00], p < 0.001). Compared with EDD, the median hospitalization time (7.00 days [6.00, 8.00] vs. 10.00 days [8.00, 11.00]; p < 0.001) and median catheterization time (113.00 hours [95.00, 143.00] vs. 160.00 hours [139.00, 168.00]; p < 0.001) were also significant shorter in HCA group. Compared with HCB, median bladder irrigation time (45.00 hours [27.00, 71.00] vs. 49.00 hours [45.00, 72.00]; p = 0.04) was shorter in the HCA group. However, there were no statistical differences in outcomes between HCA and TXA. Conclusions: HCA probably has an advantage over HC, HCB, and EDD in reducing the hospitalization time, catheterization time, and bladder irrigation time among BPH patients undergoing TUPKP.

Erratum: EFEMP2 suppresses epithelial-mesenchymal transition via Wnt/ß-catenin signaling pathway in human bladder cancer: Erratum.

[This corrects the article DOI: 10.7150/ijbs.35541.].

Sensorimotor Responses in Post-Stroke Hemiplegic Patients Modulated by Acupuncture at Yanglingquan (GB34): A fMRI Study Using Intersubject Functional Correlation (ISFC) Analysis.

Motor dysfunction is common in patients with stroke. Acupuncture has become an acceptable alternative method for stroke rehabilitation. Previous studies have shown various functional connectivity changes activated by acupuncture. We introduced intersubject correlation (ISC) and intersubject functional correlation (ISFC) analyses into the functional magnetic resonance imaging (fMRI) for ischemic stroke to seek a common activation and suppression pattern triggered by acupuncture. In this study, 63 ischemic stroke patients with motor dysfunction and 42 normal controls were analyzed. Three functional scans were conducted during the resting state, motor task, and acupuncture at Yanglingquan (GB34) task. Twenty-two sensory, motor, and movement-imagination cortices in the bilateral hemispheres were selected as the region of interest (ROI). We performed ISC and ISFC analyses among these ROIs in three fMRI runs on patients and controls. Subgroup analyses by course or severity were also conducted. The results showed that acupuncture at GB34 triggered ISFC among upper limb motor, upper limb/hand/face, lower limb, tongue/larynx sensory, and movement imagination regions in the patient group. Subgroup ISC and ISFC analyses showed that patients tended to have increasing responses in the early stage of stroke (within 1 month) and decreasing responses afterward (1-3 months). Patients with mild clinical functional damage (NIHSS 2-4) tended to generate more responses via acupuncture than those with moderate damage (NIHSS 5-15). Our findings may help understand the clinical effects and modulatory features of acupuncture based on the group-level post-stroke neuroplasticity.

Hepatic exosomes with declined MiR-27b-3p trigger RIG-I/TBK1 signal pathway in macrophages.

BACKGROUND AND AIMS: Evidence suggests that interferon alpha (IFNα) plays an essential role in decreasing the HBsAg quantification and elevating the rate of clinical cure in chronic hepatitis B (CHB). However, the mechanisms underlying the effects of the exosomes on the expression of host genes in IFNα treatment remain unclear. METHODS: CHB patients with IFNα treatment were divided into responders and non-responders according to the degree of HBsAg decline. Through microRNA sequencing and a series of molecular biology methods, the key microRNAs in serum exosomes associated with clinical antiviral response of Peg-IFNα treatment in nucleotide analogue-treated CHB patients were investigated. The roles of exosomal miRNAs on the IFNα signal pathway were explored in macrophages. RESULTS: MicroRNA sequencing and RT-qPCR assays confirmed six distinctly declined miRNAs in serum exosomes of responders at week 12 compared with levels at baseline. Exosomes with declined miR27b-3p in the serum of Peg-IFNα-treated responders activated phosphorylation of interferon regulatory factor 3/7 (IRF3/7) in IFNα synthesis pathway in macrophages. However, miR27b-3p overexpression in HepAD38 cells suppressed IFNα synthesis in macrophages, resulting in insufficient ability to eliminate HBV, whereas the inhibitory effect could be blocked by inhibitors of exosomes release. Luciferase assay showed miR-27b-3p directly suppressed retinoic acid-inducible gene I (RIG-I) and TANK-binding kinase 1 (TBK1) expressions, and these effects could be abrogated in mutation experiments. CONCLUSIONS: In IFNα treatment, exosomes with declined miR-27b-3p triggered activation of RIG-I/TBK1 signalling in macrophages against HBV. Serum exosomal miR-27-3p might represent a potential biomarker for patients with CHB.

Do type A personality and neuroticism moderate the relationships of occupational stressors, job satisfaction and burnout among Chinese older nurses? A cross-sectional survey.

BACKGROUND: The high prevalence of burnout among nurses produces huge health service losses. Existing literature found that occupational stressors and low levels of job satisfaction were related to burnout, whilst personality traits such as type A personality and neuroticism influenced occupational stressors, job satisfaction, and burnout. The purpose of this study was to investigate the mediating effect of job satisfaction on the relationship between occupational stressors and burnout among Chinese older nurses, and explore the moderating effects of type A personality and neuroticism on the relationships among occupational stressors, job satisfaction and burnout. METHODS: A cross-sectional study was conducted in five provinces and municipalities (mainly in Shandong) in China. A total of 527 female older nurses (age≧40) were included in this study. Structural equation modelling (SEM) approach was employed to investigate the mediating effect of job satisfaction on the relationship between occupational stressors and burnout. Multi-group analysis was conducted to explore the moderating effects of type A personality and neuroticism on the relationships among occupational stressors, job satisfaction and burnout. RESULTS: Both nurses with high type A personality and high neuroticism had higher occupational stressors, higher burnout and lower job satisfaction. Occupational stressors had direct effect (ß = 0.29, P = 0.001) and indirect effect mediated by low levels of job satisfaction (ß = 0.25, P = 0.001) on burnout. Type A personality had significant moderated effect (P = 0.007) on the relationships among occupational stressors, job satisfaction and burnout, whereas the moderated effect of neuroticism was not significant. CONCLUSIONS: Low levels of job satisfaction mediated the relationship between occupational stressors and burnout among Chinese older nurses, and both the direct and indirect effect of occupational stressors on burnout were moderated by type A personality. Hospital administrators should take specific measures such as transferring older nurses to easier positions to reduce their occupational stress, thereby increasing their job satisfaction and reducing their burnout, which is especially important for the older nurses with high type A personality.

A combination of laparoscopic approach and ERAS pathway optimizes outcomes and cost for adrenalectomy.

Enhanced recovery after surgery (ERAS) pathway comprises a set of comprehensive elements which have been reported to enhance patient postoperative prognosis. In the current study, we aimed to evaluate the effectiveness of the ERAS in patients undergoing laparoscopic adrenal resection. A retrospective review was performed to compare the outcomes of patients undergoing adrenalectomy for primary aldosteronism between the pre-ERAS period and the ERAS era. Data was generated from the traditional surgical period (September 1, 2019, to December 31, 2019) and the ERAS period (September 1, 2020, to December 31, 2020), respectively. Forty-seven adrenalectomy patients were enrolled (pre-ERAS, n = 21; ERAS, n = 26) in analysis. The results revealed that both total length of hospital stay and postoperative length of stay decreased in the ERAS period compared with the pre-ERAS period (14.19 ± 4.96 vs 11.27 ± 4.37, p = 0.015; 5.43 ± 1.08 vs 3.31 ± 0.97, p < 0.001). The medical expenses decreased significantly in the ERAS group (p < 0.05). While, the surgery-related complications, including urinary retention, retroperitoneal effusion and gastrointestinal discomfort, possessed no statistical difference. The ERAS pathway was safe and feasible for adrenalectomy in patients with primary aldosteronism. The ERAS could promote patients to quickly recover from the postoperative status to a physiological state, and decrease the length of hospitalization and medical cost after surgery.

Favipiravir Versus Arbidol for Clinical Recovery Rate in Moderate and Severe Adult COVID-19 Patients: A Prospective, Multicenter, Open-Label, Randomized Controlled Clinical Trial.

Background: In addition to supportive therapy, antiviral therapy is an effective treatment for coronavirus disease 2019 (COVID-19). Objective: To compare the efficacy and safety of favipiravir and umifenovir (Arbidol) to treat COVID-19 patients. Methods: We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Enrolled patients with initial symptoms within 12 days were randomly assigned in a 1:1 ratio to receive conventional therapy plus Arbidol (200 mg*3/day) or favipiravir (1600 mg*2/first day followed by 600 mg*2/day) for 7 days. The primary outcome was the clinical recovery rate at day 7 of drug administration (relief for pyrexia and cough, respiratory frequency ≤24 times/min; oxygen saturation ≥98%). Latency to relief for pyrexia and cough and the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV)/mechanical ventilation (MV) were the secondary outcomes. Safety data were collected for 17 days. Results: A total of 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive favipiravir (116 assessed), and 120 patients were assigned to receive Arbidol (120 assessed). The clinical recovery rate at day 7 of drug administration did not significantly differ between the favipiravir group (71/116) and Arbidol group (62/120) (p = 0.1396, difference in recovery rate: 0.0954; 95% CI: -0.0305∼0.2213). Favipiravir contributed to relief for both pyrexia (difference: 1.70 days, p < 0.0001) and cough (difference: 1.75 days, p < 0.0001). No difference was observed in the AOT or NMV/MV rate (both p > 0.05). The most frequently observed favipiravir-associated adverse event was increased serum uric acid (16/116, OR: 5.52, p = 0.0014). Conclusion: Among patients with COVID-19, favipiravir, compared to Arbidol, did not significantly improve the clinical recovery rate at day 7. Favipiravir significantly improved the latency to relieve pyrexia and cough. Adverse effects caused by favipiravir are mild and manageable.

Clinical analysis and a novel risk predictive nomogram for 155 adult patients with hemophagocytic lymphohistiocytosis.

Recently, more and more attention has been paid on adult hemophagocytic lymphohistiocytosis (HLH), a disease with complicated symptoms and high mortality. In order to analyze the clinical characteristics and prediction risk factors of mortality, we designed a retrospective study with 1-year follow-up and included 155 patients admitted to Tongji Hospital diagnosed as HLH. One hundred seven patients formed the training cohort for nomogram development, and 48 patients formed the validation cohort to confirm the model's performance. All patients' clinical characteristics, laboratory results, medical records, and prognosis were analyzed. Among all the 107 patients in the training cohort, 46 were male and 61 were female, with the median age of 49.0 (IQR 31.0-63.0). The 1-year mortality rate was 43.9% (47/107) and 45.8% (22/48) in the training and validation cohort, respectively. And further multivariate logistic regression analysis in the training cohort showed that male (odds ratio 5.534, 95% CI 1.507-20.318, p = 0.010), altered mental status (11.876, 1.882-74.947, p = 0.008), serum ferritin ≥ 31,381 µg/L (8.273, 1.855-36.883, p = 0.006), and IL-6 ≥ 18.59 pg/mL (19.446, 1.527-247.642, p = 0.022) were independent risk factor of mortality. A nomogram included the four prediction factors mentioned above was also tabled to help clinicians evaluate the probability of poor outcome. Area under the receiver operating characteristic curve (AUROC) analysis, calibration curves, and decision curve analysis (DCA) certify the accuracy and the clinical usefulness of the nomogram. Our research reveals that male, altered mental status, serum ferritin ≥ 31,381 µg/L, and IL-6 ≥ 18.59 pg/mL are four independent predictors for poor prognosis. Doctors should pay more attention to patients with altered mental status, high serum ferritin, and IL-6 level, who have a higher risk of death.