Learning curve in relation to health-related quality of life in long-term, disease free survivors after McKeown minimally invasive esophagectomy.

BACKGROUND: The potential impact of learning curve on long-term health-related quality of life (QoL) after esophagectomy for cancer has not been investigated. The aim of this article is to investigate the relationship between learning curve for McKeown minimally invasive esophagectomy (MIE) and health-related quality of life (QoL) in long-term, disease free survivors up to 10 years after esophageal cancer resection. METHODS: Esophageal cancer patients who underwent McKeown MIE between 2009 and 2019 were identified in which 280 who were free of disease at the time of survey and completed health-related QoL and symptom questionnaires, including EORTC QLQ-C30, EORTC QLQ-OES18, and Digestive Symptom Questionnaire. Patients were assessed in 3 cohorts according to the learning phases of expertise reported by our previous study: initial phase; plateau phase, and; experienced phase. RESULTS: Median time from operation to survey was 5.8 years (interquartile range 4.6-8.2). The QLQ-C30 mean scores of functional scales, and symptom scales of respiratory and digestive systems including dyspnea (P = 0.006), shortness of breath (P = 0.003), and dysphagia (P = 0.031) were significantly better in experienced phase group. Furthermore, in the subgroup analyses for patients without postoperative major complications, patients in the initial learning phase remained suffering from more symptoms of dyspnea (P = 0.040) and shortness of breath (P = 0.001). CONCLUSION: Esophageal cancer patients undergoing McKeown MIE in initial learning phase tend to suffer from a deterioration in long-term health-related QoL and higher symptomatic burden as compared to experienced learning phase, which did not improved over time and warranted more attention.

The spatiotemporal matching pattern of Ezrin/Periaxin involved in myoblast differentiation and fusion and Charcot-Marie-Tooth disease-associated muscle atrophy.

BACKGROUND: Clinically, Charcot-Marie-Tooth disease (CMT)-associated muscle atrophy still lacks effective treatment. Deletion and mutation of L-periaxin can be involved in CMT type 4F (CMT4F) by destroying the myelin sheath form, which may be related to the inhibitory role of Ezrin in the self-association of L-periaxin. However, it is still unknown whether L-periaxin and Ezrin are independently or interactively involved in the process of muscle atrophy by affecting the function of muscle satellite cells. METHOD: A gastrocnemius muscle atrophy model was prepared to mimic CMT4F and its associated muscle atrophy by mechanical clamping of the peroneal nerve. Differentiating C2C12 myoblast cells were treated with adenovirus-mediated overexpression or knockdown of Ezrin. Then, overexpression of L-periaxin and NFATc1/c2 or knockdown of L-periaxin and NFATc3/c4 mediated by adenovirus vectors were used to confirm their role in Ezrin-mediated myoblast differentiation, myotube formation and gastrocnemius muscle repair in a peroneal nerve injury model. RNA-seq, real-time PCR, immunofluorescence staining and Western blot were used in the above observation. RESULTS: For the first time, instantaneous L-periaxin expression was highest on the 6th day, while Ezrin expression peaked on the 4th day during myoblast differentiation/fusion in vitro. In vivo transduction of adenovirus vectors carrying Ezrin, but not Periaxin, into the gastrocnemius muscle in a peroneal nerve injury model increased the numbers of muscle myosin heavy chain (MyHC) I and II type myofibers, reducing muscle atrophy and fibrosis. Local muscle injection of overexpressed Ezrin combined with incubation of knockdown L-periaxin within the injured peroneal nerve or injection of knockdown L-periaxin into peroneal nerve-injured gastrocnemius muscle not only increased the number of muscle fibers but also recovered their size to a relatively normal level in vivo. Overexpression of Ezrin promoted myoblast differentiation/fusion, inducing increased MyHC-I+ and MyHC-II + muscle fiber specialization, and the specific effects could be enhanced by the addition of adenovirus vectors for knockdown of L-periaxin by shRNA. Overexpression of L-periaxin did not alter the inhibitory effects on myoblast differentiation and fusion mediated by knockdown of Ezrin by shRNA in vitro but decreased myotube length and size. Mechanistically, overexpressing Ezrin did not alter protein kinase A gamma catalytic subunit (PKA-γ cat), protein kinase A I alpha regulatory subunit (PKA reg Iα) or PKA reg Iß levels but increased PKA-α cat and PKA reg II α levels, leading to a decreased ratio of PKA reg I/II. The PKA inhibitor H-89 remarkably abolished the effects of overexpressing-Ezrin on increased myoblast differentiation/fusion. In contrast, knockdown of Ezrin by shRNA significantly delayed myoblast differentiation/fusion accompanied by an increased PKA reg I/II ratio, and the inhibitory effects could be eliminated by the PKA reg activator N6-Bz-cAMP. Meanwhile, overexpressing Ezrin enhanced type I muscle fiber specialization, accompanied by an increase in NFATc2/c3 levels and a decrease in NFATc1 levels. Furthermore, overexpressing NFATc2 or knocking down NFATc3 reversed the inhibitory effects of Ezrin knockdown on myoblast differentiation/fusion. CONCLUSIONS: The spatiotemporal pattern of Ezrin/Periaxin expression was involved in the control of myoblast differentiation/fusion, myotube length and size, and myofiber specialization, which was related to the activated PKA-NFAT-MEF2C signaling pathway, providing a novel L-Periaxin/Ezrin joint strategy for the treatment of muscle atrophy induced by nerve injury, especially in CMT4F.

Identification of rare variants causing urea cycle disorders: A clinical, genetic, and biophysical study.

Urea cycle disorders (UCDs) are a group of rare metabolic conditions characterized by hyperammonemia and a broad spectrum of phenotypic severity. They are caused by the congenital deficiency in the eight biomolecules involved in urea cycle. In the present study, five cases of UCD were recruited and submitted to a series of clinical, biochemical, and genetic analysis with a combination of high throughput techniques. Moreover, in silico analysis was conducted on the identified missense genetic variants. Various clinical and biochemical indications (including profiles of amino acids and urinary orotic acids) of UCD were manifested by the five probands. Sequence analysis revealed nine diagnostic variants, including three novel ones, which caused Argininosuccinic aciduria (ASA) in one case, Carbamoyl phosphate synthetase 1deficiency (CPS1D) in two cases, Ornithine transcarbamylase deficiency (OTCD) in one case, and Citrin deficiency in 1case. Results of in silico biophysical analysis strongly suggested the pathogenicity of each the five missense variants and provided insight into their intramolecular impacts. In conclusion, this study expanded the genetic variation spectrum of UCD, gave solid evidence for counselling to the affected families, and should facilitate the functional study on the proteins in urea cycle.

The Receptor-Like Cytoplasmic Kinase STRK1 Phosphorylates and Activates CatC, Thereby Regulating H2O2 Homeostasis and Improving Salt Tolerance in Rice.

Salt stress can significantly affect plant growth and agricultural productivity. Receptor-like kinases (RLKs) are believed to play essential roles in plant growth, development, and responses to abiotic stresses. Here, we identify a receptor-like cytoplasmic kinase, salt tolerance receptor-like cytoplasmic kinase 1 (STRK1), from rice (Oryza sativa) that positively regulates salt and oxidative stress tolerance. Our results show that STRK1 anchors and interacts with CatC at the plasma membrane via palmitoylation. CatC is phosphorylated mainly at Tyr-210 and is activated by STRK1. The phosphorylation mimic form CatCY210D exhibits higher catalase activity both in vitro and in planta, and salt stress enhances STRK1-mediated tyrosine phosphorylation on CatC. Compared with wild-type plants, STRK1-overexpressing plants exhibited higher catalase activity and lower accumulation of H2O2 as well as higher tolerance to salt and oxidative stress. Our findings demonstrate that STRK1 improves salt and oxidative tolerance by phosphorylating and activating CatC and thereby regulating H2O2 homeostasis. Moreover, overexpression of STRK1 in rice not only improved growth at the seedling stage but also markedly limited the grain yield loss under salt stress conditions. Together, these results offer an opportunity to improve rice grain yield under salt stress.

Exposure-time-dependent subcellular staging of gold nanoparticles deposition and vesicle destruction in mice livers.

Several advances in nanomedicine have been accompanied by rising concerns about the bioaccumulation and toxicity of gold nanoparticles (AuNPs). Here, we assessed the in vivo fate of diversely sized AuNPs that were injected into mice as a computed tomography contrast agent and examined with multi-scale analyses across the organ, tissue, cell, and subcellular levels. After focusing on the strong detected accumulation in livers, our data revealed a set of three clear, exposure-time-dependent patterns based on i) AuNPs deposit morphology and ii) readily identifiable phenotypes for AuNP-impacted subcellular vesicles. Importantly, we detected no obvious differences in liver function, liver cell apoptosis, or autophagy upon exposure to AuNPs. Thus, our study illustrates an accessible experimental and high-resolution data interpretation framework for quickly obtaining and contextualizing informative trends about any AuNP-triggered patterns of subcellular damage in nanomedicine studies; these can help guide cytotoxity and safety testing of diagnostic nanomedical technologies.

A feasibility study of realizing low-dose abdominal CT using deep learning image reconstruction algorithm.

OBJECTIVES: To explore the feasibility of achieving diagnostic images in low-dose abdominal CT using a Deep Learning Image Reconstruction (DLIR) algorithm. METHODS: Prospectively enrolled 47 patients requiring contrast-enhanced abdominal CT scans. The late-arterial phase scan was added and acquired using lower-dose mode (tube current range, 175-545 mA; 80 kVp for patients with BMI ≤24 kg/m2 and 100 kVp for patients with BMI > 24 kg/m2) and reconstructed with DLIR at medium setting (DLIR-M) and high setting (DLIR-H), ASIR-V at 0% (FBP), 40% and 80% strength. Both the quantitative measurement and qualitative analysis of the five types of reconstruction methods were compared. In addition, radiation dose and image quality between the early-arterial phase ASIR-V images using standard-dose and the late-arterial phase DLIR images using low-dose were compared. RESULTS: For the late-arterial phase, all five reconstructions had similar CT value (P > 0.05). DLIR-H, DLIR-M and ASIR-V80% images significantly reduced the image noise and improved the image contrast noise ratio, compared with the standard ASIR-V40% images (P < 0.05). ASIR-V80% images had undesirable image characteristics with obvious "waxy" artifacts, while DLIR-H images maintained high spatial resolution and had the highest subjective image quality. Compared with the early-arterial scans, the late-arterial phase scans significantly reduced the radiation dose (P < 0.05), while the DLIR-H images exhibited lower image noise and good display of the specific image details of lesions. CONCLUSIONS: DLIR algorithm improves image quality under low-dose scan condition and may be used to reduce the radiation dose without adversely affecting the image quality.

Primary central nervous system lymphoma in China: a single-center retrospective analysis of 167 cases.

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin's lymphoma and a limited number of cases have been reported from China. This study aimed to investigate the clinicopathological features of newly diagnosed PCNSLs from a single center in eastern China and to identify the potential prognostic factors for overall survival (OS) and progression-free survival (PFS). All consecutive patients with histopathologically diagnosed PCNSLs at our center between January 2003 and October 2017 were recruited. Demographic and clinicopathological data were collected and reviewed retrospectively. The potential risk factors for OS and PFS were identified using the log-rank test and Cox regression analysis. A total of 167 immunocompetent cases were enrolled. The median age was 58 years (range 17-96 years), and the male:female ratio was 3:2. Headache (n = 65; 39%) and cerebral hemisphere (n = 96; 57%) were the most common presenting complaint and location, respectively. Out of 167 cases, 150 cases were diffuse large B cell lymphomas. With a median follow-up of 25 months (range 1-152 ), the median OS and PFS were 37 months (95% CI, 25-49) and 17 months (95% CI, 13-20), respectively. Residual tumor after operation, chemotherapy without HD-MTX and palliative treatment was revealed as independent prognostic markers. Moreover, ECOG > 3, multifocal lesions, and palliative treatment were revealed as unfavorable independent prognostic markers for PFS. In conclusion, Chinese patients with PCNSL have distinct characteristics. Further studies are warranted to confirm the prognostic value of these factors and to optimize treatments for these patients.

Roles of Microembolus and Plasma D-dimer in Evaluating the Warfarin Anticoagulant Therapy Efficacies for Patients with Atrial Fibrillation.

BACKGROUND: To investigate the roles of microembolus and plasma D-dimer in evaluating the warfarin anticoagulant therapy efficacies for patients with atrial fibrillation (AF). METHODS: Fifty-six AF patients were treated with aspirin antiplatelet therapy (Group ASP) and forty AF patients were treated with warfarin anticoagulant therapy (Group WAR). The microemboli and plasma D-dimer in these two groups were monitored and compared before and after treatment. RESULTS: Group ASP had 21 and 17 cases with positive microemboli before and after treatment, respectively, and there was no significant difference in the detection rate of microemboli before and after treatment; Group WAR had 14 and 5 cases with positive microemboli before and after treatment, respectively, and the detection rate of microemboli was significantly reduced after treatment. The levels of plasma D-dimer in the two groups were significantly reduced after treatment (327±73 µg/L vs 235±61 µg/L and 313±81 µg/L vs 170±67 µg/L, respectively, P<0.05), among which the reduction level in Group WAR was more significant. CONCLUSIONS: Microemboli and D-dimer can be used as the indicators for evaluating the embolism risk and therapeutic efficacies in AF patients.

Ultrasound-Guided Continuous Femoral Nerve Block with Dexmedetomidine Combined with Low Concentrations of Ropivacaine for Postoperative Analgesia in Elderly Knee Arthroplasty.

OBJECTIVES: This study aims to investigate the clinical effect of dexmedetomidine (DEX) combined with low concentrations of ropivacaine in ultrasound-guided continuous fem-oral nerve block for postoperative analgesia in elderly patients with total knee arthroplasty (TKA). MATERIALS AND METHODS: Patients were divided into three groups: group C, group D1, and group D2. For postoperative analgesia, patients in group C were given 0.15% ropivacaine, patients in group D1 were given 0.15% ropivacaine + 0.02 µg × kg-1 × h-1 DEX, and patients in group D2 were given 0.15% ropivacaine + 0.05 µg × kg-1 × h-1 DEX. The visual analogue scores in the resting state, active state (AVAS), and passive functional exercise state (PVAS), degree of joint bending, and Ramsay scores were recorded. RESULTS: The Ramsay scores were significantly higher, AVAS scores were significantly lower, PVAS scores were significantly decreased, the degree of joint bending was significantly higher, and the time to the first postoperative ambulation was shorter in groups D1 and D2 than group C. Furthermore, the time to the first postoperative ambulation was shorter in group D2 than in group D1, patients in groups D1 and D2 were more satisfied than patients in group C, and patients in group D2 were more satisfied than patients in group D1. CONCLUSION: The protocol of 0.05 µg × kg-1 × h-1 of DEX combined with 0.15% ro-pivacaine in ultrasound-guided continuous femoral nerve block for postoperative analgesia in elderly patients with TKA provides a better analgesic effect than without DEX performance.X.-Y.Z. and E.-F.Z. have contributed equally to this research.

Polyphyllin I induces cell cycle arrest and apoptosis in human myeloma cells via modulating ß-catenin signaling pathway.

Multiple myeloma (MM) is an indolent B-cell disease characterized by clonal proliferation of malignant plasma cells. Multiple myeloma remains incurable despite new targeted drugs and development of drug resistance or intolerable toxicity emerges as a major problem. Therefore, design, identification, and validation of novel chemicals with therapeutic potential are clearly needed for MM treatment. Here, we explore polyphyllin I (PPI), a major active constituent extracted from Paris polyphyllin, its inhibitory effects and its mechanisms in MM cells in vitro. We found that PPI inhibited the proliferation of myeloma cells. The combination of PPI with dexamethasone, doxorubicin, arsenic trioxide, or bortezomib enhanced the inhibition of cell growth. As analyzed by flow cytometry, MM cells were arrested at G2/M phase and apoptotic cells increased in a time-dependent manner. Morphological changes of cells undergoing apoptosis were observed under light microscope. To explore the mechanism of apoptosis induced by PPI, we next examined whether the Wingless-Int (Wnt)/ß-catenin signaling pathway played a role in the PPI-induced growth inhibition in MM cells. The canonical Wnt signaling pathway is activated in MM cells through constitutively active ß-catenin, a messenger molecule relevant to growth, survival, and migration of MM cells. Western blotting was used to measure the protein levels of ß-catenin, and PPI treatment led to downregulating the expression of ß-catenin protein and was followed by inhibition of ß-catenin nuclear localization. As a result, ß-catenin downstream targets, such as cyclin D1 and survivin, were downregulated. To the best of our knowledge, this is the first report identifying anti-proliferative potency of PPI against myeloma cells. PPI blocks ß-catenin nuclear translocation and decreasing expression of the downstream targets of ß-catenin. Our results suggest that PPI is a novel inhibitor of ß-catenin activity with potential anti-myeloma efficacy.

Multivariate prognostic index and triplet regimen efficacy predictive index in locally advanced and metastatic gastric cancer: pooled analysis from three clinical trials using individual patient data.

Background: To construct an effective prognostic index to predict overall survival (OS) and triplet regimen efficacy for advanced gastric cancer (AGC) patients treated with platinum-based and fluorouracil-based chemotherapy. Objectives: Between 2011 and 2021, 679 patients from two randomized phase III trials and one phase II trial were enrolled. Designs: We collected 11 baseline clinicopathological and 14 hematological parameters to establish a prognostic index. Methods: Univariate and multivariate Cox analyses were used to screen prognostic factors, and a prognostic index nomogram was conducted. Results: Seven prognostic factors were identified: primary tumor site in the non-proximal gastric area, signet-ring cell carcinoma (SRCC)/mucinous carcinoma, peritoneal metastasis, neutrophil count higher than the upper limit of normal value (ULN), lymphocyte count lower than the lower limit of normal value, lactate dehydrogenase level higher than the ULN, and alkaline phosphatase level higher than the ULN as significant for prognosis. A prognostic nomogram named the Fudan advanced gastric cancer prognostic risk score (FARS) index was constructed, and patients in the high-risk group had significantly shorter OS than those in the low-risk group (median OS, 15.5 versus 8.0 months, p < 0.001). The areas under the curve of the FARS index for 1-, 2-, and 3-year OS were 0.70, 0.72, and 0.77, respectively. A validation and external cohort verified the prognostic value of the FARS index. Moreover, three triplet regimen efficacy parameters were identified: SRCC/mucinous adenocarcinoma, primary tumor location in the non-proximal gastric area, and peripheral neutrophil count higher than the ULN; a TRIS index was subsequently conducted. In patients with any two of the three parameters, the triplet regimen showed significantly longer OS than the doublet regimen (p = 0.018). Conclusion: The constructed FARS index to predict the OS of AGC patients and the TRIS index to screen out the dominant population for triplet regimens can be used to aid clinical decision-making and individual risk stratification.

A prognostic index in locally advanced and metastatic gastric cancer To date, no recognized systematic prognostic score has been established for advanced gastric cancer (AGC). Our research aims to construct an effective prognostic index to predict overall survival (OS) for AGC patients to aid clinical decision-making and individual risk stratification. In our research, seven prognostic factors were identified: primary tumor site in the non-proximal gastric area, signet-ring cell carcinoma (SRCC)/mucinous carcinoma, peritoneal metastasis, neutrophil count higher than the upper limit of normal value (ULN), lymphocyte count lower than the lower limit of normal value, lactate dehydrogenase level higher than the ULN, and alkaline phosphatase level higher than the ULN as significant for prognosis. A prognostic index named the Fudan advanced gastric cancer prognostic risk score (FARS) index was constructed, and patients in the high-risk group had significantly shorter OS than those in low-risk group (median OS, 15.5 months vs. 8.0 months, P < 0.001). Moreover, three triplet regimen efficacy parameters were identified: SRCC/mucinous adenocarcinoma, primary tumor location in the non-proximal gastric area, and peripheral neutrophil count higher than the ULN; a TRIS index was subsequently conducted. In patients with any two of the three parameters, the triplet regimen showed significantly longer OS than the doublet regimen (P = 0.018).

Th22, but not Th17 might be a good index to predict the tissue involvement of systemic lupus erythematosus.

PURPOSE: T-helper (Th) cells abnormalities are considered to be associated with the pathogenesis of Systemic lupus erythematosus (SLE). Recently, The Th22 cells have been identified and implicated in the pathogenesis of autoimmune diseases such as Rheumatoid arthritis (RA), although therir role in Systemic lupus erythematosus (SLE) remains unclear. The present study intends to investigate their roles in SLE. METHODS: Clinical data were collected in 65 SLE patients and 30 healthy controls. The patients were divided into active and inactive groups. CD4(+)IFN-γ(-)IL-17(-)IL-22(+)Tcells (Th22 cells),CD4(+) IFN-γ(-)IL-22(-)IL-17(+)T cells (Th17 cells),and CD4(+) IFN-γ(+) (Th1 cells) were assayed by flow cytometry. Serum interleukin-22 (IL-22) and IL-17 levels were measured by enzyme-linked immunosorbent assay. RESULTS: The main observation focused on increased Th22 cells in patients with sole lupus skin disease and decreased Th22 cells in patients with sole lupus nephritis. Likewise, concentrations of serum IL-22 were increased in patients with sole lupus skin disease, and decreased in patients with sole lupus nephritis. Additionally, there was a positive correlation between the percentage of Th22 cells and IL-22 production. The percentage of Th17 cells or concentration of serum IL-17 correlated positively with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). CONCLUSION: Th22 seems to be a more significant index to predict the tissue involvement of SLE than Th17, although Th17 may play a role in the activity of SLE.

[Different treatment modes for cerebral microlesions: a comparison of clinical efficacy].

OBJECTIVE: To tentatively establish a diagnosis and treatment mode for effectively controlling the progress of cerebral microlesions (CM) and preventing the incidence of cerebral infarction (CI) by comparing different intervention modes for treating CM. METHODS: Using a prospective, nonrandomized, controlled trial, 408 subjects with multiple CM were assigned to the Chinese medical pharmacy intervention group (Group A, 100 case), the aspirin intervention group (Group B, 104 cases), the negative control group (Group C, 100 cases), and the non-intervention group (Group D, 104 cases). No intervention was given to those in Group D. Patients in the other 3 groups were intervened by life style and routine therapies of vasculogenic risk factors. Those in Group A took Guizhi Fuling Pill (GFP) and earthworm powder additionally. Those in Group B took aspirin additionally. They were routinely followed-up. The CM, the changes of vasculogenic risk factors, and the incidence rate of CI were compared among the 4 groups. RESULTS: The total effective rate of CM was 66.67% in Group A, obviously higher than that of Group B (52.32%), Group C (42.86%), and Group D (37.04%), respectively. It was obviously higher in Group B than in Group D, showing statistical difference (P <0.01, P <0.05). After treatment, the serum levels of LDL-C, TC, and TG were obviously lower in Group A than in Group B (P <0.05); the serum levels of LDL-C and TC were obviously lower in Group A than in Group C (P <0.01); the systolic pressure was obviously lower in Group A than in Group D (P <0.05). The systolic pressure and the serum TC level were obviously lower in Group C than in Group D (P <0.05). The incidence rate of CI was 2.17% (2/92 cases) in Group A, obviously lower than that of Group C (11.36% ,10/88 cases) and Group D (14.44%, 13/90 cases), showing statistical difference (P <0.05). But there was no statistical difference between Group A and Group B (6.74% ,6/89 cases) (P >0.05). CONCLUSIONS: GFP combined earthworm powder could treat CM, control vasculogenic risk factors, and finally prevent the incidence of CI. Standard Chinese medical intervention mode showed the optimal effects in treating CM and preventing the incidence of CI, and perhaps it could be spread clinically.

Current and Emerging Treatment Options in Sinus and Nasal Diseases: Surgical Challenges and Therapeutic Perspectives.

Chronic rhinosinusitis (CRS), one of the most prevalent health problems worldwide, is defined as a chronic inflammation of the nasal and paranasal sinuses mucosa persisting for more than 12 weeks [...].

Can left ventricular entropy by cardiac magnetic resonance late gadolinium enhancement be a prognostic predictor in patients with left ventricular non-compaction?

PURPOSE: Left ventricular non-compaction (LVNC) is considered rare; however, the use of cardiac magnetic resonance (CMR) has shown that its incidence is not uncommon, and its clinical presentation remains variable, with an uncertain prognosis. Risk stratification of major adverse cardiac events (MACE) in patients with LVNC remains complex. Therefore, this study aims to determine whether tissue heterogeneity from late gadolinium enhancement-derived entropy is associated with MACE in patients with LVNC. METHODS: This study was registered in the Clinical Trial Registry (CTR2200062045). Consecutive patients who underwent CMR imaging and were diagnosed with LVNC were followed up for MACE, which was defined by heart failure, arrhythmias, systemic embolism, and cardiac death. The patients were divided into MACE and non-MACE groups. The CMR parameters included left ventricular (LV) entropy, LV ejection fraction (LVEF), LV end-diastolic volume, LV end-systolic volume (LVESV), and LV mass (LVM). RESULTS: Eighty-six patients (age: 45.48 ± 16.64 years; female: 62.7%; LVEF: 42.58 ± 17.20%) were followed up for a median of 18 months and experienced 30 MACE events (34.9%). The MACE group showed higher LV entropy, LVESV, and LVM and lower LVEF than the non-MACE group. LV entropy [hazard ratio (HR): 1.710, 95% confidence interval (CI): 1.078-2.714, P = 0.023] and LVEF (HR: 0.961, 95% CI: 0.936-0.988, P = 0.004) were independent predictors of MACE (P <0.050) according to the Cox regression analysis. Receiver operating characteristic curve analysis revealed that the area under the curve of LV entropy was 0.789 (95% CI: 0.687-0.869, P < 0.001), LVEF was 0.804 (95% CI: 0.699-0.878, P < 0.001), and the combined model of LV entropy and LVEF was 0.845 (95% CI: 0.751-0.914, P < 0.050). CONCLUSION: LGE-derived LV entropy and LVEF are independent risk indicators of MACE in patients with LVNC. The combination of the two factors was more conducive to improving the prediction of MACE.

Continuous exposure to isoprenaline reduced myotube size by delaying myoblast differentiation and fusion through the NFAT-MEF2C signaling pathway.

We aimed to explore whether superfluous sympathetic activity affects myoblast differentiation, fusion, and myofiber types using a continuous single-dose isoprenaline exposure model in vitro and to further confirm the role of distinct NFATs in ISO-mediated effects. Compared with delivery of single and interval single, continuous single-dose ISO most obviously diminished myotube size while postponing myoblast differentiation/fusion in a time- and dose-dependent pattern, accompanied by an apparent decrease in nuclear NFATc1/c2 levels and a slight increase in nuclear NFATc3/c4 levels. Overexpression of NFATc1 or NFATc2, particularly NFATc1, markedly abolished the inhibitory effects of ISO on myoblast differentiation/fusion, myotube size and Myh7 expression, which was attributed to a remarkable increase in the nuclear NFATc1/c2 levels and a reduction in the nuclear NFATc4 levels and the associated increase in the numbers of MyoG and MEF2C positive nuclei within more than 3 nuclei myotubes, especially in MEF2C. Moreover, knockdown of NFATc3 by shRNA did not alter the inhibitory effect of ISO on myoblast differentiation/fusion or myotube size but partially recovered the expression of Myh7, which was related to the slightly increased nuclear levels of NFATc1/c2, MyoG and MEF2C. Knockdown of NFATc4 by shRNA prominently increased the number of MyHC +, MyoG or MEF2C + myoblast cells with 1 ~ 2 nuclei, causing fewer numbers and smaller myotube sizes. However, NFATc4 knockdown further deteriorated the effects of ISO on myoblast fusion and myotube size, with more than 5 nuclei and Myh1/2/4 expression, which was associated with a decrease in nuclear NFATc2/c3 levels. Therefore, ISO inhibited myoblast differentiation/fusion and myotube size through the NFAT-MyoG-MEF2C signaling pathway.

Oestrogen-deficiency inducing haematopoiesis dysfunction via reduction in haematopoietic stem cells and haematopoietic growth factors in rats.

Haematopoiesis is a self-renewing and multi-directional differentiation process of haematopoietic stem cells (HSCs), which is modulated very precisely by the haematopoietic microenvironment in bone marrow. Our previous study has demonstrated that oestrogen-deficiency leads to haematopoiesis dysfunction which manifests as a decrease in haematopoietic tissues and an increase in adipose tissues in bone marrow. However, the mechanism involved in the oestrogen-deficiency effects on haematopoiesis dysfunction is not completely understood. In this study, we established an oestrogen-deficiency rat model by ovariectomy (OVX group). Haematopoiesis was evaluated at the 12th, 16th, 20th, 24th and 28th weeks after operation in the OVX group and its control (Sham group) by pathological examination; the number and function of HSCs were evaluated by flow cytometry analysis and colony-forming assay respectively. Haematopoietic growth factors levels including granulocyte/macrophage-colony-stimulating factor (GM-CSF), stem cell factor (SCF) and interleukin-3 (IL-3) were examined by ELISA kits at different time points. We found that in the OVX group, haematopoiesis dysfunction in bone marrow was observed (P < 0.05) from the 12th week when compared with the Sham group, and extramedullary haematopoiesis began to appear in the liver and spleen from the 16th week. The number of HSCs and colony-forming units-granulocyte/macrophage (CFUs-GM) in bone marrow was reduced significantly (P < 0.05) from the 20th and 16th week respectively. Furthermore, GM-CSF, SCF and IL-3 in the OVX group decreased significantly (P < 0.05) since the 12th, 16th and 24th week respectively. Taken together, these results suggested that oestrogen is required for normal haematopoiesis. Oestrogen-deficiency inducing haematopoiesis dysfunction may be via reduction in HSCs and haematopoietic growth factors at a late stage.

High prevalence of hepatitis B virus infection in HIV-negative Castleman's disease.

Castleman's disease (CD) is a rare non-neoplastic lymphoproliferative disorder with ambiguous etiology. This study aimed to evaluate the potential association between hepatitis B virus (HBV) and CD and to characterize the HBV-positive CD patients in China, an endemic area for HBV infection. We compared the prevalence of HBV infection in 35 consecutive CD patients initially diagnosed in our hospitals over a 10-year period with an age- and sex-matched healthy control, a national population-based control, and a non-Hodgkin's lymphoma (NHL) control. We found that the prevalence of HBV infection in CD was 17.1% (6/35), which was as high as the NHL control (19.9%, P = 0.693), but significantly higher than the age- and sex-matched healthy control (6.9%, P = 0.033) and the national population-based control (7.2%, P = 0.037). Next, we compared the clinicopathological characteristics between HBV-positive and HBV-negative CD patients. We found that HBV-positive CD patients had a significantly higher NHL malignant transformation rate (33.3% vs. 0%, P = 0.025), higher splenomegaly rate (83.3% vs. 27.6%, P = 0.019), and much poorer prognosis (estimated mean overall survival time (50.83 vs. 64.34 months, P = 0.016). In conclusion, our findings suggest an association between HBV infection and development of CD. CD patients with HBV infection have their own distinguished features.

Effects of Adaptive Statistical Iterative Reconstruction-V Technology on the Image Quality and Radiation Dose of Unenhanced and Enhanced CT Scans of the Piglet Abdomen.

To investigate the optimal pre- and post-adaptive statistical iterative reconstruction-V (ASiR-V) levels in pediatric abdominal computed tomography (CT) to minimize radiation exposure and maintain image quality using an animal model. A total of 10 standard piglets were selected and scanned to obtain unenhanced and enhanced images under different pre-ASiR-V conditions. The corresponding images were obtained using ASiR-V algorithm at different post-ASiR-V levels. CT value, signal-to-noise ratio (SNR), contrast noise ratio (CNR) of abdominal tissues, subjective image score, and radiation dose of unenhanced and enhanced scans were analyzed. With the increase of pre-ASiR-V level, the radiation dose in piglets gradually decreased (P < 0.05). Within the same group of pre-ASiR-V, the image noise was decreased (P < 0.05) by increasing post-ASiR-V level. There was no statistical difference between SNR and CNR values. In unenhanced CT, the subjective score of the images with the combination of 40% pre- and 60% post-ASiR-V levels had no statistical difference compared to the combination of 0% pre- and 60% post-ASiR-V levels, while the radiation dose decreased by 31.6%. In the enhanced CT, the subjective image score with the 60% pre- and 60% post-ASiR-V combination had no statistical difference compared to the 0% pre- and 60% post-ASiR-V combination, while the radiation dose was reduced by 48.9%. The combined use of pre- and post-ASiR-V maintains image quality at the reduced radiation dose. The optimal level for unenhanced CT is 40% pre-combined with 60% post-ASiR-V, while that for enhanced CT is 60% pre-combined with 60% post-ASiR-V in pediatric abdominal CT.

XELOX doublet regimen versus EOX triplet regimen as first-line treatment for advanced gastric cancer: An open-labeled, multicenter, randomized, prospective phase III trial (EXELOX).

BACKGROUND: There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC. METHODS: This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non-inferiority in progression-free survival (PFS) for XELOX as compared with EOX on an intention-to-treat basis. RESULTS: Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5-6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0-6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812-1.203; Pnon-inferiority = 0.003). There was no significant difference in median overall survival (mOS) (12.0 vs. 12.0 months, P = 0.384) or objective response rate (37.4% vs. 45.1%, P = 0.291) between the two groups. In patients with poorly differentiated adenocarcinoma and liver metastasis, the EOX arm had a significantly longer mOS (P = 0.021) and a trend of longer mPFS (P = 0.073) than the XELOX arm. The rate of grade 3/4 adverse events (AEs) was 42.2% (90/213) in the XELOX arm and 72.5% (156/215) in the EOX arm (P = 0.001). The global health-related quality of life (QoL) score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy. CONCLUSIONS: This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.