Tumor-associated macrophages-derived exo-let-7a promotes osteosarcoma metastasis via targeting C15orf41 in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) immune environment is complexed and the immune factors-related to OS progression need to be explored. Tumor-associated macrophages (TAMs) are regarded as immune suppressive and tumor-promoting cells. However, the underlying mechanisms through which TAMs function are still fragmentary. Here, we aim to explore the underlying mechanisms by which TAMs regulate OS progression. METHODS: TAMs from OS tissues were isolated by flow cytometry. Exosomes derived from TAMs were separated using ultracentrifugation and western blotting. Transmission electron microscopy (TEM), and flow cytometry were constructed to characterize TAMs-derived exosomes. Additionally, the differential MicroRNAs (miRNAs) and genes were detected through RNA sequencing, and further validated using real-time PCR (RT-PCR). OS cell metastasis ability was assessed using transwell invasion and scratch wound healing assays. MiRNAs mimic and lentiviral vectors were utilized to explore the effects on OS progression. RESULTS: Exosome secreted by TAMs accelerated the OS metastasis. Let-7a level was upregulated in TAMs derived exosomes, which downregulated C15orf41 by targeting 3'-untranslated region (UTR). Furthermore, overexpressing let-7a enhanced invasion and migration by blocking the transcription of C15orf41. In consistent, up-regulating let-7a promoted OS progression and made the prognosis to be worse, which can be reversed by C15orf41 overexpression. CONCLUSION: This study highlighted the critical role of TAMs-derived exosomes in OS progression and explored the potential value of the let-7a/C15orf41 axis as an indicator or target for OS.

A case of simultaneous occurrence of acute myeloid leukemia and multiple myeloma.

BACKGROUND: Although the occurrence of acute myeloid leukemia (AML) after chemotherapy for multiple myeloma (MM) is common in clinical settings, the simultaneous occurrence of these malignancies in patients without previous exposure to chemotherapy is a rare event. Etiology, disease management, and clinical treatment remain unclear for this particular occurrence. To the best of our knowledge, this study is the first to report a case of simultaneous presentation of AML and MM after exposure to ultraviolet irradiation. CASE PRESENTATION: We reported the case of a 73-year-old man (Han Chinese ethnicity) without previous medical history of AML and MM. The morphology and immunology of bone marrow cells confirmed the co-existence of AML and MM. Fluorescent in situ hybridization analysis of immunomagnetically separated abnormal plasma cells showed abnormal expression of the amplified RB-1, TP53, and CDKN2C (1p32). Cytogenetic analysis demonstrated Y chromosome deletion. After the patient was administered with bortezomib combined with cytarabine + aclarubicin + granulocyte colony-stimulating factor (CAG regimen), and evident curative effects were observed. The patient achieved and maintained complete remission for more than 6 months. Prior to the disease occurrence, the patient had received ultraviolet irradiation for 1 year and was detected with aberrant gene expression of RB-1, TP53, and CDKN2C (1p32). Nevertheless, the correlation of this phenomenon with the etiology of concurrent AML with MM remains unclear. CONCLUSION: This study discussed the case of a patient diagnosed with AML concurrent with MM, who has no previous exposure to chemotherapy. This patient was successfully treated by bortezomib combined with CAG regimen. This study provides a basis for clinical treatment guidance for this specific group of patients and for confirmation of the disease etiology.

Effectiveness of a mHealth intervention on hypertension control in a low-resource rural setting: A randomized clinical trial.

Background: Despite the increasing popularity of mHealth, little evidence indicates that they can improve health outcomes. Mobile health interventions (mHealth) have been shown as an attractive approach for health-care systems with limited resources. To determine whether mHealth would reduce blood pressure, promote weight loss, and improve hypertension compliance, self-efficacy and life quality in individuals with hypertension living in low-resource rural settings in Hubei, China. Methods: In this parallel-group, randomized controlled trial, we recruited individuals from health-care centers, home visits, and community centers in low-resource rural settings in Hubei, China. Of 200 participants who were screened, 148 completed consent, met inclusion criteria, and were randomly assigned in a ratio of 1:1 to control or intervention. Intervention group participants were instructed to use the Monitoring Wearable Device and download a Smartphone Application, which includes reminder alerts, adherence reports, medical instruction and optional family support. Changes in the index of Cardiovascular health risk factors from baseline to end of follow-up. Secondary outcomes were change in hypertension compliance, self-efficacy and life quality at 12 weeks. Results: Participants (n = 134; 66 in the intervention group and 68 controls) had a mean age of 61.73 years, 61.94% were male. After 12 weeks, the mean (SD) systolic blood pressure decreased by 8.52 (19.73) mm Hg in the intervention group and by 1.25 (12.47) mm Hg in the control group (between-group difference, -7.265 mm Hg; 95% CI, -12.89 to -1.64 mm Hg; P = 0.012), While, there was no difference in the change in diastolic blood pressure between the two groups (between-group difference, -0.41 mm Hg; 95% CI, -3.56 to 2.74 mm Hg; P = 0.797). After 12 weeks of follow-up, the mean (SD) hypertension compliance increased by 7.35 (7.31) in the intervention group and by 3.01 (4.92) in the control group (between-group difference, 4.334; 95% CI, 2.21 to -6.46; P < 0.01), the mean (SD) hypertension compliance increased by 12.89 (11.95) in the intervention group and by 5.43 (10.54) in the control group (between-group difference, 7.47; 95% CI, 3.62 to 11.31; P < 0.01), the mean (SD) physical health increased by 12.21 (10.77) in the intervention group and by 1.54 (7.18) in the control group (between-group difference, 10.66; 95% CI, 7.54-13.78; P < 0.01), the mean (SD) mental health increased by 13.17 (9.25) in the intervention group and by 2.55 (5.99) in the control group (between-group difference, 10.93; 95% CI, 7.74 to 14.12; P < 0.01). Conclusions: Among participants with uncontrolled hypertension, individuals randomized to use a monitoring wearable device with a smartphone application had a significant improvement in self-reported hypertension compliance, self-efficacy, life quality, weight loss and diastolic blood pressure, but no change in systolic blood pressure compared with controls.

Treatment of Liver Fibrosis after Hepatitis B with TCM Combined with NAs Evaluated by Noninvasive Diagnostic Methods: A Retrospective Study.

Objective. Chronic hepatitis B liver fibrosis is an important intermediate link in the development of liver cirrhosis. A retrospective cohort study was conducted in Longhua Hospital affiliated to the Shanghai University of Traditional Chinese Medicine in order to prove whether integrated traditional Chinese and Western medicine could improve the incidence of CHB complications and clinical prognosis. There are 130 patients with hepatitis B liver fibrosis (being treated from 2011-2021) included in the study, and the patients were divided into 64 TCM users (NAs combined with TCM) and 66 TCM nonusers (NAs antiviral therapy). The serum noninvasive diagnostic model (APRI, FIB-4) and LSM value were used to classify the stages of fibrosis. The results showed that the LSM value was decreased significantly in TCM users compared with TCM nonusers (40.63% versus 28.79%). Indicators of FIB-4 and APRI of TCM users have improved significantly compared with that of TCM nonusers (32.81% versus 10.61% and 35.94% versus 24.24%). The AST, TBIL, and HBsAg levels in TCM users were lower than those in TCM nonusers, and the HBsAg level was inversely correlated with the CD3+, CD4+, and CD8+ in TCM users. The PLT and spleen thickness of TCM users also were improved considerably. The incidence rate of end-point events (decompensated cirrhosis/liver cancer) in TCM nonusers was higher than that of TCM users (16.67% versus 1.56%). The long course of the disease and a family history of hepatitis B were the risk factors for disease progression, and long-term oral administration of TCM was the protective factor. As a result, the serum noninvasive fibrosis index and imaging parameters in TCM users were lower than those of TCM nonusers. Patients in the treatment of NAs combined with TCM had better prognoses such as a lower HBsAg level, a more stable lymphocyte function, and a lower incidence of end-point events. The present findings suggest the effect of TCM combined with NAs in the treatment of chronic hepatitis B liver fibrosis is better than that of single drug treatment.

Minimally invasive esophagectomy for esophageal squamous cell carcinoma: a case-control study of thoracoscope versus mediastinoscope assistance.

OBJECTIVE: Minimally invasive esophagectomy (MIE) has been widely applied for esophageal carcinoma treatment. Thoracoscope-assisted transthoracic esophagectomy (TATTE) and mediastinoscope-assisted transhiatal esophagectomy (MATHE) are two kinds of MIE. The objective of this study is to compare these two methods with respect to surgical safety and survival. METHODS: Single-institution experience with MATHE and TATTE was analyzed to assess morbidity, adequacy of tumor clearance, and survival. A pair-matched case-control study was performed to compare 54 patients who underwent either MATHE or TATTE between July 2000 and December 2009. Patients were matched by age, sex, comorbidity, forced expiratory volume in 1 s (FEV1), tumor location, and stage. RESULTS: Statistically significant differences between the MATHE group and the TATTE group were: shorter operative time for MATHE (194.4 min) versus TATTE (228.1 min), less blood loss during operation in the TATTE group (142.6 ml) versus the MATHE group (214.6 ml), and more lymph nodes retrieved in the TATTE group (19.1 nodes) versus the MATHE group (11.4 nodes). There was no difference in survival between the groups. CONCLUSIONS: MATHE and TATTE are both technically feasible. TATTE can provide better visibility. TATTE has less blood loss compared with MATHE. More adequate tumor clearance in terms of lymph node dissection can be achieved with TATTE.

Concurrent Tuberculous Meningoencephalitis and Anti-NMDAR Encephalitis: A Case Report.

Background: Cases of tuberculosis triggering the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis are absent. Case Presentation: Herein, we report, for the first time, the case of a patient who developed anti-NMDAR encephalitis likely due to tuberculosis. The patient, a 33-year-old man, experienced weight loss during the previous 2 years, along with acute headache, fever, cognitive deficits, and right ophthalmoplegia. Based on these findings and on data from magnetic resonance imaging and cerebrospinal fluid antibody analysis, tuberculous meningoencephalitis combined with anti-NMDAR encephalitis was diagnosed. Marked clinical and brain imaging improvement were observed after antituberculosis and high-dose corticosteroid treatment initiation, which persisted during the 3 months of follow-up. Conclusions: This case suggests that anti-NMDAR encephalitis may arise after tuberculosis infection. Therefore, clinicians must be aware of this possibility, especially when cognitive and new neurological symptoms suddenly occur.

Effect of renin-angiotensin system inhibitors on prevention of peritoneal fibrosis in peritoneal dialysis patients.

AIM: Long-term peritoneal dialysis (PD) may lead to peritoneal fibrosis and ultrafiltration failure. It had been demonstrated that the renin-angiotensin system (RAS) plays a key role in the regulation of peritoneal function in rats on PD. We investigated the effects of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) on long-term PD patients. METHODS: We analyzed data from 66 patients treated with PD therapy at our centre for at least 12 months retrospectively, during which time at least two peritoneal equilibration tests (PET) were performed. Thirty-eight patients were treated with ACE/angiotensin II (AII) inhibitors (ACE/ARB group); the other 28 received none of the above drugs during the entire follow up (control group). The expression of fibronectin, transforming growth factor-beta1 (TGF-beta1), Aquaporin1 (AQP1) and vascular endothelial growth factor (VEGF) in the overnight effluent were examined by enzyme-linked immunosorbent assay. RESULTS: The demographic data of the two groups showed no difference during the study. No difference between the groups was found with respect to residual renal function (RRF) at the start for both groups by the end of follow up, decreased in the vast majority of patients from both groups (P = 0.014). After 12 months, a significant difference in ultrafiltration was found between the two groups: in the control group it had decreased, while it had not changed in the ACE/ARB group (P < 0.05). In comparison with the baseline level, expression of fibronectin, TGF-beta1 and VEGF in dialysate effluent were significantly increased except for AQP1 in the control group (P < 0.05), but not in the ACE/ARB group (P > 0.05). CONCLUSION: The findings suggest that ACE/AII inhibitors appeared to have a slower rate of decline in ultrafiltration and RRF, effectively protect against peritoneal fibrosis in long-term peritoneal dialysis. Long-term follow up seems to be required to draw more conclusions.

Effective treatment of advanced cholangiocarcinoma by hepatic arterial infusion chemotherapy combination with sorafenib: one case report from China.

BACKGROUND/AIMS: Cholangiocarcinoma, especially intrahepatic type, is difficult to be found early and diagnosed at early stages. Although it was reported as rare to happen, it is a well-known devastating malignancy with little treatment effects. As a result, most of the patients suffer from poor prognosis. On the other hand, the incidence of intrahepatic cholangiocarcinoma arises worldwide. Radical surgical resection was regarded as the most effective treatment, in spite of recurrence. Unfortunately, only 30 percent of patients qualify for this at the time of diagnosis. Hence, for advanced cholangiocarcinoma, chemotherapy is the only modality left to be chosen. Recently LaRocca and Kudoh reported about effective chemotherapy for cholangiocarcinoma. Even so, because of no randomized study, no standard chemotherapy for cholangiocarcinoma has been accepted, and most of the projects were based on 5-Fu. Sorafenib, a multikinase inhibitor, which can competitively inhibit RAF/MEK/ERK pathway, human vascular endothelial growth factor receptors (VEGFR2, VEGFR3) platelet-derived growth factor receptor beta (PDGFR), Flt3, and C-kit receptors, has been successfully applied for solid tumors such as renal cancer and hepatocellular carcinoma. Sorafenib used alone or in combinations, can induce growth-inhibition and apoptosis in vitro experiments. Application of sorafenib alone for cholangiocarcinoma has also been published. The role of combination with other chemotherapy drugs in advanced cholangiocarcinoma still needs to be defined. METHODOLOGY: A patient admitted for exploratory operation was demonstrated to be suffering from unresectable, biopsy-proven intrahepatic cholangiocarcinoma. A pump was placed inside hepatic artery, for the purpose of infusion chemotherapy. Program of chemotherapy was scheduled and hepatic arterial infusion of 5-Fu/LV +oxaliplatin +hydroxycamptothecine was performed. Three months later, no effect was discovered, so sorafenib was suggested to combine with infusion chemotherapy. For the first time we applied sorafenib combination to hepatic arterial infusion chemotherapy RESULT: After lower dosage of sorafenib was used as a combination with hepatic arterial infusion chemotherapy, size of hepatic lesions and level CA19-9 of peripheral blood count were decreased, without any damage to the hepatic function, except for temporary skin hyperkeratosis as well as vomit. Efficacy of treatment was demonstrated by computed tomography (CT) scan. CONCLUSION: So far as in our patient, the application of sorafenib combination with other agents through hepatic arterial infusion chemotherapy may be an effective way for cholangiocarcinoma, but the definite mechanism has to be confirmed by methods of molecular biology.

Mitigating effect of perceived organizational support on stress in the presence of workplace ostracism in the Pakistani nursing sector.

BACKGROUND: Nursing has a reputation for being a predominantly stressful profession. Prior studies focus on the overt antecedents of stress like bullying, harassment, and verbal aggression from patients as well as colleagues. Employee stress has been receiving attention for decades, yet there is a research gap on the role of workplace ostracism as an antecedent of stress for nurses. This study aimed to consider the effect of workplace ostracism on the perceived stress of nurses while considering the moderating role of perceived organizational support. METHODS: This study is quantitative. A time-lagged survey was conducted in private and public hospitals of Pakistan. Data were collected from 241 nurses. Statistical Package for the Social Sciences (SPSS) software and analysis of a moment structures (AMOS) software were employed for data analysis, such as bootstrapping analysis, Sobel test, and regression analysis. RESULTS: Results demonstrated that workplace ostracism is positively associated with stress, while perceived organizational support has a moderating relationship. Perceived organizational support mitigates the adverse effects of workplace ostracism on nurses. CONCLUSION: This study contributes significantly to nursing literature by identifying workplace ostracism as one of the significant antecedents of stress for nurses. Perceived organizational support shows that employees are cared for and appreciated by the organization, which lessens the strength of perceived stress due to workplace ostracism.

Genistein Decreases APP/tau Phosphorylation and Ameliorates Aß Overproduction Through Inhibiting CIP2A.

BACKGROUND: Upregulation of Cancerous Inhibitor of PP2A (CIP2A) plays an important role in disease-related phosphorylation of tau/APP and tau pathology/Aß overproduction through inhibiting PP2A in AD brain. Genistein has been shown to potently reduce CIP2A in experimental cancer treatment research. Whether Genistein can ameliorate AD pathology through targeting CIP2A needs further investigation. METHODS: The inhibitory effects of Genistein on tau/APP phosphorylation and Aß overproduction in AD cell models have been explored. HEK293-T cells were co-transfected with CIP2A and APP plasmids, or CIP2A and tau plasmids, with Genistein incubation at 0, 30, 60 or 120 µM for 48 h, cell viability and PP2A activities were measured. HEK293-T cells with CIP2A/APP overexpression treated with Genistein at 30 µM for 48 h were collected and lyzed for Western blotting detection of CIP2A, PP2Ac, APP-T668, total APP, PS1, BACE1, sAPPα and sAPPß. Aß40 and Aß42 levels in cell supernatant, soluble fraction (RIPA) and insoluble fraction (formic acid soluble) of cell lysates were measured by ELISA. HEK293-T cells with CIP2A/tau overexpression treated with Genistein at 30 µM for 48 h were collected for Western blotting detection of CIP2A, PP2Ac, tau-S396, tau-S404 and total tau. RESULTS: Genistein effectively reduced CIP2A expression, and restored PP2A activities both in CIP2A/APP, CIP2A/tau co-expressed cells. Genistein reduced APP phosphorylation at T668 site and inhibited Aß production. Meantime, Genistein ameliorated tau hyperphosphorylation through repressing the inhibitory effect of CIP2A on PP2A. CONCLUSION: CIP2A is a target of Genistein in AD therapy. Genistein reduces APP/tau hyperphosphorylation and Aß production through inhibiting the effect of CIP2A on PP2A.

Attitudes of Chinese community members and psychiatrists towards forensic psychiatric assessments.

The aim of this study was to investigate the attitudes of Chinese community members and psychiatrists towards forensic psychiatric assessments. A questionnaire designed to record attitudes toward the current forensic psychiatric assessment procedures and the disposal of mentally ill offenders was developed and distributed via a mobile App. A total of 134 community members and 132 psychiatrists voluntarily completed the questionnaire. Most of responders agreed that the department of public-security has the right to apply for a forensic psychiatric assessment but should not be held solely by that department. Community members were less significantly confident in the validation of forensic psychiatric opinions than were the psychiatrists. A significantly higher proportion of community members than psychiatrists considered that offenders judged Not Criminally Responsible on Account of Mental Disorder (NCRMD) should be punished as would be sane people. In addition, only a minority of responders supported that NCRMD should not be held criminally responsible. Our results indicate that both groups have comments on the current distribution of right of startup of forensic psychiatric assessments. Compared to psychiatrists, community members have lower confidence in the validation of forensic psychiatric assessment and have stricter attitudes toward the disposal of offenders with psychiatric disorders.

Carnosic Acid-combined Arsenic Trioxide Antileukaemia Cells in the Establishment of NB4/SCID Mouse Model.

Despite great improvement in the treatment outcome of APL, treatment failure still sometimes occurs due to the toxicity of arsenic trioxide (ATO). Damage to the heart and liver often occurs even when the dose is lower than the therapeutic dose. Based on the results of cell experiments in vitro in this study, we investigated the synergistic activity of carnosic acid (CA) combined with ATO in the SCID mouse model of human promyelocytic leukaemia in vivo. A NB4/SCID mouse model was established in this study. The NB4/SCID mice were randomly divided into three treatment groups (CA alone, ATO alone and CA combined with ATO) and a control group based on factorial design. The evaluation indicators of the curative effect of the drugs included expressions of cleaved caspase-3, PTEN, p27 gene mRNA and proteins by immunohistochemistry, flow cytometry and Western blot analysis. The survival time was compared between the four groups. The results indicated that verification of the NB4/SCID mouse model was confirmed by histopathological examination. Compared with mice treated by CA or ATO alone, the mice in the combination of CA and ATO group had a higher rate of apoptosis, which was linked with expressions of cleaved caspase-3, PTEN, p27 gene mRNA and proteins. Also, the mice with the longest survival time were those treated with the combination of CA and ATO. In conclusion, the results of the present study indicated that CA and ATO in combination have strong synergistic antileukaemic effects on cell activity.

Long non-coding RNA-MIAT promotes neurovascular remodeling in the eye and brain.

Although nervous and vascular systems are functionally different, they usually share similar mechanisms for function maintenance. Neurovascular dysfunction has became the pathogenesis of several vascular and nervous disorders. Here we show that long non-coding RNA-MIAT is aberrantly expressed under neurovascular dysfunction condition. MIAT is shown as a regulator of vascular dysfunction, including retinal angiogenesis, corneal angiogenesis, and vascular permeability. MIAT is also shown as a regulator of retinal neurodegeneration under diabetic condition. Mechanistically, MIAT regulates neural and vascular cell function via MIAT/miR-150-5p/VEGF network. The eye is a valuable model to study central nervous system (CNS) disorders. We show that MIAT knockdown leads to cerebral microvascular degeneration, progressive neuronal loss and neurodegeneration, and behavioral deficits in a CNS neurovascular disorder, Alzheimer's disease. MIAT may represent a pharmacological target for treating neurovascular-related disorders.

Correlation of Alzheimer-like tau hyperphosphorylation and fMRI bold intensity.

To explore the correlation between cerebral functional alterations revealed by functional magnetic resonance imaging (fMRI) and Alzheimer disease- (AD)-like tau hyperphosphorylation, we injected bilaterally 2 microl each of 20 mM isoproterenol (IP), a PKA activator, or of saline as a vehicle control into the hippocampus of rats. FMRI was employed to measure the intensity of BOLD signal, one of the cerebral functional markers reflecting the changes of cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF), in hippocampus and cortex 24 h after the operation. Immunohistochemical staining of hippocampus and cortex was carried out using phosphorylation-dependent tau antibodies. The results showed (1) that BOLD intensity in hippocampus and cortex of IP-injected rats was obviously lower than that of sham-operated group, indicating a decrease in CMRO2 and CBF of the particular brain regions in IP-treated rats; (2) that tau was hyperphosphorylated at Ser-262/Ser-356 (12e8), Ser-396/Ser-404 (PHF-1) sites in CA1 CA2 CA3 CA4 and dentate gyrus regions of hippocampal formation and cortex area in IP group, but not in sham rats; (3) that a negative correlation between tau hyperphosphorylation and BOLD intensity in hippocampus and cortex area of IP rats was observed. The data suggested that hippocampal and cortical tau hyperphosphorylation was intimately related to BOLD intensity of the same areas. To our knowledge, this is the first report exploring the relationship between fMRI BOLD signal and AD-like tau hyperphosphorylation.

Clinical study on prospective efficacy of all-trans Acid, realgar-indigo naturalis formula combined with chemotherapy as maintenance treatment of acute promyelocytic leukemia.

Objectives. To test the efficiency and safety of sequential application of retinoic acid (ATRA), Realgar-Indigo naturalis formula (RIF) and chemotherapy (CT) were used as the maintenance treatment in patients with acute promyelocytic leukemia (APL). Methods. This was a retrospective study of 98 patients with newly diagnosed APL who accepted two different maintenance treatments. After remission induction and consolidation chemotherapy according to their Sanz scores, patients received two different kinds of maintenance scheme. The first regimen was using ATRA, RIF, and standard dose of CT sequentially (ATRA/RIF/CT regimen), while the second one was using ATRA and low dose of chemotherapy with methotrexate (MTX) plus 6-mercaptopurine (6-MP) alternately (ATRA/CTlow regimen). The OS, DFS, relapse rate, minimal residual disease, and adverse reactions in two groups were monitored and evaluated. Results. ATRA/RIF/CT regimen could effectively reduce the chance of relapse in different risk stratification of patients, but there was no significant difference in 5-year DFS rate and OS rate between the two groups. Besides, the patients in the experimental group suffered less severe adverse reactions than those in the control group. Conclusions. The repeated sequential therapeutic regimen to APL with ATRA, RIF, and chemotherapy is worth popularizing for its high effectiveness and low toxicity.