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Cellular and Molecular Life Sciences :... Jan 2024In embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), the expression of an RNA-binding pluripotency-relevant protein, LIN28, and the absence of its...
In embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), the expression of an RNA-binding pluripotency-relevant protein, LIN28, and the absence of its antagonist, the tumor-suppressor microRNA (miRNA) let-7, play a key role in maintaining pluripotency. Muse cells are non-tumorigenic pluripotent-like stem cells residing in the bone marrow, peripheral blood, and organ connective tissues as pluripotent surface marker SSEA-3(+). They express pluripotency genes, differentiate into triploblastic-lineage cells, and self-renew at the single cell level. Muse cells do not express LIN28 but do express let-7 at higher levels than in iPSCs. In Muse cells, we demonstrated that let-7 inhibited the PI3K-AKT pathway, leading to sustainable expression of the key pluripotency regulator KLF4 as well as its downstream genes, POU5F1, SOX2, and NANOG. Let-7 also suppressed proliferation and glycolysis by inhibiting the PI3K-AKT pathway, suggesting its involvement in non-tumorigenicity. Furthermore, the MEK/ERK pathway is not controlled by let-7 and may have a pivotal role in maintaining self-renewal and suppression of senescence. The system found in Muse cells, in which the tumor suppressor let-7, but not LIN28, tunes the expression of pluripotency genes, might be a rational cell system conferring both pluripotency-like properties and a low risk for tumorigenicity.
Topics: Alprostadil; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Embryonic Stem Cells; Gene Expression
PubMed: 38261036
DOI: 10.1007/s00018-023-05089-9 -
Scientific Reports Dec 2023Rapid and precise intraoperative diagnosing systems are required for improving surgical outcomes and patient prognosis. Because of the poor quality and time-intensive...
Deep UV-excited fluorescence microscopy installed with CycleGAN-assisted image translation enhances precise detection of lymph node metastasis towards rapid intraoperative diagnosis.
Rapid and precise intraoperative diagnosing systems are required for improving surgical outcomes and patient prognosis. Because of the poor quality and time-intensive process of the prevalent frozen section procedure, various intraoperative diagnostic imaging systems have been explored. Microscopy with ultraviolet surface excitation (MUSE) is an inexpensive, maintenance-free, and rapid imaging technique that yields images like thin-sectioned samples without sectioning. However, pathologists find it nearly impossible to assign diagnostic labels to MUSE images of unfixed specimens; thus, AI for intraoperative diagnosis cannot be trained in a supervised learning manner. In this study, we propose a deep-learning pipeline model for lymph node metastasis detection, in which CycleGAN translate MUSE images of unfixed lymph nodes to formalin-fixed paraffin-embedded (FFPE) sample, and diagnostic prediction is performed using deep convolutional neural network trained on FFPE sample images. Our pipeline yielded an average accuracy of 84.6% when using each of the three deep convolutional neural networks, which is a 18.3% increase over the classification-only model without CycleGAN. The modality translation to FFPE sample images using CycleGAN can be applied to various intraoperative diagnostic imaging systems and eliminate the difficulty for pathologists in labeling new modality images in clinical sites. We anticipate our pipeline to be a starting point for accurate rapid intraoperative diagnostic systems for new imaging modalities, leading to healthcare quality improvement.
Topics: Humans; Lymphatic Metastasis; Alprostadil; Neural Networks, Computer; Microscopy, Fluorescence
PubMed: 38049475
DOI: 10.1038/s41598-023-48319-7 -
International Journal of Impotence... Jun 2024Patient out-of-pocket (OOP) cost represents an access barrier to erectile dysfunction (ED) treatment. We determined OOP cost for men with ED covered by Fee-for-Service...
Patient out-of-pocket (OOP) cost represents an access barrier to erectile dysfunction (ED) treatment. We determined OOP cost for men with ED covered by Fee-for-Service Medicare. Coverage policies were obtained from the Medicare Coverage Database for treatments recommended by the 2018 American Urological Association (AUA) guidelines. OOP cost was retrieved from the 2023 Centers for Medicare & Medicaid Services Final Rule. OOP cost for treatments without Medicare coverage were extracted from GoodRx® or literature and inflated to 2022 dollars. Annual prescription costs were calculated using the published estimate of 52.2 yearly instances of sexual intercourse. Medicare has coverage for inflatable penile prostheses (IPP; strong recommendation), non-coverage for vacuum erection devices (VED; moderate recommendation) and phosphodiesterase type-5 inhibitors (PDE5i; strong recommendation), and no policies for intracavernosal injections (ICI; moderate recommendation), intraurethral alprostadil (IA; conditional recommendation), or low-intensity extracorporeal shock wave therapy (ESWT; conditional recommendation). Annual IA prescription is most costly ($4022), followed by ICI prescription ($3947), one ESWT course ($3445), IPP ($1600), PDE5i prescription ($696), and one VED ($213). PDE5i and IPP, both strongly recommended by AUA guidelines, are associated with lower OOP cost. Better understanding of patient financial burden may inform healthcare decision-making.
PubMed: 38926632
DOI: 10.1038/s41443-024-00903-9 -
The Journal of Vascular Access May 2024Long peripheral catheters (LPCs) role in Difficult IntraVenous Access (DIVA) patients admitted to the emergency department has already been studied, resulting in a...
BACKGROUND
Long peripheral catheters (LPCs) role in Difficult IntraVenous Access (DIVA) patients admitted to the emergency department has already been studied, resulting in a rapid, safe, and cost-effective procedure. Although their use in outpatient settings is established, there is a lack of studies assessing their benefits. In particular, rheumatologic outpatients affected by scleroderma, especially those affected by digital ulcers, are often treated with intravenous infusions of prostaglandin I (PGI) analog (IV-PGIA).
OBJECTIVE AND METHODS
From 1 October 2021 to 31 March 2024, we conducted a prospective study enrolling DIVA outpatients affected by systemic sclerosis or undifferentiated connective tissue disease who needed IV-PGIA therapy at L. Sacco Hospital in Milan (Italy). Each treatment cycle consisted of four consecutive days of infusion of iloprost or alprostadil. The primary aim was to assess the efficacy and potential complications associated with LPCs for IV-PGIA.
RESULTS
Twenty-six patients were enrolled 23 were females (88.5%), and the median age was 72 years (IQR 56-78.7). In total, 97 LPCs were inserted, with a mean number of insertions per patient/year of 2.3. An increase in LPCs insertion during the 30 months of the enrollment period was observed. Eighteen patients required more than one LPC placement, and in 61% of them, the second venipuncture was executed at a different site. No procedural complications were registered (accidental puncture of the brachial artery, accidental median nerve puncture, bleeding) nor late complications (Catheter-Related Thrombosis, Catheter-Related Bloodstream Infections, Accidental Removal).
CONCLUSIONS
Our experience shows that LPCs could be valuable and safe for rheumatologic outpatients. The increased number of insertions and new and total patients enrolled each year defines the satisfaction of patients and health care professionals.
PubMed: 38770673
DOI: 10.1177/11297298241252896 -
Cell and Tissue Banking Mar 2024To investigate the characteristics of multilineage-differentiating stress-enduring (Muse) cells labeled with chloromethyl dialkylcarbocyanine (CM-Dil) in culture and in...
To investigate the characteristics of multilineage-differentiating stress-enduring (Muse) cells labeled with chloromethyl dialkylcarbocyanine (CM-Dil) in culture and in skin wounds of rats. Normal human dermal fibroblasts (NHDFs) were obtained from foreskins and were confirmed by immunocytochemistry with vimentin. Muse cells were derived from NHDFs using long-term trypsinization (LTT), were confirmed using immunocytochemistry with antibodies against stage specific embryonic antigen-3 (SSEA-3) and CD105 and were expanded in suspension cultures. The Muse cells were labeled with CM-Dil and were further evaluated with respect to their biological properties using CCK-8 assays and scratch tests. One hundred µl CM-Dil-labeled Muse cells at a concentration of 5 × 10/µl were injected subcutaneously at the edges of skin wounds in adult male SD rats. At weeks 1, 3 and 5 after the injection, the distribution of CM-Dil-labeled Muse cells in skin tissues was observed using immunofluorescence microscopy. Muse cells were double-positive for CD105 and SSEA-3. ALP staining of the M-clusters were positive and they displayed orange-red fluorescence after labelling with CM-Dil, which had no adverse effects on their viability, migration or differentiation capacity. One week after the subcutaneous injection of CM-Dil-labeled Muse cells, many cells with orange-red fluorescence were observed at the edges of the skin injuries; those fluorescent spots gradually decreased over time, and only a few Muse cells with fluorescence could be detected by week 5. CM-Dil can be used to label Muse cells without affecting their proliferation, migration or differentiation, and can be used for short-term tracking of Muse cells for the treatment of skin wounds in a rat model.
Topics: Rats; Male; Humans; Animals; Alprostadil; Rats, Sprague-Dawley; Cell Differentiation; Carbocyanines
PubMed: 36617377
DOI: 10.1007/s10561-022-10067-9 -
Medicine Jun 2024Diabetes nephropathy (DN), as one of the common complications of diabetes, is characterized by persistent albuminuria, decreased glomerular filtration rate, and elevated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetes nephropathy (DN), as one of the common complications of diabetes, is characterized by persistent albuminuria, decreased glomerular filtration rate, and elevated arterial blood pressure. At present, Xuebijing injection is widely used in the treatment of DN. However, few systematic reviews and meta-analysis related to Xuebijing injection intervention in DN were published. In order to more systematically and objectively evaluate the clinical efficacy of Xuebijing injection intervention in DN, we conducted systematic reviews and meta-analysis to verify it.
OBJECTIVE
The purpose of the research was to systematically evaluate the clinical efficacy of Xuebijing injection combined with alprostadil in the treatment of diabetic nephropathy.
METHODS
We searched the China National Knowledge Infrastructure (CNKI), China Biomedical Database (SinoMed), Weipu Database (VIP), Wanfang Database, PubMed, The Cochrane Library, Embase, Web of Science and other databases by computer, and searched the randomized controlled trials of Xuebijing injection combined with alprostadil in the treatment of DN at home and abroad from the establishment of the database to 2022. The main outcome indicators included blood glucose, and the secondary outcome indicators included blood lipid, renal function, urinary protein, and safety. Two evaluators independently screened the literature, extracted the data and evaluated the risk of bias in the included studies. RevMan 5.3 software was used to analyze the data.
RESULTS
A total of 14 randomized controlled trials were included, including 1233 cases, 618 cases in the treatment group and 615 cases in the control group. The results of meta-analysis demonstrated that compared with the control group, the treatment group could effectively reduce fasting plasma glucose [mean difference [MD] = -1.90, 95% CI (-2.40, -1.40), P < .00001], glycosylated hemoglobin A1c [MD = -2.38, 95% CI (-2.51, -2.25), P < .00001], 2h postprandial blood glucose [MD = -2.92, 95% CI (-3.95, -1.89), P < .00001], triacylglycerol [MD = -1.08, 95% CI (-1.66, -0.50), P = .0003], total cholesterol [MD = -1.17, 95% CI (-1.39, -0.95), P < .00001], low-density lipoprotein cholesterol [MD = -1.19, 95% CI (-1.60, -0.78), P < .00001], high-density lipoprotein cholesterol [MD = 0.32, 95% CI (0.23, 0.42), P < .00001], serum creatinine [MD = -42.95, 95% CI (-57.46, -28.43), P < .00001], blood urea nitrogen [MD = -2.24, 95%CI (-2.62,-1.86), P < .00001], blood β2 microglobulin [SMD = -1.49, 95% CI (-1.70, -1.28), P < .00001], urine β2 microglobulin [SMD = -0.81, 95% CI (-1.04, -0.58), P < .00001], 24-hour urinary protein quantification [MD = -0.20, 95% CI (-0.26, -0.14), P < .00001], urinary albumin excretion rate [SMD = -1.15, 95% CI (-1.38, -0.93), P < .00001].
CONCLUSION
Xuebijing injection combined with alprostadil has more advantages in treating DN compared to routine Western medicine.
Topics: Humans; Drugs, Chinese Herbal; Diabetic Nephropathies; Alprostadil; Drug Therapy, Combination; Injections; Randomized Controlled Trials as Topic; Blood Glucose; Treatment Outcome; Lipids
PubMed: 38875385
DOI: 10.1097/MD.0000000000032095 -
International Journal of Molecular... Sep 2023Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the...
Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We intravenously administered the clinical product "CL2020" containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to three CL2020-treated animals to selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.
Topics: Rats; Humans; Animals; Alprostadil; Diphtheria Toxin; Spinal Cord Injuries; Cell Differentiation; Spinal Cord; Administration, Intravenous
PubMed: 37834052
DOI: 10.3390/ijms241914603 -
European Journal of Obstetrics,... Dec 2023To compare cesarean rates and maternal and neonatal morbidity according to the cervical ripening method used among obese pregnant women requiring induction of labor at...
Comparison of cesarean delivery rates after 3 methods of cervical ripening among obese women at or after 41 weeks - Secondary analysis of two French randomized controlled trials: MAGPOP and CYTOPRO.
OBJECTIVE
To compare cesarean rates and maternal and neonatal morbidity according to the cervical ripening method used among obese pregnant women requiring induction of labor at or after 41 weeks of gestation.
DESIGN
A secondary analysis of two multicenter randomized controlled trials conducted in French maternity units between 2015 and 2018.
PARTICIPANTS
336 women with a body mass index ≥30 kg/m, a pregnancy ≥41 weeks, and an induction of labor requiring cervical ripening.
INTERVENTIONS
Cervical ripening with a PGE2 dinoprostone pessary (Propess®), or low-dose vaginal PGE1 (misoprostol) or a double-balloon catheter.
MEASUREMENTS AND FINDINGS
The rates of cesarean delivery did not differ significantly according to the cervical ripening method (PGE2 pessary vs PGE1, RR: 1.18, 95% CI: 0.80-1.75; PGE2 pessary vs double balloon catheter: RR, 0.88, 95% CI: 0.60-1.29), p = 0.52; double balloon catheter vs PGE1, RR: 1.34, 95% CI: 0.77-2.32, p = 0.29). More oxytocin was required for women from the double-balloon group compared to those from both the PGE1 and PGE2 pessary groups (respectively, RR: 1.31, 95% CI: 1.08-1.58, p = 0.005; RR: 1.17, 95% CI: 1.03-1.32, p = 0.01). The risk of perineal tears or episiotomy was significantly lower for women induced with the PGE2 pessary than with PGE1 (0.85; 95% CI: 0.74-0.99), p = 0.03).
KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE
No cervical ripening method was associated with a lower cesarean rate in obese women who required cervical ripening from 41 weeks. Further trials are required among obese women to determine the cervical ripening method most efficacious for reducing the cesarean rate.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Dinoprostone; Oxytocics; Alprostadil; Labor, Induced; Cervical Ripening; Randomized Controlled Trials as Topic; Obesity
PubMed: 37806026
DOI: 10.1016/j.ejogrb.2023.09.019 -
World Neurosurgery Jun 2024Patients with Lumbar Spinal Stenosis (LSS) typically complain of back pain and leg pain. These symptoms reduce the quality of life (QoL) and also cause sleep... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Patients with Lumbar Spinal Stenosis (LSS) typically complain of back pain and leg pain. These symptoms reduce the quality of life (QoL) and also cause sleep disturbances. This study compares pregabalin and limaprost's efficacy in LSS for pain, disability, QoL, and sleep, aiming to offer insights for medication selection.
METHODS
This study was designed as a prospective, randomized, single-center, single-blinded, clinical superiority trial targeting patients with LSS. For 6 weeks, 111 patients per group were administered medication following a standard regimen, after which patient-reported outcomes were measured. The primary outcome was the Visual Analogue Scale (VAS) for back and leg pain, and the secondary outcomes included the Oswestry Disability Index (ODI), European Quality of Life 5 Dimensions (EQ-5D), and sleep quality.
RESULTS
After 6 weeks of medication, there were significant improvements over time in the primary outcome, VAS for back pain and leg pain, in both groups, but no significant difference between the 2 groups. Similarly, for the secondary outcomes, ODI and EQ-5D, both groups showed significant improvements, yet there was no significant difference between them. In the subgroup analysis targeting poor sleepers (Pittsburgh sleep quality index, PSQI >5), both groups also exhibited significant improvements in sleep quality, but again, there was no significant difference between the groups.
CONCLUSIONS
Efficacy of pregabalin, limaprost in back and leg pain, ODI, EQ-5D, and sleep quality, but there was no significant difference between the 2 groups. Thus, it is advisable to prescribe based on individual drug responses and potential complications.
Topics: Humans; Pregabalin; Spinal Stenosis; Male; Female; Aged; Middle Aged; Prospective Studies; Lumbar Vertebrae; Treatment Outcome; Single-Blind Method; Analgesics; Quality of Life; Alprostadil; Pain Measurement
PubMed: 38608818
DOI: 10.1016/j.wneu.2024.04.033 -
Zhonghua Yi Xue Za Zhi Feb 2024The data of 115 patients with nasopharyngeal masses (78 males and 37 females) aged between 12 and 78 years at the Sun Yat-sen University Cancer Center from May 2022 to...
[Diagnostic value of apparent diffusion coefficient histograms using multiplexed sensitivity encoding diffusion-weighted imaging for distinguishing nasopharyngeal carcinoma from benign hyperplasia].
The data of 115 patients with nasopharyngeal masses (78 males and 37 females) aged between 12 and 78 years at the Sun Yat-sen University Cancer Center from May 2022 to July 2023 were retrospectively reviewed, including 70 cases of nasopharyngeal carcinoma and 45 cases of benign hyperplasia. The mean, median, and percentiles (10, 25, 75, and 90) of the apparent diffusion coefficient (ADC) histogram derived from multiplexed sensitivity encoding diffusion-weighted imaging (MUSE-DWI) of the benign hyperplasia group were significantly higher than those of the nasopharyngeal carcinoma group (all <0.05). Conversely, the kurtosis and skewness of benign hyperplasia group were significantly lower than those of the nasopharyngeal carcinoma group (both <0.05). The area under receiver operating characteristic (ROC) curve of the combined ADC histogram parameters was 0.812 (95%: 0.732-0.892), and the sensitivity, specificity and accuracy were 92.86%, 57.78% and 79.13%, respectively. The current study indicates ADC histogram parameters derived MUSE-DWI exhibit significant discriminatory value between nasopharyngeal carcinoma and benign hyperplasia.
Topics: Humans; Male; Female; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Nasopharyngeal Carcinoma; Hyperplasia; Retrospective Studies; Alprostadil; Diffusion Magnetic Resonance Imaging; ROC Curve; Nasopharyngeal Neoplasms; Sensitivity and Specificity; Diagnosis, Differential
PubMed: 38326057
DOI: 10.3760/cma.j.cn112137-20230811-00201