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Scientific Reports Jul 2024The aims of this study were to determine whether human umbilical cord mesenchymal stem cells (hucMSCs) modified by miRNA-25-3p (miR-25-3p) overexpression could promote...
The aims of this study were to determine whether human umbilical cord mesenchymal stem cells (hucMSCs) modified by miRNA-25-3p (miR-25-3p) overexpression could promote venous endothelial cell proliferation and attenuate portal endothelial cell injury. HucMSCs and human umbilical vein endothelial cells (HUVEC) were isolated and cultured from human umbilical cord and characterized. Lentiviral vectors expressing miRNA-25-3p were transfected into hucMSCs and confirmed by PCR. We verified the effect of miR-25-3p-modified hucMSCs on HUVEC by cell co-culture and cell supernatant experiments. Subsequently, exosomes of miR-25-3p-modified hucMSCs were isolated from cell culture supernatants and characterized by WB, NTA and TEM. We verified the effects of miR-25-3p-modified exosomes derived from hucMSCs on HUVEC proliferation, migration, and angiogenesis by in vitro cellular function experiments. Meanwhile, we further examined the downstream target genes and signaling pathways potentially affected by miR-25-3p-modified hucMSC-derived exosomes in HUVEC. Finally, we established a rat portal vein venous thrombosis model by injecting CM-DiR-labeled hucMSCs intravenously into rats and examining the homing of cells in the portal vein by fluorescence microscopy. Histological and immunohistochemical experiments were used to examine the effects of miRNA-25-3p-modified hucMSCs on the proliferation and damage of portal vein endothelial cells. Primary hucMSCs and HUVECs were successfully isolated, cultured and characterized. Primary hucMSCs were modified with a lentiviral vector carrying miR-25-3p at MOI 80. Co-culture and cell supernatant intervention experiments showed that overexpression of miRNA-25-3p in hucMSCs enhanced HUVEC proliferation, migration and tube formation in vitro. We successfully isolated and characterized exosomes of miR-25-3p-modified hucMSCs, and exosome intervention experiments demonstrated that miR-25-3p-modified exosomes derived from hucMSCs similarly enhanced the proliferation, migration, and angiogenesis of HUVECs. Subsequent PCR and WB analyses indicated PTEN/KLF4/AKT/ERK1/2 as potential pathways of action. Analysis in a rat portal vein thrombosis model showed that miR-25-3p-modified hucMSCs could homing to damaged portal veins. Subsequent histological and immunohistochemical examinations demonstrated that intervention with miR-25-3p overexpression-modified hucMSCs significantly reduced damage and attenuated thrombosis in rat portal veins. The above findings indicate suggest that hucMSCs based on miR-25-3p modification may be a promising therapeutic approach for use in venous thrombotic diseases.
Topics: MicroRNAs; Humans; Human Umbilical Vein Endothelial Cells; Animals; Mesenchymal Stem Cells; Rats; Cell Proliferation; Exosomes; Portal Vein; Cell Movement; Rats, Sprague-Dawley; Male; Venous Thrombosis; Cells, Cultured; Coculture Techniques; Signal Transduction; Umbilical Cord
PubMed: 38956421
DOI: 10.1038/s41598-024-64263-6 -
Scientific Reports Jul 2024Craniotomy or decompressive craniectomy are among the therapeutic options to prevent or treat secondary damage after severe brain injury. The choice of procedure...
Craniotomy or decompressive craniectomy are among the therapeutic options to prevent or treat secondary damage after severe brain injury. The choice of procedure depends, among other things, on the type and severity of the initial injury. It remains controversial whether both procedures influence the neurological outcome differently. Thus, estimating the risk of brain herniation and death and consequently potential organ donation remains difficult. All patients at the University Hospital Münster for whom an isolated craniotomy or decompressive craniectomy was performed as a treatment after severe brain injury between 2013 and 2022 were retrospectively included. Proportion of survivors and deceased were evaluated. Deceased were further analyzed regarding anticoagulants, comorbidities, type of brain injury, potential and utilized donation after brain death. 595 patients were identified, 296 patients survived, and 299 deceased. Proportion of decompressive craniectomy was higher than craniotomy in survivors (89% vs. 11%, p < 0.001). Brain death was diagnosed in 12 deceased and 10 donations were utilized. Utilized donations were comparable after both procedures (5% vs. 2%, p = 0.194). Preserved brain stem reflexes as a reason against donation did not differ between decompressive craniectomy or craniotomy (32% vs. 29%, p = 0.470). Patients with severe brain injury were more likely to survive after decompressive craniectomy than craniotomy. Among the deceased, potential and utilized donations did not differ between both procedures. This suggests that brain death can occur independent of the previous neurosurgical procedure and that organ donation should always be considered in end-of-life decisions for patients with a fatal prognosis.
Topics: Humans; Decompressive Craniectomy; Male; Female; Retrospective Studies; Middle Aged; Adult; Craniotomy; Brain Death; Brain Injuries; Aged; Tissue and Organ Procurement
PubMed: 38956393
DOI: 10.1038/s41598-024-66129-3 -
Signal Transduction and Targeted Therapy Jul 2024
Topics: Humans; Liver Regeneration; Protein Kinase Inhibitors; Liver Failure; Animals
PubMed: 38956037
DOI: 10.1038/s41392-024-01879-0 -
Techniques in Coloproctology Jul 2024Laser hemorrhoidoplasty has demonstrated significant therapeutic effectiveness. To diminish postoperative bleeding and enhance overall outcomes, we have additionally...
BACKGROUND
Laser hemorrhoidoplasty has demonstrated significant therapeutic effectiveness. To diminish postoperative bleeding and enhance overall outcomes, we have additionally adopted suture ligating the feeding vessels. This study aimed to understand the treatment outcomes and any associated complications.
METHODS
This study comprised patients with symptomatic grade II-III hemorrhoids who underwent laser hemorrhoidoplasty with feeding vessel suture ligation and Milligan-Morgan hemorrhoidectomy between 1 September 2020, and 31 August 2022. Surgical-related details, postoperative pain, discomfort after discharge, hemorrhoid recurrence, and any complications were collected from inpatient records, outpatient follow-ups, and telephone interviews. Initially, we will analyze the distinctions between the laser group and the traditional group, followed by an investigation into complications and satisfaction within the laser surgery subgroup.
RESULTS
The study included 323 patients, with 173 undergoing laser hemorrhoidoplasty (LHP) and 150 undergoing Milligan-Morgan hemorrhoidectomy. Regarding pain assessment, the LHP group exhibited superior performance compared to traditional surgery at postoperative 4 h, before discharge, and during the first and second outpatient visits, with statistically significant differences. Additionally, the LHP group had a lower rate of urinary retention and experienced significantly less pain, with statistically significant differences.
CONCLUSIONS
Laser hemorrhoidoplasty with feeding vessels suture ligation has been shown to reduce postoperative pain and appears to be a promising minimally invasive treatment option for symptomatic grade II and III hemorrhoids.
Topics: Humans; Hemorrhoids; Ligation; Female; Retrospective Studies; Male; Hemorrhoidectomy; Middle Aged; Treatment Outcome; Adult; Pain, Postoperative; Laser Therapy; Suture Techniques; Aged; Recurrence; Postoperative Complications; Patient Satisfaction; Sutures
PubMed: 38955875
DOI: 10.1007/s10151-024-02940-4 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024This study was to investigate the relationship between spring pollen distribution concentration, species and the detection results of air-borne pollen allergens in...
This study was to investigate the relationship between spring pollen distribution concentration, species and the detection results of air-borne pollen allergens in Taiyuan City, Shanxi Province during March to May 2022 and March to May 2023.A retrospective study was conducted in the Otorhinolaryngology Head and Neck Surgery Clinic of the First Hospital of Shanxi Medical University.Pollen particles will be monitored by gravity sedimentation method on the roof of the outpatient department of the First Hospital of Shanxi Medical University in downtown Taiyuan from March to May 2022-2023, and pollen species and quantity will be observed and recorded under an optical microscope.The air-borne pollen allergen detection results of all allergic rhinitis patients in the otolaryngology Head and Neck surgery Department of the First Hospital of Shanxi Medical University were extracted from the relevant outpatient system. SPSS software and Pearson correlation analysis were used to compare the correlation between the allergens and the dominant air-borne pollen monitoring results. Results are as follows: (1)A total of 18 species of spring pollen in Taiyuan City were monitored in 2022-2023, with 101 177.5 grains, and the dominant airborne pollen was poplar (16.69%) and pine (29.06%) pollen. The pollen of poplar (11.96%), elm (7.89%) and cypress (8.68%) were dominant in early spring; Pine (25.16%) pollen predominated in late spring. The two peaks of pollen dispersal in Taiyuan were in late March (15 479 grains) and early and mid May (15 094/15 343 grains).(2) The positive rates of allergens in serum specific IgE detection were: wormwood (46%, 248/541 cases), tree combination (26%, 143/541 cases), ragweed (19%, 101/541 cases), humulus scandens (9%, 49/541 cases).(3)There was a linear positive correlation between the positive rate of air-borne pollen allergens in allergic rhinitis patients in the Department of Otolaryngology Head and Neck Surgery in the First Hospital of Shanxi Medical University and the dominant air-borne pollen concentration in the same period (0.05, =0.999). In conclusion, two spring pollen dispersal peaks were formed in late March and early to mid May in Taiyuan City, and the dominant air-borne pollens were poplar and pine pollens. The positive rate of air borne pollen allergen sIgE showed that wormwood allergy was the highest.There was a positive correlation between the concentration of air-borne pollen and the positive rate of air-borne pollen allergens in patients with allergic rhinitis in the Department of otorhinolaryngology and head and neck surgery in Taiyuan in 2022 and 2023.The monitoring of pollen distribution in spring can provide an important scientific basis for clinical workers to formulate prevention and treatment plans for patients with allergic rhinitis in the season, and provide data reference for the epidemiological investigation of allergic diseases in Taiyuan in the future.
Topics: Humans; Pollen; China; Retrospective Studies; Allergens; Immunoglobulin E; Seasons; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal
PubMed: 38955729
DOI: 10.3760/cma.j.cn112150-20231213-00442 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024To investigate the distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three...
To investigate the distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three urban and rural areas of Inner Mongolia. From March to October 2019, in 3 central cities (Chifeng, Hohhot, Ordos) and rural areas of Inner Mongolia, an epidemiological investigation method combining multi-stage stratified random sampling and face-to-face questionnaire survey was adopted to screen suspected AR patients, and skin prick test (SPT) was applied for diagnosis. At the same time, pollen monitoring was carried out in 3 areas to analyze the distribution and clinical sensitization characteristics of artemisia pollen.SPSS26.0 statistical software was used to process all the data. Chi-square test was used to compare rates among different age, sex, region and nationality, Spearman test was used to describe correlation analysis, and pairwise comparison of positive rates among multiple samples was used Bonferroni method. Among the 6 393 subjects, 1 093 cases were diagnosed with AR, and the prevalence of AR was 17.10% (1 093/6 393). Among them, pollen-induced allergic rhinitis, the prevalence of PiAR was 10.97% (701/6 393), accounting for 64.14%(701/1 093).The highest incidence was in the youth group (20-39 years old), accounting for 46.94% (329/701).The diagnosed prevalence was higher in females than in males (11.35% 10.64%, value 12.304, <0.001).The prevalence rate of ethnic minority was higher than that of Han nationality (13.01% 10.65%, value 6.296, =0.008).The prevalence in urban areas was also significantly higher than that in rural areas (18.40% 5.50%, value 10.497, <0.001).There was significant difference in prevalence rate among the three regions in Inner Mongolia (6.06% in Chifeng, 13.46% in Hohhot, 16.39% in Ordos, value 70.054, <0.001).The main clinical symptoms of artemisia PiAR were sneezing (95.58%), nasal congestion (91.73%) and nasal itching (89.30%).Allergic conjunctivitis accounted for 79.60% (558/701), chronic sinusitis for 55.63% (390/701), asthma for 23.25% (163/701).The pattern of artemisia pollen sensitization was mainly multiple sensitization, and the frequency of clinical symptoms and clinical diseases induced by hypersensitization with other allergens accounted for more than that caused by single artemisia pollen. The spread period of Artemisia pollen in the three regions was from June to October, and the peak state was in August in summer. The peak time of clinical symptoms in artemisia PiAR patients was about 2 weeks earlier than the peak time of pollen concentration, and the two were significantly positively correlated (=0.7671, <0.001). Artemisia pollens are the dominant pollens in late summer and early autumn in Inner Mongolia, and the prevalence of artemisia PiAR is high. Controlling the spread of Artemisia pollens is of great significance for the prevention and treatment of AR.
Topics: Humans; Artemisia; Pollen; Rural Population; China; Prevalence; Urban Population; Skin Tests; Rhinitis, Allergic; Surveys and Questionnaires; Allergens; Rhinitis, Allergic, Seasonal; Male; Female; Adult; Young Adult
PubMed: 38955727
DOI: 10.3760/cma.j.cn112150-20230927-00228 -
Journal of Orthopaedic Science :... Jul 2024The global increase in femoral neck fractures due to aging and osteoporosis is a major clinical challenge. The debate on the optimal surgical intervention for femoral...
BACKGROUND
The global increase in femoral neck fractures due to aging and osteoporosis is a major clinical challenge. The debate on the optimal surgical intervention for femoral neck fractures remains unresolved. This large-scale study explores femoral neck fractures among the elderly, focusing on the comparative outcomes of Total Hip Arthroplasty (THA) versus Bipolar Hemiarthroplasty (BHA) in Japanese patients.
METHODS
Using the Japanese National Administrative Diagnosis Procedure Combination (DPC) database, we studied cases of femoral neck fracture from April 2016 to March 2023, and after propensity score matching by age, sex, and comorbidities, we examined the association between THA, complications, and clinical outcomes, and the usefulness of THA for elderly patients with femoral neck fracture.
RESULTS
One-to-one propensity score matching identified 7741 pairs of THA and BHA cases. There was no difference in length of stay between the THA and BHA groups. Significantly more blood transfusions were required in the THA group. There was no significant difference in mortality between the THA and BHA groups, but there was a reduced risk of pneumonia in the THA group, with a ratio of 0.547 (95% CI: 0.418-0.715). On the other hand, the THA group had a higher risk of pulmonary embolism, with a ratio of 1.607 (95% CI: 1.379-1.874). The THA group shows improved discharge rates directly home from the facility where the operation was performed, with a ratio of 1.798 (95% CI: 1.675-1.929).
CONCLUSION
The findings of this research indicate that THA is more effective than BHA in enabling elderly Japanese patients with femoral neck fractures to be discharged directly home and in preventing pneumonia, despite concerns about pulmonary embolism. These findings suggest that THA may improve functional prognosis in elderly patients with femoral neck fractures, although there is a trade-off with an increased risk of pulmonary embolism.
PubMed: 38955576
DOI: 10.1016/j.jos.2024.06.011 -
Saudi Medical Journal Jul 2024To evaluated the home healthcare efficacy in managing tracheostomy patients at King Abdulaziz Medical City under the Ministry of National Guard Health Affairs. Home...
OBJECTIVES
To evaluated the home healthcare efficacy in managing tracheostomy patients at King Abdulaziz Medical City under the Ministry of National Guard Health Affairs. Home healthcare is care provided to patients in the convenience of their homes to ensure high-quality care based on healthcare providers' supervision.
METHODS
This retrospective cohort study utilizing a non-probability consecutive sampling technique, including all available tracheal patients with no exclusion criteria, was carried out in Riyadh, Saudi Arabia, between January 2019 and June 2022. The collected data included patient demographic variables and respiratory settings (ventilation type, daily ventilation need, tracheostomy duration, and ventilator settings). The outcomes included mortality rate and therapeutic outcomes of tracheal management.
RESULTS
Of the 183 patients in the study, the most common type of respiratory-related infection was pneumonia (53%). Unlike respiratory-related causes, The mortality rate of patients admitted to the intensive care unit that was unrelated to respiratory causes was statistically significant (57%) (=0.003). The mortality rate of patients who used aerosol tracheal collars (34%) was markedly higher than mechanically ventilated patients (57%) (=0.004). The mortality rate following discharge from HHC was 40%, and was higher among patients aged >70 years (47%) (=0.04).
CONCLUSION
Pneumonia was associated with the majority of ventilator-related infections and resulted in hospital readmissions. Ensuring proper practices and caregiver education is crucial to decrease the incidence of ventilator-related infections.
Topics: Humans; Tracheostomy; Retrospective Studies; Male; Home Care Services; Female; Middle Aged; Aged; Saudi Arabia; Respiration, Artificial; Adult; Pneumonia, Ventilator-Associated; Intensive Care Units; Cohort Studies
PubMed: 38955441
DOI: 10.15537/smj.2024.45.7.20240294 -
Gut Jul 2024Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy because it is often diagnosed at a late-stage. Signal transducer and activator of transcription 5...
OBJECTIVE
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy because it is often diagnosed at a late-stage. Signal transducer and activator of transcription 5 (STAT5) is a transcription factor implicated in the progression of various cancer types. However, its role in KRAS-driven pancreatic tumourigenesis remains unclear.
DESIGN
We performed studies with ; (KC) mice or LSL-Kras; ; (KPC) mice crossed with conditional disruption of STAT5 or completed deficiency interleukin (IL)-22. Pancreatitis was induced in mice by administration of cerulein. Pharmacological inhibition of STAT5 on PDAC prevention was studied in the orthotopic transplantation and patient-derived xenografts PDAC model, and KPC mice.
RESULTS
The expression and phosphorylation of STAT5 were higher in human PDAC samples than control samples and high levels of STAT5 in tumour cells were associated with a poorer prognosis. The loss of STAT5 in pancreatic cells substantially reduces the KRAS mutation and pancreatitis-derived acinar-to-ductal metaplasia (ADM) and PDAC lesions. Mechanistically, we discovered that STAT5 binds directly to the promoters of ADM mediators, hepatocyte nuclear factor (HNF) 1β and HNF4α. Furthermore, STAT5 plays a crucial role in maintaining energy metabolism in tumour cells during PDAC progression. IL-22 signalling induced by chronic inflammation enhances KRAS-mutant-mediated STAT5 phosphorylation. Deficiency of IL-22 signalling slowed the progression of PDAC and ablated STAT5 activation.
CONCLUSION
Collectively, our findings identified pancreatic STAT5 activation as a key downstream effector of oncogenic KRAS signalling that is critical for ADM initiation and PDAC progression, highlighting its potential therapeutic vulnerability.
PubMed: 38955401
DOI: 10.1136/gutjnl-2024-332225 -
Open Heart Jul 2024The extent to which differences in results from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Rivaroxaban Once...
BACKGROUND
The extent to which differences in results from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial (ROCKET) atrial fibrillation (AF)-the landmark trials for the approval of apixaban and rivaroxaban, respectively, for non-valvular AF-were influenced by differences in their protocols is debated. The potential influence of selection criteria on trial results was assessed by emulating these trials in data from the Global Anticoagulant Registry in the Field (GARFIELD)-AF registry.
METHODS
Vitamin K antagonist (VKA) and non-vitamin K oral antagonist (NOAC) users from GARFIELD-AF were selected according to eligibility for the original ARISTOTLE or ROCKET AF trials. A propensity score overlap weighted Cox model was used to emulate trial randomisation between treatment groups. Adjusted HRs for stroke or systemic embolism (SE) within 2 years of enrolment were calculated for each NOAC versus VKA.
RESULTS
Among patients on apixaban, rivaroxaban and VKA, 2570, 3560 and 8005 were eligible for ARISTOTLE, respectively, and 1612, 2005 and 4368, respectively, for ROCKET AF. When selecting for ARISTOTLE criteria, apixaban users had significantly lower stroke/SE risk versus VKA (HR 0.57; 95% CI 0.34 to 0.94) while no reduction was observed with rivaroxaban (HR 0.98; 95% CI 0.68 to 1.40). When selecting for ROCKET AF criteria, safety and efficacy versus VKA were similar across the NOACs.
CONCLUSION
Apixaban and rivaroxaban showed similar results versus VKA in high-risk patients selected according to ROCKET AF criteria, whereas differences emerged when selecting for the more inclusive ARISTOTLE criteria. Our results highlight the importance of trial selection criteria in interpreting trial results and underline the problems faced in comparing treatments across rather than within clinical trials.
Topics: Humans; Atrial Fibrillation; Factor Xa Inhibitors; Patient Selection; Stroke; Pyrazoles; Pyridones; Rivaroxaban; Male; Female; Aged; Treatment Outcome; Registries; Administration, Oral; Risk Factors; Randomized Controlled Trials as Topic; Risk Assessment; Anticoagulants; Vitamin K
PubMed: 38955399
DOI: 10.1136/openhrt-2024-002708