Analgesic effect and safety of using an epidural analgesia pump versus an intravenous analgesia pump for uterine artery embolization in the treatment of uterine fibroids / 中国基层医药

Objective:To investigate the analgesic effect and safety of using an epidural analgesia pump versus an intravenous analgesia pump for uterine artery embolization in the treatment of uterine fibroids. Methods:Fifty patients with uterine fibroids undergoing uterine artery embolization admitted to The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from January 2019 to December 2021 were included in this study. They were divided into an observation group and a control group ( n = 25/group). Patients in the observation group used an epidural analgesia pump for pain relief, while patients in the control group used an intravenous analgesia pump for pain relief. At 1, 6, 12, and 24 hours after surgery, pain severity was compared between the two groups using the Visual Analogue Scale. Comfort level was compared between the two groups using the Bruggemann Comfort scale. Before and after surgery, respiratory rate, heart rate, blood pressure, and adverse reactions were compared between the two groups. Results:At 1 hour after surgery, the Visual Analogue Scale score in the observation group was significantly lower than that in the control group [3.00 (2.00, 5.50) vs. 7.00 (6.00, 8.00), Z = -3.84, P < 0.05]. At 6, 12, and 24 hours after surgery, there was a significant difference in the Visual Analogue Scale score between the two groups (all P > 0.05). Within 24 hours after surgery, the use of opioid analgesics in the observation group was less than that in the control group [16.00% (4/25) vs. 88.00% (22/25), χ2 = 25.96, P < 0.001]. At 1 hour after surgery, the Bruggemann Comfort Scale score in the observation group was significantly higher than that in the control group [0.00 (0.00, 0.50) vs. 0.00 (0.00, 0.00), Z = 2.08, P < 0.05]. At 6, 12, and 24 hours after surgery, there was no significant difference in the Bruggemann Comfort Scale score between the two groups (all P > 0.05). After surgery, heart rate was significantly decreased in each group compared with before surgery (both P < 0.05). There were no significant differences in respiratory rate and mean arterial pressure between the two groups before and after surgery (both P > 0.05). There were no significant differences in the incidences of postoperative nausea, vomiting, and fever between the two groups (all P > 0.05). Conclusion:The epidural analgesia pump used for uterine artery embolization in the treatment of uterine fibroids has a better analgesic effect and provides more comfort and is safer than the intravenous analgesia pump. The former is worthy of clinical promotion.

SARS-CoV-2 Infects Syncytiotrophoblast and Activates Inflammatory Responses in the Placenta

SARS-CoV-2 infection during pregnancy leads to an increased risk of adverse pregnancy outcomes. Although the placenta itself can be a target of virus infection, most neonates are virus free and are born healthy or recover quickly. Here, we investigated the impact of SARS-CoV-2 infection on the placenta from a cohort of women who were infected late during pregnancy and had tested nasal swab positive for SARS-CoV-2 by qRT-PCR at delivery. SARS-CoV-2 genomic and subgenomic RNA was detected in 23 out of 54 placentas. Two placentas with high virus content were obtained from mothers who presented with severe COVID-19 and whose pregnancies resulted in adverse outcomes for the fetuses, including intrauterine fetal demise and a preterm delivered baby still in newborn intensive care. Examination of the placental samples with high virus content showed efficient SARS-CoV-2 infection, using RNA in situ hybridization to detect genomic and replicating viral RNA, and immunohistochemistry to detect SARS-CoV-2 nucleocapsid protein. Infection was restricted to syncytiotrophoblast cells that envelope the fetal chorionic villi and are in direct contact with maternal blood. The infected placentas displayed massive infiltration of maternal immune cells including macrophages into intervillous spaces, potentially contributing to inflammation of the tissue. Ex vivo infection of placental cultures with SARS-CoV-2 or with SARS-CoV-2 spike (S) protein pseudotyped lentivirus targeted mostly syncytiotrophoblast and in rare events endothelial cells. Infection was reduced by using blocking antibodies against ACE2 and against Neuropilin 1, suggesting that SARS-CoV-2 may utilize alternative receptors for entry into placental cells.

SRSF protein kinases 1 and 2 are essential host factors for human coronaviruses including SARS-CoV-2

While vaccines are vital for preventing COVID-19 infections, it is critical to develop new therapies to treat patients who become infected. Pharmacological targeting of a host factor required for viral replication can suppress viral spread with a low probability of viral mutation leading to resistance. In particular, host kinases are highly druggable targets and a number of conserved coronavirus proteins, notably the nucleoprotein (N), require phosphorylation for full functionality. In order to understand how targeting kinases could be used to compromise viral replication, we used a combination of phosphoproteomics and bioinformatics as well as genetic and pharmacological kinase inhibition to define the enzymes important for SARS-CoV-2 N protein phosphorylation and viral replication. From these data, we propose a model whereby SRPK1/2 initiates phosphorylation of the N protein, which primes for further phosphorylation by GSK-3/{beta} and CK1 to achieve extensive phosphorylation of the N protein SR-rich domain. Importantly, we were able to leverage our data to identify an FDA-approved kinase inhibitor, Alectinib, that suppresses N phosphorylation by SRPK1/2 and limits SARS-CoV-2 replication. Together, these data suggest that repurposing or developing novel host-kinase directed therapies may be an efficacious strategy to prevent or treat COVID-19 and other coronavirus-mediated diseases.

Modulating the transcriptional landscape of SARS-CoV-2 as an effective method for developing antiviral compounds

To interfere with the biology of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, we focused on restoring the transcriptional response induced by infection. Utilizing expression patterns of SARS-CoV-2-infected cells, we identified a region in gene expression space that was unique to virus infection and inversely proportional to the transcriptional footprint of known compounds characterized in the Library of Integrated Network-based Cellular Signatures. Here we demonstrate the successful identification of compounds that display efficacy in blocking SARS-CoV-2 replication based on their ability to counteract the virus-induced transcriptional landscape. These compounds were found to potently reduce viral load despite having no impact on viral entry or modulation of the host antiviral response in the absence of virus. RNA-Seq profiling implicated the induction of the cholesterol biosynthesis pathway as the underlying mechanism of inhibition and suggested that targeting this aspect of host biology may significantly reduce SARS-CoV-2 viral load.

Identification of Candidate COVID-19 Therapeutics using hPSC-derived Lung Organoids

Summary ParagraphThe SARS-CoV-2 virus has caused already over 3.5 million COVID-19 cases and 250,000 deaths globally. There is an urgent need to create novel models to study SARS-CoV-2 using human disease-relevant cells to understand key features of virus biology and facilitate drug screening. As primary SARS-CoV-2 infection is respiratory-based, we developed a lung organoid model using human pluripotent stem cells (hPSCs) that could be adapted for drug screens. The lung organoids, particularly aveolar type II cells, express ACE2 and are permissive to SARS-CoV-2 infection. Transcriptomic analysis following SARS-CoV-2 infection revealed a robust induction of chemokines and cytokines with little type I/III interferon signaling, similar to that observed amongst human COVID-19 pulmonary infections. We performed a high throughput screen using hPSC-derived lung organoids and identified FDA-approved drug candidates, including imatinib and mycophenolic acid, as inhibitors of SARS-CoV-2 entry. Pre- or post-treatment with these drugs at physiologically relevant levels decreased SARS-CoV-2 infection of hPSC-derived lung organoids. Together, these data demonstrate that hPSC-derived lung cells infected by SARS-CoV-2 can model human COVID-19 disease and provide a valuable resource to screen for FDA-approved drugs that might be repurposed and should be considered for COVID-19 clinical trials.

Identification of Drugs Blocking SARS-CoV-2 Infection using Human Pluripotent Stem Cell-derived Colonic Organoids

Summary ParagraphThe current COVID-19 pandemic is caused by SARS-coronavirus 2 (SARS-CoV-2). There are currently no therapeutic options for mitigating this disease due to lack of a vaccine and limited knowledge of SARS-CoV-2 biology. As a result, there is an urgent need to create new disease models to study SARS-CoV-2 biology and to screen for therapeutics using human disease-relevant tissues. COVID-19 patients typically present with respiratory symptoms including cough, dyspnea, and respiratory distress, but nearly 25% of patients have gastrointestinal indications including anorexia, diarrhea, vomiting, and abdominal pain. Moreover, these symptoms are associated with worse COVID-19 outcomes1. Here, we report using human pluripotent stem cell-derived colonic organoids (hPSC-COs) to explore the permissiveness of colonic cell types to SARS-CoV-2 infection. Single cell RNA-seq and immunostaining showed that the putative viral entry receptor ACE2 is expressed in multiple hESC-derived colonic cell types, but highly enriched in enterocytes. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. We used hPSC-derived COs in a high throughput platform to screen 1280 FDA-approved drugs against viral infection. Mycophenolic acid and quinacrine dihydrochloride were found to block the infection of SARS-CoV-2 pseudo-entry virus in COs both in vitro and in vivo, and confirmed to block infection of SARS-CoV-2 virus. This study established both in vitro and in vivo organoid models to investigate infection of SARS-CoV-2 disease-relevant human colonic cell types and identified drugs that blocks SARS-CoV-2 infection, suitable for rapid clinical testing.

Lumbar artery embolization for the treatment of massive hemorrhage caused by percutaneous transforaminal endoscopic discectomy: preliminary experience in 4 patients / 介入放射学杂志

Objective To evaluate the curative effect and safety of lumbar artery embolization in treating massive hemorrhage caused by percutaneous transforaminal endoscopic discectomy (PTED).Methods From January 2013 to December 2016,lumbar artery angiography was performed in 4 patients with massive hemorrhage caused by PTED.Based on the angiographic findings,lumbar artery embolization therapy with embolic microspheres and spring coils was carried out.Results Lumbar artery angiography revealed that extravasation of contrast agent was detected in 3 patients and pseudoaneurysm in one patient.The bleeding completely stopped immediately after lumbar artery embolization in all 4 patients.The patients were followed up for 1-3 months,and no re-bleeding or serious complications occurred.Conclusion It is very difficult to make medical and surgical management for massive hemorrhage caused by PTED.Lumbar artery embolization is safe,effective and minimally-invasive for the treatment of massive hemorrhage caused by PTED.This therapy is worthy of clinical use.

Changes of blood anterior pituitary hormone and its related factors in patients with severe traumatic brain injury / 中华内分泌外科杂志

Objective To explore changes of blood anterior pituitary hormone and its related factors in patients with severe traumatic brain injury (TBI).Methods 113 patients diagnosed as severe TBI and met criterions were collected from Jun.2010 to Aug.2015 in the First Affiliated Hospital of Wenzhou Medical University.Clinical data such as age,gender,site of injury,epidural hematoma,subdural hematoma,basicranial fracture,injury time,Glasgow coma scale (GCS),middle line migration,diffuse axonal injury,brain hernia,traumatic subarachnoid hemorrhage were collected and recorded.Univariatex2 test and multivariate logistic regression analysis were used to explore risk factors for changes of blood anterior pituitary hormone.Results Abnormal secretion of the anterior pituitary occurred in 48 patients.10 cases had one kind of abnormal hormone secretion,while 38 cases had 2 and more than 2 kinds of abnormal hormone secretion.GH level decreased in 20 cases,TSH level decreased in 18 cases,FSH level decreased in 12 cases,PRL level increased in 10 cases,ACTH level decreased in 9 cases,and LH level decreased in 8 cases.Univariate x2 test revealed that basicranial fracture (P=0.006),middle line migration (P=0.007),GCS score (P=0.004),diffuse axonal injury (P=0.001),cerebral hernia (P=0.001),traumatic subarachnoid hemorrhage (P=0.001) were factors related to abnormal pituitary hormone levels.Multivariate logistic regression analysis revealed that basicranial fracture (P=0.019),middle line migration (P=0.015),GCS score (P=0.024),diffuse axonal injury (P=0.008),cerebral hernia (P=0.001),traumatic subarachnoid (P=0.010) were factors related to abnormal pituitary hormone levels.Conclusions The rates of abnormal pituitary hormone level were higher in patients with severe TBI.The basicranial fracture,middle line migration,GCS score,diffuse axonal injury,cerebral hernia,traumatic subarachnoid hemorrhage are factors related to abnormal pituitary hormone levels.