ObjectivesTrigeminal neuralgia (TN) involves disruption in the integrity of the white matter, the side-specific pain topology of these alterations at the network has yet to be defined. In this study, we investigated the lateralization of structural network architecture and nodal characteristics in TN patients.MethodsWhole-brain structural networks (90 × 90 connectivity matrices) were reconstructed from diffusion tensor imaging (DTI) tractography data of 30 TN patients and 20 matched controls. We applied Network-Based Statistics (NBS) to detect altered connectivity sub-networks, and graph theoretical analysis to profile global and nodal properties. Our analysis aimed to delineate changes that were specific to the painful side.ResultsNBS analysis revealed that structural connectivity formed subnetworks involving multiple functional networks. A subnetwork involving the anterior cingulate gyrus (ACG) and postcentral gyrus (S1) was identified on the painful side, indicating that TN stimulation may enhance structural connectivity between regions related to salience and somatosensory processing, thereby facilitating the acceleration of pain perception and response. On the non-pain side, we observed enhanced structural connections between visual and attention-related regions. The third subnetwork was characterized by widespread and non-focal reductions in fiber tract connectivity. However, despite these localized alterations, the global network properties of the brain in TN patients remained stable, with node-specific properties undergoing alterations in multiple brain regions, including the cuneus, inferior parietal lobule, and superior frontal gyrus.ConclusionHerein, we applied NBS and graph theoretical analysis to investigate changes in the structural brain networks of patients with TN. Analysis revealed that specific subnetworks and key nodes can be affected by TN. We also confirmed obvious differences in the involved subnetworks between pain and non-pain sides in TN patients. These findings suggest that these specific subnetworks and nodes could represent valuable biomarkers for clinical evaluation and intervention in TN patients.
The nervous system regulates peripheral immune responses under physiological and pathological conditions, but the brain's impact on immune system development remains unknown. Meningeal mural lymphatic endothelial cells (muLECs), embedded in the leptomeninges, form an immune niche surrounding the brain that contributes to brain immunosurveillance. Here, we report that the brain controls the development of muLECs via a specialized glial subpopulation, slc6a11b+ radial astrocytes (RAs), a process modulated by neural activity in zebrafish. slc6a11b+ RAs, with processes extending to the meninges, govern muLEC formation by expressing vascular endothelial growth factor C (vegfc). Moreover, neural activity regulates muLEC development, and this regulation requires Vegfc in slc6a11b+ RAs. Intriguingly, slc6a11b+ RAs cooperate with calcium-binding EGF domain 1 (ccbe1)+ fibroblasts to restrict muLEC growth on the brain surface via controlling mature Vegfc distribution. Thus, our study uncovers a glia-mediated and neural-activity-regulated control of brain lymphatic development and highlights the importance of inter-tissue cellular cooperation in development.
Sepsis is a severe disease and induces skeletal muscle atrophy, which has a significant impact on patients. Moreover, the onset and severity of muscle atrophy can vary across different anatomical regions during sepsis. Our previous study demonstrated that ZBED6 knockout not only promotes skeletal muscle growth under physiological conditions, but also alleviates systemic muscle atrophy during sepsis. However, its region-specific effects on sepsis-induced muscle atrophy have not been analyzed. In this study, we performed RNA sequencing for 54 samples of skeletal muscle from nine different anatomical regions from male ZBED6 knockout and wild-type (WT) minipigs subjected to sepsis. We generated 364.63 Gb of high-quality bulk RNA sequencing data from the skeletal muscle samples (approximately 6.75 Gb per sample). This dataset provided insightful gene expression information to understand the role of ZBED6 in region-specific muscle atrophy during sepsis. In addition, this dataset can be used for heterogeneity analysis between skeletal muscle tissues from multiple species or female pigs.
BACKGROUND:Increased expression of fibroblast activation protein (FAP) is associated with coronary atherosclerotic plaques. However, the association of FAP with carotid plaques remains unknown. OBJECTIVES:The objective of this was study was to assess the prevalence, distribution, and intensity of FAP uptake, and its association with carotid ulcerated plaque detected by digital subtraction angiography (DSA) and cerebrovascular risk factors. METHODS:A total of 52 atherosclerotic patients (82 plaques) with significant stenosis in the carotid artery who underwent both 68Ga-FAPI-04 positron emission tomography/magnetic resonance imaging and DSA within 1 week were prospectively enrolled. Correlations between the fibroblast activation protein inhibitor (FAPI) uptake in carotid plaques and ulcerated plaque detected by DSA were assessed. Risk factors for ulcerative plaque were assessed by multivariate logistical regression, and the predictive value of ulcerative plaque was analyzed. Furthermore, an analysis was conducted on the association between FAPI uptake in plaques and severe stenosis, and cerebrovascular risk factors. RESULTS:High focal plaque FAPI uptake was recorded in 35 of 82 plaques, of which 18 were carotid ulcerative plaques. The FAPI uptake, focal maximum standardized uptake value, and FAPI-derived target-to-background ratio (TBR) were significantly greater in ulcerated plaques than in nonulcerated plaques (all P < 0.001). In the multivariate analysis, the FAPI+ uptake (P = 0.002) and FAPI-derived TBR (P < 0.001) independently predicted ulcerated plaques. Among the cerebrovascular risk factors, the FAPI-derived TBR was significantly associated with older age and past cerebrovascular events (P < 0.001). In per patient analysis, the focal maximum standardized uptake value (P = 0.004) and FAPI-derived TBR (P = 0.001) were greater in higher-risk patients than in lower-risk patients. CONCLUSIONS:68Ga-FAPI-04 positron emission tomography/magnetic resonance imaging identifies FAPI uptake and is associated with ulcerated plaques. FAPI+ plaques are also associated with cerebrovascular risk factors.
Background Carotid endarterectomy (CEA) is widely used to treat carotid artery stenosis (CAS). However, the effects of CEA on unilateral CAS‐induced cognitive impairment and the underlying mechanism remain poorly understood. Methods and Results Thirteen patients diagnosed with unilateral severe CAS underwent pre‐ and post‐CEA assessments, including 18 fluoro‐2‐deoxy‐ d ‐glucose positron emission tomography/magnetic resonance imaging, cognitive assessments, and routine blood tests before and after CEA. Unilateral carotid common artery occlusion and ligation release (reperfusion) surgeries were performed in mice to mimic CAS and CEA. Cognitive function, cerebral blood flow, and white matter damage were evaluated in mice using the Morris water maze test, Doppler flowmetry, laser‐speckle imaging, diffusion tensor imaging, Luxol fast blue staining, transmission electron microscopy, and western blot assays post unilateral carotid common artery occlusion and reperfusion. Genomic sequencing of the white matter was performed to explore the potential underlying mechanism. CEA significantly enhanced the Montreal Cognitive Assessment scores in patients with CAS and preoperative cognitive impairment. Moreover, CEA led to notable improvements in cerebral blood flow, energy metabolism, and white matter integrity, while concurrently reducing blood inflammation. In the mouse model, reperfusion surgery alleviated cognitive deficits, increased cerebral blood flow, and alleviated white matter damage following unilateral carotid common artery occlusion. Furthermore, transcriptional surveys have revealed substantial alterations in the upregulation of Nrf2 signaling and metabolic pathways, coupled with the inhibition of neuroinflammation, cellular communication, and immune cell population signaling following reperfusion. Conclusions CEA ameliorated CAS‐induced cognitive dysfunction by improving the cerebral functional structure. These beneficial effects may be attributed to their antioxidant and anti‐inflammatory properties.
BackgroundFangcang shelter hospitals are quarantine facilities offering primary medical treatment for mild and asymptomatic SARS-CoV-2 cases. Little is known about the age-specific prevalence of insomnia among patients in Fangcang shelter hospitals, particularly in older age groups.MethodsThis cross-sectional study was conducted in the three largest Fangcang shelter hospitals during the lockdown period, from March to May 2022, in Shanghai. The patients’ demographic and medical information was recorded. Insomnia was defined according to the prescriptions for zolpidem and estazolam. The overall and age-specific prevalence and the risk factors of insomnia were investigated through regression models.ResultsA total of 2,39,448 patients were included in this study (59.09% of the patients were male, the median age was 42, and 73.41% of the patients were asymptomatic), with the prevalence of insomnia being 3.1%. The prevalence of insomnia varied across different age groups (<18 years: 0.23%, 18–64 years: 2.64%, and ≥65 years: 10.36%). SARS-CoV-2 vaccine, regardless of the number of doses, was significantly associated with a decreased risk of insomnia for the group aged ≥65 years. Three doses of the vaccine reduced the risk of insomnia for patients aged 18–64 years. An extra day in the hospital significantly increased the risk of insomnia by approximately 10% for all age groups. Mild symptoms were significantly associated with a higher risk of insomnia among patients aged <65 years old, while being male and residing in the surrounding area were negatively associated with insomnia for all adults.ConclusionThis study observed that older patients were a high-risk population for developing insomnia in Fangcang shelter hospitals. SARS-CoV-2 vaccination might decrease the risk of insomnia in adults, especially the older adult, which indicates the benefits of vaccination for reducing insomnia among infected patients.
Abstract Background In-flight medical emergencies (IMEs) can have severe outcomes, including the deaths of passengers and aircraft diversions. Information is lacking regarding the incidence rate and characteristics of IMEs in most countries, especially in mainland China. Objective The objective of this study was to investigate the incidence, patterns, and associated risk factors of IMEs in mainland China and to provide medical suggestions for the evaluation and management of IMEs. Methods This population-based retrospective study examined electronic records for all IME reports between January 1, 2018, and December 31, 2022, from a major airline company in mainland China. Outcome variables included the medical category of the IMEs, the outcomes of first aid, and whether or not the IMEs led to a flight diversion. We calculated the incidence rate and death rate of IMEs based on the number of passengers and flights, respectively. A logistic regression model was used to investigate the factors associated with aircraft diversions. Results A total of 199 IMEs and 24 deaths occurred among 447.2 million passengers, yielding an incidence rate of 0.44 (95% CI 0.39‐0.51) events per million passengers and 66.56 (95% CI 50.55‐86.04) events per million flights, and an all-cause mortality rate of 0.05 (95% CI 0.03‐0.07) events per million passengers and 7.50 (95% CI 4.81‐11.16) events per million flights. From 2018 to 2022, the highest incidence and mortality rates were observed in 2019 and 2020, respectively, while the lowest were in 2020 and 2021, respectively. Additionally, the highest incidence and mortality rates were observed between 6 PM to 6 AM and noon to 6 PM, respectively. There was a higher incidence rate of IMEs in the winter months. Moreover, the highest case-fatality rates were observed in 2019 (12/74, 16.2%), on flights traveling ≥4000 km (9/43, 20.9%), and on wide-body planes (10/52, 19.2%). Seizures (29/199, 14.6%), cardiac symptoms (25/199, 12.6%), and syncope or presyncope (19/199, 9.6%) were the most common medical problems and main reasons for aircraft diversion. The incidence of aircraft diversion was 42.50 (95% CI 37.02‐48.12) events per million flights. Narrow-body planes (odds ratio [OR] 5.69, 95% CI 1.05-30.90), flights ≥4000 km (OR 16.40, 95% CI 1.78‐151.29), and the months of December to February (OR 12.70, 95% CI 3.09‐52.23), as well as the months of March to May (OR 23.21, 95% CI 3.75‐143.43), were significantly associated with a higher risk of diversion. Conclusions The occurrence of and deaths associated with IMEs are rare in mainland China, but a temporal trend shows higher incidence rates at night and in winter. The leading IMEs are cardiac symptoms, seizures, and syncope. The establishment of a unified reporting system for IMEs and ground-to-air medical support are of great value for reducing IMEs and deaths in the global community.
Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing’s disease, can result in hypertension. However, whether prolactinoma is associated with this complication remains unknown. Moreover, the effect of treatment with surgery or drugs on blood pressure (BP) is unknown. Herein, a retrospective study reviewed 162 patients with prolactinoma who underwent transsphenoidal surgery between January 2005 and December 2022. BP measurements were performed 1 day before and 5 days after surgery. Accordingly, patients’ medical characteristics were recorded. In addition, in situ rat and xenograft nude-mice prolactinoma models have been used to mimic prolactinoma. In vivo BP and serum prolactin (PRL) levels were measured after cabergoline (CAB) administration in both rats and mice. Our data suggest that surgery can effectively decrease BP in prolactinoma patients with or without hypertension. The BP-lowering effect was significantly associated with several variables, including age, sex, disease duration, tumor size, invasion, dopamine agonists (DAs)-resistance, recurrence, and preoperative PRL levels. Moreover, in situ and xenograft prolactinomas induced BP elevation, which was alleviated by CAB treatment without and with a statistical difference in rats and mice, respectively. Thus, surgery or CAB can decrease BP in prolactinoma, indicating that pre- and postoperative BP management becomes essential.
We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic sequencing methods. We examined 9 patient-derived PitNET primary cells in HTS. Based on the screening results, the potential target genes were analyzed with genomic sequencing from a total of 180 PitNETs. We identified and verified one of the most potentially effective drugs, which targeted the Histone deacetylases (HDACs) both in in vitro and in vivo PitNET models. Further RNA sequencing revealed underlying molecular mechanisms following treatment with the representative HDACs inhibitor, Panobinostat. The HTS generated a total of 20,736 single-agent dose responses which were enriched among multiple inhibitors for various oncogenic targets, including HDACs, PI3K, mTOR, and proteasome. Among these drugs, HDAC inhibitors (HDACIs) were, on average, the most potent drug class. Further studies using in vitro, in vivo, and isolated PitNET primary cell models validated HDACIs, especially Panobinostat, as a promising therapeutic agent. Transcriptional surveys revealed substantial alterations to the Nrf2 signaling following Panobinostat treatment. Moreover, Nrf2 is highly expressed in PitNETs. The combination of Panobinostat and Nrf2 inhibitor ML385 had a synergistic effect on PitNET suppression. The current study revealed a class of effective anti-PitNET drugs, HDACIs, based on the HTS and genomic sequencing. One of the representative compounds, Panobinostat, may be a potential drug for PitNET treatment via Nrf2-mediated redox modulation. Combination of Panobinostat and ML385 further enhance the effectiveness for PitNET treatment.
The purpose of this study is to establish a multivariate nonlinear regression mathematical model to predict the displacement of tumor during brain tumor resection surgery. And the study will be integrated with augmented reality technology to achieve three-dimensional visualization, thereby enhancing the complete resection rate of tumor and the success rate of surgery. Based on the preoperative MRI data of the patients, a 3D virtual model is reconstructed and 3D printed. A brain biomimetic model is created using gel injection molding. By considering cerebrospinal fluid loss and tumor cyst fluid loss as independent variables, the highest point displacement in the vertical bone window direction is determined as the dependent variable after positioning the patient for surgery. An orthogonal experiment is conducted on the biomimetic model to establish a predictive model, and this model is incorporated into the augmented reality navigation system. To validate the predictive model, five participants wore HoloLens2 devices, overlaying the patient’s 3D virtual model onto the physical head model. Subsequently, the spatial coordinates of the tumor’s highest point after displacement were measured on both the physical and virtual models (actual coordinates and predicted coordinates, respectively). The difference between these coordinates represents the model’s prediction error. The results indicate that the measured and predicted errors for the displacement of the tumor’s highest point on the X and Y axes range from −0.678 7 mm to 0.295 7 mm and −0.4314 mm to 0.225 3mm, respectively. The relative errors for each experimental group are within 10
目的 探讨心脏主动脉瓣机械瓣膜置换术后长期服用华法林抗凝后再接受颅脑手术的围手术期桥接抗凝策略.方法 回顾性分析上海交通大学医学院附属瑞金医院2021年4月收治的1例心脏主动脉瓣机械瓣膜置换术后桥接抗凝的无功能垂体腺瘤患者的临床资料,并对相关文献进行复习.结果 患者女,63岁,因轻微车祸外伤行头颅CT检查发现侵袭性垂体大腺瘤,拟行垂体腺瘤切除术;然而,术前常规检查发现主动脉瓣钙化伴重度狭窄,遂先行主动脉瓣机械瓣膜置换术,术后长期服用华法林抗凝.为改善视力视野,进一步行手术切除垂体大腺瘤,在多学科协作下采用神经内镜经鼻全切肿瘤,并对抗凝过程顺利进行桥接,患者术后无相关并发症.结论 通过本病例的回顾分析,希望加强神经外科医师对颅脑手术合并心脏重大疾病的手术时机选择,以及抗凝过程中围手术期管理的认识,以期提高手术疗效及降低手术风险.
Backgrounds The widespread coronavirus disease 2019 (COVID-19) outbreak impacted the mental health of infected patients admitted to Fangcang shelter hospital a large-scale, temporary structure converted from existing public venues to isolate patients with mild or moderate symptoms of COVID-19 infection. Objective This study aimed to investigate the risk factors of the infected patients from a new pharmacological perspective based on psychiatric drug consumption rather than questionnaires for the first time. Methods We summarised the medical information and analysed the prevalence proportion, characteristics, and the related risk factors of omicron variants infected patients in the Fangcang Shelter Hospital of the National Exhibition and Convention Center (Shanghai) from 9 April 2022 to 31 May 2022. Results In this study, 6,218 individuals at 3.57% of all admitted patients in the Fangcang shelter were collected suffering from mental health problems in severe conditions including schizophrenia, depression, insomnia, and anxiety who needed psychiatric drug intervention. In the group, 97.44% experienced their first prescription of psychiatric drugs and had no diagnosed historical psychiatric diseases. Further analysis indicated that female sex, no vaccination, older age, longer hospitalization time, and more comorbidities were independent risk factors for the drug-intervened patients. Conclusion This is the first study to analyse the mental health problems of omicron variants infected patients hospitalised in Fangcang shelter hospitals. The research demonstrated the necessity of potential mental and psychological service development in Fangcang shelters during the COVID-19 pandemic and other public emergency responses.
Abstract Background: In the beginning of March 2022, coronavirus disease-2019 (COVID-19) rapidly spread in Shanghai. In order to cope with the epidemic, more than 110 fangcang hospitals with over 250000 beds were constructed. Thus, effective batch patient admission strategies suitable to meet the characteristics of fangcang hospital are of essential importance. To summarize the experience of batch patient admission during the operation of three super large square cabin hospitals in Shanghai. Methods: A case review and effectiveness evaluation based on the batch treatment of patients in three super large Super large temporary hospitals in Shanghai. This case review investigated two methods of batch patient admission in three large Super large temporary hospitals established in Shanghai, China, between March and May 2022, and compared the efficiency and risks of the two methods, as well as summarized the coping strategies for batch patient admission in large square cabin hospitals. Results: Under the same staffing conditions, the batch patient admission mode of “treatment before triage” was used. The average number of patients admitted per hour, the average number of patients admitted within 72 h in each branch, and the maximum number of patients admitted per hour in each branch were significantly higher compared to the traditional patient admission mode of “triage before admission.” However, the proportion of patients who did not meet the admission criteria in this mode was high, and there was a significant medical risk. Conclusions: Establish a scientific, standardized, and reasonable batch patient admission strategy to effectively respond to the large number of patients admitted to the shelter hospital.
Background Thromboprophylaxis has been determined to be safe, effective and cost-effective for hospitalised patients at venous thromboembolism (VTE) risk. However, Chinese medical institutions have not yet fully used or improperly used thromboprophylaxis. The effectiveness of information technology applied to thromboprophylaxis in hospitalised patients has been proved in many retrospective studies, lacking of prospective research evidence. Methods All hospitalised patients aged >18 years not discharged within 24 hours from 1 September 2020 to 31 May 2021 were prospectively enrolled. Patients were randomly assigned to the control (9890 patients) or intervention group (9895 patients). The control group implemented conventional VTE prevention programmes; the intervention group implemented an Artificial Intelligence Clinical Assistant Decision Support System (AI-CDSS) on the basis of conventional prevention. Intergroup demographics, disease status, hospital length of stay (LOS), VTE risk assessment and VTE prophylaxis were compared using the χ2 test, Fisher’s exact test, t-test or Wilcoxon rank-sum test. Univariate and multivariate logistic regressions were used to explore the risk factor of VTE. Results The control and intervention groups had similar baseline characteristics. The mean age was 58.32±15.41 years, and mean LOS was 7.82±7.07 days. In total, 5027 (25.40%) and 2707 (13.67%) patients were assessed as having intermediate-to-high VTE risk and high bleeding risk, respectively. The incidence of hospital-associated VTE (HA-VTE) was 0.38%, of which 86.84% had deep vein thrombosis. Compared with the control group, the incidence of HA-VTE decreased by 46.00%, mechanical prophylaxis rate increased by 24.00% and intensity of drug use increased by 9.72% in the intervention group. However, AI-CDSS use did not increase the number of clinical diagnostic tests, prophylaxis rate or appropriate prophylaxis rate. Conclusions Thromboprophylaxis is inadequate in hospitalised patients with VTE risk. The role of AI-CDSS in VTE risk management is unknown and needs further in-depth study. Trial registration number ChiCTR2000035452.
Ferroptosis, a form of regulatory non-apoptotic cell death driven by iron-dependent lipid peroxidation, accounts for more than 80% of the total types of neuronal death in the acute phase of intracerebral hemorrhage (ICH). Mitochondria have essential roles in energy production, macromolecule synthesis, cellular metabolism, and cell death regulation. However, its role in ferroptosis remains unclear and somewhat controversial, especially in ICH. This study aimed to investigate whether damaged mitochondria could trigger and enhance neuronal ferroptosis in ICH. The isobaric tag for relative and absolute quantitation proteomics on human ICH samples suggested that ICH caused significant damage to the mitochondria, which presented ferroptosis-like morphology under electron microscopy. Subsequently, use of the mitochondrial special inhibitor Rotenone (Rot) to induce mitochondrial damage showed that it has significant dose-dependent toxicity on primary neurons. Single Rot administration markedly inhibited neuronal viability, promoted iron accumulation, increased malondialdehyde (MDA) contents, decreased total superoxide dismutase (SOD) activity, and downregulated ferroptosis-related proteins RPL8, COX-2, xCT, ASCL4, and GPX4 in primary neurons. Moreover, Rot enhanced these changes via hemin and autologous blood administration in primary neurons and mice, mimicking the in vitro and in vivo ICH models, respectively. Furthermore, Rot exacerbated the ICH-induced hemorrhagic volumes, brain edema, and neurological deficits in mice. Together, our data revealed that ICH induced significant mitochondrial dysfunction and that mitochondrial inhibitor Rot can trigger and enhance neuronal ferroptosis.
社会捐赠体系是国家应急物资保障的重要组成部分.物资捐赠作为疫情防控期间物资保障的一种重要形式和补充,其响应速度对解决疫情特殊时期医疗物资匮乏问题起到了至关重要的作用.该文通过在国家会展中心(上海)方舱医院物资捐赠管理工作实践中反复总结、积累实践,以分配公平性、效用优化性、信息透明性为目标,制定了大型方舱医院物资捐赠制度,创建了相关流程,形成了大型方舱医院物资捐赠管理体系,在确保国家会展中心(上海)方舱医院正常运行中发挥了重大作用.
Shanghai has faced an unprecedented COVID-19 pandemic with the BA.2.2 strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron infection. Comprehensive insights into its epidemiology, clinical manifestations, and viral shedding dynamics are currently limited. This study encompasses 208373 COVID-19 patients that were infected with the Omicron BA.2.2 sub-lineage in Shanghai, China. Demographic information, clinical symptoms, vaccination status, isolation status, as well as viral shedding time (VST) were recorded. Among the COVID-19 patients included in this study, 187124 were asymptomatic and 21249 exhibited mild symptoms. The median VST was 8.3 days. The common clinical symptoms included fever, persistent cough, phlegm, sore throat, and gastrointestinal symptoms. Factors such as advanced age, presence of comorbidities, mild symptomatology, and delayed isolation correlated with extended VST. Conversely, female gender and administration of two or three vaccine doses correlated with a reduction in VST. This investigation offers an in-depth characterization and analytical perspective on Shanghai's recent COVID-19 surge. Prolonged viral shedding of SARS-CoV-2 was observed in elderly, male, symptomatic patients, and those with comorbidity. Female, individuals with two or three vaccine doses, as well as those isolated early, shows an effective reduced VST.
Immune checkpoint blockade combined with reversal of the immunosuppressive tumor microenvironment (TME) can dramatically enhance anti-tumor immunity, which can be achieved by using multiple-agent therapy. However, the optimal dose and order of administration of different agents remain elusive. To address this dilemma, multiple agents are often grafted together to construct "all-in-one" totipotent drugs, but this usually comes at the cost of a lack of synergy between the agents. Herein, by comprehensively analyzing the conserved sites of the immune checkpoint and TME drug targets, peptide secondary structures, assembly properties, and other physicochemical properties, a high-content peptide library is designed. By using the "3D-molecular-evolution" screening strategy, an efficient and totipotent "all-in-one" peptide (TAP) is obtained, which possesses the abilities of self-assembling, blocking the PD-1/PD-L1 axis, inhibiting Rbm38-eIF4E complex formation, and activating p53. It is shown that in mice treated with TAP, with either subcutaneous tumors or patient-derived xenografts, PD-L1 is blocked, with increased activation of both T and NK cells whilst reversing the immunosuppressive TME. Moreover, TAP can mitigate tumor activity and suppress tumor growth, showing superior therapeutic effect over antibody-based drugs.
探索在新型冠状病毒(新冠)感染疫情防控中的大型方舱医院药品保障管理模式。根据方舱医院规模及收治新冠感染者特征,成立应急药品管理团队,搭建药品管理组织架构、建立规章制度;根据方舱医院的运行特点,制定和调整药品目录,规范申领、调拨流程,并加强特殊药品的管理;依据感染者的需求,开展多元化药学服务,指导患者用药。本团队建立了针对大型方舱医院运行的特色药品保障体系,分为中心药库及二级药库进行药品保障管理,在做到保障基本医疗药品供应的同时,提供药学服务以确保患者的用药安全。本团队建立的方舱药品保障管理模式,可为应对突发公共卫生事件时药品保障及完善服务患者提供参考。