BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Objective To systematically evaluate the effects of total intravenous anesthesia and inhalational anesthesia on postoperative recovery in patients undergoing transsphenoidal pituitary tumor resection.Methods A comprehensive search was conducted in international biomedical databases including Ovid Medline,Embase,CINAHL(EBSCO),Cochrane Library,and Web of Science,from inception to July 4,2023.Additionally,ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing and completed trials.The randomized controlled trials(RCT)comparing total intravenous anesthesia and inhalational anesthesia in patients undergoing transsphenoidal surgery for pituitary tumors were included.The methodological quality of the included studies was evaluated by the Cochrane Collaboration tool.Relevant data were extracted and synthesized for analysis.Results A total of 327 records were identified,of which eight RCTs met the inclusion criteria.Four studies showed that the patients receiving desflurane or sevoflurane anesthesia experienced faster emergence from anesthesia than those receiving propofol.Two studies indicated that patients in the propofol group had lower levels of emergence agitation and a lower incidence of early postoperative nausea and vomiting.The results on postoperative cognitive function were inconsistent across studies.No differences were found between the groups in terms of postoperative complications or overall recovery quality during hospitalization.Conclusions Inhalational anesthesia appears to provide an advantage in promoting faster emergence following transsphenoidal pituitary surgery,whereas total intravenous anesthesia may contribute to smoother and more stable recovery.Further high-quality studies are needed to clarify the effects of different anesthetic techniques on both short- and long-term postoperative recovery.
Humans ; Anesthesia, Intravenous ; Pituitary Neoplasms/surgery* ; Anesthesia, Inhalation ; Randomized Controlled Trials as Topic ; Anesthesia Recovery Period ; Pituitary Gland/surgery* ; Postoperative Period

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

Objective:To assess the current situation, advantages, and difficulties of standardized management in Investigator-Initiated Clinical Trials (IIT).Methods:This article summarized the requirements and policies for clinical research management, the development of clinical research domestically and internationally, the achievements and advantages of clinical research management development in China, and the main problems and difficulties with the standardized IIT management in China, and compiled the experiences and models of several medical institutions in IIT management.Results:While China has a large number of clinical medical publications and is ranked high in the world, the quality of the publications needs to be further improved. Domestic management requirements for IIT were gradually improving, providing a basis for medical institutions to implement standardized management throughout the lifecycle of IIT, and achieve certain progress. However, there were still challenges in the departmental divisions, the unification of management standards, whole-process management and quality control, the scientific review, high-risk project management, and registration.Conclusions:Drawing on the excellent experience of domestic medical institutions, measures including identifying a primary responsible department, establishing unified supervision and inspection standards, and implementing a whole life cycle management may help overcome the challenges in IIT management and improve the quality and efficiency of IIT management.

ObjectiveTo observe the therapeutic effect of BD-77 by nebulized inhalation on animal models of various respiratory viral infections and investigate the mechanism of broad-spectrum antiviral action of BD-77 using proteomics. MethodThe influenza virus H1N1/FM1 experiment used ICR mice and divided them into a normal group， model group， Tamiflu group， and BD-77 groups of 75 and 37.5 g·L^-1 for inhalation of 20 min and 25 min. Human coronavirus 229E and OC43 experiment divided the BALB/c mice into a normal group， model group， chloroquine phosphate group， and BD-77 groups of 75， 37.5， 18.75， and 9.375 g·L^-1， with 10 mice in each group. Influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection-induced pneumonia models were used to detect mouse lung index， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect related inflammatory factors in lung tissue， and proteomics analysis was performed on the lung tissue of OC43-infected mice. ResultCompared with that in the normal group， the lung index of mice in each infection group was significantly increased （P<0.01）， and viral nucleic acid could be detected in the lung tissue of mice infected with human coronaviruses 229E and OC43. The levels of interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the lung tissue of mice infected with human coronavirus 229E were all significantly increased （P<0.01）. BD-77 could significantly reduce the lung index of mice infected with influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 （P<0.05， P<0.01）， cut down the viral load in the lungs of mice infected with human coronaviruses 229E and OC43 （P<0.01）， and lower the contents of IL-6， IL-10， and TNF-α in the lung tissue of mice infected with human coronavirus 229E （P<0.01）. Proteomics analysis of the lung tissue of OC43-infected mice showed that BD-77 regulated the AMPK signaling pathway， TNF signaling pathway， NOD-like signaling pathway， IL-17 signaling pathway， Forkhead box protein O （FoxO） signaling pathway， transforming growth factor-β （TGF-β） signaling pathway， and other signaling pathways. ConclusionNebulized inhalation of BD-77 is effective in treating pneumonia caused by influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection in mice and may exert its antiviral effects by regulating the balance of cellular metabolism， enhancing the immune function of the host， and attenuating inflammatory responses.

Rare diseases have a significant and profound impact on society, the economy, and the healthcare system. The path to developing drugs for rare diseases is particularly arduous. Due to the small number of patients and limited market demand, pharmaceutical companies don′t have enough incentives and resources to invest in drug research and development. Additionally, the long development cycles, high costs, and high risks have led to a number of potential therapeutic drug failures at the early stages of development. This article summarizes a series of encouraging policies adopted by the National Medical Products Administration for rare diseases, which is an important public health issue, as well as the achievements in the review and approval of rare disease drugs in recent years. These policies have accelerated the approval process. Meanwhile, the policies ensure the safety and effectiveness of drugs and offer more treatment options and hopes to patients with rare diseases. With the continuous effort at optimizing the policy environment and the advancement of research and development technologies, China′s drug regulatory authorities will continue to focus on the clinical needs of rare diseases, to implement " patient-centered " approach to drug development, inject new vitality into the research and development of drugs of rare diseases, and offer more precise and effective treatment choices for patients with rare diseases.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.