Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Invasive fungal infections (IFIs) are a group of diseases caused by fungal pathogens, primarily Candida, Aspergillus, and Cryptococcus, which invade the body, proliferate in deep tissues, organs, or the bloodstream, and lead to localized or systemic severe infections. These infections impose significantclinical and economic burdens due to their high mortality rates, the high cost and limited availability of antifungal drugs, and the frequent adverse effects. Invasive fungal pathogens invade the host through hyphae, spores, and secreted adhesive proteins, primarily triggering disease via signal cascades resulting from the binding of fungal membrane ligands to host receptors, as well as through secreted substances and intrinsic toxins. Macrophages, as the first line of defense against invasive fungal pathogens, play a crucial role in combating IFIs. They combat fungal pathogens through mechanisms such as antigen recognition, phagocytosis, oxidative killing, polarization, and the regulation of various bioactive substances. This article reviews recent research progress on the mechanisms by which macrophages contribute to innate immunity against invasive fungal infections. Additionally, it discusses the immune evasion strategies employed by invasive fungal pathogens to counteract macrophages, aiming to provide new insights for the prevention and treatment of invasive fungal infections.
Humans ; Immunity, Innate ; Macrophages/immunology* ; Invasive Fungal Infections/microbiology* ; Animals ; Phagocytosis/immunology*

Membrane protein degradation is a cutting-edge field in targeted protein degradation (TPD). Herein, we developed glypican-3 (GPC3)-mediated lysosome-targeting chimeras (GLTACs) as a novel strategy for the targeted degradation of tumor-specific membrane proteins. GLTACs utilize tumor-specific expression and endocytosis properties of GPC3 to degrade membrane proteins. By conjugating a GPC3-targeting peptide with the ligand of protein of interest (POI), GLTACs induce the formation of a ternary complex that is internalized into lysosomes, leading to the degradation of the POI. The effectiveness and specificity of GLTACs were validated by designing PD-L1, c-Met, and FGFR1 degraders. In particular, GLTAC WP0 potently degraded PD-L1 and induced T-cell-mediated tumor killing against HepG2 cells, highlighting the potential therapeutic applications. The development of GLTAC technology expands the scope of TPD strategies and opens new avenues for discovering novel therapeutic modalities against challenging protein targets.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Objective:To explore the effect of SQLE on the biological characteristics of pan-cancer,using bioinformatics methods to predict and analyze the correlation between SQLE and the clinical prognosis and immunity of pan-cancer.Methods:The ex-pression level of SQLE in tumor and normal tissues and its correlation with different clinical stages of pan-cancer were analyzed,and the relationship between SQLE expression and overall survival and tumor microenvironment were evaluated.Gene enrichment analysis was conducted to study the biological functions and signaling pathways related to SQLE gene,then,calculate the correlation between SQLE gene and tumor mutation load and microsatellite instability,and analyze the correlation between SQLE gene and immunomodula-tory genes.Results:SQLE gene was highly expressed in variety of tumors,and differentially expressed in different tumor stages.High expression of SQLE was a risk factor in variety of tumors.Patients with high expression of SQLE hade a worse prognosis.SQLE was cor-related with TMB and MSI,and involved in tumor development through different pathways.Conclusion:SQLE,as a valuable prognos-tic biomarker and new therapeutic target for variety of cancers,has certain application value in basic research and clinical treatment of various cancers.

Objective To analyze the causes of changes in the prevalence of respiratory diseases and the reason for changes in medical visit behavior of children in Zhejiang Province during the winter and spring seasons of 2019-2021, and to provide important reference for the allocation of hospital resources, implementation of hierarchical diagnosis and treatment, and epidemic prevention and control. Methods A retrospective study was conducted on 256 937 outpatient medical records from January 23rd to April 23rd of each year from 2019 to 2021 at the Children's Hospital Affiliated to Zhejiang University School of Medicine. Statistical methods were used for data analysis. Results A total of 256 937 cases were selected in the present study, including 157 000 cases in 2019, 22 192 cases in 2020, and 77 745 cases in 2021. The number of patients to the Children's Hospital of Zhejiang University School of Medicine from outside Hangzhou accounted for 41.74%, 14.36% , and 18.53% in 2019-2021, respectively. For 0~2 years old , 3~6 years old , and 7~14 years old groups , the percentages of patients with upper respiratory tract infections were 49.54%, 45.95%, and 46.74%, respectively ; with lower respiratory tract infections were 42.90% , 31.76% , and 22.95% ; with influenza were 2.23% , 3.15% and 4.09%; and with asthma were 1.37%, 5.08%, and 8.15%, respectively. Conclusion From 2019 to 2021, there have been significant changes in the total number of respiratory diseases in children, the proportion of disease types, and the proportion of children's geographical composition. It is necessary to continue to monitor children's respiratory diseases, grasp the dynamic changes in their medical visits in real time, adjust the hospital admission model , implement the graded treatment policy, and promote the prevention and control of respiratory diseases in children.

OBJECTIVE To evaluate the cost-effectiveness of regorafenib in the treatment of hepatocellular carcinoma after failure of sorafenib from the perspective of Chinese health system. METHODS Based on a phase Ⅲ trial（RESORCE）， the partition survival model （PSM） and Markov model were constructed. The cycle was set as four weeks， the duration of the study lasted for lifetime， the annual discount rate was 5%. Drug cost data was obtained from yaozhi.com， other cost data were obtained from Anhui Provincial Medical Insurance Bureau and related literature， and utility values were obtained from literature. The incremental cost-effectiveness ratio （ICER） was used as the evaluation index， and the value of willingness to pay （WTP） was three times of China’s gross domestic product （GDP） per capita in 2022； one-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the basic analysis results. RESULTS The incremental cost of regorafenib group versus placebo group in PSM and Markov model was 112 116.95 yuan and 96 617.19 yuan， respectively. The incremental effectiveness was 0.31 QALYs and 0.32 QALYs， respectively. The ICERs were 360 751.01 yuan/QALY and 301 114.45 yuan/QALY， which were both greater than the value of WTP； regorafenib was not cost-effective. Results of one-way sensitivity analysis showed that the utility of progression-free survival and progressive disease， the unit cost of regorafenib had the greatest influence on the results， but ICER was always greater than the WTP within the floating range of each parameter. Under the WTP of 3 times China’s per capita GDP in 2022， the probabilities of regorafenib with cost-effectiveness were 0.8% （PSM） and 11.4% （Markov）. CONCLUSIONS Under the WTP of 3 times the per capita GDP of China， regorafenib is not cost-effective in the treatment of hepatocellular carcinoma after failure of sorafenib treatment， compared with placebo.

Nasal tip hypertrophy is one of the common nasal tip morphological abnormalities in clinical practice. A comprehensive treatment regimen is possible only when one can correctly understand the mechanism of nasal tip hypertrophy. In this paper, the mechanism and treatment of nasal tip hypertrophy were analyzed and summarized in order to provide some reference for rhinoplastic surgeons.

The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases, such as depression and anxiety. Meanwhile, the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor (CB₁R), which is strongly expressed in the amygdala of non-human primates (NHPs). However, it remains largely unknown how the CB₁Rs in the amygdala of NHPs regulate mental diseases. Here, we investigated the role of CB₁R by knocking down the cannabinoid receptor 1 (CNR1) gene encoding CB₁R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA. We found that CB₁R knockdown in the amygdala induced anxiety-like behaviors, including disrupted night sleep, agitated psychomotor activity in new environments, and reduced social desire. Moreover, marmosets with CB₁R-knockdown had up-regulated plasma cortisol levels. These results indicate that the knockdown of CB₁Rs in the amygdala induces anxiety-like behaviors in marmosets, and this may be the mechanism underlying the regulation of anxiety by CB₁Rs in the amygdala of NHPs.
Animals ; Callithrix ; Receptors, Cannabinoid ; Anxiety ; Amygdala ; Cannabinoids ; Phenotype