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.

Objective:To explore the potential of the novel fibroblast activation protein (FAP)-targeted theranostic agent 68Ga/ 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-2P (FAP inhibitor (FAPI)) 2 in microsatellite stable (MSS) colorectal cancer, and to evaluate the efficacy and underlying mechanism of 177Lu-DOTA-2P(FAPI) 2 in combination with immune checkpoint inhibitors (ICIs). Methods:This study was a randomized, parallel-group design. DOTA-2P(FAPI) 2 was labeled with 68Ga or 177Lu respectively. The binding performance of DOTA-2P(FAPI) 2 to FAP was validated through in vitro cell experiments. FAP-positive CT26-FAP tumor-bearing mouse model was constructed, and microPET imaging and biodistribution were performed. The in vivo antitumor efficacy was assessed for the 177Lu-DOTA-2P(FAPI) 2 monotherapy, α programmed death-ligand 1 (PD-L1) monotherapy, and the combination of 177Lu-DOTA-2P(FAPI) 2 with αPD-L1 therapy groups. Changes in the tumor microenvironment were analyzed using single-cell RNA sequencing to elucidate the mechanism of the combined treatment. Independent-sample t test was used to analyze data. Survival analysis was performed using the log-rank test. Results:The labeling yields of 68Ga/ 177Lu-DOTA-2P(FAPI) 2 were both >90%, with the radiochemical purities both >95%. In vitro cellular uptake and blocking assays showed that FAPI-46 significantly inhibited the binding of 68Ga-DOTA-2P(FAPI) 2 to FAP in CT26-FAP cells, with the cellular uptake values at 60min of (51.5±0.8)% and (1.0±0.3)%, respectively ( t=102.40, P<0.001). MicroPET imaging showed that the tumor uptake of 68Ga-DOTA-2P(FAPI) 2 remained stable even at 4 h post-injection, with a significantly higher uptake value compared to 68Ga-FAPI-46 ((7.3±1.6) vs (3.7±0.2) percentage activity of injection dose per gram of tissue (%ID/g); t=3.87, P=0.018). The biodistribution results indicated significant tumor uptake of 177Lu-DOTA-2P(FAPI) 2 even at 24 h post-injection ((4.30±0.52)%ID/g). The combination of 177Lu-DOTA-2P(FAPI) 2 and αPD-L1 achieved the 30-day survival rate of 100%, which was significantly superior to that of the control group (saline injection; χ2=9.53, P=0.002). Further mechanistic studies revealed that the combination therapy reprogramed the tumor microenvironment, enhanced anti-tumor intercellular communication, and activated signaling pathways such as Fas-FasL between T cells/natural killer (NK) cells and tumor cells, thereby synergistically inhibiting tumor progression. Conclusions:68Ga/ 177Lu-DOTA-2P(FAPI) 2 exhibits theranostic potential for MSS colorectal cancer. The combination of 177Lu-DOTA-2P(FAPI) 2 with ICIs may significantly prolong survival, demonstrating significant potential for clinical translation.

This study aims to comprehensively evaluate the analytical performance and clinical application value of an acridinium ester-based chemiluminescence assay for detecting heparin-binding protein (HBP), providing more accurate laboratory evidence for the early diagnosis of infections and sepsis. The analytical performance of the HBP detection kit based on acridinium ester chemiluminescence was verified in Hangzhou Hospital of Traditional Chinese Medicine in January 2024 to June 2024, including limit of blank (LoB), accuracy, precision, linear range, anti-interference ability, and clinical diagnostic concordance. The potential of this assay in early diagnosis and treatment monitoring of sepsis was assessed. HBP levels were measured in 97 patients with sepsis and 160 healthy controls, and intergroup differences were analyzed using the Mann-Whitney U test. The results showed that the LoB of the HBP detection kit based on acridinium ester chemiluminescence was 0.10 RLU, and low-concentration sample testing showed good discrimination. In the accuracy evaluation, the regression equation between the test reagent and the comparator was y=1.015 2 x-2.850 8 (R2=0.995 1). For precision, the CV in intra-assay was ≤3.51%, and the CV in inter-assay was ≤4.18%. Within the linear range of 0.42-493.46 ng/ml, the regression equation was y=0.996 9 x+3.066 0 (R2=0.999 1). In interference experiments, the relative deviation was <3%. Clinically, the median HBP concentration in the sepsis group (median: 121.1 ng/ml) was significantly higher than in the control group (median: 6.3 ng/ml, P<0.000 1), with a diagnostic sensitivity of 98.97% and specificity of 96.25%. Age stratification had no effect on HBP levels ( U=448 ,P=0.780 0). In conclusion,the acridinium ester-based chemiluminescence assay requires only about 10 minutes to complete the detection and deliver results, demonstrating acceptable sensitivity, precision, and anti-interference capability. Its wide linear range and rapid detection meet emergency testing needs. Clinical validation confirms HBP′s extremely high sensitivity and specificity for sepsis diagnosis, supporting its role as a key marker for early diagnosis, treatment monitoring, and prognosis assessment.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

The HDAs (a subfamily of histone deacetylases), a class of Zn²⁺-dependent histone deacetylases, are highly homologous to the reduced potassium dependency 3 (RPD3) in yeast. HDAs extensively regulate chromosome stability, gene transcription, and protein activity by catalyzing the removal of acetyl group from histone and non-histone lysine residues. HDA-mediated deacetylation is essential for plant growth, development, and responses to abiotic stress. We review the research progress in HDAs regarding the discovery, structures, classification, deacetylation process, and roles in regulating plant responses to abiotic stress. Furthermore, this paper prospects the future research on HDAs, aiming to provide theoretical support for the research on epigenetic regulation mediated by HDAs.
Histone Deacetylases/classification* ; Zinc/metabolism* ; Stress, Physiological/physiology* ; Plants/genetics*

Autophagy is an evolutionarily conserved self-degradation process in eukaryotes. It not only plays a role in plant growth and development but also is involved in plant responses to biotic and abiotic stresses. Plants can initiate autophagy to degrade the surplus or damaged cytoplasmic materials and organelles, thus coping with abiotic and biotic stresses. The initiation of autophagy depends on autophagy-related genes (ATGs). The transcription factors can directly bind to the promoters of ATGs to activate autophagy and regulate their transcriptional levels and post-translational modifications. Furthermore, ATGs can directly or indirectly interact with plant hormones to regulate plant responses to stresses. When plants are exposed to salinity, drought, extreme temperatures, nutrient deficiencies, and pathogen stress, ATGs are significantly induced, which enhances the autophagy activity to facilitate the degradation of the denatured and misfolded proteins, thereby enhancing plant tolerance to adversity stresses. This article summarizes the discovery, structures, and classification of plant ATGs, reviews the research progress in the mechanisms of ATGs in plant responses to abiotic and biotic stresses, and prospects the future research directions. This review is expected to provide the genetic resources and a theoretical foundation for the genetic improvement of crops in responses to stress tolerance.
Autophagy/physiology* ; Stress, Physiological/genetics* ; Gene Expression Regulation, Plant ; Plants/metabolism* ; Transcription Factors/metabolism* ; Plant Proteins/genetics* ; Genes, Plant ; Plant Physiological Phenomena ; Droughts

Sucrose non-fermenting 1-related protein kinase 1 (SnRK1) is one of the highly conserved Ca²⁺ non-dependent serine/threonine protein kinases, playing a crucial role in regulating the stress responses, growth, and development of plants. SnRK1 is a three-subunit complex, and it is involved in responding to the signaling transduction induced by low-energy/low-sugar conditions. SnRK1 responds biotic and abiotic stress conditions (such as salt, drought, low/high temperatures, and diseases) through phosphorylation of key metabolic enzymes and regulatory proteins, regulation of transcription, and interactions with other proteins. Furthermore, SnRK1 is not only involved in hormone signaling pathways mediated by abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA), but also regulates plant autophagy by inhibiting the activity of target of rapamycin (TOR). In this review, we summarized the current results of research on the discovery, structure, and classification of plant SnRK1 and its roles in the stress responses, growth, and development of plants. Furthermore, this article proposes the directions of future research. This review provides good genetic resources and a theoretical basis for the genetic improvement and biological breeding for enhancing the stress tolerance of crops.
Stress, Physiological/physiology* ; Protein Serine-Threonine Kinases/metabolism* ; Plant Development/genetics* ; Signal Transduction ; Gene Expression Regulation, Plant ; Plant Proteins/physiology* ; Plants/metabolism* ; Arabidopsis Proteins/physiology* ; Plant Growth Regulators/metabolism*

Calcineurin B-like protein (CBL)-interacting protein kinases (CIPKs) are a group of Ser/Thr protein kinases, playing a crucial role in the growth, development, and stress responses of plants. CIPKs can undergo autophosphorylation or target the phosphorylation of other signaling factors in responses to biotic and abiotic stresses. In addition, they are involved in the signaling pathways of plant hormones such as abscisic acid (ABA), gibberellic acid (GA), ethylene (ETH), and salicylic acid (SA) to regulate plant growth and development. Furthermore, CIPKs respond to stresses such as salinity, drought, cold, and heavy metals by forming complexes through specific interactions with CBLs. In this study, we summarized the discovery, structures, classification, regulatory mechanisms, and roles of CIPKs in plant responses to stresses and made an outlook on the future research directions. This review is expected to provide genetic resources and theoretical foundations for the genetic improvement and breeding of crops with stress tolerance.
Stress, Physiological/physiology* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/physiology* ; Plant Growth Regulators/metabolism* ; Plant Proteins/genetics* ; Plants/metabolism*

Objective:To explore the effects of Jianpi Mixture on the glucose receptor/glucagon like peptide-1 (GLP-1)/5-hydroxytryptamine (5-HT) signaling pathway and the mechanism of Jianpi Mixture in improving visceral hypersensitivity in diarrhea-predominant irritable bowel syndrome (IBS-D) rats.Methods:Totally 40 healthy male SPF rats were divided into blank group, model group, Jianpi Mixture low- and high-dosage groups according to the random number table method, with 10 rats in each group. Except for the blank group, the rest of the rats were prepared by the "senna gavage combined with restraint stress" method to replicate the IBS-D spleen deficiency model. The aqueous extract of Jianpi Mixture was 2.52 and 7.56 g/kg in the low- and high-dosage groups, and the same volume of normal saline was given to the blank group and the model group, once a day, for 14 days. On the 1st, 7th and 14th days of administration, the body weight of rats was recorded, the fecal traits of the rats were scored with Bristol score, the visceral sensitivity of IBS-D rats was evaluated by the abdominal wall retraction reflex score (AWR) under rectal dilation, the morphology of colonic mucosal tissues was observed by HE staining, and the protein expressions of T1R2, SLGT1, GLUT2, GLP-1 and 5-HT in colon tissues were detected by immunohistochemical staining.Results:On the 1st, 7th and 14th days of administration, compared with the model group, the weight of the rats in the Jianpi Mixture high-dosage group increased ( P<0.05); on the 14th day of administration, the fecal Bristol score decreased significantly ( P<0.05) and the AWR score increased ( P<0.05); HE staining showed that the mucosal epithelium of colon tissue in the model group was slightly damaged, and local edema was visible. The pathological condition of colonic mucosa in the Jianpi Mixture low- and high-dosage groups was effectively improved; compared with the model group, the expressions of T1R2 and GLP-1 in the Jianpi Mixture low- and high-dosage groups increased ( P<0.05), and the expression of 5-HT decreased ( P<0.05); the protein expressions of GLUT2 and SGLT1 in the Jianpi Mixture high-dosage group increased ( P<0.05). Conclusion:Jianpi Mixture can treat spleen-deficiency IBS-D by restoring the normal expression of intestinal glucose receptors, regulating the secretion of GLP-1/5-HT, improving intestinal motility and alleviating visceral hypersensitivity.