OBJECTIVE To establish the graded management standards for off-label use of Shenqi fuzheng injection. METHODS Systematic searches were conducted in databases including CNKI， PubMed and the Cochrane Library to retrieve guidelines/consensuses， systematic reviews/meta-analyses， and randomized controlled trials （RCTs） of Shenqi fuzheng injection. The quality of evidence was evaluated using AGREE Ⅱ， AMSTAR Ⅱ， and the Risk of Bias 1.0 tool recommended by Cochrane Collaboration， and the graded management standard for off-label use of Shenqi fuzheng injection was developed by using the Thomson grading system. RESULTS A total of 534 articles were involved， including 11 guidelines， 22 systematic reviews/meta-analysis， and 501 RCTs. They covered 79 off-label indications for Shenqi fuzheng injection： cancer-related fatigue， colorectal cancer and breast cancer， all with high-quality evidence were classified under grade A management （grade Ⅰ commendation）， allowing all physicians across the hospital to prescribe relevant treatments； five diseases， such as ovarian cancer， liver cancer， leukemia， heart failure and cerebral infarction， were classified under grade B management （grade Ⅱa commendation）， with prescription restricted to physicians with intermediate or higher professional titles in specific departments； eleven diseases， including sepsis， cervical cancer， esophageal cancer， etc.， were classified under grade C management （grade Ⅱb commendation）， requiring strict evaluation by senior physicians before prescription； the use of Shenqi fuzheng injection for other conditions was explicitly prohibited due to a lack of sufficient evidence. CONCLUSIONS Off-label use of Shenqi fuzheng injection is prevalent. The graded management standard established by evidence-based medical approach provides a scientific basis for standardizing the clinical application of traditional Chinese medicine injections and offers an operable paradigm for implementing differentiated drug use supervision in medical institutions.

Objective: To systematically evaluate the application effectiveness of the full disinfection process in blood stations, identify key optimization links, and provide a scientific evidence for the formulation of specialized disinfection and hygiene standards for blood collection and supply institutions. Methods: On-site microbiological monitoring was conducted using techniques such as the plate settling method and cotton swab method. Stratified random sampling was performed on eight key control points: including evironmental air, hand hygiene, skin disinfection, blood transport boxes, pressure steam sterilization, sewage treatment, ultraviolet disinfection, and sterile swabs. Statistical analysis was performed using SPSS 20.0. Measurement data were expressed as mean ± standard deviation(x-±s), and inter-group comparisons were conducted using t-tests or analysis of variance (ANOVA). Count data were expressed as rates, and inter-group comparisons were conducted using the χ test. Trend analysis was performed using the Cochran-Armitage test, with a significance level of α=0.05. Results: The colony removal rate of plasma air disinfection machines (94.2%±0.8%) was significantly higher than that of the ultraviolet group (P<0.05). The qualification rate of quick-drying disinfectant hand was 100% within 30 days after opening the bottle, but decreased to 93.3% after 40 days (P<0.01). The qualification rate of disinfection for blood transport boxes using 500 mg/L chlorine-containing disinfectant (100%) was significant higher 75% alcohol (60%, P< 0.05). Skin disinfection with 2% alcoholic chlorhexidine gluconate balanced effectiveness and user experience (satisfaction score 4.8±0.3). The qualification rates for core procedures such as pressure steam sterilization and sewage treatment were both 100%. Conclusion: The current disinfection procedures in blood collection and supply institutions are reliable. The effective usage period of hand disinfectants, disinfection methods for transport boxes, and usage duration of sterile swabs are the main points for optimization. It is recommended that the opened hand disinfectants be used for ≤30 days and that chlorine-containing disinfectants be prioritized for wiping transport boxes, providing empirical support for the revision of protocols and the formulation of standards.

BACKGROUND:Human periodontal stem cells have a certain inhibitory effect on the pro-inflammatory function of M1-type macrophages,and it is not clear whether icariin,which has anti-inflammatory and other pharmacological activities,can enhance the inhibitory effect of human periodontal stem cells on M1-type macrophages. OBJECTIVE:To investigate the effect of icariin on M1 macrophages after pretreatment of human periodontal stem cells. METHODS:Primary human periodontal stem cells were isolated,cultured and characterized.THP-1 was induced and M1-type macrophages were identified by immunofluorescence staining and PCR.Human periodontal stem cells were cultured with α-MEM complete medium containing concentrations of 10-7,10-6,10-5,and 10-4 mol/L icariin,and the cytotoxicity of Icariin on human periodontal stem cells was detected by the CCK-8 assay at 1,3,5,and 7 days,respectively.α-MEM complete medium,untreated α-MEM conditioned medium for human periodontal stem cells and α-MEM conditioned medium for human periodontal stem cells pretreated with icariin for 24 hours were conditioned with RPMI-1640 complete medium in a 1:1 ratio for M1-type macrophages in the control,untreated,and pretreated groups,and 24 hours later,the mRNA expression of inflammatory factors in M1 macrophages was detected by RT-PCR.The protein expression of inflammatory factors in M1 macrophages was detected by ELISA.The expression of surface markers and nuclear factor-κB pathway-related proteins in M1/M2 macrophages was detected by western blot assay. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that 10-7,10-6,10-5,10-4 mol/L icariin was not cytotoxic to the human periodontal stem cells,and from day 5 onwards,all the concentrations increased the cell viability,and promoted the cell proliferation.10-4 mol/L icariin was selected for follow-up experiment.(2)RT-PCR and ELISA results showed that compared with the control group,the untreated group and the pretreated group both decreased the expression and secretion of interleukin-1β,interleukin-6,and tumor necrosis factor-α of M1-type macrophages(P<0.05),and the pretreated group was lower than the untreated group(P<0.05).(3)Western blot assay results showed that compared with the untreated group,the expression of CD86 was significantly lower in the pretreated group(P<0.05);compared with the control group,the expression of CD206,a surface marker of M2-type macrophages,was elevated in both the untreated and pretreated groups(P<0.01),and it was significantly higher in the pretreated group than in the untreated group(P<0.01).In M1-type macrophages after 24 hours of conditioned culture,compared with the control group,the expression of nuclear factor-κB/P65 was decreased in the untreated group and the pretreated group(P<0.01),and the expression of p-IκBα was decreased only in the pretreated group(P<0.01);the expression of both nuclear factor-κB/P65 and p-IκBα was significantly reduced in the pretreated group compared with the untreated group(P<0.05),while the difference of IκBα in the three groups was not statistically significant.(4)These results indicated that icariin enhanced the inhibitory effect of human periodontal stem cells on M1-type macrophages,and this effect may be related to the inhibition of the nuclear factor-κB signaling pathway of macrophages.

Objective: To explore the relationship of family function with sleep and externalizing problem behaviors of preschool children, so as to provide a guidance for externalizing problem prevention and intervention among preschool children. Methods: From October 2023 to January 2024, a convenience sampling method was used to select 5 138 preschool children from kindergartens in 8 districts of Wuhan City, Hubei Province. Parents completed the survey for Family Adaptability and Cohesion Scale, children s sleep habits and Child Behavior Checklist (CBCL). Spearman correlation analysis was used to examine the correlation of family function with scores of sleep quality and externalizing problem behaviors among preschool children. A mediation model analysis and bootstrap test were conducted to further investigate the mediating role of sleep quality between family function and externalizing problem behaviors. Mplus 8.7 software was used for latent profile analysis of family function. Results: The reported rates of poor sleep quality and externalizing problem behaviors among preschool children were 11.8% ( n =607), 20.0% ( n =1 026). The relevant analysis results showed that family function was negatively correlated with sleep quality and externalizing problem behaviors ( r = -0.20, -0.23), and sleep quality was positively correlated with externalizing problem behaviors ( r =0.27) ( P <0.01). The mediation effect test showed that family function negatively predicted externalizing problem behaviors ( β =-0.079) and sleep quality ( β = -0.075), while sleep quality positively predicted externalizing problem behaviors ( β =0.215) ( P <0.01). The latent profile analysis results showed that family function could be classified into 4 categories: high family function group (23.01%), upper middle family function group (44.65%), moderate family function group (26.24%) and low family function group (6.11%). Compared to high family function, the other three categories significantly positively predicted externalizing problem behaviors, and the mediating effects of sleep quality on different categories of family function were statistically significant [upper middle family function: mediation effect value was 0.022 (95% CI =0.004-0.041) and direct effect value was 0.329 (95% CI =0.263-0.396); middle family function: mediation effect value was 0.087 (95% CI =0.063-0.115) and direct effect value was 0.491 (95% CI =0.416-0.565); low family function: mediation effect value was 0.144 (95% CI =0.107-0.185) and direct effect 0.621 (95% CI =0.503-0.740)] ( P < 0.05 ). Conclusion Family function negatively predicts the externalizing problem behaviors of preschool children, and sleep quality plays a partial mediating role.

Objective: To understand the status and related factors of knowledge, attitude and practice (KAP) on vision health among young children s parents in Bao an District, Shenzhen, so as to provide reference for further controlling myopia and promoting children s visual health. Methods: From May 16th to 26th, 2024, a stratified cluster random sampling method was used to conduct an online questionnaire survey on 7 666 parents of kindergarten children across 41 kindergartens in a street of Bao an District, Shenzhen. The t-test, variance analysis and multiple linear regression analysis were used to analyze the related factors of KAP on vision health among children s parents. Results: The pass rates of parental vision KAP and overall assessment were 25.10%, 98.49 %, 71.18% and 58.26%, respectively. The results of the multiple linear regression analysis showed that only fathers with myopia, only mothers with myopia, both parents with myopia, children in the bottom classes, middle classes, senior classes, and pre school had higher standardized scores for KAP on vision health among parents ( β=0.08, 0.11, 0.16, 0.17, 0.16, 0.16, 0.05, P <0.05), compared to both parents without myopia and children in daycare classes. Parents of young children with myopia, and who didn t know their children s visual acuity and their own visual acuity had a lower KAP standardized scores ( β=-0.02, -0.04, -0.05 , P< 0.05). Conclusions Young children s parents in Bao an District hold a positive attitude towards vision health, but are lack of knowledge and practice. It is imperative to transmit accurate information and concepts about children s vision health to parents in a targeted manner. In particular, knowledge and guidance should be strengthened for children s parents.

Objective To explore the role of neogambogic acid in the characteristics of colorectal cancer stem cells (CRC-CSCs) through the Wnt/β-catenin signaling pathway. Methods The colorectal cells SW480 and HCT166 were divided into control group and neogambogic acid groups (1.5, 3, 6, and 12 μmol/L). The viability of CRC-CSCs was determined by MTT method, and spheroid and clone formation assays were used to assess the capacity of spheroid formation and self-renewal ability of the cells. The effects of neogambogic acid on the apoptosis and cell cycle of CRC-CSCs were evaluated by flow cytometry assays. Real-time quantitative PCR was used to detect the mRNA expression levels of relative markers (CD133, CD44, ALDH1, Oct4, and Nanog) of CRC-CSCs, and the protein expression levels of the self-renewal marker (PCNA), apoptosis markers (cleaved caspase-3 and cleaved caspase-9), and Wnt/β-catenin signaling pathway markers (p-GSK3β, GSK3β, β-catenin, and Wnt) were analyzed using Western blot. Results Compared with the control group, after neogambogic acid treatment, the viability of SW480 and HCT116 cells decreased (P<0.05), the spheroid forming ability and the clone numbers of CRC-CSCs decreased (P<0.001, P<0.01) but the cell apoptosis rate increased (P<0.01), and cell cycle was arrested in G₀/G₁ phase. Moreover, neogambogic acid downregulated the mRNA and protein expression of relative markers of CRC-CSCs (CD133, CD44, ALDH1, Oct4, and Nanog), PCNA, p-GSK3β, β-catenin, and Wnt (P<0.05) and upregulated the expression of cleaved caspase-3, cleaved caspase-9, and GSK3β (P<0.01). Conclusion Neogambogic can inhibit the stem cell properties of colorectal cells via inhibition of Wnt/β-catenin signaling pathway. As a result, neogambogic acid may be an attractive agent against colorectal cancer.

Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder influenced by both genetic and environmental factors, remains poorly understood regarding how its polygenic risk score (PRS) impacts functional networks and symptomology. This study capitalized on data from 11,430 children in the Adolescent Brain Cognitive Development study to explore the interplay between PRS_ADHD, brain function, and behavioral problems, along with their interactive effects. The results showed that children with a higher PRS_ADHD exhibited more severe attention deficits and rule-breaking problems, and experienced sleep disturbances, particularly in initiating and maintaining sleep. We also identified the central executive network, default mode network, and sensory-motor network as the functional networks most associated with PRS and symptoms in ADHD cases, with potential mediating roles. Particularly, the impact of PRS_ADHD was enhanced in children experiencing heightened sleep disturbances, emphasizing the need for early intervention in sleep issues to potentially mitigate subsequent ADHD symptoms.
Humans ; Attention Deficit Disorder with Hyperactivity/physiopathology* ; Male ; Female ; Sleep Wake Disorders/physiopathology* ; Adolescent ; Child ; Brain/diagnostic imaging* ; Multifactorial Inheritance ; Genetic Predisposition to Disease

Objective To construct a risk prediction model for post-stroke dysphagia(PSD)based on clinical and laboratory indicators of elderly stroke patients with explainable machine learning.Methods A retrospective analysis was conducted on 3994 stroke patients hospitalized in Depart-ment of Neurology of First Medical Center of Chinese PLA General Hospital from October 2010 to December 2021.Among them,the 1390 cases admitted during January 2019 and December 2021 were assigned into an external validation set,and the 2604 cases admitted during October 2010 to January 2019 were into a training group.Those from the training group were further divided into a training set(1823 cases)and an internal validation set(781 cases)in a 7∶3 ratio,and also grouped into a PSD subgroup(773 cases)and a non-PSD group(1831 cases).With occurrence of swallowing difficulties as an endpoint,risk prediction models were constructed using random for-est(RF),eXtreme Gradient Boosting(XGBoost),Support Vector Machine(SVM),and logistic regression.ROC curve analysis was employed to evaluate the performance of our models.After the optimal model was selected,SHAP was employed to interpret feature contributions.Results There were significant differences in muscle strength,right/left-sided stroke,and area of brain in-jury between the PSD and the non-PSD groups(P＜0.01).The PSD group had obviously larger proportions of hypertension,diabetes,and drinking history,increased neutrophil counts,and de-creased levels of potassium and albumin when compared with the non-PSD group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that age,drinking history,diabetes,hyper-tension,muscle strength grade,area of brain injury,hemispheric stroke,neutrophil count,and al-bumin and potassium levels were risk factors for PSD(P＜0.05,P＜0.01).The external validation results showed that the area under curve value of the RF model,XGBoost model,SVM model,and our logistic model was 0.883,0.902,0.877,and 0.868,respectively.The distribution of SHAP value showed that drinking history,hypertension and diabetes were positively correlated with PSD risk;Muscle strength was negatively correlated with the risk;Age growth was positively correlated with the risk;Subtentorial lesions showed stronger predictive efficacy than supratentorial lesions and entire lesions;The bilateral and right-sided stroke had higher risk for PSD than the left-sided stroke.Conclusion The model based on the XGBoost model shows best performance in predicting the risk for swallowing disorders in elderly patients after stroke.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

(+)-Strebloside, a significant bioactive compound isolated from the roots of Streblus asper Lour., demonstrates inhibitory effects against multiple malignancies. However, its specific function and underlying mechanistic pathways in Non-Hodgkin lymphoma (NHL) remain unexplored. This investigation sought to elucidate the role and potential mechanisms of (+)-strebloside-induced NHL cell death. The results demonstrated that (+)-strebloside significantly induced apoptosis and ferroptosis in NHL cells, including those from Raji cell-derived xenograft models. Mechanistic analyses revealed that (+)-strebloside enhanced six-transmembrane epithelial antigen of prostate 3 (STEAP3)-induced ferroptosis in NHL, and STEAP3 inhibition reduced the proliferation-inhibitory effects of (+)-strebloside. Furthermore, (+)-strebloside suppressed NHL proliferation through the mitogen-activated protein kinase (MAPK) pathway, and extracellular signal-regulated kinase (ERK) inhibition diminished the proliferation-inhibitory activity induced by (+)-strebloside. These findings indicate that (+)-strebloside presents promising therapeutic potential for NHL treatment.
Humans ; Ferroptosis/drug effects* ; Lymphoma, Non-Hodgkin/physiopathology* ; Cell Line, Tumor ; MAP Kinase Signaling System/drug effects* ; Animals ; Cell Proliferation/drug effects* ; Mice ; Apoptosis/drug effects* ; Membrane Proteins/genetics* ; Xenograft Model Antitumor Assays ; Male ; Mice, Nude