Background Liver cancer is one of the common malignant tumors. Phthalates (PAEs), as a widely used class of plasticizers, can participate in the occurrence and progression of liver diseases through multiple pathways. Objective To explore the association between PAEs exposure and liver cancer risk and to provide a scientific basis for the prevention of environment-related tumor risk events. Methods Chi-square test and logistic regression were employed to analyze data from the National Health and Nutrition Examination Survey (NHANES) database between 2001 and 2018, to investigate the association between PAEs exposure and liver cancer. Network toxicology combined with machine learning was used to screen independent prognostic genes associated with PAEs and liver cancer, and to evaluate their correlations with tumor immunity, tumor pathway activation, and tumor drug resistance. Finally, the prediction results were validated using GEO datasets, molecular docking, and molecular dynamics simulations. Results After screening, 11378 eligible samples were obtained from the NHANES database, including 108 patients with liver cancer and 11270 healthy controls. The logistic regression analysis revealed that exposure to nine types of PAEs was positively correlated with liver cancer (OR > 1, P < 0.05). The network toxicology analysis indicated that the association between PAEs exposure and liver cancer was related to three independent prognostic genes: uridine-cytidine kinase 2 (UCK2), glucose-6-phosphate dehydrogenase (G6PD), and albumin (ALB). These three independent prognostic genes were significantly associated with the tumor immune microenvironment, tumor pathway activation, and tumor drug resistance, and exhibited complex interactions with each other. All three independent prognostic genes showed significant differential expression in the validation datasets GSE58043 and GSE115469 (P < 0.05). The results of both molecular docking and molecular dynamics simulations confirmed that these three independent prognostic genes can freely bind to PAEs and form stable complexes. Conclusion Exposure to PAEs is positively correlated with liver cancer. The intrinsic association between the two may involve metabolic disorders, immunosuppression, and activation of inflammatory and tumor-related pathways.

Objective: Blood safety surveillance is a critical measure for the objective assessment of blood quality and enhancing transfusion safety. This study aims to comprehensively understand the current status of blood safety surveillance and management in blood collection and supply institutions in Sichuan Province, systematically analyze existing problems and vulnerabilities, and provide a basis for optimizing management strategies and improving capabilities to ensure blood safety. Methods: The Blood Safety Surveillance questionnaire was designed, covering adverse donor reaction reporting, management of adverse events, and transfusion adverse reaction feedback. An online survey was conducted via Questionnaire Star platform among 21 blood collection and supply institutions in the province, gathering information on management systems, process implementation, and utilization of monitoring data. The collected data were organized and statistically analyzed using Excel. Results: The questionnaire response rate and validity rate were both 100%. Blood collection and supply institutions in Sichuan Province have generally established a blood safety surveillance system and achieved positive outcomes. Regarding adverse events in blood collection and supply, 95.24% (20 institutions) have established reporting procedures, and 66.67% (14) collect information through multiple channels such as internal reports, external reports, and statistical trend feedback. A total of 90.48% (19) institutions regularly summarize and analyze adverse event data, and 85.71% (18) produce reports with improvement recommendations based on this analysis.71.43% (15) institutions implement reward and penalty measures, and 71.43% (15) report underreporting or omission due to accountability or performance concerns. In terms of monitoring adverse blood donation reactions, all blood collection and supply institutions have established full-process management systems.76.19% (16) collect data through multiple approaches, including on-site donation records, voluntary donor reports, and donor follow-ups. Adverse reactions were followed up in 95.24% (20) of institutions with 65% (13) completing follow-ups within 24 hours.80.95% (17) have established investigation procedures, while 66.67% (14) believe underreporting or omission still occurs. All blood collection and supply institutions regularly compile statistics on adverse donation reactions. Of these, 85.71% (18) institutions providing feedback to management departments and 90.48% (19) analyzing the data and making recommendations.76.19% (16) institutions use monitoring data for return donor management and targeted care, and 71.43% (15 stations) incorporate it into management reviews. Regarding adverse transfusion reactions, 95.24% (20) institutions have established and implemented procedures for isolating, recalling, and tracing of problematic blood units. However, only 42.86% (9) have established feedback mechanisms of adverse transfusion reaction with hospitals, and only 19.05% (4) support direct reporting via information systems.47.62% (10) institutions regularly analyze adverse transfusion reaction data, and 19.05% (4) provide feedback and recommendations to relevant hospitals. All blood collection and supply institutions reported challenges in collecting hospital feedback, citing complexities in data collection and reporting processes. Conclusion: Blood safety surveillance systems have been preliminarily established in Sichuan Province. However, further strengthening is still required, including conducting in-depth data analysis and utilization, standardizing the configuration of emergency medications and equipment, and improving feedback mechanisms for adverse transfusion reactions. To improve the overall level of blood safety management, it is recommended to strengthen closed-loop data management, improve feedback mechanisms between blood collection and supply institutions and hospitals, foster a non-punitive reporting culture, and systematically advance the regionalization and standardization of the monitoring system. These efforts will contribute to sustainably improving the overall effectiveness and sustainability of blood safety management.

As the volume of medical research using large language models (LLM) surges, the need for standardized and transparent reporting standards becomes increasingly critical. In January 2025, Nature Medicine published statement titled by TRIPOD-LLM reporting guideline for studies using large language models. This represents the first comprehensive reporting framework specifically tailored for studies that develop prediction models based on LLM. It comprises a checklist with 19 main items (encompassing 50 sub-items), a flowchart, and an abstract checklist (containing 12 items). This article provides an interpretation of TRIPOD-LLM’s development methods, primary content, scope, and the specific details of its items. The goal is to help researchers, clinicians, editors, and healthcare decision-makers to deeply understand and correctly apply TRIPOD-LLM, thereby improving the quality and transparency of LLM medical research reporting and promoting the standardized and ethical integration of LLM into healthcare.

This study explores the diagnosis and treatment of needle knife therapy for ankylosing spondylitis (AS) at middle and advanced stage based on the theory of meridian tendons, from a holistic perspective and syndrome differentiation. The treatment strategy includes "harmonizing yin and yang" to address root causes and "tendons-based release" to harmonize qi and blood, with the "tendons nodule points" as the core acupoint selection criterion. Based on this approach, the study systematically elaborates on two needle knife methods for AS: "governor vessel bone-piercing technique" and "below-the-umbilicus release technique", covering indications, acupoint location, and procedures. Clinical case examples are provided to enrich needle knife therapy guided by the theory of meridian tendons, offering insights for clinical and research work on AS.
Humans ; Acupuncture Points ; Acupuncture Therapy/methods* ; Meridians ; Spondylitis, Ankylosing/physiopathology* ; Tendons/physiopathology*

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

ObjectiveTo investigate the potential mechanism of the Jianpi Yishen Huatan Formula （健脾益肾化痰方，JPYSHF） in treating squamous cell lung cancer through the LncRNA ALAL-1/USP4/HDAC2 signaling pathway. MethodsForty Sprague-Dawley （SD） rats were randomly divided into a control group and high-， medium-， and low-dose JPYSHF group with 10 rats in each group. Rats in the JPYSHF groups were administered JPYSHF concentrated liquid at doses of 45， 30， and 15 g/（kg·d） via intragastric gavage， respectively， while the control group received 10 ml/（kg·d） of normal saline， once daily for 10 consecutive days before preparation of drug containing serum. Human lung squamous carcinoma SK-MES-1 cells were divided into a control group and low-， medium-， and high-dose JPYSHF-medicated serum groups. The control group was cultured with 10% saline-containing serum， while the JPYSHF groups were cultured with 10% low-， medium-， or high-dose medicated serum. After 48 hours of incubation， flow cytometry was used to detect apoptosis rates， and a cell scratch assay was performed to evaluate migration areas at 0 h and 24 h to calculate migration rate. Additional SK-MES-1 cells were divided into control serum， JPYSHF-medicated serum （low-， medium-， high-） dose， LncRNA-silenced group （transfected with ALAL-1 siRNA）， USP4-inhibited group （treated with 35 μmol/L PR-619， a deubiquitinase inhibitor）， and HDAC2-inhibited group （treated with 60 μmol/L Vorinostat）. After 24 and 48 hours of culture， cell viability was assessed using the CCK-8 assay； LncRNA ALAL-1， USP4， and HDAC2 mRNA levels were quantified by qPCR after 24 hours； USP4 and HDAC2 protein levels were measured by Western Blot after 48 hours. ResultsCompared with the control serum group， the total apoptosis rate of cells in middle- and high-JPYSHF-medicated serum group significantly increased， and the cell migration rate of cells in the low-， middle- and high-JPYSHF-medicated serum group significantly decreased （P＜0.05 or P＜0.01）. The cell migration rate of the low-， medium- and high-JPYSHF-medicated serum groups decreased with the increase of concentration in a concentration-dependent manner （P＜0.05 or P＜0.01）. Compared with the control serum group at the same time， the cell viability at 24 h and 48 h significantly decreased in all groups （P＜0.05 or P＜0.01）. Compared with the low-JPYSHF-medicated serum group at the same time， the cell viability at 24 h and 48 h also decreased in the high-JPYSHF-medicated serum group and the LncRNA silencing group （P＜0.05）. Compared with the control serum group， the expression of USP4 and HDAC2 mRNA reduced in the low- and medium-dose JPYSHF-medicated serum groups and the USP4 inhibitor group， and the expression of LncRNA ALAL-1， USP4 and HDAC2 mRNA reduced in the high-dose JPYSHF-medicated serum group and LncRNA-silencing group， and HDAC2 mRNA expression reduced in the HDAC2 inhibitor group. USP4 and HDAC2 protein levels were reduced in cells of all groups except for USP4 protein level in HDAC2 inhibitor group （P＜0.05 or P＜0.01）. ConclusionJPYSHF-medicated serum inhibits proliferation and promotes apoptosis of human lung squamous carcinoma cells， and its mechanism of action may be related to its inhibition of the LncRNA ALAL-1/USP4/HDAC2 pathway， with best effect at a high concentration.

Orthostatic hypotension （OH） is the main symptom of cardiovascular autonomic dysfunction in the elderly population，which often manifests as orthostatic dizziness，syncope，and traumatic falls. OH often has a poor prognosis and is one of the causes of cognitive impairment in the elderly，and therefore，it is important to explore the pathogenesis of OH and related interventions. The vestibular system participates in orthostatic blood pressure regulation through vestibular sympathetic reflex，and dysfunction of the vestibular system can lead to the dysfunction of orthostatic blood pressure regulation，which further leads to OH. Previous studies have shown that galvanic vestibular stimulation （GVS） can regulate the function of the cardiovascular system，and different stimulation parameters have different target effects on blood pressure. This article summarizes the role of vestibular system and GVS in orthostatic blood pressure regulation，in order to provide a reference for the future research on the application of GVS in the treatment of OH.

ObjectiveTo study the effect of Taikong Yangxin Pills on the metabolism of simulated weightless rats based on metabolomics and discuss the metabolism mechanism. MethodsIn the simulated space capsule environment on the ground， the rat model of simulated weightlessness was established by the tail suspension method. Rats were randomly grouped as follows： out-of-capsule control， in-capsule control， model， and high （3.0 g·kg^-1） and low （1.5 g·kg^-1） doses of Taikong Yangxin Pills， and they were administrated with corresponding drugs by gavage for 28 days. The serum levels of endogenous metabolites in rats were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）. The obtained data were processed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） to screen for differential metabolites and potential biomarkers. MetaboAnalyst 5.0 was used for pathway enrichment analysis to explain the metabolic regulation mechanism of the drug. ResultsCompared with the out-of-capsule control group， the in-capsule control group showed elevated levels of thirteen metabolites， including 14-hydroxyhexadecanoic acid， linoleic acid， and α-linolenic acid （P<0.05）， which suggested that the space capsule environment mainly affected the metabolism of α-linolenic acid and linoleic acid in the rats. Compared with the in-capsule control group， the model group showed lowered levels of fourteen metabolites， including 4-imidazolone-5-propionic acid， isocitric acid/citric acid， and L-tyrosine （P<0.05）， which were recovered after the treatment with Taikong Yangxin pills （P<0.05）. The pathway enrichment analysis revealed that weightlessness induced by tail suspension and drug intervention mainly involved the phenylalanine， tyrosine， and tryptophan biosynthesis， tyrosine metabolism， histidine metabolism， and citric acid cycle. ConclusionThe simulated space capsule environment and simulated weightlessness induced by tail suspension can both affect the metabolism level of rats. Taikong Yangxin pills can ameliorate the metabolic abnormality in the rat model of weightlessness by regulating various amino acids and energy metabolism-related pathways.