Objective: To investigate the distribution frequency and molecular mechanism of the rare blood type Lu(a-b-) in Shenzhen, and to compare the polymorphisms of the Lutheran blood group system encoding gene LU and the In (Lu) phenotype-related gene KLF1 among Han Chinese, Indian, and Uyghur populations in Xinjiang. Methods: Serological methods were used to screen the Lu(a-b-) phenotype of blood donors in Shenzhen. Third-generation sequencing was employed to sequence the full-length of the LU and KLF1 genes in Lu (a-b-) phenotype samples as well as the samples from the Han Chinese, Indians, and Uyghur population, followed by analysis of gene haplotypes frequencies. Results: Ten individuals with the Lu(a-b-) phenotype were screened out of 14 367 blood donors in Shenzhen, yielding a frequency of approximately 0.07%. Only 2 cases showed mutations in the coding region of the LU gene, while all individuals showed heterozygous mutations in the coding region of the KLF1 gene. The highest mutation frequencies of the LU and KLF1 genes were observed in the Uyghur population in Xinjiang and the Han Chinese in Shenzhen, respectively. Conclusion: All Lu(a-b-) phenotypes are of the In (Lu) type, and their formation mechanism is mainly related to KLF1 gene mutations. Both the LU and KLF1 genes exhibit significant polymorphism in the Han Chinese, Indians, and Uyghur populations.

Objective: To develop QingNangTCM, a specialized large language model (LLM) tailored for expert-level traditional Chinese medicine (TCM) question-answering and clinical reasoning, addressing the scarcity of domain-specific corpora and specialized alignment. Methods: We constructed QnTCM_Dataset, a corpus of 100 000 entries, by integrating data from ShenNong_TCM_Dataset and SymMap v2.0, and synthesizing additional samples via retrieval-augmented generation (RAG) and persona-driven generation. The dataset comprehensively covers diagnostic inquiries, prescriptions, and herbal knowledge. Utilizing P-Tuning v2, we fine-tuned the GLM-4-9B-Chat backbone to develop QingNangTCM. A multi-dimensional evaluation framework, assessing accuracy, coverage, consistency, safety, professionalism, and fluency, was established using metrics such as bilingual evaluation understudy (BLEU), recall-oriented understudy for gisting evaluation (ROUGE), metric for evaluation of translation with explicit ordering (METEOR), and LLM-as-a-Judge with expert review. Qualitative analysis was conducted across four simulated clinical scenarios: symptom analysis, disease treatment, herb inquiry, and failure cases. Baseline models included GLM-4-9B-Chat, DeepSeek-V2, HuatuoGPT-II (7B), and GLM-4-9B-Chat (freeze-tuning). Results: QingNangTCM achieved the highest scores in BLEU-1/2/3/4 (0.425/0.298/0.137/0.064), ROUGE-1/2 (0.368/0.157), and METEOR (0.218), demonstrating a balanced and superior normalized performance profile of 0.900 across the dimensions of accuracy, coverage, and consistency. Although its ROUGE-L score (0.299) was lower than that of HuatuoGPT-II (7B) (0.351), it significantly outperformed domain-specific models in expert-validated win rates for professionalism (86%) and safety (73%). Qualitative analysis confirmed that the model strictly adheres to the “symptom-syndrome-pathogenesis-treatment” reasoning chain, though occasional misclassifications and hallucinations persisted when dealing with rare medicinal materials and uncommon syndromes. Conclusion Combining domain-specific corpus construction with parameter-efficient prompt tuning enhances the reasoning behavior and domain adaptation of LLMs for TCM-related tasks. This work provides a technical framework for the digital organization and intelligent utilization of TCM knowledge, with potential value for supporting diagnostic reasoning and medical education.

The ethical review exemption system was introduced to meet the needs of modernized ethical governance， implement hierarchical management for ethical review projects involving human subjects， and explore an ethical management model that reduces procedural supervision for specific types of research involving no greater than minimal risk. Through a comparative study， this paper seeks to elaborate on the differences between China and the United States （US） in the ethical review exemption system from multiple aspects， such as ethical regulations， risk definition， preconditions， applicable scenarios， and operational procedures. The aim is to provide references for ethical review committees to better implement the ethical review exemption system， enhance policy research， and ensure the fairness and objectivity of ethical review. Through the comparative study of the ethics review exemption system in China and the US， the following recommendations are proposed for institutions implementing the ethical review exemption system for reference. First， the system should clearly define the meaning of ethical review exemption to prevent researchers or even committee members from misunderstanding it as falling outside the scope of ethical review， thereby exposing research participants’ rights and interests to unnecessary risks. Second， the system should specifically explain the preconditions， including the requirements for research types and research risks. Among them， risks should be considered from multiple dimensions such as physiology， psychology， society， and economy. Clear explanations should be provided for involving commercial interests and sensitive personal information. Finally， the system should establish basic principles and judgment criteria for applicable scenarios， including specifying exactly what the public data refers to and legal requirements that need to be met， providing a concept of anonymization to distinguish it from deidentified information data， and clarifying the relevant regulations and ethical principles to be followed， as well as the clear requirements for informed consent.

OBJECTIVE:Although wearable electronic devices have demonstrated potential utility as intervention tools to enhance physical activity,comprehensive evaluations of their specific effects on the healthy adolescent population remain scarce.Consequently,this article aims to systematically explore and summarize the impact of interventions based on wearable electronic devices on the physical activity and sedentary behavior of healthy adolescents,thereby providing more precise and reliable evidence-based support for public health practices. METHODS:Randomized controlled trials assessing the effects of wearable electronic device-based interventions on the physical activity and sedentary behavior of healthy adolescents were retrieved from databases including Web of Science,PubMed,Scopus,The Cochrane Library,and EBSCO.Meta-analysis was conducted using Review Manager 5.4 and Stata 17,evaluating the effects of interventions on physical activity and sedentary behavior through the standardized mean difference.To ensure the robustness of the research findings,a Leave-One-Out sensitivity analysis was conducted,and subgroup analyses were carried out to explore the potential influence of different factors on the results.The review protocol was registered with the International Prospective Register of Systematic Reviews(CRD42023406645). RESULTS:(1)Twelve publications were ultimately included,consisting of three randomized controlled trials and nine cluster-randomized controlled trials,involving a total of 4 933 healthy adolescents.(2)Meta-analysis results revealed that interventions based on wearable electronic devices had a positive effect on moderate to vigorous physical activity[standardized mean difference(SMD)=0.10;95%confidence interval(CI):0.04 to 0.17;P<0.05).However,the interventions did not significantly improve low-intensity physical activity(SMD=-0.15;95%CI:-0.32 to 0.02;P>0.05),daily step count(SMD=0.13;95%CI:-0.65 to 0.91;P>0.05),and sedentary behavior(SMD=0.00;95%CI:-0.09 to 0.09;P>0.05).(3)Subgroup analyses indicated that short-term interventions(≤12 weeks)(SMD=0.11;95%CI:0.03 to 0.18;P=0.008),studies using pedometers worn at the waist or hip(SMD=0.10;95%CI:0.04 to 0.17;P=0.002),and experiments registered at clinical trial centers(SMD=0.11;95%CI:0.04 to 0.17;P=0.001)had a more significant effect on enhancing daily moderate to vigorous physical activity. CONCLUSION:The current evidence suggests that interventions based on wearable electronic devices possess certain advantages in enhancing the daily moderate-to-vigorous physical activity of healthy adolescents.It is recommended that interventions not exceeding 12 weeks and utilizing pedometers positioned at the waist or hip may yield more favorable results.However,the effects of these interventions on daily step count,low-intensity physical activity,and sedentary behavior exhibit some limitations.Consequently,future investigations necessitate higher-quality,larger-scale randomized controlled trials for further validation.

Chronic heart failure （CHF） is the terminal stage of various heart diseases， with high morbidity， mortality， and hospitalization rate. According to the theory of collateral diseases， the core pathogenesis of CHF is blood stasis of collaterals， water retention and stagnation， and pathogen accumulation in collaterals. Accordingly， the treatment should focus on reinforcing healthy Qi to warm Yang， activating blood to dredge collaterals， and excreting water to alleviate edema. On this basis， Qili Qiangxin capsules （QLQX） are created. This prescription can effectively treat chronic heart failure. Modern studies have shown that QLQX contains a variety of pharmacological components such as flavonoids， alkaloids， terpenoids， phenylpropanoids， phenolic acids， and cardiac glycosides. QLQX can improve the cardiac function， inhibit myocardial fibrosis， improve hemodynamics， mitigate inflammation， reduce cardiomyocyte apoptosis， and regulate the nervous system， with mild adverse reactions. This study analyzed the etiology and pathogenesis of CHF based on the theory of collateral diseases， explored the relationship between the prescription and syndrome， and delved into the material basis and mechanism of QLQX in the treatment of CHF， aiming to provide reference for the clinical application and scientific research of QLQX.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

This paper summarizes Professor SHI Zaixiang's clinical experience in treating high fever caused by sepsis using Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）. He holds that the key pathogenesis of sepsis involves constrained heat in the shaoyang and internal accumulation of water and fluids. The clinical manifestations such as high fever， chills， and alternating sensations of cold and heat are attributed to pathogenic heat constrained in the shaoyang. Meanwhile， soft tissue edema and serous cavity effusions are due to shaoyang dysfunction and internal water retention. In clinical practice， treating sepsis-related high fever requires addressing both the shaoyang-constrained heat and the associated edema and effusions. The therapeutic approach focuses on harmonizing the shaoyang and resolving internal fluids， using Chaihu Guizhi Ganjiang Decoction as the base formula with flexible modifications. Professor SHI emphasizes that this formula shows a rapid antipyretic effect， particularly in cases where multiple anti-infective treatments have failed.

Obejective To explore whether it is possible to detect the 123I-prostate-specific membrane antigen(PSMA)radiation value of the puncture tissue during prostate biopsy to achieve real-time,rapid,and accurate identification of benign and malignant prostate tissues,so as to improve the current clinical biopsy strategy and achieve accurate diagnosis of prostate cancer during operation with fewer puncture needles.Method In this prospective,diagnostic trial,we included 29 patients with suspected prostate cancer.All patients underwent transperineal biopsy guided by ultrasound within 24 hours after injection of 123I-PSMA,a total of 435 punctures were performed.The radiation value of punctured tissue was measured in real-time with a gamma counter.Pearson test is used to correlate radiation value with histopathology.Result The median radiation value of prostate cancer tissue(1 906.50 cpm)was significantly higher than that of benign prostate tissue(415.00 cpm).The optimal cut-off value for distinguishing benign and malignant prostate tissues was 828.50 cpm.The median radiation value of clinically significant prostate cancer tissue(2 652.50 cpm)was significantly higher than that of clinically insignificant prostate cancer(1 386.00 cpm).The optimal cut-off value for distinguishing clinically significant and clinically insignificant prostate cancer tissues was 1 767.00 cpm.In additional,there was a significant positive correlation between the radiation value of puncture tissue and ISUP pathological grade(r=0.834).Conclusion It is preliminarily confirmed that detection of 123I-PSMA radiation value of prostate puncture tissue can realize real-time,rapid and accurate identification of benign and malignant prostate tissues during operation.

OBJECTIVE To assess the scientific rigor， clarity and feasibility of the recommendations of the Guidelines for Evidence-based Use of Biological Agents for the Clinical Treatment of Osteoporosis （hereinafter referred to as the Guideline） through external review， in order to further revise and improve the Guideline recommendations. METHODS This study employed a cross-sectional survey research design， a convenience sampling method was adopted to select frontline medical workers in the field of osteoporosis （including clinical doctors， clinical pharmacists， and nurses） as well as patients or their family members. External review was conducted through a combination of closed-ended and open-ended electronic questionnaires to get feedback from them on the appreciation，clarity and feasibility of the 32 preliminary recommendations in the Guideline. RESULTS A total of 90 external review subjects from 15 hospitals were collected， including 45 clinical doctors， 15 clinical pharmacists， 15 nurses and 15 patients or their family members. The overall appreciation degree of recommendations was 99.38%， the overall clarity degree of recommendations was 98.92%， and the overall feasibility degree of recommendations was 99.65%. At the same time， 111 subjective suggestions were collected， which provided an important reference for the further improvement of the Guideline recommendations. Based on the above feedback， the Guideline steering committee and core expert group revised the wording of 12 draft recommendations without deletion， and finally determined 32 recommendations. CONCLUSIONS The external review provides an important basis for the final formation of the Guideline， further improves the scientific rigor， clarity and feasibility of the recommendations， and ensures the standardization， practicality and implementability of the Guideline.

This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
Animals ; Male ; Mice ; Aquatic Organisms/chemistry* ; Biological Availability ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Microsomes, Liver/metabolism* ; Molecular Structure ; Biological Products/pharmacokinetics* ; Pyridines/pharmacokinetics*