OBJECTIVE To investigate the effect of pharmaceutical services guided by root cause analysis （RCA） in a problem-oriented manner combined with knowledge-attitude-practice （KAP） theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group， and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials， while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge， attitude and practice on the basis of routine pharmaceutical services， according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products， as well as the incidences of minor and major protocol violations， were all significantly lower in the observation group than in the control group （ P ＜0.001）. The main types of protocol violations in both groups included missed/under-/over-dosing of medications， non-adherence to administration time， failure to adjust dosage as required， and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations， the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group （ P ＜0.001， P ＜0.001， P ＝0.025）. However， there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups （ P ＞0.05）. CONCLUSIONS Pharmaceutical services led by pharmacists， based on problem-oriented RCA and combined with KAP theory， can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials， thereby safeguarding the safety and rights of study participants.

Abstract The prevention and control of myopia in Chinese children and adolescents has become a major public health issue. While maintaining increased outdoor activity as a cornerstone intervention, there is an urgent need to explore new complementary approaches that can be effectively implemented in both indoor and outdoor settings. In recent years, environmental spatial frequency has gained increasing attention as one of the key environmental factors influencing the development and progression of myopia. Both animal studies and human research have confirmed that indoor environments lacking mid to high spatial frequency components, often characterized as "visually impoverished", can promote axial elongation and myopia through mechanisms such as disruption of retinal neural signaling, impaired accommodative function, and altered expression of related molecules. Based on the scientific consensus, it is recommended that "enriching of environmental spatial frequency" should be integrated into the myopia prevention and control framework. Following the principles of schoolled organization, family cooperation, community involvement, and student participation, specific measures are put forward in three areas：optimizing school visual settings, improving home spatial environments, and promoting healthy visual behavior. The aim is to create "visually friendly" indoor environments as an important supplement to outdoor activity, thereby providing a novel perspective and strategy for comprehensively advancing myopia prevention and control among children and adolescents.

Abstract The study examines the development and application of microclimate standards for primary and secondary school classrooms, so as to ensure and promote the healthy growth of primary and secondary school students. The paper systematically reviews relevant domestic and international standards, analyzes the problems and shortcomings arising from their practical application and proposes effective countermeasures, in order to provide robust references aimed at optimizing the classroom environment in primary and secondary schools for student health, as well as offering practical support to advance the construction of a healthy China.

Objective: To evaluate the classroom environmental management and CO 2 volume concentration in primary and secondary schools from Liaoning, Tianjin, and Shanghai, thereby providing a scientific basis for developing targeted strategies to improve classroom air quality. Methods: From December 16 to 26, 2024, by using stratified random cluster sampling method, the questionnaire survey was conducted in 72 primary and secondary schools (24 each of primary, junior high, and regular high schools) across Liaoning, Tianjin and Shanghai. Information on heating, ventilation and other classroom environmental management was collected. Additionally, 108 classrooms were selected for on site microclimate measurements, including temperature, humidity, wind speed and CO 2 volume concentration. Univariate analysis and multiple linear regression models were employed to explore related factors of classroom CO 2 volume concentration. Results: Among the three provinces/municipalities, 20.8% of schools regularly monitored the microclimate. The overall compliance rate for classroom CO 2 volume concentration was 17.6%. Multiple linear regression analysis showed that CO 2 volume concentration in regular and junior high school classrooms were higher than in primary school classrooms ( β=0.067, 0.046, 95%CI =0.036-0.099, 0.013-0.080); classrooms ventilated regularly in the morning and afternoon had higher CO 2 volume concentration than those ventilated during every break between classes ( β=0.043, 95%CI = 0.007- 0.080); both temperature ( β=0.010, 95%CI =0.004-0.016) and humidity ( β=0.003, 95%CI =0.002-0.004) were positively correlated with CO 2 volume concentration (all P <0.05). Conclusions Excessive CO 2 volume concentration in primary and secondary school classrooms is a prominent issue, and ventilation frequency is a key intervenable factor for controlling CO 2 levels. It is recommended to promote ventilation during every break between classes as a core management measure and to emphasize air quality supervision in regular high school classrooms.

Objective To analyze the influenza-like illness (ILI) data in Ordos City from 2017 to 2023 and conduct nucleic acid detection of the virus to understand the local influenza epidemic situation, and to provide a reliable basis for influenza prevention and control in the city. Methods Real-time quantitative polymerase chain reaction (qPCR) was used to identify virus subtypes in ILI throat swab samples. Comparisons of positive rates were conducted using the chi-square test, with a significance level of α=0.05. Results From 2017 to 2023, a total of 3,283,434 outpatient and emergency visits were recorded at the Ordos City Central Hospital, including 74,159 ILI cases, with an ILI proportion of 2.26%. The majority of ILI cases (74.43%) occurred in children aged 0~14 years old. The overall positive rate of influenza virus nucleic acid detection was 10.87%, with the highest proportion being subtype A (seasonal H3) at 43.03%. The highest detection rate was observed in the 5~14 years age group, with statistically significant differences in positive rates across age groups (χ²=155.638, P<0.001). Influenza peaks occurred mainly from November to March of the following year. From January to April, three types of influenza were prevalent alternately or mixed, while from October to December, subtype A (seasonal H3) predominated. Positive rates varied significantly across months (χ²=250.923, P<0.001). The temporal trends of ILI proportions and PCR-positive rates were consistent. Conclusion Influenza in Ordos City exhibits distinct seasonal and age distribution characteristics, with alternating or mixed circulation of three virus types. Continued efforts are needed to strengthen influenza surveillance, especially the prevention and control of influenza in infants and adolescents.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Exosomes are ubiquitous in all types of body fluids, exhibiting a high degree of abundance and diversity. Given their distinctive structure and function, exosomes are involved in a range of life activities, including intercellular communication, material transport, and immune regulation. An increasing number of studies have identified exosomes as a source of diagnostic markers for diabetic retinopathy. Furthermore, exosomes represent a novel avenue for therapeutic intervention, with promising clinical applications. This paper examines the diagnostic and therapeutic mechanisms of exosomes in diabetic retinopathy, reviews the advancements in exosomes-based diagnostics and therapeutics for diabetic retinopathy, and aims to enhance the precision and efficiency of clinical diagnosis and treatment of diabetic retinopathy.

Objective:To observe the effects of moxibustion at Shenshu(BL23)and Zusanli(ST36)on Toll-like receptor 4(TLR4)-myeloid differentiation factor 88(Myd88)signaling pathway-mediated inflammatory factors in the synovial tissue of ankle joints of rats with rheumatoid arthritis(RA),and to explore the molecular and biological mechanisms underlying the anti-inflammatory and analgesic effects.Methods:A total of 24 male Sprague-Dawley(SD)rats were randomly divided into a normal group,a model group,and a moxibustion group,with 8 rats in each group.The RA model was established with exposure to wind,cold,and damp environmental factors,along with Freund's complete adjuvant.After three days of modeling,mild moxibustion was applied to bilateral Shenshu(BL23)and Zusanli(ST36)in the moxibustion group using moxa sticks of 0.9 cm in diameter for 30 min each time,once a day for 14 d.Structural changes in the synovial tissue and cells were then observed using hematoxylin-eosin staining and transmission electron microscopy,while immunohistochemistry analysis was used to detect tumor necrosis factor(TNF)-α,interleukin(IL)-17,IL-1β,and IL-6 levels.Moreover,the protein expression levels of Myd88,TLR4,and transient potential receptor vanilloid type 1(TRPV1)in the synovial tissue were detected using Western blotting,while their mRNA expression levels were detected using reverse transcription-polymerase chain reaction.Finally,the levels of IL-1β,IL-2,IL-6,IL-17A,and TNF-α in rat serum were detected using enzyme-linked immunosorbent assay.Results:Compared to the normal group,the model group exhibited notable pathological synovial tissue damage,along with significantly higher IL-1β,IL-6,and TNF-α levels(P<0.01)and a slightly higher IL-17 content(P>0.05).Furthermore,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly higher in the model group than in the normal group(P<0.01).Compared to the model group,the moxibustion group exhibited a lower degree of synovial tissue pathological damage,along with significantly lower IL-1β,IL-6,and TNF-α levels(P<0.05 or P<0.01)and a lower IL-17 content without statistical significance(P>0.05).Moreover,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels,and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly lower in the moxibustion group than in the model group(P<0.01 or P<0.05).Conclusion:Mild moxibustion at Shenshu(BL23)and Zusanli(ST36)can effectively inhibit TLR4-MyD88 signaling pathway-mediated inflammatory factor expression in the synovial tissue of ankle joints of RA rats.Furthermore,the effect of moxibustion on synovial tissue inflammation in RA rats may be attributed to TRPV1 channel activation.

Cognitive dysfunction has emerged as a significant health challenge in aging societies, among which Alzheimer's disease(AD)and related dementia have become one of the leading causes of death among the elderly.These diseases are characterized by insidious onset and progressive deterioration, often reaching irreversible advanced stages at initial diagnosis, making early detection and prevention imperative.As the frontline of public health management, communities bear the responsibility for screening and managing major chronic diseases.However, community-based cognitive screening in China still remains in its nascent stages, lacking systematic management and prevention guidelines.This guideline, established under a multidisciplinary collaborative framework and adhering to evidence-based medicine principles, systematically reviews and analyzes the latest clinical evidence worldwide.Utilizing the GRADE(Grading of Recommendations Assessment, Development and Evaluation)system to evaluate evidence quality and following the RIGHT(Reporting Items for Practice Guidelines in Healthcare)statement for standardized guideline development, it ultimately presents 17 recommendations through three rounds of Delphi expert consultations.The core recommendations of this guideline is mainly to use digital cognitive scales to conduct large-scale community cognitive screening for the active individuals aged 60 or above.Stratification and staging should be performed based on screening results, and digital cognitive files with quantified risk factor grading should be established, followed by the formulation of personalized artificial intelligence(AI)prevention and control programs.This guide is the first in China and internationally to propose a quantitative grading system for low, medium, and high-risk factors associated with AD and vascular dementia(VD). It aims to provide standardized principles and practical pathways to advance China's ambitious goals: achieving ≥80% public awareness of dementia prevention knowledge, ≥80% cognitive screening rate among the elderly, ≥80% intervention guidance rate for at-risk populations, and ≥50% medical consultation rate for suspected cognitive impairment cases.

Objective:To investigate the operation of water improvement projects in villages affected by drinking-water-borne endemic arsenic poisoning in Shaanxi Province, the arsenic level in both internal and external environments, the trend of disease development and patient management, and evaluate the effectiveness of prevention and control measures.Methods:From March to December 2023, in accordance with the requirements of the "Notice of the Office of Shaanxi Provincial Health Commission on Issuing the Monitoring Plan for Key Endemic Diseases such as Kashin-Beck Disease" and the "Monitoring Plan for Endemic Fluorosis and Arsenism in Shaanxi Province", all villages affected by drinking-water-borne arsenic disease were monitored. Water arsenic testing was carried out in accordance with the "Standard Test Methods for Drinking Water Inorganic Nonmetallic Indicators" (GB/T 5750.5-2006), and the evaluation of whether water arsenic exceeded the standard was conducted based on the "Sanitary Standards for Drinking Water" (GB 5749-2022). According to the "Diagnosis of Endemic Arsenism" (WS/T 211-2015), the arsenic poisoning status of all population in the disease affected areas was investigated. In 5 villages of 3 monitoring counties, 358 people were randomly selected to determine the urinary arsenic level, and the determination was made according to the "Safety Guideline Value of Urinary Arsenic for Human Population" (WS/T 665-2019). According to the "Notice of the National Health Commission on Issuing the Evaluation Measures for Control and Elimination of Key Endemic Diseases (2019 Edition)", elimination evaluation was conducted.Results:A total of 2 cities, 3 counties, 9 towns, and 13 endemic villages were monitored, with a water improvement rate of 100% (13/13), and all were operating normally. The arsenic level in residents' drinking water was < 0.01 mg/L. A total of 12 688 people were examined, and 338 cases of arsenic poisoning were detected, all of whom were historical cases. There were no new cases of arsenic poisoning or skin cancer patients. The geometric mean of urinary arsenic was 0.026 0 mg/L, which was lower than the safety guideline value of 0.032 mg/L for urinary arsenic in the population. All 338 existing arsenic poisoning patients had received family doctor contract services and implemented follow-up management. The drinking-water-borne endemic arsenic poisoning areas counties in Shaanxi Province have reached the elimination standard.Conclusions:The water improvement project in drinking-water-borne endemic arsenic poisoning areas in Shaanxi Province is operating normally. The arsenic content in both the internal and external environments of the population meets the standard. The condition is stable and no new cases have been detected. Follow up management has been implemented for all current cases. All affected counties have reached the elimination standard.