Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Objective To investigate iodine content in drinking water and clarify the distribution characteristics of iodine in water in Shaanxi Province.Methods A cross-sectional survey method was used to collect water samples from administrative villages in the province.Two tap water samples were taken from the centralized water supply villages,and 10％samples were taken from the decentralized water supply villages.Water iodine was detected by arsenic cerium catalytic spectrophotometry.Water iodine areas were divided according to national standards:＜40 μg/L was iodine deficiency area,40-100 μg/L was iodine adequate area,＞100 μg/L was high iodine area.According to the ecological regionification scheme of the Chinese Academy of Sciences,Shaanxi Province was divided into three types:the central and eastern Inner Mongolia Platea-Loess Plateau ecological region,the Fenwei Basin ecological region,and the Qinba Mountains ecological region.SPSS 25.0 was used for statistical analysis.Results The median of water iodine in Shaanxi Province was 6.66 μg/L.The survey of water iodine content was conducted in 22 848 administrative villages,1 309 townships,112 counties and 14 municipalities in the whole province.The median water iodine was less than 40 μg/L in 91.75％(20 963/22 848)of the administrative villages,between 40 and 100 μg/L in 7.40％(1 691/22 848)of the administrative villages,and more than 100 μg/L in 0.85％(194/22 848)of the administrative villages.The median of water iodine in the central and eastern Inner Mongolia Platea-Lose Plateau ecological zone,the Fenwei Basin ecological zone,and Qinba Mountains ecological zone was 12.35,8.88,and 2.00 μg/L,respectively,and the differences among different ecological zones were statistically significant(H=6 616.23,P＜0.001).The median of water iodine of centralized and decentralized water supply was 6.72 and 6.21 μg/L,respectively,and differences between different water supply methods were statistically significant(Z=5.638,P＜0.01).Conclusion The overall external environment of Shaanxi Province is iodine deficient,and most of the administrative villages are iodine deficient areas.There are a certain proportion of high iodine water source areas and suitable iodine areas.

Objective:To study the spatial distribution and characteristics of iodine content in residential drinking water in Shaanxi Province, and provide a basis for scientific prevention and control of iodine deficiency disorders.Methods:From March to October 2022, an investigation was conducted in all counties (districts, referred to as counties) of Shaanxi Province, with administrative villages as survey units. For centralized water supply systems, two terminal water samples were collected, and iodine content was measured separately, with the average value representing the drinking water iodine content at that location. For decentralized water supply systems, a 10% sampling method was used to divide each administrative village into five areas (east, south, west, north, and center), with 10% of water wells sampled from each area (if fewer than 10 water wells, the well with the largest drinking population was selected; if fewer than 5 wells, all wells were sampled). One water sample was collected from each water well, and iodine content was determined using the arsenic-cerium catalytic spectrophotometry method. Spatial autocorrelation and spatial scan analysis were used to analyze the spatial distribution and characteristics of drinking water iodine content.Results:A total of 53 990 drinking water samples were collected, with a median water iodine content of 6.66 μg/L, ranging from 0.10 to 779.40 μg/L. Drinking water iodine content was detected in 112 counties, showing a significant spatial positive correlation (global autocorrelation, Moran's I = 0.74, Z = 43.83, P < 0.001). Local autocorrelation analysis showed that the difference in the distribution of iodine content in drinking water among 36 counties was statistically significant ( P < 0.05), with 22 counties showing low-low clustering and 12 counties showing high-high clustering. Spatial scanning identified three water iodine clustering areas, including two high-water iodine cluster areas and one low-water iodine cluster area. Conclusions:The distribution of iodine content in residential drinking water in Shaanxi Province shows significant spatial clustering and heterogeneity, requiring targeted interventions to achieve precise prevention and control of iodine deficiency disorders.

Objective To investigate iodine content in drinking water and clarify the distribution characteristics of iodine in water in Shaanxi Province.Methods A cross-sectional survey method was used to collect water samples from administrative villages in the province.Two tap water samples were taken from the centralized water supply villages,and 10％samples were taken from the decentralized water supply villages.Water iodine was detected by arsenic cerium catalytic spectrophotometry.Water iodine areas were divided according to national standards:＜40 μg/L was iodine deficiency area,40-100 μg/L was iodine adequate area,＞100 μg/L was high iodine area.According to the ecological regionification scheme of the Chinese Academy of Sciences,Shaanxi Province was divided into three types:the central and eastern Inner Mongolia Platea-Loess Plateau ecological region,the Fenwei Basin ecological region,and the Qinba Mountains ecological region.SPSS 25.0 was used for statistical analysis.Results The median of water iodine in Shaanxi Province was 6.66 μg/L.The survey of water iodine content was conducted in 22 848 administrative villages,1 309 townships,112 counties and 14 municipalities in the whole province.The median water iodine was less than 40 μg/L in 91.75％(20 963/22 848)of the administrative villages,between 40 and 100 μg/L in 7.40％(1 691/22 848)of the administrative villages,and more than 100 μg/L in 0.85％(194/22 848)of the administrative villages.The median of water iodine in the central and eastern Inner Mongolia Platea-Lose Plateau ecological zone,the Fenwei Basin ecological zone,and Qinba Mountains ecological zone was 12.35,8.88,and 2.00 μg/L,respectively,and the differences among different ecological zones were statistically significant(H=6 616.23,P＜0.001).The median of water iodine of centralized and decentralized water supply was 6.72 and 6.21 μg/L,respectively,and differences between different water supply methods were statistically significant(Z=5.638,P＜0.01).Conclusion The overall external environment of Shaanxi Province is iodine deficient,and most of the administrative villages are iodine deficient areas.There are a certain proportion of high iodine water source areas and suitable iodine areas.

Objective:To explore the effect of the interaction between plasma aluminum concentration and schooling year on cognitive function, it provides the basis for early identification of its damaging effect.Methods:From October to December, 2014, 1114 on-the-job aluminum exposed workers in a large aluminum factory in Shanxi Province were investigated. The plasma aluminum concentrations were measured by inductively coupled plasma-mass spectrometry (ICP-MS) as an internal exposure indicator. The subjects were divided into low, medium, and high aluminum exposure group based on the blood lead concentration levels. The general information was collected with a self-designed questionnaire, and their cognitive function was evaluated with the mini-mental state examination and the clock drawing test. The interaction between plasma aluminum concentration level and education level was analyzed by using unconditional logistic regression fitting multiplication model and cross analysis fitting addition model.Results:The average level of plasma aluminum of the subjects was 21.68 (10.51, 45.78) μg/L. The detection rate of cognitive impairment was 19.9%. The influencing factors of cognitive function were plasma aluminum concentration, age, education level and marital status, among which high schooling year, and being married were the protective factors (all P<0.05), plasma aluminum concentration, and age were the risk factors (all P<0.05) ; After adjusting the confounding factors, such as age, marital status, schooling year, income level, smoking, and drinking, logistic regression model and the multiple linear regression model showed that there was a dose response relationship between plasma aluminum concentration and cognitive impairment. With the increase of plasma aluminum concentration, the score gradually decreased, and the risk of cognitive impairment increased ( Ptrend<0.05) ; There were multiplicative interaction ( AOR=2.15, 95% CI: 1.10-4.19) and additive interaction ( RERI=5.38, 95% CI: 2.60-8.16; AP=0.65, 95% CI: 0.51-0.80; S=3.88, 95% CI: 2.00-7.56) between plasma aluminum concentration and low schooling year on cognitive function. Conclusion:There was a dose-response relationship between aluminum exposure and cognitive impairment. There was an interaction between aluminum exposure and low schooling year. When both of them worked together, the risk of cognitive impairment increases.

OBJECTIVE To explore comprehensive management and potential issues associated with long-term prescriptions medications of psychiatry， in order to provide a reference for the comprehensive management of long-term prescriptions of psychiatry in psychiatric hospitals and other medical institutions’ pharmacies. METHODS Starting from the applicable principles for long-term prescriptions of psychiatry， this study introduced the standardized assessment and precautions before issuing long-term prescriptions， the formulation and adjustment of the drug list， as well as the rational management of the long-term prescriptions. It also analyzed potential issues that may arise in the comprehensive management of long-term prescription medications and proposed corresponding countermeasures and suggestions. RESULTS & CONCLUSIONS Prior to initiating long-term prescriptions， a standardized assessment should be conducted on patients from the aspects of their psychiatric condition and long-term potential risk factors， pharmacological treatment plans and other non-pharmacological therapies， physical illnesses. Additionally， healthcare providers should fulfill their obligation to inform patients or their family members. The comprehensive management of long-term prescription medications should be jointly established and improved by multiple departments， and the formulation of drug catalogs should avoid including drugs with potential social harm or medication risks while complying with policy requirements. Furthermore， measures such as adding special identifiers to long-term prescriptions， providing patients with reminders about （No.YGLX202537） prescription expiration， or offering online consultations can also effectively enhance the rationality of medication use under long-term prescriptions. Currently， the implementation of long-term prescriptions in psychiatry remains challenged by inconsistencies in prescription duration， incomplete coverage of diagnostic categories， poor patient adherence， and the risk of deviation in clinical assessments. In this regard， measures such as collaborating with multiple departments to strengthen long-term prescription information management， providing matching pharmaceutical services， ensuring the quality and rationality of long-term prescription implementation， and using modern methods to screen high-risk patients can be taken to improve patient medication compliance and safety.

Objective:To evaluate the short-and medium-term therapeutic efficacy of shockwave balloon therapy for TASCⅡ C/D femoropopliteal artery atherosclerosis obliteration.Methods:This retrospective cohort study included 25 patients who received shockwave balloon therapy in five vascular centers from August 2022 to June 2023. All patients were diagnosed with TASC Ⅱ C/D femoropopliteal arteriosclerosis obliterans (13 cases of type C and 12 cases of type D), and underwent intravascular shock wave lithotripsy (IVL) to treat calcified lesions. The immediate effectiveness (residual stenosis<30% and no flow-limiting dissection), safety (whether there were adverse vascular events during the operation) and the rate of salvage stent implantation were recorded. The observation indexes of patients before operation, early postoperative period (immediately after operation or before discharge) and postoperative follow-up period (3, 6, 12 months after operation) were collected. The observation indexes included ankle-brachial index (ABI), Rutherford classification, and minimum lumen diameter (MLD). Repeated measures ANOVA was used to evaluate the changes of observation indexes in the early postoperative and follow-up stages compared with those before operation; Kaplan-Meier survival analysis was used to evaluate the one-stage patency rate at follow-up and the target lesion revascularization rate free from clinical drive.Results:The immediate effectiveness of surgery was 100% in all patients, with no vascular related adverse events occurred, and no remedial stent implantation was performed. The ABI, Rutherford grade and MLD of the patients in the early postoperative period and each follow-up stage were improved compared with those before operation, with statistically significant differences ( P<0.05). Kaplan-Meier survival analysis showed that the primary patency rate at 12 months after surgery was 0.78 (95% CI 0.64-0.84), and the revascularization rate of target lesions free from clinical drive was 0.87 (95% CI 0.85-0.95). Conclusion:Shockwave balloon therapy for complex calcified femoropopliteal artery lesions is safe and reliable, with satisfactory short-and medium-term efficacy.

Objective:To systematically evaluate the incidence and influencing factors of postoperative stroke in patients with acute type A aortic dissection (ATAAD).Methods:Nine Chinese and English databases, including PubMed, Embase, CINAHL, JAMA, The Cochrane Library, CNKI, Wanfang, Vip and Chinese Biomedicine, were searched by computer to include literatures evaluating the incidence of postoperative stroke and its influencing factors in ATAAD patients. The search period was from the establishment of the database to September 2024. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Stata 14.0 software was used to combine the prevalence rate, and descriptive analysis of influencing factors was performed.Results:A total of 22 articles were included, including 16 734 ATAAD patients, published from 2018 to 2024. Meta-analysis results showed that the incidence of postoperative stroke in ATAAD patients was 16% (14%-18%). Subgroup analyses showed a higher incidence of postoperative stroke in patients with ATAAD in Europe (19%, 95% CI: 15%-23%), with a sample size of 1 to 300 patients (18%, 95% CI: 14%-22%), and in 2024 (20%, 95% CI: 14%-28%). Descriptive analysis shows that the factors influencing the occurrence of postoperative stroke in ATAAD patients include preoperative history (preoperative hypotension, preoperative history of stroke, history of carotid artery disease, history of cardiac arrest), intraoperative measures (total arch replacement, femoral artery intubation, anterograde cerebral perfusion, intraoperative oxygen satiation), and various types of time (cryopreservation time, extracorporeal circulation time, operation time). Conclusion:The incidence of postoperative stroke is higher in ATAAD patients. Preoperative hypotension, history of stroke before surgery, history of carotid artery disease, history of cardiac arrest, total arch replacement, femoral artery intubation, anterograde cerebral perfusion, decrease of cerebral oxygen saturation during operation, and longer hypothermia stop time, cardiopulmonary bypass time and operation time may increase the risk of postoperative stroke in ATAAD patients.

In the context of aging population, the issue of polypharmacy among elderly patients with mental disorders has become increasingly prominent.Cognitive decline and depressive symptoms render these patients more vulnerable to medication-related risks, while poorly managed physical illnesses further complicate their treatment.To address these challenges, this paper proposes a series of management strategies that emphasize the critical role of pharmacists in conducting medication reviews.A comprehensive assessment of drug risks, benefits, and patient adherence is essential.The proposed strategies not only require careful consideration of patients' clinical needs and individual preferences but also highlight the importance of multidisciplinary team collaboration to reach a consensus on medication therapy.The use of clinical decision support systems as an auxiliary tool is recommended to enhance the scientific rigor of medication decision-making.Furthermore, pharmacists can optimize medication regimens through scientifically validated methods and promote patient or family involvement in self-management to improve acceptance and adherence to treatment adjustments.

Objective:To explore the effect of the interaction between plasma aluminum concentration and schooling year on cognitive function, it provides the basis for early identification of its damaging effect.Methods:From October to December, 2014, 1114 on-the-job aluminum exposed workers in a large aluminum factory in Shanxi Province were investigated. The plasma aluminum concentrations were measured by inductively coupled plasma-mass spectrometry (ICP-MS) as an internal exposure indicator. The subjects were divided into low, medium, and high aluminum exposure group based on the blood lead concentration levels. The general information was collected with a self-designed questionnaire, and their cognitive function was evaluated with the mini-mental state examination and the clock drawing test. The interaction between plasma aluminum concentration level and education level was analyzed by using unconditional logistic regression fitting multiplication model and cross analysis fitting addition model.Results:The average level of plasma aluminum of the subjects was 21.68 (10.51, 45.78) μg/L. The detection rate of cognitive impairment was 19.9%. The influencing factors of cognitive function were plasma aluminum concentration, age, education level and marital status, among which high schooling year, and being married were the protective factors (all P<0.05), plasma aluminum concentration, and age were the risk factors (all P<0.05) ; After adjusting the confounding factors, such as age, marital status, schooling year, income level, smoking, and drinking, logistic regression model and the multiple linear regression model showed that there was a dose response relationship between plasma aluminum concentration and cognitive impairment. With the increase of plasma aluminum concentration, the score gradually decreased, and the risk of cognitive impairment increased ( Ptrend<0.05) ; There were multiplicative interaction ( AOR=2.15, 95% CI: 1.10-4.19) and additive interaction ( RERI=5.38, 95% CI: 2.60-8.16; AP=0.65, 95% CI: 0.51-0.80; S=3.88, 95% CI: 2.00-7.56) between plasma aluminum concentration and low schooling year on cognitive function. Conclusion:There was a dose-response relationship between aluminum exposure and cognitive impairment. There was an interaction between aluminum exposure and low schooling year. When both of them worked together, the risk of cognitive impairment increases.