ObjectiveTo investigate the disruptive effects of perinatal exposure to the environmental endocrine disruptor bisphenol AF (BPAF) on hepatic lipid metabolism in prepubertal (postnatal day 21, PND21) male offspring rats, and to provide scientific evidence for assessing the obesogenic effect of BPAF. MethodsSprague-Dawley (SD) rats aged 8 weeks were used in this study. Pregnant rats were divided into BPAF dose groups (2, 10, 50 mg·kg⁻¹) and a vehicle control group (corn oil), with 6 confirmed pregnant females per group. Gavage administration started from gestational day 0 and continued until the end of lactation. At PND21, one male offspring per litter was randomly selected. Serum concentrations of glucose (GLU), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), leptin (LEP), free fatty acid (FFA), as well as oxidative stress markers superoxide dismutase (SOD) and malondialdehyde (MDA), were measured. Pathological changes in liver and adipose tissues were evaluated, and the expression levels of genes related to hepatic lipid metabolism were measured. ResultsCompared to the vehicle control group, the 50 mg·kg⁻¹ group showed significantly increased serum LEP and MDA levels in male offspring (P<0.05), and significant upregulation of hepatic lipoprotein lipase (Lpl), fatty acid synthetase (Fas), and peroxisome proliferator-activated receptor γ (Pparg) gene expression (P<0.05). The 2 mg·kg⁻¹ group exhibited a significant increase in adipocyte length (P<0.05), while the 50 mg·kg⁻¹ group showed significant increases in both adipocyte area and length (P<0.05). No significant abnormalities were observed in liver histopathological examination. ConclusionPerinatal exposure to 50 mg·kg⁻¹ BPAF induced adipocyte hypertrophy, elevated leptin levels, upregulation of lipid synthesis gene expression, and enhanced oxidative stress in prepubertal male offspring, suggesting that BPAF may exert environmental obesogenic effects by disrupting lipid metabolism pathways.

OBJECTIVE To introduce the development of an intelligent prescription review decision-support system for anti-tumor drugs and assess its clinical application outcomes. METHODS Relevant data sources， including national and local pharmaceutical administration policies， clinical practice guidelines/consensus， hospital information systems data， and genetic testing results， were integrated. Adhering to the principles of structure， standardization and dynamic updating， a knowledge base covering chemotherapeutic， targeted and immunotherapeutic agents was constructed using a dual-dimensional modeling approach that combined “drug attributes” and “clinical contexts”. This knowledge base was then embedded into the hospital’s electronic medical order system to establish the prescription review decision-support system. The application and performance of the system were evaluated at Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. RESULTS A knowledge base containing 18 318 prescription review rules for anti-tumor drugs was constructed， and a closed-loop prescription review system was successfully established， encompassing pre-prescription real-time intervention， in-process interactive review， and post-prescription evaluation and analysis. From 2021 to 2024， the system generated a total of 57 879 alerts for prescriptions of five typical categories of anti-tumor drugs. For platinum-containing prescriptions， 22 577 alerts were generated， with Cisplatin for injection （lyophilized） being the most frequently alerted drug （13 445 alerts）， and “ototoxicity risk due to combined use” alerts remained high （7 682 alerts）. For methotrexate-containing prescriptions， 3 721 alerts were recorded， primarily related to “precaution-related issues” （76.4%， 2 843/3 721）. For doxorubicin-containing prescriptions， 17 301 alerts were triggered， primarily related to “dosage and administration” （14 315 alerts）. For human epidermal growth factor receptor 2-targeted agents-containing prescriptions， 1 007 alerts were issued， mostly related to “reimbursement restrictions” （956 alerts）. For programmed death-1/programmed death-ligand 1 inhibitors-containing prescriptions， the alerts increased year by year， totaling 13 273 alerts， primarily related to “inappropriate indication” （9 118 alerts）. Over the 4 years， the physician response rates to system alerts were 21.4%， 27.1%， 33.5% and 51.6%， respectively. CONCLUSIONS An intelligent decision-support system for anti-tumor drug prescription review， encompassing a closed-loop process of “real-time pre-event intervention， interactive in-event prescription review， post-event evaluation and analysis”， has been successfully constructed and implemented throughout the entire workflow. There is a discernible trend in this hospital， where the focus on monitoring anti-tumor drugs is shifting towards immunotherapy drugs. Additionally， the acceptance rate of physicians regarding prescription review opinions has been steadily increasing year by year.

The negative “second childhood” theory in the West has raised the medical ethical issues of infantilizing elderly patients with Alzheimer’s disease. In contrast， Chinese classical childlike thought represents a positive and simple idea of the overall life course， which contains four core connotations， including seemingly weak yet resilient， returning to simplicity and being gifted with nature， purity without hypocrisy and sincere feelings， and enjoying playfulness while hating restraint. Drawing on the essence of Chinese classical childlike thought， learning from the past to guide the present， and fully exploring its ethical implications in contemporary Alzheimer’s disease care， can help overcome the stigma of the disease and establish a positive bioethics value in the whole society； help caregivers adjust their mindsets and optimize nursing ethics； help build a care approach that returns to nature and enhance patients’ physical and mental health； help create a game-oriented rehabilitation environment to help patients regain their happiness； and help promote emotional communication between doctors and patients and explore new methods of emotional healing. The classical childlike thought provides a novel approach to building a friendly society for Alzheimer’s disease in China and offers Chinese wisdom and solutions for the global care and treatment of Alzheimer’s disease.

OBJECTIVE To provide reference for medical institutions to establish the record management mode and review rules of off-label use of 5-aminolevulinic acid （ALA） in photodynamic therapy based on the level of evidence. METHODS All ALA-containing outpatient prescriptions in the rational drug use system in our hospital from January 1， 2024 to December 31， 2025 were retrospectively collected. Based on the drug instructions， the current status of off-label use of ALA in photodynamic therapy was identified . The relevant studies in Micromedex， PubMed， CNKI， Wanfang Data and other databases were systematically searched as the relevant evidence-based evidence of ALA off-label use. According to the Off-label Drug Use Filing Standard of the hospital，the evidence-based evaluation method was used to evaluate the evidence-based evidence of ALA off-label use and carry out hierarchical management. RESULTS A total of 1 803 effective prescriptions were included， of which 676 （37.49%） were off-label use， distributed in the dermatology department （564 prescriptions，83.43%） and the plastic surgery department （112 prescriptions，16.57%）. All 676 prescriptions were off-indications medication， involving ten types of skin diseases， primarily including moderate to severe acne （39.94%）， skin warts （25.44%）， Bowen’s disease （11.98%）， and others. According to evidence-based evidence，off-label uses such as moderate to severe acne， actinic keratosis， and Bowen’s disease were managed according to the evidence categoryⅠ orⅡ.The uses of extramammary Paget’s disease and rosacea were managed according to the evidence category Ⅲ.The uses of lichen sclerosus and keloids were managed according to the evidence category Ⅳ.The results of evidence-based evaluation showed that 92.01% of off-label use in our hospital had high-level evidence-based support （ evidence category was gradeⅠ-Ⅱ）. CONCLUSIONS Off-label uses supported by high-level evidence， such as moderate to severe acne， skin warts， and Bowen’s disease， can be managed under filing category Ⅰ or Ⅱ. For the use of lichen sclerosus and keloids， evidence-based evidence is insufficient and should be strictly restricted.The vast majority of ALA off-label use in our hospital has sufficient evidence-based basis.

ObjectiveTo investigate the mechanism by which Xiebai San regulates respiratory tract and intestinal mucosal immunity in rats with allergic asthma. MethodsForty male SD rats were randomly divided into four groups based on body weight: control group, model group, positive control group, and Xiebai San group. The model group, positive control group, and Xiebai San group were sensitized with ovalbumin to establish a rat model of allergic asthma. From day 21 (the aerosol challenge phase), each group received daily gavage interventions simultaneously: the positive control group was administered dexamethasone (0.068 mg/kg), the Xiebai San group received Xiebai San solution (2 g/mL, 11.3 mL/kg), while the control and model groups were given an equal volume of normal saline, once daily for 14 consecutive days. After euthanasia, lung and intestinal tissues were collected. Hematoxylin and eosin staining was used to observe histopathological changes. Transmission electron microscopy was employed to examine tissue ultrastructure. Immunohistochemistry was applied to detect the positive reaction areas of phosphatidyl-inositol 3-kinase (PI3K) and protein kinase B (Akt) proteins. Total protein and total RNA were extracted from lung and intestinal tissues, then the protein and mRNA expression levels of PI3K and Akt genes were detected by Western blotting and real-time quantitative PCR, respectively. ResultsHistopathological results showed alveolar emphysema accompanied by inflammatory cell infiltration, and intestinal mucosal injury with inflammatory cell infiltration in the model group as compared with the control group; the cellular structure of lung tissues was disrupted in the model group, with reduced organelles, while the ultrastructural lesions in the intestine were relatively mild. Compared with the model group, Xiebai San group exhibited milder pathological changes in lung tissues, with occasional alveolar wall damage and a small amount of inflammatory cell infiltration; the intestinal mucosal structure was improved, glands were arranged regularly, and pathological changes such as tissue loosening and inflammatory infiltration were alleviated; the cellular structure of lung tissues was relatively intact with reduced severity of lesions, and no ultrastructural pathological changes were observed in intestinal tissues. Immunohistochemistry and Western blotting results showed that compared with the control group, the specific positive reaction areas of PI3K and Akt in lung and intestinal tissues were significantly increased in the model group (all P<0.001); meanwhile, the protein expression levels of PI3K and Akt were significantly upregulated (all P<0.05). Compared with the model group, the positive area of Akt protein in lung tissue was significantly reduced in the Xiebai San group (P<0.001), and the positive area of PI3K in intestinal tissue was also significantly decreased (P<0.000 1). Additionally, the protein expression levels of PI3K and Akt in lung and intestinal tissues were significantly downregulated (all P<0.01). Real-time quantitative PCR results showed that compared with the control group, the mRNA expression levels of PI3K and Akt genes in lung and intestinal tissues were significantly elevated in the model group (all P<0.05). Compared with the model group, the mRNA expression levels of PI3K and Akt genes in lung and intestinal tissues were significantly reduced in the Xiebai San group (all P<0.05). ConclusionXiebai San exerts protective effects on rats with allergic asthma by inhibiting the expression of key nucleic acids and proteins in the PI3K-Akt signaling pathway in lung and intestinal tissues, improving the morphological structure of lung tissue, and maintaining intestinal mucosal integrity, and regulating intestinal mucosal immune function.

OBJECTIVE: To analyze the functional impact of a rare heterozygous variant of SOS1 gene (c.283G>A, p.E95K) identified in a fetus with cervical cystic hygroma and to explore its association with the disease phenotype. METHODS: A pedigree analysis was carried out to evaluate the co-segregation of the variant with the disease phenotype. Bioinformatic tools were employed to assess the conservation, protein structure and stability. Functional validation was conducted on HEK293T cells using fluorescence quantitative reverse transcription-PCR and Western blotting to measure the expression of SOS1 and phosphorylation levels of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinase. A literature review of previously reported disease-associated SOS1 variants was also carried out. This study has been approved by the Medical Ethics Committee of West China Second University Hospital, Sichuan University (Ethics No.: 201940). RESULTS: The variant was inherited from the husband of the woman with distinctive facial features and has co-segregated with the phenotype. Bioinformatics analysis indicated that the variant is located in a highly conserved region, and that p.E95K could disrupt key amino acid interactions and protein stability. Multiple bioinformatic predictions consistently suggested the pathogenicity of this variant. Functional assays demonstrated reduced SOS1 protein expression and decreased ERK phosphorylation. CONCLUSION This study has revealed the functional impact of the SOS1 c.283G>A (p.E95K) variant, suggesting that it may contribute to the developmental phenotypes through a haploinsufficiency mechanism.
Humans ; SOS1 Protein/chemistry* ; Female ; HEK293 Cells ; Male ; Pedigree ; Phenotype ; Adult

Vascular endothelial growth factor (VEGF) inhibitors are drugs that target and inhibit tumor angiogenesis. By blocking the signaling pathway of VEGF and its receptor, they suppress tumor proliferation and play a crucial role in tumor treatment. However, their side effects, such as hypertension, proteinuria, hand-foot skin reactions, and myelosuppression, during treatment seriously affect patients' treatment compliance and quality of life. The development of intervention strategies for the side effects of VEGF inhibitors is of great importance for tumor treatment. This article reviews the clinical characteristics and toxic mechanisms of common side effects caused by VEGF inhibitors during tumor treatment and summarizes intervention strategies that combine traditional Chinese and Western medicines. Drug dosages were precisely monitored and adjusted to achieve antitumor treatment. Patients' discomfort symptoms are improved through prescriptions that act by tonifying qi and promoting blood circulation, strengthening the spleen, and tonifying the kidney. The combination of traditional Chinese and Western medicines is used to treat patients, thus providing a safe and effective treatment plan for patients with cancer.

Objective: To investigate the prevalence and influencing factors of the co-occurrence of elevated blood pressure and depressive symptoms among junior and senior high school students in Anhui Province, so as to provide evidence for comprehensive interventions on physical and mental health among adolescents. Methods: From September to December 2024, a multi stage random cluster sampling method was used to select 103 225 junior and senior high school students from 16 prefecture level cities in Anhui Province. Data were collected through questionnaire surveys and physical measurements. Elevated blood pressure was determined according to the Reference of Screening for Elevated Blood Pressure among Children and Adolescents Aged 7-18 Years. Depressive symptoms among middle school students were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Chi-square test, Chi-square test for trend, and multivariate Logistic regression model were used to analyze the risk factors for the co-occurrence of elevated blood pressure and depressive symptoms. Results: The detection rate of elevated blood pressure was 15.22%, the detection rate of depressive symptoms was 18.56%, and the co-occurrence rate of the two conditions was 2.67% among junior and senior high school students. Multivariate Logistic regression analysis showed that after controlling for gender, school stage, household registration, and overweight and obesity status,compared with those who don t drink sugary drink and eat fried food, and get enough sleep, sugar sweetened beverage intake <1 and ≥1 time/d( OR =1.28,1.61), fried food consumption ≥1 time/d( OR =1.37), and insufficient sleep ( OR =1.54) were all associated with an increased risk of the co-occurrence of elevated blood pressure and depressive symptoms(all P <0.05). Daily fresh vegetable intake ≥1 time/d( OR =0.78) and fresh fruit intake ≥1 time/d( OR =0.85) were both associated with a decreased risk of the co-occurrence(both P <0.05). Compared with students who did not eat breakfast, students who ate breakfast sometimes and every day ( OR =0.62,0.36) had a lower co-occurrence risk(both P < 0.05). Junior and senior high school students with daily outdoor activity duration≥1 h ( OR =0.81) had a lower risk of the co-occurrence of elevated blood pressure and depressive symptoms ( P <0.05). Conclusions Sugar sweetened beverage drink and fried food consumption, inadequate consumption of fresh vegetables, fruits and breakfast, lack of outdoor activity, and insufficient sleep are risk factors for the co-occurrence of elevated blood pressure and depressive symptoms among junior and senior high school students in Anhui Province. It is necessary to establish school health promotion strategies integrating nutrition, exercise and sleep management as intervention targets to reduce the co-occurrence risk of elevated blood pressure and depressive symptoms among junior and senior high school students.

Objective To examine the impact of extreme temperature and drought stress on the survival of Bulinus globosus, so as to provide the theoretical evidence for the genomic research of Bulinus in absence of reference genes. Methods B. globosus snail samples were collected from Kiwani Shehia in Pemba Island, Zanzibar, Tanzania, and offspring snails were obtained through laboratory breeding and reproduction. A total of 120 10-week-old B. globosus snails from the same generation were selected and randomly assigned into four groups, including the high-temperature drought (HD) group, normal temperature drought (D) group, low-temperature drought (LD) group, and the control (C) group, of 30 snails in each group. Snails in HD, D, and LD groups were placed in beakers containing dry soil at the bottom and subsequently housed in climate chambers at 35, 26 ℃, and 10 ℃, respectively, while snails in Group C were maintained in 500 mL petri dishes containing dechlorinated tap water at 26 ℃. Following 3 days of breeding, living snails in each group were collected, and soft tissues were dissected and isolated. Total RNA was extracted from snail soft tissues for library construction, followed by high-throughput sequencing on the Illumina HiSeq 4000 sequencing system. De novo transcriptome assembly was performed using the Trinity software, and the longest transcripts were selected as unigenes. Gene functional annotations of unigenes were conducted using the Diamond software against Gene Ontology (GO) knowledgebase, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, NCBI non-redundant (NR) protein sequences database, Protein Family (Pfam) database, and UniProtKB/Swiss-Prot (Swiss-Prot) knowledgebase. GO and KEGG enrichment analyses of differentially expressed genes (DEGs) were performed using the topGO and clusterProfiler software, respectively. In addition, four relevant genes were selected for validation using a real-time quantitative PCR (qRT-PCR) assay to verify the reliability of transcriptome sequencing results. Results Following 3 days of breeding, there were 7, 20, 28, and 30 survival B. globosus snails in HD, LD, D, and C groups, with corresponding survival rates of 23.33% (7/30), 66.67% (20/30), 93.33% (28/30), and 100.00% (30/30), respectively (χ² = 52.72, P < 0.001). De novo transcriptome assembly generated 176 942 unigenes, with annotation rates of 0.98%, 13.49%, 26.46%, 12.48%, and 14.39% against GO knowledgebase, KEGG pathway database, NR protein sequences database, Pfam database, and Swiss-Prot knowledgebase, respectively. There were 33 up-regulated and 72 down-regulated genes in Group D, 483 up-regulated and 815 down-regulated genes in Group HD, and 245 up-regulated and 172 down-regulated genes in Group LD relative to in Group C. Following removal of overlapping genes across groups and unmatched genes, 11 candidate genes were identified. GO and KEGG analyses revealed 3 heat shock protein (HSP)-related DEGs in these 11 candidate genes, which were annotated as HSP12.2, HSP70, and HSP20 genes and were all significantly up-regulated in each treatment group. Three immune and nervous system-related DEGs were identified, and were all significantly down-regulated in each treatment group, which were involved in the neural cell adhesion molecule L1-like protein pathway, fibrinogen binding protein pathway, and leukocyte elastase inhibitor-like protein pathway. qRT-PCR assay quantified that the expression trends of four genes related to temperature and drought stress across different treatment groups were highly consistent with transcriptome sequencing data. Conclusion The survival rate of B. globosus significantly reduces under combined stresses of extreme temperature and drought, possibly due to an imbalance in its cellular homeostasis regulatory system.

Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.