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.

[摘 要] 目的：探讨环指蛋白8（RNF8）对子宫内膜癌（EC）细胞顺铂（CDDP）敏感性的影响及可能机制。方法：基于在线数据库分析RNF8在EC组织中的表达及拷贝数变异；采用慢病毒介导shRNA稳定敲低Ishikawa细胞中RNF8表达并进行CDDP处理，按sh-NC+溶剂对照、sh-RNF8+溶剂对照、sh-NC + CDDP、sh-RNF8 + CDDP分组处理，并设置sh-RNF8 + CDDP + KU60019抑制实验。采用CCK-8、克隆形成、Annexin V-FITC/PI流式细胞术、Hoechst 33258/PI染色、WB及γ-H2AX免疫荧光检测细胞活力、克隆形成、凋亡、DNA损伤累积及ATM/CHK2通路相关蛋白表达。结果：RNF8在EC组织和细胞中表达升高。RNF8敲低降低细胞存活率和IC50，抑制克隆形成，并进一步增强CDDP诱导的凋亡；同时BAX、Cleaved-Caspase-3和γ-H2AX表达升高，BCL-2、p-ATM、p-CHK2和RAD21表达降低。KU60019处理进一步促进DNA损伤累积和细胞凋亡，并降低细胞活力。结论：RNF8可能通过ATM/CHK2轴促进DNA损伤应答并降低EC细胞对CDDP的敏感性；敲低RNF8可增加DNA损伤累积并增强CDDP敏感性。

Objective To investigate the risk factors for ICU-acquired weakness (ICU-AW) in patients with sepsis, and to construct a nomogram prediction model. Methods A total of 360 patients with sepsis admitted from January 2020 to December 2025 were enrolled as study subjects. The risk factors for ICU-AW were identified by logistic regression analysis. A nomogram prediction model was constructed, and the model was validated. Results Multivariate logistic regression analysis indicated that age, APACHE II score, duration of mechanical ventilation, duration of immobilization, duration of sedation, and NLR were risk factors for the occurrence of ICU-AW (P<0.05), while ALB was a protective factor (P<0.05). A nomogram model was constructed based on these seven variables. After validation via Bootstrap resampling, ROC curve showed an AUC of 0.949 (0.929–0.969) and a corrected AUC of 0.942 (0.940–0.948), indicating good discrimination degree of the model. Hosmer-Lemeshow test for calibration curve revealed a chi-square value of 10.188 (P=0.252), suggesting that the predicted value of fitting was generally consistent with the actual value. Decision curve analysis demonstrated that when the threshold was in the range of 0.05–0.9, the model had a good net benefit. Conclusion The nomogram prediction model for sepsis ICU-AW based on seven indicators including age, APACHE II score, NLR, ALB, and the durations of mechanical ventilation, immobilization, and sedation exhibits good predictive efficiency and stability. This nomogram prediction model is helpful for the clinical rapid screening of ICU-AW high-risk groups in patients with sepsis, and meets clinical needs for early warning and precise prevention and control.

ObjectiveTo investigate the mechanism through which Wendan Tang ameliorates atherosclerosis （AS） in mice by regulating ferroptosis via the Janus kinase 2（JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsTwelve 8-week-old male C57BL/6J mice of SPF grade were selected as the blank control group and fed a standard diet. Additionally， sixty age-matched male apolipoprotein E knockout （ApoE^-/-） mice of the same strain and SPF grade were selected and assigned through a random number table into the following groups （n=12 per group）： a model group， a low-dose （3.9 g·kg^-1·d^-1） Wendan Tang group， a medium-dose （7.8 g·kg^-1·d^-1） Wendan Tang group， a high-dose （15.6 g·kg^-1·d^-1） Wendan Tang group， and an atorvastatin calcium （0.01 g·kg^-1·d^-1） group. All ApoE^-/- mice were fed a high-fat diet for the modeling of AS. Starting from week 9， the blank and model groups were administrated with an equal volume of normal saline by gavage， and the remaining groups with corresponding agents by gavage. After 8 weeks of intervention， samples were collected for analysis. Oil red O staining and Masson staining were used to observe lipid deposition in the aorta， and hematoxylin-eosin （HE） staining was employed to examine AS plaque formation. The serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by an automatic biochemical analyzer. The serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， malondialdehyde （MDA）， and reduced glutathione （GSH） were determined by enzyme-linked immunosorbent assay （ELISA）. The level of Fe²⁺ in the aortic tissue was measured by ELISA. Western blot was performed to determine the protein levels of JAK2， phosphorylated JAK2 （p-JAK2）， STAT3， phosphorylated STAT3 （p-STAT3）， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to measure the mRNA levels of JAK2， STAT3， SLC7A11， and GPX4 in the aortic tissue. ResultsCompared with the blank control group， the model group exhibited increased aortic plaque number and area， enhanced lipid deposition， elevated serum levels of TC， TG， LDL-C， TNF-α， IL-6， and MDA （P<0.05， P<0.01）， declined serum levels of HDL-C， SOD， and GSH， and downregulated protein levels of SLC7A11 and GPX4 in the aortic tissue （P<0.05， P<0.01）. The aortic tissue of the model group exhibited an elevated Fe²⁺ level and upregulated protein levels of p-JAK2 and p-STAT3 and mRNA levels of JAK2 and STAT3 （P<0.05， P<0.01）. Compared with the model group， low-， medium-， and high-dose Wendan Tang， as well as atorvastatin calcium， significantly attenuated these pathological alterations. Specifically， the treatments decreased aortic plaque burden and lipid deposition and lowered serum TC， TG， LDL-C， TNF-α， and MDA levels （P<0.05， P<0.01）. Concurrently， these interventions raised serum HDL-C， SOD， and GSH levels， upregulated the protein levels of SLC7A11 and GPX4 in the aortic tissue （P<0.05， P<0.01）， reduced the Fe²⁺ level， and downregulated the protein levels of p-JAK2 and p-STAT3 and the mRNA levels of JAK2 and STAT3 in the aortic tissue （P<0.05， P<0.01）. ConclusionWendan Tang ameliorates aortic lesions， dyslipidemia， and oxidative stress， decreased the phosphorylation levels of JAK2/STAT3， and increased the expression of SLC7A11 and GPX4 in the mouse model of AS. The results suggest that the anti-AS effect of Wendan Tang may be associated with the modulation of the JAK2/STAT3 signaling pathway and inhibition of ferroptosis.

During orthodontic treatment, clinical monitoring of patients is a crucial factor in determining treatment success. It aids in timely problem detection and resolution, ensuring adherence to the intended treatment plan. In recent years, digital technology has increasingly permeated orthodontic clinical diagnosis and treatment, facilitating clinical decision-making, treatment planning, and follow-up monitoring. This review summarizes recent advancements in digital technology for monitoring orthodontic tooth movement, related complications, and appliance-wearing compliance. It aims to provide insights for researchers and clinicians to enhance the application of digital technology in orthodontics, improve treatment outcomes, and optimize patient experience. The digitization of diagnostic data and the visualization of dental models make chair-side follow-up monitoring more convenient, accurate, and efficient. At the same time, the emergence of remote monitoring technology allows orthodontists to promptly identify oral health issues in patients and take corresponding measures. Furthermore, the multimodal data fusion method offers valuable insights into the monitoring of the root-alveolar relationship. Artificial intelligence technology has made initial strides in automating the identification of orthodontic tooth movement, associated complications, and patient compliance evaluation. Sensors are effective tools for monitoring patient adherence and providing data-driven support for clinical decision-making. The application of digital technology in orthodontic monitoring holds great promise. However, challenges like technical bottlenecks, ethical considerations, and patient acceptance remain.

ObjectiveTo establish an educational intervention framework of electronic picture books for children with autism spectrum disorder (ASD) based on Creative Problem Solving (CPS) model, and observe the effect on social function. MethodsElectronic picture books were designed using CPS model, including the program of reading, interactive animation design and associated artistic activities. From March to June, 2023, 24 children with mild to moderate ASD were recruited from Maanshan Institute of Special Education, and randomly assigned into experimental group 1 (CPS-based cognitive picture book interventions, n = 8), experimental group 2 (CPS-based social picture book interventions, n = 8) and control group (Bloom's Taxonomy-based picture book interventions, n = 8), and received the interventions for four weeks, with a total of twelve times. They were assessed with speech, social, perceptual and health behavior using Autism Treatment Evaluation Checklist (ATEC) before and after treatment, and the differences were calculated. ResultsThere was a significant difference among the groups in the social and perceptual scores differences (F > 4.344, P < 0.05) and a near-significant difference in the health behaviour score difference (F = 2.921, P = 0.076). Post Hoc test showed that the differences in social scores were higher in both experimental groups than in the control group (P < 0.05); the difference in perceptual scores was significantly higher in experimental group 1 than in experimental group 2 (P < 0.01), but there was no significant difference with the control group (P > 0.05); the difference in health behavior scores was higher in experimental group 2 than in the control (P < 0.05), and the difference in experimental group 1 was slightly higher than in the control group (P = 0.072). ConclusionElectronic picture book interventions based on the CPS model may be more effective in enhancing social, perceptual and health behavior in children with ASD, but there may be differences among models.

ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

Objective Melatonin has been shown to have neuroprotective effects.This study is aimed at observing the effects of copper deposition on cognitive function in a toxic milk(TX)mouse model of Wilson disease(WD),and investigating the effects and mechanisms of action of Gandou Bushen Decoction(GDBSD)on melatonin synthesis and pineal function in the WD model mice.Methods A total of 30 homozygous TX mice were randomly assigned to 3 groups(n=10 in each group),including a WD group,a GDBSD group,and a dimercaptosuccinic acid(DMSA)group.A total of 10 DL mice were included in the normal control(NC)group.The structure and copper content of pineal gland tissues,oxidative stress and apoptosis-related markers,and serum melatonin levels were evaluated using hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA),flow cytometry,and Western blot.Results Compared with the NC group,the WD group exhibited decreased learning and cognitive abilities(P＜0.05),damaged pineal gland structure,increased copper content,reactive oxygen species(ROS)levels,and mitochondrial damage rate in the pineal gland(P＜0.01),altered levels of melatonin and oxidative stress-related markers(P＜0.05),upregulated expression levels of pro-apoptotic proteins Bax and Caspase-3,and decreased expression of the anti-apoptotic protein Bcl-2(P＜0.01).After treatment with GDBSD and DMSA,the SIRT3/FOXO3α signaling pathway was activated,the copper content in the pineal gland was reduced,and oxidative stress and apoptosis-related damages were improved,leading to an improvement in learning and memory abilities(P＜0.05).Conclusion GDBSD can alleviate cognitive impairments in WD mice caused by pineal gland copper deposition by inhibiting oxidative stress and apoptosis in the pineal gland.The underlying molecular mechanism is associated with the regulation of the SIRT3/FOXO3α signaling pathway.

Objective: To explore the regulatory effects of ginkgo biloba extract on airway inflammatory injury and Toll⁃like receptor 4(TLR4)/nucleotide⁃binding oligomerization domain⁃containing 3(NLRP3) pathway in rats with vided into four groups : the normal control group , Methods: Thirty⁃six male SD rats were selected and randomly divided into four groups : the normal control group , the model group , the prednisone treatment group , and the ginkgo biloba extract treatment group , with 9 rats in each group. Except for the normal control group , the COPD rat mod⁃els in the other groups was constructed by intratracheal instillation of lipopolysaccharide (LPS) combined with ciga⁃rette smoke exposure. After successful modeling , the rats were continuously administered drugs for 12 weeks , fol⁃lowed by sampling. The general conditions and respiratory symptoms of the rats were observed. The pathological changes of lung tissues were observed by hematoxylin⁃eosin (HE) staining technique ; the mRNA and protein ex⁃pression levels of TLR4 , tumor necrosis factor⁃α (TNF⁃α ) , interleukin⁃1β (IL⁃1β) and NLRP3 in rat lung tissueswere detected by real⁃time quantitative polymerase chain reaction (RT⁃qPCR) and Western blot. Results: Com⁃pared with the normal control group , the lung tissues of rats in the model group were significantly damaged , and the protein and mRNA expression of TLR4 , TNF⁃α , IL⁃1β , and NLRP3 increased ( P < 0. 05 ) . Compared with the model group , lung tissue damage was reduced in the prednisone group and the ginkgo biloba extract group , and TLR4 , TNF⁃α , IL⁃1β , NLRP3 protein and mRNA expression decreased (P < 0. 05) . Conclusion Ginkgo biloba airway inflammatory response by inhibiting the TLR4/NLRP3 signaling pathway.

Objective : To investigate the impact of fecal microbiota transplantation (FMT) on the composition of 15 intestinal-derived estrogens and their metabolites (EMs) and its correlation with non-alcoholic fatty liver disease (NAFLD) . Methods: Thirty male C57BL/6J mice were divided into a normal control group (Control) , a high- sugar high-fat diet combined with low-dose CCl4 -induced NAFLD model group ( Model) , and a group of model mice treated with fecal microbiota from normal female mice (FMT) . After 17 weeks of modeling , liver pathology in each group was observed using HE staining , biochemical methods were used to measure serum alanine aminotrans- ferase (ALT) and aspartate aminotransferase (AST) levels , as well as hepatic triglyceride (TG) and total choles- terol (TC) levels. and the content of 15 EMs in portal vein serum was detected using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) . The correlation between disease phenotype and intesti- nal EMs was analyzed using Pearson ′s method. Results: The NAFLD model was successfully established , and the FMT group showed improved liver structure and morphology , with significant decreases in liver function and hepatic lipids compared to the Model group. In NAFLD mice , the contents of E1 , E2 , and their 2- and 4-position metabo- lites in portal vein blood serum was reduced compared to normal mice , while the content of most 16- and 17-posi- tion metabolites ( except 16α-OHE1) increased compared to normal mice. Correlation analysis showed that ALT was strongly positively correlated with E3 and 17-epiE3 , and strongly negatively correlated with E1 , E2 , 4- MeOE1 , and 16α-OHE1 . The TC was strongly positively correlated with 17-epiE3 and strongly negatively correla- ted with E1 , 4-MeOE1 , and 16α-OHE1 . Conclusion FMT restores the disrupted composition of intestinal EMs and improves NAFLD.