ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan （GFW） inhibits ferroptosis in endometriosis （EMT） through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 （HIF-1α/HO-1） signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT， including core targets. Functional enrichment analysis was conducted to explore the biological processes， molecular functions， cellular components， and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley （SD） rats were randomly divided into five groups： sham-operated， model， positive control （dienogest at 0.2 mg·kg^-1）， low-dose GFW （2.5 g·kg^-1）， and high-dose GFW （5 g·kg^-1）. After modeling， the rats received their respective treatment by oral gavage for 28 consecutive days， while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin （HE） staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to assess mRNA and protein expression of HIF-1α， HO-1， glutathione peroxidase 4 （GPX4）， spermidine/spermine N1-acetyltransferase （SAT1）， and prostaglandin-endoperoxide synthase 2 （PTGS2）. Tissue levels of malondialdehyde （MDA）， glutathione （GSH）， and ferrous iron （Fe²⁺） were quantified using commercial assay kits. Serum levels of interleukin-6 （IL-6） and transforming growth factor-β₁ （TGF-β₁） were measured via enzyme-linked immunosorbent assay （ELISA）. ResultsFive ferroptosis-related biomarkers in EMT were identified： ALOX12， CHAC1， SAT1， AST1， and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment， with FOS， JUN， HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group， the model group exhibited significant increases in both mRNA and protein expression of HIF-1α， HO-1， and PTGS2， as well as elevated tissue levels of Fe²⁺ and MDA. Conversely， GSH levels and the expression of GPX4 and SAT1 were markedly reduced， and serum levels of IL-6 and TGF-β₁ levels were significantly higher （P<0.01）. Compared with the model group， all GFW-treated groups showed significant downregulation of HIF-1α and HO-1， reduced Fe²⁺ levels， and downregulated expression of MDA， PTGS2， IL-6， and TGF-β₁. Meanwhile， GSH， GPX4， and SAT1 expression levels were significantly increased （P<0.05， P<0.01）， effectively ameliorating iron overload and oxidative stress， thereby demonstrating therapeutic efficacy in EMT， with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation， providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.

Aromatherapy refers to the method of using the aromatic components of plants in appropriate forms to act on the entire body or a specific area to prevent and treat diseases. Essential oils used in aromatherapy are hydrophobic liquids containing volatile aromatic molecules， such as limonene， linalool， linalool acetate， geraniol， and citronellol. These chemicals have been extensively studied and shown to have a variety of functions， including reducing anxiety， relieving depression， promoting sleep， and providing pain relief. Terpenoids are a class of organic molecules with relatively low lipid solubility. After being inhaled， they can pass through the nasal mucosa for transfer or penetrate the skin and enter the bloodstream upon local application. Some of these substances also have the ability to cross the blood-brain barrier， thereby exerting effects on the central nervous system. Currently， the academic community generally agrees that products such as essential oils and aromatherapy from aromatic plants have certain health benefits. However， the process of extracting a single component from it and successfully developing it into a drug still faces many challenges. Its safety and efficacy still need to be further verified through more rigorous and systematic experiments. This article systematically elaborated on the efficacy of aromatic substances， including plant extracts and natural small molecule compounds， in antibacterial and antiviral fields and the regulation of nervous system activity. As a result， a deeper understanding of aromatherapy was achieved. At the same time， the potential of these aromatic substances for drug development was thoroughly explored， providing important references and insights for possible future drug research and application.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

AIM:To investigate the ameliorative effect of nociceptin/orphanin(N/OFQ)on anxiety-like be-havior in nicotine(NIC)withdrawal-induced rats and its regulatory mechanisms on the expression of neurotransmitters as-sociated with the hypothalamic-pituitary-adrenal(HPA)axis and inflammatory factors.METHODS:Thirty-two adult male Sprague-Dawley rats were randomly divided into 4 groups:normal control group,NIC withdrawal model group,low-dose N/OFQ treatment group,and high-dose N/OFQ treatment group,with 8 rats in each group.To establish NIC with-drawal model,the rats in the NIC model and N/OFQ treatment groups were subcutaneously injected with NIC(0.4 mg/kg),twice a day for 7 consecutive days followed by 3 days of withdrawal.During the withdrawal period,the rats in the low and high-dose N/OFQ treatment groups received intracerebroventricular injection of N/OFQ(1 nmol or 10 nmol)once per day for 3 consecutive days.Ten minutes after the third administration,all rats underwent open filed(OF)and elevated plus maze(EPM)tests to detect behavioral changes.The serum concentrations of corticotrophin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),corticosterone(CORT),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 were measured by ELISA.The mRNA expression levels of TNF-α,IL-1β and IL-6 in the central nu-cleus of the amygdala(CeA)of the brain were detected by RT-qPCR.Histological changes in neuron morphology in the CA1 region of the hippocampus were observed under a light microscope following hematoxylin and eosin(HE)staining.Norepinephrine(NE)levels in the CeA of the brain were determined by HPLC.The protein expression of tyrosine hydroxy-lase(TH)in the CeA of the brain was detected by Western blot.RESULTS:Compared with the NIC withdrawal model group,rats in the low and high-dose N/OFQ treatment groups showed significant increase in the distance and time spent in the central area of the open field(P<0.05 or P<0.01),as well as significant increase in the number of entries and the per-centage of time spent in the open arms of the EPM(P<0.05 or P<0.01).Furthermore,both low and high-dose N/OFQ treatment groups significantly inhibited serum concentrations of CRH,ACTH and CORT in NIC withdrawal rats(P<0.01).N/OFQ administration also significantly reduced the levels of inflammatory cytokines TNF-α,IL-1β,and IL-6 in the serum,as well as expression levels of TNF-α,IL-1β and IL-6 mRNA in the CeA(P<0.05 or P<0.01).The treatment with N/OFQ at both doses significantly alleviated neuronal damage in the CA1 region of the hippocampus and markedly re-duced thelevels of NE and TH protein expression in the CeA of NIC withdrawal rats(P<0.01).CONCLUSION:N/OFQ alleviates anxiety-like behavior in NIC withdrawal rats through mechanisms related to the regulation of HPA axis hormone levels and inflammatory factors.

Objective To observe the value of diffusion kurtosis imaging(DKI)radiomics for evaluating Parkinson disease(PD).Methods Totally 76 PD patients(PD group)and 80 healthy controls(HC group)were retrospectively analyzed.The subjects were divided into training set(n=125,including 61 PD and 64 HC)and test set(n=31,including 15 PD and 16 HC)at the ratio of 8:2.ROI of bilateral substantia nigra,caudate nucleus,putamen,globus pallidus and thalamus were automatically delineated on mean kurtosis(MK)images of cerebral DKI.The mean MK values(MKmean)of the above ROIs were obtained and compared between groups.Support vector machine(SVM)model was constructed based on 50 selected optimal texture features.Receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of SVM model for evaluating PD.Results MKmean of bilateral substantia nigra,caudate nucleus and thalamus in PD group were all significantly lower than those in HC group(all P＜0.05).No significant difference of MKmean of bilateral putamen nor globus pallidus was found between groups(all P＞0.05).The sensitivity,specificity,accuracy and AUC of SVM model for evaluating PD in training set was 86.89％,93.75％,90.40％and 0.982,respectively,which in test set was 86.67％,93.75％,90.32％and 0.958,respectively.Conclusion DKI radiomics could be used to effectively evaluate PD through description of microstructural changes of cerebral nuclei.

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8⁺ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Objective:To analyze the risk factors for asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL) after treatment with pegaspargase and evaluate the predictive value of pediatric sequential organ failure assessment (SOFA) score, pediatric acute pancreatitis severity (PAPS) score, Ranson′s score and pediatric Ministry of Health, Labour and Welfare of Japan (JPN) score for severe AAP.Methods:Cross-sectional study.The clinical data of 328 children with ALL who received pegaspargase treatment in the Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University from January 2014 to August 2021, as well as their clinical manifestations, laboratory examinations, and imaging examinations were collected.The SOFA score at the time of AAP diagnosis, PAPS score and Ranson′s score at 48 hours after AAP diagnosis, and JPN score at 72 hours after AAP diagnosis were calculated, and their predictive value for severe AAP was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 6.7%(22/328) of children had AAP, with the median age of 6.62 years.AAP most commonly occurred in the induced remission phase (16/22, 72.7%). Three AAP children were re-exposed to asparaginase, and 2 of them developed a second AAP.Among the 22 AAP children, 16 presented with mild symptoms, and 6 with severe symptoms.The 6 children with severe AAP were all transferred to the Pediatric Intensive Care Unit (PICU). There were no significant differences in gender, white blood cell count at first diagnosis, immunophenotype, risk stratification, and single dose of pegaspargase between the AAP and non-AAP groups.The age at diagnosis of ALL in the AAP group was significantly higher than that in the non-AAP group ( t=2.385, P=0.018). The number of overweight or obese children in the AAP group was also higher than that in the non-AAP group ( χ2=4.507, P=0.034). The areas under the ROC curve of children′s JPN score, SOFA score, Ranson′s score, and PAPS score in predicting severe AAP were 0.919, 0.844, 0.731, and 0.606, respectively.The JPN score ( t=4.174, P=0.001) and the SOFA score ( t=3.181, P=0.005) showed statistically significant differences between mild and severe AAP. Conclusions:AAP is a serious complication in the treatment of ALL with combined pegaspargase and chemotherapy.Older age and overweight or obesity may be the risk factors for AAP.Pediatric JPN and SOFA scores have predictive value for severe AAP.

BACKGROUND:Satisfactory clinical results have been achieved in the treatment of Sanders Ⅲ calcaneal fractures by percutaneous compression fixation with three-dimensional frame screws.However,whether the stability of minimally invasive plate internal fixation can be achieved in terms of biomechanics,and the advantages and disadvantages after comparison are still unknown. OBJECTIVE:To investigate the fixation effect of different internal fixation devices on Sanders Ⅲ calcaneal fractures by finite element analysis. METHODS:A finite element model of Sanders Ⅲ calcaneal fracture was made based on CT data of a 26-year-old healthy male volunteer.The calcaneal fracture models were fixed by minimally invasive three-dimensional frame screws and minimally invasive Y-plate.The longitudinal loads of 350 and 700 N were applied respectively.The displacement and stress distribution of the two models were analyzed,and the stability of each model was compared. RESULTS AND CONCLUSION:(1)The peak stress of bone block and implant in the minimally invasive three-dimensional frame screw model was significantly lower than that in the minimally invasive minimally invasive plate model.The average stress of bone block and implant in the three-dimensional frame screw model was also significantly lower than that in the minimally invasive plate model.(2)The maximum displacement of the two models was located at the medial side of the articular surface of the posterior talus,and the maximum displacement of the three-dimensional frame screw model was smaller than that of the minimally invasive plate model.(3)The longitudinal displacement between the anterior fragment and the medial fragment of the minimally invasive plate model was smaller,and the transverse and vertical displacement between the medial fragment and the middle fragment of the three-dimensional group screw model was smaller.(4)It is concluded that both of the two internal fixation models can provide satisfactory fixation effect.The three-dimensional frame screw model can provide better transverse and vertical stability with more uniform stress distribution and smaller comprehensive displacement of bone fragments,while the minimally invasive plate has more advantages in maintaining longitudinal stability.

Objective:To test the validity and reliability of the Chinese version of the Pre-sleep Arousal Scale(PSAS)in patients with brief insomnia disorder(BID).Methods:Totally 170 patients with BID and 150 normal sleepers(NS)were recruited.All participants were assessed with the PSAS,Hospital Anxiety and Depression Scale(HADS)and Insomnia Severity Index(ISI).After 3 months,72 patients with BID were retested with the PSAS,HADS and ISI.Results:The PSAS scores of BID group were characteristic of a normal distribution.The PSAS total scores were positively correlated with the scores of HADS and ISI(r=0.55,0.40,Ps＜0.01).Two factors of so-matic and cognitive arousal were extracted in PSAS by the exploratory factor analysis and parallel analysis,interval variance value was 55.84％,and the load scores of items were 0.46-0.89.The scores of PSAS and its subscales were higher in the BID group than in the NS group(Ps＜0.001).The best cut-off score for the overall PSAS was found at 32/33 and had high sensitivity(0.72)and specificity(0.81).The Cronbach's α coefficient and the Spearman Brown split reliability were 0.91 and 0.76,respectively,the correlation coefficients between the items and total score ranged from 0.46 to 0.89(Ps＜0.01),and the test-retest reliability was 0.37(P＜0.01).Addi-tionally,rate of change of PSAS scores was positively correlated with the rate of change of HADS scores and ISI scores(Ps＜0.05).Conclusion:The Chinese version of PSAS is a reliable and valid instrument to assess pre-sleep arousal in patients with brief insomnia disorder.