OBJECTIVE To provide references for the accurate identification and management of immune-related cutaneous adverse events （irCAEs） caused by durvalumab， and ensuring safe clinical drug use. METHODS Clinical pharmacists participated in the diagnosis and treatment process of a patient with gallbladder cancer who developed irCAEs caused by durvalumab. The clinical pharmacists systematically reviewed the patient’s past medical history and medication history， and assisted physicians in assessing the association between adverse drug reactions and administered drugs. Meanwhile， the clinical pharmacists conducted a graded assessment of the adverse reaction， proposed recommendations such as discontinuing durvalumab and adjusting the administration regimen of glucocorticoids， assisted physicians in restarting immunotherapy， and carried out medication education and other pharmaceutical care. RESULTS The occurrence of irCAEs in this patient was “highly likely” related to durvalumab and was classified as severe. The physicians adopted the clinical pharmacist’s opinion， and after symptomatic treatment， the patient’s skin symptoms improved， and discharged with medication. After the completion of glucocorticoid therapy for the patient， the physician restarted immunotherapy with tislelizumab， and no related adverse reactions occurred again in the patient. CONCLUSIONS Durvalumab can cause irCAEs such as severe skin maculopapular rash. In clinical practice， it is crucial to promptly identify and discontinue suspicious drugs， immediately implement effective symptomatic treatment measures， and actively resume immunotherapy to ensure the continuity and safety of the patient’s treatment.

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.

With the deepening of population aging and the persistent decline of the fertility rate in China， assisted reproductive technology （ART） has gained increasing attention as a crucial methods of addressing infertility issues. From the perspective of Chris Shilling’s sociology of the body， this paper analyzed the multiple dimensions of females’ bodies in the field of assisted reproduction through the framework of “the body as a source of society， a locating venue of society， and a means for individuals to position themselves in society”. The results demonstrated that females’ bodies in the assisted reproductive field exhibited characteristics of multidimensional mediation. As a source of society， females’ bodies have become concrete carriers of reproductive culture and policy implementation， reflecting continuity and reconstruction of traditional fertility concepts. As a locating venue of society， females’ bodies were disciplined by medical discourse， gazed upon by the medical examinations， and affected by the unequal distribution of healthcare resources. As a means for individuals to position themselves in society， females constructed their subjectivity through active knowledge acquisition， interactive experience exchange， and proactive body management. Females in ART constructing subjectivity within structural constraints is a complex interactive process. Sociocultural expectations and medical power discipline constitute structural constraints. However， females carve out spaces for agency through various strategic practices within these constraints， achieving self-positioning and the reconstruction of meaning.

OBJECTIVE To investigate the improving effect and mechanism of Wenyang huayu formula on cerebral ischemia-reperfusion injury in rats based on nuclear factor-erythroid 2-related factor 2 （Nrf2）/glutathione peroxidase 4 （GPX4） signaling pathway and mitochondrial ferroptosis pathway. METHODS SD rats were randomly divided into sham operation group， model group，Nimodipine tablet group （10.8 mg/kg ）， and Wenyang huayu formula group （28 g/kg）， with 24 rats in each group. Except for the sham operation group， rats in other groups were all subjected to middle cerebral artery occlusion model by Longa thread occlusion method. After successful modeling， rats in each administration group were intragastrically gavaged with corresponding liquid for 7 days or 14 days， while rats in sham operation group and model group were given equal volume of normal saline once a day. At 7 and 14 days after administration， neurological deficit scores of rats were calculated； the ultrastructure of neuronal mitochondria in ischemic brain tissue of rats was observed；the contents of malondialdehyde （MDA）， glutathione （GSH） and Fe 2+ ， as well as the protein and mRNA expression levels of Nrf2， solute carrier family 7 member 11 （SLC7A11） and GPX4 in ischemic brain tissue of rats were detected. RESULTS At 7 and 14 days after administration， compared with the sham operation group， the neuronal mitochondria in ischemic brain tissue of rats in the model group showed typical changes of ferroptosis， and the injury continued to worsen over time； the neurological deficit scores， the contents of MDA and Fe 2+ were significantly increased （ P ＜0.05），while the content of GSH and the protein and mRNA expression levels of Nrf2， SLC7A11 and GPX4 were significantly decreased （ P ＜0.05）. Compared with the model group， the morphology of neuronal mitochondria in ischemic brain tissue of rats in Nimodipine tablet group and Wenyang huayu formula group was gradually improved over time， and the above quantitative indicators were significantly reversed （ P ＜0.05）；moreover， the improvement effect of most indicators in Wenyang huayu formula group was significantly better than that in Nimodipine tablet group （ P ＜0.05）. CONCLUSIONS Wenyang huayu formula can improve cerebral ischemia-reperfusion injury in rats， and its mechanism may be related to activating Nrf2/GPX4 signaling pathway and inhibiting mitochondrial ferroptosis.

BACKGROUND: Immunosuppression is closely related to the pathogenesis of sepsis, but the underlying mechanisms have not yet been fully elucidated. In this study, we aimed to examine the role of the Sterile Alpha Motif, Src Homology 3 domain and nuclear localization signal 1 (SAMSN1) in sepsis and elucidate its potential molecular mechanism in sepsis induced immunosuppression. METHODS: RNA sequencing databases were used to validate SAMSN1 expression in sepsis. The impact of SAMSN1 on sepsis was verified using gene knockout mice. Flow cytometry was employed to delineate how SAMSN1 affects immunity in sepsis, focusing on immune cell types and T cell functions. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated gene editing in RAW264.7 macrophages enabled interrogation of SAMSN1 's regulatory effects on essential macrophage functions, including cell proliferation and phagocytic capacity. The mechanism of SAMSN1 in the interaction between macrophages and T cells was investigated using the RAW264.7 cell line and primary cell lines. RESULTS: SAMSN1 expression was significantly increased in patients with sepsis and was positively correlated with sepsis mortality. Genetic deletion of Samsn1 in murine sepsis model improved T cell survival, elevated T cell cytolytic activity, and activated T cell signaling transduction. Concurrently, Samsn1 knockout augmented macrophage proliferation capacity and phagocytic efficiency. In macrophage, SAMSN1 binds to Kelch-like epichlorohydrin-associated protein 1 (KEAP1), causing nuclear factor erythroid 2-related factor 2 (NRF2) to dissociate from the KEAP1-NRF2 complex and translocate into the nucleus. This promotes the transcription of the coinhibitory molecules CD48/CD86/carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), which bind to their corresponding receptors natural killer cell receptor 2B4/CD152/T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) on the surface of T cells, inducing T-cell exhaustion. CONCLUSIONS SAMSN1 deletion augmented adaptive T cell immunity and macrophage phagocytic-proliferative dual function. Furthermore, it mediates the KEAP1-NRF2 axis, which affects the expression of coinhibitory molecules on macrophages, leading to T-cell exhaustion. This novel immunosuppression mechanism potentially provides a candidate molecular target for sepsis immunotherapy.
Animals ; NF-E2-Related Factor 2/metabolism* ; Mice ; Macrophages/immunology* ; Sepsis/metabolism* ; Kelch-Like ECH-Associated Protein 1/genetics* ; T-Lymphocytes/immunology* ; Humans ; Signal Transduction/physiology* ; RAW 264.7 Cells ; Mice, Knockout ; Mice, Inbred C57BL ; Male ; Flow Cytometry ; T-Cell Exhaustion

BackgroundIn recent years， the prevalence of obstructive sleep apnea （OSA） is escalating in China， leading to a serious disease burden. However， previous studies on the influencing factors of OSA， such as obesity and sleep position， were mostly cross-sectional studies. This approach inherently hinders the identification of dynamic interaction mechanism among multiple variables， consequently obstructing the formulation of individualized intervention strategies. ObjectiveTo investigate the differences in body mass index （BMI）-oxygen saturation-sleep position-heart rate variability （HRV） network models between OSA and non-OSA populations， thereby offering a reference for the early detection and management of OSA. MethodsA total of 384 adult participants undergoing sleep monitoring at the Affiliated Hospital of Southwest Medical University from July 12， 2022 to October 11， 2023 were included. Subjects were categorized into OSA group （n=203） and control group （n=181） based on an apnea-hypopnea index （AHI） threshold of 5 events per hour. Subsequently， BMI-oxygen saturation-sleep position-HRV networks were constructed and compared between two groups. ResultsThere was no significant difference in the overall edge weight （P=0.55） and overall strength （P=0.28） of the network model between control group and OSA group. Notable differences emerged in both the node connection strength （e.g.， minimum oxygen saturation with BMI， sleep in prone position， and mean RR interval） and node centrality indices （mean oxygen saturation， minimum oxygen saturation， AHI in upright position， AHI in right lateral position and mean heart rate） within the two network models （P<0.05）. ConclusionSignificant differences are observed between the non-OSA and OSA populations in specific factors， including sleep position， heart rate and oxygen saturation.

Objective To analyze risk factors for sleep disorders in patients with chronic heart failure(CHF)and construct a nomogram prediction model.Methods Using simple random sampling,306 hospital-ized CHF patients meeting inclusion criteria were enrolled from four Grade A tertiary hospitals in Guangxi Zhuang Autonomous Region(two in Nanning,one each in Yulin and Guilin)between March 2023 and March 2024.LASSO regression analysis was initially employed for variable screening,followed by logistic regression to identify predictive variables for constructing the nomogram model.Model validation and performance evalua-tion were conducted using receiver operating characteristic(ROC)curves,calibration curves,and clinical decision curves,with internal validation performed through Bootstrap resampling(1 000 iterations).Results The incidence of sleep disorders among the 306 patients was 57.5%(176/306).Logistic regression analysis identified eight independent risk factors for sleep disorders in CHF patients(P＜0.05):age,education level,monthly house-hold income per capita,NYHA cardiac function classification,number of comorbidities,triglyceride levels,ano-rexia,and anxiety.The model demonstrated good discrimination for the AUC of 0.91(95%CI:0.77-0.88)and calibration consistency.Conclusion The prediction model established in this study shows good predictive performance,serving as a valuable reference for healthcare providers to early identify sleep disorders and im-plement preventive care strategies in patients with CHF.

Objective To evaluate the degree of invasion of placental implantation by quantitative delin-eation of MRI placental bed abnormal hyperplasia vessels by 3D-Slicer software.Methods Fifty-seven pa-tients with placenta implantation requiring MRI in Quanzhou Maternal and Child Health Hospital from July 2020 to December 2023 were retrospectively collected and divided into the penetrating placenta implantation group(n=11)and the non-penetrating placenta implantation group(n=46),and the differences of MRI mor-phological signs between the two groups were analyzed.Among them,37 patients with placental bed xenogenic vessels scanned by MRI were screened and there were 11 cases in the penetrating placental implantation group and 26 cases in the non-penetrating placental implantation group.3D-Slicer software was used to delineate the surface area and volume of placental bed xenogenic vessels,the differences between the two groups were ana-lyzed.Results There were significant differences in the surface area and volume of xenogenic blood vessels in placental bed between the two groups(P＜0.05).The large surface area of xenogenic vessels in the placental bed was an independent risk factor for penetrative placental implantation,and the predicted area under the curve(AUC)of penetrative placental implantation was 0.927.When the surface area of the placental bed was 1 079.25 mm2,the sensitivity was 81.8%and the specificity was 88.5%.Conclusion According to 3D-Slicer soft-ware,the diagnostic efficacy of placental bed allogenic blood vessel surface area for penetrating placental implanta-tion is high.The larger the allogenic blood vessel surface area is,the deeper the placental invasion of uterus is.

Objective To analysed the related studies on varicocele in children and adolescents,and investigate the development status,research focus and frontiers in this field.Methods The literatures on varicocele in children and adolescents published between 2000 and 2023 was retrieved from Web of Science and visualized with R language software.Results A total of 684 articles were included,and the annual number of publications showed a steady growth trend.The United States ranked the first in the world and formed a core group of authors.Key words clustering showed that"semen parameters/infertility/oxidative stress","repair/ligation of spermatic vein","measurement and evaluation of testicular volume","testis and ultrasound examination","laparoscopic examination and treatment","sclerotherapy and embolization of spermatic vein"were the focus of current research.The mechanism of sperm quality decline was a research frontier.Conclusion The correlation between varicocele and male fertility in children and adolescents is a clinical problem worthy of further study.

Objective To develop a machine learning(ML)-based prediction model for assessing the therapeutic effects of resveratrol(RES)on the pathological damage of acute pancreatitis(AP),and to optimize RES administration strategies for AP through validation using an animal model.Methods AAn ML-based prediction model was constructed using published data.Interpretability analysis was applied to identify high-efficacy zones within the parameter space of administration dose and frequency,which was followed by rigorous screening to select the optimal dosing strategy that balanced therapeutic efficacy and experimental feasibility.A total of 32 C57BL/6 mice were randomly assigned to 4 groups(n=8 per group),including a control group(Ctrl),an AP model group induced by caerulein(CER)and referred to as CER-AP,a treatment group receiving RES via intraperitoneal injection(RES i.p.),and a treatment group receiving RES via intragastric gavage(RES i.g.).The Ctrl group received intraperitoneal injection of normal saline.The CER-AP and the treatment groups were induced with 10 intraperitoneal injections of CER at 50 μg/kg.RES was administered to the RES i.p.and RES i.g.groups according to the optimal dose and timing predicted by the ML model.Blood and tissue samples were collected 12 hours after the experiment started.Results The gradient boosting decision tree model,optimized via Hyperopt,yielded the best performance,predicting that the optimal dose and administration frequency were 19.992 mg/kg and 3.828 times,respectively.Accordingly,a regimen of 20 mg/kg RES,administered four times,was used in the animal experiments.Compared with the Ctrl group,the CER-AP group exhibited higher pancreatic pathology scores and elevated levels of serum amylase,lipase,pancreatic myeloperoxidase,and trypsin,with all differences reaching statistical significance(all P<0.05).The administration of 20 mg/kg RES via both intraperitoneal injection and intragastric gavage mitigated pancreatic inflammatory cell infiltration and necrosis,improved the overall pathology score,and reduced serum amylase,lipase,and pancreatic myeloperoxidase levels to varying degrees(all P<0.05).Conclusion A regimen of 20 mg/kg RES administered four times effectively alleviates the severity of CER-induced AP.The therapeutic benefits appear to arise from a multi-target regulatory network that simultaneously suppresses inflammatory cascades,mitigates oxidative stress,and reduces apoptosis,thereby reducing pancreatic tissue damage and systemic inflammatory responses.