ObjectiveTo investigate the effect and mechanism of simvastatin pretreatment on kidney ischemia reperfusion injury （IRI） in mice. MethodsFifteen male C57BL/6 mice aged 6-8 weeks were divided into three groups： Sham operation group （Sham group）， kidney IRI group （IR group）， and simvastatin pretreatment+kidney IRI group （SIM group）. Hematoxylin-eosin （HE） staining of kidney tissue and detection of serum creatinine （SCr） and lactate dehydrogenase （LDH） were used to evaluate kidney injury. The levels of superoxide dismutase （SOD）， reduced glutathione （GSH）， malondialdehyde （MDA） and reactive oxygen species （ROS） were detected to evaluate oxidative stress. The contents of ferrous iron （Fe²⁺） and ferric iron （Fe³⁺） in kidney tissue were detected， and the morphological changes of mitochondria were observed by transmission electron microscope. The relative expression levels of Kruppel-like factor 2 （KLF2）， glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， and acyl-coa synthetase long chain family member 4 （ACSL4） protein in kidney tissue were detected. ResultsCompared with the IR group， the SIM group had significantly reduced renal tubular injury and decreased contents of Scr and LDH in serum （P < 0.001）. It also showed increased expression of SOD and GSH and decreased expression of MDA and ROS （P < 0.01）. Simvastatin pretreatment reduced the contents of Fe²⁺ and Fe³⁺ in the tissues （P < 0.01） and alleviated mitochondrial damage. It also promoted the expression of KLF2 （P < 0.01）， up-regulated the expression of ferroptosis-related protective proteins GPX4 and SLC7A11， and down-regulated the expression of ferroptosis-related damage protein ACSL4 （P < 0.05）. ConclusionSimvastatin pretreatment may inhibit kidney ferroptosis by promoting the expression of KLF2 to alleviate kidney IRI.

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.

[摘 要] 目的：探讨lncRNA DLEU2通过EZH2/H3K27me3途径调控IKKα介导甲状腺癌（TC）放射性碘抵抗的作用机制。方法：利用TCGA数据库分析TC中DLEU2的表达及其与EZH2的相关性。构建放射性碘抵抗的TPC-1细胞（RR-TPC-1细胞）模型及裸鼠移植瘤模型，通过敲低或过表达DLEU2（si-DLEU2/OE-DLEU2）、抑制EZH2（UNC1999）、过表达IKKα（OE-IKKα）进行干预，采用qPCR、WB、RIP、ChIP、CCK-8、流式细胞术、TUNEL染色及体内成瘤实验检测基因与蛋白表达、表观修饰、细胞增殖、凋亡及肿瘤生长。结果：TCGA分析显示，DLEU2在TC组织中显著上调（P < 0.001），与患者不良预后相关（P = 0.008 4），且与EZH2表达呈正相关（r = 0.390, P < 0.001）；RIP证实EZH2与DLEU2存在相互作用/结合（P < 0.05）。体外实验表明，敲低DLEU2可显著下调RR-TPC-1细胞中EZH2、IKKα表达及H3K27me3修饰水平，抑制NF-κB通路活化（P < 0.05或P < 0.01），抑制细胞增殖、促进凋亡（均P < 0.05）。联合敲低DLEU2与抑制EZH2进一步增强上述效应，而过表达IKKα则可部分逆转上述效应（P < 0.05或P < 0.01）。体内实验进一步证实，敲低DLEU2联合抑制EZH2可显著抑制移植瘤生长，增加肿瘤细胞凋亡（均P < 0.01）；IKKα过表达则部分逆转上述抗肿瘤效应（P < 0.05或P < 0.01）。结论：lncRNA DLEU2通过招募EZH2催化H3K27me3修饰，间接激活IKKα/NF-κB信号并形成正反馈环路，介导TPC-1细胞131I抵抗。

Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Effective symptom management can alleviate the physical and psychological distress experienced by patients with cancer, improve quality of life, and contribute to treatment adherence and improve clinical outcomes. However, most existing guidelines are developed for healthcare professionals, and patients and the public have limited access to standardized and comprehensible guidance on symptom management. To address this gap and to facilitate effective communication and shared decision-making, this study proposes the development of a patient version of the cancer symptom management guideline. The development process will adhere to the methodological framework recommended by the Guidelines International Network and the World Health Organization. The GRADE approach will be employed to assess the certainty of evidence and to formulate recommendations. In addition, the process will be informed by the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument and the Reporting Items for Practice Guidelines in Healthcare-Public or Patient Versions of Guidelines (RIGHT-PVG). This protocol outlines the establishment of the guideline working group, the identification and prioritization of key questions, evidence retrieval and appraisal, and the formulation of recommendations, with the aim of ensuring methodological rigor and transparency in the development of the patient guideline and providing methodological reference for similar guideline initiatives.

This paper has summarized current studies on retinitis pigmentosa （RP） from two perspectives， which were disease mechanism insights from western medicine， and etiology， pathogenesis and therapeutic principles in traditional Chinese medicine （TCM）. From the perspective of western medicine， the understanding of RP has evolved from an early single-factor explanation focusing on pathogenic gene mutations to a more comprehensive， multifactorial model involving genetic abnormalities， photoreceptor cell degeneration， retinal pigment epithelium dysfunction， oxidative stress， inflammatory responses， microenvironmental imbalance， and vascular insufficiency. In TCM， RP is considered to be a disorder manifested in the eyes but rooted in dysfunction of the zang-fu （脏腑） organs. Its pathogenesis is primarily associated with congenital insufficiency， liver-kidney depletion， impaired spleen function of transportation and transformation， and stasis obstructing the meridians. The core pathological mechanism can be summarized as "deficiency complicated by stasis"， emphasizing holistic imbalance， dynamic disease progression， and syndrome differentiation and treatment. The differences and complementarities between the two medical systems in understanding disease progression are further discussed. RP is proposed to be more appropriately regarded as a complex disease characterized by long-term progression， stage-dependent evolution， and persistent decompensation. Western medicine contributes to elucidating the molecular mechanisms underlying RP and provides the foundation for targeted therapeutic interventions， whereas TCM offers a holistic perspective for understanding disease evolution through the assessment of overall functional status， disease-stage stratification， and long-term syndrome-based regulation.

This paper has summarized current studies on retinitis pigmentosa （RP） from two perspectives， which were disease mechanism insights from western medicine， and etiology， pathogenesis and therapeutic principles in traditional Chinese medicine （TCM）. From the perspective of western medicine， the understanding of RP has evolved from an early single-factor explanation focusing on pathogenic gene mutations to a more comprehensive， multifactorial model involving genetic abnormalities， photoreceptor cell degeneration， retinal pigment epithelium dysfunction， oxidative stress， inflammatory responses， microenvironmental imbalance， and vascular insufficiency. In TCM， RP is considered to be a disorder manifested in the eyes but rooted in dysfunction of the zang-fu （脏腑） organs. Its pathogenesis is primarily associated with congenital insufficiency， liver-kidney depletion， impaired spleen function of transportation and transformation， and stasis obstructing the meridians. The core pathological mechanism can be summarized as "deficiency complicated by stasis"， emphasizing holistic imbalance， dynamic disease progression， and syndrome differentiation and treatment. The differences and complementarities between the two medical systems in understanding disease progression are further discussed. RP is proposed to be more appropriately regarded as a complex disease characterized by long-term progression， stage-dependent evolution， and persistent decompensation. Western medicine contributes to elucidating the molecular mechanisms underlying RP and provides the foundation for targeted therapeutic interventions， whereas TCM offers a holistic perspective for understanding disease evolution through the assessment of overall functional status， disease-stage stratification， and long-term syndrome-based regulation.

Objective To investigate the effects of Zuogui Jiangtang Tongmai Prescription on short-chain fatty acids(SCFAs)and G protein-coupled receptor 109A(GPR109A)in diabetic atherosclerotic mice;To explore its mechanism of improving diabetic atherosclerosis.Methods ApoE-/-mice were fed with high sugar and high fat diet and intraperitoneal injection of streptozotocin to establish atherosclerosis model of diabetes.After modeling,the mice were randomly divided into the model group,Western medicine group(metformin hydrochloride+atorvastatin),and Zuogui Jiangtang Tongmai Prescription low-,medium-and high-dosage groups(19,38,76 g/kg);and the other C57BL/6J mice were set as the control group,with 6 mice in each group.Each group was given solution for gavage,once a day for 4 weeks.Blood glucose of the mice were detected,HE staining was used to observe the morphology of the aorta,TG,TC,LDL-C and HDL-C contents were detected by fully automated biochemistry analyzers,ELISA was used to detect the contents of serum HbA1c,fasting insulin(FINS),interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α,gas chromatography was used to detect the content of intestinal SCFAs,and RT qPCR and Western blot were used to detect the mRNA and protein expressions of GPR109A in ileal tissue and nuclear factor(NF)-κB p65 in aortic tissue,respectively.Results Compared with the control group,obvious plaques and inflammatory cells infiltration were seen in the aorta of the model group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL-1β,IL-6 and TNF-α contents increased(P<0.01),FINS and HDL-C content decreased(P<0.01),intestinal acetate,propionate,butyric acid,isobutyric acid and isovaleric acid contents decreased(P<0.01),GPR109A mRNA and protein expression in ileal tissue decreased,NF-κB p65 mRNA and protein expression in aortic tissue increased(P<0.01).Compared with the model group,the aortic plaque area and inflammatory cells infiltration were significantly improved in each drug intervention group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL-1β,IL-6 and TNF-α contents decreased(P<0.05,P<0.01);the FINS and HDL-C content increased(P<0.05,P<0.01),intestinal acetic,propionic,butyric acid,isobutyric acid and isovaleric acid contents increased(P<0.05,P<0.01),GPR109A mRNA and protein expression in ileal tissue increased and NF-κB p65 mRNA and protein expression in ileal tissue decreased decreased(P<0.05,P<0.01).Conclusion Zuogui Jiangtang Tongmai Prescription can improve glucolipid metabolism and inflammatory response in diabetic atherosclerotic mice,which may be related to regulating SCFAs/GPR109A pathway.

Objective To explore the role of plasma exosome microRNA-622(miR-622)in cachexia of hep-atocellular carcinoma(HCC).Methods Select preoperative blood samples from 40 patients with stage Ⅲ-ⅣHCC and 33 patients with non HCC liver benign diseases collected at Huashan Hospital,Fudan University from 2021 to 2024 as the research subjects.Exosomes were isolated from the plasma of patients,human HCC cell lines(HepG2,Hep3B,PLC,Huh7),and the culture supernatants of primary human hepatocytes(PHH)by differential centrifugation.The relative expression level of miR-622 was detected by real-time fluorescence quantitative polymerase chain reaction.The level of lipolysis was assessed by determining the concentration of glycerol and fatty acids in adipocyte culture medium.Results Plasma exosome miR-622 levels in HCC pa-tients were positively correlated with subcutaneous adipose index and visceral adipose index(r=0.516,0.539,P＜0.05).HCC cell conditional medium was able to significantly increase the lipolysis level of adipo-cytes.The relative expression levels of miR-622 in exosomes from HCC cells(HepG2,Hep3B,PLC,Huh7)were significantly lower than those in exosomes from PHH,with values of 0.13±0.04,0.28±0.08,0.23±0.07,and 0.24±0.04,respectively,compared to 1.00±0.18 in PHH exosomes.Further studies revealed that plasma exosome of HCC patients treatment was able to lead to a decrease in the relative expression level of miR-622 in adipocytes,as well as an enhancement of lipolysis.Conclusion The expression of plasma exosomal miR-622 is downregulated in HCC patients.HCC cells can deliver miR-622 to adipocytes via exosomes to reg-ulate lipolysis.Plasma exosomal miR-622 may serve as a potential biomarker for predicting HCC cachexia and a therapeutic target.

This article summarizes Professor Li Ziyong's clinical experience with the round-sharp needle.As one of the core needle types in the Huang Di Nei Jing(The Yellow Emperor's Inner Classic)nine-needle system,the round-sharp needle has long been marginalized in clinical practice due to historical discontinuities in its transmission and insufficient research on its morphological characteristics,resulting in its unique therapeutic value remaining largely unrecognized.Through nearly three decades of clinical practice,Professor Li innovatively proposed the acupuncture concept of"unblocking passages and guarding the pivotal mechanism",guided by the Yellow Emperor's Inner Classic principle that"ordinary practitioners focus on the joints,while superior practitioners focus on the pivotal mechanisms".Under this theoretical framework,he has extensively applied the round-sharp needle in clinical settings.With its unique design combining rounded and sharp features,the round-sharp needle demonstrates remarkable clinical efficacy by intervening at the fascial layer and releasing local fascial adhesions.It exhibits rapid onset and stable therapeutic outcomes.This article systematically reviews Professor Li's understanding of the round-sharp needle,its key operational techniques,and clinical case studies,aiming to establish a replicable paradigm for its modern application and promote the clinical translation of classical acupuncture theory.