ObjectiveTo observe the effect of Qishao capsules on renal injury in db/db mice with diabetic kidney disease （DKD），and explore its mechanism of protecting the kidney by inhibiting podocyte apoptosis. Methodsdb/m mice （7 mice） were used as the normal group，and db/db mice （35 mice） were randomly divided into a model group，a dapagliflozin group （0.001 g·kg^-1·d^-1），and low-，medium-，and high-dose groups of Qishao capsules （0.341 3，0.682 5，and 1.365 g·kg^-1·d^-1，respectively）. Drug intervention lasted for 8 consecutive weeks. After sampling，the serum renal function indicators ［creatinine（SCr），and urea nitrogen（BUN）］，fasting blood glucose （FBG），24 h urinary protein quantification （24 h-UTP）， and other indicators of the mice were measured. The pathological tissue morphology of the kidney was observed by periodic acid-silver methenamine （PASM） and Masson's trichrome （Masson） staining. Immunohistochemical detection of cysteine-dependent aspartate-specific protease （Caspase）-3 and B-cell lymphoma 2 （Bcl-2） was performed. Western blot was used to detect the protein expression of Caspase-8，Caspase-7，Caspase-3， and other molecules. Terminal deoxynucleotidyl transferase dUTP nick End labeling （TUNEL） staining was used to observe apoptosis in renal tissue. Immunofluorescence staining of Wilms tumor suppressor gene-1 （WT-1） was used to observe podocyte injury. Real-time polymerase chain reaction （Real-time PCR） was employed to detect Caspase-8 and Caspase-3 mRNA expression in the kidneys of experimental mice. Data analysis was conducted using statistical software GraphPad Prism 10. ResultsCompared with the normal group，the model group showed significantly increased 24 h-UTP，SCr，BUN，and FBG （P<0.01）. Additionally， PASM staining of renal tissue showed increased glycogen deposition，glomerular hypertrophy，and thickening of the basement membrane. Masson staining showed collagen fiber proliferation in renal tissue. Transmission electron microscopy showed thickening of the renal tissue basement membrane and fusion or loss of foot processes in the model group. The immunohistochemical results showed that Caspase-3 in the kidneys of the mice in the model group significantly increased （P<0.01），while the Bcl-2 protein expression level decreased significantly （P<0.01）. The number of TUNEL positive cells in renal tissue significantly increased （P<0.01）. The positive expression of WT-1 in podocytes was significantly reduced （P<0.01）. Western blot analysis showed significant upregulation of Caspase-8，Caspase-7，and Caspase-3 protein expression in renal tissue （P<0.01）. The mRNA expression levels of Caspase-8 and Caspase-3 in the kidneys increased significantly （P<0.01）. Compared with the model group，the Qishao capsules groups can significantly reduce the levels of 24 h-UTP，SCr，BUN，and FBG （P<0.01）. The pathological damage of renal tissue and podocyte injury were improved to some extent. Immunohistochemistry in the kidney showed a significant decrease in Caspase-3 （P<0.01） and a significant increase in Bcl-2 protein expression level （P<0.01）. Additionally， there were a significant decrease in the number of TUNEL positive cells in renal tissue （P<0.01），a significant increase in WT-1 positive expression in podocytes （P<0.01），marked downregulation of Caspase-8，Caspase-7，and Caspase-3 protein expression in renal tissue （P<0.05，P<0.01），and a significant decrease in Caspase-8 and Caspase-3 mRNA expression levels （P<0.01）. ConclusionQishao capsules can inhibit podocyte apoptosis by regulating the expression of Caspase-8，Caspase-7， and Caspase-3，thereby improving the diabetic renal injury in db/db mice.

Introduction: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a predilection for metastasis to the liver, lungs, and lymph nodes. Bone involvement is less common and typically occurs alongside widespread disease. Isolated skeletal progression without visceral involvement is unusual and not well characterized. Case: A 60-year-old female underwent left adrenalectomy in 2019 for an incidentally detected adrenal mass, which was reported as a benign adrenal cortical adenoma (Ki67 <3%). In 2022, she presented with persistent low back pain. Imaging demonstrated fluorodeoxyglucoseavid lesions involving the T12 vertebra and right ilium, without evidence of local recurrence or visceral metastases. Histopathological evaluation of a bone biopsy initially suggested a neuroendocrine neoplasm based on synaptophysin positivity. Following multiple expert reviews and integration of clinical, radiological, and immunohistochemical findings, a consensus diagnosis of metastatic ACC was established. She received palliative radiotherapy to symptomatic skeletal sites and subsequently completed six cycles of etoposide, doxorubicin, and cisplatin chemotherapy in 2023, achieving disease stabilization. Surveillance imaging in May 2025 demonstrated progression confined to the axial and appendicular skeleton, with no involvement of the adrenal bed or visceral organs. Mitotane therapy was initiated in December 2025. Ongoing management focuses on systemic disease control, symptom palliation, and multidisciplinary supportive care. Conclusion This case illustrates an uncommon pattern of ACC progression characterized by bone-dominant metastases in the absence of visceral disease. It also highlights the importance of reconsidering the initial histopathological diagnosis when clinical behavior is discordant. Vigilance for atypical metastatic patterns is warranted, even years after resection of an adrenal lesion initially classified as benign.
Adrenocortical Carcinoma

Introduction: Thyroid hormone resistance syndrome (THR) is a disorder characterized by reduced responsiveness of target tissues to thyroid hormones with non-suppressed thyroidstimulating hormone (TSH) despite elevated free thyroxine 4 (FT4). Diagnosing and managing THR in athyreotic patients, however, is challenging; indeed, TSH levels post thyroidectomy for Differentiated Thyroid Carcinoma in patients with THR have been reported to reach levels as high as 112.59 mIU/L despite high-dose thyroxine-suppressive therapy. This case highlights the complexities in diagnosing Resistance to Thyroid Hormone (RTH) post-thyroidectomy. Case: A 63-year-old female with end-stage renal failure (ESRF) on hemodialysis and prior parathyroidectomy for tertiary hyperparathyroidism underwent total thyroidectomy in 1997 for presumed benign goiter. Following surgery, she demonstrated persistently elevated TSH, ranging from 93.2 to 670.4 mIU/L (0.55–4.78 mIU/L), with normal to mildly elevated FT4 levels, ranging from 17 to 35 pmol/L (11.5–22.7 pmol/L), while on thyroxine replacement doses as low as 0.86 ug/kg. Discordant thyroid function tests (TFTs) were consistent across different assay platforms. Polyethylene glycol precipitation excluded macro-TSH interference. Intermittent levothyroxine increments suppressed TSH but led to thyrotoxic symptoms, including weight loss, heat intolerance, insomnia, and fragility fracture. Uncontrasted pituitary magnetic resonance imaging (risk of nephrogenic systemic fibrosis with gadolinium in ESRF) showed a small pituitary gland without adenoma, excluding TSH-oma. T3 suppression test was relatively contraindicated due to her advanced age and co-morbidities. There was no family history of thyroid disorder; the patient’s only child had a normal TFT, and her parents/siblings could not be tested. A working diagnosis of RTHβ was made. She declined genetic testing for RTH. She is currently on levothyroxine 50 mcg OD (1.07 ug/kg) with FT4 16.1 pmol/L and TSH 562 mIU/L with no symptoms/signs of hypo or hyperthyroidism. Conclusion This case highlights the diagnostic challenges in managing possible RTHβ post-total thyroidectomy. Treatment should be guided by clinical status and target of mid-to-normal FT4 rather than TSH to avoid iatrogenic thyrotoxicosis.
Thyroidectomy ; Thyroid Hormones

AIM To compare the chemical constituents in traditional decoction and formula granule decoction of classical famous prescription Wendan Decoction.METHODS The HPLC fingerprints were established,after which the contents of adenosine,synephrine,liquiritin,naringin,hesperidin,6-gingerol and adenosine cyclophosphate were determined,cluster analysis,principal component analysis and multidimensional scaling analysis were adopted in the investigation of component differences,and the equivalent of formula granules was adjusted.RESULTS The similarities of HPLC fingerprints for 10 batches of traditional decoctions were higher than those of HPLC fingerprints for 9 batches of formula granule decoctions(P＜0.01).Adenosine,synephrine,liquiritin,hesperidin and cyclic adenosine monophosphate demonstrated higher contents in traditional decoctions than those in formula granule decoctions(P＜0.05),6-gingerol displayed lower content than that in the latter produced by manufacturers A,C(P＜0.05),which was higher than that in the latter produced by manufacturer B(P＜0.01).Various batches of traditional decoctions and formula granule decoctions could be obviously distinguished,adenosine,synephrine and hesperidin exhibited great influences on the classification of principal component analysis,and the quality of formula granule decoctions produced by manufacturer C was closer to that of traditional decoctions.After equivalent correction,the contents of various constituents in formula granule decoctions produced by manufacturers A,C showed no significant differences as compared with those in traditional decoction(P＞0.05).CONCLUSION The formula granules of Wendan Decoction from different manufacturers exist quality differences,so the preparation process and extraction process of this preparation should be optimized to improve quality,and equivalent ratio should be adjusted according to actual requirements to ensure its scientific and rational clinical application.

Objective:To examine the roles played by peer attachment and cognitive fusion in the association between negative life events and depression,as well as the differences in these relationships of variables among pri-mary and secondary school students.Methods:A total of 2 767 students(1 950 elementary school students and 817 middle school students)were selected.The Adolescent Life Events Scale,the Experiences in Close Relationships-Relationship Structures Questionnaire,the Cognitive Fusion Questionnaire,and the Patient Health Questionnaire were used to measure negative life events,peer attachment,cognitive fusion,and depression,respectively.Results:Negative life events,peer attachment,cognitive fusion and depression were positively correlated with each other(r=0.36-0.75,Ps＜0.001);the mediation effects of peer attachment and cognitive fusion and their chain mediation effects were 0.04,0.30,and 0.04,respectively,accounting for 6.7％,50％,and 6.7％of the total effect.There were significant differences in the chain mediation model between primary and secondary school students(△x2=47.12,△df=6,P＜0.001),and significant gender differences in the chain mediation effect among primary school students(△x2=43.72,△df=6,P＜0.001).Conclusion:Negative life events influence depression in primary and secondary school students both directly and indirectly through peer attachment and cognitive fusion.Negative life e-vents have greater impact on primary school students'(particularly girls)peer attachment.Peer attachment has grea-ter impact on secondary school students' cognitive fusion.Cognitive fusion has greater impact on primary school students' depression.Peer attachment has greater impact on primary school boys' depression.

Purpose This study aimed to evaluate the consistency of human epidermal growth factor receptor 2(HER2)status between primary breast cancer lesions and lung metastatic lesions and to establish a prognostic model for predicting the survival rate of HER2 low expression(HER2-low)breast cancer patients with lung metastasis.Methods Clinicopathological data from a cohort of 252 patients with breast cancer and lung metastasis were retrospec-tively analyzed.Results 50.00％of the patients had HER2-low expression in metastatic lesions,and HER2-low ex-pression was the most prevalent subgroup in both primary and metastatic lesions.A discordance in HER2 status be-tween primary and metastatic sites was observed in 28.07％of cases.The most frequent shift was from HER2-zero in the primary tumor to HER2-low expression in the metastasis(12.28％of all cases).Estrogen receptor(ER)status,menopausal status,and histological type were identified as independent prognostic factors for overall survival(OS)by univariate and multivariate Cox regression analyses.A prognostic model incorporating these factors was constructed to predict 3-year and 5-year survival.The model demonstrated area under the curve(AUC)values of 0.765 and 0.780 for 3-year and 5-year OS in the training cohort,and 0.667 and 0.706 in the validation cohort,respectively.Conclu-sion HER2-low expression is the most common subtype among breast cancer patients with lung metastasis.The ob-served shift from HER2-zero in primary lesions to HER2-low in metastases underscores the clinical necessity of re-biop-sy at metastatic sites.The developed prognostic model effectively predicts OS in this patient population.

Naringin is a flavonoid compound with a wide range of biological and pharmacologi-cal activities,which can be used in treating tumor,diabetes,neurodegenerative diseases,cardiovascu-lar diseases,metabolic syndrome,etc.Among them,the application of naringin in cardiovascular diseases has attracted the attention of many re-searchers.This article mainly reviews the role of naringin in cardiovascular disease(regulating blood lipids,anti atherosclerosis,lowering blood pres-sure,inhibiting myocardial hypertrophy,anti myo-cardial infarction,protecting myocardial ischemia/reperfusion injury,reducing myocardial ischemia/reperfusion injury and improving pulmonary arteri-al hypertension),the protective effect on cardiotox-icity,and the signal pathways in cardiovascular dis-ease(PI3K-Akt-mTOR,p-eNOS/p-Akt/p-ERK,miR-126/GSK-3 β/β-Catenin),clinical trials,etc.This pa-per is expected to review the current research sta-tus of naringin in cells and animal models so as to reveal its clinical application prospects and provide reference for further research in related fields.

MicroRNA(miRNA),an important type of non-coding RNAs existing widely in viruses and eukaryotes,regulate gene expression at transcriptional and post-transcriptional levels.Recent studies have demonstrated that plant miRNAs could enter microorganisms,animals and human bodies to affect their physiological and pathological processes by cross-kingdom regulation of gene expression.This review summarized the current knowledge of cross-kingdom regulation of gene expression by plant miRNAs,introduced the research progress in intervention of human diseases with plant miRNAs,including anti-virus,anti-tumor,anti-inflammation,immune regulation,anti-fatigue,anti-fibrosis,vascular protection,nerve protection,etc.,and analyzed the reasons why plant miRNAs remain stable in vivo and in vitro and the underlying mechanisms how they regulate human gene expression.Furthermore,the impact of cross-kingdom regulation by plant miRNAs on exploring new active ingredients of traditional Chinese herbs and elucidating their pharmacology were evaluated.Finally,"constructing the complex regulatory network of traditional Chinese medicine miRNAs in human body"and"exploring new mechanisms of gene expression regulation by traditional Chinese medicine miRNAs"were pointed out,which were two scientific problems worthy of further investigation.

Objective:To examine the roles played by peer attachment and cognitive fusion in the association between negative life events and depression,as well as the differences in these relationships of variables among pri-mary and secondary school students.Methods:A total of 2 767 students(1 950 elementary school students and 817 middle school students)were selected.The Adolescent Life Events Scale,the Experiences in Close Relationships-Relationship Structures Questionnaire,the Cognitive Fusion Questionnaire,and the Patient Health Questionnaire were used to measure negative life events,peer attachment,cognitive fusion,and depression,respectively.Results:Negative life events,peer attachment,cognitive fusion and depression were positively correlated with each other(r=0.36-0.75,Ps＜0.001);the mediation effects of peer attachment and cognitive fusion and their chain mediation effects were 0.04,0.30,and 0.04,respectively,accounting for 6.7％,50％,and 6.7％of the total effect.There were significant differences in the chain mediation model between primary and secondary school students(△x2=47.12,△df=6,P＜0.001),and significant gender differences in the chain mediation effect among primary school students(△x2=43.72,△df=6,P＜0.001).Conclusion:Negative life events influence depression in primary and secondary school students both directly and indirectly through peer attachment and cognitive fusion.Negative life e-vents have greater impact on primary school students'(particularly girls)peer attachment.Peer attachment has grea-ter impact on secondary school students' cognitive fusion.Cognitive fusion has greater impact on primary school students' depression.Peer attachment has greater impact on primary school boys' depression.

Purpose This study aimed to evaluate the consistency of human epidermal growth factor receptor 2(HER2)status between primary breast cancer lesions and lung metastatic lesions and to establish a prognostic model for predicting the survival rate of HER2 low expression(HER2-low)breast cancer patients with lung metastasis.Methods Clinicopathological data from a cohort of 252 patients with breast cancer and lung metastasis were retrospec-tively analyzed.Results 50.00％of the patients had HER2-low expression in metastatic lesions,and HER2-low ex-pression was the most prevalent subgroup in both primary and metastatic lesions.A discordance in HER2 status be-tween primary and metastatic sites was observed in 28.07％of cases.The most frequent shift was from HER2-zero in the primary tumor to HER2-low expression in the metastasis(12.28％of all cases).Estrogen receptor(ER)status,menopausal status,and histological type were identified as independent prognostic factors for overall survival(OS)by univariate and multivariate Cox regression analyses.A prognostic model incorporating these factors was constructed to predict 3-year and 5-year survival.The model demonstrated area under the curve(AUC)values of 0.765 and 0.780 for 3-year and 5-year OS in the training cohort,and 0.667 and 0.706 in the validation cohort,respectively.Conclu-sion HER2-low expression is the most common subtype among breast cancer patients with lung metastasis.The ob-served shift from HER2-zero in primary lesions to HER2-low in metastases underscores the clinical necessity of re-biop-sy at metastatic sites.The developed prognostic model effectively predicts OS in this patient population.