Cardiomyopathy, Dilated ; etiology ; pathology ; therapy ; Humans ; Myocardium ; pathology

Abstract: Objective　To investigate the cause of poisoning leading to multi-organ damage in a patient with an unexplained condition, to confirm the type and exposure amount of the pathogenic factor, to identify the sources of pathogenic factors, and to provide references and bases for the clinical treatment and the prevention of such events. Methods　Starting with the unknown traditional Chinese medicine taken by patients for a long time, the targeted screening strategy was initially used to screen for alkaloid poisoning. Subsequently, a non-targeted screening strategy using Information-dependent Acquisition Mode (IDA) was used to screen the patient's blood, urine, and drug samples. Combining the toxicological effects of suspected compounds with the patient′s clinical manifestations, the main pathogenic factors were determined. Quantitative methods were established according to standard substances to quantify the pathogenic factors in all the samples. An epidemiological investigation was conducted to obtain the patient's medication history, and combined with the examination of the medication's specifications and content, the exposure dose of each pathogenic factor was determined. Finally, a Data data-independent acquisition (DIA) mode termed Sequential Window Acquisition of All Theoretical Fragment-Ion Spectra (SWATH) was used to screen all samples, unbiasedly collecting secondary mass spectrometry information of compounds, thereby verifying and supplementing the confirmed pathogenic factors. Results　Targeted screening ruled out common alkaloid poisoning. Tadalafil was detected in the patient's blood and urine. Tadalafil, sildenafil, chloropretadalafil, acetaminophen, and diclofenac were detected in unknown traditional Chinese medicine. The side effects of these compounds were consistent with the clinical manifestations of the patient. The highest daily average exposure doses of tadalafil, sildenafil, chloropretadalafil, acetaminophen, and diclofenac were 30.5 mg, 15.8 mg, 0.05 mg, 45.6 mg, and 3.2 mg respectively, which were seriously excessive. The SWATH mode also screened out the above five drugs. In addition, palmatine chloride was also detected. Conclusions　Combining the patient's clinical manifestations and epidemiological data, this study integrated targeted screening, untargeted screening, targeted quantitative strategies, data-dependent, and DIA mode to confirm that this case is a drug poisoning event caused by long-term overdose consumption of traditional Chinese medicine adulterated with chemical components. This study provides insights for the diagnosis and investigation of patients with poisoning for unknown causes, offering references for emergency detection and management of related poisoning incidents.

Factor VII Deficiency ; genetics ; Humans

Objective: To investigate the expressions of signal transducer and activators of transcription 3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) protein in the breast carcinoma tissue and their relationship with tumor differentiation, invasion, and metastasis. Methods: The expression of STAT3, phospho-STAT3 and SOCS3 protein were determined by tissue microarray and immunohistochemistry with EnVision system in 71 cases of archival breast carcinoma tissues and 41 cases of noncancerous tissues. The relationship between their expression and the clinical pathological parameters were analyzed. Results: (1) The positive rates of STAT3, phospho-STAT3, and SOCS3 was 78.9%, 69.0%, and 29.6%, respectively. The difference was significantly different compared with control (P<0.01, P<0.01, and P<0.05). (2) The expressions of STAT3 and phospho-STAT3 were positively related with the histological grade, the axillary lymph node metastasis, and the clinical stage (P<0.01), but not related with the age, the tumor size, and the histological grade of breast carcinoma tissues (P>0.05). The expression of SOCS3 was negatively related with the histopathologic grade and the axillary lymph node metastasis (P<0.05), but was not related with the age, histological type, the tumor size, and the clinical stage (P>0.05). (3) The expression of STAT3 and phospho-STAT3 had negative correlation with the expression of SOCS3 in breast carcinoma tissues (P<0.01). Conclusion: The overexpressions of STAT3 and phospho-STAT3 and the down-regulated expression of SOCS3 closely correlated with the tumor carcinogenesis, progression, invasion, and metastasis of breast carcinoma. Detection of their expression is helpful in accessing the malignant degree and the biological behaviors of breast carcinoma.

Animals ; Aortitis ; pathology ; Biopsy ; Dendritic Cells ; pathology ; Diagnosis, Differential ; Giant Cell Arteritis ; drug therapy ; etiology ; metabolism ; pathology ; Glucocorticoids ; therapeutic use ; Humans ; Interleukin-12 ; metabolism ; Oxidative Stress ; Polymyalgia Rheumatica ; pathology ; Temporal Arteries ; pathology

Angiogenesis Inducing Agents ; metabolism ; Angiogenesis Inhibitors ; therapeutic use ; Animals ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; therapeutic use ; Bevacizumab ; Drug Delivery Systems ; Endostatins ; therapeutic use ; Humans ; Neoplasms ; drug therapy ; Neovascularization, Pathologic ; drug therapy ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; physiology ; Vascular Endothelial Growth Factors ; metabolism ; physiology

Cytokines ; Hashimoto Disease ; diagnosis ; prevention & control ; Humans

Child ; Female ; Humans ; Polyendocrinopathies, Autoimmune ; classification ; diagnosis ; therapy ; Treatment Outcome

Animals ; Cell Cycle Proteins ; biosynthesis ; genetics ; Cell Differentiation ; Cell Line, Tumor ; metabolism ; Gene Expression Regulation, Neoplastic ; drug effects ; Genes, Tumor Suppressor ; Humans ; Intracellular Signaling Peptides and Proteins ; Molecular Sequence Data ; Neoplasm Metastasis ; RNA, Messenger ; biosynthesis ; genetics ; Tretinoin ; pharmacology

Objective To study the effects and current mechanism of low concentration of lidocaine on evoked-bursting (EB) firing of dorsal root ganglion (DRG) neurons in rat model of chronic compression (CCD) of DRG . Methods Twenty-four SD rats were divided into normal control group (n=12) and CCD model group (n=12). CCD group was treated with chronic oppression on L4 and L5 DRG with L shape bar. Normal control group received no treatment. In vivo intracellu?lar recording was used to record the incidence of EB and the effect of lidocaine on subthreshold membrane potential oscilla?tion (SMPO). Patch clamp recording was used to record the effect of lidocaine on persistent sodium current (INaP). Results The incidence of EB increased in CCD group( 45.97%, 57/124), which was significantly different when compared with nor?mal group (χ2=26.810, P<0.01). The magnitude of SMPO, INaP and EB were inhibited in a reversible way by lidocaine (50μmol/L). Conclusion The low concentration of lidocaine might play an analgesic effect in peripheral nervous system by se?lectively inhibiting INap, which participates in SMPO formation.