Objective:To establish a pure water direct dilution-inductively coupled plasma mass spectrometry (ICP-MS) detection method for rapid determination of urinary iodine.Methods:Pure water was used to directly dilute the urine samples. The washing solution was 5.0 g/L ascorbic acid, the internal standard solution was 5.0 g/L ascorbic acid and 100 μg/L 128Te, the standard solution was prepared with the solution of lyophilized urine iodine biological component analysis reference material. The method was evaluated in terms of linear range, detection limit, quantification limit, precision and method comparision experiment. Results:The linear correlation coefficient of the standard curve for iodine concentration range from 0 to 50.0 μg/L was 0.999 7, with a detection limit of 0.2 μg/L and a quantification limit of 0.6 μg/L. The spiked recovery rates of low, medium, and high concentration iodine standard solutions added to actual urine samples were 100.8%, 99.1% and 99.7%, respectively, with relative standard deviations of 0.8%, 1.3% and 1.6%, respectively. There was no statistically significant difference ( t = - 0.14, P = 0.890) between the results of measuring actual urine and assessment urine using this method and "Determination of Iodine in Urine-Part 2: Inductively Coupled Plasma Mass Spectrometry (WS/T 107.2-2016)". Conclusions:We have successfully established a pure water direct dilution-ICP-MS method for determining urinary iodine. This method provides accurate and highly sensitive results, making it suitable for sudden public health emergencies and large-scale clinical measurement of urinary iodine.

Objective:To establish a pure water direct dilution-inductively coupled plasma mass spectrometry (ICP-MS) detection method for rapid determination of urinary iodine.Methods:Pure water was used to directly dilute the urine samples. The washing solution was 5.0 g/L ascorbic acid, the internal standard solution was 5.0 g/L ascorbic acid and 100 μg/L 128Te, the standard solution was prepared with the solution of lyophilized urine iodine biological component analysis reference material. The method was evaluated in terms of linear range, detection limit, quantification limit, precision and method comparision experiment. Results:The linear correlation coefficient of the standard curve for iodine concentration range from 0 to 50.0 μg/L was 0.999 7, with a detection limit of 0.2 μg/L and a quantification limit of 0.6 μg/L. The spiked recovery rates of low, medium, and high concentration iodine standard solutions added to actual urine samples were 100.8%, 99.1% and 99.7%, respectively, with relative standard deviations of 0.8%, 1.3% and 1.6%, respectively. There was no statistically significant difference ( t = - 0.14, P = 0.890) between the results of measuring actual urine and assessment urine using this method and "Determination of Iodine in Urine-Part 2: Inductively Coupled Plasma Mass Spectrometry (WS/T 107.2-2016)". Conclusions:We have successfully established a pure water direct dilution-ICP-MS method for determining urinary iodine. This method provides accurate and highly sensitive results, making it suitable for sudden public health emergencies and large-scale clinical measurement of urinary iodine.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

BACKGROUND: Epoxyeicosatrienoic acids (EETs), which are metabolites of arachidonic acid catalyzed by cytochrome P450 epoxygenase, are degraded into inactive dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Many studies have revealed that sEH gene deletion exerts protective effects against diabetes. Vascular calcification is a common complication of diabetes, but the potential effects of sEH on diabetic vascular calcification are still unknown. METHODS: The level of aortic calcification in wild-type and Ephx2-/- C57BL/6 diabetic mice induced with streptozotocin was evaluated by measuring the aortic calcium content through alizarin red staining, immunohistochemistry staining, and immunofluorescence staining. Mouse vascular smooth muscle cell lines (MOVAS cells) treated with β-glycerol phosphate (0.01 mol/L) plus advanced glycation end products (50 mg/L) were used to investigate the effects of sEH inhibitors or sEH knockdown and EETs on the calcification of vascular smooth muscle cells, which was detected by Western blotting, alizarin red staining, and Von Kossa staining. RESULTS: sEH gene deletion significantly inhibited diabetic vascular calcification by increasing levels of EETs in the aortas of mice. EETs (especially 11,12-EET and 14,15-EET) efficiently prevented the osteogenic transdifferentiation of MOVAS cells by decreasing nidogen-2 (NID2) expression. Interestingly, suppressing sEH activity by small interfering ribonucleic acid or specific inhibitors did not block osteogenic transdifferentiation of MOVAS cells induced by β-glycerol phosphate and advanced glycation end products. NID2 overexpression significantly abolished the inhibitory effect of sEH gene deletion on diabetic vascular calcification. Moreover, NID2 overexpression mediated by adeno-associated virus 9 vectors markedly increased insulin-like growth factor 2 (IGF2) and phospho-ERK1/2 expression in MOVAS cells. Overall, sEH gene knockout inhibited diabetic vascular calcification by decreasing aortic NID2 expression and, then, inactivating the downstream IGF2-ERK1/2 signaling pathway. CONCLUSIONS sEH gene deletion markedly inhibited diabetic vascular calcification through repressed osteogenic transdifferentiation of vascular smooth muscle cells mediated by increased aortic EET levels, which was associated with decreased NID2 expression and inactivation of the downstream IGF2-ERK1/2 signaling pathway.
Animals ; Mice ; Vascular Calcification/metabolism* ; Mice, Inbred C57BL ; Epoxide Hydrolases/metabolism* ; Diabetes Mellitus, Experimental/genetics* ; Male ; Gene Deletion ; MAP Kinase Signaling System/genetics* ; Cell Line ; Immunohistochemistry ; Muscle, Smooth, Vascular/metabolism* ; Signal Transduction/genetics* ; Mice, Knockout

Objective:To explore the characteristics and mechanism of Chinese herbs with fertility toxicity.Methods:Chinese herbs with reproductive toxicity, developmental toxicity and genetic toxicity were retrieved from Traditional Chinese Medicine System Toxicology Database. The property, taste, meridian tropism, toxicity classification and performance, and the toxic component and action target of each medicinal material were collected and descriptive statistical analysis was performed.Results:A total of 55 kinds of Chinese herbs with fertility toxicity were screened out. They were mostly warm [20 (36.4%)] or cold [15 (27.3%)] in property, and mostly bitter and pungent in taste [bitter-pungent, bitter, and pungent accounted for 30.9% (17/55), 23.6% (13/55) and 18.2% (10/55)]. The channel tropisms were mainly liver, lung, spleen, and kidney [58.2% (32/55), 38.2% (21/55), 38.2% (21/55) and 34.5% (19/55)], and the main manifestations of its reproductive toxicity were reproductive function damage in males and females, abnormal embryonic growth and development and genetic/cytotoxicity, which might lead to reduced pregnancy rate, miscarriage, abnormal fetal growth and development, etc. There were 29 kinds of Chinese herbs with 35 known fertility toxic components. Among them, 30 toxic components had 11 known toxic targets. The more common toxic targets included thyroid hormone receptor beta, cytochrome P450 1A1, sex hormone-binding globulin and interleukin-1 beta.Conclusions:Chinese herbs with fertility toxicity are mostly warm or cold in property, and bitter and pungent in taste; their channel tropisms are mainly liver, lung, spleen and kidney; they mainly affect fertility and embryonic development by changing the body′s endocrine and interfering with sex hormone metabolism.

Objective:To explore the characteristics and mechanism of Chinese herbs with fertility toxicity.Methods:Chinese herbs with reproductive toxicity, developmental toxicity and genetic toxicity were retrieved from Traditional Chinese Medicine System Toxicology Database. The property, taste, meridian tropism, toxicity classification and performance, and the toxic component and action target of each medicinal material were collected and descriptive statistical analysis was performed.Results:A total of 55 kinds of Chinese herbs with fertility toxicity were screened out. They were mostly warm [20 (36.4%)] or cold [15 (27.3%)] in property, and mostly bitter and pungent in taste [bitter-pungent, bitter, and pungent accounted for 30.9% (17/55), 23.6% (13/55) and 18.2% (10/55)]. The channel tropisms were mainly liver, lung, spleen, and kidney [58.2% (32/55), 38.2% (21/55), 38.2% (21/55) and 34.5% (19/55)], and the main manifestations of its reproductive toxicity were reproductive function damage in males and females, abnormal embryonic growth and development and genetic/cytotoxicity, which might lead to reduced pregnancy rate, miscarriage, abnormal fetal growth and development, etc. There were 29 kinds of Chinese herbs with 35 known fertility toxic components. Among them, 30 toxic components had 11 known toxic targets. The more common toxic targets included thyroid hormone receptor beta, cytochrome P450 1A1, sex hormone-binding globulin and interleukin-1 beta.Conclusions:Chinese herbs with fertility toxicity are mostly warm or cold in property, and bitter and pungent in taste; their channel tropisms are mainly liver, lung, spleen and kidney; they mainly affect fertility and embryonic development by changing the body′s endocrine and interfering with sex hormone metabolism.

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

Purpose The aim of this study is to explore the application value of ALK(1A4)in ALK fused non-small cell lung cancer(NSCLC).Methods A total of 1 035 NSCLC specimens were collected.The expression of ALK(1A4)and ALK(D5F3)antibodies was detected by immunohistochemical(IHC)staining,and their consistency was analyzed.FISH and next-generation sequencing(NGS)were used to detect ALK positive,and the sensitivity and specificity of ALK in the two groups were evaluated.Results ALK fused NSCLC patients accounted for about 5.4％(56/1 035).The positive rate of ALK(1A4)was 7.2％(75/1 035),and that of ALK(D5F3)was 5.7％(59/1 035).The consistency between them was high,with a Kappa value of 0.874.The consistency of ALK(1A4)and ALK(D5 F3)antibodies with FISH was high,with Kappa values of 0.845 and 0.954,respectively.The consisten-cy of ALK(1A4)and ALK(D5F3)with NGS was also high,with Kappa values of 0.836 and 0.988,respectively.According to the FISH results,the sensitivities of ALK(1A4)and ALK(D5F3)antibodies were 100％and 98.2％,and the specifici-ties were 98.1％and 99.6％,respectively.Conclusion ALK(1A4)antibody has high sensitivity and slightly low specificity,and can be used for clinical screening of ALK fused NSCLC.

Objective:To investigate the effect of transcatheter arterial chemoembolization (TACE) combined with ultrasound-guided radiofrequency ablation (RFA) on the efficacy and immune function in patients with primary liver cancer.Methods:The clinical data of 152 patients with primary liver cancer from February 2019 to February 2021 in the Second Affiliated Hospital of Xi′an Jiaotong University were retrospectively analyzed. Among them, 76 patients were treated with TACE combined with RFA (combined group), and 76 patients were treated with TACE (control group). The efficacy was compared; the α-L fucosidase, T lymphocyte subsets (CD 3, CD 4, CD 8 and CD 4/CD 8), B lymphocyte subsets (CD 19) and tumor markers (alpha-fetoprotein, AFP; carcinoembryonic antigen, CEA; carbohydrate antigen 125, CA125) before treatment and 1 month after treatment were detected. Results:The total clinical effective rate in combined group was significantly higher than that in control group: 81.58% (62/76) vs. 52.63% (40/76), and there was statistical difference ( χ2 = 4.54, P<0.05). There were no statistical difference in all indexes before treatment between 2 groups ( P>0.05); the α-L fucosidase, AFP and CD 8 1 month after treatment in combined group were significantly lower than those in control group: (18.06 ± 5.33) U/L vs. (26.58 ± 7.75) U/L, (87.93 ± 22.55) μg/L vs. (146.83 ± 21.85) μg/L and 0.295 ± 0.052 vs. 0.367 ± 0.064, the CD 3, CD 4 and CD 4/CD 8 were significantly higher than those in control group (0.489 ± 0.054 vs. 0.462 ± 0.063, 0.363 ± 0.059 vs. 0.303 ± 0.075 and 1.43 ± 0.27 vs. 0.89 ± 0.14), and there were statistical differences ( P<0.01 or<0.05); there was no statistical difference in CEA, CA125 and CD 19 1 month after treatment between 2 groups ( P>0.05). Conclusions:TACE combined with RFA in the treatment of primary liver cancer patients can not only improve the total clinical effective rate, but also significantly improve the immune function, and help to reduce level of the liver tumor marker of AFP.