Objective Aimed at investigating the effect and molecular mechanism of artemisinin on hemo-dynamics and vascular remodeling in monocrotaline(MCT)-induced pulmonary arterial hypertension(PAH)rats.Methods 30 male SD rats were randomly divided into 3 groups(n=10):control group,MCT-induced PAH group(MCT group,60 mg/kg)and artemisinin intervention group(50 mg/kg).At 28 days after modeling,the right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),heart rate and right ventricular hypertrophy index(RVHI)were measured to evaluate the development of PAH.HE staining and α-SMA immuno-histochemistry were used to observe the morphology and assess muscularization of pulmonary arterioles,and the percentage of medial wall thickness(WT%),the percentage of vascular wall area(WA%)and the proportion of muscular vessels were calculated to evaluate the degree of pulmonary vascular remodeling.The mRNA and protein levels of HIF-1α and LDHA were detected by real-time PCR and Western blot,respectively.Pyruvate and lactate concentration in lung tissue was measured using pyruvate and lactateassay kit.Results Compared with the control group,the RVSP,mPAP,heart rate and RVHI were significantly increased in MCT-induced PAH rats(all P<0.05).Histological analysis showed that the increasedmedial wall thickness of small pulmonary arteries and vascular muscularization were observed in MCT-treated rats compared with control rats.WT%,WA%and muscularization degrees of pulmonary arterioles were higher in MCT-treated rats than those in the control group(all P<0.05),suggesting successful construction of PAH model.Compared with the MCT group,the RVSP,mPAP,heart rate and RVHI decreased in the rats treated with artemisinin(all P<0.05),accompanied with lower WT%and WA%(P<0.05),and muscularization of pulmonary arterioles was improved(P<0.05).Further study showed the mRNA and protein levels ofHIF-1α and LDHA in lung tissue of MCT-induced PAH rats were higher than those in the control group,the content of lactate and pyruvate and the ratio of lactate to pyruvate were higher than that in the control group(all P<0.05).However,the mRNA and protein levels of HIF-1α and LDHA in lung tissue of rats treated with artemisinin were lower than those in the MCT group,the content of lactate and pyruvate and the ratio of lactate to pyruvate were lower than that in the MCT group(all P<0.05).Conclusion Artemisinin improves hemodynamic and pulmonary vascular remodeling in PAH rats through inhibiting HIF-1α/LDHA signaling pathway-mediated glycolysis.

Objective:To study the lipid metabolism and its relationship with iodine nutrition status in patients with papillary thyroid carcinoma (PTC) and benign thyroid nodules.Methods:A case-control study was conducted on patients with thyroid nodules initially diagnosed at Harbin Medical University Cancer Hospital from November 2015 to April 2019. Basic information, thyroid function indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb)], and pathological diagnosis results were collected from all subjects. Fasting venous blood and morning urine samples were collected for serum iodine concentration (SIC), urine iodine concentration (UIC) and blood lipid indicators [total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), lipoprotein (a), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), apolipoprotein E (ApoE), and non-esterified fatty acid (NEFA)] measurements. Results:A total of 1 090 subjects were included, including 907 PTC patients and 183 benign thyroid nodule patients. The UIC [ M ( Q1, Q3)] for the PTC group and benign thyroid nodule group were 143.36 (94.08, 227.94) and 146.28 (112.89, 236.07) μg/L, respectively, with statistically significant differences between the groups ( Z = 4.16, P = 0.042). Among PTC patients with different clinical pathological features, those with lymph node metastasis had higher FT 3 levels than those without lymph node metastasis ( t = 5.42, P = 0.021). The levels of TSH, TgAb, and TPOAb in patients with PTC combined with autoimmune thyroid disease (AITD) were higher than those without AITD ( Z = 11.87, 81.55, 475.96, P < 0.05). There was no statistically significant difference in the comparison of various blood lipid indicators ( P > 0.05). The correlation analysis showed that SIC in patients with thyroid nodules was positively correlated with FT 3, FT 4, ApoB, lipoprotein (a), NEFA, TG, LDL-C, and LDL-C/HDL-C ( P < 0.05). FT 3 was positively correlated with NEFA and LDL-C/HDL-C ( r = 0.12, 0.09, P < 0.05), and negatively correlated with ApoA1, TC, and HDL-C ( r = - 0.14, - 0.14, - 0.15, P < 0.001). FT 4 was positively correlated with NEFA ( r = 0.11, P < 0.001), and negatively correlated with TG ( r = - 0.10, P = 0.003). According to the iodine nutritional level, the ApoE level of PTC patients in the SIC < 45 μg/L group was higher than that in the 45 - 90 μg/L group ( P < 0.05). The levels of LDL-C and ApoB in patients with benign thyroid nodules in the SIC > 90 μg/L group were higher than those in the 45 - 90 μg/L group ( P < 0.05). The ApoE level of patients with benign thyroid nodules in the UIC < 100 μg/L group was significantly higher than that in the 100 - 299 and ≥300 μg/L groups ( P < 0.05). There was no statistically significant difference in thyroid function indicators of patients with PTC and benign thyroid nodules between different levels of SIC and UIC ( P > 0.05). Conclusions:Compared to benign thyroid nodules, PTC does not significantly affect patients' blood lipid levels. In patients with PTC and benign thyroid nodules, insufficient or excessive iodine nutrition can affect lipid metabolism.

Objective:To study the lipid metabolism and its relationship with iodine nutrition status in patients with papillary thyroid carcinoma (PTC) and benign thyroid nodules.Methods:A case-control study was conducted on patients with thyroid nodules initially diagnosed at Harbin Medical University Cancer Hospital from November 2015 to April 2019. Basic information, thyroid function indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb)], and pathological diagnosis results were collected from all subjects. Fasting venous blood and morning urine samples were collected for serum iodine concentration (SIC), urine iodine concentration (UIC) and blood lipid indicators [total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), lipoprotein (a), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), apolipoprotein E (ApoE), and non-esterified fatty acid (NEFA)] measurements. Results:A total of 1 090 subjects were included, including 907 PTC patients and 183 benign thyroid nodule patients. The UIC [ M ( Q1, Q3)] for the PTC group and benign thyroid nodule group were 143.36 (94.08, 227.94) and 146.28 (112.89, 236.07) μg/L, respectively, with statistically significant differences between the groups ( Z = 4.16, P = 0.042). Among PTC patients with different clinical pathological features, those with lymph node metastasis had higher FT 3 levels than those without lymph node metastasis ( t = 5.42, P = 0.021). The levels of TSH, TgAb, and TPOAb in patients with PTC combined with autoimmune thyroid disease (AITD) were higher than those without AITD ( Z = 11.87, 81.55, 475.96, P < 0.05). There was no statistically significant difference in the comparison of various blood lipid indicators ( P > 0.05). The correlation analysis showed that SIC in patients with thyroid nodules was positively correlated with FT 3, FT 4, ApoB, lipoprotein (a), NEFA, TG, LDL-C, and LDL-C/HDL-C ( P < 0.05). FT 3 was positively correlated with NEFA and LDL-C/HDL-C ( r = 0.12, 0.09, P < 0.05), and negatively correlated with ApoA1, TC, and HDL-C ( r = - 0.14, - 0.14, - 0.15, P < 0.001). FT 4 was positively correlated with NEFA ( r = 0.11, P < 0.001), and negatively correlated with TG ( r = - 0.10, P = 0.003). According to the iodine nutritional level, the ApoE level of PTC patients in the SIC < 45 μg/L group was higher than that in the 45 - 90 μg/L group ( P < 0.05). The levels of LDL-C and ApoB in patients with benign thyroid nodules in the SIC > 90 μg/L group were higher than those in the 45 - 90 μg/L group ( P < 0.05). The ApoE level of patients with benign thyroid nodules in the UIC < 100 μg/L group was significantly higher than that in the 100 - 299 and ≥300 μg/L groups ( P < 0.05). There was no statistically significant difference in thyroid function indicators of patients with PTC and benign thyroid nodules between different levels of SIC and UIC ( P > 0.05). Conclusions:Compared to benign thyroid nodules, PTC does not significantly affect patients' blood lipid levels. In patients with PTC and benign thyroid nodules, insufficient or excessive iodine nutrition can affect lipid metabolism.

Objective Aimed at investigating the effect and molecular mechanism of artemisinin on hemo-dynamics and vascular remodeling in monocrotaline(MCT)-induced pulmonary arterial hypertension(PAH)rats.Methods 30 male SD rats were randomly divided into 3 groups(n=10):control group,MCT-induced PAH group(MCT group,60 mg/kg)and artemisinin intervention group(50 mg/kg).At 28 days after modeling,the right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),heart rate and right ventricular hypertrophy index(RVHI)were measured to evaluate the development of PAH.HE staining and α-SMA immuno-histochemistry were used to observe the morphology and assess muscularization of pulmonary arterioles,and the percentage of medial wall thickness(WT%),the percentage of vascular wall area(WA%)and the proportion of muscular vessels were calculated to evaluate the degree of pulmonary vascular remodeling.The mRNA and protein levels of HIF-1α and LDHA were detected by real-time PCR and Western blot,respectively.Pyruvate and lactate concentration in lung tissue was measured using pyruvate and lactateassay kit.Results Compared with the control group,the RVSP,mPAP,heart rate and RVHI were significantly increased in MCT-induced PAH rats(all P<0.05).Histological analysis showed that the increasedmedial wall thickness of small pulmonary arteries and vascular muscularization were observed in MCT-treated rats compared with control rats.WT%,WA%and muscularization degrees of pulmonary arterioles were higher in MCT-treated rats than those in the control group(all P<0.05),suggesting successful construction of PAH model.Compared with the MCT group,the RVSP,mPAP,heart rate and RVHI decreased in the rats treated with artemisinin(all P<0.05),accompanied with lower WT%and WA%(P<0.05),and muscularization of pulmonary arterioles was improved(P<0.05).Further study showed the mRNA and protein levels ofHIF-1α and LDHA in lung tissue of MCT-induced PAH rats were higher than those in the control group,the content of lactate and pyruvate and the ratio of lactate to pyruvate were higher than that in the control group(all P<0.05).However,the mRNA and protein levels of HIF-1α and LDHA in lung tissue of rats treated with artemisinin were lower than those in the MCT group,the content of lactate and pyruvate and the ratio of lactate to pyruvate were lower than that in the MCT group(all P<0.05).Conclusion Artemisinin improves hemodynamic and pulmonary vascular remodeling in PAH rats through inhibiting HIF-1α/LDHA signaling pathway-mediated glycolysis.

Objective:To investigate the neuroprotective effect of cerebroprotein hydrolysate (CH) -Ⅰ on cerebral ischemia-reperfusion injury in rats and its mechanism.Methods:Eighty adult healthy male SD rats were randomly divided into sham operation group, model group, CH-Ⅰ intervention group and cerebrolysin (CBL) positive control group. The model of ischemia-reperfusion injury was induced by temporarily occluding the left middle cerebral artery with suture-occluded method. The CH-Ⅰ and CBL groups intraperitoneally injected with CH-Ⅰ and CBL at 0, 3, 6 and 12 h after reperfusion at the dose of 20 mg/kg. The sham operation group and the model group were injected with the same volume of normal saline. At 24 h after reperfusion, the behavior changes of the rats were detected by the modified neurological severity score (mNSS). The volume of cerebral infarction was detected by TTC staining. The morphology and structure of neurons in ischemic cortex were observed by Nissl staining. The apoptosis of neurons in ischemic cortex was detected by TUNEL staining. The expression changes of phosphorylated extracellular signal-regulated kinase (pERK) 1/2, phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase (pMEK) 1/2, phosphorylated cAMP response element binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) in the ischemic cortex were detected by Western blot.Results:At 24 h after reperfusion, the mNSS score and cerebral infarct volume in the model group were significantly higher and larger than those in the sham group (all P<0.001). The mNSS scores and cerebral infarct volumes in the CH-Ⅰ and CBL groups were significantly reduced compared with those in the model group (all P<0.05), but there was no significant difference between the CH-Ⅰ group and the CBL group. Nissl and TUNEL staining showed that the degenerative cell index and apoptotic cell index in the CH-Ⅰ group were significantly lower than those in the model group (all P<0.01), but there were no significant difference between the CH-Ⅰ group and the CBL group. Western blot analysis showed that compared with the sham operation group, the pMEK1/2, pERK1/2 and pCREB expressions in ischemic cortex were significantly enhanced and the BDNF expression was significantly attenuated in the model group ( P<0.05). Compared with the model group, pMEK1/2, pERK1/2, and pCREB expressions in the CH-Ⅰ group were significantly decreased (all P<0.05), and the BDNF expression was significantly increased ( P<0.05). Conclution:CH-Ⅰ can reduce cerebral infarct volume and improve neurological function, and its mechanism may be associated with the inhibition of the MEK-ERK-CREB pathway as well as the enhancement of BDNF expression.

Iodine is an essential component of thyroid hormone biosynthesis. It plays an important role in the growth, development, maturation and the function of organs and systems. Epidemiological and animal studies have shown that the effect of iodine on human body is bidirectional. Insufficient and excessive intake of iodine will cause adverse consequences and affect human health. At present, the research on the harm of iodine nutritional abnormalities to human health mostly focuses on morphology and function of thyroid. In fact, iodine nutritional abnormalities not only affect thyroid, but also have many adverse effects on other aspects of the body. There is evidence of a link between abnormal iodine nutrition, dyslipidemia and cardiovascular disease, which will lead to abnormal levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in the body. This paper reviews the research progress on the relationship between iodine nutrition, thyroid function and body lipid metabolism, in order to provide a theoretical basis for the "scientific and precise" prevention and treatment of iodine deficiency disorders in China.