Objective To investigate the relationship between enlarged perivascular spaces in the hippocampus(H-EPVS)and cognitive function in patients with type 2 diabetes mellitus(T2DM),and to explore whether the H-EPVS can be used as an imaging marker of cognitive impairment in T2DM.Methods A total of 93 T2DM patients were selected(including 56 patients with cognitive impair-ment and 37 patients with normal cognition).All patients received head MRI scanning and neuropsychological tests.The differences of the H-EPVS counts and various parameters between the two groups were compared.Multiple linear regression was used to evalu-ate the association between H-EPVS and cognitive function.Results Compared with the T2DM patients with normal cognition,the cognitive impairment had significantly higher total H-EPVS counts(P=0.015),and worse performance of global cognitive function,processing speed,immediate memory and delayed recall(P＜0.05).After adjusting for confounding factors by multiple linear regres-sion,total H-EPVS were associated with global cognitive function and immediate memory.Conclusion The H-EPVS are correlated with global cognitive function and memory function in patients with T2DM.The H-EPVS may be used as an imaging marker of cog-nitive impairment in T2DM patients.

Objective:To follow up the iodine nutrition and intellectual development of school children aged 8-10 years old in Nangqian County of Qinghai Province after 9 years of the implementation of iodine deficiency disorders intervention measures with iodine supplement as the main measure.Methods:In order to improve the iodine nutritional status of the population in Nangqian County, free iodized salt distribution, health education and other intervention measures for iodine deficiency disorders were implemented for 9 consecutive years since 2013. In May 2012 (before iodine supplementation) and September 2021 (after iodine supplementation), the same 5 townships (towns) were selected, and children aged 8-10 years old (half male and half female, age balanced) born locally in the central primary school of each township (town) were selected as the survey subjects. Household edible salt samples and random urine samples were collected for salt iodine and urinary iodine detection; the second revised version of the Chinese Combined Raven's Test (rural version) was used to assess the intelligence quotient (IQ) of children. The Flynn effect (FE) gain was used to adjust IQ, the corrected IQ = (IQ starting point value - current year's IQ value) - FE gain (calculated by 0.74/year). The differences of salt iodine and urinary iodine related indexes, IQ value and corrected IQ were compared before and after iodine supplementation.Results:After iodine supplementation, the coverage rate of iodized salt reached 100.00% (300/300), and the consumption rate of qualified iodized salt reached95.00% (285/300), the median urinary iodine increased to 157.20 μg/L, and all indexes met the elimination standard of iodine deficiency disorders. The IQ value of children aged 8-10 years old after iodine supplementation was 99.00 ± 14.90, significantly higher than that before iodine supplementation (82.00 ± 13.20, F = 156.82, P < 0.001). The FE gain in 9 years was 6.66, and the actual IQ gain of children aged 8-10 years old after iodine supplementation was 10.34. There were statistically significant differences in IQ value before and after iodine supplementation in male and female children ( F = 78.84, 78.88, P < 0.001). After iodine supplementation, there was a statistically significant difference in IQ value between children in the 8-year-old group and the 10-year-old group ( P = 0.010). There were statistically significant differences in IQ value before and after iodine supplementation in 8, 9 and 10 years old groups ( F = 55.23, 65.79, 36.85, P < 0.001). Conclusion:Intervention measures for iodine deficiency disorders, mainly iodine supplement, can significantly improve the iodine nutrition status of children aged 8-10 years old, and significantly promote the intellectual development of children.

Objective:To analyze the external quality control assessment results of urinary iodine, salt iodine and water iodine in iodine deficiency disorders laboratories in Qinghai Province, to evaluate the testing capacity of provincial, municipal and county-level laboratories and the operation of external quality control network, so as to provide quality assurance for consolidating and eliminating iodine deficiency disorders.Methods:In 2021, 1 provincial, 8 municipal, and 43 county-level laboratories in Qinghai Province had participated in the assessment of urinary iodine and salt iodine, while 1 provincial and 8 municipal-level laboratories had participated in the assessment of water iodine. The assessment results were evaluated using the method of reference value ± uncertainty of external quality control samples.Results:All laboratories that participated in the assessment had provided feedback. One provincial-level laboratory passed the assessment of urinary iodine, salt iodine, and water iodine. Among 8 municipal-level laboratories, 2 laboratories failed the urinary iodine assessment, with a pass rate of 6/8; the assessment of salt iodine and water iodine in 8 laboratories were all qualified. Among 43 county-level laboratories, 7 laboratories failed the urinary iodine assessment, with a pass rate of 83.7% (36/43); the assessment of salt iodine in 43 laboratories were all qualified.Conclusions:The external quality control network of iodine deficiency disorders laboratories in Qinghai Province has fully covered all municipal and county-level laboratories. The testing capability of provincial-level laboratory is stable and maintains a high level; the testing quality of some municipal and county-level laboratories is still unstable and needs to be further strengthened.

Objective:To seek any correlation between and prognosis and hospitalization costs of stroke survivors with dysphagia.Methods:The records of 1370 stroke survivors admitted to the rehabilitation departments of 3 public hospitals in Weifang were studied. Of them, 499 (36.4%) were diagnosed with dysphagia and 871 were not. Binary logistic regression and multiple linear regression were employed to analyze the correlation between dysphagia and the occurrence of pneumonia, modified Rankin Scale (mRS) scores, modified Barthel index (MBI) scores, length of stay and total hospitalization cost.Results:After adjusting for confounding factors, the risk of pneumonia in the dysphagia group was 2.4 times higher. At discharge, the risk of an mRS≥3 was 3.3 times greater and that of an MBI score <60 was 1.7 times greater with dysphagia. Multiple stepwise linear regression showed that dysphagia was significantly associated with higher mRS scores at discharge, lower MBI scores, and longer hospital stays. The standardized regression coefficients predict that after the length of stay, dysphagia is the strongest predictor of the cost of hospitalisation, followed by ADL ability, pneumonia, supratentorial, haemorrhagic stroke and CCI.Conclusions:Dysphagia is a significant predictor of the hospitalization costs of stroke patients. It is recommended to identify and treat dysphagia as early as possible to improve the prognosis of such patients and reduce the economic burden.

Objective:To investigate the molecular mechanism of excessive iodine induced experimental autoimmune thyroiditis (EAT) in mice.Methods:Sixty female non-obese diabetic (NOD) mice were selected and divided into 5 groups according to body weight [(25 ± 3) g] via the random number table method, with 12 mice in each group: control group (group A), 10-fold high iodine group (group B), 100-fold high iodine group (group C), 1 000-fold high iodine group (group D) and 1 000-fold high iodine combined with polyinosinic acid-polycytidylic acid [Poly (I:C)] group (group E). The experiment period was 16 weeks. Mice in each group drank purified water with sodium iodine (NaI) content of 0.000, 0.005, 0.050, 0.500 and 0.500 mg/L, respectively; mice in group E were intraperitoneally injected with Poly (I:C) at week 7 and week 15, respectively. At the end of the 16th week, mice were dissected and blood samples and thyroid tissue were taken. The levels of serum thyroid function indexes [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), and thyroid peroxidase antibody (TPOAb)] were detected by enzyme-linked immunosorbent assay (ELISA); the pathological changes of thyroid tissue were observed after hematoxylin-eosin (HE) staining; differentially expressed genes in thyroid tissue were detected by RNA-sequencing (RNA-seq), and analyzed by KEGG pathway; mRNA and protein levels of p38, intercellular adhesion molecule-1 (ICAM-1) and chemokine 10 (CXCL10) in thyroid tissue were detected by real-time fluorescence quantitative PCR (qPCR) and Western blotting, respectively. Results:There were statistically significant differences in serum levels of TSH (ng/ml: 6.53 ± 0.86, 6.61 ± 0.82, 7.68 ± 0.55, 7.93 ± 0.60, 8.73 ± 1.60), FT 3 (pg/ml: 59.35 ± 10.16, 53.73 ± 10.96, 46.19 ± 8.03, 41.01 ± 8.67, 34.21 ± 11.75), FT 4 (pg/ml: 136.74 ± 10.06, 124.33 ± 14.34, 101.80 ± 6.78, 91.37 ± 6.75, 73.29 ± 17.31), and TPOAb (U/ml: 130.81 ± 24.53, 145.47 ± 28.89, 166.52 ± 41.59, 199.78 ± 42.19, 201.99 ± 44.03) among the 5 groups of mice ( F = 4.77, 4.96, 23.12, 3.68, P < 0.05). Compared with group A, the serum TSH levels of mice in groups C, D and E were higher, the levels of FT 3 and FT 4 in groups B, C, D and E were lower, and the levels of TPOAb in groups D and E were higher, and the differences were statistically significant ( P < 0.05). HE staining showed that the thyroid follicle lesion in groups D and E was serious, and the EAT phenotype appeared in both groups. The differentially expressed genes were analyzed by KEGG pathway. Compared with group A, 8 metabolic pathways related to thyroid autoimmunity and inflammation were found in groups B, C, D and E. Further analysis found that 3 genes appeared in multiple pathways, namely p38, ICAM-1 and CXCL10. There were significant differences in the mRNA levels of p38, ICAM-1 and CXCL10 in thyroid tissue of the 5 groups of mice ( F = 14.77, 12.76, 16.39, P < 0.05); compared with group A, the mRNA levels of p38 in groups B, C, D and E were higher, and the mRNA levels of ICAM-1 and CXCL10 in groups C, D and E were higher ( P < 0.05). There were significant differences in the protein levels of p38, ICAM-1 and CXCL10 in thyroid tissue of the 5 groups of mice ( F = 7.97, 73.86, 18.02, P < 0.05); compared with group A, the protein levels of ICAM-1 and CXCL10 in groups B, C, D and E were higher ( P < 0.05). Conclusion:Excessive iodine promotes the occurrence and development of EAT in mice by up-regulating the expressions of p38 and ICAM-1 genes that are closely related to thyroid autoimmune and inflammatory responses.

Hepatocellular carcinoma （HCC）， an insidious malignant tumor with high incidence and lethality， poses a major threat to physical and mental health of human beings. The pathological mechanism needs to be further studied. Surgery， radiotherapy， chemotherapy， and targeted drugs are effective but induce many adverse reactions. Traditional Chinese medicine （TCM） has unique advantages and abundant clinical experience in the treatment of HCC. There has been an explosion of research on the pathways， targets， and mechanism of TCM against HCC from the perspective of molecular biology. According to previous research， Chinese medicinals or compound Chinese medicine prescriptions， directly or indirectly prevent the occurrence and progression of HCC through multiple pathways and targets， which is closely related to the pathophysiological processes such as cell proliferation， metastasis， apoptosis， autophagy， inflammatory response， and immune response. This paper summarizes and analyzes research on the action pathways and mechanisms of Chinese medicine against HCC. Specifically， isoliquiritigenin， dendrobium candidum and Yexiazhu compound Ⅱ regulate phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to inhibit the growth， proliferation and metastasis of tumor cells. Toad venom and dioscorea zingiberensis induce and enhance HCC autophagy by modulating mammalian target of rapamycin （mTOR） signaling pathway. Myricetin， asparagus， and Biejiajian Wan regulate mitogen-activated protein kinase （MAPK） signaling pathway to promote HCC cell cycle arrest， inhibit angiogenesis， and induce apoptosis. Polygonum odoratum， tetragonum， and plantainoside modulate nuclear factor-kappa B （NF-κB） to inhibit inflammatory response and HCC metastasis and reduce drug resistance. Quercetin and erigeron breviscapus control the Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway to suppress epithelial-mesenchymal transition （EMT） and remodel cytoskeleton. This paper is expected to lay a theoretical basis for the in-depth research on and clinical application of Chinese medicine in the treatment of HCC.

Objective:To investigate the dietary iodine intake of people in different areas of Qinghai Province, and to provide the basis for scientific iodine supplementation and continuous elimination of iodine deficiency hazards.Methods:From 2018 to 2019, according to administrative division, natural geographical regions, population distribution and economic development level of Qinghai Province, a total of 14 survey sites were selected. One village was selected from each survey site, and 20 households were selected from each village, the salt samples and 24 h urine samples of all family members were collected to detect salt iodine and urinary iodine. One drinking water sample was collected at the five directions of east, west, south, north and middle of each village to detect water iodine. Salt iodine was detected by direct titration, urinary iodine and water iodine were detected by arsenic-cerium catalytic spectrophotometry. At the same time, the 3-day weighing method was used to investigate the diet, the daily dietary iodine intake per capita (the result was expressed as average) and the proportion of dietary iodine in urinary iodine were calculated, the daily dietary iodine intake per capita of different production modes (agricultural region and pastoral region), different geographical environment (Hehuang Valley, Qaidam Basin, Qilian Mountain and Qingnan Plateau), different nationalities (Han, Tibetan, Hui, Mongolian, Tu, Salar) and different economic levels (< 8 000, 8 000 -, 10 000 -, ≥12 000 Yuan) were compared.Results:A total of 999 people from 280 families were surveyed, including 511 males and 488 females. The median water iodine of each survey site was less than 10 μg/L, all of which were environmentally iodine-deficient areas. A total of 280 salt samples were collected, the median salt iodine was 26.0 mg/kg, and the consumption rate of qualified iodized salt was 100% (280/280). A total of 999 urine samples were tested, and the median urinary iodine of people was 192.5 μg/L, which was at an appropriate level of iodine. There was no statistically significant difference ( t =-1.599, P > 0.05) in the daily dietary iodine intake per capita (28.53, 33.44 μg) of people in agricultural region ( n = 643) and pastoral region ( n = 356). The daily dietary iodine intake per capita (25.38, 33.30, 32.98, 34.79 μg) of people in Hehuang Valley ( n = 448), Qaidam Basin ( n = 125), Qilian Mountain ( n = 157), and Qingnan Plateau ( n = 269) were compared, the difference was statistically significant ( F = 2.883, P < 0.05); among them, the daily dietary iodine intake per capita in Hehuang Valley was lower than that in Qingnan Plateau ( P < 0.05). The daily dietary iodine intake per capita of different nationalities were compared, the difference was statistically significant ( F = 3.647, P < 0.05), Salar ( n = 68) and Tibetan ( n = 239) were higher (37.21 and 32.21 μg). The daily dietary iodine intake per capita (38.97, 17.01, 30.86, 33.14 μg) of annual per capita disposable income < 8 000 ( n = 194), 8 000-( n = 221), 10 000-( n = 302), ≥12 000 Yuan ( n = 282) were compared, the difference was statistically significant ( F = 9.407, P < 0.05). The proportions of dietary iodine in urinary iodine of various population ranged from 5.35% to 15.54%. Conclusions:The iodine nutrition of people in Qinghai Province is suitable, the dietary iodine intake of people is closely related to geographical environment, nationality and economic level. But the proportion of dietary iodine in urinary iodine is relatively low, the consumption of iodized salt is still the main way for people to intake iodine, and it is also the main measure to continuously eliminate the harm of iodine deficiency in Qinghai Province.

Objective:To understand the water iodine content in Qinghai Province and draw a distribution map of water iodine, so as to provide a basis for scientific supplementation of iodine and continuous elimination of iodine deficiency hazards.Methods:In 2017, in all counties (cities, districts) in Qinghai Province, with townships (towns, streets, referred to as townships) as the unit, the residents' drinking water samples were collected, water iodine content was tested, the median water iodine was calculated, and the water iodine distribution map of Qinghai Province was drew.Results:Totally 1 836 drinking water samples were collected in 392 townships, the median water iodine was 1.7 μg/L. Townships that had the median water iodine < 5 μg/L, in the range of 5 to 10 μg/L and > 10 μg/L accounted for 80.6% (316/392), 17.1% (67/392) and 2.3% (9/392), respectively. Among all townships, the highest of the median water iodine was 24.8 μg/L. Based on the results, water iodine distribution map of Qinghai Province, water iodine distribution map of Xining City and water iodine distribution map of Haidong City were compiled.Conclusions:Iodine deficiency is widespread throughout natural environment in Qinghai Province. Hence, salt iodization measures to prevent iodine deficiency disorders should be implemented continuously. According to the water iodine distribution map, the people should be guided to supplement iodine scientifically.

Objective:To analyze the assessment results of the external quality control in iodine deficiency disorders laboratories at all levels in Qinghai Province so as to provide quality assurance for monitoring and control effect evaluation of iodine deficiency disorders.Methods:The results of urinary iodine, salt iodine, and water iodine quality control assessments at the provincial, city (state) and county-level iodine deficiency disorders laboratories were analyzed in Qinghai Province from 2013 to 2018 (sourced from the annual evaluation results issued by National Reference Laboratory for Iodine Deficiency Disorders). Among them, there were 1 provincial, 8 city (state) and 43 county-level (2017, 2018) laboratories participated in the urinary iodine assessment; 1 provincial, 8 city (state) and 30 county-level (43 in 2017 and 2018) laboratories participated in the salt iodine assessment; 1 provincial and 8 city (state)-level laboratories participated in the water iodine assessment.Results:From 2013 to 2018, the feedback rates and qualified rates of provincial and city (state)-level laboratories participated in the urinary iodine external quality control assessment were 100.0%; the feedback rates of 43 county-level laboratories (2017 and 2018) were 100.0%, and the qualified rates were 93.0%(40/43) and 88.4%(38/43), respectively. The feedback rates and qualified rates for salt iodine assessment in provincial and city (state)-level laboratories were 100.0%; the county-level laboratories feedback rates were 100.0%, and the qualified rates were > 90.0% except for 2014. And the feedback rates of provincial and city (state)-level laboratories for water iodine assessment were 100.0%; the qualified rate of provincial-level laboratory was 100.0%, and the city (state)-level laboratories were 100.0% except 2016 (7/8).Conclusions:The quality control network of Qinghai Province's iodine deficiency disorders laboratories has fully covered all city (state) and county-level laboratories. Provincial, city (state)-level laboratories have stable and reliable levels of urinary iodine, salt iodine, and water iodine; some individual county-level laboratories testing capabilities still need to be improved.

Objective To investigate the relationship between thyroid volume and multiple body indexes such as urinary iodine level,height,and weight,respectively,in order to provide a theoretical basis for evaluation of goiter disease in the future. Methods The height and weight were measured, and urine samples were collected from children aged 8 to 10 years old from 10 township schools of Nangqian County in Qinghai Province in 2014 and urinary iodine was tested via the As (Ⅲ)-Ce4+catalytic spectrophotometry method. Meanwhile, the thyroid volume was immediately measured via the B-ultrasound method. Statistical analyses were employed finally to assess the difference and correlation between thyroid volume and multiple physiological indexes including urinary iodine level, height, weight, gender and age. Results The thyroid volume of 773 children aged 8 to 10 years old showed skewed distribution (W = 0.088, P < 0.05), with median of 3.53 ml and quartile of 3.05, 4.15 ml. The thyroid volume was not significantly different between different urinary iodine levels (H = 1.644, P > 0.05). There were significant differences of the thyroid volume among different height groups, weight groups and age groups (H=59.845,64.888,28.590,P<0.05),and the thyroid volume was positively correlated with height weight and age,respectively(r = 0.389, 0.359, 0.155, P < 0.05). Conclusions The thyroid volume is related to the level of children's physiological parameters, such as age, height, weight. Therefore, the diagnosis of thyroid volume via the B-ultrasound method for a individual child should not only take age,but also height and weight into account, to reduce the diagnostic error of goiter disease.