Thyroid-associated ophthalmopathy(TAO)is an organ-specific autoimmune disease. A series of symptoms related to it cause serious harm to the physical and mental health of patients, and then seriously affect their quality of life. However, there is stilly lack of specific treatment methods at present. Even after effective treatment, it is difficult to fully recover the appearance changes. Therefore, it is very important to avoid or reduce the risk factors associated with the occurrence and progress of TAO. Hypercholesterolemia, as one of the potential risk factors for the occurrence and progression of TAO, has been concerned by more clinical researchers. Recent studies have found that statins can significantly reduce the incidence of ophthalmopathy and the risk of ophthalmopathy progression in patients with Graves disease. Based on the inflammatory pathological mechanism of TAO, statins may become a new hope to prevent and delay the occurrence and progression of TAO.

OBJECTIVE:To establish a method for the dissolubility determination of Manidipine Hydrochloride tablet and eval-uate the quality consistency of generic and original preparation. METHODS:HPLC was performed on the column of Waters Sym-metry C18 column with mobile phase of potassium phosphate monobasic solution (potassium phosphate monobasic 6.8 g was well-mixed with water 1 000 ml,and pH was adjusted to 4.6 by potassium hydroxide solution)-acetonitrile (49∶51,V/V) at flow rate of 1.0 ml/min,detection wavelength was 228 nm,column temperature was 25℃,and the injection volume was 20μl. The dis-solution mediums were 0.1 mol/L hydrochloric acid solution,acetic acid-sodium acetate buffer solution(pH 4.0)and phosphate buf-fer solution [pH 6.8,adding into 0.5% sodium dodecyl sulfonate(SDS)],volume of dissolution medium was 900 ml and rotating rate was 50 r/min,and the dissolubility of Manidipine hydrochloride tablet generic and original preparation was investigated and the similarity of dissolution profile was evaluated by calculating similar factor (f2). RESULTS:The linear range of manidipine hydro-chloride was 0.625-20 μg/ml;RSDs of instrument precision and stability tests were lower than 2.0%;recoveries of 3 dissolution mediums were 92.86%-102.97%(RSD=1.9%,1.8% and 2.7%,n=9),respectively. The dissolubility of 3 batches of Manidipine hydrochloride tablet generic and original preparations was higher than 85% in 0.1 mol/L hydrochloric acid solution in 15 min;f2 was >50 in acetic acid-sodium acetate buffer solution (pH 4.0) and phosphate buffer solution (pH 6.8,adding into 0.5% SDS). CONCLUSIONS:The method is suitable for the dissolubility determination of Manidipine hydrochloride tablet;meanwhile,the dis-solution profile in vitro of Manidipine hydrochloride tablet generic and original preparations has similarities,so the quality consis-tency is good.

Objective To explore the method for early diagnosis of masked polycythemia vera (mPV) by comparing and analyzing the features of mPV and polycythemia vera (PV). Methods A total of 200 newly diagnosed male patients were collected based on diagnostic criteria, including 100 cases of PV and 100 cases of mPV. Erythropoietin (EPO), neutrophil alkaline phosphatase (NAP) score, bone marrow biopsy (BMB), and JAK2 V617F mutation were evaluated in all cases. After 6 months, hemoglobin (Hb) and JAK2 V617F mutation load were detected in patients without special treatment in two groups during follow-up. Results EPO, NAP score, BMB hematopoietic volume and the number of megakaryocyte had no statistical differences between PV group and mPV group [(3.4 ± 0.7) U/ml vs. (3.2±0.6) U/ml, (276±20) score vs. (278±21) score, (78±10) % vs. (76±9) %, (53±6) vs. (51±5), respectively], while JAK2 V617F mutation load in PV group was higher than that in mPV group[(89.2±9.4) % vs. (78.1±8.6) %, P<0.05]. In mPV patients without special treatment, Hb ≥185 g/L was found in 37 patients after 6 months, and the level of Hb and JAK2 V617F mutation load in these 37 patients reached (194±8) g/L and (90.7±9.1) %, respectively. Conclusions There is no significant difference in EPO, NAP score and BMB between PV and mPV, but the JAK2 V617F mutation load is different. In mPV patients without special treatment, Hb level can reach the typical PV diagnostic criteria after 6 months, meanwhile, JAK2 V617F mutation load is also increased.

OBJECTIVE:To explore the trend of cooper enrichment in hirudinidae influenced by culture environment. MET-HODS:The soil containing low-content,medium-content and high-content of cooper groups(30.00,60.00,90.00 μg/g)and water culture control group were set up. Hirudinidae leech were culture for 60 d,and sampled every 15 days. ICP-MS techniques was used to determined and compared the contents of cooper in W. pigra and soil. RESULTS:In first 15 days,the contents of cooper in leech from 4 groups increased greatly,compared with before;in the following 15 days,the content of cooper kept stable in high-content group while decreased in other 3 groups;in the 30-45 day,the contents of cooper increased rapidly in 4 groups,and those of low-content group and high-content group reached the peak in this experiment;in the last 15 days,the contents of cooper in control group and high-content group increased continuously,while those of low-content and medium-content groups decreased to some extent. Compared with before,the contents of cooper in leech from control group,low-content,medium-content and high-content groups increased by 292%,186%,293%,464% respectively;those of soil from latter 3 groups increased by 81.12%,35.98% and 21.28% respectively. CONCLUSIONS:The content of cooper in leech increase with time,and is positively correlated with the content of cooper in soil. It is suggested to control the content of cooper in hirudinidae through controlling cul-ture environment when hirudinidae are cultured as medicinal material,in order to meet the quality standard of heavy metal in medic-inal material.

Objective To observe the effects of different levels of sodium arsenite ( NaAsO2) on mRNA expression of pigment epithelium-derived factor (PEDF) and apoptosis-related factors in PC12 cells ( rat neuron properties pheochromocytoma). Methods PC12 cells were treated with different levels of NaAsO2 [0 (control group), 2, 5, 10 μmol/L] for 24 hours. The mRNA expression of PEDF and apoptosis-related factors (Bax, Bcl-2) were detected by real-time quantitative PCR. Results There were significant differences in the mRNA expressions of PEDF between the 4 groups (F=102.28, P<0.05), the mRNA expressions of PEDF in the group of 2, 5, 10μmol/L (0.70 ± 0.07, 0.33 ± 0.04, 0.23 ± 0.10) was lower than that of control group (1.15 ± 0.11, P< 0.05); there were no significant differences in the mRNA expressions of Bax between the 4 groups (0, 2, 5, 10 μmol/L groups: 0.95 ± 0.12, 0.80 ± 0.11, 0.88 ± 0.11, 1.01 ± 0.11, F= 2.01, P> 0.05); there were significant differences in the mRNA expressions of Bcl-2 between the 4 groups (F=19.87, P<0.05), the mRNA expressions of Bcl-2 in the group of 2, 5, 10 μmol/L (0.65 ± 0.03, 0.49 ± 0.04, 0.57 ± 0.09) were lower than that of control group (0.95 ± 0.11, all P<0.05);there were significant differences in the mRNA expressions of Bax/Bcl-2 between the 4 groups (F=8.352, P<0.05), the mRNA expressions of in the group of 5, 10μmol/L (1.80 ± 0.72, 1.82 ± 0.36) were higher than that of control group (1.02 ± 0.24, all P<0.05). Conclusion NaAsO2 may increase the expression of apoptosis-related factorsBax/Bcl-2 mRNA by decreasing the expression of PEDF mRNA in PC12 cells, leading to apoptosis in PC12 cells.

The clinical data, laboratory test, and gene mutations were collected from a family with Liddle syndrome. Literatures on Liddle syndrome published in domestic and abroad since 1994 were reviewed and the types of gene mutations were summarized. The proband was diagnosed with hypertension at the age of 24. Laboratory test showed that serum potassium was 3.65 mmol/L, plasma renin was <0.5 mU/L, and plasma aldosterone was 1.5 ng/dL. Proband′s father was diagnosed with hypertension at the age of 34 with the serum potassium 3.34 mmol/L, plasma renin 3.72 mU/L, and plasma aldosterone 6.04 ng/dL. A nonsense mutation(1724G>A, p.Trp575*) in exon 13 of SCNN1G gene was detected in the proband and his father. In 288 cases from 107 families reported in the review of domestic and foreign literature, the incidence of hypertension, hypokalemia, and low renin/low aldosterone were 95.1%, 55.2%, and 49.6%, respectively. This case suggests that the clinical phenotype of Liddle syndrome is heterogeneous. Patients with early-onset hypertension, regardless of whether they are accompanied by hypokalemia, should be screened for renin-angiotensin-aldosterone and genetic testing related to Liddle syndrome should be further detected in patients with low plasma renin/aldosterone.

Objective To investigate the ultrasonography discrepancy of hepatic neuroendocrine neoplasm ( hNEN ) derived from different primary locations and pathological grades . Methods From August 2010 to April 2016 ,50 consecutive patients with 54 hNENs confirmed by pathology and imaging diagnosis underwent baseline ultrasound ( BUS ) and contrast-enhanced ultrasound ( CEUS ) in the First Affiliated Hospital of Sun Yat-sen University were enrolled in the retrospective study . On the basis of primary sites ,all hNENs were divided into three groups :pancreas ,gastrointestinal tract and other location groups . According to the pathological grading ,the hNENs were divided into hNET ( hepatic neuroendocrine tumor) group and hNEC ( hepatic neuroendocrine carcinoma) group . The imaging features of BUS and CEUS were retrospectively investigated and the ultrasonography discrepancy of hNEN derived from different primary focus and pathological grades were compared . Results ① Comparison of hNEN derived from different primary sites :hNEN derived from pancreas and gastrointestinal tract were smaller than hNEN derived from other sites[ ( 3 .8 ± 2 .6) cm vs ( 8 .7 ± 7 .0) cm , P = 0 .037 ;( 2 .9 ± 2 .1) cm vs ( 8 .7 ± 7 .0) cm , P = 0 .005] ,but the difference between the pancreas and gastrointestinal tract was not statistically significant ( P = 1 .0 ) . As for the pattern of CEUS enhancement ,hNEN derived from pancreas and gastrointestinal tract usually showed homogenous enhancement ( 13/19 ,15/23) while hNEN derived from other primary sites usually showed heterogeneous enhancement ( 10/13) ,and the difference was statistically significant ( P = 0 .025) . ② Comparison of hNET and hNEC :the distinction of enhancement level in the portal phase of contrast-enhanced ultrasound was statistically significant ( P = 0 .033) . All hNEC appeared hypo-enhancement ,while a small part of hNET ( 7/31 ) appeared iso-enhancement .More hNEC lesions showed heterogenous enhancemnt than hNET in the arterial phase ( 14/21 vs 9/31 , P = 0 .007) ,and there were less hNEC lesions presented tumor bleeding vessels than hNET ( 8/21 vs 22/31 , P = 0 .019 ) . Conclusions hNEN derived from pancreas and gastrointestinal tract are in a manner similar to hNEN derived from other primary sites on ultrasonography , so it' s difficult to identify in ultrasound . The ultrasonographic features of hNEC are more resemble to malignancy and it can be distinguished from hNET .

Objective To analyze the features of hepatic neuroendocrine neoplasm ( HNEN ) with conventional ultrasound and contrast-enhanced ultrasound sonography (CEUS) ,and to evaluate the value in the diagnosis and differential diagnosis of HNEN by ultrasound . Methods Fifty patients of HNEN confirmed pathologically or clinically were enrolled . All patients underwent conventional ultrasound and CEUS . Among the patients ,5 cases were primary hepatic neuroendocrine neoplasm ( PHNEN) ,and 45 cases were metastatic hepatic neuroendocrine neoplasm ( MHNEN) . Conventional ultrasound and CEUS features of HNEN were analyzed and the distinctions between PHNEN and MHNEN were compared . Results Baseline ultrasound showed that 37 (74％ ) HNEN were multiple lesions located in liver ,23 ( 46％ ) lesions with hyperechoic appearance ,35 ( 70％ ) lesions with homogeneous echoic ,28 ( 56％ ) lesions were clearly marginated ,8 (16％ ) lesions were surrounded by acoustic halo ,and 12 ( 24％ ) lesions with posterior echo attenuation . CEUS showed that the majority of HNEN exhibited the enhanced pattern of rapid wash-in and wash-out" . Forty-six ( 92％ ) lesions showed hyper-enhancement in the arterial phase ,44 ( 88％ ) lesions showed iso-enhancement in the portal phase ,and 47 ( 94％ ) lesions showed hypo-enhancement in the late phase .Feeding vessels were observed in 31 ( 62％ ) lesions ,intralesional non-enhancement zone was observed in 17(34％ ) lesions ,and capsule enhancement in the delay phase was found in 10( 20％ ) lesions . MHNEN had smaller diameter [ ( 3 .92 ± 2 .77) cm vs (12 .82 ± 8 .85) cm , P = 0 .004] and less likely to present cystic structure intralesional than PHNEN ( 1/45 vs 2/5 , P < 0 .001 ) . The differences of other baseline ultrasonographic characteristics ,enhanced characteristics and enhanced time on CEUS between PHNEN and MHNEN were not statistically significant ( all P > 0 .05) . Conclusions HNEN has a certain characteristic that can be identified on ultrasonography . Ultrasound can provide some valuable information to diagnose HNEN . While it′s difficult to differentiate PHNEN and MHNEN owing to their similar ultrasonographic characteristics .

The four properties of Chinese herbal medicine have a history of several thousand years and are one of the important theoretical guides for the clinical application of Chinese herbal medicine. However， there have been few reviews of research methods and techniques for the four properties of Chinese herbal medicine in recent years. Therefore， this article summarized the advances and techniques for the four properties of Chinese herbal medicine by screening relevant literature on the four properties of Chinese herbal medicine and clarifying the characteristics， advantages， and applicable objects of each technique， in order to provide references for in-depth research on the four properties in the future. Chinese databases such as China national knowledge infrastructure （CNKI）， Wanfang data， and VIP， as well as international databases including PubMed， Cochrane Library， and EMbase were searched for relevant literature on the four properties of Chinese herbal medicine. The advances， research objects， and research techniques involved in the literature were extracted， classified， and summarized. Currently， the research techniques for the four properties of Chinese herbal medicine mainly include six categories， i.e.， literature data research， network pharmacology， biothermodynamics， cell biology， proteomics， and metabolomics. The research hierarchy can be divided into micro-level， small-level， medium-level， and macro-level. The research objects used in each experimental study are different， mainly single Chinese herbal medicine， Chinese herbal monomers， targets， microbial communities， cells， mice， and rats. Different research techniques explain the four properties of Chinese herbal medicine from different dimensions， which overall indicate the material basis of the four properties of Chinese herbal medicine. In future research， the interpretation of the four properties of Chinese herbal medicine can be first located at the research hierarchy， then corresponding research techniques can be selected according to the research hierarchy， and research indicators can be determined to obtain research conclusions. This can help researchers of traditional Chinese medicine effectively carry out research design and perform related experiments on the four properties of Chinese herbal medicine.