Background and purpose: Thyroid carcinoma cells spread mainly through lymph node metastasis, and lymphangiogenesis plays an important role during the lymph node metastasis, but it is not very clear to understand the formation mechanism. This study was to investigate the correlative expressions of HPSE, VEGF-C, D2-40 and lymphangiogenesis in thyroid carcinoma. Methods: Immunohistochemistry SP method was used to detect the expressions of HPSE, VEGF-C and D2-40 in 77 patients with thyroid carcinoma including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC),medullary thyroid carcinoma (MTC), 32 of them with lymph node metastasis was enrolled into the study, D2-40 stained the lymphatic vessels, and lymphatic vessel density (LVD) was scanned under the light-microscope, and the correlation among the above indexes in different thyroid carcinoma types were analyzed respectively. Results: The expressions of HPSE, VEGF-C and D2-40 were observed to have a different degree in thyroid carcinoma, and the highest expression of the protein could be seen in the patients with papillary carcinoma (P<0.05),The expression ratios of HPSE,VEGF-C and D2-40 in different carcinoma types were 54.9%, 68.6%, 12.8±5.7 for PTC, 37.5%, 50%, 8.6±1.7 for FTC, 20% and 20%, 4.9±0.8 for MTC, respectively. There were significant different expressions of HPSE, VEGF-C and D2-40 between the patients with lymph node-positive group and node-negative group (P=0.014, P=0.048, respectively). In addition, the expressions of them were positively correlated (P<0.001, r=0.616). Conclusion: HPSE, VEGF-C and D2-40 have a close relationship with lymph node metastasis, HPSE and VEGF-C are related to the lymphangiogenesis.

Objective To search for application ways for the safe and effective clinical methods of arsenic-containing Compound Qinghuang Powder (Compound QHP) for the treatment of myelodysplastic syndrome (MDS). Methods Totally 200 patients with MDS were included in the study and treated with Compound QHP. After one-month treatment, the 60 patients with the blood arsenic concentrations <20 μg/L were randomly divided into control group and treatment group, with 30 cases in each group. Control group was given stable treatment, while the treatment group was given increased dose of realgar; blood arsenic concentration was detected monthly; realgar 0.1 g was increased each time until blood arsenic concentrations ≥20 μg/L and realgar ≤0.3 g/d. The blood arsenic concentration, clinical efficacy and safety in the two groups were observed. Results Totally 24 cases in each group were included for evaluation finally. The average blood arsenic concentration of treatment group was significantly higher than those of control group (P<0.05). The rate of hematologic improvement was significantly higher in treatment group (54.2％, 13/24) than that in control group (29.2％, 7/24) , with significant difference (P<0.05). The Hb, ANC, and PLT significantly increased in treatment group after treatment (P<0.05). There was no significant difference of incidence rate of adverse reaction observed between treatment group and control group (P>0.05). Conclusion In application of Compound QHP, the blood arsenic concentration can be monitored to adjust the daily dose of realgar, thus to increase the effective blood arsenic concentration, and then improving efficacy without increasing the clinical toxicity.

Objective To analyze the clinical efficacy and safety of compound Qinghuang powder (compound QHP) for treatment of myelodysplastic syndromes (MDS) and its association with blood arsenic concentration (BAC). Methods 40 patients with MDS were treated with compound QHP, and the clinical efficacy, safety, and its association with BAC were evaluated after treatment for 6, 9 months, respectively. Results After treatment for 6 months, the rate of hematology improvement was 32.5 % (13/40), and the effective rate was 87.5%(35/40). 21 cases depended on the blood transfusion before treatment, after treatment 6 cases completely got rid of blood transfusion and the blood transfusion of another 6 cases was decreased by more than 50 %. The absolute neutrophil count was increased from (0.50±0.13)×109/L to (0.93±0.33)×109/L (t= 4.130, P= 0.0008). The hemoglobin content was increased from (71.06±14.82) g/L to (80.41±27.35) g/L (t= 2.233, P= 0.0321). After treatment for 9 months, 76.2 % (16/40) of the patients got rid of blood transfusion or blood transfusion reduction was more than 50%. The platelet count was increased from (45.04 ± 24.38)×109/L to (60.65±29.46)×109/L (t= 2.241, P= 0.0335). The incidence of abdominal pain and diarrhea after treatment for 1, 3 and 6 months were 12.5 % (5/40), 10.0 % (4/40) and 5.0 % (2/40), respectively, all belonging to mild level . Before treatment , there were 12 patients with abnormal liver function , including 6 cases back to normal after treatment, and 6 cases of significantly relieved, without new case with abnormal liver function. Before treatment, there were 10 cases with abnormal myocardial enzymes, including 1 cases back to normal after treatment and 9 cases significantly relieved, without new case with abnormal myocardial enzymes. No patient with abnormal renal function was observed before and after treatment. The BAC was (7.71±5.65) μg/L before treatment, which was significantly lower than that of 1, 3 and 6 months [(29.27±9.07)μg/L, (27.79 ±10.18) μg/L and (31.98 ±12.55) μg/L respectively, all P< 0.0001]. There was no significant change of BAC among the patients after treatment for 1, 3 and 6 months (P> 0.05). The BAC in efficacy group [(33.48 ±12.56) μg/L] was significantly higher than that in non-efficacy group [(21.46 ±6.00) μg/L] (t=2.089, P=0.035). 12.5% (5/40) of the patients had mild gastrointestinal side effects after treatment for 1 month, while the BAC of them [(16.93 ±1.80) μg/L] was significantly lower than that in patients without gastrointestinal side effects [(31.78±1.39 ) μg/L, P<0.0001]. The occurrence rate of abdominal pain and diarrhea was decreased after treatment for 3 and 6 months, while the BAC was increased gradually. Conclusions Compound QHP is effective in the treatment of MDS with mild adverse reactions. There is no damage to the heart, liver, and renal function. Besides, it shows that reducing the gastrointestinal adverse reactions and maintaining the effective concentration of BAC play a significant role in the effect of compound QHP in the treatment of MDS.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).