Clinical efficacy of thalidomide for various genotypes of beta thalassemia.

OBJECTIVE: The objective of this study was to investigate the therapeutic efficacy of thalidomide across various genotype presentations of ß-thalassemia so as to facilitate the early screening of thalidomide-sensitive thalassemia cases and to understand the impact of iron overload on thalidomide. METHODS: From our initial sample of 52 patients, we observed 48 patients with ß-thalassemia for two years after administration of thalidomide. This cohort included 34 patients with transfusion-dependent thalassemia (TDT) and 14 patients with non-transfusion-dependent thalassemia (NTDT). We recorded the values of hemoglobin (Hb), fetal hemoglobin (HbF), and serum ferritin (SF) in the baseline period and at 1, 3, 6, 12, 18, and 24 months after enrollment, as well as the pre- and post-treatment blood transfusion volume in all 48 cases. According to the increase in Hb levels from baseline during the 6-month observation period, the response to thalidomide was divided into four levels: main response (MaR), minor response (MiR), slow response (SLR), and no response (NR). A decrease in serum ferritin levels compared to baseline was considered alleviation of iron overload. We calculated the overall response rate (ORR) as follows: ORR = MaR + MiR + SLR/number of observed cases. RESULTS: The ORR was 91.7% (44/48 cases), and 72.9% showed MaR (35/48 cases). Among the 34 patients with TDT, 21 patients (61.8%) were free of blood transfusion, and the remaining 13 patients still required blood transfusion, but their total blood transfusion volume reduced by 31.3% when compared to the baseline. We found a total of 33 cases with 10 combinations of advantageous genes, which included 5 cases with ßCD41-42/ßCD17 and 6 cases with ßCD41-42/ß-28. Based on the treatment outcomes among the 48 cases in the observation group, there were 33 cases in the MaR group and 15 cases in the SLR/NR group. There was a difference in HbF between the two groups at baseline (P = 0.041). There were significant differences between the two groups in Hb and HbF at the time points of 6 and 12 months, respectively (P < 0.001). Compared to the baseline measurement, there was a significant decrease in the level of SF at months 12 and 24 (P < 0.001). CONCLUSION: In this study, we identified 10 ß-thalassemia gene combinations that were sensitive to thalidomide. These gene combinations can be used for initial screening and to predict the therapeutic effect of thalidomide in clinical practice. We examined the therapeutic response to thalidomide and found that the administration of thalidomide in combination with standardized iron removal was more beneficial in reducing iron overload.

ACK1 upregulated the proliferation of head and neck squamous cell carcinoma cells by promoting p27 phosphorylation and degradation.

Head and neck squamous cell carcinoma (HNSCC) is a malignancy with a worldwide distribution. Although intensive studies have been made, the underlying oncogenic mechanism of HNSCC requires further investigation. In this study, we examined the oncogenic role of activated Cdc42-associated kinase 1 (ACK1), an oncogenic tyrosine kinase, in regulating the proliferation of HNSCC cells and its underlying molecular mechanism. Results from immunohistochemical studies revealed that ACK1 was highly expressed in HNSCC tumors, with 77% (77/100) of tumors showing a high ACK1 immunoreactivity compared to 40% (8/20) of normal mucosa. Knockdown of ACK1 expression in HNSCC cells resulted in elevated p27 expression, reduced cell proliferation, and G1-phase cell cycle arrest. Rescue of ACK1 expression in the ACK1-knockdown cells suppressed p27 expression and restored cell proliferation. Compared to ACK1-knockdown cells, ACK1-rescued cells exhibited a restored p27 expression after MG132 treatment and showed an elevated level of ubiquitinated p27. Our data further showed that knockdown of ubiquitin ligase Skp2 resulted in elevated p27 expression. Importantly, the expression of p27(WT), p27(Y74F), or p27(Y89F) in ACK1-overexpressed 293T cells or ACK1-rescued SAS cells showed higher levels of tyrosyl-phosphorylated p27 and interaction with ACK1 or Skp2. However, the expression of p27(Y88F) mutant exhibited a relatively low phosphorylation level and barely bound with ACK1 or Skp2, showing a basal interaction as the control cells. These results suggested that ACK1 is highly expressed in HNSCC tumors and functions to promote cell proliferation by the phosphorylation and degradation of p27 in the Skp2-mediated mechanism.

Correlation between Traditional Chinese Medicine Constitution and Dyslipidemia: A Systematic Review and Meta-Analysis.

OBJECTIVE: To study the correlation between Traditional Chinese Medicine (TCM) constitution and dyslipidemia. METHODS: CNKI, VIP, Wanfang database, CBMdisc, PubMed, and Embase were searched, and meta-analysis was performed by Review Manager 5.2 software. RESULTS: Altogether 11 studies were included with 12890 individuals. The results showed that balanced constitution was a protective factor of dyslipidemia (OR = 0.62, 95% CI 0.47~0.82) while phlegm-dampness constitution was a risk factor of it (OR = 2.50, 95% CI 2.22~2.80), and the effect of phlegm-dampness constitution in South China (OR = 3.31, 95% CI 1.71~6.43) was more obvious than that in East (OR = 2.40, 95% CI 2.06~2.80) and North China (OR = 2.24, 95% CI 1.81~2.78). CONCLUSION: This study provides evidence for the prevention and treatment of dyslipidemia in TCM. However, most of the studies included are of moderate quality; more high quality, multicenter, large-sample studies are expected to provide higher level evidence.

Clinical observation of Conbercept intravitreal injection combined with retinal laser photocoagulation therapy on macular edema secondary to retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To study the efficacy of conbercept intravitreal injection combined with retinal laser photocoagulation therapy and simple laser photocoagulation therapy on macular edema (ME) secondary to retinal vein occlusion (RVO).METHODS:Forty-eight patients (53 eyes) with macular edema secondary to retinal vein occlusion diagnosed by clinical examination from October 2014 to March 2015 were retrospectively analyzed.Among them,28 patients (31 eyes) were treated with conbercept intravitreal injection combined with retinal laser photocoagulation,which was defined as Group A.And simple laser group contained 20 patients (22 eyes),which was defined as Group B.The clinical data including the patients' best-corrected visual acuity (BCVA) and central retinal thickness (CMT) before treatment and 1wk and 3mo after treatment were observed.RESULTS:Followed up for 3mo,the average BCVA values of A and B were 0.44±0.25,0.56±0.24,respectively and the average CMT were 330.50 ± 121.71,354.67 ± 102.79μm at first week of treatment.There was no significant difference in BCVA and CMT of Group A compared with Group B.There was statistically significant in BCVA and CMT of Group A and Group B compared with before treatment (P＜0.05).The average BCVA values of A and B were 0.24±0.18,0.39±0.20,respectively and the average CMT were 252.62 ± 83.01,332.67 ± 102.33μ m at third month of treatment.There were statistically significant differences between the two groups and compared with before treatment (P＜0.05),and Group A was superior to Group B.CONCLUSION:Conbercept intravitreal injection combined with retinal laser photocoagulation therapy and simple laser photocoagulation treatment of macular edema secondary to retinal vein occlusion are both effective that macular edema is significantly reduced,and vision is stable and improved.But for serious cases,conbercept intravitreal injection can reduce retinal edema at first,then combine with retinal laser photocoagulation which has obvious therapeutic effect and it is better than simple laser photocoagulation treatment.

[Effect of length of tibial stump on proprioceptive recovery after the reconstruction of anterior cruciate ligament].

OBJECTIVE: To evaluate the effect of length of tibial stump on proprioceptive recovery after anterior cruciate ligament (ACL) reconstruction. METHODS: From March 2011 to December 2011,42 patients with ACL tear were performed with reconstruction. The patients were divided randomly into three groups: group A, the patients with remained length of tibial stump ranging from 15 to 20 mm, including 8 males and 6 females, with an average age of (28.2 ± 6.6) years old; group B, the patients with remained length of tibial stump ranging from 5 to 10 mm, including 9 males and 5 females, with an average age of (27.9 ± 6.4) years old; group C, the patients with remained length of tibial stump less than 2 mm, including 9 males and 5 females, with an average age of (28.6 ± 6.8) years, old. The stability of knee were assessed by Lanchman test and anterior drawer test. The function of knee was assessed by Lysholm score and Tegner activity rating. The proprioceptive recovery was evaluated by assessing the passive reproduction of the angles with limb movement into flexion and extension in no weight bearing position. RESULTS: Lanchman test and anterior drawer test of all patients were negative at 6 months postoperatively., and there was one case of positive outcome in each group at 12 month and 18 month postoperatively. Lysholm score and Tegner activity score of all patients at 18 month postoperatively were significantly better than that preoperatively, and there were no significant difference among three groups at 18 month postoperatively. There were no significant difference in the production of the angles at flexion to 20° and extention to 80° and 20° among these groups before and after operation. The reproduction of the angles of group A and B at flexion to 50° and extention to 50° at 6 month postoperatively were significantly better than that of group A and B preoperatively and that of group C at 6 month postoperatively, and there were no significant difference among three groups at 18 month postoperatively. The reproduction of the angles of group A and B at flexion to 80° at 12 month postoperatively were significantly better than that of group A and B preoperatively and that of group C at 12 month postoperatively, and there were no significant difference among three groups at 18 month postoperatively. CONCLUSION: Preservation of tibial stump in ACL reconstruction has benefit in proprioceptive recovery at early stage postoperatively and the length of tibial stump should be reserved with a range from 5 to 10 mm.