Objective:To investigate the preparation, optimization and in vitro properties of riboflavin sodium phosphate floating microspheres. Methods: The floating microspheres composed of riboflavin sodium phosphate and calcium alginate were prepared using ion gelatin-oven drying method. Results: The properties of the microspheres were investigated, including the buoyancy, release, appearance and entrapment efficiency. The formulation was optimized by response surface methodology (RSM). Conclusion: The optimized microspheres were round. The entrapment efficiency was 57.49%. All the microspheres could float on the artificial gastric juice over 8 hours. The release of the drug from the microspheres complied with Fick' s diffusion.

Objective    To investigate the predictive value of recurrent laryngeal nerve lymph nodes (RLN) status for supraclavicular lymph node (SLN) metastasis in esophageal squamous cell carcinoma. Methods    We retrospectively analyzed the clinical data of 83 patients with esophageal squamous cell carcinoma who underwent McKeown three-field lymphadenectomy from January 2017 to April 2018 in our hospital, including 53 males and 30 females with an average age of 64.07±7.05 years. Results    The SLN metastasis rate of the patients was 24.1%. The rate in the thoracic and abdominal metastases positive (N1-3) group and negative (N0) group was 37.8% and 13.0%, respectively, with a statistical difference (P<0.05). The rate of SLN metastasis was significantly different between the RLN metastasis positive (RLN+) and negative (RLN–) groups (39.1% vs. 18.3%, P<0.05). One side of RLN metastasis could lead to SLN metastasis on the opposite side. No correlation between the SLN metastasis and age, gender, location, differentiation degree, maximum tumor diameter, T-staging or histologic type was observed (P>0.05). Multivariate analysis showed that lymph node metastasis in chest or abdomen was an independent predictor of SLN metastasis. Conclusion    RLN+ is not the independent predictor for SLN metastasis. SLN should be dissected in N1-3 patients with esophageal squamous cell carcinoma without considering tumor location and T-staging. Bilateral SLN dissection should be recommended even if RLN metastasis is only unilateral.

OBJECTIVETo evaluate and compare the clinical efficacy and safety of recombinant human thrombopoietin(rhTPO) and recombinant human interleukin11(rhIL-11) for the treatment of chemotherapy-induced thrombocytopenia in adult acute myeloid leukaemia patients.

METHODSTotal of 96 adult acute myeloid leukaemia patients were divided into 3 groups according to randomized controlled method: rhTPO group, rhIL-11 group and control group, 32 cases in each group. The patients in rhTPO group and rhIL-11 received rhTPO of 15000 IU/d and rhIL-11 of 1.5 mg/d, respectively after the standard combined chemotherapy within 24 hours, and patients in control group, received nothing drugs to promote thrombocyte recovery. And rhTPO and rhIL-11 should be stopped when the Plt≥100× 10/L. After chemotherapy, the platelet recovery degree, duration of Plt<50× 10/L, ≥50× 10/L and ≥100× 10/L, the count of infusion thrombocytes, and incidence of adverse reactions all were compared.

RESULTSThe duration of Plt<50× 10/L was obviously less than that in control group(P<0.01). The duration of rhIL-11 was less than that in control group, but there was no statistical significance(P>0.05). As compared with that in control group, the Plt count in rhTPO and rhIL-11 groups can faster increase to Plt≥50× 10/L (P<0.01, P<0.05), among them the Plt count in rhTPO group faster increase, but there was no statistical signiticance. As compared with that in control group, the Plt count in rhTPO group and rhIL-11 group can increase to Plt≥100× 10/L (P<0.01), the Plt count in rhTPO group was more obviously increase than that in rhIL-11 group(P<0.05). The count of infusion Plt in rhTPO and rhIL-11 groups was lese than that in control group(P<0.01, P<0.05), and the count of infusion Plt in rhTPO group was less than that in rhIL-11 group(P<0.05). After using rhTPO and rhIL-11, the adverse reactions, such as low fever, induration of injection site, athralgia, nausea and vomiting occured in rhTPO group and rhIL-11 group, but all can be tolerated.

CONCLUSIONBoth rhTPO and rhIL-11 can reduce the duration of thrombocytopenia and the amount of infused thrombocyte, promote platelet recovery in the patients with acute myeloid leukaemia after chemotherapy, to decreae the risk of bleeding, and reduce incidence of adverse reactions, both of them can be tolerated by patients, and rhTPO is more advantage than rhIL-11, worthy of clinical popularization and application.

The effects of electric currents applied during absolute refractory period(ARP)on the cardiac function of rabbits with heart failure due to myocardial infarction(MI),and the safety of this method were investigated.Thirty rabbits were randomly assigned equally to 3 groups: sham-operated group,LV-anterior wall cardiac contractility modulation(LV-CCM)group,and septum-CCM(S-CCM)group.A thoracotomy was performed on all the rabbits.Electric pulses were delivered during the ARP on the anterior wall of left ventricle in CCM group and in the septum in S-CCM group,respectively.The left ventricular systolic pressure(LVSP)and maximum positive left ventricular pressure change(+dp/dtmax),heart rates,ventricular tachycardia,ventricular fibrillation were observed.It was found that,as compared with the baseline,LVSP,and+dp/dtmax were significantly increased,on average,by 15.2% and 19.5% in LV-CCM group(P<0.05),and by 8.5% and 10.8% in S-CCM group(P<0.05).LVEDP was significantly decreased and-dp/dtmax increased both in LV-CCM group and S-CCM group(P<0.05).CCM had no effect on heart rate and induced no arrhythmia in short time.It is concluded that electric currents delivered during the ARP could significantly enhance the contractility of myocardium safely,suggesting that CCM stimulation is a novel potent method for contractility modulation.

AIM: To observe the application effect of single-pass four-throw pupilloplasty in combined surgery of cataract and glaucoma.

METHODS: Twenty eight patients(30 eyes)suffered from acute attack of glaucoma with large pupil and cataract, received cataract phacoemulsification and intraocular lens implantation combined with angle separation or trabeculectomy and single-pass four-throw pupilloplasty in apllication. Preoperative and postoperative visual acuity, pupil diameter and complications were observed, and postoperative visual quality were measured.

RESULTS: The visual acuity of 7d after operation was significantly improved without double vision and glare. The preoperative pupil diameter was 5.9+0.25mm, and the postoperative was 4.1±0.13mm(P<0.05). Postoperative visual quality was significantly improved(P<0.05). Among the intraoperative complications, there were 5 cases 5 eyes of iridodelamination avulsion after suture, 1 case 1 eye of small holes near the formed pupil and 3 cases 3 eyes of small blood seepage at the iris root, which recovered well after the corresponding treatment. The inflammation of anterior chamber were common at the early postoperative period, and inflammatory absorption after anti-inflammatory treatment. Long-term observation showed no loosening or shedding of the line knot in the pupil area.

CONCLUSION: Single-pass four-throw pupilloplasty is simple, safe and effective. It can obviously eliminate the visual impairment caused by the large pupil after acute glaucoma attack.

Three new labdane diterpenoids, leojaponicone A (1), isoleojaponicone A (2) and methylisoleojaponicone A (3), were isolated from the herb of Leonurus japonicus. The chemical structures of these secondary metabolites were elucidated on the basis of 1D and 2D NMR, including HMQC, and HMBC spectroscopic techniques. All the new compounds were tested in vitro for their acetylcholinesterase and α-glucosidase inhibitory activity. Compounds 1-3 exhibited low inhibitory effects on α-glucosidase with respect to acarbose and exhibited high inhibitory effects on acetylcholinesterase with respect to huperzine A.
Acetylcholinesterase ; metabolism ; Cholinesterase Inhibitors ; chemistry ; isolation & purification ; pharmacology ; Diterpenes ; chemistry ; isolation & purification ; pharmacology ; Glycoside Hydrolase Inhibitors ; chemistry ; isolation & purification ; pharmacology ; Leonurus ; chemistry ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Plant Extracts ; chemistry ; pharmacology

OBJECTIVETo explore the factors influencing total complete remission (CR), recurrence, disease-free survival (DFS) rate and overall survival (OS) rate in adults with Philadelphia (Ph) chromosome negative acute lymphoblastic leukemia (ALL) and the effect of subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT) on prognosis.

METHODSThe clinical data of 87 adult patients with Ph negative ALL were retrospectively analyzed, the CHOP regimen plus L-asparaginase (L-Asp) was used for the induction therapy, and the CHOP+ modified Hyper-CVAD or methotrexate was set up as the consolidation chemotherapy regimen. After consolidation chemotherapy for 3-6 courses, 45 patients (51.72%) received allo-HSCT , and 42 patients (48.28%) continually received the maintained consolidation chemotherapy. The average follow up time of the surviving patients was 40.13 (3-60 months).

RESULTSOut of 87 patients with PhALL one patient died (1.15%). In 86 patients who could be evaluated, 68 cases (79.67%) reached CR at the end of 1 course, 80 cases obtained CR (93.02%). Multivariate regression analysis showed that the enlargement of lever, spleen and lymphomode, WBC count≥ 100×10/L were affecting factors for total CR (P<0.05). Among 80 cases with CR, 27 cases (33.75%) relapsed, 5 years' overall survival (OS) rate and disease-free survival (DFS) rate were 47.50% and 45.00% respectively. Multivariate regression analysis yet showed that the induction chemotherapy without L-Asp, presence of CNS leukemia at diagnosis, absence of allo-HSCT and no CR after indution chemotherapy for 4 weeks were affecting factors for relapse and poor prognosis of patients (P<0.05). According to 4 prognostic factors such as presence of CNS leukemia or no, WBC count≥100×10/L or no, induction chemotherapy with L-Asp or no and CR after induction chemotherapy for 4 weeks or no, 86 patients were divided into low-risk group (without poor prognostic factor), middle-risk group (with 1 poor prognostic factor), high-risk group (with 2-4 poor prognostic factors). Statistical results showed that allo-HSCT treatment in low-risk group had no significant effect on OS and DFS (P>0.05). The rate of OS and DFS in middle and high-risk group were significantly higher than those of patients without allo-HSCT treatment (P<0.05).

CONCLUSIONPatients with central nervous system leukemia, high white blood cell count (≥100×10/L), induction chemotherapy without L-Asp, no CR after 4 weeks of chemotherapy and absence of allo-HSCT treatment are the factors influencing the prognosis of adult patients with Ph negative ALL, so the patients with those poor prognostic factors should take active treatment of allo-HSCT.

Adult ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Humans ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Remission Induction ; Retrospective Studies

Objective: To study the VP1 gene of coxsackievirus A6 (CVA6) and to reveal the molecular epidemiologic characteristics of CVA6 related to hand, foot and mouth disease (HFMD) in Anyang city from 2011 to 2015. Methods: Serotypes of human enterovirus (HEV) were detected with the real-time RT-PCR from the clinical specimens. Primers were designed and used to amply and sequence the VP1 region of CVA6. Phylogenetic tree was constructed and phylogenetic analysis was performed. Selection pressures of the VP1 gene were evaluated for different subgenotypes of CVA6 circulating in China in recent years. Results: A total of 365 specimens with CVA6 positivity were identified in Anyang city during 2011—2015. CVA6 specimens accounted for 19.59% of all HEV-positive specimens. Phylogenetic analysis showed that all CVA6 strains were divided into four genotypes and the genotype D was further divided into two subgenotypes. Among the twenty-two Anyang sequences involved in the phylogeny of CVA6, five sequences belonged to subgenotype D1 and the other seventeen sequences belonged to subgenotype D2. The values of selection pressure of the Chinese CVA6 strains within subgenotype D1 and subgenotype D2 were 0.031 and 0.075, respectively. Only one positively selected site was detected in the VP1 gene of subgenotype D1, meanwhile four were detected in the VP1 gene of subgenotype D2. Conclusions Subgenotype D1 and its successor, subgenotype D2, circulated in Anyang city during 2011—2015. The subgenotype replacement from CVA6 subgenotype D1 to CVA6 subgenotype D2 and the continuous transmission of CVA6 subgenotype D2 were the two major causes of HFMD epidemic related to CVA6 in Anyang city during 2013—2015.

OBJECTIVETo investigate the predictive value of P53, Ki-67, HER2 protein detection in neoadjuvant chemotherapy for adenocarcinoma of gastroesophageal junction (AGEJ).

METHODSPreoperative biopsy specimens and clinical data of 72 patients of locally advanced Siewert II AGEJ between June 2010 and December 2013 were reviewed. All the patients received SOX scheme neoadjuvant chemotherapy, and were divided into effective group (complete response plus partial response) and ineffective group (stable disease plus progressive disease). Expressions of above 3 proteins were detected by immunohistochemistry in all the patients before neoadjuvant chemotherapy. The relationship between various proteins and efficacy of chemotherapy was analyzed by univariate and logistic multivariate regression analyses.

RESULTSAll the 72 patients successfully completed 2 cycles of SOX neoadjuvant chemotherapy, among them, 5 cases (6.9%) with complete response, 30 cases (41.7%) with partial response, 31 cases (43.1%) with stable disease, 6 cases (8.3%) with progressive disease, including 35 cases in effective group and 37 cases in ineffective group. Compared with ineffective group, the positive expression rate of P53 was significantly reduced (25.0% vs. 45.9%, P=0.020), and that of Ki-67 significantly increased (77.1% vs. 43.2%, P=0.003), however, there was no significant difference in the expression rate of HER2 between the two groups (P>0.05). Multivariate analysis showed that Ki-67 was the independent predictive factor for the efficacy of neoadjuvant chemotherapy (P=0.015). Spearman rank correlation showed that Ki-67 expression was positively correlated with HER2 expression (r=0.259, P=0.028), but P53 expression was not correlated with Ki-67 or HER2 (r=0.140, 0.042, P=0.240, 0.725, respectively).

CONCLUSIONSSOX neoadjuvant chemotherapy is safe and effective for AGEJ, especially for patients with depressed expression of P53 and elevated expression of Ki-67, which both may be used as reference for the prediction of chemotherapy efficacy. There is no correlation between P53 and Ki67 proteins, so combined detection may improve the predictive value.

Adenocarcinoma ; diagnosis ; drug therapy ; Esophageal Neoplasms ; diagnosis ; drug therapy ; Esophagogastric Junction ; pathology ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Neoadjuvant Therapy ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Tumor Suppressor Protein p53 ; metabolism

【Objective】 To explore critical regulatory genes in the hemoglobin switch process by analyzing transcriptomic data from the GSE6236, GSE17639 and GSE35102 datasets. 【Methods】 The mRNA expression profiles of the three datasets were downloaded from the GEO database and gene annotation was performed using the AnnoProbe package.The remove-BatchEffect function of the Limma package was used to remove batch effects. Weighted gene co-expression network analysis (WGCNA) was used to explore the most relevant modular genes in reticulocytes. The receiver operating characteristic curve (ROC) was used to assess the value of differential genes in differentiating between cord blood and adult peripheral blood reticulocytes. The GSE35102 dataset was used to validate changes in differential gene expression during hemoglobin transformation. Finally, real-time quantitative PCR was used to verify differential gene expression in cord blood and adult peripheral blood reticulocytes. 【Results】 Twelve genes showed differential expression in reticulocytes from cord blood and adult peripheral blood ( |logFC|≥1.5, P<0.05). WGCNA found that genes in the blue module were most strongly associated with reticulocytes (R² =0.76,P<0.001). Of the five genes that overlapped between the two, only CDC42 showed differential expression in the combined dataset (t =3.776, P<0.001) and was able to better differentiate between reticulocytes in cord blood and adult peripheral blood. The expression of CDC42 varied significantly during the hemoglobin transformation process (Z = -2.908, P<0.01), and was significantly lower in adult reticulocytes compared to reticulocytes from cord blood (t =7.824, P <0.001). 【Conclusion】 The CDC42 gene is involved in the hemoglobin switching of reticulocytes and could be a potential therapeutic target for sickle cell disease.