Tenecteplase Plus Butyphthalide for Stroke Within 4.5-6 Hours of Onset (EXIT-BT): a Phase 2 Study.

To date, the benefit of intravenous thrombolysis is confined to within 4.5 h of onset for acute ischemic stroke (AIS) without advanced neuroimaging selection. The current trial aimed to investigate the safety and efficacy of intravenous tenecteplase (TNK) plus Dl-3-n-Butylphthalide (NBP) in AIS within 4.5 to 6 h of onset. In this randomized, multicenter trial, eligible AIS patients were randomly assigned to receive intravenous TNK (0.25 mg/kg) plus NBP or NBP within 4.5 to 6 h of onset. The primary endpoint was symptomatic intracranial hemorrhage (sICH). Secondary endpoints included excellent functional outcome defined as a modified Rankin Scale score of 0 to 1 at 90 days. 100 patients diagnosed by non-contrast CT (NCCT) were enrolled, including 50 in TNK group and 50 in control group. sICH occurred in 2.0% (1/50) in TNK group and 0.0% (0/49) in control group with no difference (unadjusted P = 0.998). The proportion of excellent functional outcome was 77.6% (38/49) in TNK group and 69.4% (34/49) in control group with non-significance (absolute difference 8.2%, P = 0.36). A significant decrease in NIHSS score at 24 h (P = 0.004) and more early neurological improvement (20.4% vs 4.1%; P = 0.026) was observed in TNK vs control group, but there was no difference in other secondary outcomes. This phase 2 study suggests that intravenous TNK with adjuvant NBP seems safe, feasible and may improve early neurological function in AIS patients within 4.5 to 6 h of symptom onset selected using NCCT.Clinical Trials Registration: This trial was registered with ClinicalTrials.gov (NCT05189509).

Fingolimod protects against neurovascular unit injury in a rat model of focal cerebral ischemia/reperfusion injury.

Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms. Fingolimod (FTY-720) is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities, and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases. In the current research, the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model. Our results revealed that FTY-720 markedly decreased infarct volume, promoted neurological function recovery, and weakened the blood-brain barrier permeability of ischemic rats. The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels. These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.

A preliminary study of the role of neutrophil extracellular traps in patients with primary biliary cholangitis / 临床肝胆病杂志

Objective To investigate the expression level of neutrophil extracellular traps (NET) in the peripheral blood and liver tissue of primary biliary cholangitis (PBC) patients and its correlation with clinical biochemical parameters. Methods A total of 24 PBC patients who were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine, from August 2016 to August 2020 were enrolled, as well as 8 patients with primary sclerosing cholangitis (PSC) and 19 patients with autoimmune hepatitis (AIH) matched for age, and 19 healthy individuals were enrolled as healthy control group (HC group). The serum level of myeloperoxidase (MPO) was measured, and its correlation with clinical indices were analyzed. Immunofluorescence assay was used to measure the expression of NET in the liver of PBC patients, and an in vitro experiment was to compare the ability of peripheral blood neutrophils to produce NET between PBC patients and healthy controls. Normally distributed continuous data were expressed as mean±standard deviation, and the independent samples t -test was used for comparison between two groups; for the non-normally distributed continuous data expressed as M ( P 25 - P 75 ), the Kruskal-Wallis H test was used for comparison between multiple groups, and the Mann-Whitney U test was used for comparison between two groups. A correlation analysis was performed for MPO level and liver-related laboratory markers, and the Spearman's correlation coefficient was calculated. Results The serum level of MPO in the PBC group was increased to 811.21 (450.67-1 216.20) ng/mL, which was significantly higher than that in the AIH group [468.58 (142.63-812.43) ng/mL] and the HC group [357.54 (203.52-811.21) ng/mL] ( P < 0.05), suggesting that there was a significant increase in the production of NET in peripheral blood of PBC patients. The PSC patients had a serum MPO level of 763.56 (489.59-1 633.14) ng/mL, which was significantly higher than that in the HC group ( P < 0.05). MPO level was positively correlated with alkaline phosphatase ( r =0.500, P < 0.05), gamma-glutamyl transpeptidase ( r =0.426, P < 0.05), alanine aminotransferase ( r =0.521, P < 0.05), and aspartate aminotransferase ( r =0.547, P < 0.01). Confocal immunofluorescence showed colocalization of H3Cit and MPO in the liver of PBC patients. In vitro experiment showed that compared with the HC group, the PBC group had an increase in NET produced by peripheral blood neutrophils after in vitro stimulation and an increase in spontaneous production of NET. Conclusion There is an increase in NET in peripheral blood and liver of PBC patients, and the content of peripheral blood NET is positively correlated with biochemical parameters of liver function. NET may become a novel biomarker for assessing the severity of PBC.

Clinical observation on uterine and breast development in girls with Turner syndrome with the estrogen hormone replacement therapy / 中国实用儿科杂志

OBJECTIVE: To research an appropriate estrogen therapy for in the pubertal development in Turner syndrome(TS)achievedbyestradiolvalerate.METHODS: In 57 TS girls of no spontaneous puberty or puberty arrest,we retrospectively studied pubertalstageanduterinedimensionduringtheestrogenreplacementtherapy.Datafrompatientrecordswascollected,described thepubertaldevelopingprocedure,and compared in groups which grouped by estrogen dosage to detect an appropriate dosage andthatcanleadabetterbreastanduterinedevelopment.RESULTS: The median age at start of puberty induction was 15.00 years,witharangeof11.5-21.0 years.(1)Breast development:Breast development to Tanner stage B2 was achieved in 0.29(0.25-0.33)years,stage B3 in 0.75(0.46,1.08)years,stage B4 in 2.20(0.92,3.08)years and B5 in 3.67(1.71,4.44)years.(2)Uterine development:The uterine volume and length in TS girls before treatment was 0.51(0.14,0.86)ml and 1.89(1.23,2.18)cm. We groupedthepatientsofTannerstageB2 ingroupsofestrogendosage≤0.5 mg/dand>0.5 mg/d and the uterine dimension and weightshowednodifference.Whenthepatientsweregroupedasgroupsofdosage<1.0 mg/d and group of dosage≥1.0 mg/d in stageB3,the uterine indexes in lower dosage group were less than group with larger dosage. When they were grouped as groups ofdosage<1.5 mg/d and ≥1.5 mg/d,the uterine volume 6.96(3.15-11.00)ml in lower dosage group was smaller than that in group withlargerdosage.CONCLUSION: During estrogen treatment in TS girls,normal breast development can be achieved. In a clinical setting,the uterine volume and length under pubertal induction developed properly with the breast stages progressing. when the breastdevelopedtostageB2,the uterine development was more dependable on estrogen. We recommend a low daily beginning estrogendosageuntilstageB2,which can be increased gradually after B2 to speed up the uterine development.

Carboxymethyl cellulose modified graphene oxide as pH-sensitive drug delivery system.

Nanotechnology has been studied to improve drug delivery and cancer treatment. The aim of this study is to introduce amino groups into graphene oxide (GO) to form aminated fumed graphene (GO-ADH) and combine GO-ADH with carboxymethyl cellulose (CMC) to produce GO-CMC complex as a drug carrier matrix. The anti-cancer drug small molecule doxorubicin hydrochloride (DOX) was bond to GO-CMC by π-π bond interaction and hydrogen bonding to form GO-CMC/DOX drug loading system. Via the FT-IR, transmission electron microscopy (TEM) and Zeta potential analyzer analysis showed that GO-CMC complex was successfully synthesized. Studies have shown that when pH=5.0, the cumulative release rate of drugs can reach 65.2%, which means it has pH-sensitive ability. The cells were treated with MTT method and human cervical cancer cells (Hela cells) and mouse fibroblasts (NIH-3T3 cells). The results showed that GO-CMC had no obvious cytotoxicity and good biocompatibility.

Enzymatic synthesis of quaternary ammonium chitosan-silk fibroin peptide copolymer and its characterization.

Free radicals are closely related to the occurrence and development of aging, cancer and inflammation. The aim of the present study was to improve the antioxidant effects of quaternary ammonium chitosan (QCS) by modified with silk fibroin peptide (SFP). The modification had been confirmed by FT-IR and 1H NMR spectroscopy. Degree of substitution (DS) of QCS-SFP could be controlled by adjusting the reaction conditions. In this paper, the results of moisture absorption and retention test showed that QCS-SFP had excellent moisture absorption and retention properties. In vitro antioxidant activity assays demonstrated that, with the DS and concentration increasing of QCS-SFP, the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, hydroxyl radical and hydrogen peroxide (H2O2) increased. Furthermore, the methyl thiazolyl tetrazolium assay (MTT) was applied to evaluate the biocompatibility of QCS-SFP, and the result indicated that QCS-SFP with the DS of 0.32 displayed pronounced cell viability at 100ppm. These results suggested that QCS-SFP would appear to be a promising candidate for wound dressing application.

Preparation and characterization of chitosan - collagen peptide / oxidized konjac glucomannan hydrogel.

In this paper, the microbial transglutaminase (MTGase) was used as a catalyst to graft the collagen peptide (COP) molecules on the amino group of chitosan to obtain water-soluble chitosan-collagen peptide (CS-COP) derivatives. The preparation of composite hydrogel was via the Schiff-base reaction between the amino of CS-COP and the aldehyde of oxidized konjac glucomannan (OKGM). The hydrogels were characterized by various techniques including Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The results of SEM showed that the hydrogel sample had a clear and stable three-dimensional network structure. Meanwhile, these effects of the addition of OKGM on gelation time, swelling behaviors, water evaporation rate and blood coagulation capacity were investigated. The shortest gelation time for hydrogels was 99.3s. The hydrogels showed a good swelling ability and appropriate water retention capacity. The maximum swelling ratio of the hydrogel was 265%. Dynamic blood clotting test showed that the hydrogels materials had good blood coagulation capacity. Moreover, The biocompatibility of hydrogels was evaluated with NIH-3T3 cells by MTT method. The results indicated that the hydrogels exhibited better biocompatibility. Therefore, this hydrogel has a promising potential to be applied as wound dressing.

The feasibility and practice of Nurse Practitioner in China / 中华护理杂志

With the development of China's economy and aging of the population,patient's demands for nursing are increasingly high,thus it is very important to cultivate high-end and practical nursing personnel.This paper analyzes the necessity and feasibility of the development of Nurse Practitioner in China,and explores the qualifications and management of Nurse Practitioner,the job content of Nurse Practitioner,and the training of Nurse Practitioner.

Design and Application of Virtual Isolation Private Cloud Storage in Hospital / 医学信息学杂志

In order to improve the access and control of core data in medical information security,the paper builds a virtual isolation private cloud storage architecture in hospital,including virtualized reconstruction,metadata model application based on hierarchical model,access to remote clients design and application based on virtual isolation and so on,providing a reliable method for the isolation and intercommunication between the intranet and extranet.

Clinical observation of isolated immunoglobulin G4-related sclerosing cholangitis and immunoglobulin G4 sclerosing cholangitis combined autoimmune pancreatitis / 中华肝脏病杂志

Objective@#To compare and analyze patient’s general condition, laboratory testing and therapeutic responses of isolated immunoglobulin G4- related sclerosing cholangitis (IgG4-SC) and immunoglobulin G4 sclerosing cholangitis combined autoimmune pancreatitis (IgG4-SC/AIP).@*Methods@#A retrospective study was conducted on IgG4-SC patients who attended outpatient and inpatients department of our hospital from April 2014 to March 2018 and their demographic characteristics, laboratory testing, and therapeutic responses were statistically analyzed. Normal distribution of continuous variables was compared with t-test, non-normal distribution of continuous variables was compared using the Mann-Whitney U test, and the categorical variables were compared with χ 2 test.@*Results@#29 IgG4-SC patients were included, including 19-isolated IgG4-SC and 10 IgG4-SC combined AIP (IgG4-SC/AIP). The average age of onset in the isolated IgG4-SC group was (46.06±19.03) years which was lower than IgG4-SC/AIP group (62.60±15.11), t = -2.360, P < 0.05. The median IgG4 in IgG4-SC/AIP patients is higher than that in isolated IgG4-SC, respectively 10.87 (3.73 ~ 20.13) and 3.14 (2.37 ~ 4.78)g/L(U = 159.000, P < 0.05). IgG4/IgG ratio is higher in IgG4-SC/AIP, than that in isolated IgG4-SC, respectively 0.62(0.23 ~ 0.86) and 0.16(0.10 ~ 0.21), U = 130.000, P < 0.05. Liver cirrhosis was more common in isolated IgG4-SC group (47%) than the IgG4-SC/AIP group (0), χ 2 = 9.637, P < 0.05. The median biochemical response time of isolated IgG4-SC group was 3.00 (2.00 to 4.00) months, which was longer than 1.00 (1.00 to 1.25) months of IgG4-SC/AIP group, U = 30.000, P < 0.05. The biochemical recurrence rate of isolated IgG4-SC group was 32%, which was lower than that of IgG4-SC/AIP (χ 2 = 6.461, P < 0.05).@*Conclusion@#Serum IgG4 level and IgG4/IgG ratio were higher in patients with IgG4-SC/AIP group, and therapeutic responses in isolated IgG4-SC patients were worse than that of IgG4-SC/AIP patients. The efficacy of glucocorticoid monotherapy and immunosuppressive agents combined with glucocorticoid therapy demonstrated no considerable difference in IgG4-SC patients.

Application of nasogastric feeding tube placed by endoscopy to give enteral nutrient solution in the pediatric intensive diseases / 中华临床营养杂志

Objective To investigate the efficacy and safety of nasogastric feeding tube placed by endoscopy to give enteral nutrient solution in the pediatric intensive diseases.Methods A retrospective analysis of 30 children with serious illness who were given enteral nutrient solution through the nasogastric feeding tube placed by endoscopy from January 2013 to May 2016 in our hospital was conducted including 12 boys and 18 girls aging from 2 months to 14 years with the mean as (6.86±3.44) years old.Catheterization condition including catheter insertion time after hospitalization,catheter maintenance time,hospital stay and retention time after discharge,postoperative complications after catheterization,prognostic indications including anal exhaust and defecation time,blood urine amylase and returning to normal time,and changes of the indicators for nutrition including total protein,albumin,prealbumin,retinol binding protein were analyzed.Results Catheter insertion time after hospitalization was (16.13 ± 10.51) days,catheter maintenance time (21.35± 9.62) days,hospitalization time after catheterization (20.10±8.96) days and hospital stay (36.23± 14.20) days.10 cases (33.3％) maintained the catheter for (11.10±4.65) days after the discharge.The anal exhaust time was (2.84±3.32) days and the defecation time (4.55±3.35) days;The urinary amylase significantly deceased three days after catheterization compared with that of one day before catheterization (P =0.047);Serum total protein,albumin,prealbumin and retinol binding protein increased three days after catheterization compared with that of one day before catheterization,but the difference was not statistically significant (P＞0.05).5 children (17％) had complications including 3 children of abdominal distension and 2 children of vomiting.Conclusions Nasogastric feeding tube placed by endoscopy to give enteral nutrient solution in the pediatric intensive diseases can improve the intestinal and pancreatic function,recover their nutritional status to some extent and be controlled safely.However,the waiting time for catheterization and the hospital stay after catheterization are relatively long.The implementation of this technology and the awareness of its safety need be strengthened.

Dyslipidemia and Its Related Factors in Chinese Children and Adolescents with Turner Syndrome / 中山大学学报(医学科学版)

[Objective] To analyze blood lipid and its related factors in Chinese children and adolescents with Turner syndrome.[Methods] The untreated TS patients were divided into two groups according to age (＜11 years old and 11～15 years old) and enrolled two groups of age-matched control girls,blood lipid and the incidence of dyslipidemia were compared between the four groups,the related factors of blood lipid were also analyzed.Moreover,TS patients were divided into two groups according to karyotype,including 45,XO karyotype (55 cases) and other karyotypes (53 cases),blood lipid and the incidence of dyslipidemia in two groups were compared.[Result] Compared to age-matched control girls,TS patients of age 11～15 years group had higher TG levels and higher incidence of hypertriglyceridemia and borderline-hypertriglyceridemia (P＜0.05) and the incidence of borderline-hypercholesterolemia was also significantly higher (P＜0.01).But there were no differences in blood lipid level,incidence of dyslipidemia and the incidence of borerline-dyslipidemia between TS patients who were less than 11 years old and age-matched control girls.Total cholesterol of TS patients was negatively related to bone age (P＜0.05).Triglyceride of TS patients was positively related to waist circumference (P＜0.01).TS patients of 45,XO karyotype had lower TG levels,higher HDL levels and lower incidence of low HDL,borderline-high non-HDL and borderline-hypertriglyceridemia compared with those of other karyotypes (P＜0.05).[Conclusions] Triglyceride in TS patients of age 11-15 years were higher than the control subjects,which may be related to estrogen deficiency and chromosome karyotype.

Effect of Letrozole on the Reproductive Function and Linear Growth in the Early and Mid Puberty Boys / 中山大学学报(医学科学版)

[Objective] To investigate the effect of letrozole on the reproductive function and linear growth in the early and mid pubertal boys.[Methods] 43 early and middle pubertal boy with seriously damaged predict adult height,treated with letrozole 1.5 mg/m2/d Po ((＞)2.5mg/d) were enrolled as treatment group.48 cases of healthy pubertal boys were enrolled as control.Growth parameters,sex hormone profiles,IGF-1,AMH and Inhibin B (INHB) were elevated at the beginning and after letrozole treatment.[Results] At baseline,no significant differences appeared in age,bone age,observation time,height for chronological age,height for bone age,midparental target height,BMI,or testis volume between two groups.After intervention,treatment group of bone age delayed,predict adult height increased,testicular volume increased and BMI increased compared with the control group (P=0.001,0.018,0.002,and 0.027,respectively).The serum FSH,△FSH,LH,△LH,LH/FSH,T,and △T in the treatment groups were much higher (all P＜0.001),while the serum E2 and △ E2 levels were obviously lower than the control group (P=0.043 and P=0.033,respectively).17 cases of control group and 13 cases of treatment group had serum AMH,INHB level tested before and after letrozole treatment.Serum AMH level in the control group appeared with a decreasing trend with the progress of puberty,while the treatment group showed the opposite tendency.And the △ AMH was significant difference between control group and treatment group (P＜0.001).The serum INHB in the two groups increased in varying degrees after the intervention,the INHB level in control group increased more than the treatment group,but the difference was not statistically significant (P=0.517).[Conclusion] Letrozole treatment can elevated levels of serum T with E2 reduce,bone age delay,predict adult height improved,and can obviously promote the secondary sex characters development in adolescent boys.And the longer letrozole treatment time,the more obvious growth effect.As to the reproductive function,letrozole may have inhibitory effect on testis maturity and cannot deny testis sertoli cells function affected with letrozole exposure.

The association between polymorphisms of Eotaxin gene and the allergy to cow's milk protein in infants / 中华实用儿科临床杂志

Objective To assess the association between-426C＞T,-384A＞G,+ 67G＞A polymorphisms in Eotaxin gene and cow's milk protein allergy (CMPA) in infants.Methods One hundred and six patients with CMPA who were hospitalized at Children's Hospital Affiliated to Nanjing Medical University from July 2014 to July 2015 were selected as CMPA group,and 124 healthy infants chosen from Ninghai Road Community Health Service Centers at the same time were selected as healthy control group,and the serum levels of Eotaxin in 2 groups were measured by enzyme-linked immunosorbent assay (ELISA),polymerase chain reaction (PCR) and DNA direct sequencing technology were used to detect the genotypes for single nucleotide polymorphisms (SNPs) of-426C ＞ T,-384A ＞ G,and + 67G ＞ A in Eotaxin gene.The association between the SNPs of-426C ＞ T,-384A ＞ G,and + 67G ＞ A in Eotaxin gene and CMPA,the peripheral blood eosinophil counts,serum Eotaxin levels,and serum total immunoglobulin E levels were analyzed.Results For-426C ＞ T,the frequency of each genotype of the CMPA group was CC,CT,TF (79.25％,19.81％,0.94％),while the frequency of each genotype of the healthy control group was CC,CT,TT(88.71％,8.06％,3.23％).There was a significant difference in the genotype frequency in-426C ＞ T between the CMPA group and the healthy control group (x2 =7.83,P ＜ 0.05).The individuals with heterozygous genotype(CT) had a 1.75-fold increased risk of developing CMPA compared with the individuals with wild-type genotype (CC) [odds ratio (OR) =2.75,95％ confidence interval(CI):1.23-6.15,P ＜ 0.05].For position + 67G ＞ A,CMPA patients with a genotype including variant nucleotide had lower peripheral blood eosinophil counts [(0.48 ± 0.06) × 109/L] and serum Eotaxin levels [(157.67 ± 12.72) ng/L] than those with wild-type genotype [(0.85 ± 0.09) × 109/L,(286.96 ± 33.23) ng/L] (F =10.30,5.75,all P ＜ 0.05).Conclusions Polymorphism of the Eotaxin gene (-426C ＞ T) was associated with the susceptibility to CMPA.Polymorphism of the Eotaxin gene(+ 67G ＞ A) was related to the blood eosinophil counts and the serum Eotaxin levels in children with CMPA.

Preparation and characterization of hydroxypropyl chitosan modified with nisin.

Nisin had been grafted to hydroxypropyl chitosan (HPCS) using microbial transglutaminase (MTGase) as biocatalyst. HPCS was synthesized from chitosan and propylene oxide under alkali condition. The chemical structures of derivatives were characterized by FT-IR and 1H NMR spectroscopy. The process conditions were optimized from the aspects of the reaction time, the reaction temperature, the molar ratio of nisin to HPCS and the mass ratio of MTGase to HPCS. In this study, the results of moisture absorption and retention tests showed HPCS-nisin had moisture absorption and moisture retention abilities. In addition, in vitro antibacterial activity assessment, HPCS-nisin with the concentration of 0.008mg/mL showed pronounced inhibitory effect against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli). Furthermore, the methyl thiazolyl tetrazolium assay (MTT) was applied to evaluate the biocompatibility of HPCS-nisin, and the result indicated that HPCS-nisin with the degree of substitution (DS) of 0.18 displayed pronounced cell viability at 500ppm in the range of certain toxicity. Therefore, the results suggest that HPCS-nisin could be potential wound dressings for pharmaceutical applications.

Synthesis and in vitro antimicrobial and antioxidant activities of quaternary ammonium chitosan modified with nisin.

Nisin had been grafted onto quaternary ammonium chitosan (QCS) through an enzyme-catalyzed reaction to enhance its limited antimicrobial activity. QCS was synthesized by incorporating N-(3-chloro-2-hydroxypropyl) trimethyl ammonium chloride (CHPTAC) onto chitosan's primary amine group. The modification had been confirmed by FT-IR and 1H NMR spectroscopy. Degree of substitution (DS) of QCS-nisin could be controlled by adjusting the reaction conditions. The synthesized compounds were screened in vitro to evaluate their antimicrobial and antioxidant activities. The results suggested that QCS-nisin significantly suppressed the growth of both gram-positive bacteria and gram-negative bacteria; The antioxidant effects on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, hydroxyl radical and hydrogen peroxide (H2O2) proved to be enhanced with increasing DS and concentration. In addition, QCS-nisin showed excellent moisture absorption and retention properties; MTT assay exhibited that QCS-nisin revealed low cytotoxicity effects on cultured NIH-3T3 fibroblasts. These results suggest that QCS-nisin would appear to be a promising candidate for wound dressing application.

Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies.

OBJECTIVE: We assessed the efficacy and safety of a weekly pegylated human growth hormone (PEG-rhGH) (Jintrolong) vs daily rhGH for children with growth hormone deficiency (GHD). DESIGN: Phase II and III, multicenter, open-label, randomized controlled trials. METHODS: 108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively. Patients in the phase II study were randomized 1:1:1 to weekly Jintrolong (0.1 mg/kg/week PEG-rhGH complex), weekly Jintrolong (0.2 mg/kg/week PEG-rhGH complex) or daily rhGH (0.25 mg/kg/week) for 25 weeks. Patients in the phase III study were randomized in a 2:1 ratio to weekly Jintrolong (0.2 mg/kg/week) or daily rhGH (0.25 mg/kg/week) for 25 weeks. The primary endpoint for both studies was height velocity (HV) increase at the end of treatment. Other growth-related parameters, safety and compliance were also monitored. RESULTS: The phase II study established the preliminary efficacy, safety and recommended dose of Jintrolong PEG-rhGH. In the phase III study, we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment (from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year) vs daily rhGH (from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year) at the end of treatment (P < 0.05). Additionally, significantly greater improvement in the height standard deviation scores was associated with Jintrolong throughout the treatment (P < 0.05). Adverse event rates and treatment compliance were comparable between the two groups. CONCLUSION: Jintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH.

Preparation, characterization and antioxidant activity of silk peptides grafted carboxymethyl chitosan.

Free radicals are closely related to the occurrence and development of aging, cancer and inflammation, the ability to scavenge free radicals is an important indicator of the antioxidant activity. In this study, we prepared a water soluble, free radical scavenging and biocompatible copolymer for regenerative therapy. Carboxymethyl chitosan (CMC) was modified with silk peptide (SP) by microbial transglutaminase (MTGase), FT-IR and NMR spectroscopy were used to confirm the successful grafting of SP to CMC. The degree of substitution was determined by ultraviolet spectrophotometry. In vitro antioxidant activity assays demonstrated that, within the scope of study the highest scavenging activity of DPPH was 24.86%, 91% of hydroxyl radical and 36.8% of H2O2. Finally, no relevant cytotoxicity against NIH-3T3 mouse fibroblasts was found for the copolymers. Briefly, our results suggested the potential application of CMC-SP as an antioxidant for regenerative therapy.

Sequential treatment strategy for malignant pleural effusion in non-small cell lung cancer with the activated epithelial grow factor receptor mutation.

With the advent of molecularly targeted therapy, it is necessary to reconsider the strategy for malignant pleural effusion in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The aim of this study was to evaluate the efficacy of a two-line sequential treatment strategy in this patient subgroup. First-line treatment was gefitinib (250 mg/day) until disease progression. Second-line treatment was thoracoscopic talc pleurodesis followed by chemotherapy. Primary endpoints were the overall response and progression-free survival rates after first-line treatment, and the overall survival rate after first- and second-line treatment. Secondary endpoints were the success rate of thoracoscopic talc pleurodesis and gefitinib toxicity. Among the 76 patients enrolled, 61 (80%) were female and the median age was 62 years. The overall response rate after first-line treatment was 92.1% and median progression-free survival was 15 months. The success rate for thoracoscopic talc pleurodesis in 33 patients was 94%. Median follow-up was 35 months. Median overall survival was 39 months. The 1- and 3-year overall survival rates were 86.4% and 46.1%, respectively. The two-line sequential treatment strategy enhanced survival. These preliminary findings provide an insight into novel therapeutic models for malignant pleural effusion in NSCLC harbouring EGFR mutations.

Protective effect of 2-deoxy-D-glucose on the brain tissue in rat cerebral ischemia-reperfusion models by inhibiting Caspase-apoptotic pathway.

We observed the effect of 2-deoxy-D-glucose (2-DG) on the brain tissue in rat cerebral ischemia-reperfusion (I/R) and explored its mechanism. After observing the effect of 2-DG on endoplasmic reticulum stress (ERS), rats were randomly divided into sham-operation group, I/R group and I/R+2-DG group (each group with 60 rats). I/R models were prepared by middle cerebral artery occlusion. In I/R+2-DG group, each rat was given intraperitoneal 2-DG of 100 mg/kg once a day for 7 days before brain ischemia. According to different time points (3h, 6h, 12h, 24h and 48h) after I/R, each group was divided into 5 subgroups (each subgroup with 12 rats). Nerve cell apoptosis, and the expressions of mRNA and protein of glucose regulated protein 78 (GRP78), cleaved-caspase-9 and cleaved-caspase-3 were determined with TUNEL, Western blotting and RT-PCR, respectively, in rat cerebral hippocampal CA1 area at each time point. TUNEL-positive cells were significantly less in I/R+2-DG group than in I/R group at each time point (all P<0.01). In I/R and I/R+2-DG groups, the expressions of mRNA and protein of GRP78 reached the maximum 12 h after I/R, and cleaved-caspase-9 and cleaved-caspase-3 reached the maximum 24 h after I/R. Compared with sham-operation group, the expressions of mRNA and protein of GRP78, cleaved-caspase-9 and cleaved-caspase-3 were all significantly increased (all P<0.01) in I/R and I/R+2-DG groups. However, the expressions of mRNA and protein of GRP78 were significantly higher in I/R+2-DG group than in I/R group (all P<0.05), but the expressions of mRNA and protein of cleaved-caspase-9 and cleaved-caspase-3 were all significantly lower in I/R+2-DG group than in I/R group (all P<0.05). We conclude that 2-DG has a neuroprotective effect on the brain tissue in rat cerebral ischemia-reperfusion models. The mechanism may be that 2-DG starts ERS followed by up-regulation of mRNA and protein of GRP78 and down-regulation of mRNA and protein of cleaved-caspase-9 and cleaved-caspase-3, which blocks the apoptotic pathway.