Boosting synergism of chemo- and immuno-therapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Characteristics of the chloroplast genome of Dracaena marginata and phylogenetic analysis / 生物工程学报

Dracaena marginata is a widely cultivated horticultural plant in the world, which has high ornamental and medicinal value. In this study, the whole genome of leaves from D. marginata was sequenced by Illumina HiSeq 4000 platform. The chloroplast genome were assembled for functional annotation, sequence characteristics and phylogenetic analysis. The results showed that the chloroplast genome of D. marginata composed of four regions with a size of 154 926 bp, which was the smallest chloroplast genome reported for Dracaena species to date. A total of 132 genes were identified, including 86 coding genes, 38 tRNA genes and 8 rRNA genes. Codon bias analysis found that the codon usage bias was weak and there was a bias for using A/U base endings. 46 simple sequence repeat and 54 repeats loci were detected in the chloroplast genome, with the maximum detection rate in the large single copy region and inverted repeat region, respectively. The inverted repeats boundaries of D. marginata and Dracaena were highly conserved, whereas gene location differences occurred. Phylogenetic analysis revealed that D. serrulata and D. cinnabari form a monophyletic clade, which was the closest relationship and conformed to the morphological classification characteristics. The analysis of the chloroplast genome of D. marginata provides important data basis for species identification, genetic diversity and chloroplast genome engineering of Dracaena.

Rapid displacement of SARS-CoV-2 variant B.1.1.7 by B.1.617.2 and P.1 in the United States

This study reports on the displacement of Alpha (B.1.1.7) by Delta (B.1.617.2 and its substrains AY.1, AY.2, and AY.3) in the United States. By analyzing RT-qPCR testing results and viral sequencing results of samples collected across the United States, we show that the percentage of SARS-CoV-2 positive cases caused by Alpha dropped from 67% in May 2021 to less than 3.0% in just 10 weeks. We also show that the Delta variant has outcompeted the Iota (B.1.526) variant of interest and Gamma (P.1) variant of concern. An analysis of the mean quantification cycles (Cq) values in positive tests over time also reveal that Delta infections lead to a higher viral load on average compared to Alpha infections, but this increase is only 2 to 3x on average for our study design. Our results are consistent with the hypothesis that the Delta variant is more transmissible than the Alpha variant, and that this could be due to the Delta variants ability to establish a higher viral load earlier in the infection compared to the Alpha variant.

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States

As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Overexpression of a leucine transfer RNA gene tL(CAA)K improves the acetic acid tolerance of Saccharomyces cerevisiae / 生物工程学报

Acetic acid is a common inhibitor present in lignocellulosic hydrolysate. Development of acetic acid tolerant strains may improve the production of biofuels and bio-based chemicals using lignocellulosic biomass as raw materials. Current studies on stress tolerance of yeast Saccharomyces cerevisiae have mainly focused on transcription control, but the role of transfer RNA (tRNA) was rarely investigated. We found that some tRNA genes showed elevated transcription levels in a stress tolerant yeast strain. In this study, we further investigated the effects of overexpressing an arginine transfer RNA gene tR(ACG)D and a leucine transfer RNA gene tL(CAA)K on cell growth and ethanol production of S. cerevisiae BY4741 under acetic acid stress. The tL(CAA)K overexpression strain showed a better growth and a 29.41% higher ethanol productivity than that of the control strain. However, overexpression of tR(ACG)D showed negative influence on cell growth and ethanol production. Further studies revealed that the transcriptional levels of HAA1, MSN2, and MSN4, which encode transcription regulators related to stress tolerance, were up-regulated in tL(CAA)K overexpressed strain. This study provides an alternative strategy to develop robust yeast strains for cellulosic biorefinery, and also provides a basis for investigating how yeast stress tolerance is regulated by tRNA genes.

The advantages and drawbacks of dual mobility acetabular cups and its clinical application / 中华骨科杂志

Total hip arthroplasty plays a key role in the end-stage diagnosis and treatment of a variety of femoral and hip diseases, but the risk of dislocation caused by traditional bone cement prosthesis has always been one of the key constraints of total hip arthroplasty. Bousquet added a polymer lining between the femoral head and acetabulum to separate the activities between the lining and acetabulum. The dual mobility acetabular cup system can effectively reduce the incidence of prosthesis dislocation. The first generation of the dual mobility acetabular cup system is lined with polyethylene. With the progress of modern material medicine technology, a new type of the dual mobility acetabular cup system with smooth surface, bionic coating and high cross-linked polyethylene liner has been gradually formed, and its performance has been improved. Because of the existence of the inner liner, the distance between the femoral head and acetabulum of the dual mobility acetabular cup system is larger, which can allow greater range of motion, has higher stability, is not easy to dislocate, and has lower wear degree of the prosthesis at the same time. Therefore, the dual mobility acetabular cup system is more and more widely used in clinical practice, especially for the elderly with high risk of dislocation, revision surgery or neuromuscular dysfunction. But on the other hand, based on the design principle of dual motion total hip prosthesis, the disadvantages such as intraprosthetic dislocation caused by multiple factors and the lack of fixation holes result in the dual motion total hip system easily triggering acetabular loosening when targeting patients such as severe bone defects, thus limiting its further use. The dual motion total hip system can be tailored to different clinical applications, such as for populations with different characteristics, and for different methods of primary surgery, with different application strategies, thereby reducing the incidence of postoperative revision. In this paper, we take the application of the dual motion total hip acetabular system in the total hip arthroplasty as the core, and the system puts forth the principle of the dual motion total hip acetabular system, compared with traditional bone materials, introduces its advantages and disadvantages, and reveals its application strategy in the clinic, and gives an outlook for the future application of the dual motion total hip acetabular system in orthopedics.

The role of caveolin-1 in the biofate and efficacy of anti-tumor drugs and their nano-drug delivery systems

As one of the most important components of caveolae, caveolin-1 is involved in caveolae-mediated endocytosis and transcytosis pathways, and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction. In recent years, the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored. In addition, the interplay between caveolin-1 and nano-drugs is bidirectional. Caveolin-1 could determine the intracellular biofate of specific nano-drugs, preventing from lysosomal degradation, and facilitate them penetrate into deeper site of tumors by transcytosis; while some nanocarriers could also affect caveolin-1 levels in tumor cells, thereby changing certain biophysical function of cells. This article reviews the role of caveolin-1 in tumor prognosis, chemotherapeutic drug resistance, antibody drug sensitivity, and nano-drug delivery, providing a reference for the further application of caveolin-1 in nano-drug delivery systems.

Using symptom-based case predictions to identify host genetic factors that contribute to COVID-19 susceptibility

Epidemiological and genetic studies on COVID-19 are currently hindered by inconsistent and limited testing policies to confirm SARS-CoV-2 infection. Recently, it was shown that it is possible to predict potential COVID-19 cases using cross-sectional self-reported disease-related symptoms. Using a previously reported COVID-19 prediction model, we show that it is possible to conduct a GWAS on predicted COVID-19, and this GWAS benefits from the larger sample size to provide new insights into the genetic susceptibility of the disease. Furthermore, we find suggestive evidence that genetic variants for other viral infectious diseases do not overlap with COVID-19 susceptibility and that severity of COVID-19 may have a different genetic architecture compared to COVID-19 susceptibility. Our findings demonstrate the added value of using self-reported symptom assessments to quickly monitor novel endemic viral outbreaks in a scenario of limited testing. Should there be another outbreak of a novel infectious disease, we recommend repeatedly collecting data of disease-related symptoms.

A magnetism/laser-auxiliary cascaded drug delivery to pulmonary carcinoma

Although high-efficiency targeted delivery is investigated for years, the efficiency of tumor targeting seems still a hard core to smash. To overcome this problem, we design a three-step delivery strategy based on streptavidin-biotin interaction with the help of c(RGDfK), magnetic fields and lasers. The ultrasmall superparamagnetic iron oxide nanoparticles (USIONPs) modified with c(RGDfK) and biotin are delivered at step 1, followed by streptavidin and the doxorubicin (Dox) loaded nanosystems conjugated with biotin at steps 2 and 3, respectively. The delivery systems were proved to be efficient on A549 cells. The co-localization of signal for each step revealed the targeting mechanism. The external magnetic field could further amplify the endocytosis of USPIONs based on c(RGDfK), and magnify the uptake distinctions among different test groups. Based on photoacoustic imaging, laser-heating treatment could enhance the permeability of tumor venous blood vessels and change the insufficient blood flow in cancer. Then, it was noticed that only three-step delivery with laser-heating and magnetic fields realized the highest tumor distribution of nanosystem. Finally, the magnetism/laser-auxiliary cascaded delivery exhibited the best antitumor efficacy. Generally, this study demonstrated the necessity of combining physical, biological and chemical means of targeting.

Efficacy and safety of letrozole in treatment of McCune-Albright syndrome girls with peripheral precocious puberty / 浙江大学学报·医学版

OBJECTIVE@#To evaluate the efficacy and safety of the third-generation aromatase inhibitor letrozole in the treatment of McCune-Albright syndrome (MAS) girls with peripheral precocious puberty.@*METHODS@#Twenty-one MAS girls with peripheral precocious puberty treated in Pediatrics Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from March 2012 to June 2017 were enrolled in the study. Patients presented with repeated vaginal bleeding, premature breast enlargement, café-au-lait spots or dysplasia of bone fibers, and low levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH); and the congenital adrenal hyperplasia, estrogen-producing tumors, and exogenous estrogen intake were excluded. Letrozole were administrated at a dose of 0.5-2 mg·m ·d for 6 to 12 months. The patients were observed for changes in breast staging, vaginal bleeding, sex hormone levels, liver function and bone age changes, and changes in uterine and ovarian volume.@*RESULTS@#After treatment, bone age/chronological age (BA/CA)was decreased from 1.23±0.30 to 1.11±0.18 ( < 0.01); the predicted adult height (PAH) increased from (156.2±5.9)cm to (158.4±2.1)cm after treatment ( < 0.05); the vaginal bleeding was reduced and the estradiol level decreased, while the teststosterone level and the uterus showed no significant increase, and no adverse reactions such as ovarian torsion and abnormal liver function were observed.@*CONCLUSIONS@#Precocious puberty is one of the most common endocrine manifestations in MAS. Our findings suggest that letrozole may be an effective and safe therapy to precocious puberty in girls with McCune-Albright Syndrome.

Dual-targeting nanovesicles enhance specificity to dynamic tumor cells

The dynamic or flowing tumor cells just as leukemia cells and circulating tumor cells face a microenvironment difference from the solid tumors, and the related targeting nanomedicines are rarely reported. The existence of fluidic shear stress in blood circulation seems not favorable for the binding of ligand modified nanodrugs with their target receptor. Namely, the binding feature is very essential in this case. Herein, we utilized HSPC, PEG-DSPE, cholesterol and two

Sexual knowledge, attitude and associated factors among primary and middle school students / 中国学校卫生

Objective@#To understand the awareness of sexual knowledge among primary and secondary school students, as well as their attitudes towards school sex education and to provide a reference for school-based sex education.@*Methods@#A total of 5 531 primary and secondary school students were selected from Beijing, Chongqing, Heilongjiang (Harbin and Jiamusi) and Hubei (Wuhan and Xiaogan) by stratified cluster sampling and were investigated with self-reported questionnaire.@*Results@#Sex-related knowledge scored 62.33±19.35, with a pass rate of 61.9%, and the excellent rate 17.5%. Sexual knowledge of junior high school students scored 64.30±19.07, with the pass rate of 64.7%, and the excellent rate 22.0%. A large proportion of primary students reported unaware of pubertal growth and HIV/AIDS-related knowledge, and a large proportion of junior high students unaware of reproductive physiology. Multivariate Logistic regression analysis showed region, grade, gender, and suburban areas were related to the level of sexual knowledge(P<0.05). More than 76.0% primary students and 85.9% middle school students agreed on the importance of school sexuality education. 59.7% of primary school students and 73.3% of junior high school students hoped to include school sexuality education in compulsory education courses; 59.8% of primary school students and 68.3% of junior high school students felt that school sexuality education should be equipped with specialized teachers.@*Conclusion@#Chinese primary and secondary school students are lack of sexual knowledge. As students have strong wills to get more information on sexual knowledge, schools should provide them with more comprehensive and effective sex education through appropriate courses and activities.

Analysis of clinical pathological characteristics and treatment trend in colorectal laterally spreading tumor / 中华消化杂志

Objective To explore clinical pathological characteristics and treatment changed with time in patients with colorectal laterally spreading tumors (LST) from 2001 to 2015.Methods The clinical data of 549 patients with colorectal LST who received endoscopic resection or surgical operation between 2001 and 2015 were retrospectively collected.According to the time of diagnosis,patients were divided into 2001 to 2005,2006 to 2010 and 2011 to 2015 groups.The gender,age,lesion size and lesion subtypes,clinical pathologic features and their therapeutic methods were analyzed.Chi-square test was used for statistical analysis.Results The detective rates of colorectal LST in 2001 to 2005 period,2006 to 2010 period and 2011 to 2015 period were 0.38％ (50/13 319),(0.60％ (144/23 912) and 0.79％ (355/ 44 715),respectively,and the differences were statistically significant (x2 =29.34,P ＜ 0.01).During these three period,the male to female ratio was about 1:1,mean age about 59 years old,and the mean maximum diameter of the LST lesions remained about 30 mm.The percentages of granular type laterally spreading tumor (LST-G) in 2001 to 2005 period,2006 to 2010 period and 2011 to 2015 period were 82.4％(42/51),67.7％ (105/155) and 78.2％(283/262),respectively;while those of non-granular type laterally spreading tumor (LST-NG) were 17.6 ％ (9/51),32.3 ％ (50/155) and 21.8 ％ (79/362),respectively;and the differences were statistically significant (x2 =7.77,P =0.02).The proportions of LST located at the proximal colon in the three periods were 21.6 ％ (11/51),34.2 ％ (53/155) and 41.4 ％ (150/362),respectively;while the percentages of LST at distal colon were 78.4％ (40/51),65.8％ (102/ 155) and 58.6 ％ (212/362),respectively;and the differnces were statistically significant (x2 =8.61,P=0.01).The percentages of high grade neoplasia (HGN) in the three periods were 13.7 ％ (7/51),21.9 ％(34/155) and 48.6％(176/362),respectively;while the percentages of invasive carcinoma were 2.0％(1/51),5.2％ (8/155) and 8.3％ (30/362),respectively;and the differnces were statistically significantly (x2 =58.89,P＜0.01).The percentages of endoscopic mucosal resection (EMR) in the three periods were 56.9％(29/51),58.7％ (91/155) and 32.0％ (116/362),respectively;the percentages of endoscopic piecemeal mucosal resection (EPMR) were 41.2 ％ (21/51),23.9 ％ (37/155) and 14.1％ (51/362),respectively;the percentages of endoscopic submucosal dissection (ESD) were 0,12.3％ (19/155) and 46.1 ％ (167/362),respectively;the percentages of surgical operation were 0,5.2 ％ (8/155) and 7.7 ％ (28/362),respectively;and the differences were statistically significant (x2 =112.46,P＜ 0.01).Conclusions From 2001 to 2015,the clinical pathological features and therapeutic methods of colorectal LST changed along with time.The proportion of colorectal LST located at proximal colon increased,and the percentage of LST-G decreased.ESD became the primary treatment,and the proportion of pathological diagnosis of HGN and invasive carcinomas increased after operation.

Preparation of Redox-responsive Pluronic F127 Micelles with High Drug-loading Efficiency / 中国药房

OBJECTIVE:To prepare redox-responsive pluronic F127 micelles with high drug-loading efficiency. METHODS:The thiol derivative F127-SH with strong hydrophobicity was synthesized by introducing tert-butyl methacrylate and cysteamine to the hydrophobic segments of F127. Paclitaxel (PTX)-loaded redox-responsive pluronic F127 micelles with high drug-loading effi-ciency(F127-SS/PTX)were prepared by film-hydration method as well as oxidation reaction of thiol groups. The diameter,encap-sulation efficiency and drug-loading amount were detected,and the change of diameter and drug release behavior of micelles were investaged under reducing environment or non-reducing environment. RESULTS:Mean diameter of F127-SS/PTX micelles was about(77.87±1.79)nm,and encapsulation efficiency and drug-loading amount were(92.73±2.35)% and(16.25±0.99)%,re-spectively. The diameter of the micelles increased rapidly and drug release rate of PTX increased significantly in the presence of 10 mmol/L dithiothreitol. CONCLUSIONS:The redox-responsive pluronic F127 micelles with high drug-loading efficiency are pre-pared successfully.

Mechanism and clinical progress of molecular targeted cancer therapy / 药学学报

Molecular target-based cancer therapy is playing a more and more important role in cancer therapy because of its high specificity, good tolerance and so on. There are different kinds of molecular targeted drugs such as monoclonal antibodies and small molecular kinase inhibitors, and more than 50 drugs have been approved since 1997. When the first monoclonal antibody, rituximab, was on the market. The development of molecular target-based cancer therapeutics has become the main approach. Based on this, we summarized the drugs approved by FDA and introduced their mechanism of actions and clinical applications. In order to incorporate most molecular targeted drugs and describe clearly various characteristics, we divided them into four categories: drugs related to EGFR, drugs related to antiangiogenesis, drugs related to specific antigen and other targeted drugs. The purpose of this review is to provide a current status of this field and discover the main problems in the molecular targeted therapy.

Stabilized thiomer PAA-Cys-6MNA / 药学学报

The aimed of this study was to prepare stabilized thiomers to overcome the poor stability character of traditional thiomers. Poly(acrylic acid)-cysteine (PAA-Cys) was synthesized by conjugating cysteine with poly(acrylic acid) and poly(acrylic acid)-cysteine-6-mercaptonicotinic acid (PAA-Cys-6MNA, stabilized thiomers) was synthesized by grafting a protecting group 6-mercaptonicotinic acid (6MNA) with PAA-Cys. The free thiol of PAA-Cys was determined by Ellmann's reagent method and the ratio of 6MNA coupled was determined by glutathione reduction method. The study of permeation enhancement and stabilized function was conducted by using Franz diffusion cell method, with fluorescein isothiocyanate dextran (FD4) used as model drug. The influence of polymers on tight junctions of Caco-2 cell monolayer was detected with laser scanning confocal fluorescence microscope. The results indicated that both PAA-Cys and PAA-Cys-6MNA could promote the permeation of FD4 across excised rat intestine, and the permeation function of PAA-Cys-6MNA was not influence by the pH of the storage environment and the oxidation of air after the protecting group 6MNA was grafted. The distribution of tight junction protein of Caco-2 cell monolayer F-actin was influenced after incubation with PAA-Cys and PAA-Cys-6MNA. In conclusion, stabilized thiomers (PAA-Cys-6MNA) maintained the permeation function compared with the traditional thiomers (PAA-Cys) and its stability was improved. The mechanism of the permeation enhancement function of the polymers might be related to their influence on tight junction relating proteins of cells.

Morphologic diagnosis analysis of CTA technical on myocardial bridge-wall coronary artery / 中国医学装备

Objective: To discuss the morphologic diagnosis value of CTA technical on myocardial bridge-wall coronary artery. Methods: Three hundred and seventy seven patients suspected MB-MCA and with CTA and CAG inspection voluntary in cardiology clinic or hospital were analyzed, and the occurrence of type MB-MCA and MCA MB length and degree of stenosis were recorded, the results were analyzed using SPSS17.0 statistical software. Results:103 cases of 377 were diagnosed as final MB-MCA, and there were 110 MB-MCA in total. CTA and CAG checked by means of two kinds of shallow and deep in the model type MB-MCA diagnostic analysis were compared through Kappa analysis, the Kappa value were 0.803 and 1.000. Two methods had a good consistency in the diagnosis of MB-MCA;There were statistically significant in CTA and CAG two kinds of examination methods in the diagnosis of superficial in type (t=-5.149)and deep in the type MB (t=-2.457, P=0.024)(P<0.05). Conclusion:The multi-slice spiral CT angiography CTA technology has good consistency with CAG in MB-MCA diagnosis, can achieve complementary advantages, can combine their respective advantages MB-MCA to improve the diagnostic accuracy for clinical richer diagnostic information.

Evaluation of the renal hemodynamic changes in early diabetic nephropathy rats by color Doppler ultrasound and its correlation with podocyte damage / 中华超声影像学杂志

Objective To evaluated the renal hemodynamic changes in early diabetic nephropathy rats by color Doppler ultrasound and its correlation with podocyte damage.Methods Twenty male SD rats were randomly divided into 2 groups:,control group and diabetic nephropathy group.After 8 weeks,the systolic peak velocity (Vmax),diastolic minimum velocity (Vmin) and resistance index (RI) were measured by color Doppler ultrasound,the pathological changes in kidney tissues were obseved by HE staining,nephrin deposits were observed by immunofluorescence,and the nephrin mRNA expression in the renal cortex were detected by RT-PCR method.The difference of those results between two groups were compared,and the relationship between nephrin mRNA expression and index of renal hemodynamic were analysed.Results Compared with rats in control group,the Vmax and Vmin was lower among rats in diabetic nephropathy group [(16.63 ± 2.85)cm/s vs (24.16 ± 3.35)cm/s,P ＜0.001 and (5.41 ± 1.11)cm/s vs (9.87 ± 2.26) cm/s,P ＜0.001].However,the RI was higher than that of control group (0.73 ± 0.14 vs 0.57 ± 0.12,P =0.034).Bigger glomerular volume,increased mesangial matrix,increased mesangial cells,and visible focal lymphocytic or mononuclear cell infiltrated were observed in diabetic nephropathy group.The expressions of nephrin were lower in the cortex of renal in diabetic nephropathy group compared to control group (0.276 ± 0.015 vs 0.507 ± 0.024,P ＜0.001).Correlation analysis suggested nephrin mRNA expression was positively correlated with the Vmax and Vmin (r =0.931 and r =0.944,all P ＜0.001),and negatively correlated with RI (r =0.786,P ＜0.001).Conclusions Renal hemodynamic changes assessed by color Doppler ultrasound associated with podocyte damage in diabetic nephropathy rat,which is a noninvasive method of evaluation of early kidney damage.

The effects of hyperbaric oxygen in combination with rehabilitation training on motor recovery from hemiplegia caused by acute cerebral infarction / 中华物理医学与康复杂志

Objective To observe the effects of hyperbaric oxygen combined with rehabilitation training on the motor ability of ischemic stroke patients.Methods Eighty ischemic stroke patients were randomly divided into a treatment group and a control group,with 40 cases in each group.The control group was treated with Bobath' s approach,while the treatment group was treated with Bobath's methods supplemented by hyperbaric oxygen therapy.The United States National Institutes of Health Stroke Scale (NIHSS),the Fugl-Meyer motor assessment scale (FMA) (lower part) and each patient's maximum walking speed (MWS) were used to evaluate the patients before,and after 8 weeks of treatment.Results After treatment the average NIHSS score,FMA score and MWS were 4.17 ± 1.4％,31.2 ± 3.3 and 54,.3 ± 16.2 m/min,respectively,in the treatment group.The control group' s results were 6.81 ± 1.2％,26.2 ± 2.2 and 45.6 ± 18.3 m/min.The intra-group differences in evaluation results before and after treatment were statistically significant in both groups.An inter-group comparison showed that the treatment group performed significantly better after treatment than the control group in terms of FMA and MWS.After treatment,the treatment group showed significantly better walking performance in terms of cadence,stride length,step length on the affected side,gait cycle and double support duration.Conclusion Hyperbaric oxygen can make rehabilitation training more effective in improving the neurologic deficits,motor function and walking ability of hemiplegic stroke survivors.

Cellular toxicity and anti-tumor efficacy of iRGD modified doxorubixin loaded sterically stabilized liposomes / 药学学报

iRGD-modified sterically stabilized liposomes loaded doxorubicin (iRGD-SSL-DOX) were prepared and their cellular toxicity and anti-tumor efficacy were evaluated, comparing to doxorubixin loaded sterically stabilized liposomes (SSL-DOX) and RGD modified doxorubixin loaded sterically stabilized liposomes (RGD-SSL-DOX). The iRGD peptide, with both tumor targeting and cell penetrating functions, was conjugated to DSPE-PEG-NHS and DSPE-PEG-iRGD was obtained. DSPE-PEG-RGD was gained in the same way. iRGD-SSL-DOX, RGD-SSL-DOX and SSL-DOX were prepared by ammonium sulfate gradient method. The size and zeta potential of the liposomes were characterized by dynamic laser light scattering. The cellular toxicity study was done on B16 melanoma cell line and the anti-tumor efficacy study was carried on B16 cell line bearing C57BL/6 mice. The results showed that the particle sizes of liposomes were all around 90-100 nm. DOX entrapment efficiency was above 95%. The formulations were with good preparation reproducibility. iRGD-SSL-DOX showed no significant difference in B16 cellular toxicity with SSL-DOX and RGD-SSL-DOX, but the anti-tumor efficacy on B16 melanoma bearing C57BL/6 mice was significantly better than that of SSL-DOX, similar as that of RGD-SSL-DOX. Therefore, iRGD modified liposomes loaded DOX would be a promising drug delivery system for tumor therapy.