A Non-inferiority Randomized Controlled Trial of Topical Bisaitong （鼻塞通） in Treatment of Moderate to Severe Allergic Rhinitis / 中医杂志

ObjectiveTo evaluate the efficacy and safety of topical Bisaitong （鼻塞通） in treating moderate-to-severe allergic rhinitis （AR）. MethodsA randomized， positive-controlled， non-inferiority clinical trial design was adopted. Totally， 108 cases of moderate-to-severe AR were randomly divided into Bisaitong group and mometasone furoate group，with 54 cases in each group. The Bisaitong group was treated with Bisaitong smeared at the nasal cavity twice a day， and the mometasone furoate group received inhalation of mometasone furoate nasal spray 100 μg in each nostril， once a day. Both groups were treated for 4 weeks and followed up after additional 4 weeks. Both groups were compared on the rhinoconjunctivitis quality of life questionnaire （RQLQ）， rhinoconjunctivitis total symptom score （RTSS）， visual analogue score （VAS） of sneezing， runny nose， nasal itching， nasal congestion degree， days of AR episodes at enrollment， after 2- and 4-week， and at follow-up. The peripheral blood eosinophil （EOS） count and percentage （EOS%）， serum eosinophil cationic protein （ECP）， serum dust mite， dermatophagoides farinae， and cockroach allergen-specific IgE （sIgE） levels were compared between groups at enrollment and after 4-week treatment. Drug overuse rate was calculated， and the safety was evaluated. The analysis of all efficacy outcomes was based on both full analysis set （FAS） and per-protocol set （PPS）. ResultsThe lower limit of the 95% confidence interval for the differences in RQLQ scores were greater than -0.6 measured after 2- and 4-week treatment and at follow-up compared to that measured at the enrollment in both groups， indicating of the Bisaitong group being non-inferior to the mometasone furoate group. There was no statistically significant difference between groups on RTSS score， VAS scores of sneezing， runny nose， nasal itching， nasal congestion degree and days of episodes at all timepoints （P＞0.05）， but each outcome changed significantly over time in both groups （P＜0.01）. The differences between groups in EOS count， EOS%， ECP levels， serum dust mite， dermatophagoides farinae， cockroach sIgE levels， and drug overuse rate were not statistically significant at enrollment and after 4-week treatment （P＞0.05）. Adverse events occurred in eight cases （15.10%） in the Bisaitong group and five cases （9.30%） in the mometasone furoate group， showing no significant difference between groups （P＞0.05）. ConclusionTopical Bisaitong is non-inferior to mometasone furoate nasal spray in the treatment of moderate to severe AR in terms of clinical symptom relief，reduction in the episodes， improvement of quality of life， and sound safety.

Research progress of enzyme-instructed self-assembly molecules for tumor therapy and imaging / 中国药科大学学报

@#Self-assembly is the basis of the formation of biological macromolecular structure. Enzyme-instructed self-assembly (EISA) with the help of tool enzymes, realizing the conversion of small molecular compounds to supramolecular nanostructures at specific sites, become a new strategy for drug discovery.In recent years, the exploration of EISA for developing malignant cancer therapy and imaging has made considerable progress, achieving the precise regulation and tumor targeting of nanostructures. This paper reviews the latest progress of EISA in the field of tumor diagnosis and treatment, the functions and characteristics of tool enzymes such as alkaline phosphatase, sirtuin, tyrosinase, γ-glutamyltranspeptidase and caspase-3,summarizes the research status of EISA targeting multiple organelles in tumor therapy, and introduces the application of EISA in tumor imaging, aiming to provide reference forthe research of EISA strategy in tumor diagnosis and treatment.

Analysis of the efficacy of a modified posteromedial approach for Klammer III posterior Pilon fractures / 中华创伤杂志(英文版)

PURPOSE@#To analyze the curative effect and technical points of a modified posteromedial approach in the treatment of Klammer III posterior Pilon fracture.@*METHODS@#A retrospective analysis of patients with Klammer III posterior Pilon fractures were conducted in our department from January 2018 to December 2019. Before the surgery, the patients were fully relieved of swelling and pain, and a comprehensive examination was carried out. The posteromedial approach exposed the posterior and medial fracture block of the distal tibia. According to the fracture of external malleolus, it is determined whether to combine a lateral incision and protect tendons and vascular nerves by a retractor, and then perform a fracture reduction and internal fixation. Postoperatively, the patients were treated with analgesia, detumescence, anticoagulation and rehabilitation exercise. The American orthopaedic foot and ankle society (AOFAS) score and visual analogue score were recorded at regular follow-up after surgery. A t-test was used for the comparison of the preoperative and final AOFAS score.@*RESULTS@#There were 7 male and 13 female (n = 20) included in the study, aged 22 to 88 years (average age 54.2 years). The injury mechanisms were falling from a height (n = 7), traffic accident (n = 6), walking injury (n = 2) and heavy injury (n = 5). The postoperative follow-up duration was 12-24 months (mean 16.95 months). The AOFAS score of the 20 patients before and after surgery were compared. The preoperative AOFAS score was 38.90 ± 3.91, and the final AOFAS score was 80.55 ± 4.20, (p < 0.001). The mean final visual analogue scores at rest, active and weight-bearing walking were 0.30, 0.85 and 1.70, respectively. One patient reported poor postoperative wound healing and required a return to hospital for debridement and anti-infection treatment.@*CONCLUSION@#In the treatment of Klammer III posterior Pilon fractures, the modified posteromedial approach can fully expose the fracture block and the collapsed articular surface of the medial malleolus, achieve good reduction and internal fixation with limited injury of the tendon and vascular nerves, and have a better prognosis.

A real world study on the relationship between drug resistance of targeted therapy and prognosis of HER-2-positive advanced breast cancer / 中华肿瘤杂志

Objective: To explore the effect of primary and acquired resistance to anti-human epidermal growth factor receptor 2 (HER-2) on the overall survival of patients with HER-2 positive advanced breast cancer. Methods: The clinical characteristics of HER-2 positive patients with advanced breast cancer admitted to Cancer Hospital of Chinese Academy of Medical Sciences from January 1998 to December 2018 were collected, and their neoadjuvant/adjuvant and advanced three-line chemotherapy were summarized. Among them, targeted drugs for HER-2 included trastuzumab, pertuzumab, T-DM1, RC48-ADC, lapatinib, pyrotinib, allitinib, sipatinib, seratinib. Based on the duration of benefit from anti HER-2 treatment, the patients were divided into two groups: primary anti HER-2 resistance group and acquired anti HER-2 resistance group. In this study, the overall survival (OS) was used as the main end point. Kaplan-Meier analysis and Cox proportional risk regression model were used to analyze the effects of different drug resistance mechanisms on the overall survival. Results: The whole group of 284 patients were included. The median age of recurrence and metastasis was 48 years old, 155 (54.6%) were hormone receptor (HR) positive and 129 (45.4%) were HR negative, 128 cases (45.1%) were premenopausal and 156 cases (54.9%) were postmenopausal, 277 cases (97.5%) had a score of 0-1 in ECoG PS and 7 cases (2.5%) had a score of more than 2 in the first diagnosis of relapse and metastasis. There were 103 cases (36.3%) in the primary drug resistance group and 181 cases (63.7%) in the secondary drug resistance group. The median overall survival time of the two groups was 24.9 months and 40.4 months, respectively, with statistical significance (P<0.001). Conclusion: Primary resistance to HER-2 is one of the factors of poor prognosis in HER-2 positive breast cancer, and its mechanism needs to be further explored.

Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021 / 中华肿瘤杂志

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

Efficacy and survival outcomes of dose-dense carboplatin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer / 中华肿瘤杂志

Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.

Risk factors for polycystic ovary syndrome with nonalcoholic fatty liver disease / 临床肝胆病杂志

Polycystic ovary syndrome (PCOS) manifests as a series of disorders in reproductive system, endocrine, and metabolism, and there is a significant increase in the prevalence rate of nonalcoholic fatty liver disease (NAFLD) in the population with PCOS. At present, the risk factors for PCOS with NAFLD have not been fully clarified. This article introduces the research advances in PCOS with NAFLD from the aspects of hyperandrogenism, insulin resistance, obesity, dyslipidemia, chronic low-grade inflammation, and intestinal flora imbalance, so as to provide ideas and methods for improving the awareness and management of PCOS with NAFLD.

Risk factors for polycystic ovary syndrome with nonalcoholic fatty liver disease / 临床肝胆病杂志

Polycystic ovary syndrome (PCOS) manifests as a series of disorders in reproductive system, endocrine, and metabolism, and there is a significant increase in the prevalence rate of nonalcoholic fatty liver disease (NAFLD) in the population with PCOS. At present, the risk factors for PCOS with NAFLD have not been fully clarified. This article introduces the research advances in PCOS with NAFLD from the aspects of hyperandrogenism, insulin resistance, obesity, dyslipidemia, chronic low-grade inflammation, and intestinal flora imbalance, so as to provide ideas and methods for improving the awareness and management of PCOS with NAFLD.

Establishment of the reference intervals of four biochemical parameters for liver function among adults in Changchun, China based on the indirect method / 临床肝胆病杂志

Objective To establish the reference intervals (RIs) of the four biochemical parameters for liver function [aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP)] in adults by using the indirect method based on the data of subjects undergoing physical examination in laboratory information system (LIS). Methods With the help of the LIS, related data were collected from the healthy adults who underwent physical examination in Physical Examination Center of The First Hospital of Jilin University from October 2019 to October 2020. The Kolmogorov-Smirnov test was used to check the normal distribution of the original data; data with skewed distribution were transformed into data with approximate normal distribution using the BOX-COX method; the Turkey method was used to remove outliers; the Mann-Whitney U test or the Z -test was used for comparison between groups; the non-parametric method was used to calculate RIs. Results A total of 27 218 subjects were included after the removal of outliers. All four parameters showed age and sex differences. The RIs of AST were 14-39 U/L for male individuals aged 20-79 years, 12-32 U/L for female individuals aged 20-49 years, and 14-39 U/L for female individuals aged 50-79 years; the RIs of ALT were 10-71 U/L for male individuals aged 20-54 years, 10-49 U/L for male individuals aged 55-79 years, 7-43 U/L for female individuals aged 20-49 years, and 9-49 U/L for female individuals aged 50-79 years; the RIs of GGT were 11-70 U/L for male individuals aged 20-64 years, 10-64 U/L for male individuals aged 65-79 years, 6-45 U/L for female individuals aged 20-49 years, and 7-54 U/L for female individuals aged 50-79 years; the RIs of ALP were 38-96 U/L for male individuals aged 20-79 years, 33-89 U/L for female individuals aged 20-49 years, and 40-106 U/L for female individuals aged 50-79 years. The RIs of AST, ALT, and GGT established in this study were similar to those in the industry standards of China (relative deviation < reference change value), and the RIs of all four biochemical parameters were verified by applicability. Conclusion The RIs of the four biochemical parameters for liver function established by the indirect method are relatively consistent with those established by the direct method, which holds promise for application in clinical laboratory.

Picky eating behavior and its association with health status among school-age children in Wuhan / 中国学校卫生

Objective@#To investigate the picky eating behavior among school-age children and to analyze its association with their health status, providing scientific basis for health promotion of school-age children in China.@*Methods@#A total of 796 students of grade 3 to grade 6 from two primary schools in Hongshan, Wuhan were selected through cluster sampling. Statistical analysis was conducted according to the results of the 3-day food record and questionnaire survey on children and their caregivers.@*Results@#In the current study, 40.58% of the children had picky eating problems, the incidence of picky eating behaviors of migrant children was higher than that of local children(χ2=3.92, P<0.05). Most of the picky eaters(23.87%) tended to reject vegetables. Compared to the others, picky eaters had lower intake of vitamin B 2 [(0.49±0.01)(0.46±0.01)mg] and vitamin C [(57.35±0.76)(54.32±0.90)mg] (t=2.03, 2.57, P<0.05) and had a higher risk of stunting(OR=1.42, P<0.05).@*Conclusion@#Picky eating behaviors are common among school-age children, which is significantly associated with stunting. Nutritional education for children (especially migrant children) are urgently needed to improve their dietary structure and promote healthy growth and development.

Simultaneous Determination of 6 Components in Volatile Oil from Citrus medica by GC-QAMS / 中国药房

OBJECTIVE：To establish a metho d for simultaneous determinat ion of α-pinene，β-pinene，myrcene，limonene， γ-terpinene and α-terpineol in volatile oil from Citrus medica . METHODS ：GC-QAMS method was adopted. The determination was performed on Agilent DB- 17 capillary column. Flame ionization detector was adopted with nitrogen as carrier gas （purity 99.999％） at the flow rate of 0.5 mL/min. The flow rate of nitrogen （make-up gas ）was 25 mL/min，the flow rate of hydrogen was 30 mL/min， and the flow rate of air was 400 mL/min. The inlet temperature was 250 ℃，and the detector temperature was 280 ℃（programmed temperature），and injection volume was 0.5 μL with split ratio of 35 ∶ 1. Using limonene as internal reference ，relative correction factors of α-pinene，β-pinene，myrcene and γ-terpinene were calculated. The contents of 4 components in the samples were calculated according to the relative correction factors. The results were compared between QAMS and internal standard method （ISM，using dodecane as internal substance ，6 components to be determined ）. RESULTS ：The linear range of α-pinene，β-pinene， myrcene，limonene，γ-terpinene and α-terpineol were 0.030 5-0.213 8，0.066 6-0.466 0，0.021 8-0.152 3，0.765 2-5.356 4，0.387 3- 2.710 8，0.034 2-0.239 6 mg/mL（all r＞0.999）. The limits of detection were 4.82，7.89，4.01，4.54，5.53，2.47 µg/mL，and the limits of quantification were 15.34，25.91，13.69，15.70，18.68，8.36 µg/mL，respectively. RSDs of precision ，repeatability and stability tests （24 h）were all less than 2％. The average recovery rates were 96.08％，97.48％，100.90％，101.22％，100.54％， 95.84％（all RSD ＜3％，n＝6）. The average relative correction factors of α-pinene，β-pinene，myrcene and γ-terpinene were 0.997 8， 1.530 7，0.952 4 and 1.025 5 （all RSD ＜1％）. The contents of α-pinene，β-pinene，myrcene，limonene，γ-terpinene and α-terpineol by ISM were 3.296 9-20.994 1，11.300 6-39.440 9，3.684 2-11.291 4，174.857 8-511.611 8，0-285.127 3，0-48.858 6 mg/g， respectively. The contents of α-pinene，β-pinene，myrcene and γ-terpinene determined by QAMS were 3.296 8-20.994 0，11.300 3- 39.439 7，3.684 1-11.291 1，0-285.126 6 mg/g，respectively. Relative content errors of 4 components as α-pinene determined by 2 methods were all less than 1％ . CONCLUSIONS ： The Δ 基金项目：四川省科技厅应用基础研究项目（No.2021YJ0114）； established GC-QAMS method is simple ，rapid，accurate and 泸州市重点科技项目 [No.2011-S-31（3/3）]；合江县人民政府—西南医 科大学战略合作项目（No.2018-HJXNYD-2） repeatable，and can be used for quantitative analysis and ＊硕士研究生 。研究方向 ：中药制备工艺及质量评价 。电话： quality control of volatile oil from C. medica . 0830-3162291。E-mail：493359958@qq.com

Association of drinking behavior and self injury behavior in adolescents / 中国学校卫生

Objective@#To explore the association between drinking behavior and self injury behavior in adolescents.@*Methods@#A total of 9 247 students from 4 middle schools were investigated. Drinking behavior and self injury behavior were collected from questionnaire survey. Univariate and multivariate Logistic regression analysis were used to analyze the relationship between drinking behavior and self injury behavior.@*Results@#Among the 9 247 middle school students, 52.8% reported ever drinking, 24.9% reported drinking behavior in the past 30 days, and 14.6% reported been drunk in the past year. The average age of drinking for the first time was 12.47±3.05. About 47.2% of the participants had self injury behavior. Male with younger drinking age ( OR =1.52), had been drunken ( OR =1.35) and frequent drinking ( OR =1.54) increased the incidence of self injury. Female reported drinking at younger age ( OR =1.69), had been drunk ( OR =1.82) and lived in cities and towns ( OR =1.20) had a higher risk of self injury.@*Conclusion@#Drinking at younger age, heavy and frequent drinking are associated with higher risk of self injury in adolescents in sex specific fashion.

Application of diffusion weighted imaging with background suppression in evaluating the injury of lower limb nerves in patients with Guillain-Barre syndrome / 中华放射学杂志

Objective:To evaluate the value of DWI with background suppression (DWIBS) in evaluating the injury of the low limb nerves in patients with Guillain-Barre syndrome (GBS).Methods:The clinical and imaging data of 30 patients with GBS and 30 healthy volunteers matched with their age and gender in Zibo Central Hospital from January 2018 to December 2019 were analyzed retrospectively. All patients received lower limb nerve electrophysiological examination and all subjects received lower limb nerve DWIBS examination one week later. The display of tibial nerve and common peroneal nerve after DWIBS image reconstruction in normal volunteers and GBS patients was scored by two senior radiologists. Kappa consistency test was used to analyze the consistency of the two senior radiologists′ scores. One-way ANOVA was used to compare the motor nerve conduction velocity (MCV) and motor nerve conduction amplitudes of tibial nerve and common peroneal nerve in patients with GBS among different DWIBS scores. Spearman correlation analysis was used to evaluate the correlation between DWIBS tibial nerve and common peroneal nerve scores and electrophysiological parameters in patients with GBS.Results:In the DWIBS images of 30 healthy volunteers, 60 tibial nerves and common peroneal nerves showed clear, sharp edges, good signal intensity, uniformity, and the scores were 4. The consistency between the two radiologists was good (Kappa value=1.0). In the 60 tibial nerves and common peroneal nerves of 30 GBS patients, 53 tibial nerves and 52 common peroneal nerves showed abnormal changes in varying degrees, including blurred edges, distortions, difficulty in recognition, and weakened signal strength, etc. The consistency between the two readers was good (Kappa value=0.879,0.863,respectively.).With the decrease of DWIBS score, the MCV and motor nerve conduction amplitude values of tibial nerves and common peroneal nervesin GBS patients decreased, and the differences between the score groups were statistically significant ( P<0.01). The scores of tibial nerves and common peroneal nerves in DWIBS were positively correlated with MCV ( r=0.83, 0.84, respectively, P<0.05) and motor nerve conduction amplitude ( r=0.81, 0.79, respectively, P<0.05). Conclusion:DWIBS could provide a three dimensional visualization of tibial nerves and common peroneal nerves, and evaluate the disorders of peripheral nerves in patients with GBS. There has correlation between the scores of tibial nerves and common peroneal nerves in DWIBS with electrophysiology parameters.

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.

Research progress of white fat browning in regulation of fat metabolism / 国际外科学杂志

The adipose tissue in mammalian can be classifieded into white adipose tissue and brown adipose tissue according to color and function. White adipose tissue can change into a new type of adipocyte - -Beige adipocyte under the condition such as sympathetic excitation. The process white adipose tissue is induced to produce beige adipose tissue is called browning of white adipose tissue. The dynamic balance between white adipose tissue and beige adipose tissue is closely related to the homeostasis of metabolism. Studying the signal transduction pathway of the white to brown transformation of adipose tissue can provide a new way to correct obesity and alleviate the disorder of obesity related glucose and lipid metabolism. The role, significance and influencing factors in metabolic regulation of white adipose tissue browning were discussed in this paper.

Erratum: Author correction to 'Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer' Acta Pharmaceutica Sinica B 2019; 9(5):1061-1077

[This corrects the article DOI: 10.1016/j.apsb.2019.03.006.].

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.

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

The effect of the shape of nanocarriers on their transmembrane across Caco-2 cell monolayer / 药学学报

Cerasomes with different shapes were constructed to investigate the effect of the nanocarriers' shape on the cellular uptake and transmembrane capacity. Cerasome-forming lipid (CFL) was synthesized via halogenation, nucleophilic addition and acylation reaction and detected by mass spectrometry and nuclear magnetic resonance spectroscopy. CFL and short chain 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) were employed to prepare organic-inorganic hybrid bicelles in discal shapes (nanodisc) by the thin-film hydration method, and CFL was also used to prepare spherical cerasomes (nanosphere). The particle size and zeta potential of nanocarriers were measured by dynamic light scattering analysis, and the morphology was observed by transmission electron microscopy. With human colon cancer cell line Caco-2 as the model, the effect of the shape of nanocarriers on cellular uptake and transmembrane capacity was investigated qualitatively by confocal laser scanning microscope (CLSM), and the transmembrane capacity was analyzed quantitatively by high performance liquid chromatography (HPLC). The results showed that nanosphere and nanodisc had similar particle diameters around 110 nm and similar zeta potential around -25 mV, with regular morphology under transmission electron microscope. The cellular uptake rate of nanodisc was significantly higher than that of nanosphere in 20 minutes. Further research on Caco-2 cell monolayer demonstrated that nanodisc with faster uptake had less accumulation in the monolayer, which means it had a higher transmembrane rate on Caco-2 cell monolayer and the transmembrane capacity of the nanodisc was better than that of nanosphere within 2 h. These results suggest that rational design of the shape of nanocarriers is expected to regulate nano-bio interactions, promote the transmembrane transport of nanocarriers, and improve the drug absorption.

Simultaneous Determination of 7 Constituents in Xiao ’er Jinqiao Granules by QAMS / 中国药房

OBJECTIVE：To e stablish a method for simultaneous determination of 7 constituents in Xiao ’er jinqiao granules . METHODS：QAMS method was adopted. The determination was performed on Lubex Kromasil C 18 column with mobile phase consisted of acetonitrile- 0.1％ phosphoric acid solution （gradient elution ）. The detection wavelength was set at 326 nm，the flow rate was 1.0 mL/min. The column temperature was 40 ℃，and sample size was 10 µL. Using chlorogenic acid as the internal reference，the relative correction factors （RCF）of neochlorogenic acid ，cryptochlorogenic acid ，forsythiaside A ，isochlorogenic acid B ，isochlorogenic acid A and isochlorogenic acid C were calculated. The effects of different chromatogram system ， chromatogram column ，the ratio of mobile phase ，flow rate and column temperature on RCF were investigaten. According to the two-point correction method combined with the relative retention time correction of the components to be tested ，the peak location was carried out. The contents of 7 components were determined by QAMS and SCM respectively and then compared. RESULTS： The linear range of neochlorogenic acid ，chlorogenic acid ，cryptochlorogenic acid ，forsythoside A ，isochlorogenic acid B ，isochlorogenic acid A ，isochlorogenic acid C were 9.27-92.70，37.36-373.60，13.02-130.20，7.15-71.50，4.56-45.60，6.32-63.20，14.69-146.90 µg/mL （r≥0.999 7）. The limits of quantification were 1.38，1.41，1.40，1.99，1.10，1.17，1.10 ng，respectively；and the limits of detection were 0.41，0.42，0.42，0.60，0.33，0.35，0.33 ng，respectively. RSDs of precision ，repeatability and stability tests were all less than 2％；average recoveries were 98.28％-99.15％ （RSD＜2.0％ ， n＝9）. RCFs of neochlorogenic acid ， （No.2013LZLY-K61） cryptochlorogenic acid ，forsythiaside A ，isochlorogenic acid B，isochlorogenic acid A and isochlorogenic acid C relative to xinyuliang@stu.cqmu.edu.cn chlorogenic acid were 0.995，1.007，0.580，1.243，1.252 and 1.247，respectively. RSDs of RCFs were all lower than 3％ under different chromatogram conditions. Absolute value of relative error between the relative retention time of components to be tested predicted by two-point correction combined with relative retention time correction and measured value was less than 2％. The contents measured by QAMS were 2.790-3.416， 14.526-17.907，3.763-4.531，1.625-1.982，1.087-1.523，1.434-2.219，3.631-5.078 mg/g；the contents measured by SCM method were 2.811-3.438，14.512-17.893，3.739-4.508，1.656-2.012，1.108-1.544，1.460-2.245，3.597-5.045 mg/g；relative errors of the two methods were within ±2％. CONCLUSIONS ：Two-point correction method combined with relative retention time correction can accurately locate the peaks of each constituent ；established QAMS method is simple ，rapid，accurate and reliable ，it can be used for simultaneous determination of 7 constituents in Xiao ’er jinqiao granules.