Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.

EIDD-2801 is an orally bioavailable prodrug, which will be applied for emergency use authorization from the U.S. Food and Drug Administration for the treatment of COVID-19. To investigate the optimal parameters, EIDD-2801 was optimized

The delivery of exogenous insulin is very important for the treatment of type 1 and advanced type 2 diabetes.Traditional injectable administration is prone to cause hypoglycemia, while the intelligent insulin system has the advantages of safety, long-term effectiveness, and high responsiveness.Glucose oxidase (GOx) can consume O2 and catalyze glucose to produce gluconic acid and H2O2.Therefore, the O2 level, H2O2 content and pH of GOx system are closely related to the glucose level in the system.This review introduces the application of GOx in closed-loop insulin delivery systems at home and abroad in recent years, which can be divided into single response and multiple response of pH-response, hypoxia-response, and H2O2-response according to the mechanism.It also discusses the opportunities and challenge facing by the application of GOx in the future.

Objective To investigate the correlation between the level of presenilin-associated rhomboidlike protein (PARL) and the sperm motility,survival rate and deformity rate of sperm in workers exposed to aluminum.Methods A total of 162 male workers exposed to aluminum in a large aluminum enterprise in Guangxi were selected as the exposure group,and the 162 staff members of the service company were selected as the control group by matching the age and length of service.The concentration of aluminum in the working environment and the aluminum content in the blood and urine were determined by graphite furnace atomic absorption spectrometry and high performance liquid chromatography.Enzyme linked immunosorbent assay was used to measure the level of PARL protein in sperm and sperm function was evaluated.Results The average concentrations of aluminum in the batching,electrolysis and casting of aluminum exposure group were (6.72± 1.45),(7.23± 1.50) and (7.35± 1.72)mg/m3,which were significantly higher than those of the control group (F=8.314,P＜0.001).The content of aluminum in blood and urine of exposed group were significantly higher than those of control group (P＜0.05),while the levels of PARL of exposed group were significantly lower than those of control group (P＜0.05).Moreover,the sperm survival rate and sperm motility of exposed group were significantly lower than those of the control group,and the sperm deformity rates of exposed group were significantly higher than those of the control group(P＜0.05).Pearson correlation analysis showed that there was a positive correlation of sperm motility,sperm survival rate and protein level of PARL (rsprm motility=0.713,P=0.012;rsperm survival rate =0.628,P=0.008);while the sperm deformity rate and protein level of PARL showed a significant negative correlation (rsperm deformity rate =0.953,P =0.002).Conclusion The sperm function was significantly impaired in aluminum exposed workers,and the changes of sperm motility,survival rate and malformation rate were closely related to the protein level of PARL.

Objective To assess the efficacy and safety of morinidazole combined with appendectomy in treating purulent or gangrenous appendicitis.Methods Double-blind randomized controlled multicenter clinical trial was designed and conducted.Totally 437 patients were included,219 in the control group and 218 in the experimental group.Cases of purulent or gangrenous appendicitis were enrolled and assigned to each of the two groups.The control group received ornidazole injection for 5 to 7 days while the experimental group received morinidazole injection.Both groups underwent appendectomy.Clinical response,micrombiological outcomes,overall response were evaluated.Adverse events and side effects were recorded.Results No significant difference was observed between the two groups regarding the clinical healing rate at 5-10 days after medicine withdrawal,anaerobia clearance and overall healing rates.Adverse events occurred in 140 patients (32.1％).Incidence of adverse events in the control group and the experimental group was 34.7％ and 29.4％,respectively (P ＞ 0.05).The overall incidence of side effects was 15.1％ (66 cases).Side effects were less seen in the experimental group compared with that in the control group (11.5％ vs.18.7％,P ＜ 0.05).The most frequent side effects were aminotransferase rising,thrombocytosis,nausea,vomiting and electrocardiographic abnormality.Conclusions The effect of morinidazole plus operation was comparable with ornidazole in treating purulent or gangrenous appendicitis.The safety of morinidazole is better than ornidazole.

BACKGROUND:At present, spleen tyrosine kinase is the new target of studying and treating rheumatoid arthritis. OBJECTIVE:To study the influence of smal molecule tyrosine kinase inhibitor HL131078 on the inflammatory cel infiltration and cartilage destruction of the knee joint of mice with col agen-induced arthritis. METHODS:Forty DBA/1 mice were randomly and evenly divided into blank, model, positive and experimental groups. Col agen type II (CII) solution and Freund’s complete adjuvant (including mycobacterium tuberculosis) were injected into the mice of the latter three groups through the tail to establish mouse models of col agen-induced arthritis. At 2 weeks after the the first immunization with CII, the mice in the positive group were intragastrical y given R406 (10 mg/kg), once a day, for 28 consecutive days. The mice in the experimental group were intragastrical y given HL131078 (10 mg/kg), once per day, for 28 consecutive days. RESULTS AND CONCLUSION:Compared with the model group, the mean arthritis indexes of mice in the experimental and positive groups started to decline at 29 and 26 days. In the experimental group, the cartilage destruction of mouse knee joint was obviously reduced and the inflammatory cel infiltration in the knee joints was obviously reduced, which was close to that in the positive group. The results demonstrate that the smal molecule tyrosine kinase inhibitor HL131078 can effectively reduce inflammatory cel infiltration and cartilage destruction in the knee joints of mice with col agen-induced arthritis.

Ibuprofen/ethyl-cellulose (EC)-polyvinylpyrrolidone (PVP) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading as the main evaluation index, orthogonal experimental design was used to optimize the preparation process of EC-PVP/ibuprofen composite particles. The experiments such as encapsulation efficiency, particle size distribution, electron microscope analysis, infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 40 degrees C, crystallization pressure 12 MPa, PVP concentration 4 mgmL(-1), and CO2 velocity 3.5 Lmin(-1). Under the optimal conditions, the drug loading and encapsulation efficiency of ibuprofen/EC-PVP composite particles were 12.14% and 52.21%, and the average particle size of the particles was 27.621 microm. IR and DSC analysis showed that PVP might complex with EC. The experiments of in vitro dissolution showed that ibuprofen/EC-PVP composite particles had good sustained-release effect. Experiment results showed that, ibuprofen/EC-PVP sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.

Objective To compare the outcome of proximal femoral nail antirotation (PFNA)and third generation of Gamma nail (TGN) in the treatment of femoral intertrochanteric fracture in the elderly. Methods From January 2007 to June 2008, the patients with intertrochanteric fractures were divided into PFNA group ( n = 55 ) and TGN group ( n = 52 ) randomly. The two treatment groups were comparable in aspect of general data. The clinical data of surgical trauma, complications and postoperative function of the two groups were compared in our study. Results The mean operation time was (66.6 ± 15.4) min in PFNA group and (73. 1 ± 20.8 ) min in TGN group (P ＞ 0. 05 ). The mean intraoperative blood loss differed significantly, (219.5 ± 107.5 ) ml in PFNA group compared with (269.0 ±123.9) ml in TGN group ( P ＜ 0. 05 ). The mean fluoroscopy time was ( 2.97 ± 1.14 ) min in PFNA group and (3.43 ± 1.18) min in TGN group (P＜0.05). Unilateral femoral shaft splits at the distal end of the nail was observed intra-operatively in four patients of the PFNA group and in one of the TGN group,with no statistical difference between two groups. Of all, 91 patients ( n =46 in the PFNA group and n =45 in the TGN group) were followed up for a duration of ( 17.5 ±3.69) months. There was one re-fracture and one implant failure during the follow up period in PFNA group, which was not found in TGN group. Fiftyone patients recovered to normal activity status, including 27 in the PFNA group and 24 in the TGN group,with no statistical differences. Conclusions Intertrochanteric fracture can be treated successfully with PFNA and TGN. There is no significant difference in complications and functional outcome between the two groups. However, PFNA takes advantages of less blood loss, less operative time and less fluoroscopy time over TGN.

BACKGROUND:There are a variety of surgical approaches for minimally invasive total hip replacement,such as anterolateral,posterolateral and two-incision.However,it is unknown which one is more in line with the concept of minimally invasive and easy to carry out.OBJECTIVE:To observe the clinical application effect of total hip replacement using anterlateral modified Watson-Jones approach.METHODS:From January 2005 to December 2006,35 patients were performed total hip replacement with the new anterlateral approach at the Department of Orthopaedics,the First Affiliated Hospital of Soochow University,including 16 males and 19 females,aged 52-78 years,mean aged 65.9 years;the average body mass index was 24.4 kg/m~2 (19.3-30.1 kg/m~2).The length of incision,operative duration,transfusion,complications,postoperative movement,postoperative hospital stay,prosthesis position and Harris score after operation were observed.RESULTS AND CONCLUSION:The patients were followed up 6-24 months,with an average of 17.3 months.The average length of incision was 8.3 cm (7-12 cm).The mean operative duration was 92.1 minutes (70-120 minutes).The average blood transfusion was 300 mL (0-800 mL).All the patients were practice their limb muscles immediately after the operation and they were activity the day after operation under the guidance of doctor.The average postoperative hospital stay was 7.9 days (5-15days).Eleven hip pains occurred at 3 months,9 cases at 6 months and 5 cases at 12 months,the Harris scores were (79.5±4.4)points,(84.0±3.6) points,and (85.4±3.0) points,respectively.No infection,dislocation,vessel or nerve injury happened.From the follow up,all of the patients had good prosthesis position and rang of hip motion.The results revealed that the new anterolateral approach is minimally invasive total hip replacement,and the patients can recover faster via some proper exercise.

Objective The purpose of this study is to investigate the influence of comprehensive intervention on the family and social functions in patients with schizophrenia. Methods The stratified randomization, controlled experiment was designed for this study. 300 cases were diagnosed as schizophrenia in accordance with the Chinese classification and diagnostic criteria of mental disorder-3 (CCMD-3) diagnosis standard, and they were randomly divided into intervention group and control group. All the cases were followed up for three years after hospital discharge. Comprehensive interventions were only taken in intervention group, but not in control group. All of the cases were e-valuated by family assessment device (FAD) and social disability screening schedule ( SDSS) at the time of pre - therapy, hospital discharge and the end of 1st, 2nd and 3rd year after hospital discharge. Results In the 3rd year after hospital discharge, the scores of PANSS, FAD and SDSS of intervention group were significantly lower than those of control group ( P < 0.05 ). Conclusion Comprehensive intervention can significantly improve the family and social functions in the patients with schizophrenia.