Tumor microenvironment responsive liposomes blocking CXCL12/CXCR4 pathway and synergistically enhancing immune efficacy of anti-PD-L1 / 药学学报

Blocking immune checkpoint programmed cell death receptor 1 (PD-1) or programmed death receptor-ligand 1 (PD-L1) can enhance anti-tumor activity of effector T cells. However, the lack of response in many patients to PD-1/PD-L1 therapy remains a question. Improving the immunosuppressive tumor microenvironment (TME) to enhance the efficacy of immune checkpoint inhibitors has become a promising cancer treatment strategy. We constructed a liposome system (PD-L1/siCXCL12-Lp) of CXCL12 siRNA and anti-PD-L1 peptide with matrix metalloproteinases (MMPs) responsiveness, which combined the TME regulation of siCXCL12 and the immune regulation of anti-PD-L1 peptide. All animal experiments were approved by the Biomedical Ethics Committee of Peking University. The authors found that PD-L1/siCXCL12-Lp directly down-regulated the expression of CXCL12 in vitro (33.8%) and in vivo (15.5%). It also effectively increased the ratio of CD8+/Treg by 20.0%, which helped the anti-PD-L1 peptide to better exert its immune effect. The combination therapy significantly inhibited tumor growth (52.08%) with great safety, which explored a new idea for cancer immunotherapy.

Preparation and characterization of paclitaxel microspheres in situ gel and its antitumor efficacy by local injection / 北京大学学报(医学版)

OBJECTIVE@#The current difficulties in the treatment of tumor include repeated administration and high recurrence rate after tumor resection. In order to reduce the number of doses, avoid side effects of chemotherapeutic drugs, suppress tumor growth and delay tumor recurrence after surgery, a temperature-sensitive in situ gel with paclitaxel microspheres (PTX/M gel) was prepared. PTX/M gel was administered by intratumoral injection once a month.@*METHODS@#First of all, paclitaxel microspheres (PTX/M) were prepared by emulsion solvent evaporation method. A laser particle size distribution analyzer was used to investigate the size, distribution, specific surface area of microspheres. Paclitaxel content was determined by high performance liquid chromatography (HPLC). Then encapsulation efficiency of paclitaxel was calculated and in vitro release characteristics were studied. Secondly, PTX/M gel was prepared by cold dissolution method. The phase transition temperature, elastic modulus, dissolution curve, correlation between dissolution and release were measured. Finally, U87 MG and 4T1 subcutaneous tumor models were established respectively to study the efficacy of PTX/M gel in suppressing tumor growth and delaying tumor recurrence after surgery.@*RESULTS@#The median diameter of the selected PTX/M was (32.24±1.09) μm, the specific surface area was (206.61±10.23) m2/kg, the encapsulation efficiency was 85.29%±1.34%, and the cumulative release percentage of paclitaxel from PTX/M was 33.56%±3.33% in one month. Phase transition temperature of PTX/M gel was 33 °C. The elastic modulus of PTX/M gel at 25 °C and 37 °C were 4.2×103 Pa and 18×103 Pa, respectively. The gel could stay in the body for up to 48 hours. It could be seen from the results of animal experiments that were compared with the saline group and the Taxol group, and the tumor-bearing mice of the PTX/M gel group had the slowest tumor growth (P<0.05). Similarly, in the tumor recurrence experiments, the mice of PTX/M gel group had the latest tumor recurrence after surgery.@*CONCLUSION@#As a local sustained-release preparation, PTX/M gel can effectively suppress tumor growth and delay postoperative recurrence of tumors. It has potential advantages in tumor treatment.

The value of plasma ADAMTS4 in evaluating the stability of carotid plaque / 中华普通外科杂志

Objective To explore the relationship between the level of plasma ADAMTS4 and the vulnerability of carotid atherosclerotic plaque in patients with carotid artery stenosis and the clinical value of evaluating the vulnerability of the carotid atherosclerotic plaque.Methods 60 patients with carotid artery stenosis were divided into stable plaque group and vulnerable plaque group according to the histopathological typing after carotid endarterectomy (CEA).30 patients who had atherosclerosis but no carotid plaque formation served as control.Using ELISA to measure the level of plasma ADAMTS4.Results The level of plasma ADAMTS4 was significantly higher in the vulnerable-plaque group (112.74 ± 17.47) ng/ml compared with the stable plaque group (56.67 ± 22.14)ng/ml and the control group (56.67 ± 22.14)ng/ ml,P ＜ 0.001.Logistic analysis showed that high level of plasma ADAMTS4 was risk factor for vulnerability of carotid atherosclerotic plaque (P ＜ 0.05,OR =8.240,95 ％ CI:1.512-22.915).ROC curve showed that ADAMTS4 =100.935 ng/ml could accurately predict significant vulnerability with accuracy of 94.3％.Conclusion ADAMTS4 is an effective,sensitive and non-invasive biomarker to evaluate the vulnerability of carotid atherosclerotic plaque.

Epidemiological features on 3 important viral diarrhea among children in Zhuhai during winter and spring / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the epidemiological characteristics of viral diarrhea of norovirus (NV), sapovirus (SV) and astrovirus (AstV) among children in Zhuhai during winter and spring.</p><p><b>METHODS</b>Stool specimens were collected from children with viral diarrhea in Maternal and Child Health Hospital of Zhuhai from November 21, 2009 to April 3, 2010. Nucleic acid of NV, SV and AstV from negative specimens of rotavirus and adenovirus were detected by using Reverse transcription-polymerase chain reaction (RT-PCR), and the types of positive samples of NV were also classified at the same time.</p><p><b>RESULTS</b>The total detection rate of the three viruses is 21.49 percent, the highest detection rate is 29.05% in December 2009, the lowest detection rate is 12.20% in February 2010, 87.96% of positive specimens were from children patients aged from 0 to 30 months. The season detection rate of NV, SV and AstV are 14.70%, 2.75% and 4.04% respectively. There were significant differences of NV and SV detection rates in every month of the season, whereas the AstV detection rate was comparatively stable. The highest detection rate of NV is 34.09% in children patients aged from 12 to 18 months, the highest SV detection rate is 12.5% in children patients aged from 60 to 120 months, and the highest AstV detection rate is 16.67% in children patients aged from 24 to 30 months. All the NV were belong to G II genogroup.</p><p><b>CONCLUSIONS</b>NV is one of the main pathogens causing viral diarrhea among children in Zhuhai during winter and spring, SV and AstV are also important pathogens. So we should strengthen the monitoring of viral diarrhea caused by NV, SV and AstV in infants and young children.</p>

A retrospective study on the long-term clinical outcomes of 310 porcelain laminate veneers / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the long-term clinical outcomes of porcelain laminate veneers 1-8 years following delivery.</p><p><b>METHODS</b>A total of 310 feldspathic porcelain laminate veneers on anterior teeth or premolars in 49 patients were included in the present study 1-8 years following delivery. All the subjects underwent a detailed clinical examination utilizing modified United States Public Health Service (USPHS) criteria. Restoration integrity, abrasion, color satisfaction, marginal discoloration, marginal adaptation, secondary caries, postoperative sensitivity, and gingival index (GI) of the prostheses were evaluated according to modified USPHS criteria. The 1-8 year survival rates of the veneers were statistically analyzed using the life table method.</p><p><b>RESULTS</b>The survival rates of porcelain laminate veneers were 98.7%, 98.0%, 93.8%, 93.2%, 89.7%, 81.8%, 76.3%, and 76.3% in 1 to 8 years, respectively.</p><p><b>CONCLUSIONS</b>The long-term clinical outcomes of porcelain laminate veneers are satisfying.</p>