Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P＜0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Aim To study the effect of gender differences in C57BL / 6J mice on antigen induced Sjogren's syndrome(SS)model. Methods The submandibular gland protein of C57BL/6J female and male mice was extracted and mixed with the same amount of Freund's complete adjuvant(FCA)for the first three times, the antigen concentration was adjusted to 2.5 g·L-1, mixed with Freund's incomplete adjuvant(FIA)for the fourth time, and the same-sex mouse antigen was injected into the back of mice for a total of four times to induce the mouse SS model. The mouse SS model was induced by multi-point intradermal injection of antigen on the back of mice for four times,the body weight of female and male mice was measured every week, the general condition was observed, the saliva volume of mice was measured at the sixth week of modeling. After the mice were sacrificed, the pathological changes of submandibular gland and the changes of T and B lymphocyte subsets in spleen were detected, and the differences in SS model preparation between female and male mice were compared. Results The SS model of male and female mice was successfully established, and there was no significant difference in general condition, saliva volume, submandibular gland pathology, plasma cells and memory B cells between male and female SS mice. The success rate of SS model was 75% in female mice and 60% in male mice. Compared with normal mice of the same sex, the weight loss of female SS mice was earlier and more obvious than that of male SS mice; the submandibular gland index of male mice was significantly higher than that of female mice. Compared with normal mice of the same sex, the proportion of Th17 and Treg cells in spleen of female SS mice was more statistically significant than that of male SS mice. Conclusions The success rate of SS modeling in female mice is higher than that in male mice. Compared with male SS mice, female SS mice have more significant SS like manifestations and pathological manifestations, which can provide a reference basis for the selection of gender when establishing SS model.

【Objective】To evaluate the efficacy of ziprasidone injection and the related influencing factors for treating agitation in schizophrenic patients based on published literature in English or Chinese. 【Methods】We searched PubMed， EMBASE， Web of Knowledge， Cochrane Library， Wanfang data， Chinese Journal Full- Text Database（CJFD），Chinese Biomedical Literature Database（CBMdisc）and VIP Chinese Technology Periodical Database（VIP）. The Consolidated Standards of Reporting Trials（CONSORT）statement was used as a criterion for screening and assessing the literature. Meta-analysis and meta-regression were conducted by using STATA. With the effect size as the dependent variable and sex，age，baseline PANSS scale total score and oral antipsychotics as the covariates ，the meta- regression model was analyzed. 【Results】The Grades of Recommendation ，Assessment ，Development and Evaluation（GRADE） approach was employed to rate the overall quality of evidence. A total of 14 studies（5 in English and 9 in Chinese）were included in meta analysis and meta regression. The samples were ，respectively，1 197 and 1 149 at baseline and after treatment. Random effect Meta analysis showed that ziprasidone injection had significant efficacy in the treatment of agitation symptoms［SMD=2.04，95%CI（1.47，2.61），P = 0.000］. Meta regression revealed that the efficacy was related to baseline PANSS scores（t = 5.57 ，P = 0.011）and oral antipsychotics（t = 4.07 ，P = 0.027），but irrelevant to age（t = 0.74，P = 0.539）and language published（t = -0.57，P = 0.625）. The efficacy was better in female patients than that in male patients （t = -2.95 ，P = 0.060）. 【Conclusion】 Ziprasidone injection has significant efficacy in schizophrenia patients with agitation symptoms and the efficacy may be enhanced in those patients with higher baseline PANSS score and added with oral antipsychotics.

There are many chemical components in the volatile oil of Dictamni Cortex. The complex network relationship of "component-target-disease" can be revealed by using the network pharmacology method, and the mechanism of the efficacy of Dictamni Cortex can be revealed. In this study, we used Swiss Target Prediction database to predict the target of action, STRING database to build protein interaction network, and Cytoscape software to build "component-target-disease" network. The results showed that the antibacterial, anti-inflammatory and antiallergic effects of Dictamni Cortex were closely related to the components of thymol methyl ether, elemenol, anethole, and the related targets of each component were cross-linked to play a multi-target pharmacodynamic role. This study laid a foundation for the study of the effective substance basis and quality control evaluation of the Dictamni Cortex, and provided a scientific basis for further revealing its mechanism.
Dictamnus/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Oils, Volatile/pharmacology* ; Protein Interaction Maps ; Quality Control ; Software

OBJECTIVETo investigate the efficacy of hematopoietic stem cells cryopreserved by ladder-style freezing from low temperature refrigerator to liquid nitrogen in treatment of hematological malignancies, and to analyze the survival condition of patients after hematopoietic stem cell transplantation.

METHODSThe coyoprotectant formed by 3% hydroxyethyl starch, 4% albumin and 5% dimethyl sulfoxide (DMSO) was need for cryopreservation of hematopoietic stem cells,which were first placed in -80C low temperature refrigerator and then were stored in -196C liquid nitrogen tank. 98 cases of hemafologic malignancies (io cases of ALL, 24 cases of AML, L-cases of MM and 53 case of malignant lymphoma) were selected from January 2002 to December 2016, and recived transplantatin auto-hematopoiehc stem cells cryopresorved by above-mentined method. The overall survival rate (OS), progression-free survival (PFS) were analyzed statistically.

RESULTSOne case failed in implantation due to intracranial hemorrhage and the other 97 cases all succeeded in hematopoietic reconstitution. The average time needed for neutrophil count ≥0.5×10/L was 9.24±1.89 d, and the average time needed for blood platelet ≥20×10/L without platelet transfusion for 3 days was 11.04±1.84 d. The median survival time was 47.6 months (1-80 months). The 3 and 5 year OS rates were (97.2±1.9) %, (84.2±4.6) % and (77.8±5.6) %, respectively. 3- and 5-year PFS of patients were (74.4±5.1)% and (61.2±6.2)%.

CONCLUSIONladder-style freezing from low temperature refrigerator to liquid nitrogen can reach the same clinical transplantation effect with traditional programmed cooling freezing method in autologous hematopoietic stem cells transplantation. moreover the incidence of complications after transpeantatim does not show increase.

Objective To develop a remote diabetic retinopathy (DR) screening system and to evaluate the effectiveness of the screening system in community.Methods A cross-sectional study was carried out under the informed consent of subjects in Peking University People's Hospital and Beijing Xicheng District Desheng Community Health Service Center from June 2015 to December 2016.A remote DR screening system was established in Peking University People's Hospital and Beijing Xicheng District Desheng Community Health Service Center during June 2015 to December 2016.Based on non-mydriatic digital eye fundus camera photography and the internet transmission technology,anterior ocular segment and fundus images of 2 473 eyes from 1 355 community subjects with type 2 diabetes mellitus were transmitted from Beijing Xicheng District Desheng Community Health Service Center to the reading center of Peking University People's Hospital,and the results were provided to the subjects after analysis,including visual examination,diagnosis and follow-up rate of the subjects,the agreement between remote screening system and conventional screening method was analyzed and compared.Results The visual acuities of the 2 473 eyes of 1 355 subjects were obtained by trained community physician,and the visual acuity was ≤0.05 in 103 eyes (4.2％),＞0.05-0.3 in 780 eyes (31.5％),＞0.3 in 1 590 eyes (64.3％).A good consistency was found in the diagnosis and grading of DR (Kappa value =0.895) and in diagnosis of macular disorder (Kappa value =0.763)between the remote screening system and conventional screening method.In addition,the diagnosis results of retinal photocoagulation were consistent between the two methods (Kappa value =1.000).The mean duration of the remote screening system for one subject was 10 minutes,which was shorter than 23 minutes of conventional screening method.The follow-up rate of remote screening system was 75.2％.Conclusions There is a high consistency in the DR diagnosis and evaluation between the remote non-mydriatic screening system and conventional screening method.The screening program with follow-up requests has a satisfying follow-up rate,which could meet the demand of DR screening.

BACKGROUND:It has been reported that 70％ of patients with chronic myeloid leukemia (CML) are negative for cytogenetic and genetic markers within 1-5 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT),but there are still some patients who have repeatedly varied outcomes in cytogenetic and genetic marker detection.Overall,the negative rate is up to 89.5％ at 3-12 months after allo-HSCT.OBJECTIVE:To monitor the changes in cytogenetic and genetic marker expression and to explore the prognostic significance in CML patients undergoing allo-HSCT.METHODS:Seventeen CML patients who had undergone allo-HSCT were enrolled.Chromosome G banding pattern of the bone marrow from these patients were analyzed using short-term culture method and direct method at 30 days,2,3,4,6,12,24,36,48,60,72 months after allo-HSCT.Dual-color fluorescence in situ hybridization was used to detect bcr-abl fusion gene;bcr-abl expressions in primary bone marrow ceils from CML patients were detected using RQ-PCR.Results and conclusion:There were 8/17 cases of male patient/male donor and 7/17cases of male patient/female donor (compatriots).46XX karyotype (women) was detected by multiple reexaminations after transplantation,and there was no Y chromosome or other aberration of chromosome karyotype in their karyotype.Among the 17 cases,1 case of female patient/female donor (compatriots) and 1 case of female patient/male donor (unrelated) manifested 46 XY chromosome karyotype and bcr-abl positive at 1 month after transplantation;after 4 months,these two cases still maintained 46 XY chromosome karyotype but bcr-abl negative;after 4-96 months,the karyotype continued to remain as 46 XY,and bcr-abl (-).Among the 17 cases,1 case of male patient/male donor of full-matched compatriot (brother) manifested that Ph chromosomal bcr-abl gene continuously expressed within 1-12 months after allo-HSCT;then the cases was given donor lymphocyte infusion,and the bcr-abl expression returned to be negative at 48 months after transplantation.To conclude,chromosomal karyotype analysis and bcr-abl fusion gene monitoring provide important reference value for subsequent treatment options and prognosis judgment for CML patients with allo-HSCT.

OBJECTIVETo study the radiologic and pathologic features of primary intermediate hemangioendothelioma of the bone.

METHODSFive cases of primary intermediate hemangioendothelioma of bone encountered in the past three years were enrolled into the study. The clinical, radiologic, pathologic and immunohistochemical features of the tumors were reviewed.

RESULTSThe patients included 3 children with Kaposiform hemangioendothelioma and 2 elderly with retiform hemangioendothelioma. Four of the cases affected long bones and the remaining case affected the clavicle. One case showed multifocal involvement of the humerus. Radiologically, the tumors showed borderline to low-grade bony destruction, with various degrees of cortical defect. Intralesional or perilesional bone formation was demonstrated in 4 cases and radial spicules were seen in 1 case. The histopathologic features of primary intermediate hemangioendothelioma of bone were similar to those of soft tissue, except for the presence of reactive bone formation. Immunohistochemically, the tumor cells were positive for CD31 (5/5), CD34 (5/5), vimentin (5/5) and smooth muscle actin (3/5) but negative for cytokeratin and epithelial membrane antigen.

CONCLUSIONSPrimary intermediate hemangioendothelioma of bone is a distinct entity and similar histologic classification applies as in its soft tissue counterparts. Comparison of the biologic behavior requires long-term follow-up studies.

Actins ; metabolism ; Antigens, CD34 ; metabolism ; Bone Neoplasms ; diagnostic imaging ; metabolism ; pathology ; Child ; Clavicle ; pathology ; Diagnosis, Differential ; Female ; Femur ; pathology ; Hemangioendothelioma ; diagnostic imaging ; metabolism ; pathology ; Hemangiosarcoma ; pathology ; Humans ; Humerus ; pathology ; Immunohistochemistry ; Infant ; Kasabach-Merritt Syndrome ; diagnostic imaging ; metabolism ; pathology ; Male ; Middle Aged ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Radiography ; Sarcoma, Kaposi ; diagnostic imaging ; metabolism ; pathology ; Vimentin ; metabolism