The role of a drug-loaded poly(lactic co-glycolic acid)(PLGA) copolymer stent in the treatment of ovarian cancer

Objectives:Cisplatin(CDDP)is a widely used and effective basic chemotherapeutic drug for the treatment of a variety of tumors,including ovarian cancer.However,adverse side effects and acquired drug resistance are observed in the clinical application of CDDP.Identifying a mode of administration that can alleviate side effects and reduce drug resistance has become a promising strategy to solve this problem.Methods:In this study,3 D printing technology was used to prepare a CDDP-poly(lactic-co-glycolic acid)(CDDP-PLGA)polymer compound stent,and its physicochemical properties and cytotoxicity were evaluated both in vitro and in vivo.Results:The CDDP-PLGA stent had a significant effect on cell proliferation and apoptosis and clearly decreased the size of subcutaneous tumors in nude mice,whereas the systemic side effects were mild compared with those of intraperitoneal CDDP injection.Compared with the control group,CDDP-PLGA significantly increased the mRNA and protein levels of p-glycoprotein(P<0.01;P<0.01)and decreased vascular endothelial growth factor mRNA(P<0.05)and protein levels(P<0.01),however,CDDP-PLGA significantly decreased the mR NA and protein levels of p-glycoprotein(P<0.01;P<0.01)and vascular endothelial growth factor(P<0.01;P<0.01),which are associated with chemoresistance,in subcutaneous tumor tissue.Immunohistochemistry assay results revealed that,in the CDDP-PLGA group,the staining of the proliferation-related genes Ki67 and PCNA were lightly,and the apoptosis-related gene caspase-3 stained deeply.Conclusions:PLGA biomaterials loaded with CDDP,as compared with the same amount of free CDDP,showed good efficacy in terms of cytotoxicity,as evidenced by changes in apoptosis.Continuous local CDDP release can decrease the systemic side effects of this drug and the occurrence of drug resistance and angiogenesis,and improve the therapeutic effect.This new approach may be an effective strategy for the local treatment of epithelial ovarian cancer.

TLR4 May Accelerate Hypoxia Reaction to Promote the Occurrence and Progress of Cervical Lesions by Infected Pathogenic Microorganisms Other than HPV

Objective: To explore what role the inflammatory immune response is playing in the occurrence and development of HPV related cervical disease. Methods: To detect the expression of TLR4, HIF-1α and HPV16 E7 in the specimens of HPV related cervical lesions, for example normal cervix, cervicitis, cervical intraepithelial neoplasia and cervical cancer by RT PCR methods. Results: The expression of TLR4 and HIF-1α ascent from normal cervix to cervicitis, then to CIN tissue, and then to cervical cancer (P 0.05). The expression of HPV16 E7 was higher in cervicitis than that in normal cervix (P 0.05) while there was no significant ascendance from cervicitis to CIN tissue, either from CIN tissue to cervical cancer although it seemed ascending (P > 0.05). Conclusion: TLR4 may promote the occurrence and progress of cervical lesions by accelerating the hypoxia reaction. And the natural immune reaction mediated by TLR4 may be correlated to other pathogenic microorganisms infecting the cervical tissue, rather than HPV.

Clinical significance of survivin in the diagnosis and prognosis of endometrial carcinoma

Objective： To investigate the clinical significance of survivin in endometrial carcinoma and to investigate the relationship between the expression of survivin and Ki-67. Methods： Immunohistochemical S-P （streptavidin-biotin-peroxidase complex）method was performed to detect the expression of survivin and Ki-67 antigen in 15 cases of normal endometrium, 21 cases of endometrial simple and complex hyperplasia, 22 cases of endometrial atypical hyperplasia, and 61 cases of endometrial carcinoma. Results： Survivin was hardly detected in some normal endometrium in the proliferative phase and in the secretory phase. However, the level of survivin expression in atypical hyperplasia endometrium（72.73%）was higher than that in normal en- dometrium （7.14%）（P 〈 0.05）, including simple and complex hyperplasia （42.38%）（P 〈 0.01 ）, and was lower than that in endometrial carcinoma（90.17%）（P 〈 0.05）. Moreover, significant correlation was present between the expression of survivin and the characteristics of endometrial carcinoma, including clinical stage, histological grade and the presence of invasion to myometrium （P 〈 0.05）. In addition, Ki-67 antigen expression was positively correlated with survivin expression in all specimen. Ki-67 labeled indexes （LIs）in hyperplasia endometrium were significantly lower than those in atypical hyperplasia endometrium and endometrial carcinoma （P 〈 0.01 ）, while there was no significant difference in Ki-67 LIs between atypical hyperplasia endometrium and endometrial carcinoma（P 〉 0.05）. There was no significant relationship between Ki-67 LIs and the characteristics of endometrial carcinoma, including histological grade, clinical stage or the invasion to myometrium（P 〉 0.05）. Conclusion： Survivin may participate in the onset and progression of endometrial carcinoma through inhibiting apoptosis and promoting proliferation. Survivin expression is correlated with the malignant degree and prognosis of tumor. Ki-67 is also associated with carcinogenesis and progression of endometrial carcinoma. The results suggest that survivin could be a diagnostic and prognostic marker for endometrial carcinoma and might provide pathways to treat the patients with recurrent or refractory or rudimental endometrial carcinoma.

An integrative review on the applications of 3D printing in the field of in vitro diagnostics

Biomedicine is one of the fastest growing areas of additive manufacturing.Especially,in the field of in vitro diagnostics(IVD),contributions of 3D printing include i)rapid prototyping and iterative IVD proof-of-concept designing ranging from materials,devices to system integration;ii)conceptual design simpli-fication and improved practicality of IVD products;iii)shifting the IVD applications from centralized labs to point-of-care testing(POCT).In this review,the latest developments of 3D printing and its advantages in IVD applications are summarized.A series of 3D-printed objects for IVD applications,including single-function modules,multi-function devices which integrate several single-function modules for specific an-alytical applications such as sample pre-treatment and chemo-/bio-sensing,and all-in-one systems which integrate multi-function devices and the instrument operating them,are analyzed from the perspective of functional integration.The current and potential commercial applications of 3D-printed objects in the IVD field are highlighted.The features of 3D printing,especially rapid prototyping and low start-up,en-able the easy fabrication of bespoke modules,devices and systems for a range of analytical applications,and broadens the commercial IVD prospects.

Carbazole ring: A delicate rack for constructing thermally activated delayed fluorescent compounds with through-space charge transfer

Three carbazole derivatives, Ac PTC, Px PTC and Pt PTC, consisting of two 9,9-dimethyl-9,10-dihydroacridine,phenoxazine or phenothiazine donor groups and one diphenyltriazine acceptor group fixed at 1,8,9-positions of a single carbazole ring via phenylene, are designed and synthesized. X-ray diffraction analysis of Ac PTC reveals that there exist multiple π-π interactions between the donor and acceptor groups to form a sandwich-like structural unit with edge-to-face interaction model. The compounds thus show obvious thermally activated delayed fluorescence with through-space charge transfer character and possess considerable photoluminescence quantum yields of up to 73% in doped films with sky-blue to yellow emissions. The solution-processed electroluminescent devices achieve the highest maximum external quantum efficiencies of 10.0%, 11% and 5.6% for Ac PTC, Px PTC and Pt PTC, respectively, with small efficiency roll-offs.

Touchable cell biophysics property recognition platforms enable multifunctional blood smart health care

As a crucial biophysical property,red blood cell(RBC)deformability is pathologically altered in numerous disease states,and biochemical and structural changes occur over time in stored samples of otherwise normal RBCs.However,there is still a gap in applying it further to point-of-care blood devices due to the large external equipment(high-resolution microscope and microfluidic pump),associated operational difficulties,and professional analysis.Herein,we revolutionarily propose a smart optofluidic system to provide a differential diagnosis for blood testing via precise cell biophysics property recognition both mechanically and morphologically.Deformation of the RBC population is caused by pressing the hydrogel via an integrated mechanical transfer device.The biophysical properties of the cell population are obtained by the designed smartphone algorithm.Artificial intelligence-based modeling of cell biophysics properties related to blood diseases and quality was developed for online testing.We currently achieve 100%diagnostic accuracy for five typical clinical blood diseases(90 megaloblastic anemia,78 myelofibrosis,84 iron deficiency anemia,48 thrombotic thrombocytopenic purpura,and 48 thalassemias)via real-world prospective implementation;furthermore,personalized blood quality(for transfusion in cardiac surgery)monitoring is achieved with an accuracy of 96.9%.This work suggests a potential basis for next-generation blood smart health care devices.

The role of TLRs in cervical cancer with HPV infection:a review

The main cause of cervical cancer is persistent infection with high-risk human papilloma virus(HR-HPV),but not all human papilloma virus(HPV)infections lead to cervical cancer.The key factors that determine the outcome of HPV infection remain poorly understood,and how the host immune system protects against HPV infection is unclear.Toll-like receptors(TLRs)are a group of pattern recognition receptors present in the cytoplasm and cell membrane,and can specifically recognize pathogen-associated molecular patterns.As the key molecules of innate and acquired immunity,TLRs not only play important roles in the immune defense against infectious diseases,but also are involved in the occurrence and development of a variety of malignant tumors.In cervical cancer caused by HR-HPV infection,TLRs have been found to regulate the local immune microenvironment.The role of TLRs in HR-HPV infection and HPV-induced cervical cancer and its relationship with HPV vaccine are reviewed in this article.