Immunotherapy has significantly improved clinical outcomes of non-small cell lung cancer (NSCLC), however, along with the popularization of immunotherapy, immune resistance has become an unavoidable problem. Immunotherapy can induce extensive cellular and molecular alterations in the tumor microenvironment. Considering the mechanisms of immune resistance are not yet fully understood and the efficacy of standard chemotherapy regimens is limited, more effective coping strategies based on resistance mechanisms are urgently needed. In this review, we intend to summarize the known mechanisms of immune resistance and feasible strategies, so as to provide a foundation for clinicians to develop more individualized and precise regimens and finally improve patients' prognosis.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Prognosis ; Immunotherapy ; Tumor Microenvironment

Prosthetic loosening and periprosthetic inflammation, as serious complications after joint replacement surgery, often require the secondary surgery for repair, which is easy to adversely affect the physical/mental health and economic status of patients.Studies have shown that the functional phenotype expressed by macrophages by different stimuli, namely macrophage polarization state, prolonged M1 polarization can lead to the continuation of long-term inflammation, while timely and effective M2 macrophage phenotype will lead to enhanced osteogenesis and tissue remodeling cytokine secretion and subsequent osseointegration, which play a crucial role in the development and outcome of prosthetic loosening and periprosthetic inflammation.The local micro-environment of extracellular matrix (ECM) is an important factor in the activation, migration, proliferation and fusion of macrophages. Researchers have deeply understood it mainly through the crosstalk between surface properties of biomaterials and macrophages. As an effector cell, macro-phages can perform complex spatiotemporal cellular functional responses by sensing the physical and chemical environment (surface topography, wettability, chemical composition, biological proteins) represented by surface properties of biomaterials.This paper summarizes the recent findings on macrophage polarization and material surface properties.

Introductions: The emergence of multidrug-resistant bacteria such as Methicillin-Resistant Staphylococcus aureus (MRSA) complicates the treatment of the simplest infection. Although glycopeptides such as vancomycin still proves to be effective in treating MRSA infections, the emergence of vancomycin-resistant strains limits the long term use of this antibiotic. Bacteriophages are ubiquitous bacterial viruses which is capable of infecting and killing bacteria including its antibiotic-resistant strains. Bactericidal bacteriophages use mechanisms that is distinct from antibiotics and is not affected by the antibioticresistant phenotypes. Objectives: The study was undertaken to evaluate the possibility to isolate bacteriolytic bacteriophages against S.aureus from raw sewage water and examine their efficacy as antimicrobial agents in vitro. Methods: Bacteriophages were isolated from the raw sewage using the agar overlay method. Isolated bacteriophages were plaque purified to obtain homogenous bacteriophage isolates. The host range of the bacteriophages was determined using the spot test assay against the 25 MRSA and 36 MSSA isolates obtained from the Sarawak General Hospital. Staphylococcus saprophyticus, Staphylococcus sciuri and Staphylococcus xylosus were included as non-SA controls. The identity of the bacteriophages was identified via Transmission Electron Microscopy and genomic size analysis. Their stability at different pH and temperature were elucidated. Results: A total of 10 lytic bacteriophages infecting S.aureus were isolated and two of them namely ΦNUSA-1 and ΦNUSA-10 from the family of Myoviridae and Siphoviridae respectively exhibited exceptionally broad host range against >80% of MRSA and MSSA tested. Both bacteriophages were specific to S.aureus and stable at both physiologic pH and temperature. Conclusion: This study demonstrated the abundance of S.aureus specific bacteriophages in raw sewage. Their high virulence against both MSSA and MRSA is an excellent antimicrobial characteristic which can be exploited for bacteriophage therapy against MRSA.

Objective:To establish a hypergravity loading model with a high-acceleration centrifugal loading device and to investigate the effects of different hypergravity loading and icariin on osteoblast adhesion and cytoskeleton.Methods:MC3T3-E1 cells were seeded in the dishes of cell culture at a density of 2×10 5/cm 2. And the experiment was divided into 6 groups: control group (without icariin and loading); simple administration group (only icariin); 10 G loading group (only loading); 10 G administration group (with icariin and loading); 40 G loading group (only loading); 40 G administration group (with icariin and loading). The experimental loading group was loaded with MC3T3-E1 cells using a high-acceleration centrifugal loader. And continuous loading for 3 d, 30 min per d. The control group and the simple administration group were exposed to normal gravity, and the remaining conditions were not different from the experimental group. Icariin was used at a concentration of 10 -7 mol/L in all administration groups, and the experiments were carried out according to the method of preventive administration. At the same time, the related molecular biological techniques such as alizarin red staining, alkaline phosphatase (ALP) activity measurement, CCK-8 cell proliferation experiment, cytoskeleton phalloidin staining, qPCR and Western Blot were used to detect the effects of icariin on osteoblasts adhesion protein integrin α5 and integrin β1 and cytoskeleton protein F-actin under hypergravity extreme mechanical environment. Results:All models were successfully prepared. The alizarin red staining: The icariin could significantly promote the formation of osteoblastic calcified nodules. And the 10 G loading could also promote the mineralization of osteoblasts and increase the number of mineralized nodules, while the mineralization and the number of mineralized nodules of osteoblasts are significantly reduced in 40 G loading. ALP activity test: The OD values of simple administration group, 10 G loading group and 40 G loading group were 0.246, 0.331 and 0.163, respectively. Compared with 0.207 in the control group, the differences were statistically significant ( P<0.05). The 10 G administration group and the 40 G administration group were 0.373 and 0.180, and the differences were statistically significant ( P<0.05). The results of CCK-8 proliferation experiments: The OD value of simple administration group were 0.650, which was statistically significant compared with 0.551 of control group ( P=0.031). The 10 G loading group and 40 G loading group were 1.193 and 0.245, and their differences with the control group were both statistically significant ( P<0.05). The OD value of 10G administration group and the 40 G administration group were 1.300 and 0.310, which were significantly different from the respective loading groups ( P<0.05). Phalloidin staining: 10 G loading significantly increased the number of cells, but the changes in cells morphology and skeleton were not obvious. 40 G loading significantly inhibited the increase of the number of cells, meanwhile, made the pseudopods of cells more shorter and even disappeared. 40 G loading made the seriously damage of the cytoskeleton and even cause the cells to death. Icariin had no effect on the cells morphology, but it did has a certain repair effect after the cells loading. The results of qPCR and Western Blot experiments all confirmed that the expressions of integrin α5, integrin β1 and F-actin were up-regulated after icariin treatment. 10 G loading could promote the expression of integrin α5, integrin β1 and F-actin, and 40 G loading significantly inhibited the expression of the mRNA and proteins. Conclusion:Both 10 G condition and icariin can promote the development, cell adhesion and the cytoskeleton's stability of osteoblasts, while 40 G has a significant inhibitory effect.

With the development of the 3rd-generation high-throughput sequencing technology and tissue engineering, recent studies show that many long-chain non-coding RNAs (LncRNAs) have played an important role in osteogenic differentiation of mesenchymal stem cells (MSCs). LncRNAs, which are involved in the regulation of mechanical regulation, further regulate bone-related cell functions and play a regulatory role at multiple levels, including transcription, post-transcriptional and epigenetic. LncRNAs may be involved in the osteogenic differentiation and bone remodeling of MSCs, the regulation of bone-related cell functions as a mechanical response molecule, as well as the pathological process of skeletal diseases.

Objective To construct a two-dimensional (2D) composite membrane and a three-dimensional (3D) biomimetic scaffold by silk fibroin (SF), type I collagen (Col-I) and hydroxyapatite (HA) blends in vitro, so as to study its physicochemical properties, as well as biocompatibility and explore the feasibility of its application in tissue engineering scaffold materials. Methods 2D composite membranes and 3D scaffolds were prepared by blending SF/Col-I/HA at the bottom of cell culture chamber and low temperature 3D printing combined with vacuum freeze drying. The biocompatibility was evaluated by mechanical property testing, scanning electron microscope and Micro-CT to examine the physicochemical properties of the material, and cell proliferation was detected to evaluate its biocompatibility. Results Stable 2D composite membrane and 3D porous structural scaffolds were obtained by blending and low temperature 3D printing. The mechanical properties were consistent. The pore size, water absorption, porosity and elastic modulus were all in accordance with the requirements of constructing tissue engineering bone. The scaffold was a grid-like white cube with good internal pore connectivity; HA was evenly distributed in the composite membrane, and the cells were attached to the composite membrane in a flat shape; the cells were distributed around pore walls of the scaffold. The shape of the shuttle was fusiform, and the growth and proliferation were good. Conclusions The composite membrane and 3D scaffold prepared by SF/Col-I/HA blending system had better pore connectivity and pore structure, which was beneficial to cell and tissue growth and nutrient transport. Its physicochemical properties and biocompatibility could meet the requirements of bone tissue engineering biomaterials.

BACKGROUND: The silk fibroin/type II collagen composite scaffold has been prepared by low-temperature bio-3D printing technology in the previous study and the scaffold has good mechanical properties. Studies have shown that mechanical stimulation is beneficial to bone remodeling, and gradient loading strain is beneficial to the activation of osteoblasts and osteoclasts. OBJECTIVE: To co-culture silk fibroin/type II collagen composite scaffolds with chondrocytes under compression loading, to observe the proliferation of cells, and to observe the preliminary repair effect of silk fibroin/type II collagen composite scaffold on cartilage defects. METHODS: The silk fibroin/type II collagen composite scaffold was prepared by low-temperature 3D printing to detect the porosity of the scaffold. The passage 3 mouse chondrocytes ADTC-5 were inoculated on the silk fibroin/type II collagen composite scaffold and cultured under static culture and mechanical load respectively. (1) Static culture: blank scaffold was set as control, and cell proliferation was detected by MTT assay at 1, 3, 5, 7, 10, 14 days of inoculation. (2) Culture under mechanical load: blank scaffold was set as control. At 1 day after inoculation, 0％, 1％, 5％, 10％, 15％, 20％ compressive strains were applied to the cell-scaffold complex, and continued to load for 3 days. Cell proliferation was detected by MTT assay, and the distribution, adhesion and morphology of the cells on the scaffold were observed by scanning electron microscopy and hematoxylin-eosin staining. A cartilage defect of 3.5 mm in diameter was made in the bilateral knee joint of New Zealand rabbits. The silk fibroin/type II collagen composite scaffold was implanted onto the left side, and no material was implanted onto the right side. The repair site was observed at 8 weeks after surgery. RESULTS AND CONCLUSION: (1) The porosity of the scaffold was (89.3±3.26)％, which was conducive to cell attachment. (2) After 5 days of static culture, the chondrocytes proliferated well on the surface of the composite scaffold. Under 0％, 1％, 5％, 10％, 15％, 20％ compressive strains, the cell proliferation on the scaffold first increased and then decreased, wherein the cell proliferation was highest under 10％ compressive strain, and lowest under 20％ compressive strain. (4) Under the scanning electron microscopy, the chondrocytes in the 0％ load group were distributed in the surface of the scaffold with irregularities, the cell morphology was obvious, and the cell protrusions were fully extended. There were few or no chondrocytes on the contact surface of the 10％ load group, and more cells distributed on the lateral and internal surfaces of the first layer, but the cell morphology was flat with obvious protrusions. (5) Hematoxylin-eosin staining showed that the chondrocytes in the 0％ load group were concentrated on the surface of the scaffold, and there were almost no cells in the pores, while the chondrocytes in the 10％ load group were distributed in the scaffold pores. (6) There was still a circular defect model with no scaffold implantation, and no obvious repair appeared; similar hyaline cartilage appeared in the defect after scaffold implantation, but there was no adhesion to the surrounding defected cartilage, and the new hyaline cartilage was independent. Overall, the adsorption, proliferation and growth of chondrocytes on the silk fibroin-type II collagen scaffolds is better when the compressive strain is 10％, and the composite scaffold can be used as a repair material for cartilage defects.

Objective To investigate the effect of humidex combined with mean temperature and relative humidity on the incidence of bacillary dysentery in Hefei. Methods Daily counts of bacillary dysentery cases and weather data in Hefei were collected from January 1, 2006 to December 31, 2013. Then, the humidex was calculated from temperature and relative humidity. A Poisson generalized linear regression combined with distributed lag non-linear model was applied to analyze the relationship between humidex and the incidence of bacillary dysentery, after adjusting for long-term and seasonal trends, day of week and other weather confounders. Stratified analyses by gender, age and address were also conducted. Results The risk of bacillary dysentery increased with the rise of humidex. The adverse effect of high humidex (90 percentile of humidex) appeared in 2- days lag and it was the largest at 4-days lag (RR=1.063, 95%CI:1.037-1.090). Subgroup analyses indicated that all groups were affected by high humidex at lag 2-5 days. Conclusion High humidex could significantly increase the risk of bacillary dysentery, and the lagged effects were observed.

Objective To observe the clinical efficacy of bipolar hemi arthroplasty and PFNA internal fixation for elderly patients with unstable intertrochanteric fracture.Methods The data of 79 elderly patients with unstable intertrochanteric fracture in our hospital from Au-gust 2013 to August 2014 were analyzed retrospectively.According to different surgical methods,79 cases were divided into observation group (n =40)and control group(n =39).The observation group were treated by artificially double-acting avascular replacement,and the control group received PFNA internal fixation.The operation time,intraoperatve blood soss,bedridden time,clinical effecacy and complications were recorded and observed.Results The operative time and bed time of observation group were significantly shorter than those of control group, the difference was statistically significant(P <0.05).The total postoperative complication rate of observation group was 20.00%,which was higher than 20.51% of control group,the difference was statistically significant (P <0.05).The Harris scores in observation group 3 months and 6 months after surgery were significantly higher than those in control group,the differences were statistically significant(P <0.05).Con-clusion Both artificially double-acting avascular replacement and PFNA internal fixation have a good effect on elderly patients with unstable intertrochanteric fracture.The artificially double-acting avascular replacement has the advantages of less blood loss,faster recovery and less postoperative complications,which is conducive to improving the quality of life of patients.

Objective To explore the MRI features of pelvic endometriosis outside the ovary.Methods 13 patients with pelvic endometriosis outside the ovary were imaged.Their clinical and imaging data were reviewed retrospectively.All cases were con-firmed by pathology.An enhanced MR using T1 WI sequence both in sagittal and transverse position was performed after T2 WI fat-suppression sequence and T1 WI sequence.Our MRI study was focused on the distribution of lesions locating in the deep pelvic cavity and abdominal wall,and the features of MRI signals .Results 13 lesions were found,in which 4 lesions located in the rectouterine pouch of Douglas,2 cases the bladder wall,2 cases the unilateral cystic inlet of ureter,1 case the anal canal wall,and 4 cases the ab-dominal wall.10(10/13)lesions were shown as solid nodules while 3(3/13)lesions as cyst-solid ones.All lesions showed moderate-ly heterogeneous enhancement.Conclusion Pelvic endometriosis outside the ovary mainly shows solid or cyst-solid lesions that lo-cates in the urinary,uterus,rectal wall and spaces around them.MR images show a higher value for the detection of the lesions out-side the ovary.