Effects of combined microplastic and cadmium pollution on sorghum growth, Cd accumulation, and rhizosphere microbial functions.

The interaction between microplastics (MPs) and cadmium (Cd) poses a threat to agricultural soil environments, and their effects on plant growth and rhizosphere microbial community functions are not yet clear. In this study, energy sorghum was used as a test plant to investigate the effects of two types of MPs, polystyrene (PS) and polyethylene (PE), at different particle sizes (13 µm, 550 µm) and concentrations (0.1%, 1% w/w), and Cd, as well as their interactions, on the growth of sorghum in a soil-cultivation pot experiment. The results showed that the combined effects of MP and Cd pollution on the dry weight and Cd accumulation rate in sorghum varied depending on the type, concentration, and particle size of the MPs, with an overall trend of increasing stress from combined pollution with increasing Cd content and accumulation. High-throughput sequencing analysis revealed that combined MP and Cd pollution increased bacterial diversity, and the most significant increase was observed in the abundance-based coverage estimator (ACE), Shannon, and Sobs indices in the 13 µm 1% PS+Cd treatment group. Metagenomic analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed that 19 groups of metabolic pathways, including microbial metabolism and methane metabolism, differed significantly under combined MP and Cd pollution. Hierarchical clustering results indicated that Cd treatment and combined MP and Cd treatment affected the abundances of sorghum rhizosphere soil nitrogen (N) and phosphorus (P) cycling genes and that the type of MP present was an important factor affecting N and P cycling genes. The results of this study provide a basis for exploring the toxic effects of combined MP and Cd pollution and for conducting soil environmental risk assessments.

[Antitumor effects of redox-responsive nanoparticles containing platinum（⠣）in ovarian cancer].

Objectives: To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)-NP@Pt(Ⅳ) in ovarian cancer. Methods: Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)-Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured. Results: The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment (P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 µmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 µmol/L) and cisplatin (5.21, 11.85, and 71.98 µmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm3, which was significantly lower than those in control group [(1 349±161) mm3, P<0.001] and cisplatin group [(715±293) mm3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion: Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

The lateral cervical stria approach to selective neck dissection: a preliminary study.

BACKGROUND: This study aims to propose a lateral cervical stria approach for selective neck dissection (SND) in patients of early-stage oral malignancies. MATERIAL AND METHODS: The lateral cervical stria approach was used in 11 patients undergoing SND between December 2020 and March 2022. The surgical incision was located in submandibular cervical stria, with a length of 5.0 cm. The ipsilateral SND was performed according to the pathological type, covering part or all of I-V levels. Perioperative variables including operation time, blood loss, drainage volume, number of lymph node as well as complications were assessed. The score of appearance using the University of Washington Quality of Life Questionnaire (UW-QOL) was recorded 6-month postoperatively. RESULTS: Direct closure of primary lesion was performed in ten patients and a forearm free flap reconstruction was used in one patient. No wound breakdown or infection was found in all cases. The mean operative time of SND was 157.63±27.39 min. The volume of intraoperative blood loss and postoperative drainage was 120.45±36.77 ml and 314.09±98.82 ml, respectively. The mean number of retrieved lymph nodes was 17.89±6.03 (ranging from 12 to 31). Postoperative complications included mild static lower lip deviation (n=1), shoulder discomfort (n=1) and mild auricular paraesthesia (n=1). The mean score of appearance was 86.36±13.06, with 100 scores in 5 patients and 75 scores in 6 patients. CONCLUSIONS: The lateral cervical stria approach for SND in early-stage oral malignancies is reliable, achieving to satisfactory functional and aesthetic outcomes.

[Mechanism of podocyte pyroptosis aggravated by up-regulation of phospholipase A2 receptor by hepatitis B virus X protein].

Objective: To explore the effect and underlying mechanism of increased expression of M-type phospholipase A2 receptor (PLA2R) on podocyte membrane induced by hepatitis B virus X protein (HBx) on podocyte pyroptosis in hepatitis B virus-associated glomerulonephritis (HBV-GN). Methods: Transfection of the HBx gene into human kidney podocytes was used to mimic the HBV-GN pathogenesis process. Subsequently, podocytes were divided into the following eight groups: normal control plus secretory phospholipase A2-ⅠB (sPLA2-ⅠB) group, empty plasmid plus sPLA2-ⅠB group, HBx group, HBx plus sPLA2-ⅠB group, HBx plus sPLA2-ⅠB plus PLA2R control siRNA group, HBx plus sPLA2-ⅠB plus PLA2R-siRNA group, HBx plus sPLA2-ⅠB plus ROS control siRNA group, and HBx plus sPLA2-ⅠB plus ROS-siRNA group. Podocyte morphology was observed under a transmission electron microscope, and PLA2R expression was detected under a fluorescence microscope. Podocyte pyroptosis and reactive oxygen species (ROS) expression were analyzed by flow cytometry, and the mRNA and protein expression of PLA2R, nucleotide-binding oligomerization domain-like receptor 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, interleukin (IL)-1ß and IL-18 were determined by real-time fluorescence quantitative PCR and Western blot. Results: Compared with the control group, the expression of PLA2R on podocyte membrane significantly increased after transfection with HBx plasmid in vitro (4.07±0.41 vs 1.01±0.17, P<0.001). Transmission electron microscope and fluorochrome-labeled inhibitor of caspases/propidium iodide (FLICA/PI) double staining suggested that overexpressed PLA2R combined with sPLA2-ⅠB caused aggravated podocyte injury and increased pyroptosis (20.22%±0.36% vs 7.86%±0.28%, P<0.001). Moreover, the expression levels of ROS (4 324 515±222 764 vs 12 920±46, P<0.001), NLRP3 (48.30±2.73 vs 1.00±0.11, P<0.001), ASC (4.02±0.84 vs 1.01±0.15, P<0.001), caspase-1 (3.99±0.42 vs 1.00±0.11, P<0.001), IL-1ß (9.08±0.75 vs 1.00±0.09, P<0.001) and IL-18 (19.20±0.70 vs 1.00±0.02, P<0.001) increased when PLA2R was overexpressed. In contrast, with the addition of PLA2R-siRNA or ROS-siRNA to knockdown the expression of related substances, podocyte injury was alleviated and the degree of pyroptosis decreased, and the expressions of genes related to the downstream signaling pathway (NLRP3, ASC, caspase-1, IL-1ß and IL-18) decreased (all P<0.01). Conclusion: HBx may promote podocyte pyroptosis in HBV-GN by targeting the ROS-NLRP3 signaling pathway via the upregulation of PLA2R.

[Effects of different crosslinking treatments on the properties of decellularized small intestinal submucosa porous scaffolds].

OBJECTIVE: To compare the effects of three different crosslinkers on the biocompatibility, physical and chemical properties of decellularized small intestinal submucosa (SIS) porous scaffolds. METHODS: The SIS porous scaffolds were prepared by freeze-drying method and randomly divided into three groups, then crosslinked by glutaraldehyde (GA), 1-ethyl-3-(3-dimethylaminopropyl) carbodi-imide (EDC) and procyanidine (PA) respectively. To evaluate the physicochemical property of each sample in different groups, the following experiments were conducted. Macroscopic morphologies were observed and recorded. Microscopic morphologies of the scaffolds were observed using field emission scanning electron microscope (FESEM) and representative images were selected. Computer software (ImageJ) was used to calculate the pore size and porosity. The degree of crosslinking was determined by ninhydrin experiment. Collagenase degradation experiment was performed to assess the resistance of SIS scaffolds to enzyme degradation. To evaluate the mechanical properties, universal mechanical testing machine was used to determine the stress-strain curve and compression strength was calculated. Human bone marrow mesenchymal cells (hBMSCs) were cultured on the scaffolds after which cytotoxicity and cell proliferation were assessed. RESULTS: All the scaffolds remained intact after different crosslinking treatments. The FESEM images showed uniformed interconnected micro structures of scaffolds in different groups. The pore size of EDC group[(161.90±13.44) µm] was significantly higher than GA group [(149.50±14.65) µm] and PA group[(140.10±12.06) µm] (P < 0.05). The porosity of PA group (79.62%±1.14%) was significantly lower than EDC group (85.11%±1.71%) and GA group (84.83%±1.89%) (P < 0.05). PA group showed the highest degree of crosslinking whereas the lowest swelling ratio. There was a significant difference in the swelling ratio of the three groups (P < 0.05). Regarding to the collagenase degradation experiment, the scaffolds in PA group showed a significantly lower weight loss rate than the other groups after 7 days degradation. The weight loss rates of GA group were significantly higher than those of the other groups on day 15, whereas the PA group had the lowest rate after 10 days and 15 days degradation. PA group showed better mechanical properties than the other two groups. More living cells could be seen in PA and EDC groups after live/dead cell staining. Additionally, the proliferation rate of hBMCSs was faster in PA and EDC groups than in GA group. CONCLUSION: The scaffolds gained satisfying degree of crosslinking after three different crosslinking treatments. The samples after PA and EDC treatment had better physicochemical properties and biocompatibility compared with GA treatment. Crosslinking can be used as a promising and applicable method in the modification of SIS scaffolds.

Functional cell phenotype induction with TGF-ß1 and collagen-polyurethane scaffold for annulus fibrosus rupture repair.

Appropriate cell sources, bioactive factors and biomaterials for generation of functional and integrated annulus fibrosus (AF) tissue analogues are still an unmet need. In the present study, the AF cell markers, collagen type I, cluster of differentiation 146 (CD146), mohawk (MKX) and smooth muscle protein 22α (SM22α) were found to be suitable indicators of functional AF cell induction. In vitro 2D culture of human AF cells showed that transforming growth factor ß1 (TGF-ß1) upregulated the expression of the functional AF markers and increased cell contractility, indicating that TGF-ß1-pre-treated AF cells were an appropriate cell source for AF tissue regeneration. Furthermore, a tissue engineered construct, composed of polyurethane (PU) scaffold with a TGF-ß1-supplemented collagen type I hydrogel and human AF cells, was evaluated with in vitro 3D culture and ex vivo preclinical bioreactor-loaded organ culture models. The collagen type I hydrogel helped maintaining the AF functional phenotype. TGF-ß1 supplement within the collagen I hydrogel further promoted cell proliferation and matrix production of AF cells within in vitro 3D culture. In the ex vivo IVD organ culture model with physiologically relevant mechanical loading, TGF-ß1 supplement in the transplanted constructs induced the functional AF cell phenotype and enhanced collagen matrix synthesis. In conclusion, TGF-ß1-containing collagen-PU constructs can induce the functional cell phenotype of human AF cells in vitro and in situ. This combined cellular, biomaterial and bioactive agent therapy has a great potential for AF tissue regeneration and rupture repair.

[Biodegradation properties of multi-laminated small intestinal submucosa].

OBJECTIVE: To study the biodegradation properties of multi-laminated small intestinal submucosa (mSIS) through in vitro and in vivo experiments, comparing with Bio-Gide, the most widely used collagen membrane in guided bone regeneration (GBR) technique, for the purpose of providing basis to investigate whether mSIS meets the requirements of GBR in dental clinics. METHODS: The degradation properties were evaluated in vitro and in vivo. In vitro degradation was performed using prepared collagenase solution. Morphology of mSIS and Bio-Gide in degradation solution were observed and the degradation rate was calculated at different time points. In in vivo experiments, nine New Zealand rabbits were used for subcutaneous implantation and were divided into three groups according to observation intervals. Six unconnected subcutaneous pouches were made on the back of each animal and were embedded with mSIS and Bio-Gide respectively. At the end of weeks 4, 8, and 12 after operation, gross observation and HE staining were used to evaluate the degree of degradation and histocompatibility. RESULTS: In vitro degradation experiments showed that mSIS membrane was completely degraded at the end of 12 days, while Bio-Gide was degraded at the end of 7 days. Besides, mSIS maintained its shape for longer time in the degradation solution than Bio-Gide, indicating that mSIS possessed longer degradation time, and had better ability to maintain space than Bio-Gide. In vivo biodegradation indicated that after 4 weeks of implantation, mSIS remained intact. Microscopic observation showed that collagen fibers were continuous with a few inflammatory cells that infiltrated around the membrane. Bio-Gide was basically intact and partially adhered with the surrounding tissues. HE staining showed that collagen fibers were partly fused with surrounding tissues with a small amount of inflammatory cells that infiltrated as well. Eight weeks after operation, mSIS was still intact, and was partly integrated with connective tissues, whereas Bio-Gide membrane was mostly broken and only a few residual fibers could be found under microscope. Only a small amount of mSIS debris could be observed 12 weeks after surgery, and Bio-Gide could hardly be found by naked eye and microscopic observation at the same time. CONCLUSION: In vitro degradation time of mSIS is longer than that of Bio-Gide, and the space-maintenance ability of mSIS is better. The in vivo biodegradation time of subcutaneous implantation of mSIS is about 12 weeks and Bio-Gide is about 8 weeks, both of which possess good biocompatibility.

The Region of Interest in Boundary Calibration for Palatal Rugae Image of Forensic Identification.

ABSTRACT: Objective To examine the method of least-square fitting for calibrating the palatal rugae boundary. Methods According to the distribution of the teeth, the feature points were selected; when they were fit, the boundary of the palatal rugae area was created, thereby constructing a mask. The mask was used to remove the part located outside the boundary and filter out the interference. Three samples were utilized for the experiments and analyses to come. Results To evaluate the quantitative results of the fitting curves, the correlation coefficients （r） of the samples and the relationship between the actual mean value and ideal mean value was obtained through six fitting processes. The differences between the actual mean and ideal mean were found to be significantly small （from 0.285 7 to 2.500 0） in the six fitting processes, with the range of r close to 1 （from 0.989 6 to 0.999 5）. Conclusion The effect of the cubic polynomial fitting method adopted in this study was stable.The proposed boundary calibration method can effectively locate the palatal rugae boundary and remove the interference area, further promoting the practice of forensic identification.

[Effects of CAD/CAM titanium alloy surface treatment and resin luting on shear bond strength and durability of composite resin].

OBJECTIVE: To assess the effects of two surface treatments (sandblasting, SB; microarc-oxidation, MAO) and resin luting on shear bond strength and durability of titanium alloy and composite-resin. METHODS: Eighty cylindrical titanium alloy specimens with a diameter of 10 mm and a height of 8 mm were fabricated by CAD/CAM technique. It was divided into two groups according to the surface treatment methods: sandblasting with Al2O3 particles on the surface of SB specimens; porous ceramic film structure could be formed on the surface of MAO specimens after surface treatment. Each group was classified into SB-resin luting-N group (not used), SB-resin luting-Y group (used), MAO-resin luting-N group (not used), MAO-resin luting-Y group (used) depending on whether or not resin luting was applied. Each specimen was bonded and cured with the Cemerage resin, and the shear bond strength after 0 and 5 000 thermocycling was tested. The results were statistically analyzed. The surface morphology of titanium alloy specimens before and after the shear bond strength test was observed by scanning electron microscopy (SEM). RESULTS: The shear bond strength between titanium alloy and composite-resin was the highest in the SB combined with resin luting group after 0 thermocycling (16.2±1.8) MPa; was the lowest in MAO group after 5 000 thermocycling (8.9±1.5) MPa. The shear bond strength of SB and MAO surface treatment methods combined without resin luting group after 5 000 thermocycling were (10.7±2.2) MPa and (8.9±1.5) MPa, which were statistically lower than those in the thermocycling 0 (P=0.000 and P=0.001). The shear bond strength of SB and MAO surface treatment methods combined with resin luting group after 5 000 thermocycling were (15.5±2.1) MPa and (11.7±1.3) MPa, respectively, which were lower than those in the thermocycling 0 group, but there was no statistical significance (P=0.087 and P=0.234). CONCLUSION: Both the surface treatment methods of SB and MAO combined with resin luting can improve the shear bond strength and durability of titanium alloy and composite-resin. The SB combined with resin luting is more significant. At present, the effect of SB is better than that of MAO due to the limitation of technical parameters of micro-arc oxidation.

[Preparation of aspirin sustained-release microsphere and its in vitro releasing property].

OBJECTIVE: It has been proven that acetylsalicylic acid (aspirin), as a kind of classical non-steroidal anti-inflammatory drug, not only has the effect of anti-inflammatory, but also has the function of immunity regulation and mineralization. However, it needs further investigation to study how to delay release of aspirin for a long time and enable to promote bone regeneration. Herein, we demonstrated that the longterm delayed release pattern of aspirin through the construction of microsphere scaffolds is promising to achieve the excellent bone regeneration. METHODS: Here we synthesized three kinds of scaffolds as follows: (1) aspirin loaded calcium silicate (CaSiO3) microsphere (CaSiO3-aspirin) via simple immersion; (2) aspirin loaded polylactic-co-glycolic acid (PLGA) microsphere (PLGA-aspirin) via oil/water (O/W) emulsion; (3) aspirin loaded PLGA-CaSiO3 scaffold (PLGA-CaSiO3-aspirin) via O/W emulsion, optimal morphology and structure of PLGA-CaSiO3-aspirin scaffold was acquired through modulating the ratio between PLGA and CaSiO3. Furthermore, spectrophotometer was used to monitor the concentration of the extract of the three scaffolds for different releasing time, including 1, 2, 4, 6, 9, 13, 17, 21, 24, 30, 36, and 45 days, aspirin loading efficiency and its accumulation releasing curves were both achieved according to the concentration of aspirin. Their sustained release effects of aspirin were evaluated eventually. RESULTS: Environmental scanning electron microscope (ESEM) results showed that the surface structure of the three kinds of scaffolds were smooth and had uniform size distribution. In addition, a small amount of PLGA-aspirin microspheres occurred to aggregation, while a small amount of CaSiO3-aspirin microspheres were broken. Moreover, the PLGA-aspirin microspheres in the PLGA-CaSiO3-aspirin scaffolds were uniformly adhered to the surface of CaSiO3 microspheres. The aspirin loadings of CaSiO3-aspirin, PLGA-aspirin, and PLGA-CaSiO3-aspirin were (1.06±0.04)%, (7.05±0.06)%, and (6.75±0.18)%, respectively. In addition, their corresponding time for releasing 95% of aspirin was 3, 24, and 36 days, respectively. The releasing time of PLGA-CaSiO3-aspirin was longer than that of the others and the releasing rate was more stable. CONCLUSION: The microsphere scaffold of PLGA-CaSiO3-aspirin composites has excellent delayedrelease effect on aspirin, which is promising for using as osteogenic materials.

[Barrier effect of improved porcine small intestinal submucosa absorbable membrane on early healing of mandibular defects in rabbits].

OBJECTIVE: To evaluate the barrier effect of an absorbable barrier membrane made by small intestinal submucosa (SIS) compared with Bio-Gide collagen membrane. METHODS: 12 healthy New Zealand male white rabbits were randomly assigned. A or B round bone defects with a depth of 2 mm and a diameter of 5 mm or 8 mm was made in each rabbit's mandibular. The following treatments were given respectively: covered with SIS membrane (S), covered with Bio-Gide membrane (G) and blank control (O). Then we got six groups: AS, AG, AO, BS, BG, and BO (n=4). After 4 weeks, the rabbits were sacrificed. The specimens were examined by naked-eye observation, new bone percentage (BV/TV) and bone mineralized density (BMD), which were measured and analyzed by Micro-CT. The data were analyzed with one-way ANOVA. RESULTS: After 4 weeks, Bio-Gide membranes were fused with the surrounding tissue while SIS membranes held the form with no significant degradation. In the AS, BS and AG groups, the absorbable membranes smoothly covered on the new bone. While in the BG group, Bio-Gide membranes collapsed to the center of the bone defects. The 3D reconstruction of Micro-CT showed that a large number of newly formed trabeculae were found in the four groups of AS, BS, AG, and BG. In the central subsidence area of the BG group, the newly formed trabeculae were sparse. However only a small amount of new bone trabecula appeared at the bottom of the defects in groups AO and BO. Micro-CT quantitative results showed that BV/TV (39.10%±0.79%) and BMD [(517.73±11.22) mg/cm3] of AS group were significantly higher than those of AO group [26.67%±1.12%, (319.81±8.00) mg/cm3] (P<0.05), and there was no significant difference between AS group and AG group [38.15%±0.91%, (518.65±7.48) mg/cm3] (P>0.05). BV/TV (34.90%±1.35%) and BMD [(409.09±8.14) mg/cm3] of BS group were significantly higher than those of BO group [23.63%±2.07%, (171.00±16.24) mg/cm3] (P < 0.05). Meanwhile, there was no significant difference between BS and BG groups [33.40%±1.06%, (412.70±8.6) mg/cm3] (P>0.05). HE staining analysis revealed that significant bone formation was achieved in the AS, AG, BS and BG groups, and trabecular bone of AS and AG groups were thicker and denser. In AO and BO group, there were scattered new bone tissues in edges of host bone, and no coarse trabecular bone formed. CONCLUSION: In the early healing of two sizes bone defects in rabbit mandibular, SIS membrane and Bio-Gide membrane have a similar barrier effect in guided bone regeneration. And SIS membrane's ability to maintain space for bone regeneration seems to be better.

[Efficacy and side effect analysis of paclitaxel liposome for neoadjuvant chemotherapy in locally advanced cervical cancer].

Objective: To investigate the efficacy and side effect of paclitaxel liposome for neoadjuvant chemotherapy (NACT) in locally advanced cervical cancer. Methods: This study were included 265 cervical cancer patients staging Ⅰb2 and Ⅱa2 who underwent paclitaxel-platinum NACT followed by radical surgery from June 2008 to December 2016 in the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences. All patients were classified into two groups with 106 patients in paclitaxel liposome group and 159 patients in traditional paclitaxel group. The difference in clinicopathologic characteristics, efficacy and side effect were analyzed retrospectively between the two groups. Results: (1) Clinicopathologic characteristics: there were no significant difference in clinicopathologic characteristics between the two groups, including age, body mass index, clinical stage, pathological histology, cycles of NACT, combined platinum regimen, lymph-vascular space invasion, lymph node metastasis, deep stromal invasion, and postoperative adjuvant therapy (all P>0.05). (2) Efficacy: after NACT, the overall response occurred in 90 (15 complete response plus 75 partial response) of 106 cases in the paclitaxel liposome group versus 131 (21 complete response plus 110 partial response) of 159 cases in the traditional paclitaxel group without statistical significance (84.9% vs 82.4%; χ(2)=0.291, P=0.590). A total of 248 patients received surgery after NACT and were evaluable in survival. The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate of these patients was 85.1% and 88.2%. The 5-year RFS rate in the paclitaxel liposome group was 85.9% compared with 85.2% in the traditional paclitaxel group, while the corresponding 5-year OS rate was 88.5% and 88.7%, respectively. There was no statistically significant difference in efficacy between the two groups (P=0.968, P=0.797). (3) Side effect: the incidence of allergic reaction between the paclitaxel liposome group and the traditional paclitaxel group was 0 versus 1.9% (3/159) without statistical significance (P=0.277). But the incidence of neurotoxicity in the paclitaxel liposome group significantly decreased compared with the traditional paclitaxel group (6.6% vs 15.7%, P<0.05), as well as the incidence of alopecia (67.9% vs 79.2%, P<0.05) and myalgia (17.9% vs 28.9%, P<0.05). However, significant differences were not found in terms of hematological toxicity, gastrointestinal reaction, and hepatic function damage (P>0.05). Conclusion: In paclitaxel-platinum NACT of local advanced cervical cancer, paclitaxel liposome can achieve similar efficacy compared with traditional paclitaxel, but paclitaxel liposome is helpful in decreasing the toxicity of neurotoxicity, alopecia and myalgia.

[A multicenter, randomized, controlled, phase â £ clinical study of PEG-rhG-CSF for preventing chemotherapy induced neutropenia in patients with breast cancer].

Objective: To explore the efficacy and safety of polyethylene glycal recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patiens with breast cancer. Methods: There were two parts in the present phase Ⅳ clinical study. One was a randomized, controlled clinical study. Patients in this study received PEG-rhG-CSF or rhG-CSF in the first cycle and followed with both PEG-rhG-CSF in the rest of 3 cycles. The other one was a single arm study. Patients who developed Ⅲ/Ⅳ grade neutropenia in the screening cycle received PEG-rhG-CSF in the rest of 3 cycles chemotherapy. Results: In the first cycle of randomized, controlled study, the incidence of Ⅳ grade neutropenia are 31.48% and 35.58% respectively in PEG-rhG-CSF and rhG-CSF group, with no statistically significant differences (P=0.527 6). The duration of Ⅳ grade neutropenia respectively are 2.22±1.58 and 3.00±1.59 days, with a statistically significant difference (P=0.016 6). In the single arm study, the incidence of Ⅳ grade neutropenia was 57.76% in screening cycle. And the incidence decreased to 16.35%, 10%, and 8.57% in the followed 3 cycle after the use of PEG-rhG-CSF. The incidence of adverse effects was 5.06%, and the major adverse effect was bone pain which with an incidence of 2.8%. Conclusion: The fixed 6mg dose of PEG-rhG-CSF can effectively prevent neutropenia in patients with breast cancer in multicycle chemotherapy and it has a low incidence of adverse events and mild adverse reaction.

An electromyographic study on the sequential recruitment of bilateral sternocleidomastoid and masseter muscle activity during gum chewing.

Mandibular functions are associated with electromyographic activity of the jaw muscles and also the sternocleidomastoid muscle (SCM). The precise spatiotemporal relation of SCM and masticatory muscles activities during chewing is worthy of investigation. To analyse the sequential recruitment of SCM and masseter activities during chewing as indicated by the spatiotemporal locations of their activity peaks. Jaw movements and bilateral surface electromyographic activity of SCM and masseter were recorded during gum chewing in 20 healthy subjects. The timing order was decided by comparing the length of time from the time when the opening started to the time when the surface electromyographic activity reached its peak value. Spatial order was analysed by locating the peak electromyographic activity onto a standard chewing cycle which was created based on 15 unilateral chewing cycles. Paired t-test, one-way ANOVA and Student-Newman-Keuls post-test were used for comparisons. Although the Time to Peak for the balancing side SCM appeared shorter than for the other three tested muscles, most often it did not reach a level of significance. However, the location of the balancing side SCM's peak activity was further from the terminal chewing position (TCP) than the working side SCM and bilateral masseters (P < 0·05). The balancing side SCM activity reached its peak significantly further away from TCP than the other three tested muscles during chewing. Further studies with spatiotemporal variables included should be helpful to understand the roles of the head, neck and jaw muscles in orofacial and cervical dysfunctional problems.

[Influence of EDC ethanol solution on dentin shear bond strength with a self-etch adhesive system].

OBJECTIVE: To evaluate the bonding ability of one representative self-etch adhesive system by applying the micro-shear bond strength test method with different concentrations of carbodiimide [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, EDC] ethanol solution pretreatment. METHODS: Extracted sound human third molars were collected from patients ranging 18 to 40 years. In the study, 80 molars were first sectioned to prepare a flat middle coronal dentin surface and then were randomly divided into 5 groups (n=16) according to without/with different surface treatments [blank control; 80% (volume fraction) ethanol control; EDC ethanol solution of three concentrations (0.01 mol/L, 0.3 mol/L and 0.5 mol/L)]. Each specimen underwent a micro-shear bond strength test and failure mode observation. The data collected were subjected to statistical analysis using one-way ANOVA and post hoc Tukey's test to analyze the difference of the micro-shear bond strength, and chi-square test/Fisher's exact test for the failure mode frequency of the micro-shear bond strength test specimens at a significance level of P=0.05. RESULTS: The micro-shear bond strength of the three concentration EDC treatments were (35.29±8.97) MPa (0.01 mol/L EDC treatment group), (40.24±9.68) MPa (0.3 mol/L EDC treatment group), (37.38±9.66) MPa (0.5 mol/L EDC treatment group) separately; and that of the 80% ethanol group was (37.49±7.76) MPa. All micro-shear bond strength value of the above four groups was statistically higher than that of the blank control group [(33.81±7.98) MPa]. The immediate micro-shear bond strength and failure mode was of no statistically significant difference among all the groups. It was noticed that the immediate micro-shear bond strength of 0.3 mol/L was higher than that of all the other groups, especially higher than that of the 80% ethanol pretreatment group despite that there was no significant difference among all the groups. And the test of failure mode indicated that the cohesive failure was more common, while the frequency of adhesive failure was rare in each experimental group. CONCLUSION: EDC pretreatment had no adverse effect on the immediate micro-shear bond strengths of Clearfil SE Bond. Meanwhile, EDC treatment did not cause more adhesive failure in immediate micro-shear test, which had further denoted what was said above. However, it needs more research to illustrate the anti-enzymatic role of EDC in dentin bonding.

[Clinical effect and safety of pegylated interferon-α-2b injection (Y shape, 40 kD) in treatment of HBeAg-positive chronic hepatitis B patients].

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion: In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

Enhancing immune responses of EV71 VP1 DNA vaccine by co-inoculating plasmid IL-12 or GM-CSF expressing vector in mice.

Enterovirus 71 (EV71) is a major causative viral agent for large outbreaks of hand, foot, and mouth disease in children and infants, yet there is no vaccine or effective antiviral treatment for severe EV71 infection. The immunogenicity of EV71 VP1 DNA vaccine and the immunoregulatory activity of interleukin-12 (IL-12) or granulocyte-monocyte colony stimulating factor (GM-CSF) were investigated. DNA vaccine plasmids, pcDNA-VP1, pcDNA-IL-12 and pcDNA-GM-CSF were constructed and inoculated into BALB/c mice with or without pcDNA-IL-12 or pcDNA-GM-CSF by intramuscular injection. Cellular and humoral immune responses were assessed by indirect ELISA, lymphocyte proliferation assays, cytokine release assay and FACS. The VP1 DNA vaccine had good immunogenicity and can induce specific humoral and cellular immunity in BALB/c mice, while IL-2 or GM-CSF plays an immunoadjuvant role and enhances specific immune responses. This study provides a frame of reference for the design of DNA vaccines against EV71.

Experimental studies of thermal environment and contaminant transport in a commercial aircraft cabin with gaspers on.

Gaspers installed in commercial airliner cabins are used to improve passengers' thermal comfort. To understand the impact of gasper airflow on the air quality in a cabin, this investigation measured the distributions of air velocity, air temperature, and gaseous contaminant concentration in five rows of the economy-class section of an MD-82 commercial aircraft. The gaseous contaminant was simulated using SF6 as a tracer gas with the source located at the mouth of a seated manikin close to the aisle. Two-fifths of the gaspers next to the aisle were turned on in the cabin, and each of them supplied air at a flow rate of 0.66 l/s. The airflow rate in the economy-class cabin was controlled at 10 l/s per passenger. Data obtained in a previous study of the cabin with all gaspers turned off were used for comparison. The results show that the jets from the gaspers had a substantial impact on the air velocity and contaminant transport in the cabin. The air velocity in the cabin was higher, and the air temperature slightly more uniform, when the gaspers were on than when they were off, but turning on the gaspers may not have improved the air quality.

Unbalanced lateral mandibular deviation associated with TMJ sound as a sign in TMJ disc dysfunction diagnosis.

The aim was to study the characteristics of lateral mandibular horizontal deviations during opening-closing movements and their association with TMJ sounds of the clicking type. Subjects were 28 healthy volunteers and 38 patients diagnosed with MRI imaging as having TMJ disc dysfunction, 22 with disc displacement without (DD) and 16 as having disc displacement with reduction (DDR). TMJ sounds were recorded with miniature microphones placed in the ear canals, and jaw movements were documented with a kinesiograph. A sign, unbalanced lateral deviation (ubd) was defined as a rapid, short duration, change in jaw movement direction from, and back to, a smooth deviation path in the horizontal plane. The hypotheses were that degrees of maximal deviations, proportions of unbalanced deviation (ubd) and such deviation associated with TMJ sounds (ubdS), differ between healthy subjects and patients with DD or DDR. Comparisons between groups were made using one-way anova and chi-square analysis, as appropriate. No differences were found between groups regarding degree of lateral deviation per se. The proportions of ubd and ubdS were significantly higher in patients with DDR than in healthy subjects and than in patients with DD (P < 0·001), but no such differences were found between healthy subjects and patients with DD. For prediction of DDR, the sensitivity and specificity of the sign ubdS were found to be 68·8% and 89·3%, respectively. For the sign ubd, they were 100·0% and 64·3%. This indicates that the sign ubdS has diagnostic value in screening for DDR.

Expression of OPG, RANKL, and RUNX2 in rabbit periodontium under orthodontic force.

This study aims to investigate the expression changes of RANKL, RUNX2, and OPG in rabbit periodontal tissues under orthodontic force and explore its effect on the remodeling of periodontal tissues. A total of 16 specific pathogen-free rabbits were used in this study. The maxillary appliance was worn on the right (experimental) side, and the appliance-free left side was used as the control. Rabbits were sacrificed after 3, 5, 7, and 14 days of treatment. Changes in the expression levels of OPG, RANKL, and RUNX2 in the periodontium were detected using real-time PCR and western blotting methods. The OPG expression levels decreased after 3 to 14 days of treatment, while the expression levels of RANKL and RUNX2 increased after 3 to 14 days. The OPG expression levels decreased while those of RANKL and RUNX2 increased during orthodontic tooth movement, which suggested that they play a role in the osteogenesis process and the reconstruction of periodontal tissue.