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As an important part of radiation therapy quality assurance, dose verification can verify the accuracy of the treatment dose to the patient’s tumor target area before treatment. At present, the dose verification technology has developed to the stage of three-dimensional dose verification. However, the existing clinical dose verification tools cannot meet the demand for three-dimensional dose verification in heavy ion therapy. In order to quickly and accurately realize three-dimensional dose verification of carbon ion therapy plan, a three-dimensional ionization chamber array was designed by using plexiglass PMMA(polymethyl methacrylate) as the ionization chamber wall and water equivalent phantom. And the structural design of the three-dimensional ionization chamber array was thoroughly studied and verified by Geant4 software. Firstly, by simulating the depth dose distribution of carbon ion beam deposited in water and PMMA phantom with different energies, the distal range ratio of the Bragg peak of the carbon ion beam in water and PMMA phantom was calculated, and the water equivalent thickness factor of PMMA phantom was characterized. Its value is 1.151. Then the effects of the spacing between adjacent ionization chambers and the signal leads on the accuracy of the dose measurement in the three-dimensional ionization chamber array were investigated. The signal crosstalk between adjacent ionization chambers mainly originates from the front ionization chamber, and the degree of crosstalk is inversely proportional to the spacing, the degree of crosstalk accounts for 3% of the dose within the ionization chamber at spacing of 1 mm, and the crosstalk effect can be completely eliminated at spacing of 30 mm. And the interference effect of the signal leads on the dose within the rear ionization chamber is about 1%. Finally, the dose distribution of 100 MeV/u and 200 MeV/u carbon ion beams deposited in the three-dimensional ionization chamber array was simulated, and the distal range of the Bragg peak was obtained in which the carbon ion beam was deposited. It has good agreement compared to the distal range of the Bragg peak in the PMMA phantom, and the deviation is 0.5 mm. The research show that the three-dimensional ionization chamber array can realize the three-dimensional dose verification of heavy ion therapy at the same time, and provides a reference for the development of three-dimensional ionization chamber array. The quality assurance level of carbon ion therapy should be further improved.

Objective To analyze and summarize the clinical features of one patient with anti-GQ1b antibody syndrome presenting with rare and atypical manifestations of headache and visual disturbance. Methods Clinical data of a patient with anti-GQ1b antibody syndrome presenting with rare and atypical manifestations of headache and visual impairment were reported. Relevant case reports were retrieved from PubMed, Web of Science, CNKI and Wanfang Data using Chinese search terms of “visual disturbance”“visual impairment”“headache” and “head pain”, and English search terms of “GQ1b”“vision disorders”“visual disorders”“visual disturbance”“headache”“head pain” and “cephalalgia”, etc. Combined with literature review, the pathogenesis, clinical manifestations, laboratory and auxiliary examination and treatment prognosis of patients presenting with this type of manifestations were summarized. Results The 71-year-old male patient had a history of diarrhea at 3 weeks before the onset, manifested with headache and visual disturbance. Cerebrospinal fluid was detected for anti-GQ1b antibody （+） and anti-aquaporin 4 （AQP-4） antibody （-）. He was diagnosed with anti-GQ1b antibody syndrome. Headache symptoms were relieved by steroid treatment, and visual acuity was basically restored after 20 d. According to literature reviews, 9 patients with anti-GQ1b antibody syndrome were manifested with visual impairment and 5 patients presented with headache. All these patients had a history of pre-infection before the onset of disease. Serum or cerebrospinal fluid anti-ganglioside antibody detection contributed to early diagnosis. Prompt use of steroid hormone or immunoglobulin therapy yielded favorable prognosis. Conclusions Patients with anti-GQ1b antibody syndrome can only present with isolated atypical symptoms, such as headache and visual disturbance, if patients have pre-infection histories, early diagnosis and treatment should be performed.

Firstly, the paper established the link bar coordinate system based on axis direction of manipulator joint. Secondly, according to Denavit-Hartenberg(D-H)notation, the coordinate system transformation matrix was derived.Thirdly, the forward kinematics model was established based on the coordinate system transformation matrix.Finally, we set up the inverse kinematics model based on reversely solving the forward kinematics model.The inverse kinematics model is a kind of multiple object optimization problems, and the optimal solution of the inverse kinematics model has characteristics of high accuracy with minimized rotation extent, and the solution is continuous. For the sake of solving the inverse kinematics model, we proposed an improved multiple population differential evolution (IMPDE) algorithm, which can destroy the aggregation level of the population by choosing different mutation operation based on mutation probability so as to enhance the ability of global search. The numerical results show that the new algorithm can solve the inverse kinematics model efficiently. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the effect of Angelica sinensis polysaccharide (ASP) on the osteogenic differentiation of the bone marrow mesenchymal stem cells (BMSCs) of rats with high glucose levels., Methods: Rat BMSCs were isolated and identified by osteogenic and adipogenic differentiation. Then, the BMSCs were divided into three groups as follows: normal control group (5.5 mmol·L⁻¹ glucose), high glucose group (25.5 mmol·L⁻¹ glucose), and ASP+high glucose group (25.5 mmol·L⁻¹ glucose +40 mg·L⁻¹ ASP). The proliferation activities of the BMSCs were detected by CCK8. Alizarin red staining, and alkaline phosphatase activity were used in the examination of osteogenic activity. Quantitative real time-polymerase chain reaction was used to detect the expression levels of the osteogenic genes (Runx2, Osx, OCN, Col-Ⅰ) and the key factors of Wnt/β-catenin signal pathway (CyclinD1, β-catenin). In vivo, a type 2 diabetes rat model was established. The rats were divided into three groups, namely, the normal control group (normal rats), diabetes group (diabetic rats), diabetes+ASP group (diabetic rats, ASP feeding). Then, the tibia bone defect was established. The repair of bone defects in each group was observed through histological examination., Results: The proliferation of BMSCs was higher in the high glucose group and ASP+high glucose group than in the normal control group (P<0.05). No significant difference was observed between the high glucose group and ASP+high glucose group (P>0.05). The number of calcium nodules of BMSCs; alkaline phosphatase activity; and the mRNA expression of Runx2, OCN, Osx, Col-Ⅰ, CyclinD1, β-catenin in the high glucose group were lower than those in the normal control and ASP+high glucose groups (P<0.05). No significant difference was observed between the normal control and ASP+high glucose groups (P>0.05). The bone mass was significantly lower in the bone defect of the diabetes group than in the bone defect of the normal control or diabetes+ASP group (P<0.05). No statistical difference was found between the normal control and diabetes+ASP groups (P>0.05)., Conclusions: ASP can promote the osteogenic differentiation of rat BMSCs under high glucose culture and induce bone regeneration in rats with type 2 diabetes. These features may be related to the activation of the Wnt/β-catenin signaling pathway.

Objective: To investigate the effect of Notch signaling pathways on differentiation of mouse embryonic stem cells(ESC) into haematopoietic stem cells or haematopoietic progenitors cells(HSC/HPC)., Methods: Mouse embryonic stem cells were proliferated in vitro to form embryoid bodies; the differentiation of embryoid bodies should be induced in vitro, the experiments were divided into BE, control, VEGF, DAPT and VEGF-DAPT groups; HSC/HPC ohenotype: CD117 + D34 + Sca1 + was detected by flow cytometry; the related gene expression was detected by RT-PCR., Results: The number of VEGF-induced HSC/HPC in VEGF group was significantey higher than that in the control and EB group (P<0.05), suggesting that VEGF promotes ESC differentiation to HSC/HPC; the number of DAPT-induced HSC/HPC in DAPT group was significanty higher than that in the Control and EB groups(P<0.05), suggesting that DAPT promotes ESC differentiation to HSC/HPC; the number of VEGF+DAPT-induced HSC/HPC in VEGF-DAPT group was significantly higher than that in VEGF and DAPT groups(P<0.05), suggesting that DAPT and VEGF play a synergistic role to promote differentiation of ESC into HSC/HPC., Conclusion: Notch signal pathway inhibits differentiation of ESC into HSC / HPC by VEGF.

Objective: This study aims to investigate the effect of human osteoprotegerin (hOPG) gene-modified rat bone marrow mesenchymal stem cells (rBMSCs) combined with hydroxyapatite (HA) scaffolds on the repair of mandibular defects in ovariectomized rats., Methods: rBMSCs were transfected with adenovirus carrying pDC316-hOPG-EGFP. The expression of hOPG and the inhibition of osteoclast function were detected by Western blot and bone-grinding experiment respectively. The model of mandibular bone defect in rats with osteoporosis was established; HA, untransfected rBMSCs-conjugated HA, and transfected rBMSCs-conjugated HA scaffolds were implanted into the mandibular bone defects. After six weeks, tartrateresistant acid phosphatase staining and hematoxylin-eosin staining were used to observe the number of osteoclasts and repair of bone defect., Results: Adenovirus carrying hOPG gene in vitro were successfully transfected into rBMSCs. The hOPG with anti-osteoclast activity was expressed by hOPG-rBMSCs, and rBMSCs expressing hOPG combined with HA scaffolds promoted mandibular defect repair., Conclusions: rBMSCs transfected with hOPG gene inhibited the function of osteoclasts both in vitro and in vivo, and transfected rBMSCs combined with HA scaffolds promoted the repair of mandibular defects in rats with osteoporosis.

To establish a method for detecting microdialysis recovery of tetramethylpyrazine (TMP) and ferulic acid (FA) and investigating the influencing factors, providing the basis for further in vivo microdialysis experiments. The concentration of FA and TMP in dialysates were determined by high pressure liquid chromatography ( HPLC) and probe recovery were calculated respectively. The influence of the flow rates, medium concentration, temperature and in vivo probe stability on the recovery of FA and TMP were investigated by using concentration difference method (incremental method and decrement method). The recovery obtained by incremental method were similar to by decrement method. The in vitro recovery rate of FA and TMP decreased with the increase of 1-2.5 μL min(-1), and increased obviously with the temperature of 25-42 degrees C under the same conditions. The concentration of FA and TMP had no obvious effect on the probe recovery under the same flow rate. In addition, the recovery of TMP and FA remained stable and showed similar trends under the condition of four concentration cycles, indicating that the intra day reproducibility of the concentration difference method was good. The recovery of brain microdialysis probes in vivo 8 h maintained a relatively stable, but certain differences existed between different brain microdialysis probes, demonstrating that each probe was required for recovery correction in vivo experiment. Microdialysis sampling can be used for the local brain pharmacokinetic study of FA and TMP, and retrodialysis method can be used in probe recovery of FA and TMP in vivo.

Objective: To evaluate the efficacy of SLIT with Dermatophagoides farinae drops in children with allergic rhinitis and allergic asthma according to its different duration., Methods: The efficacy of Dermatophagoides farinae SLIT in 100 children (aged 3-14 yr) with allergic rhinitis and allergic asthma induced by house dust mites was retrospectively analyzed. All children were treated with Dermatophagoides farinae drops for 4 years and followed-up at the interval of 3 months. Total nasal symptom scores (TNSS), total rhinitis symptomatic medication scores (TRMS), daytime asthma symptom scores (DASS), nighttime asthma symptom scores (NASS), total asthma symptomatic medication scores (TAMS), visual analog scale scores (VAS) and lung function were assessed during follow-up visit. SPSS 20.0 software was used for data analysis., Results: After 2 years' SLIT, compared with 1-year duration, besides NASS (0.00[0.00;0.00], 0.00[0.00;0.00]; Z = 1.811; P > 0.05), TNSS (2.00[1.00;2.00], 0.00[0.00;0.00]; Z = 7.021, P < 0.01), TRMS (2.00[2.00;2.00], 0.00[0.00;0.00]; Z = 8.855; P < 0.01), VAS scores (3.00[2.00;4.00], 1.00[0.00;1.00]; Z = 4.494, P < 0.01), DASS (1.00[0.00;1.00]; 0.00[0.00;0.00]; Z = 4.383, P < 0.01) and TAMS (0.00[0.00;1.00], 0.00[0.00;0.00]; Z = 8.944; P < 0.01) all showed significant improvement. After 3-year duration, compared with 2-year duration, VAS scores (1.00[0.00;1.00], 0.00[0.00;0.00]; Z = 3.645, P < 0.05) in patients were significantly decreased. Other results showed no significant difference. The comparison of efficacy between 3 and 4-year duration showed no significant difference in global clinical outcomes (all P > 0.05)., Conclusions: Patients receiving 2 year' SLIT achieve more clinical benefits than those who receiving 1-year duration. The higher efficacy of 3-year duration compared with 2-year duration is supported by a significant improvement in VAS. Besides, the comparison between 3 and 4-year duration shows no significant difference in global clinical outcomes. Therefore, 3 years' duration is optimal in this study.

Objective: To study the clinical symptoms and the condition of skin barrier of different facial dermatitis., Methods: The patients with facial dermatitis were divided into 4 groups based on their diagnosis: hormone-dependent dermatitis (HDD) group, sensitive skin (SS) group, cosmetic intolerance (CI) group and normal control group. All patients received the evaluation on clinical symptoms with measuring scale, measurements of stratum corneum water content (SCWC), sebum, pH, trans-epidermal water loss (TEWL) and blood flow. The skin scales were collected for the measurements of the ratio of immature cornified envelope (CE) via immunofluorescence and the concentration of kallikrein 5 (KLK5) via enzyme-linked immunosorbent assay., Results: There were total 146 patients included (HDD 38, SS 53, CI 15, control group 30), most of them had their symptoms evaluated as moderate to severe. Compared with the control, the disease groups had lower SCWC and sebum (P < 0.05), higher pH, TEWL and blood flow (P < 0.05), higher ratio of immature CE (P = 0.011) and lower concentration of KLK5 (P = 0.000); while these parameters among the disease groups did not show statistical significant difference., Conclusion: There is no difference in the clinical symptoms and the condition of skin barrier between facial dermatitis with different inducements. The growth of CE may be inhibited and the concentration of KLK5 decreases in facial dermatitis.

Objective: To evaluate the efficacy of specific sublingual immunotherapy (SLIT) with Dermatophagoides farinae drops on children with allergic asthma and allergic rhinitis of the preschool and school-age groups of children and adolescents., Method: This study analyzed the efficacy of SLIT in 122 children (aged 3-14 yr) with house dust mites-induced allergic asthma and allergic rhinitis. According to the age, patients were defined as the preschool group ( ≤ 6 years old, n = 59) and school-age group (> 6 years old, n = 63). All children were treated with Dermatophagoides farinae drops for at least 2 years. Clinical observation and follow-up study were conducted during the treatment. Before and after SLIT for half a year, 1 year and 2 years, asthma symptom scores (day and night), rhinitis symptom scores and medication scores were evaluated. The adverse events were assessed during the study., Result: After SLIT for half a year, 1 year and 2 years, there were no significant differences between the preschool group (0.3 ± 0.5,0.0 ± 0.1,0.0 ± 0.0) and school-age group (0.3 ± 0.4,0.0 ± 0.1,0.0 ± 0.0) in day scores of asthma (Z value was -1.687, -0.613,0.000, all P > 0.05). There were no significant differences between the preschool group (0.2 ± 0.5,0.1 ± 0.3,0.0 ± 0.0) and school-age group (0.2 ± 0.4,0.1 ± 0.3, 0.0 ± 0.0) in night scores of asthma (Z value was -0.496, -0.486,0.000, all P > 0.05). There was no significant differences between the preschool group (1.4 ± 0.9,0.4 ± 0.5,0.1 ± 0.3) and school-age group (1.3 ± 0.9,0.5 ± 0.6,0.2 ± 0.4) in symptom scores of allergic rhinitis (Z value was -0.394, -1.166, -1.075, all P > 0.05). There were no significant differences between the preschool group (1.6 ± 0.8,0.0 ± 0.0,0.0 ± 0.0) and school-age group (1.7 ± 0.7,0.0 ± 0.0,0.0 ± 0.0) in medication scores of allergic rhinitis (Z value was -0.655,0.000,0.000, all P > 0.05). After SLIT for 2 years, most children in the preschool and school-age groups were no longer using asthma controlling medication, with no significant difference between the two groups (Z value was 0.000, P > 0.05). The overall incidence of adverse reactions was only 7%, and there was no significant difference in the incidence of adverse reactions between the two groups (χ(2) = 0.000, P > 0.05). The local adverse events were mild gastrointestinal discomfort and rash, a majority of local adverse events in the preschool group were diarrhea. No severe adverse events happened in the treatment., Conclusion: SLIT with Dermatophagoides farinae drops is safe and effective in children with allergic asthma and allergic rhinitis of the preschool and school-age groups of children and adolescents, which provides evidences for early SLIT intervention of the disease.

In past decade, hydrogen sulfide (H₂S) as a novel gasotransmitter, covered many fields in biological and medical research. However, there is no effective, convenient and high-throughput method for determination of circulatory H₂S until now. Here, we aim to develop an easy method for measurement of circulatory H₂S by modified methylene blue method. In the present study, we added Zn²⁺ to plasma sample to deposit H₂S, HS⁻ and S²⁻, as well as plasma protein, then used NaOH to re-dissolve plasma protein. ZnS deposition was re-dissolved by the addition of N, N-dimethyl-p-phenylenediamine, and the remnant protein was deposited by trichloroacetic acid. After centrifugation, ferriammonium sulfate was added to the supernatant fluid to generate methylene blue, which was analyzed by spectrophotometer at 665 nm. Using the present method, we found that most ions including sulfate and thiosulfate did not affect detection of H₂S concentration, but albumin (physiological concentration) reduced the detection value, which suggested the binding of serum albumin and a certain amount of H₂S. The relative recovery ratio of present method is 81.9%, which implies that the method is relative accurate for the determination of H₂S concentration in plasma or serum. H₂S levels of frozen plasma samples from 65 healthy volunteers detected by the present method were (13.93 ± 4.98) µmol/L. There was no obvious difference between the detection values of fresh and frozen samples from the same SD rats. These results suggest the modified methylene blue assay is stable, sensitive, convenient and high-throughput. The method can be used to analyze the circulatory H₂S in clinical and basic research.

Objective: To investigate the expression of tumor necrosis factor-alpha (TNF-alpha) in the lung tissue of rats with lung injury induced by brain ischemia., Methods: The rat model of lung injury induced by brain ischemia was established. At 24 h, 48 h, 72 h after brain ischemia, lung tissues were harvested from each rats, the expressions of TNF-alpha mRNA and protein and its distributions in the lung tissue were measured by the methods of RT-PCR (n=8), Western blot (n=8), and immunohistochemistry (n=5), respectively., Results: The increase of TNF-alpha mRNA and protein levels were found in the lung tissues after brain ischemia, when compared with sham group (P<0.05). The morphological study with immunohistochemical staining observed TNF-alpha positive reaction in epithelial cells and some macrophages in the lung tissues after brain ischemia., Conclusion: The expression of TNF-alpha in the lung tissue could be upregulated in the rats with brain ischemia.

Objective: To investigate the correlations of serum interleukin-18 (IL-18) level and IL-18 gene promoter polymorphisms to the development of sepsis in children., Method: Using enzyme-linked immunosorbent assay (ELISA), the authors tested the serum IL-18 level in 90 patients with sepsis and 123 normal controls, and their single nucleotide polymorphisms of the promoter region of IL-18 gene at position -607C/A and -137G/C were detected using polymerase chain reaction with sequence specific primers method and sequencing technique., Result: (1) The serum IL-18 level in sepsis groups was (196.56 +/- 157.32) pg/ml that was significantly higher than (66.16 +/- 41.63) pg/ml in normal controls (P < 0.01), the more severe the degree of sepsis was, the more significantly higher the serum IL-18 level was. The serum IL-18 level in non serious sepsis group was (152.87 +/- 114.96) pg/ml that was significantly higher than (66.16 +/- 41.63) pg/ml in normal controls, the serum IL-18 level in serious sepsis group was (191.98 +/- 169.72) pg/ml that was significantly higher than that in non serious sepsis group, and the serum IL-18 level in extremely serious sepsis patients was (323.89 +/- 159.35) pg/ml, the difference was highly significant (P = 0.000). The difference was significant among the groups with different severity of sepsis (P < 0.01). There was a negative correlation between PCIS (pediatric critical illness score) of sepsis and the serum IL-18 level (P < 0.01). (2) There were polymorphisms in IL-18 gene promoter of matched healthy children and sepsis in children. The GG genotype frequency (61.8%) of IL-18-137G/C in healthy children was the highest, followed by GC genotype (35.8%) and CC genotype (2.4%) in sequence. The G allele frequency (79.7%) was higher in IL-18-137G/C of healthy children than C allele (20.3%). The GG genotype frequency (71.1%) of IL-18-137G/C in septic children was the highest, the next were GC genotype (26.7%) and CC genotype (2.2%). The G allele frequency (84.4%) was higher in IL-18-137G/C of septic children than C allele (15.6%). The CA genotype frequency (61.0%) of IL-18-607C/A in healthy children was the highest, followed by CC genotype (26.8%) and AA genotype (12.2%). The C allele frequency (57.3%) was higher in IL-18-607C/A of healthy children than A allele (42.7%). The CA genotype frequency (76.7%) of IL-18-607C/A in septic children was the highest, followed by CC genotype (21.1%) and AA genotype (2.2%) in sequence. The C allele frequency (59.4%) was higher in IL-18-607C/A of septic children than A allele (40.6%). (3) The genotype frequency of IL-18-607 CA was 76.7% in sepsis groups that was significantly higher than 61.0% in normal controls, and the genotype frequency of -607 AA was 2.2% in sepsis groups that was significantly lower than 12.2% in normal controls, the difference was significant (P < 0.05). (4) In the order of -137CC, -137GC, -137GG, the serum IL-18 level in normal controls were as follows: (45.67 +/- 28.36) pg/ml, (53.27 +/- 37.91) pg/ml, (76.91 +/- 42.44) pg/ml, and with (140.50 +/- 60.10) pg/ml, (184.42 +/- 157.33) pg/ml, (237.02 +/- 161.76) pg/ml respectively in sepsis groups. In the order of -607AA, -607CA, -607CC, the serum IL-18 level in normal controls were: (48.80 +/- 32.11) pg/ml, (68.41 +/- 42.53) pg/ml, (70.17 +/- 43.87) pg/ml; and with (141.50 +/- 64.35) pg/ml, (151.21 +/- 121.19) pg/ml, (211.16 +/- 163.64) pg/ml respectively in sepsis groups. The difference was not significant among different groups (P > 0.05)., Conclusion: The serum IL-18 level in sepsis groups was significantly higher than that in normal controls, which was related to the severity of sepsis. It was possible that the genotype of -607CA carriers was susceptible to sepsis, which mean that the genotype of -607CA might be susceptible genotype of sepsis. However, the genotype of -607AA might play an oppose role in the risk of sepsis.