ObjectiveTo analyze the differences in color， odor and volatile components of Citri Reticulatae Pericarpium（CRP） before and after being stir-fried with Halloysitum Rubrum， and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the volatile components were analyzed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. According to the principle of variable importance in the projection（VIP） value>1.5， volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose， the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum， of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected， including α-pinene， β-myrcene， linalool， sabinene， ocimene isomer mixture， A-ocimene， and δ-elemene. After being processed with Halloysitum Rubrum， the brightness value（L^*）， yellow-blue value（b^*） and total chromatic value（E^*_ab） of CRP were decreased（P<0.01）， and red-green value（a^*） was increased（P<0.01）， the response values of S4， S5， S10 and S13 sensors were significantly increased（P<0.05）， and the response values of S3 and S8 sensors were significantly decreased（P<0.05）. Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L^* and E^*_ab， but positively correlated with a^*. Sabinene was positively correlated with L^* and E^*_ab. Linalool was positively correlated with L^* and E^*_ab， and negatively correlated with a^*. The ocimene isomer mixture was positively correlated with the L^*. ConclusionAfter being processed with Halloysitum Rubrum， the appearance color， odor and volatile components of CRP change significantly， and α-pinene， β-myrcene， sabinene， linalool and A-ocimene are the characteristic volatile components before and after processing， which can provide references for the quality evaluation and clinical application of CRP and its processed products.

ObjectiveTo analyze the differences in color， odor and volatile components of Citri Reticulatae Pericarpium（CRP） before and after being stir-fried with Halloysitum Rubrum， and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the volatile components were analyzed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. According to the principle of variable importance in the projection（VIP） value>1.5， volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose， the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum， of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected， including α-pinene， β-myrcene， linalool， sabinene， ocimene isomer mixture， A-ocimene， and δ-elemene. After being processed with Halloysitum Rubrum， the brightness value（L^*）， yellow-blue value（b^*） and total chromatic value（E^*_ab） of CRP were decreased（P<0.01）， and red-green value（a^*） was increased（P<0.01）， the response values of S4， S5， S10 and S13 sensors were significantly increased（P<0.05）， and the response values of S3 and S8 sensors were significantly decreased（P<0.05）. Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L^* and E^*_ab， but positively correlated with a^*. Sabinene was positively correlated with L^* and E^*_ab. Linalool was positively correlated with L^* and E^*_ab， and negatively correlated with a^*. The ocimene isomer mixture was positively correlated with the L^*. ConclusionAfter being processed with Halloysitum Rubrum， the appearance color， odor and volatile components of CRP change significantly， and α-pinene， β-myrcene， sabinene， linalool and A-ocimene are the characteristic volatile components before and after processing， which can provide references for the quality evaluation and clinical application of CRP and its processed products.

OBJECTIVE To investigate the improvement effects of 3，5，6，7，8，3′，4′-heptamethoxyflavone （HMF） of Fructus Aurantii on rats with damp blockage of the middle energizer. METHODS The rats were randomly divided into normal group， model group， positive control group （Raceanisodamine tablet， 1 mg/kg）， HMF low-dose， medium-dose and high-dose groups （0.3， 0.6， 0.9 mg/kg）， with 7 rats in each group. Except for the normal group， the other groups were modeled by internal and external composite factors. After successful modeling， the rats in each group were given the corresponding drug or normal saline， once a day， for 14 days. The general behavioral states such as dietary intake， water intake and mental state of the rats were observed， and the fecal water content rate and saliva flow rate were measured. Hematoxylin-eosin （HE） staining was used to observe the pathological and morphology in gastric and small intestinal tissues of rats. The plasma content of aldosterone was detected， and the expression of aquaporins （AQP3） in the gastric tissue of rats was determined. RESULTS Compared with the normal group， the dietary intake and water intake of the model group rats were significantly decreased （P＜0.01）， the fecal water content rate， salivary flow rate， plasma content of aldosterone and the expression of AQP3 in gastric tissue were increased significantly （P＜0.01）. Gastric tissue injury invaded the mucosal muscle layer， resulting in mucosal muscle layer rupture； pathological and morphological changes such as small intestinal villous erosion and glandular structure destruction were observed in the small intestine. Compared with the model group， the dietary intake and water intake of rats were increased in HMF groups； fecal water content rate， salivary flow rate， plasma content of aldosterone， the expression of AQP3 in gastric tissue were decreased， most of the above differences were statistically significant （P＜0.05 or P＜0.01）. The pathological and morphological changes in the gastric and small intestine tissues of rats had been improved to varying degrees. CONCLUSIONS HMF of Fructus Aurantii with dry property HMF could improve the symptoms of rats with damp blockage of middle energizer， the mechanism of which may be associated with reducing the content of plasma aldosterone and down-regulating the expression of gastric AQP3.

To analyze the positivity rate and titer of antinuclear antibody (ANA), as well as nuclear pattern and target antigen of ANA in healthy pregnant women during early pregnancy in Qingdao area. A prospective cohort study design was used to include a total of 9 528 healthy pregnant women registered at the Women and Children′s Hospital Affiliated to Qingdao University from March 2023 to June 2024.Indirect immunofluorescence assay (IIF) was used to detect ANA, its titer and cell staining pattern. Fifteen specific antibodies were tested using the magnetic bar code immunofluorescent luminescence method. Logistic regression model was used to analyze the risk factors of pregnancy with autoimmune disease(AID). The results showed that among 9 528 pregnant women in early pregnancy, 1 346 cases (14.1%) were positive of ANA, including 1 011 cases with a titer of 1∶100 (10.6%), 236 cases (2.5%) with a titer of 1∶320, and 99 cases (1.0%) were detected at a titer >1∶320. Among the 1 346 ANA-positive pregnant women, nuclear granular type accounted for the highest proportion (483 cases, 35.9%), followed by speckled type (347 cases, 25.8%) and cytoplasmic type (176 cases, 13.1%).Then, pregnant women with ANA titers ≥1∶100 were detected 15 specific antibodies.Anti-SSA was tested in 121 cases accounted for the majority, followed by 110 cases with anti-Ro-52, 56 cases with anti-SSB, 51 cases with anti-mitochondrial M2 subtype antibodies and 37 cases with anti-centromere B. In conclusion,in healthy pregnant women in Qingdao area, ANA positivity rate was 14.1%, and the titer of ANA was mainly at 1∶100.The predominant nuclear patterns were nuclear granular and speckled types.The specific autoantibodies were mainly anti-SSA antibodies and anti-Ro-52 antibodies.The detection of ANA and specific autoantibodies is of great significance for early prediction, diagnosis, and intervention of autoimmune diseases during pregnancy.

To analyze the positivity rate and titer of antinuclear antibody (ANA), as well as nuclear pattern and target antigen of ANA in healthy pregnant women during early pregnancy in Qingdao area. A prospective cohort study design was used to include a total of 9 528 healthy pregnant women registered at the Women and Children′s Hospital Affiliated to Qingdao University from March 2023 to June 2024.Indirect immunofluorescence assay (IIF) was used to detect ANA, its titer and cell staining pattern. Fifteen specific antibodies were tested using the magnetic bar code immunofluorescent luminescence method. Logistic regression model was used to analyze the risk factors of pregnancy with autoimmune disease(AID). The results showed that among 9 528 pregnant women in early pregnancy, 1 346 cases (14.1%) were positive of ANA, including 1 011 cases with a titer of 1∶100 (10.6%), 236 cases (2.5%) with a titer of 1∶320, and 99 cases (1.0%) were detected at a titer >1∶320. Among the 1 346 ANA-positive pregnant women, nuclear granular type accounted for the highest proportion (483 cases, 35.9%), followed by speckled type (347 cases, 25.8%) and cytoplasmic type (176 cases, 13.1%).Then, pregnant women with ANA titers ≥1∶100 were detected 15 specific antibodies.Anti-SSA was tested in 121 cases accounted for the majority, followed by 110 cases with anti-Ro-52, 56 cases with anti-SSB, 51 cases with anti-mitochondrial M2 subtype antibodies and 37 cases with anti-centromere B. In conclusion,in healthy pregnant women in Qingdao area, ANA positivity rate was 14.1%, and the titer of ANA was mainly at 1∶100.The predominant nuclear patterns were nuclear granular and speckled types.The specific autoantibodies were mainly anti-SSA antibodies and anti-Ro-52 antibodies.The detection of ANA and specific autoantibodies is of great significance for early prediction, diagnosis, and intervention of autoimmune diseases during pregnancy.

Objective:To analyze food intolerance status in children in Qingdao by detecting the serum levels of food-specific IgG (sIgG).Methods:In this cross-sectional study, a total of 4 249 children aged 0 to 14 years (all were permanent residents of Qingdao City) admitted to Women and Children′s Hospital Affiliated to Qingdao University from May 2017 to December 2020 for suspected food intolerance were selected as the study objects with the whole sampling method. According to the age, the objects were divided into 4 groups: 0-<1 year group (440 cases), 1-<3 years group (1 761 cases), 3-<6 years group (1 193 cases), and ≥6 years group (855 cases). Positive condition of serum sIgG antibodies of 14 kinds of food in the children were detected by enzyme-linked immunosorbent assay. Chi-square test was used to compare the positive rate of the antibodies among different foods, gender and age groups.Results:The total positive rate of food sIgG antibody in 4 249 children was 95.32% (4 050/4 249), the highest positive rate was found in eggs (81.50%) and the lowest positive rate was found in pork (1.15%). The positive rates of sIgG antibody in milk (54.98% vs 49.69%, χ2=11.627), crab (5.59% vs 3.71%, χ2=8.049) and shrimp (4.62% vs 2.75%, χ2=9.784) in boys were significantly higher than those in girls, and the positive rates of sIgG antibody in tomato (49.19% vs 45.54%, χ2=5.510), cod (8.53% vs 5.96%, χ2=10.512) and beef (2.58% vs 1.70%, χ2=3.959) in girls were significantly higher than those in boys (all P<0.05). The total positive rate of sIgG antibody in 14 foods was the lowest in 0-<1 year group (89.09%), and it was the highest in 3-<6 years group (96.98%) ( χ2=63.950, P<0.001). The highest positive rate in 0-<1 year group was found in tomato (56.36%), and it was eggs (85.29%, 88.94%, 85.50%) in all the other 3 groups. The positive rates of corn and beef decreased with age ( χ2=44.098, 20.106, P<0.001), while those of cod and mushroom increased with age ( χ2=32.315, 40.338, P<0.001). The positive rate of wheat (57.13%, χ2=42.273), tomato (57.01%, χ2=209.862), soybean (24.99%, χ2=92.580), crab (6.81%, χ2=33.201), shrimp (6.25%, χ2=47.863) were all the highest in 1-<3 years group among the 4 groups (all P<0.001), and the positive rate of chicken was the highest in 3-<6 years group (7.88%, χ2=29.875; P<0.001). Conclusions:Children in Qingdao have a high level of food intolerance, and the highest positive rate is for eggs. Milk, crab and shrimp should be focused on for boys, while tomatoes, cod and beef shoud be paid more attention to for girls. Children of different ages have different kinds of food intolerance, and their diets should be adjusted reasonably according to the characteristics.

Acute myeloid leukemia (AML) is a malignant clonal proliferative disease of immature myeloid cells in hematopoietic system. Although chemotherapy and hematopoietic stem cell transplantation could improve the survival of AML patients, their prognoses are still poor. Previous studies have shown that the abnormal regulation of bone marrow microenvironment (BMM) on leukemia stem cells is one of the important factors that make AML difficult to completely cure and easy to relapse. Studies on AML molecular biology and BMM are increasing. In-depth investigation on the changes of acute leukemia microenvironment and targeted intervention of abnormal BMM are expected to make new breakthroughs in the targeted therapy of AML and to improve the prognosis of patients. This review reviews the progress of BMM and targeted microenvironment therapy in AML.

Objective:To investigate the thermal injury effects on human HaCaT cells under simulated microgravity environment.Methods:The human HaCaT cells were collected and divided into simulated microgravity thermal injury (SMGTI) group, normal gravity thermal injury (NGTI) group, and normal gravity false injury (NGFI) group according to the random number table. Cells in NGTI and NGFI groups were cultured routinely in culture bottle, and cells in SMGTI group were cultured in the rotary cell culture system to simulate microgravity environment. Cells in SMGTI and NGTI groups were bathed in hot water of 45 ℃ for 10 minutes to make thermal injury model, and cells in NGFI group were bathed in warm water of 37 ℃ for 10 minutes to simulate thermal injury. At post injury hour (PIH) 12, cell morphology of 3 groups was observed under inverted phase contrast electron microscope. At PIH 2, 6, and 12, single cell suspension in the 3 groups was collected to detect the cell cycle by flow cytometer and the mRNA expressions of heat shock protein 70 (HSP70), matrix metalloproteinase 9 (MMP-9), and cysteine-aspartic protease 3 (caspase-3) by real time fluorescence quantitative reverse transcription polymerase chain reaction, and the experiments were repeated for 3 times. At PIH 2, 6, and 12, cell culture supernatant in the 3 groups was collected to detect the concentration of heparin-binding epidermal growth factor (HB-EGF) by enzyme linked immunosorbent assay method, the experiment was repeated for 3 times. The sample in each group and each time point was 3. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, least significant difference test, Kruskal-Wallis H test, and Mann-Whitney U test. Results:(1) At PIH 12, cells in NGFI group showed regular shape and regular arrangement, with no cell debris. The cell shape in NGTI group was generally regular, with fewer cell debris and closer arrangement than that in NGFI group. The cells in SMGTI group showed more irregular shapes, different sizes, and dead cell debris. (2) The percentage of G1 phase cells in NGTI group was significantly higher than that in NGFI group and SMGTI group at PIH 2, respectively ( P<0.05), and the percentage of G1 phase cells in NGTI group was significantly lower than that in NGFI group and SMGTI group at PIH 6 and 12, respectively ( P<0.05). The percentage of G2/M phase cells in NGTI group was significantly lower than that in SMGTI group at PIH 2 ( P<0.05), and the percentage of G2/M phase cells in NGTI group was significantly higher than that in NGFI group and SMGTI group at PIH 6 and 12, respectively ( P<0.05). The percentage of S phase cells in NGTI group at PIH 2, 6, and 12 was significantly higher than that in SMGTI group ( P<0.05), and the percentage of S phase cells in NGTI group at PIH 2 and 6 was significantly lower than that in NGFI group ( P<0.05). (3) The HSP70 mRNA expressions of cells in NGTI group were 2.50±0.30 and 3.99±0.35 at PIH 2 and 6, which were significantly higher than 1.14±0.15 and 0.82±0.27 in NGFI group ( P<0.05), and 1.17±0.53 and 1.65±0.59 in SMGTI group ( P<0.05). The MMP-9 mRNA expression of cells in SMGTI group was significantly higher than that in NGTI group at PIH 2, 6, and 12, respectively ( Z=-2.319, -2.882, -2.908, P<0.05). At each time point after injury, the mRNA expression of caspase-3 of cells in NGTI group was similar to that in NGFI group and SMGTI group, respectively ( P>0.05). (4) The concentration of HB-EGF in cell culture supernatant of NGTI group was significantly lower than that in NGFI group at PIH 2, 6 and 12 ( P<0.05), and the concentration of HB-EGF in cell culture supernatant of SMGTI group was significantly higher than that in NGTI group at PIH 2 and 6 ( P<0.05). Conclusions:The proliferation and secretion functions and expression of wound repair related protein of human HaCaT cells inflicted with thermal injury in simulated microgravity environment showed complex and diversified changes, which provide theoretical basis for further research on damage repair under weightlessness.

Objective: To evaluate the feasibility of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES). Methods: The CT26 colorectal cancer xenograft model of BALB/c mice were established and divided into rhES group and control group, with 20 mice in each group. The mice of rhES group were intravenously injected with rhES 5 mg·kg^-1·d^-1 once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9% saline. 5 mice of rhES group and control group were randomly selected to perform IVIM-DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM-DWI were recorded, including true diffusion coefficient(D), pseudo-diffusion coefficient (D^*) and perfusion fraction (f). Meanwhile, microvessel density (MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results: The tumor volumes of control group and rhES group before treatment were (154.42±24.65) mm³ and (174.24±28.27)mm^3, respectively, without statistically significant difference (P=0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group (all P<0.05). There were no statistical significances of D value between the rhES group and control group before and after treatment (all P>0.05). The D^* values of the rhES group were (10.940±2.834)×10^-3mm²/s and (12.940±2.801)×10^-3mm²/s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10^-3mm²/s and (7.898±1.603)×10^-3mm²/s of control group (P<0.05). Moreover, compared with control group, the D^* value of rhES group was significantly lower in day 12 (6.848±1.460)×10^-3mm²/s vs (9.950±2.596)×10^-3mm²/s, (P<0.05). The f value of rhES group in day 8 was (0.226±0.021)%, significantly higher than (0.178±0.016)% of control group (P<0.01). The MVD of rhES group was significantly lower than that of control group (P<0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment (all P<0.05). In addition, we found D^* value of IVIM-DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.354, r=0.555, r=0.559, all P<0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.391, r=0.538, r=0.315, all P<0.05). Conclusions IVIM-DWI MRI can effectively evaluate the vascular normalization in rhES-induced CT26 colorectal tumor.The parameters D^* and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.

Objective To evaluate the feasibility of intravoxel incoherent motion diffusion?weighted magnetic resonance imaging (IVIM?DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES).Methods The CT26 colorectal cancer xenograft model of BALB／c mice were established and divided into rhES group and control group, with 20 mice in each group.The mice of rhES group were intravenously injected with rhES 5 mg·kg－1·d－1 once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9%saline. 5 mice of rhES group and control group were randomly selected to perform IVIM?DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM?DWI were recorded, including true diffusion coefficient( D), pseudo?diffusion coefficient ( D?) and perfusion fraction ( f).Meanwhile, microvessel density ( MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results The tumor volumes of control group and rhES group before treatment were (154.42 ± 24.65) mm3 and (174.24 ± 28.27) mm3, respectively, without statistically significant difference ( P＝0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group ( all P＜0.05).There were no statistical significances of D value between the rhES group and control group before and after treatment ( all P＞0.05).The D? values of the rhES group were (10.940±2.834)×10－3mm2／s and (12.940±2.801)×10－3 mm2／s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10－3mm2／s and (7.898±1.603)×10－3mm2／s of control group (P＜0.05). Moreover, compared with control group, the D?value of rhES group was significantly lower in day 12 (6.848±1.460)×10－3mm2／s vs (9.950±2.596)×10－3 mm2／s, (P＜0.05). The f value of rhES group in day 8 was (0.226± 0.021)%, significantly higher than (0.178±0.016)% of control group (P＜0.01). The MVD of rhES group was significantly lower than that of control group (P＜0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment ( all P＜0.05).In addition, we found D?value of IVIM?DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.354, r＝0.555, r＝0.559, all P＜0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.391, r＝0.538, r＝0.315, all P＜0.05). Conclusions IVIM?DWI MRI can effectively evaluate the vascular normalization in rhES?induced CT26 colorectal tumor.The parameters D? and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.[Subject words] Colorectal neoplasms; Intravoxel incoherent motion; Diffusion magnetic resonance imaging; Vascular normalization; Recombinant human endostatin; Angiogenesis