Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope / 中国中药杂志

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.

METTL14 is a chromatin regulator independent of its RNA N6-methyladenosine methyltransferase activity

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.

The rules of acupoint selection of acupuncture and moxibustion for scrofula in ancient times / 中国针灸

Based on data mining technology, the rules of acupoint selection of acupuncture-moxibustion for scrofula in ancient times were analyzed. The relevant articles of acupuncture and moxibustion for scrofula were searched in the Chinese Medical Code, and the original article, acupoint name, acupoint characteristic, and acupoint meridian tropism, etc. were screened and extracted. The Microsoft Excel 2019 was used to establish a acupoint prescription database, and the frequency of acupoints as well as their meridian tropism and characteristics were analyzed. The SPSS21.0 was applied to perform cluster analysis of acupuncture prescriptions; the SPSS Modeler 18.0 was used to perform the association rules analysis of the neck and the chest-armpit acupoints, respectively. As a result, 314 acupuncture prescriptions were extracted, including 236 single-acupoint prescriptions and 78 multiple-acupoints prescriptions (53 for neck and 25 for chest-armpit). A total of 54 acupoints were involved, with a total frequency of 530. The top 3 commonly-used acupoints were Tianjing (TE 10), Zulinqi (GB 41) and Taichong (LR 3); the most commonly-used meridians were hand shaoyang meridian, foot shaoyang meridian, hand yangming meridian and foot yangming meridian; the most commonly-used special acupoints were he-sea points and shu-stream points. The cluster analysis obtained 6 clusters, and the association rule analysis obtained that the core prescriptions of the neck were Quchi (LI 11), Jianyu (LI 15), Tianjing (TE 10) and Jianjing (GB 21), while the core prescriptions of the chest-armpit were Daling (PC 7), Yanglingquan (GB 34), Danzhong (CV 17), Jianjing (GB 21), Waiguan (TE 5), Zhigou (TE 6), Yuanye (GB 22) and Zhangmen (LR 13). The core prescriptions obtained from association rule analysis by difference areas were basically consistent with those by cluster analysis of total prescriptions.

PK/PD model of Chuanxiong gel plaster in treatment of rheumatoid arthritis / 中国中药杂志

In this experiment, the PK/PD fitting model of Chuanxiong(Chuanxiong Rhizoma) in the treatment of rheumatoid arthritis was established in the form of acupoint combined with external application gel paste. Firstly, the rheumatoid arthritis model was induced by ovalbumin, and the articular fluid of rabbits was extracted by microdialysis. The pharmacokinetic process of Chuanxiong in rabbit articular fluid was analyzed by UPLC-MS/MS, and the pharmacokinetic model was established. The pharmacodynamic effects of Chuanxiong on inflammatory factors IL-1β, TNF-α, and IL-6 were analyzed by enzyme-linked immunosorbent assay(ELISA). The pharmacodynamic model was established, and the PK/PD model was obtained by fitting the data of pharmacokinetics and pharmacodynamics. The results of pharmacokinetics showed that the concentration of ligustrolide A in the articular cavity by drug administration on classical acupoint Zusanli(ST 36) was higher than that by Yanglingquan(GB 34), which reflected the advantage of typical acupoint, while ligustrazine concentration was higher after administration through Yanglingquan than through Zusanli, which was different from the traditional acupoint theory. The results of pharmacodynamics showed that the drug had lag effect. The PK/PD model was constructed by fitting the data. When IL-1β was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=115.28C_e/(3 316.72+C_e), E=108.73C_e/(2 993.47+C_e), and E=101.34C_e/(3 028.51+C_e). When TNF-α was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=68.31C_e/(3 285.16+C_e), E=59.27C_e/(2 919.86+C_e), and E=53.61C_e/(2 862.87+C_e). When IL-6 was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=59.92C_e/(3 461.17+C_e), E=58.34C_e/(2 723.51+C_e), and E=49.17C_e/(2 862.76+C_e). The parameters showed that there were significant differences in E_(max), EC_(e50) and k_(eo). The analysis of data found that the PK/PD fitting effect of Zusanli, a typical acupoint, was the best, which proved that it was still the best site for drug administration. To sum up, it shows that there may be bidirectional selectivity between drugs and acupoints.

LC-MS fingerprint and multi-indicator components analysis of classical formula Gualou Xiebai Banxia Decoction / 中国中药杂志

This study developed an optimal pre-processing technique for the reference substance of the classic formula Gualou Xiebai Banxia Decoction(GXBD) and established a comprehensive quality control method for GXBD reference substance to provide a reference for its overall quality evaluation. The authors prepared 15 batches of GXBD samples and innovatively used the extracted ion chromatogram under the base peak chromatogram mode to establish a liquid chromatography-mass spectrometry(LC-MS) fingerprint, identify characteristic peaks, and perform quantitative analysis of indicator components. The yield of the 15 batches of GXBD samples ranged from 50.28% to 76.20%. In the positive ion mode, 12 common characteristic peaks were detected in the LC-MS fingerprint, and the structures of five common peaks were identified by comparison with reference standards. The similarity between the fingerprint profiles of different batches of samples and the reference fingerprint profile ranged from 0.920 to 0.984. Finally, liquid chromatography-triple quadrupole mass spectrometry(LC-QQQ/MS) in multiple reaction monitoring(MRM) mode was used to determine the content of eight indicator components in GXBD, including loliolide, chrysoeriol, rutin, cucurbitacin D, macrostemonoside Ⅰ, 25S-timosaponin B Ⅱ, 25R-timosaponin B Ⅱ, and peptide proline-tryptophan-valine-proline-glycine(PWVPG). The method established in this study can reduce matrix interference in the compound, and it has good accuracy, stability, and practical value. It effectively reflects the quality attributes of GXBD samples and can be used for the comprehensive quality control of GXBD.

Mechanism of total flavonoids of Ziziphora clinopodioides in improving atherosclerosis by regulating PI3K/Akt/mTOR pathway / 中国中药杂志

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.

Therapeutic Effect of Mesenchymal Stem Cells Overexpressing Interleukin-10 on Inflammatory Bowel Disease / 中国生物化学与分子生物学报

Inflammatory bowel disease (IBD) is an, intractable inflammatory autoimmune disease characterized by T-cell infiltration to the colon. Mesenchymal stem cells (MSCs), owing to their immunosuppressive capabilities, have the potential to rescue IBD. But the therapeutic effectiveness of MSCs is sometime thwarted by their variable immunomodulatory ability in vivo. In the present study, we produced engineered MSCs that secrete interleukin10 (IL-10) and evaluated their therapeutic potential in IBD mouse model. The MSCs maintained the phenotype and cell proliferation rate after overexpression of IL-10 by lentivirus (LV) infection. Immune cells and MSCs in vitro co-culture systems exhibited that relative to unmodified MSCs, immune cells co-cultured with IL-10-overexpressing MSCs had significantly lower numbers of T helper 1 cells (Th1) and T helper 17 cells (Th17) (P0.05). Overall, LV induced MSCs overexpressing IL-10 might be a promising alternative therapeutic option for the treatment of IBD.

The effect of maternal internal and uterine environmental changes during pregnancy on asthma in offspring / 中华实用儿科临床杂志

Childhood asthma is one of the most-common chronic respiratory diseases in the world.The incidence of asthma is increasing, and therefore, controlling the occurrence and development of asthma has been the current research hotspot.A growing number of evidences have shown that the changes of maternal internal and uterine environment during pregnancy are related to the occurrence of asthma in offspring.The influence of maternal mental, disease, nutrition, environment, drug exposure on the occurrence of asthma in offspring were summarized, providing a new idea for understanding the mechanism, prevention and treatment of children asthma.

Effect of maternal exposure to lipopolysaccharide during pregnancy on allergic asthma in offspring in mice / 中华儿科杂志

Objective: To investigate the effect of maternal exposure to lipopolysaccharide during pregnancy on allergic asthma in offspring in mice. Methods: Animal experimental research was carried out from June 2019 to June 2021.Pregnant C57BL/6J mice were randomly divided into 2 groups by intraperitoneal injection with 7 μg/kg lipopolysaccharide (LPS) or phosphate buffered saline (PBS) at day 15.5 of gestation. After birth, 6 offspring were randomly chosen from each group at the age of 4 weeks, and stimulated with house dust mites (HDM) or PBS, further divided into 4 groups, such as LPS+PBS group, LPS+HDM group, PBS+PBS group, PBS+HDM group, with 3 mice in each group. The cough and wheezing were observed, the histological changes in lung tissue were examined after HE staining, and the expression of inflammatory factors including interleukin (IL)-4, IL-6, IL-17A, IL-23, interferon (IFN)-α and IFN-β in the lung tissue were detected by high-throughput liquid protein chip detection. T test or rank sum test was used for the comparison among these groups. Results: The asthma-like airway inflammation was more obvious in PBS+HDM group after stimulated by HDM than that in PBS+PBS group, nevertheless, this manifestation in LPS+HDM group was milder than that in PBS+HDM group. HE staining showed that inflammatory cell aggregation in the lung tissue in PBS+HDM group was significantly higher than that in PBS+PBS group (4.0 (3.5, 4.0) vs. 0 (0, 0.5), Z=2.02, P=0.043), while it was much lower in LPS+HDM group compared to PBS+HDM group (1.0 (0.5, 1.5) vs. 4.0 (3.5, 4.0), Z=1.99, P=0.046). High-throughput liquid protein chip detection of lung tissue showed that IL-6, IL-23 and IFN-β levels were significantly higher in PBS+HDM group when compared to those in PBS+PBS group ((114±3) vs. (94±4) ng/L, (210±4) vs. (173±7) ng/L, (113±2) vs. (94±4) ng/L, t=4.37, 4.84, 3.96, all P<0.05), while the levels of IL-6, IL-23, IFN-α, IFN-β in LPS+HDM group were significantly lower than those in PBS+HDM group ((87±5) vs. (114±3) ng/L, (171±7) vs. (210±4) ng/L, (16.1±0.6) vs. (20.9±0.3) ng/L, (95±1) vs. (113±2) ng/L, t=5.07, 5.07, 7.28, 7.47, all P<0.05). Conclusions: Prenatal low dose LPS exposure can reduce offspring's airway inflammatory reactions and prevent the development of allergic disease. Maternal infection during pregnancy may affect the occurrence and development of allergic asthma in offspring.

Preliminary exploration of the metabolic profile and metabolic pathways in newly diagnosed multiple myeloma / 中华肿瘤杂志

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.

The Expression of WTAP Gene in Acute Myeloid Leukemia and Its Clinical Significance / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of WTAP gene in acute myeloid leukemia (AML) and its clinical significance.@*METHODS@#74 acute myeloid leukemia patients with non-M3 type and 19 normal donors were selected, and real-time quantitative polymerase chain reaction was used to detect the mRNA expression level of WTAP gene in their bone marrow cells. The relationship between the mRNA expression level of WTAP gene and the clinical characteristics was analyzed.@*RESULTS@#The relative mRNA expression of WTAP gene in the non-M3 AML group was significantly higher than that in the healthy control group, and the difference showed statistically significant (P0.05) according to the classification of FAB. The mRNA expression level of WTAP gene in FLT3-ITD mutated AML patients was higher than that in FLT3-ITD unmutated group (P=0.016), and the mRNA expression level of WTAP gene in AML patients with CEBPα mutation was lower than that in CEBPα unmutated group (P=0.016). The expression level of WTAP mRNA was positively correlated with WT1 expression (r=0.6866, P0.05). The expression level of WTAP mRNA showed no obvious effect on the complete remission of patients after first treatment. The different expression level of WTAP gene at initial diagnosis showed also no effect on the overall survival time of patients.@*CONCLUSION@#The expression level of WTAP gene is increasing in new diagnosed non-M3 acute myeloid leukemia. There is a positive correlation between the expression level of WTAP gene and the expression level of WT1 fusion gene. WTAP mRNA always shows higher expression in patients with FLT3-ITD mutation than that in patients without FLT3-ITD mutation, and shows lower expression in patients with CEBPα mutation than that in unmutated group.

Endoscopic ultrasonography improving the operation effect for detecting precisely the origin and histology characteristics of esophageal leiomyoma / 解剖学报

Objective To investigate whether assessment of the tumor origin and histological features through endoscopic ultrasonography could improve the operative efficacy of endoscopic resection of esophageal leiomyoma. Methods The clinical data of patients with esophageal submucosal tumor who were treated in our department and diagnosed as leiomyoma pathologically from January 2016 to June 2020 was retrospectively analyzed. A total of 58 patients with esophageal leiomyoma underwent endoscopic resection following evaluation of endoscopic ultrasonography. The en bloc resection rate, operation time, hospitalization day, and complications were evaluated. Results Preoperative endoscopic ultrasonography showed that leiomyoma originated from muscularis mucosa in 39 cases and muscularis propria in 19 cases. The mean tumor size was 1.50 (0.2-6.5) cm, and 20 cases underwent endoscopic mucosal resection (EMR), 32 cases underwent endoscopic submucosal excavation (ESE), and 6 cases underwent submucosal tunneling endoscopic resection (STER). The overall en bloc rate was 96.6%. The mean operation time was 38.29 (15-100) min. The postoperative complication rate was 15.5% (9/58), and all were recovered after conservative treatment. Among the 39 cases originated from the muscularis mucosa, 20 cases underwent EMR and 19 cases underwent ESE. There were no significant differences in tumor size and complications between the two groups, but the operative time and the length of postoperative hospitalization in the EMR group were significantly shorter (P < 0.05). Among the 19 patients originated from the muscularis propria, 13 cases underwent ESE and 6 cases underwent STER. There were no significant differences in tumor size, operative time, the length of postoperative hospitalization and complications between the two groups. Conclusion Preoperastive endoscopic ultrasonography could precisely detect the origin and histology characteristics of esophageal leiomyoma and improves the operation effect.

Research on culture perception of hospital staff based on text mining / 中华医院管理杂志

Objective:To analyze original medical humanities articles written by staff of the hospital and extract key elements of hospital culture for staff perception, for recommendations on homogenous development of multiple campuses of the hospital.Methods:Original medical humanities articles written by staff of the hospital were collected from the WeChat accounts, websites and printouts of a tertiary hospital in Beijing from January 2013 to December 2019, with text mining made by Python3.7; Bert and Tencent open-source 8 million Chinese word dataset were used as entity identification training dataset; K-Means cluster analysis was used to analyze and select cluster results of higher degree of fitting; TextRank was used to screen keywords of each clustered category. Significance of each category was summarized in the end based on keywords following the screening.Results:Among the 341 articles collected, high frequency words were work, hospital, patient, sick person, development, medicine, medical treatment, doctor, outpatient service and clinic. The words fell into ten categories: process recall, work attribute, work responsibility, diagnosis and treatment behavior, growth experience, team cooperation, professionalism, management innovation, doctor-patient communication and others.Conclusions:Research on hospital staff culture perception is conducive to identifying the cultural content of the hospital. In the homogenous development of multiple campuses of the hospital, it is imperative to nurture the staff′s sense of identify and belonging to the hospital, enhance their sense of gain and happiness, and strengthen the scientific management system centering on patients.

Application of FLASH radiotherapy with an ultra-high dose rate in malignant tumor / 中华放射医学与防护杂志

As a method for local treatment, radiotherapy plays a key role in the management of tumors. In the past few decades, great progress has been made in radiotherapy technology, with improvements in conformity, homogeneity, and radiotherapy efficiency, and the results are encouraging. Nevertheless, the maximum tolerated dose of normal tissue has limited the further increase in radiotherapy dose in the tumor area. If radiation-induced toxicities can be reduced, a higher radiotherapy dose can be delivered to tumor tissue, so as to achieve a better treatment response. In recent years, the unique FLASH effect of ultra-high-dose-rate radiotherapy (FLASH-RT) is capable of maintaining a consistent tumor response whilst reducing radiation-induced toxicities in normal tissue, and therefore, FLASH-RT has become a research hotspot in the field of radiotherapy across the world. At present, some scholars tend to explain the FLASH effect using the theory of acute oxygen depletion, but the protective effect of FLASH-RT on normal tissue remains to be clarified. In addition, preliminary clinical studies have been conducted for FLASH-RT, and the results are promising. Based on existing evidence, this article elaborates on the research advances in FLASH-RT in the treatment of malignant tumor, so as to provide a reference for the translation and application of this new technique.

Activating effect of extracellular histones on heparinase in chlorine-induced acute lung injury / 中国职业医学

OBJECTIVE: To investigate the induction and activation of heparinase by extracellular histones in acute respiratory distress syndrome(ARDS) induced by chlorine in mice.METHODS: The specific pathogen free adult male C57 BL/6 mice were randomly divided into control group, chlorine injured group, histone injured group, anti-histone antibody group and heparinase inhibitor group, with six mice in each group.The mice in the control group and histone injured group were exposed to clean air, and the mice in the other three groups were exposed to chlorine gas at a dose of 580.0 mg/m~3 for 30 minutes by systemic dynamic inhalation.Mice in the histone injured group were injected with 50 mg/kg body weight calf thymus histone by tail vein.One hour before exposure, mice in the anti-histone antibody group were pretreated with 20 mg/kg body weight anti-histone H4 antibody by tail vein injection, and mice in the heparinase inhibitor group were injected with 2 mg/kg body weight OGT2115(heparinase inhibitor). The other three groups were given equal volume of 0.9% sodium chloride solution by tail vein injection. After 24 hours of exposure, arterial blood was collected for blood gas analysis and the lung tissue was collected for histopathological examination. The protein level of heparinase in lung tissue were detected using enzyme-linked immunosorbent assay, and the activity of heparinase were detected by measuring the product of heparan degradation. The protein expression of pro-heparinase and active heparinase were detected by Western blotting.RESULTS: The dyspnea developed of mice in the chlorine injured group and histone injured group, diffuse inflammation occurred in lung tissue, the oxygenation index in arterial blood decreased(all P<0.05), and the protein level and activity of heparinase in lung tissue, as well as the relative expression of pro-heparinase and active heparinase were increased compared with the control group(all P<0.05). The dyspnea, hypoxemia and acute lung injury of mice in the anti-histone antibody group were alleviated, and the protein level of heparinase in lung tissue, as well as the relative expression levels of pro-heparinase and active heparinase were decreased(all P<0.05), compared with chlorine injury group and histone injury group.The dyspnea, hypoxemia and acute lung injury were alleviated in the heparinase inhibitor group, and the activity of heparinase and the relative expression of pro-heparinase in the lung tissue were decreased compared with the chlorine injury group(all P<0.05). CONCLUSION: During the occurrence and development of chlorine-induced ARDS in mice, extracellular histones aggravate lung injury by inducing the expression and activation of heparinase. Acute lung injury can be alleviated by inhibiting the expression and activation of heparinase.

Physical activity and influencing factors of preschool children in Nanchang / 中国学校卫生

Objective@#To understand the present situation of physical activity and its influencing factors, and to provide a reference for improving the level of physical activity and making the intervention measures.@*Methods@#The method of random stratification was used to select 4 740 pre school children aged 3-6 from 17 kindergartens in 12 counties and districts of Nanchang City, The questionnaire of physical activities of young children and the questionnaire of parents of physical activities of young children were applied to conduct a survey.@*Results@#Compared with weekday PA and MVPA, preschool children’s weekends decreased, SB increased. The differences in PA, MVPA and SB on weekdays and weekends were statistically significant( P <0.01). The proportion of PA and MVPA reaching the recommended amount during the working day of preschool children were 44.9%-59.2%, 45.4%- 61.7%.The proportion reaching the recommended amount of PA and MVPA on weekends were 24.7%-27.8%, 24.5%-29.9%, and the proportion reaching the recommended amount on weekdays was higher than that on weekends.@*Conclusion@#There is still gap between actual amount of physical activity and the recommended amount. There are different modes of activity on weekdays and weekends, and weekends are the least active periods. Parents and teachers should pay enough attention to the establishment of "social campus family" model to improve the lack of physical activity of preschool children.

Relationship between sex hormones, lipids and visceral fat area in postmenopausal women with type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective@#To study the characteristics and correlation of sex hormone levels, blood lipids, and visceral fat area in postmenopausal women with T2DM.@*Methods@#A total of 258 cases of postmenopausal T2DM were recruited, including 46 cases of menopause for 1-5 years (group A), 49 cases of menopause for 6-10 years (group B), and 163 cases with menopause more than 10 years (C group). The related clinical information of patients was recorded.@*Results@#Compared among the three groups, there were statistical differences in total cholesterol(F=3.287, P=0.039) and testosterone(Chi-Square=8.324, P=0.016). No significant difference in FSH, LH, estradiol, low density lipoprotein, triglyceride, visceral fat area and subcutaneous fat area(P>0.05) among three groups was observed. After correction of confounding factors, FSH was independently positively related with for total cholesterol and low-density lipoprotein respectively (P=0.006, P=0.009). LH was independently positively related with total cholesterol(P=0.003) and low-density lipoprotein respectively(P=0.003). Estradiol was independently negatively related with total cholesterol(P=0.014) and low-density lipoprotein(P=0.020), respectively. Testosterone was correlated independently with visceral fat area(P=0.008); FSH, LH, estradiol, and testosterone were not correlated to triglyceride and subcutaneous fat area(P>0.05).@*Conclusion@#(1)In T2DM patients with the increase of postmenopausal time, the total cholesterol increases first, and then decreases; testosterone decreases first, and then increases. (2)In T2DM patients, the total cholesterol and low-density lipoprotein increase with the increase of FSH and LH, increase with the decrease of estradiol, and the area of visceral fat increases with the testosterone together.

Effects of long-term studying abroad on scientific research ability of clinical doctors / 中华医院管理杂志

Objective To analyze whether studying abroad has any influence on clinicians′scientific research ability, and study the rationality of the indicators reflecting the scientific research ability. Methods A total of 36 clinicians who studied abroad more than 3 months between 2008 and 2010 were selected as the abroad group, and the control group of 36 clinicians was selected from the clinician information database of the hospital by the method of Propensity Score Match.A comparison and analysis were made regarding the number of papers(SCI), grants and scientific and technological achievements between the two groups. Meanwhile, covariance analysis was used to compare the difference in the number of scientific research achievements between the two groups.Logistic regression analysis was used to compare the changes in scientific research achievements of clinicians before and after their abroad study. Results The number of articles( SCI) published and grants obtained in the 3 years after going abroad was significantly higher than that of the control group, and the number of grants obtained in the 4-6 years after going abroad was also significantly higher than that in the control group.The number of papers(SCI)published in the three years after going abroad was more than that in the 3 years before going abroad.The number of grants obtained in the 4-6 years after going abroad was more than that in the 3 years before going abroad.These differences were statistically significant. Conclusions Studying abroad has a beneficial effect on the improvement of clinicians′ scientific research ability. It is reasonable and practical to take the number of SCI articles published as the indicator of short-term changes and the number of funds obtained as the indicator of long-term changes in scientific research ability.

Effects of Exendin-4 on cognitive function and Nrf2 signaling pathway in rats with traumatic brain injury / 中华行为医学与脑科学杂志

Objective To explore the effect of Exendin-4 on dementia after traumatic brain injury (TBI) in rats and its related mechanism.Methods Thirty SD rats were randomly divided into sham group (n=10),TBI group(n=10) and Exendin-4 group(n=10).Cortical impact injury was used to construct the TBI model.Morris water maze test was used to test the memory function of rats one month after TBI.The beta-amyloid protein (Aβ1-42) and nuclear factor erythroid-2-related factor 2 (Nrf2) were detected by Western blot.Results One month after TBI compared with the sham group,the escape latency (EL) ((35.31 ± 13.23)s vs (8.79±9.71)s) was prolonged and the target quadrant stay time ((17.78±4.68)s vs (26.35± 5.83)s) was shortened,the number of crossing platforms ((1.40±1.75) vs (3.50±1.45)) decreased,the relative content of Aβ1-42 in hippocampus ((1.0140±0.0328) vs (0.4355±0.0152)) increased the relative content of tau protein ((0.8039±0.0251) vs (0.5170±0.0185)) increased,and Nrf2 expression levels ((0.3851±0.0188) vs (0.4901±± 0.0140)) decreased significantly,and the differences were statistically significant (t=5.110,3.625,4.068,16.010,9.208,4.474,all P＜0.01);Compared with TBI group,EL ((23.74±10.95) vs (35.31±13.23)) shortened,target quadrant dwell time ((24.28±5.37) vs (17.78±± 4.68)) shortened,the number of crossing platforms ((3.30±1.88) vs (1.40±1.75)) decreased,and the relative content of Aβ1-42 in hippocampus ((0.8370±0.0188) vs (1.0140±0.0328)) significantly decreased,the relative content of tau protein ((0.6693±0.0166) vs (0.8039±0.0251)) significantly decreased,and the expression level of Nrf2 ((0.4738 ± 0.0166) vs (0.3851 ± 0.0188)) significantly increased,and the differences were statistically significance (t=2.052,2.866,5.196,4.693,3.480,3.538,all P＜0.01).Conclusion Exendin-4 can significantly improve the learning and memory function of TBI rats,increase the expression of Nrf2,decrease the content of Aβ1-42 and tau in hippocampus,and improve the prognosis of neurological function of TBI rats.

Therapeutic effects on rheumatoid arthritis treated with -deep needling and bloodletting techniques / 中国针灸

OBJECTIVE@#To observe the difference in the therapeutic effects on rheumatoid arthritis (RA) between the combined -deep needling and bloodletting technique and the regular needling technique.@*METHODS@#A total of 70 patients were randomized into an observation group (35 cases) and a control group (35 cases, 4 cases dropped-out). Dazhui (GV 14), Shenzhu (GV 12), Zhiyang (GV 9), Jinsuo (GV 8), Ganshu (BL 18), Shenshu (BL 23), Zhibian (BL 54), Weizhong (BL 40), Taixi (KI 3) and Tianzong (SI 11), etc. were selected in the two groups. Additionally, in the observation group the -deep needling technique was adopted at Tianzong (SI 11) and Zhibian (BL 54), the bloodletting technique at the local swollen area and the even-needling technique at the rest acupoints. In the control group, the even-needling technique was applied to all of the acupoints. Acupuncture treatment was given once every two days, 3 times a week and for 12 weeks totally. The numbers of tender points at the knee joint, the numbers of swollen sites at the knee joint, the visual analogue scale (VAS) score and the American health assessment questionnaire (HAQ) score were observed in the two groups before and after treatment, as well as the changes in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The American College of Rheumatology (ACR) criteria was adopted to evaluate the therapeutic effects of the two groups.@*RESULTS@#After treatment, the numbers of tender points, the numbers of swollen sites, VAS score and HAQ score were all improved as compared with those before treatment in the two groups (all 0.05). The standard-reaching rates of ACR 20 and ACR 50 in the observation group were 94.3% (33/35) and 31.4% (11/35) respectively, which were better than 67.7% (21/31) and 6.5% (2/31) in the control group (<0.01, <0.05).@*CONCLUSION@#The acupuncture with the -deep and bloodletting techniques and the acupuncture with regular needling technique are all effective on RA. The therapeutic effects of the acupuncture treatment with the -deep and bloodletting techniques are better than that with regular needling technique.