Research Progress of the Effect of Microgravity on Cellular Senescence / 医用生物力学

Microgravity is a typical feature of the space. A large number of space flights and foundation simulation experiments have shown that cells show typical biological characteristics of aging, such as reduced cell proliferation and cell cycle arrest under microgravity or simulated microgravity. However, the molecular mechanism by which microgravity or simulated microgravity affects cellular senescence is not well understood. Understanding the mechanism controlling cellular senescence induced by microgravity environment is helpful for exploring anti-aging strategies and targeted interventions in space. In recent years, domestic and foreign scholars have carried out a number of researches and explorations on the effect of microgravity and simulated microgravity on cellular senescence as well as the related mechanisms. In this review, the latest research progress of this filed was summarized.

Evaluation of subjective scale in allergen nasal provocation test / 临床耳鼻咽喉头颈外科杂志

Objective:To compare the clinical value of visual analogue scale （VAS）, Lebel scale and total nasal symptom scores （TNSS） in evaluating nasal allergen provocation test （NAPT）. Methods:A total of 151 patients suspected of allergic rhinitis admitted to the Department of Otolaryngology-Head and Neck Surgery of our hospital from April 2020 to September 2020 were included, of which 76 were positive for house dust mites and 75 were negative for allergens. Nasal airway resistance（NAR） was measured by active anterior nasal manometry. Nasal symptoms were evaluated by VAS, Lebel and TNSS. House dust mite allergen was used for NAPT by spray method. An increase≥40% in NAR was used as the gold standard for objective evaluation of NAPT. ROC curves of VAS, Lebel and TNSS were drawn to compare the evaluation effectiveness of different subjective evaluation methods, and the optimal critical point of each ROC curve was obtained. Results:With NAR increased by ≥40% as the gold standard, the area under ROC curve of VAS was 0.884, and the sensitivity and specificity were 97.75% and 80.65%, respectively. The area under ROC curve of Lebel was 0.773, and the sensitivity and specificity were 68.54% and 75.81%, respectively. The area under ROC curve of TNSS was 0.792, and the sensitivity and specificity were 68.54% and 79.03%, respectively. There was no significant difference between Lebel and TNSS（P>0.05）. The VAS differed significantly from Lebel and TNSS（P<0.05）. The Kappa values of VAS, Lebel, TNSS and NAR were 0.803, 0.432 and 0.459, respectively. Conclusion:The VAS, Lebel, TNSS subjective scale and NAR are consistent in evaluating the efficacy of NAPT, with the VAS assessment showing highest consistency with NAR. As objective assessment instruments are not widely used in China, subjective assessment method could be adopted to evaluate the efficacy of NAPT in clinical practice, and VAS scale is recommended as a priority.

Genetic analysis of a Chinese pedigree with 18q21.2-q22.3 duplication and deletion in two offspring respectively resulting from a maternal intrachromosomal insertion / 中华医学遗传学杂志

OBJECTIVE@#To provide prenatal diagnosis, pedigree analysis and genetic counseling for a pregnant woman who had given birth to a child featuring global developmental delay.@*METHODS@#A pregnant woman who underwent prenatal diagnosis at the Affiliated Hospital of Southwest Medical University in August 2021 was selected as the study subject. Peripheral blood samples were collected from the woman, her husband and child, in addition with amniotic fluid sample during mid-pregnancy. Genetic variants were detected by G-banded karyotyping analysis and copy number variation sequencing (CNV-seq). Pathogenicity of the variant was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was traced in the pedigree to assess the recurrence risk.@*RESULTS@#The karyotypes of the pregnant woman, her fetus, and affected child were 46,XX,ins(18)(p11.2q21q22), 46,X?,rec(18)dup(18)(q21q22)ins(18)(p11.2q21q22)mat and 46,XY,rec(18)del(18)(q21q22)ins(18)(p11.2q21q22)mat, respectively. Her husband was found to have a normal karyotype. CNV-seq has revealed a 19.73 Mb duplication at 18q21.2-q22.3 in the fetus and a 19.77 Mb deletion at 18q21.2-q22.3 in her child. The duplication and deletion fragments were identical to the insertional fragment in the pregnant woman. Based on the ACMG guidelines, the duplication and deletion fragments were both predicted to be pathogenic.@*CONCLUSION@#The intrachromosomal insertion of 18q21.2-q22.3 carried by the pregnant woman had probably given rise to the 18q21.2-q22.3 duplication and deletion in the two offspring. Above finding has provided a basis for genetic counseling for this pedigree.

Mechanism of Zhibai Dihuang decotion in treating postmenopausal osteoporosis / 药学学报

In this study, the ovarian surgery (ovariectomy, OVX) was used to establish the osteoporosis mice model of primary menstruation, in order to evaluate the protective effects and mechanisms of Zhibai Dihuang decotion on postmenopausal osteoporosis (PMOP). The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University (number: 20210315-03), in compliance with the Institutional Animal Care Guidelines. C57BL/6 mice were divided into five groups, including Sham group, OVX group, low (32 g·kg-1·day-1) and high dose (64 g·kg-1·day-1) of Zhibai Dihuang decotion groups, positive drug group (alendronate, 9.9 mg·kg-1·q3d). After modeling, mice were given medication intervention for 8 weeks, and then femoral and tibial tissues were taken to detect indicators such as bone microstructure, bone resorption, and oxidative stress. The experimental results showed that after Zhibai Dihuang decotion administration, the bone microstructure damage caused by OVX surgery was alleviated, and the relevant parameters bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular number (Tb. N) and connectivity density (Conn. D) both significantly increased. At the same time, the number of TRAP positive osteoclasts decreased significantly, and the levels of proteins and genes related to osteoclast differentiation decreased, indicating that Zhibai Dihuang decoction could inhibit the increased activity of osteoclast caused by OVX. Afterwards, network pharmacology was used to construct the active compound action target network of Zhibai Dihuang decotion, and it was found that the target genes of its active ingredients were closely related to the oxidative stress pathway. Finally, the detection results of oxidative stress levels in bone tissues showed that after treatment with Zhibai Dihuang decotion, the levels of oxidative stress products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) in bone tissues of mice significantly decreased, while the levels of antioxidant stress substance L-glutathione (GSH) increased. These above results indicated that Zhibai Dihuang decotion can regulate the level of oxidative stress in the body and inhibit osteoclast activity, which played a therapeutic role in PMOP, as well as provided theoretical basis for the prevention and treatment of PMOP with traditional Chinese medicine.

Improving Clinician-Patient Communication Alleviates Stigma in Patients With Functional Dyspepsia Receiving Antidepressant Treatment

Background/Aims@#Antidepressants are effective in patients with functional dyspepsia (FD). However, stigma associated with FD and antidepressants may affect treatment adherence. This study aims to explore possible communication strategies to alleviate stigma and improve adherence in patients with FD. @*Methods@#In this randomized, single-center, and single-blind trial, 160 patients with FD initiating antidepressant treatment were recruited. Different communication strategies were performed when prescribing antidepressants. Participants in Group 1 were told that brain is the “headquarters” of gut, and that antidepressants could act as neuromodulators to relieve symptoms of FD through regulating the functions of gut and brain. Participants in Group 2 were told that antidepressants were empirically effective for FD. Stigma scores, medication-related stigma, treatment compliance, and efficacy were analyzed. @*Results@#After 8-week antidepressant treatment, the proportion of patients with FD with decreased stigma scores in Group 1 was significantly higher than in Group 2 (internalized stigma: 64.10% vs 12.00%; perceived stigma: 55.13% vs 13.33%; P < 0.01). Medication-related stigma was lower in Group 1 than in Group 2 (P < 0.05 for 3 of 4 questions). Concurrently, patients in Group 1 had better treatment compliance (0.71 ± 0.25 vs 0.60 ± 0.25, P < 0.01) and efficacy. In Group 1, participants with decreased post-treatment stigma scores showed better treatment compliance and efficacy than those with non-decreased scores. Decrease in stigma scores positively correlated with treatment compliance. @*Conclusion@#Improving knowledge of patients with FD of the disease and antidepressants via proper communication may be an effective way to alleviate stigma and promote adherence.

Survey on visual acuity and refractive status of preschool children in Xining City, Qinghai Province / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:A total of 1 084 preschool children in 4 kindergartens in Xining City were surveyed on their visual acuity and refraction status to find out abnormal vision and refraction beyond the normal range. METHODS: A cross-sectional survey study. The overall sampling method was used on October 2019, a total of 1 084 preschool children aged 3-6 years were selected from a kindergarten in the east, west, south and north of Xining City. The children were checked for uncorrected distance vision and refractive status was checked by using a refractive screener.RESULTS: The detection rate of abnormal vision in preschool children in Xining City was 12.21%, and the detection rate of abnormal vision increased with the increasing age(χ2lineartrend=94.40, P&#x003C;0.05), and there were differences among different age groups(χ2=293.55, P&#x003C;0.05). Refractive abnormalities accounted for 6.09% of the total number of examinations. With the increasing age, the proportion of compound hyperopic astigmatism decreased(χ2lineartrend=1.79, P&#x003E;0.05).CONCLUSION: The abnormal visual acuity of preschool children in Xining City gradually increases with the increasing age; The refractive state is dominated by astigmatism, among which the proportion of mixed astigmatism and pure myopia astigmatism is the highest, followed by pure hyperopic astigmatism and compound hyperopic astigmatism; With the increase of age, the diopter of compound hyperopic astigmatism gradually decreases, which is in line with the law of children's eye refractive development.

Deletion of CD36 gene ameliorates glucose metabolism abnormality induced by high-fat diet and promotes liver lipid accumulation / 生理学报

This study aimed to investigate the effects and the underlying mechanism of CD36 gene on glucose and lipid metabolism disorder induced by high-fat diet in mice. Wild type (WT) mice and systemic CD36 knockout (CD36

Effect on Treatment of Addition and Subtraction Therapy of Zhuyu Zhixuetang to Chronic Endometritis with Syndrome of Qi Deficiency and Blood Stasis / 中国实验方剂学杂志

Objective:To discuss clinical effect of Zhuyu Zhixuetang to chronic endometritis （CE） with syndrome of Qi deficiency and blood stasis and to study improvement effect to pregnancy outcome. Method:One hundred and forty-four patients were randomly divided into two groups， patients in control group were 72 cases and in observation group were 72 cases. In control group， 66 patients completed the therapy because of 4 falling off or missing visit and 2 eliminated， and in observation group， 65 patients completed the therapy because of 3 falling off or missing visit and 5 eliminated. In two groups. anti-infection treatment was gicen to patients. Patients in control group got Fuke Qianjin Pian， 6 tablets/time， 3 times/day. Patients in observation group got Zhuyu Zhixuetang， 1 dose/day. The treatment was continued for 3 months and the follow up was recorded for 6 months. Before and after treatment， changes of menstrual volume， period and cycle were recorded. And hysteroscopy and color Doppler ultrasound of vagina were made， and endometrial morphology and endometrial receptivity were evaluated ［endometrial thickness， resistance index （RI）， pulsation index （PI） and blood flow index （FI）］ were evaluated， and pathology of endometrial were tested. And scores of syndrome of Qi deficiency and blood stasis were graded， levels of interleukin-1 <italic>β</italic> （IL-1<italic> β</italic>）， IL-6 and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and T-lymphoid subsets （CD3⁺， CD4⁺， CD8⁺） in peripheral blood were measured. Pregnancy and miscarriage were recorded and the safety was evaluated. Result:After treatment， menstrual volume， menstrual period， cycle and complete normal rate of menstruation in observation group were all higher than those in control group （<italic>P</italic><0.05）. Endometrial thickness and FI were more than those in control group （<italic>P</italic><0.01）， RI and PI were lower than RI and PI in control group （<italic>P</italic><0.01）. And compared with control group， levels of IL-1<italic>β</italic>， IL-6， TNF-<italic>α</italic> and CD8⁺were less （<italic>P</italic><0.01）. And levels of CD3⁺， CD4⁺ and CD4⁺/ CD8⁺ were higher than the data in control group （<italic>P</italic><0.01）. During 6 months follow-up， pregnancy rate in observation group was 46.97% （31/66） was higher than 27.69% （18/65） in control group （<italic>χ</italic>²=5.197， <italic>P</italic><0.05）. Total effective rate of endometrial morphology was 96.97% （64/66） higher than 86.15% （56/65） in control group （<italic>χ</italic>²=4.981， <italic>P</italic><0.05）. Total effective rate endometrial pathology was 95.45% （63/66） higher than 84.62% （55/65） in control group （<italic>χ</italic>²=4.304， <italic>P</italic><0.05）. Total effective rate of comprehensive clinical effect was 93.94% （62/66） higher than 81.54% （55/65） in control group （<italic>χ</italic>²=4.696， <italic>P</italic><0.05）. There was no adverse reactions related to traditional Chinese medicine. Conclusion:Zhuyu Zhixuetang can regulate menstruation， relieve clinical symptoms， improve endometrial morphology under hysteroscopy， regulate systemic and local immune inflammatory response， improve CP， thus improve pregnancy outcome， with better comprehensive effect and safety.

Mechanical Heterogeneity of Tumor Tissues and Epithelial-Mesenchymal Transition of Tumor Cells / 医用生物力学

In the process of tumor growth, with the proliferation and expansion of cancer cells, the reconstruction of extracellular matrix (ECM) of cancer tissues, the restriction of surrounding tissues and the flow of cancer tissue interstitial fluid, the special stress environment is formed in the tumor tissues. Significant differences are found in the mechanical environment and mechanical characteristics of different regions of tumor tissues, that is, mechanical heterogeneity. The reseach shows that the mechanical properties of tumor tissue invasion frontier areas are more significant and complex. In particular, the epithelial-mesenchymal transition (EMT) of tumor cells also prefers to concentrate on this area. The mechanical stress generated by the invasion front can induce EMT of tumor cells through TWIST1, TGF-β, WNT and other force signal transduction pathways, and promote tumor cell invasion. From the perspective of tumor biomechanics, this review focuses on the relationship between mechanical heterogeneity of tumor cells and EMT, so as to provide the theoretical basis for mechanoenvironment-targeted therapy of tumors.

The Role of Lubricin in Wound Repair of Musculoskeletal System / 医用生物力学

Lubricin is widely expressed in tissues in the musculoskeletal system, including articulate cartilage, tendon and synovium, which shows a close relationship with the structure and pathology of these tissues. Lubricin plays an important role in lubrication, anti-adhesion, proliferation inhibition and inflammation regulation, which may facilitate the healing of impaired tissues in the musculoskeletal system. This article reviews the research progress on expression and regulation of lubricin as well as its structure and function in wound repair of the musculoskeletal system, so as to provide theoretical evidences for further researches on the role of lubricin in the musculoskeletal system with its related mechanisms and the clinical application of lubricin.

Autophagic activity of piperine on small intestine in dementia model mice with Parkinson's disease / 中国中药杂志

This article is to investigate the effect of piperine on the small intestine of mice with Parkinson's disease with dementia(PDD). Ninety-six C57 BL/6 mice of SPF grade were randomly divided into 8 groups(male, 12 in each group): normal group, model group, autophagy inhibitor group(6-amino-3-methylpurine, 3 MA, 30 mg·kg~(-1)), autophagy activator group(rapamycin, 1 mg·kg~(-1)), low, medium, and high dose piperine groups(10, 20, 40 mg·kg~(-1)), and medopar group(112.5 mg·kg~(-1)). Except for the normal group, mice in each group were injected subcutaneously with reserpine(0.1 mg·kg~(-1)) once every 48 hours for 40 days. In addition, on the 20 th day of administration, except for the normal group, the mice in the other groups were subjected to bilateral common carotid artery occlusion to finally prepare PDD models. At the same time, each group was given the corresponding drug treatment once a day for 40 days. After the last administration, the behavioral changes of mice were observed by autonomic activity experiment and hot plate experiment. The expression levels of α-synuclein(α-syn) and tyrosine hydroxylase(TH) in the small intestine were detected by immunohistochemistry. The expression levels of beclin-1, microtubule-associated protein 1 light chain 3 B(LC3 B) and p62 in the small intestine were detected by immunofluorescence assay. Hematoxylin-eosin staining was used to observe the pathological morphology of small intestine tissues in each group. Enzyme-linked immunosorbent assay was adopted for detection of β-amyloid precursor protein(APP), p-tau, acetylcholine transferase(ChAT), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in small intestine. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression of α-syn, TH, beclin-1, microtubule-associated protein 1 light chain 3(LC3), and p62 mRNA and mmu-miR-99 a-5 p in the small intestine. The results of this study showed that, as compared with the model group, the number of activities, the expression levels of ChAT, TH, and p62 were significantly increased in the 3 MA group, the various piperine dose groups, and the medopar group(P<0.05), and their first foot licking time was shortened; APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly reduced(P<0.05). However, as compared with the model group, the number of activities, ChAT, TH, and p62 expression levels in the rapamycin group were significantly reduced(P<0.05), and the APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly increased(P<0.05). As compared with the 3 MA group, the number of activities, ChAT, TH, and p62 expression levels were significantly reduced in the low and medium dose piperine groups and rapamycin group(P<0.05); howe-ver, their first foot licking time was significantly prolonged, APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were increased significantly(P<0.05). As compared with the medopar group, the number of activities, ChAT, TH, and p62 expression levels were significantly reduced in low dose piperine group and rapamycin group(P<0.05), but their first foot licking time was significantly extended, and APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly increased(P<0.05). In addition, as compared with the normal group, the small intestinal epithelial cells of the model group and the rapamycin group were shed off a lot, with severe damages of intestinal mucosa as well as edema and shedding of the small intestine villi. After administration of the therapeutic interventions, the small intestinal epithelial cells of the 3 MA group, each dose group of piperine, and the medopa group were slightly damaged and the villi were slightly shed off. In summary, piperine has a protective effect on the small intestine of PDD model mice, showing reduced expression of mmu-miR-99 a-5 p, pro-inflammatory factors and autophagy factors, and the mechanism of slowing PDD pathological symptoms may be related to the inhibition of autophagy.

Analysis in diagnosis and treatment of 29 cases of cervical esophageal perforation / 中华耳鼻咽喉头颈外科杂志

Objective@#To analyze and summarize the method and effect of cervical esophagus perforation.@*Methods@#A total of 29 cervical esophageal perforation patients caused by foreign body were retrospectively analyzed from January 2012 to June 2018 in Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Nanchang University.@*Results@#Among the 29 cervical esophageal perforation patients, 28 patients were extracted by lateral neck incision, 1 patient with carotid artery hemorrhea was rescued by repairing the fistula between carotid artery and esophage. All patients recovered and successfully discharged. There were no severe complications among all patients.@*Conclusions@#The cervical CT scan is important for diagnosing a cervical esophageal perforation. Enhancement CT scan is necessay for a patient with haematemesis. Lateral neck incision would be first choice for patients with big foreign bodies. Inflammatory reaction and finger palpation are helpful for locating foreign bodies.

Effects of Matrix Stiffness on Proliferation and Glucose Metabolism of Hepatocellular Carcinoma Cells / 医用生物力学

Objective To investigate the influences of different matrix stiffness on proliferation ability and glucose metabolism of hepatocellular carcinoma (HCC) cells and to explore the correlation between metabolism and biological behavior changes of HCC cells resulted from the stiffness of extracellular matrix (ECM)．Methods The proliferation changes of HepG2 cells cultured on matrix with different stiffness were detected by CCK-8 assay and cell count assay. 2-NBDG and flow cytometry were used to detect the effect of matrix stiffness on glucose uptake. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of Glut1. Then, 2-DG was used to inhibit glycolysis, and the influences of matrix stiffness on proliferation of HepG2 cells were detected. Results The proliferation ability, glucose uptake and the expression of Glut1 of HepG2 cells increased with the matrix stiffness increasing. When glycolysis was inhibited, the proliferation ability of HepG2 cells grown on matrix with different stiffness was similar. Conclusions The mechanical microenvironment had an important effect on proliferation of HCC cells; matrix with a larger stiffness might promote proliferation of HCC cells through regulating glycolysis. The research findings provide a corresponding experimental basis for the clinical treatment of HCC cells and drug development targeting glucose metabolism.

Study on the expression of FoxM1 in chronic rhinosinusitis and the effect of inflammatory factors on FoxM1 expression / 中华耳鼻咽喉头颈外科杂志

Objective@#To check Forkhead box M1 (FoxM1) expression in nasal mucosal of chronic rhinosinusitis (CRS) patients and the effect of inflammatory factors on FoxM1 expression, in order to research the significance of FoxM1 in CRS.@*Methods@#From January to October of 2018, 50 patients hospitalized in the Department of Otorhinolaryngology, Head and Neck Surgery, First Affiliated Hospital of Nanchang University were enrolled in this study. Twenty CRS patients with polyps (CRSwNP), 20 CRS patients without nasal polyps (CRSsNP) and 10 patients with simple deviation of nasal septum (the control groups) were selected. The expression of FoxM1 in nasal mucosa of these patients was detected by immunohistochemistry (IHC) and real-time fluorescent quantitative PCR (qRT-PCR). Meanwhile, HE stain was used to observe the pathologic changes in each sample. By establishing human nasal epithelium cells cultivating model in vitro and identifying via immumofluorescence method, experimental group and control group were set up, then activation factors including interleukin (IL)-1β, IL-4, IL-5, IL-17, interferon-γ (IFN-γ) and staphylococcal entemtoxin B (SEB) were added in the models after stabilizing passage, and qRT-PRC and Western blot method were applied to check the expressing change of FoxM1. Software SPSS 18.0 was used for statistical analysis.@*Results@#HE stain showed that the mainly pathologic change in nasal mucosa of CRS patients with or without nasal polyp was mucosal epithelial cells, goblet cell and submucosal gland hyperplasia, accompanied by a large number of inflammatory cells infiltration. The result of IHC demonstrated that both of the expression of FoxM1 in nasal mucosal tissue of CRS patients in the CRSwNP and CRSsNP groups exceed that of the control group (80% vs 75% vs 20%, χ2 value was 10.000, 8.213, respectively, all P<0.05); there was no difference of expression between the two groups of CRS patients (χ2=0.143, P>0.05). The result of qRT-PCR demonstrated that the expression of FoxM1 mRNA in nasal mucosa of CRSwNP and CRSsNP was increased compared with that of the control group (3.309±1.511 vs 3.261±1.336 vs 1.000±0.774, t value was 4.519, 4.928, respectively, all P<0.05), but the difference between the two groups of CRS patients had no statistic significance (t=0.107, P=0.909). Nasal mucosa epithelial cells cultivating models was established successfully. Q-RT PCR and Western blot were conducted after stimulation of 100 ng/ml IL-1β, IL-4, IL-5, IL-17, IFN-γ and SEB for 36 h, and the proteins expression levels of FoxM1 exceeded the groups without stimulation with statistic significance.@*Conclusions@#The expression of FoxM1 in CRS increases and many types of cytokine can induce the increase of FoxM1 in human nasal epithelial cells. FoxM1 may participate in the process of pathogenesis in CRS.

The progress of immune escape-related molecule B7-H1 on malignant tumors with multidrug resistance / 医学研究生学报

Malignant tumors with multidrug resistance is one of the major reasons for the failure of tumor treatment, and it is also an important issue in the field of cancer treatment. In recent years, with the continuous research on tumor immune microenvironment, the status of tumor immune escape is deeply understood. The close relationship between the abnormal expression of related molecules B7-H1 and tumor resistance is constantly recognized that multidrug resistant tumor may be more sensitive to immune system surveillance and killing than chemotherapy-sensitive tumor. The article reviews the progress of immune escape-related molecule B7-H1 in multidrug resistance of malignant tumors.

Isolation of homogeneous polysaccharide from Poria cocos and effect of its sulfated derivatives on migration of human breast cancer MDA-MB-231 cells / 中国中药杂志

SATB1 plays a crucial role in the invasion and metastasis of breast cancer,and inhibition of SATB1 expression can effectively control breast cancer metastasis. In this study,homogeneous polysaccharides were isolated from Poria cocos and their sulfated derivatives were prepared to screen out the polysaccharide compositions with inhibitory effects on SATB1 expression. Smal-molecule components were removed from P. cocos by ethanol extraction,and P. cocos crude polysaccharide PPS was obtained by water extraction and ethanol precipitation. Then PPS was successively separated by DEAE Sepharose fast flow anion-exchange and Superdex-75 gel permeation chromatographic steps to give PPSW-1. The structure of PPSW-1 was identified and its sulfated derivatives were prepared. Then their inhibitory effects on human breast cancer MDA-MB-231 cells were investigated. A kind of polysaccharide,PPSW-1 with inhibitory effect on human breast cancer MDA-MB-231 cells,was obtained from P. cocos,with a relative molecular weight of 3. 06×104,and structure of 1,6-branched 1,3-α-D-galactan. PPSW-1 and its sulfated derivative Sul-W-1 showed good inhibitory effect on cells migration,and the water solubility of Sul-W-1 was better than that of PPSW-1. In addition,it was found that polysaccharide of P. cocos and its sulfated derivative can inhibit expression of SATB1. In this study,a kind of homogeneous polysaccharide with inhibitory effect on human breast cancer MDA-MB-231 cells was isolated from P. cocos,and its sulfated derivative with similar efficacy but better solubility was prepared,laying the foundation for the substance basis study of P. cocos.

Meta-analysis of efficiency and safety of WBRT±temozolomide in treatment of brain metastases from NSCLC / 中华放射肿瘤学杂志

Objective To compare the efficacy and safety between whole brain radiotherapy (WBRT) and WBRT combined with temozolomide (TMZ) in the treatment of non-small cell lung cancer with brain metastases.Methods According to the retrieval strategy,the Chinese and English literatures before February 2018 were retrieved from EMbase,Cochrane,PubMed,Wanfang database,Chongqing VIP and CNKI,The target literatures were selected according to the inclusion and exclusion criteria,The quality of the included studies and extracted data was independently assessed by 3 researchers,The RevMan 5,3 and STATA 12,0 software was used for statistical analysis,The objective remission rate (ORR),the total survival period (OS),the progression-free survival (PFS),and the side effects of chemotherapy were evaluated.Results In total,17 trials consisting of 1128 patients were included,The results of Meta-analysis demonstrated that compared with the WBRT group,the ORR was significantly higher (OR=2.54;95％CI:1.93-3.36;P＜0.001),the PFS was significantly longer (MS R=1.329;95％CI:1.143-1.545;P＜0,001),and the incidence of hematological toxicity (OR=3.44;95％CI:1.63-7.26;P＜ 0.05) and the gastric intestinal reaction (OR=1.69;95％CI:1.24-2.31;P＜0.05) was significantly higher in the WBRT+TMZ group,The heterogeneities were within the acceptable range with statistical significance,The results of OS were invalid due to relatively large heterogeneity,The incidence of headache did not significantly differ between two groups (OR=1.05;95％CI:0.72-1.55;P=0,79).Conclusions Compared with WBRT alone,WBRT combined with TMZ is beneficial to improve the short-term efficacy,whereas the incidence of hematological toxicity and gastrointestinal reaction is higher,The occurrence of headache does not significantly differ between two groups,The benefit of long-term survival remains uncertain.

Effects of IDH2 Gene Mutation on Clinical Characteristics and Prognostic of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the prevalence, clinical characteristics and prognostic significance of the isocitrate dehydrogenase 2(IDH2) mutations in patients with acute myeloid leukemia(AML).@*METHODS@#The bone marrow samples of 223 patients with newly diagnosed AML confirmed by MICM typing from January 2015 to October 2018 were collected. The mutation of exon 4 of IDH2 gene was detected by direct sequancing of PCR product; the incidence and types of IDH2 gene mutation in AML patients were analyzed; the clinical characteristics of AML patients with IDH2 gene mutation were analyzed and the therapeutic efficacy for these patients was evaluated.@*RESULTS@#In a cohort of 223 AML patients, mutations were detected in 23(10.31％) patients, among them, 15 with R140Q mutations(65.22%) , 6 with R172K mutations(26.09%) and 2 with R140W mutations(8.70%). The median age in IDH2 mutated group was older than that in non.mutated group(P=0.008). The platelet level at initial diagnosis in IDH2 mutated group was higher than that in non.mutated group(P=0.010). There was no significant statistical difference between IDH2 mutated group and non.mutated group in FAB subtypes of AML(P>0.05). But the rate of IDH2 mutation in M4 and M5 was higher. The rate of IDH2 mutations was higher in AML with normal karyotype and in AML with NPM1 mutations. R140Q mutations associated with NPM1 mutations(χ=8.481，P=0.004), but R172K mutations not associated with NPM1 mutation(P>0.05). IDH2 mutated patients had a lower complete remission rate than non.mutated patients(57.14% vs 80.46%, χ=5.927，P=0.015). The complete remission rate of R140Q mutated patients was not significantly statistically different from non.mutated patients. The complete remission rate of R172K mutated patients was very significantly lower than non.mutated patients(χ=7.734，P=0.005). In the patients without NPM1 mutation, the 2 years overall survival in IDH2 mutated group was lower than in non.mutated group(36.36% vs 66.40%,χ=3.958，P=0.047), the 2 years overall survival of R172K mutated group was significantly lower than non.mutated group(although P>0.05). In all patients, the 2 years overall survival between IDH2 mutated group and non.mutated group was not statistically different(50% vs 66.88%,P>0.05), the 2 years overall survival of R172K mutated group was significantly lower than non.mutated group(although P>0.05). In the patients with normal karyotype or with mutated NPM1, the 2 years overall survival between IDH2 mutated group and non.mutated group was not statistically different(P>0.05).@*CONCLUSION@#IDH2 gene mutations are more common in AML patients at older age, higher platelets level and normal karyotype. The rate of IDH2 mutation in M4 and M5 is higher. IDH2 gene mutations associate with NPMl gene mutations, but R172K mutations not associates with NPM1mutation. IDH2 gene mutations associate with prognosis of AML patients, R140Q mutations have no effect on prognosis of patients, but R172K mutations may be the molecular markers for poor prognosis in AML patients.

Optimization of fresh-cuting process and its pharmacodynamics of Aurantii Fructus / 中草药

Objective To study the effect of different cutting time and drying methods on the index components of pharmacopeia in different fresh-cutting Aurantii Fructus, and investigate the difference of component and efficacy between the preferred fresh-cutting Aurantii Fructus and the traditional slices. Methods The HPLC system consisted of a Diamonsil C18 (250 mm × 4.6 mm, 5 μm) with acetonitrile/phosphoric acid water (20∶80, pH 3.0) as the mobile phase, the flow rate was 1.0 mL/min, column temperature was 30 ℃, detection wavelength was 283 nm, and the injection volume was 20 μL. The content of naringin and neohesperidin in fresh-cutting Aurantii Fructus with different processing methods was determined to optimize the cutting time and drying method. At the same time, the effects of sclices from fresh-cutting and traditional process on the small intestine propulsion rate, gastric emptying rate, gastrin, and hemorheology were determined. Results The content of naringin and neohesperidin of the fresh-cutting Aurantii Fructus that dried in sun was higher than that dried at 60 ℃ in oven at the corresponding days from the same origin, and the highest content was from fresh-cutting slices dried in sun for 3 d. There was no significant difference in the indexes of small intestine propulsion rate, gastric emptying rate, and gastrin between the preferred fresh-cuting Aurantii Fructus and the traditional ones, but the indexes of hemorheology showed significant difference (P < 0.05). Conclusion The preferred fresh-cutting Aurantii Fructus (processed by half cutting horizontally, drying for 3 d, and then cutting into thin slices and drying in the sun) showes no significant difference in gastrointestinal motility indexes when compared with the traditional ones.

Circular RNA circHIPK3 acts as the sponge of microRNA-124 to promote human oral squamous cell carcinoma cells proliferation / 中华口腔医学杂志

Objective@#To explore the expression and clinical significance of circular RNA circHIPK3 in oral squamous cell carcinoma (OSCC), analyze the effect of circHIPK3 on the proliferation of OSCC cells.@*Methods@#The expression of circHIPK3 in OSCC tissues, adjacent non-cancerous tissues and OSCC cell lines were detected by quantitative real-time polymerase chain reaction (qPCR). The correlations between the expression of circHIPK3 in OSCC tissues and the clinicopathological features were analyzed as well. circHIPK3-specific siRNA si-circHIPK3 and negative control siRNA si-NC were designed and synthesised and used to transfect CAL27 and SCC15 cells respectively. The proliferation capacity of CAL27 and SCC15 cells after transfection with si-circHIPK3 was detected by CCK-8 assay. The expression of miR-124 in OSCC was detected by qPCR, and the correlation between expression of circHIPK3 and the expression of miR-124 was analyzed. Using qPCR to detect the expression of miR-124 in CAL27 and SCC15 cells after transfection with si-circHIPK3 and si-NC respectively. Furthermore, using CCK-8 assay to detect the proliferation capacity of CAL27 and SCC15 cells after transfection with si-NC, si-circHIPK3, miR-124 mimic, si-circHIPK3+miR-124 inhibitor.@*Results@#The expression of circHIPK3 in OSCC tissues [2.23 (1.86, 3.00)] was significantly higher than that of the adjacent non-cancerous tissues [1.05 (0.85, 1.26)] (U=1 094, P=0.000). The expression of circHIPK3 in CAL27 (3.02±0.51) and SCC15 cells (3.16±0.75) was higher than those of human normal oral keratinocytes (hNOK) (1.26±0.30) (P=0.000). The expression of circHIPK3 was found to be closely associated with TNM stage (P<0.05) and tumor grades (P<0.05). Knockdown of circHIPK3 can inhibit proliferation of CAL27 and SCC15 cells (P<0.05). The expression of miR-124 in OSCC tissues (0.61±0.35) was significantly lower than that in adjacent non-cancerous tissues (1.13+0.39) (t=-5.36, P<0.05). Correlation analysis showed that the expression of circHIPK3 in OSCC was negatively correlated with the expression of miR-124 (r=-0.767, P<0.001). Moreover, down-regulation of miR-124 rescued the phenotype induced by knockdown of circHIPK3.@*Conclusions@#The expression of circHIPK3 in OSCC was increased, and silencing of circHIPK3 expression can inhibit the proliferation of OSCC cells. Our results suggest that circHIPK3 may play a key role in the occurrence and development process of OSCC through the regulation of miR-124 expression.