2.Effect of silicon dioxide exposure on airway surface microenvironment and NEK7/NLPR3 inflammasome in rats
Wenlu HANG ; Qi WU ; Wanjun LI ; Yun BO ; Xianmei ZHOU
Journal of Preventive Medicine 2023;35(2):180-184
Objective:
To examine the effect of SiO2 exposure on the airway surface microenvironment and NIMA-related kinase 7 (NEK7)/nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome in rats.
Methods:
Twenty-four specific pathogen-free male rats of the SD strain were randomly divided into the control group and the model group, of 12 rats in each group. Rats in the model group were given SiO2 suspensions through disposable tracheal intubation perfusion to model silicosis in rats, while rats in the control group was perfused with the same amount of physiological saline. The pH value and glucose level were measured in the rat bronchoalveolar lavage fluid (BALF) 14 and 28 days after modeling. Lung tissues were stained with HE and Masson and the distribution of inflammatory cells and the deposition of pulmonary interstitial collagens were observed in lung tissues under a light microscope. The expression of transforming growth factor β1 (TGF-β1), collagen type Ⅰ(ColⅠ), collagen type Ⅲ (Col Ⅲ), interleukin-1β (IL-1β), NLRP3, N-terminal domain of Gasdermin D (GSDMD-NT), caspase-1, and NEK7 was quantified in lung specimens using immunohistochemistry.
Results:
Lower pH values were measured in rat BALF in the model group than in the control group 14 [(6.38±0.05) vs. (6.68±0.08), P<0.05] and 28 days after modeling [(6.63±0.14) vs. (6.86±0.05), P<0.05], while higher glucose levels were seen in the model group than in the control group 14 [(0.39±0.06) vs. (0.31±0.04) mg/dL, P<0.05] and 28 days after modeling [(0.39±0.08) vs. (0.31±0.06) mg/dL, P<0.05]. HE and Masson staining showed mild to moderate alveolitis and pulmonary fibrosis in rats 14 days post-exposure to SiO2, and showed moderate to severe alveolitis and pulmonary fibrosis 28 days post-exposure. Immunohistochemistry detected higher TGF-β1, ColⅠ, Col Ⅲ, IL-1β, NLRP3, GSDMD-NT, caspase-1 and NEK7 expression in rat lung tissues in the model group than in the control group (all P<0.05).
Conclusions
SiO2 exposure may cause changes in rat airway surface microenvironment, including BALF acidification and elevated glucose. Pyroptosis induced by activation of NEK7-associated NLRP3 inflammasome may be an important mechanism of pulmonary fibrosis caused by silicosis.
3.Advances of artificial intelligence technology in the discovery and optimization of lead compounds
Zi-yue LI ; Kai-yuan CONG ; Shi-qi WU ; Qi-hua ZHU ; Yun-gen XU ; Yi ZOU
Acta Pharmaceutica Sinica 2024;59(9):2443-2453
In recent years, artificial intelligence (AI) technology has advanced rapidly and has been widely applied in various fields such as medicine and pharmacy, accelerating the drug development process. Focusing on the application of AI in the discovery and optimization of lead compounds, this review provides a detailed introduction to AI-assisted virtual screening and molecular generation methods for discovering lead compounds, while particularly highlighting the cases of AI-drived drugs into clinical trials. Additionally, we briefly outline the application of AI basic algorithm models in quantitative structure-activity relationship (QSAR) and drug repurposing, offering insights for AI-based drug discovery.
4.A genetic adaptive pattern-low hemoglobin concentration in the Himalayan highlanders.
Tian-Yi WU ; Feng-Yun LIU ; Ouzhou-Loubu ; Chao-Ying CUI ; Xue-Bin QI ; Bing SU
Chinese Journal of Applied Physiology 2013;29(6):481-493
Mean hemoglobin (Hb) concentration of about 3 500 subjects derived from 17 studies of Himalayan highlanders (Tibetans, Sherpas, and Ladakhis) was compared with lowlanders (Chinese Han, Indian Tamils) lived in the Himalayas, and European climbers during Everest expeditions as well as Andean natives. The results found that Hb concentration in Himalayan highlanders was systemically lower than those reported for Andean natives and lowland immigrants. These comparative data demonstrated that a healthy native population may successfully reside at high altitude without a significant elevation in Hb, and the lower Hb levels of Himalayan highlanders than those of migrated lowlanders and Andean natives are an example of favourable adaptation over the generations. In addition, excessive polycythemia has frequently been used as a marker of chronic mountain sickness (CMS). Altitude populations who have a higher Hb concentration also have a higher incidence of CMS. The low Hb in Himalayans suggested as showing adaptation over many generations in Tibetan stock. Recent work in Tibet, suggested that Tibetans there may have adapted to high altitude as a result of evolutionary pressure selecting for genes which give an advantage at altitude. All of the population genomic and statistical analysis indicated that EPAS1 and EGLN1 are mostly likely responsible for high altitude adaptation and closely related to low Hb concentration in Tibetans. These data supported the hypothesis that Himalayan highlanders have evolved a genetically different erythropoietic response to chronic hypoxia by virtue of their much longer exposure to high altitude.
Adaptation, Physiological
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Altitude
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Asian Continental Ancestry Group
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genetics
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Basic Helix-Loop-Helix Transcription Factors
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genetics
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Evolution, Molecular
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Hemoglobins
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genetics
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Humans
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Hypoxia-Inducible Factor-Proline Dioxygenases
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genetics
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Tibet
5.The application of ThinPrep cytology in the diagnosis of superficial tumors
Hongai JI ; Jinghua WANG ; Xiaojun ZHOU ; Yun JI ; Hongjuan LIU ; Weilin WU ; Zhengmao QI
Journal of Medical Postgraduates 2004;0(01):-
Objective: To investigate the advantage of ThinPrep cytological test in tumor diagnosis by fine needle aspiration cytology. Methods: Using fine needle aspiration for smears,some of smears were made in conventional smears,the remains aspirating needles were washed with a transport washing solution.ThinPrep slides were made using the ThinPrep Processor. Results: In 84 cases FNA samples,49 cases were breast,29 cases were lymph node and 6 cases were others.Comparing with conventionally prepared specimens,ThinPrep processed samples showed the advantage in sensitivity or specificity.The lack of cellular debris,blood and exudates improve the ability to detect cellular abnormalities and speed up the time required for screening in ThinPrep processed samples.Rapid cell transfer from the sampling device to the transporing fluid containing the fixative ensure preservation of cell details with minimal artifactual changes. Conclusion: The use of Thinprep and by combination of FNAC and immunocytochemistry cytopathological diagnosis can be improved significantly.
6.Rapid detection of molecular variation of Rice stripe virus in China by PCR-SSCP assay
Han-xin, LIN ; Tai-yun, WEI ; Zu-jian, WU ; Qi-ying, LIN ; Lian-hui, XIE
Virologica Sinica 2001;16(2):166-169
A reverse transcription polymerase chain reaction (RT-PCR) and single-strand conformation polymorphisms (SSCP) assay were applied to rapidly detect the molecular variability in CP and SP genes among seven isolates of Rice stripe virus in China. The PCR results showed that the CP gene of JD isolate and SP gene of PJ isolate could not be amplified. SSCP analysis showed that there were completely different electrophoretic pattern of CP gene among six isolates. To SP gene, SSCP results also discovered polymorphisms. There were five patterns among these isolates, and the pattern of YL and BS isolates were same.
7.Clinical effect of anterior vitrectomy for congenital cataract
Hua, HE ; Feng, ZHOU ; Qi, ZHU ; Qian, WANG ; Xue-Mei, WU ; Jian, MA ; Ya-Yun, WANG
International Eye Science 2015;(5):825-827
?AlM: To evaluate the clinical efficacy of posterior continuous curvilinear capsulorhexis ( PCCC ) combined with anterior vitrectomy in preventing posterior capsule opacification of congenital cataract surgery.
?METHODS:Postoperative clinical follow-up data of 82 cases ( 87 eyes ) with congenital cataract treated in Eye Center of our hospital from January 2011 to August 2014 were retrospectively analyzed. The patients were divided into the surgical control group ( 38 cases, 40 eyes, recieved phacoemulsification + PCCC ) and the study group ( 44 cases, 47 eyes, accepted phacoemulsification+ PCCC + anterior vitrectomy). The incidence of central optic axis opaque and postoperative visual acuity distribution were recorded at 1a follow - up. lntraoperative and postoperative complications were observed.
?RESULTS:The rate of central optic axis opaque grade 0 in control group was 37. 5%, compared to 76. 6% in study groups. The opacity distribution ratio of grade 1,2,3 and 4 in study group were lower than that of control group, and the central optic axis opacity distribution ratio in study group was significantly better than that of control group (P<0. 05). The 19 eyes(47. 5%) of visual acuity testing ≤0. 5 in control group , was higher than the 7 eyes(14. 89%) of that in the study group, The 21 eyes (52. 5%) of visual acuity testing >0. 5 in control group was lower than the 40 eyes ( 85. 11%) of that in study group. The visual acuity between two groups has statistical significance difference after 1a follow-up ( P<0. 05 ) , and the visual acuity in study group was significantly better than that in the control group. The postoperative intraocular pressure at 1mo and 1a follow-up was lower than before operation in two groups ( P<0. 05), but there was no significant difference between two groups in intraocular pressure (P<0. 05).
?CONCLUSlON: Combination of phacoemulsification, PCCC and anterior vitrectomy presents reliable clinical effects on postoperative central optic axis opacity distribution ratio and visual acuity, and it should be adopted to prevent the occurrence of posterior capsule opacification.
8.Expression and purification of spike protein of severe acute respiratory syndrome coronavirus in Saccharomyces cerevisiae
Lei YANG ; Hong-Qin ZHANG ; Shu-Zhen WU ; Yun-Tian BI ; Qi-Yu BAO ;
Chinese Journal of Infectious Diseases 2007;0(09):-
Objective To construct the recombinant plasmid pYES6-S and express and purify spike protein of severe acute respiratory syndrome(SANS)coronavirus in Saccharomyces cerevisiae. Methods DNA fragments of SANS coronavirus were obtained by reverse transeription.Four over- lapped fragments of spike protein genes were amplified by polymerase chain reaction(PCR)and ligated into an integral spike protein gene by restriction enzyme digestion.The spike protein gene recombined with pYES6 and cloned into E.coll.The recombinant plasmid pYES6-S was induced and expressed in Saccharomyces cerevisiae(INVScl)by galactose.Results The recombinant plasmid pYES6-S was confirmed that inserted fragment was right in length,direction and base matching by restriction enzyme digestion and sequencing.The purified protein encoded by the whole spike protein gene was about Mr 110?10~3 identified by electrophoresis.Conclusion The whole spike protein gene of SARS coronavirus is cloned into E.coli and the protein is expressed in Saccharomyces cerevisiae successful ly.which can be helpful in SARS vaccine research.
9.Prevalence of ideal cardiovascular health in south Jiangsu adults
Yun LU ; Huajin QI ; Feng LI ; Ling WANG ; Zhenhai SHEN ; Dongchang QIANG ; Liuxin WU
Chinese Journal of Health Management 2016;(1):37-44
Objectives To estimate the prevalence of the cardiovascular health (CVH) status in south Jiangsu adults. Methods A cross-sectional study was conducted, a total of 11 996 participants that took health examination in hospitals from March 2013 to August 2013 and live in south Jiangsu were selected. Results Totally 136 participants (1.1%) met all 7 ideal CVH metrics;while 27.6%participants met 5 to 7 ideal CVH metrics, women had higher proportion (47.2%) than men (16.9%). The percentage of participants who met 5 to 7 ideal CVH metrics, whether male or female, decreased with increasing age. Ideal total cholesterol (TC) was the most prevalent (72.0%), whereas ideal salt intake was the least (19.9%). The mean (± SD) number of ideal CVH metrics for urban participants was (3.61 ± 1.46), higher than the rural participants (3.45±1.49). Old age, male and residence in rural area were risk factors for ideal CVH metrics≥5. Conclusions The prevalence of ideal CVH was extremely low in South Jiangsu adults, and there were differences in the distribution of ideal CVH metrics across gender and age. To improve CVH, specific promotion and interventions at the population and individual levels should be developed and implemented actively.
10.Protective effects of Salvia miltiorrhiza on rats with streptozotocin diabetes and its mechanism
Gang LIU ; Guangju GUAN ; Tonggang QI ; Yuqin FU ; Xuegang LI ; Yun SUN ; Tao WU ; Rongzhu WEN
Journal of Integrative Medicine 2005;3(6):459-62
OBJECTIVE: To explore the effects of Salvia miltiorrhiza on renal morphology and renal function of rats with streptozotocin diabetes. METHODS: Thirty male Wistar rats were randomly divided into three groups, which were normal control group, untreated group and Salvia miltiorrhiza-treated group. Diabetic nephropathy was induced in rats of the last two groups by intraperitoneal injection of streptozotocin after unilateral nephrectomy. Then the rats in the normal control and untreated groups were fed with normal saline while those in the Salvia miltiorrhiza-treated group were fed Salvia miltiorrhiza preparation for 8 weeks. The glomerular volume (VG), kidney-to-body weight ratio (KW/BW), urinary albumin excretion rate (UAER) and creatinine clearance (Ccr) were observed. The expression levels of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), fibronectin (FN) and plasminogen activator inhibitor-1 (PAI-1) were detected by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) at the end of the experiment. RESULTS: UAER, Ccr, VG and KW/BW ratio were significantly higher in the untreated group than those in the normal control group (P<0.05). The expression levels of TGF-beta1, CTGF, PAI-1 and FN in the untreated group were also significantly higher as compared with those in the normal control group (P<0.05). UAER, Ccr, VG, KW/BW ratio and the levels of TGF-beta1, CTGF, PAI-1 and FN in the Salvia miltiorrhiza-treated group were obviously lower than those in the untreated group (P<0.05). CONCLUSION: Salvia miltiorrhiza can protect rats with streptozotocin diabetes from diabetic nephropathy by suppressing the over-expressions of TGF-beta1, CTGF, PAI-1 and FN in renal cortex.