1.Changes in m6A demethylase ALKBH5 expression in form-deprivation myopic guinea pigs and its significance
Xiaoling XIANG ; Xuan LIAO ; Jiayu MENG ; Guimei ZHOU ; Hong ZHOU ; Xianmei ZHOU
Chinese Journal of Experimental Ophthalmology 2024;42(4):315-321
Objective:To investigate the alteration of m6A demethylase AlkB homolog 5 (ALKBH5) expression and its impact on form-deprivation myopia (FDM) retina in guinea pigs.Methods:Thirty normal SPF grade 3-week-old tricolor guinea pigs were randomly divided into normal control group and experimental group, with 15 in each group.In the experimental group, the right eyes were covered as FDM group and the left eyes uncovered were set as self-control group.Ocular biometry was performed at one-week intervals from baseline to week 4 of the experiment.Spherical equivalent was detected by streak retinoscopy and axial length was measured by A-scan ultrasonography.Animals were sacrificed after 4 weeks of modeling.The distribution and expression of ALKBH5 protein in the guinea pig retina was detected by immunohistochemical and immunofluorescence staining.Expression of ALKBH5 mRNA and protein in guinea pig retina was detected by real-time fluorescence quantitative PCR and Western blot, respectively.The use of animals in ophthalmic and vision research followed the tenets of Animal Research in Vision and Ophthalmology, and the study was approved by the Ethics Committee of North Sichuan Medical College (No.2023087).Results:At weeks 2, 3, and 4 after myopia induction, diopters and axial lengths were significantly higher in the FDM group than in the normal control group and the self-control group (all at P<0.001). Immunohistochemistry and immunofluorescence assays showed that ALKBH5 protein was expressed in the retinal nerve fiber layer, rod/cone photoreceptor cells, and retinal pigment epithelium (RPE) layer, and was highly expressed in the retinal nerve fiber layer and RPE layer.The relative ALKBH5 immunofluorescence intensity in the normal control group, self-control group and FDM group was 1.000±0.204, 0.874±0.076 and 0.571±0.053, respectively, which was lower in the FDM group than in the normal control and self-control groups, showing statistically significant differences ( t=4.069, P=0.006; t=5.176, P=0.014). After 4 weeks of modeling, ALKBH5 mRNA and protein expressions were significantly lower in FDM group than in normal control and self-control groups (both at P<0.01). Conclusions:The expression of m6A demethylase ALKBH5 is decreased in the retina of FDM guinea pigs, suggesting that ALKBH5 and related m6A methylation modification may be involved in the development and progression of myopia.
2.Clinical Efficacy of Maiwei Yangfei Decoction in the Treatment of Idiopathic Pulmonary Fibrosis of Qi-Yin Deficiency Type
Dongwei ZHU ; Qi ZHAO ; Le BAI ; Tingyu PAN ; Jing WANG ; Shenhao GUO ; Yong XU ; Xianmei ZHOU
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(9):962-969
OBJECTIVE To explore the therapeutic effect and safety of Maiwei Yangfei Decoction(MWYF)in the treatment of idiopathic pulmonary fibrosis of qi-yin deficiency type.METHODS A total of 58 patients with idiopathic pulmonary fibrosis of qi-yin deficiency type were randomly divided into an experimental group and a control group with 29 cases in each group according to a 1:1 ratio.Two cases dropped out of the experimental group and three cases dropped out of the control group.The control group received standardized treatment of Western medicine,and the experimental group received MWYF on the basis of the treatment of the control group.The treatment course of both groups was 3 months.The TCM syndrome score,lung function,6-minute walking distance(6MWD),transcutaneous blood oxygen saturation(SpO2),high-resolution computed tomography(HRCT)score,St.George's respir-atory questionnaire(SGRQ)score and serum sialoglycoprotein antigen(KL-6)level of the two groups were compared before and after treatment.Blood routine and liver and kidney function of the two groups were detected before and after treatment,and the occurrence of adverse reactions during treatment was recorded.RESULTS After treatment,the total score of TCM syndrome of the two groups was significantly improved(P<0.01),and the experimental group was better than the control group(P<0.01);the DLCO%of the experi-mental group increased(P<0.05),and the experimental group was higher than the control group(P<0.05).The experimental group showed significant improvement in 6MWD,HRCT grid shadow,SGRQ symptom score and total score,and serum KL-6 level(P<0.05,P<0.01),which was better than the control group(P<0.05,P<0.01).No serious adverse events occurred in either group dur-ing the treatment.CONCLUSION MWYF combined with standardized Western medicine treatment can effectively improve the clini-cal symptoms of patients with idiopathic pulmonary fibrosis of qi-yin deficiency type,reduce the expression level of serum KL-6,and has a definite effect and good safety.
3.Prenatal ultrasound measured fetal cauda equina nerve parameters for diagnosing tethered cord syndrome
Yao TANG ; Shengli LI ; Zhaoping ZHANG ; Nana HUANG ; Yun WANG ; Ning LUO ; Zhou ZHOU ; Xianmei CAO
Chinese Journal of Medical Imaging Technology 2024;40(11):1647-1650
Objective To observe the value of prenatal ultrasound measuring fetal cauda equina nerve parameters for diagnosing tethered cord syndrome(TCS).Methods Forty six fetuses with TCS(TCS group)and 591 healthy fetuses(control group)were retrospectively enrolled.The length,area and angle of cauda equina nerve were measured with prenatal ultrasound and compared between groups,and the value for diagnosing TCS was analyzed.Results Significant differences of the length,area and angle of fetal cauda equina nerve were found between groups(all P<0.05),with the area under the curve for diagnosing TCS of 0.924,0.809 and 0.972,respectively.Conclusion Prenatal ultrasound measuring fetal cauda equina nerve parameters had high value for diagnosing TCS.
4.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.
5.Inhibition of gasdermin D-dependent pyroptosis attenuates the progression of silica-induced pulmonary inflammation and fibrosis.
Meiyue SONG ; Jiaxin WANG ; Youliang SUN ; Junling PANG ; Xiaona LI ; Yuan LIU ; Yitian ZHOU ; Peiran YANG ; Tianhui FAN ; Ying LIU ; Zhaoguo LI ; Xianmei QI ; Baicun LI ; Xinri ZHANG ; Jing WANG ; Chen WANG
Acta Pharmaceutica Sinica B 2022;12(3):1213-1224
Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide, but the molecular basis underlying its development remains unclear. An accumulating body of evidence supports gasdermin D (GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases. However, there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis. In this work, we investigated the role of GSDMD-mediated pyroptosis in silicosis. Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression. Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica. Measurement of interleukin-1β release, lactic dehydrogenase activity, and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages. Additionally, we verified that both canonical (caspase-1-mediated) and non-canonical (caspase-4/5/11-mediated) signaling pathways mediated silica-induced pyroptosis activation, in vivo and in vitro. Notably, Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes, which highlighted the pivotal role of pyroptosis in this disease. Taken together, our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.
6.Research progress of traditional Chinese medicine extracts in intervention of fibrosis caused by silicosis
Wenlu HANG ; Qi WU ; Ying ZHAO ; Xianmei ZHOU
Journal of Environmental and Occupational Medicine 2022;39(2):229-235
Silicotic nodules and pulmonary fibrosis are histopathological appearance in silicosis patients after long-term inhalation of crystalline silica particles, and are difficult to reverse and recover. Research on the pathogenesis and treatment strategies of silicosis has significantly lagged behind medical progress and clinical needs, resulting in the disease remaining a thorny clinical problem. Traditional Chinese medicine extracts or compound preparations have become a hot issue in exploring silicosis treatment strategies in recent years. This paper described the main pathological processes of pulmonary fibrosis caused by silicosis, followed by introducing its main pathogenesis mechanisms, including transforming growth factor-β1 (TGF-β1)/Smad signaling pathway, oxidative stress reaction, apoptosis, and autophagy. In addition, it briefly described the research progress, targets, and intervention effects of selected traditional Chinese medicine extracts, which provides a scientific basis for the theoretical and clinical research of traditional Chinese medicine extracts in inhibiting pulmonary fibrosis. To change the clinical status quo of silicosis fibrosis which is difficult to control and reverse, the paper proposed that we can further explore the pathogenesis and progression mechanisms of silicosis and drug treatment strategy, and focus on the transformation of basic research into clinical practice.
7.Changes and clinical significance of body mass index, blood lipid and fat soluble vitamin levels in patients with different types of severe preeclampsia
Chinese Journal of Primary Medicine and Pharmacy 2021;28(5):748-753
Objective:To investigate the changes and clinical significance of body mass index (BMI), blood lipid and fat soluble vitamin levels in patients with different types of severe preeclampsia.Methods:Sixty-eight pregnant women with severe preeclampsia who received antenatal examination in Lishui Maternal and Child Health Care Hospital, China from February 2017 to February 2019 were included in the study group. According to the onset time, the pregnant women were divided into an early onset group (≤ 34 weeks of gestation, n = 38) and a late onset group (> 34 weeks of gestation, n = 30). An additional 50 healthy pregnant women who concurrently received antenatal examination in the same hospital were included in the control group. Serum levels of triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), vitamin A (VA), vitamin E (VE) and vitamin D 3 (VD 3) were determined in all pregnant women. Logistic regression was used to analyze severe preeclampsia-related influential factors. Results:There were no significant differences in age, number of births and number of pregnancies among the three groups (all P > 0.05). BMI and serum levels of VA, VE, TC, TG, and LDL-C were (22.99 ± 4.39) kg/m 2, (0.48 ± 0.08) ng/mL, (11.91 ± 1.74) ng/mL, (4.93 ± 0.34) mmol/L, (1.57 ± 0.26) mmol/L, (2.68 ± 0.27) mmol/L, respectively, which were significantly higher than those in the control group [(20.68 ± 3.68) kg/m 2, (0.40 ± 0.07) ng/mL, (10.32 ± 2.56) ng/mL, (4.12 ± 0.67) mmol/L, (1.25 ± 0.32) mmol/L, (2.15 ± 0.32) mmol/L, t = 3.725, 6.698, 4.352, 8.731, 6.282, 10.512, all P < 0.05]. Serum levels of HDL-C and VD 3 in the study group were (1.51± 0.32) mmol/L and (16.16 ± 2.37) ng/mL, respectively, which were significantly lower than those in the control group [(1.88 ± 0.57) mmol/L, (17.86 ± 2.39) ng/mL, t = - 6.959, - 4.520, both P < 0.05]. BMI and serum levels of TC, TG, LDL-C, VA and VE in the early onset group were (23.13 ± 4.13) kg/m 2, (5.05 ± 0.34) mmol/L, (1.62 ± 0.27) mmol/L, (2.95 ± 0.32) mmol/L, (0.52 ± 0.06) ng/mL, (12.16 ± 1.80) ng/mL, respectively, which were significantly higher than those in the control group ( t = 6.507, 17.462, 11.217, 16.593, 9.075 and 4.142, all P < 0.05). Serum levels of HDL-C and VD 3 in the early onset group were (1.43 ± 0.28) mmol/L and (15.76 ± 2.42) ng/mL, respectively, which were significantly lower than those in the control group ( t = 14.635, 5.871, both P < 0.05). BMI and serum levels of TC, TG and VE in the late onset group were (22.70 ± 4.32) kg/m 2, (4.67±0.32) mmol/L, (1.49 ± 0.25) mmol/L and (11.45 ± 1.61) ng/mL, respectively, which were significantly higher than those in the control group ( t = 5.821, 12.857, 8.059, 3.482, all P < 0.05). Serum level of VD3 in the late onset group was (16.72 ± 2.31) ng/mL, which was significantly lower than that in the control group ( t = 4.319, P = 0.01). There were no significant differences in serum levels of LDL-C, HDL-C and VA between late onset group and control group (all P > 0.05). There were no significant differences in BMI, and serum levels of TC, TG, HDL-C, LDL-C, VA, VD 3 and VE between early onset and late onset groups (all P > 0.05). Logistic regression analysis results revealed that BMI and serum levels of TG, TC, HDL-C, LDL-C, VA, VD 3 and VE are independent influential actors of early onset severe preeclampsia ( P = 0.000, 0.008, 0.032, 0.043, 0.032, 0.002, 0.041, 0.009). BMI and serum levels of TG, TC, VD 3 and VE are independent influential actors of late onset severe preeclampsia ( P = 0.002, 0.016, 0.013, 0.031, 0.042). BMI, blood lipid and fat soluble vitamin in combination are of high value for the prediction of early onset severe preeclampsia (sensitivity 87.81% and specificity 76.67%), but they are not of high value for the prediction of late onset severe preeclampsia (sensitivity 52.51% and specificity 55.10%). Conclusion:BMI, serum lipid and fat soluble vitamin in combination are of high value in the prediction of early-onset severe preeclampsia.
8.Relationship between Doppler ultrasound examination of blood flow of uterine arteries in the second trimester and the outcomes of preeclampsia,prognosis of neonates
Fei CHEN ; Yixiong WANG ; Ying ZHOU ; Xianmei HUANG ; Qin QIAN
Journal of Clinical Medicine in Practice 2018;22(9):75-78
Objective To explore indicator value of blood flow of uterine arteries in second trimester uterine artery by Doppler ultrasound and early diastolic notch in the prediction of preeclampsia development,and to analyze the relationship between these values and pregnancy outcomes and neonatal prognosis.Methods A total of 89 puerperae cases with preeclampsia underwent pregnant examinations in our hospital were retrospectively reviewed,and were divided into mild preeclampsia (group A) and severe preeclampsia (group B),and 100 women with normal singleton pregnancies were selected as control group(Group C).Four-dimensional ultrasound was adopted to detect pulsatility indices (PI),resistance indices (RI) and early-diastolic notch of bilateral uterine arteries in the three groups from 20 to 26 gestational weeks.The pulsatility index (PI) and resistance index (RI) of the uterine artery were measured,and the number of early diastolic waves was recorded.The relationship between these values and the outcomes of pregnancy and neonates was analyzed.Results Neonatal prognosis of Group B was worse than that of group A and group C (P < 0.05);The uterine artery PI and RI of group B were higher than that of group A and group C (P < 0.05).The early diastolic notch of group A and group B was higher than that of group C (P < 0.05).Conclusion The indicator value of blood flow in uterine artery and the early diastolic notch in the second trimester could monitor the occurrence of preeclampsia,especially severe preeclampsia and they are useful to predict preeclampsia severity and prenatal prognosis.
9.Relationship between Doppler ultrasound examination of blood flow of uterine arteries in the second trimester and the outcomes of preeclampsia,prognosis of neonates
Fei CHEN ; Yixiong WANG ; Ying ZHOU ; Xianmei HUANG ; Qin QIAN
Journal of Clinical Medicine in Practice 2018;22(9):75-78
Objective To explore indicator value of blood flow of uterine arteries in second trimester uterine artery by Doppler ultrasound and early diastolic notch in the prediction of preeclampsia development,and to analyze the relationship between these values and pregnancy outcomes and neonatal prognosis.Methods A total of 89 puerperae cases with preeclampsia underwent pregnant examinations in our hospital were retrospectively reviewed,and were divided into mild preeclampsia (group A) and severe preeclampsia (group B),and 100 women with normal singleton pregnancies were selected as control group(Group C).Four-dimensional ultrasound was adopted to detect pulsatility indices (PI),resistance indices (RI) and early-diastolic notch of bilateral uterine arteries in the three groups from 20 to 26 gestational weeks.The pulsatility index (PI) and resistance index (RI) of the uterine artery were measured,and the number of early diastolic waves was recorded.The relationship between these values and the outcomes of pregnancy and neonates was analyzed.Results Neonatal prognosis of Group B was worse than that of group A and group C (P < 0.05);The uterine artery PI and RI of group B were higher than that of group A and group C (P < 0.05).The early diastolic notch of group A and group B was higher than that of group C (P < 0.05).Conclusion The indicator value of blood flow in uterine artery and the early diastolic notch in the second trimester could monitor the occurrence of preeclampsia,especially severe preeclampsia and they are useful to predict preeclampsia severity and prenatal prognosis.
10.Treatment of Hormone Dependent Asthma by Combination of Chinese and Western Medicines
Journal of Zhejiang Chinese Medical University 2017;41(2):153-155
[Objective]To observe the clinical effect of the treatment of hormone dependent asthma by Bushen Yiqi Decoction. [Methods]84 cases of hormone dependent asthma in the Affiliated Hospital of Nanjing University of Chinese Medicine from December 2011 to December 2015 were selected. According to the random number table, 84 cases were randomly divided into two groups:control group and observation group, 42 cases in each group. Control group was in accordance with the GINA guidelines recommended fourth level of treatment. Observation group, on the basis of the control group, treated hormone dependent asthma by western medicine in combination with Bushen Yiqi Decoction. [Results] The total effective rate of observation group was 88.1%, and the total effective rate of control group was 71.43%. Two groups of comparison, the difference was statistically significant( P<0.05); IL-5, IL-4, EOS levels were decreased after treatment in the two groups(P<0.05), but the observation group decreased more significantly, compared with the control group, the difference was statistically significant(P<0.05);During treatment and after treatment, reduction rate of using hormone and antiasthmatics in control group and observation group was respectively(85.7%VS64.3%) and(78.6%VS61.9), two groups of comparison, the difference was statistically significant( P<0.05). [Conclusion]Compared with the pure oral hormone plus inhalation in the treatment of hormone dependent asthma, application of Bushen Yiqi Decoction has obvious curative effect and can reduce the dosage of hormone and side effects. It is worthy of clinical promotion.


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