1.Qidi Tangshen Prescription (QDTS) Regulate Akt1/HIF-1α/Bcl-xl Signaling Pathway to Improve Podocyte Autophagy in Diabetic Nephropathy
Fei GAO ; Huidi XIE ; Borui YU ; Ying ZHOU ; Yang SHI ; Xianhui ZHANG ; Hongfang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):90-97
ObjectiveTo explore the mechanism of Qidi Tangshen prescription (QDTS) in alleviating podocyte injury and reducing urinary protein in diabetic nephropathy (DN). MethodUsing network pharmacology methods, we collected the chemical components and targets of QDTS, as well as the targets related to DN. Subsequently, we constructed a "drug-ingredient-target-disease" network for QDTS in the treatment of DN to systematically elucidate the mechanism. The db/db mice were assigned into the model, QDTS (3.34 g·kg-1), and losartan capsules (10.29 mg·kg-1) groups, and db/m mice served as the normal group. Each group consisted of 8 mice, and they underwent continuous intervention for 8 weeks. After the last administration, mice were euthanized, and the urinary albumin excretion rate (UAER) and renal pathological changes were measured and observed. The expression levels of protein kinase B1 (Akt1), hypoxia-inducible factor-1 alpha (HIF-1α), phosphorylated B-cell lymphoma-extra-large (p-Bcl-xl), as well as autophagy-related indicators microtubule-associated protein 1 light chain 3 (LC3), ubiquitin-binding protein p62 (p62), and autophagy-related gene 6 homolog (Beclin1), were determined. Furthermore, mouse podocytes were divided into the normal glucose (5.5 mmol·L-1), high glucose (35 mmol·L-1), DMSO (35 mmol·L-1 glucose+200 mg·L-1 DMSO), and QDTS (35 mmol·L-1 glucose+200 mg·L-1 QDTS freeze-dried powder) groups. After 48 h of intervention, the protein levels of Akt1, HIF-1α, p-Bcl-xl, LC3, p62, and Beclin1 in podocytes were measured. ResultQDTS had 34 active components acting on 143 targets in the treatment of DN, and 55 targets were related to autophagy, in which Akt1, HIF-1α, and Bcl-xl were the key targets. Compared with the normal group, mice in the model group exhibited significantly increased UAER, glomerular hypertrophy, deposition of blue collagen fibers, thickening of the glomerular basement membrane, and noticeable fusion of podocyte foot processes in some segments. Furthermore, the modeling up-regulated the protein levels of p-Akt1, HIF-1α, and p62 and down-regulating the protein levels of p-Bcl-xl, LC3, and Beclin1 in the renal tissue (P<0.05). Compared with the model group, QDTS and losartan decreased UAER (P<0.05) and alleviated the pathological damage in the renal tissue. Moreover, QDTS and losartan down-regulated the protein levels of p-Akt1, HIF-1α, and p62 and up-regulated the protein levels of p-Bcl-xl, LC3, and Beclin1 in the renal tissue (P<0.05). In comparison to the normal glucose group, the high glucose group displayed up-regulated protein levels of p-Akt1, HIF-1α, and p62 and down-regulated protein levels of p-Bcl-xl, LC3, and Beclin1 in podocytes (P<0.05). Compared with the high glucose group, QDTS down-regulated the protein levels of p-Akt1, HIF-1α, and p62 and up-regulated the protein levels of p-Bcl-xl, LC3, and Beclin1 in podocytes (P<0.05). ConclusionQDTS alleviates podocyte damage and reduced urinary protein in DN by regulating the Akt1/HIF-1α/Bcl-xl signaling pathway, thereby enhancing podocyte autophagy.
2.Implication of Qidi Tangshen Prescription (QDTS) on Podocyte Pyroptosis in Diabetes Nephropathy by Regulating MAPK14/RELA/Caspase-8 Signaling Pathway
Fei GAO ; Borui YU ; Huidi XIE ; Ying ZHOU ; Yang SHI ; Xianhui ZHANG ; Hongfang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):67-75
ObjectiveTo explore the molecular mechanism of Qidi Tangshen prescription (QDTS) in regulating podocyte pyroptosis in diabetes nephropathy (DN). MethodThrough in vivo experiment, db/db mice were divided into the model group, QDTS group (3.34 g·kg-1), valsartan capsule group (10.29 mg·kg-1), with db/m mice serving as the normal control. Each group consisted of 8 mice, and they underwent continuous intervention for 8 weeks. After the last administration, mice were euthanized, and kidney pathological changes were observed. Additionally, the expression levels of pyroptosis-related indicators, including NOD-like receptor protein 3 (NLRP3), Gasdermin D protein (GSDMD), and interleukin-1β (IL-1β) protein, were examined. Through in vitro experiment, mouse podocytes were divided into the normal glucose group (5.5 mmol·L-1 glucose), high glucose group (35 mmol·L-1 glucose), DMSO group (35 mmol·L-1 glucose+200 mg·L-1 DMSO), and QDTS group (35 mmol·L-1 glucose+200 mg·L-1 QDTS freeze-dried powder). After 48 hours of intervention, the expression levels of NLRP3, GSDMD, and IL-1β proteins were measured in podocytes. A drug-ingredient-target-disease interaction network for QDTS in the treatment of DN was constructed by network pharmacology methods. The key signaling pathways regulating podocyte pyroptosis were analyzed, and validation was conducted through in vivo and in vitro experiments. ResultCompared with normal group, glomerular hyperplasia and glomerular basement membrane thickening were observed in model group, and some segments were accompanied by obvious podocellular process fusion. The protein expressions of NLRP3, GSDMD and IL-1β in mouse kidney were increased, the protein expressions of mitogen-activated protein kinase 14 (MAPK14), V-Rel reticuloendotheliosis virus oncogene homology A (RELA) and Caspase-8 in mouse kidney were increased (P<0.05). Compared with model group, kidney pathological injury of mice in QDTS group was significantly reduced, and the expressions of NLRP3, GSDMD and IL-1β in kidney of mice in QDTS group and valsartan group were decreased (P<0.05). The protein expressions of MAPK14, RELA and Caspase-8 in kidney of mice in QDTS group and valsartan group were decreased (P<0.05). Network pharmacology results showed that there were 16 targets for QDTS to regulate DN cell pyrodeath, among which MAPK14, RELA and Caspase-8 were the key targets. Compared with normal glucose group, the protein expressions of NLRP3, GSDMD and IL-1β in high glucose group were increased (P<0.05), and the protein expressions of MAPK14, RELA and Caspase-8 in mouse podocytes were increased (P<0.05). Compared with high glucose group, the expressions of NLRP3, GSDMD and IL-1β in podocytes of mice in QDTS group were decreased (P<0.05), and the expressions of MAPK14, RELA and Caspase-8 in podocytes of mice in QDTS group were decreased (P<0.05). ConclusionQDTS reduces damage to DN podocytes, which is associated with its regulation of the MAPK14/RELA/Caspase-8 signaling pathway and inhibition of podocyte pyroptosis.
3.Teaching guidelines for curriculum ideological and political of the nursing ethics
Ying ZOU ; Junrong LIU ; Chunjuan LIU ; Yawen LUO ; Lei WANG ; Chaoyang ZHONG ; Xiaofeng XIE ; Lei HUANG ; Fengying ZHANG
Chinese Medical Ethics 2024;37(8):988-994
The guidelines for curriculum ideological and political of nursing ethics explored the ideological and political elements of Chinese nursing,and proposed the curriculum's ideological and political goals.The development framework and basic ideas of guidelines were formed from the aspects of the integration path of curriculum ideological and political,and professional teaching,searching for the entry point of curriculum ideological and political,reforming the teaching methodology,enriching the form of teaching,and constructing the case base of curriculum ideological and political.It promoted the deep integration of nursing professional knowledge transmission and ideological value guidance,created a distinctive education system of curriculum ideological and political for nursing ethics,and provided a reference for the curriculum ideological and political construction of national nursing ethics.
4.Role of LC3-associated phagocytosis in regulating infection
Yu WANG ; Xianhui HUANG ; Ren SHEN ; Chaoyang ZHOU ; Yongliang LOU ; Danli XIE
Chinese Journal of Microbiology and Immunology 2023;43(2):158-163
LC3-associated phagocytosis (LAP) is a special phagocytosis occurring at the intersection of the two pathways of phagocytosis and autophagy. A hallmark event of the LAP process is the recruitment of microtubule-associated proteinⅠlight chain type 3-Ⅱ(LC3Ⅱ) to the phagosome surface of the monolayer membrane structure. The LAP pathway relies on the functions of the RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein (Rubicon) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The LC3-associated phagosome (LAPosome) binds to the lysosome to digest and degrade the contents. In recent years, increasing studies have found that LAP plays an important role in the infections caused by pathogenic microorganisms including fungi and bacteria. LAP is a crucial way in the host to resist and degrade the infection of pathogenic microorganisms. However, some pathogenic microorganisms can effectively escape from LAP in the host and even use LAPosome as a place for colonization and replication. This article summarized the recent progress in the role of LAP in host defense against pathogenic microorganism infection and the significance of it in the occurrence and development of diseases.
6.Optimization and Developmental Validation of 38-plex InDel Panel for Ancestry Inference.
Qing-Guo WANG ; Lei ZHAO ; Tang-Song LI ; Wang FU ; He-Xin XIE ; Yuan MA ; Wen-Ping SUN ; Jun-Ping HAN
Journal of Forensic Medicine 2022;38(5):611-617
OBJECTIVES:
The previously established 38-plex InDel system was optimized and its performance was validated according to the Scientific Working Group on DNA Analysis Method (SWGDAM) application guidelines. The ancestry inference accuracy of individuals from East Asian, European, African and mixed populations was verified.
METHODS:
DNA standard sample 9947A was used as the template to establish the optimal amplification conditions by adjusting primer balance, Mg2+ final concentration and optimizing PCR thermal cycle parameters and amplification volume. The allelic dropout, nonspecific amplification and whether the origin of the inferred samples matched the known information were compared to evaluate the performance of this system.
RESULTS:
The optimal dosage of this system was 0.125-2 ng DNA template. The results of InDel typing were accurate, the amplification equilibrium was good, and the species specificity was good. This system showed certain tolerance to DNA samples including the inhibitor such as hemoglobin (≤80 μmol/L), indigo (≤40 mmol/L), calcium ion (≤1.0 mmol/L), and humic acid (≤90 ng/μL). The system enabled the direct amplification of DNA from saliva and blood on filter paper, and the results of ethnic inference were accurate. The system successfully detected the mixed DNA sample from two individuals. The test results of the system for common biological materials in practical cases were accurate.
CONCLUSIONS
The results of the 38-plex InDel system are accurate and reliable, and the performance of the system meets the requirement of the SWGDAM guidelines. This system can accurately differentiate the ancestry origins of individuals from African, European, East Asian, and Eurasian populations and can be implemented in forensic practice.
Humans
;
Polymorphism, Single Nucleotide
;
Genotype
;
Polymerase Chain Reaction
;
DNA/genetics*
;
DNA Fingerprinting/methods*
;
INDEL Mutation
;
Genetics, Population
;
Gene Frequency
7.Delivery room resuscitation and short-term outcomes of extremely preterm and extremely low birth weight infants: a multicenter survey in North China.
Shuai-Jun LI ; Qi FENG ; Xiu-Ying TIAN ; Ying ZHOU ; Yong JI ; Yue-Mei LI ; Shu-Fen ZHAI ; Wei GUO ; Fang ZHANG ; Rong-Xiu ZHENG ; Hai-Ying HE ; Xia LIU ; Jun-Yi WANG ; Hua MEI ; Hong-Yun WANG ; Hua XIE ; Chao-Mei ZENG ; Li MA ; Ping-Ping ZHANG ; Jin-Yu LI ; Xiao-Ying WANG ; Li-Hua LI ; Hong CUI ; Shu-Lan YANG ; Lu CHEN ; Xiao-Hong GU ; Yan-Ju HU ; Sheng-Shun QUE ; Li-Xia SUN ; Ming YANG ; Wen-Li ZHAO ; Qiu-Yan MA ; Hai-Juan WANG ; Jiu-Ye GUO
Chinese Medical Journal 2021;134(13):1561-1568
BACKGROUND:
Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China.
METHODS:
The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD.
RESULTS:
A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05).
CONCLUSION
Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight
;
Bronchopulmonary Dysplasia
;
China/epidemiology*
;
Delivery Rooms
;
Female
;
Gestational Age
;
Humans
;
Infant
;
Infant, Extremely Low Birth Weight
;
Infant, Extremely Premature
;
Infant, Newborn
;
Male
;
Pregnancy
8.Overexpression of programmed cell death-1 (PD-1) affects circulatory Th1 and Th2 cells in patients with cardiac arrest in the early period after the return of spontaneous circulation.
Yanan YU ; Miaorong XIE ; Jiabao LI ; Chenchen HANG ; Fei SHAO ; Chunsheng LI
Chinese Medical Journal 2021;135(1):95-97
9.Automated grading of glioma based on density and atypia analysis in whole slide images.
Jineng HAN ; Jiawei XIE ; Song GU ; Chaoyang YAN ; Jianrui LI ; Zhiqiang ZHANG ; Jun XU
Journal of Biomedical Engineering 2021;38(6):1062-1071
Glioma is the most common malignant brain tumor and classification of low grade glioma (LGG) and high grade glioma (HGG) is an important reference of making decisions on patient treatment options and prognosis. This work is largely done manually by pathologist based on an examination of whole slide image (WSI), which is arduous and heavily dependent on doctors' experience. In the World Health Organization (WHO) criteria, grade of glioma is closely related to hypercellularity, nuclear atypia and necrosis. Inspired by this, this paper designed and extracted cell density and atypia features to classify LGG and HGG. First, regions of interest (ROI) were located by analyzing cell density and global density features were extracted as well. Second, local density and atypia features were extracted in ROI. Third, balanced support vector machine (SVM) classifier was trained and tested using 10 selected features. The area under the curve (AUC) and accuracy (ACC) of 5-fold cross validation were 0.92 ± 0.01 and 0.82 ± 0.01 respectively. The results demonstrate that the proposed method of locating ROI is effective and the designed features of density and atypia can be used to predict glioma grade accurately, which can provide reliable basis for clinical diagnosis.
Brain Neoplasms/diagnostic imaging*
;
Glioma/diagnostic imaging*
;
Humans
;
Magnetic Resonance Imaging
;
Neoplasm Grading
;
Support Vector Machine
10.Comparison of continuous negative pressure wound therapy and conventional packing and pressure bandage in medium thick skin transplantation of difficult to fix wounds
Fengsong XIE ; Chaoyang LYU ; Chuanliang CHEN ; Lei DENG ; Cheng HUANG ; Fan JIANG
Journal of Chinese Physician 2021;23(11):1686-1689
Objective:To compare the application of continuous negative pressure wound therapy and conventional packing and pressure bandage in medium thick skin transplantation of difficult to fix wounds.Methods:96 patients who underwent medium thick skin transplantation of difficult to fix wounds in Suizhou Hospital Affiliated to Hubei Medical College from March 2019 to March 2020 were divided into two groups according to whether the patients were treated with continuous negative pressure wound therapy. 48 patients in the control group were treated with conventional packaging and pressure bandage, and 48 patients in the observation group were treated with continuous negative pressure wound therapy. The levels of white blood cell (WBC), C-reactive protein (CRP), skin graft survival area, skin graft survival ratio, skin hematoma ratio, length of hospital stay and incidence of complications were compared between the two groups.Results:The levels of WBC and CRP in the two groups at 7 and 14 days after treatment were significantly lower than those before treatment ( P<0.05); The levels of WBC and CRP in the observation group were significantly lower than those in the control group at 7 and 14 days after treatment ( P<0.05); The survival area and survival ratio of skin graft in the observation group were significantly higher than those in the control group ( P<0.05); The area and ratio of skin hematoma in the observation group were significantly lower than those in the control group ( P<0.05); The hospital stay in the observation group was significantly shorter than that in the control group ( t=10.472, P=0.001); The incidence of skin graft complications in the observation group was significantly lower than that in the control group (2.08% vs 12.50%) (χ 2=10.174, P=0.015). Conclusions:Continuous negative pressure wound in medium thickness skin transplantation of difficult to fix wound has obvious advantages in improving the survival area of skin graft, reducing skin graft complications and shortening hospital stay, which is worthy of clinical recommendation.

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