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.Nursing care of a patient with gastric cancer who developed cytokine release syndrome after the use of immune checkpoint inhibitors
Huidi ZHU ; Meiyun ZHANG ; Yuehong JIANG ; Beiei LI ; Qiaoying XU
Chinese Journal of Nursing 2024;59(4):469-473
To summarize the nursing experience of a patient with gastric cancer who developed cytokine release syndrome after using immune checkpoint inhibitors.Key points of nursing care:development of nursing assessment decisions with a holistic view to guide safe nursing care;taking into account the contradiction between bleeding and thrombosis and providing good care for upper gastrointestinal bleeding;implementing a nursing strategy focusing on cleaning and anti-infection for IV oral mucositis;implementing risk management for severe pulmonary lesions;providing good hormone medication care and discharge follow-up management.The patient was successfully discharged on 52nd day with a 3-month follow-up in good condition.
3.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.
4.Establishment and application of an artificial intelligence-assisted platform for detection of parasite eggs
Huiyin ZHU ; Yuting LI ; Daiqian ZHU ; Yaqian WANG ; Jinhong ZHANG ; Shaoxuan CHEN ; Xiaoyuan MA ; Huidi WANG ; Hongjun LI ; Jian LI
Chinese Journal of Schistosomiasis Control 2024;36(6):643-648
Objective To establish an artificial intelligence (AI)-assisted platform for detection of parasite eggs, and to evaluate its detection efficiency and accuracy, so as to provide technical supports for elimination of parasitic diseases. Methods A total of 1 003 slides of Enterobius vermicularis, horkworm, Trichuris trichiura, Clonorchis sinensis, Taenia, Ascaris lumbricoides, Schistosoma japonicum, Paragonimus westermani and Fasciolopsis buski eggs were collected, and converted into digital images with an automatated scanning microscope to create a dataset. Based on the Object Detection platform on the Baidu Easy DL model, an AI-assisted platform for detection of parasite eggs was created through procedures of uploading, labeling, training, evaluation and optimization. Then, 70% of the datasets were randomly selected for model training, and the precision, recall and average accuracy were calculated to evaluate the effectiveness of platform for recognition of parasite eggs. In addition, the platform was deployed on the computer and smart phone terminals for use. Results An AI-assisted platform for detection of parasite eggs was successfully created. If the platform was deployed using the public cloud application programming interface (API), the average accuracy, precision and recall of the platform were 93.42%, 92.55% and 89.32% for recognition of parasite eggs. If the platform was deployed using the offline software development kit (SDK), the average accuracy, precision and recall of the platform were 92.97%, 94.78% and 87.63% for recognition of parasite eggs. In addition, the precision of the platform was 97.00% and 96.23% for identification of Taenia and C. sinensis eggs, respectively. Conclusions The AI-assisted platform for detection of parasite eggs has been successfully created, which is high in the accuracy for recognition of parasite eggs and convenient in use. This platform may provide a powerful technical support for parasitic disease diagnosis.
5.Effects of Jianpi Bushen Jiedu Prescription regulating JAK2/STAT3 pathway on proliferation and migration of hepatocellular carcinoma cells
Huidi LI ; Yuanyuan FENG ; Youying LAI ; Ru JIA ; Pingping ZHANG ; Xiaojun ZHU ; Hongjie LIU
International Journal of Traditional Chinese Medicine 2024;46(2):186-190
Objective:To explore the effects of Jianpi Bushen Jiedu Prescription on the proliferation and migration of hepatocellular carcinoma cells; To discuss its possible mechanism.Methods:Using human highly metastatic liver cancer cell line (HCCLM3) as the research object, they were randomly divided into control group and TCM group (100, 200, 400, 800, 1 600, 3 200 μg/ml Jianpi Bushen Jiedu Prescription) and Western medicine group (2.5, 5, 10, 20, 40 μmol/L sorafenib) using a random number table method. Cell viability was detected using cell counting reagent (CCK-8) method; HCCLM3 cells were divided into control group and TCM (Jianpi Bushen Jiedu Prescription 800 μg/ml) group and combined group (Jianpi Bushen Jiedu Prescription 800 μg/ml +sorafenib 20 μmol/L). Western blot method was used to detect the protein expressions of kinase/signaling transducer and transcriptional activator (JAK2/STAT3) pathway related proteins (p-JAK2, JAK2, p-STAT3, STAT3) in each group.Results:Compared with the control group, viability and mobility of HCCLM cell in TCM group and Western medicine group decreased ( P<0.01 or P<0.05); compared with the control group, the protein expressions of P-JAK2, JAK2, P-STAT3 and STAT3 in the TCM group and the combined group decreased ( P<0.05), and the JAK2 protein expression in the combined group was lower than that in the TCM group ( P<0.05). Conclusion:Jianpi Bushen Jiedu Prescription can inhibit the proliferation and migration of HCC cells by regulating JAK2/STAT3 pathway.
6.Nursing care after segmental small bowel resection in a patient with acute mesenteric vein embolism:a case report
Huidi ZHU ; Meiyun ZHANG ; Yuehong JIANG ; Qiaoying XU ; Yehong CHEN
Chinese Journal of Nursing 2024;59(14):1757-1760
To summarize the nursing experience of a patient with multiple enterostomies after segmental small bowel resection for acute mesenteric vein embolism.Nursing points:early identification of necrosis of retained intestinal tubes and improvement of early warning care;active improvement of tissue perfusion for retained indeterminate necrotic intestinal tubes;relay enteral nutritional support for 4 stomas based on the collaborative care model;implementation of combined dressing changes for surgical incisions and stomas,control of incisional infections and peristoma dermatitis;attention to the psychological aspects of the patients and their families and provision of psychological support.The patient successfully underwent stoma retraction on the 42nd day after surgery,and no obvious short bowel syndrome occurred in the postoperative period.
7.Nursing care of a patient with median arcuate ligament compression syndrome
Huidi ZHU ; Meiyun ZHANG ; Lili YAN ; Yuehong JIANG ; Qiaoying XU
Chinese Journal of Nursing 2024;59(15):1891-1895
To summarize the nursing experience of a patient with median arcuate ligament compression syndrome.Nursing points:to implement effective measures to relieve local compression and improve gastrointestinal symptoms;to establish a monitoring and evaluation plan focusing on abdominal pain to prevent serious adverse vascular events;to implement pre-rehabilitation care with psychological and nutritional support to reduce surgical risks;to actively provide postoperative gastroparesis care and discharge follow-up care.The patient was discharged from the hospital 22 days after surgery and was followed up for 6 months.His weight increased and his quality of life was high.
8.The significance of detecting human cytomegalovirus UL95 antigenic epitope peptide in the diagnosis of SLE
Ya HU ; Chenyu XU ; Wei QIANG ; Huidi ZHANG ; Fangfang FENG
Chinese Journal of Laboratory Medicine 2024;47(9):1042-1051
Objective:To explore the clinical significance of the dominant B-cell epitope peptide of the human cytomegalovirus (HCMV) UL95 gene, as well as the correlation between the plasma UL95 specific antibody levels and clinical indicators in systemic lupus erythematosus (SLE) patients, in order to find auxiliary diagnostic indicators for SLE.Methods:A non-randomized control study was conducted to analyze the sequencial characteristics and polymorphisms of HCMV UL95 gene, and bioinformatics analysis and chemical synthesis were used to synthesize UL95 dominant B cell epitope short peptides, which were used as coating antigens. Enzyme-linked immunosorbent assay (ELISA) assay was used to detect the specific antibody levels of plasma UL95 of 97 SLE patients and 35 healthy controls (HC). Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of UL95 short peptide antibodies for SLE diagnosis. Pearson correlation test was used to analyze the correlation between UL95 specific antibody levels and clinical indicators in SLE patients.Results:The nucleotide sequence similarity of UL95 gene was 92.9%-100%, and the amino acid sequence similarity was 92.1%-100%, whose sequences were highly conserved and homologous. A comprehensive prediction of multiple parameters resulted in 6 possible dominant B cell epitopes, named (Bp1, Bp2, Bp3, Bp4, Bp5, Bp6) respectively. The ELISA results showed that the levels of plasma UL95 specific antibodies (0.35±0.12) in SLE patients were significantly higher than those of the HC group (0.28±0.10)( t=3.091, P=0.002). The area under the ROC curve for distinguishing SLE and HC was 0.703, with a sensitivity of 54.6% and a specificity of 88.6%. In addition, the UL95 specifific antibody levels ( OD value) in the middle-high activity subgroup (systemic lupus erythematosus disease activity index, SLEDAI≥4) were higher (0.36±0.10) than those in the low activity subgroup (SLEDAI<4)(0.30±0.07) ( t=?2.055, P=0.044). UL95 specific antibody levels were positively correlated with clinical indicators such as total immunoglobulin G (IgG) and total immunoglobulin M (IgM), while negatively correlated with complement component 3 (C3), complement component 4 (C4), and platelet count. Conclusions:The antibody level of UL95 is closely related to the activity of lupus disease. The Bp1 (10-21) peptide segment of UL95 has important significance for the auxiliary diagnosis of SLE and is expected to become a new reference indicator.
9.Clinicopathological characteristics and prognostic correlation of stage Ⅰ pulmonary adenocarcinoma:analysis of 447 cases of invasive pulmonary adenocarcinoma by using WHO new grading system(2021)
Jue ZOU ; Qianqian ZHANG ; Lihua SHENG ; Huidi HU ; Yan DONG ; Xiaoyan JING
Chinese Journal of Clinical and Experimental Pathology 2023;39(11):1351-1355,1361
Purpose To investigate the clinicopathological characteristics and prognostic correlation of the WHO(2021)new grading system of invasive pulmonary adenocarcinoma in stageⅠ pulmonary adenocarcinoma.Methods The clinical data of 447 patients with stage Ⅰ pulmonary adenocarcinoma were collect-ed,and all cases were evaluated according to the new grading system for invasive pulmonary adenocarcinoma.The immunohis-tochemical EnVision two-step method and elastic fiber staining were used to analyze the clinicopathological features with review of the relevant literature.Results In 447 patients with stage Ⅰlung adenocarcinoma,Napsin A and TTF-1 expression were posi-tive,p40 expression was negative,and Ki-67 proliferation index was higher than 5%in 177 patients(39.6%).There were 39 cases(8.7%)of positive pleural invasion in the visceral layer revealed by elastic fiber staining.The pleural invasion in stage Ⅰpulmonary adenocarcinoma patients was significantly higher than that in grades 2 and 3,the difference was statistically significant(P<0.05).Patients with different grades of stage Ⅰ pulmonary adenocarcinoma were associated with gender,smoking history,surgical mode,chemotherapy,targeted medication,clinical stage,pathological classification,degree of differentiation,tumor size,vascular invasion,visceral pleural invasion,spread through air space(STAS)and Ki-67 index(P<0.05).Survival analy-sis showed that there were statistically significant differences in disease free survival(DFS)and overall survival(OS)among different grades(grade 1>grade 2>grade 3)(P<0.05).Cox regression analysis showed that WHO(2021)new grading of invasive pulmonary adenocarcinoma,visceral pleural invasion and Ki-67 proliferation index were independent risk factors for prognosis of patients with stage Ⅰ pulmonary adenocarcinoma.Conclusion The WHO(2021)new grading system of invasive pulmonary adenocarcinoma has good prognostic significance for stage Ⅰ pulmonary adenocarcinoma,and appropriate intervention for high-risk patients.It can effectively assist its postoperative treatment and has application value.
10.Study on Jianpi Bushen Jiedu Decoction for inhibiting epithelial-mesenchymal transformation of hepatocellular carcinoma through JAK2/STAT3 pathway
Pingping ZHANG ; Huidi LI ; Hongjie LIU ; Xiaojun ZHU
International Journal of Traditional Chinese Medicine 2023;45(5):581-585
Objective:To study the effects of Jianpi Bushen Jiedu Decoction on the epithelial-mesenchymal transformation of nude mice with HCCLM3 subcutaneous transplanted tumor by regulating JAK2/STAT3 pathway.Methods:HCCLM3 subcutaneous transplanted tumor model was established in mice. After the successful modeling, 24 nude mice were divided into blank group, TCM group and combined group according to random number table method, with 8 mice in each group. Mice in the TCM group were given 0.68 mg/ml alcohol extract of Jianpi Bushen Jiedu Decoction for gavage, and the combined group were given sorafenib suspension plus alcohol extract of Jianpi Bushen Jiedu Decoction 3.5 mg/ml for gavage, once a day, for consecutive 4 weeks. The effects of Jianpi Bushen Jiedu Decoction on tumor volume, tumor weight of HCCLM3 subcutaneous transplanted tumor and mice body weight were observed; Western blot was used to detect the expressions of E-cadherin, N-cadherin, Vimentin and JAK2/STAT3 pathway-related proteins in subcutaneous transplanted tumor tissues of hepatocellular carcinoma of mice in each group.Results:Compared with the control group, the average tumor weight of subcutaneous transplanted tumor decreased significantly in the TCM group and the combined group ( P<0.05), and the expressions of JAK2, STAT3, p-JAK2, p-STAT3, N-cadherin, and Vimentin decreased significantly in subcutaneous transplanted tumor tissue ( P<0.05), while E-cadherin increased ( P<0.05). Conclusion:Jianpi Bushen Jiedu Decoction can inhibit the growth of subcutaneous transplanted tumor of hepatocellular carcinoma in mice. The mechanism may be related to inhibiting the activation of JAK2/STAT3 pathway, thereby inhibiting the epithelial-mesenchymal transformation of hepatocellular carcinoma.

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