1.Research status of the correlation between ferroptosis and renal fibrosis
Li-Juan LIANG ; En-Lai DAI ; Jun-Yuan BAI ; Can LIU ; Zhao-Ran DING ; Jie ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(15):2278-2282
Renal fibrosis is a common pathological manifestation of all chronic kidney diseases.Ferroptosis is closely related to the pathogenesis of renal fibrosis and can influence the onset of renal fibrosis,and it is the most critical step in the development of renal fibrosis.The paper describes the relationship between ferroptosis and renal fibrosis,discusses the research progress of ferroptosis on renal fibrosis,and further summarizes,analyzes,and describes the effective and highly targeted natural active ingredients of traditional Chinese medicines against ferroptosis,and concludes that the reversal of renal fibrosis is achieved through the regulation of the key targets of ferroptosis,with a view to providing a broad new direction for its prospects in the field of renal fibrotic disease prevention and treatment;and to provide a scientific guide for clinical treatment and basis for clinical treatment.
2.Multidimensional supportive psychological intervention in clinical practice teaching of andrological nursing
Li-Hong LI ; Ya-Ting SUN ; De-Yu KONG ; Shan-Na SU ; Xue ZHANG ; Liang ZHANG ; Hong-En XIANG ; Xuan LUO ; Xu-Qiang WANG
National Journal of Andrology 2024;30(3):229-232
Objective:To examine the application of a novel pedagogical approach multidimensional supportive psychological intervention(MSPI)in the clinical practice teaching of andrological nursing care.Methods:Using the Hamilton Depression Scale(HAMD),we assessed the psychology of 100 nursing interns about to enter clinical practice in the Department of Andrology from De-cember 2021 to December 2022.We equally randomized the subjects into an experimental and a control group,the former receiving MSPI and the latter trained on the conventional teaching model without any psychological support intervention.Results:Compared with the baseline,the HAMD scores were significantly decreased in the experimental group after intervention(12.4±2.1 vs 8.9±2.4,P<0.01),but increased in the controls(13.1±1.8 vs 14.7±1.9,P<0.01);the skill scores dramatically increased in the experimental group(82.6±4.7 vs 91.2±2.4,P<0.01),but decreased in the control group after intervention(81.0±3.5 vs 80.4±2.7,P=0.28).Conclusion:MSPI can significantly enhance the learning enthusiasm of nursing students in a short period,re-duce their psychological stress and improve teaching outcomes.This approach,combining psychology with teaching,can also strength-en the mental resilience of nursing students and better confront them with future professional challenges.
3.Serum lipoprotein-associated phospholipase A2 level is positively correlated with the recurrence risk of acute ischemic cerebral infarction in hypertensive patients.
Li Bing LIANG ; Jing Juan CHEN ; Cheng Guo ZHANG ; Yu Kai WANG ; Bai Gui LUO ; Tian En ZHOU ; Xiao Feng WANG
Journal of Southern Medical University 2023;43(2):317-322
OBJECTIVE:
To explore the relationship between serum lipoprotein-associated phospholipase A2 (Lp-PLA2) level and the risk of acute ischemic stroke (AIS) recurrence in hypertensive patients.
METHODS:
This retrospective case-control study was conducted among 211 hypertensive patients with AIS treated in Foshan First People's Hospital, including 35 patients with recurrence of AIS during the 1-year follow-up as confirmed by head CT/MR. In the overall patients, 60 had grade 1 hypertension (including 5 recurrent cases), 76 had grade 2 hypertension (with 11 recurrent cases), and 75 had grade 3 hypertension (with 19 recurrent cases). Univariate analysis, multivariate logistic regression analysis, trend analysis, and smooth curve fitting analysis were performed to explore the correlation between serum Lp-PLA2 level within 24 h after admission and the risk of AIS recurrence. The predictive efficacy of serum Lp-PLA2 level for AIS recurrence in different hypertension grades was evaluated using ROC curve analysis.
RESULTS:
Serum Lp-PLA2 level, age, NIHSS score at admission, mRS scores at 7 days, homocysteine level and smoking status differed significantly between patients with and without AIS recurrence (P < 0.05). After adjustment for confounding factors, multivariate regression analysis showed that the highest tertile of Lp-PLA2 level was associated with a 4.13-fold increase of AIS recurrence risk compared with the lowest tertile (OR=5.13, 95% CI: 1.35-19.40), and each 1 ng/mL increase of Lp-PLA2 level was associated with a 1% increase of AIS recurrence risk (OR= 1.01, 95% CI: 1.01-1.02). Serum Lp-PLA2 level was shown to positively correlate with AIS recurrence risk, and in patients with grade 3 hypertension, its areas under the ROC curve for predicting AIS recurrence was 0.869 with a specificity of 0.893 and a sensitivity of 0.737.
CONCLUSION
Serum Lp-PLA2 concentration is an independent risk factor and potentially an effective predictor for AIS recurrence in patients with grade 3 hypertension.
Humans
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Infant, Newborn
;
1-Alkyl-2-acetylglycerophosphocholine Esterase
;
Acute Disease
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Biomarkers
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Brain Ischemia/etiology*
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Case-Control Studies
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Cerebral Infarction
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Hypertension/complications*
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Ischemic Stroke/complications*
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Retrospective Studies
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Risk Factors
;
Stroke
4.Activation of TGR5 Attenuates Renal Fibrosis after Renal Ischemia Reperfusion Injury
Meng LI ; Luo-sha LONG ; Bai-en LIANG ; Long XU ; Xiao-duo ZHAO ; Wei-dong WANG ; Chun-ling LI
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(4):617-624
ObjectiveTo investigate the role of bile acid receptor TGR5 activation in renal fibrosis induced by unilateral ischemia reperfusion injury and contralateral nephrectomy (uIRIx) model. MethodsIn vivo: C57BL/6J mice were randomly divided into Sham group, uIRIx group and uIRIx+ lithcholic acid (LCA) group with 6 mice in each group. Kidney fibrosis was induced by uIRIx model, kidney function was evaluated by blood and urine biochemical indexes, and the degree of kidney injury was evaluated by HE staining. Masson staining and immunohistochemistry were used to evaluate the degree of renal fibrosis, and Western Blotting was used to detect the expression of related index proteins of renal cortical fibrosis. Sham group and uIRIx group were set in TGR5+/+ mice and TGR5-/- mice respectively, with 6 mice in each group. The degree of renal fibrosis in each group was detected by Western Blotting. In vitro: TGF-β1 was administered to induce pro-fibrosis response in human renal tubular epithelial cell line (HK2 cells), LCA was used for drug intervention, cytoskeleton was labeled with phalloidin-FITC staining and the expression of fibrosis related indicator protein in HK2 cells was detected by Western Blotting. ResultsIn vivo: Compared with the Sham group, plasma creatinine level (P=0.007) and urinary albumin/creatinine ratio (P=0.041) in uIRIx group were significantly increased, renal cortical protein TGR5 expression (P=0.002) was decreased, Fibronectin expression (P=0.020) and COL1A1 expression (P<0.001) were increased. At the same time, the kidney structure was damaged and collagen deposition was aggravated. LCA intervention effectively improved the kidney function and alleviated the degree of kidney injury and fibrosis. TGR5 gene knockout increased uIRIx-induced Fibronectin expression (P<0.001) and COL1A1 expression (P=0.001) compared with TGR5+/+ mice. In vitro: TGF-β1 induced morphological changes of HK2 cells, cytoskeletal depolymerization and recombination, and promoted the up-regulation of fibrosis index protein. LCA effectively inhibited the morphological changes and skeletal depolymerization induced by TGF-β1, and down-regulated the expression of fibrosis related indicator proteins. ConclusionsLCA alleviated renal fibrosis induced by uIRIx model, and knockout of TGR5 gene aggravated uIRIx induced renal fibrosis; In HK2 cells, LCA alleviated fibrogenic reaction induced by TGF-β1. This indicates that activation of TGR5 alleviates renal fibrosis induced by uIRIx.
5. Effects of lentinan on dendritic cell metabolism
Li LIU ; Bao-Chen ZHANG ; Xiu-Yun LI ; En-Hui WU ; Zhong-Feng SHI ; Xiang-Liang DENG ; Xiang-Liang DENG
Chinese Pharmacological Bulletin 2023;39(5):932-938
Aim To study the effects of lentinan(LNT)on the metabolism of dendritic cells(DCs)by metabonomics, and uncover the potential mechanism of its regulation of DC function. Methods DC2.4 cells were co-incubated with LNT for 24 h, and the activity of the cells was detected by thiazolyl blue tetrazolium bromide(MTT)assay. The contents of interleukin-6(IL-6), tumor necrosis factorα(TNF-α)and interleukin-12(IL-12)in supernatant were detected by enzyme-linked immunosorbent assay(ELISA). The metabolic general changes of DC2.4 cells were detected by Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS), and the differential metabolites were analyzed by multi-distance covariates and bioinformatics, partial least squares-discriminant analysis(PLS-DA). Finally, metabolic pathway analysis was performed by MetaboAnalyst 5.0. Results LNT did not significantly inhibit the activity of DC2.4 cells at the dose of 25100 mg·L-1. LNT(100 mg·L-1)could significantly stimulate the secretion of IL-6, TNF-α and IL-12 in DC2.4 cells. 20 differential metabolites were identified in DC2.4 cells after being stimulated by LNT(100 mg·L-1), which involved 25 metabolic pathways including urea cycle, arginine and proline metabolism. Conclusion The regulation of LNT on DC function involves a variety of amino acid metabolism.
6.Phosphodiesterase 5 Inhibitors Attenuate Unilateral Ureteral Obstruction-Induced Renal Fibrosis
Qing-xian ZHAI ; Meng LI ; Luo-sha LONG ; Bai-en LIANG ; Wei-dong WANG
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(6):931-942
ObjectiveTo investigate whether phosphodiesterase (PDE) 5 inhibitors sildenafil (SIL) or LW1646 prevented renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). MethodsMale C57BL/6 mice were randomly divided into four groups (n =6), namely the Sham group, 7UUO group, 7UUO+SIL group and 7UUO+LW1646 group. Sildenafil (SIL) or LW1646, or vehicle was administered 1 hour before surgery, and the mice were continuously treated once daily (i. g., 50 mg/kg) for 7 days. The obstructed kidneys were harvested on day 7. Hematoxylin-eosin (HE) and Masson’s staining was used to examine renal histology. Immunoblotting and RT-qPCR were used to detect the expression levels of protein and mRNA for fibrosis, apoptosis, endoplasmic reticulum (ER) stress, autophagy, and pro-fibrotic factors. Human proximal tubule epithelial cells (HK-2) were treated with TGF-β1 for 48 hours or tunicamycin for 24 hours, respectively, to evaluate whether cyclic guanosine monophosphate (cGMP) or PDE5 inhibitors prevents ER stress and pro-fibrotic responses. ResultsAt the 7th days after UUO, the body weight of the mice showed a significant decrease (P< 0.000 1) compared with that in the sham group. The obstructed kidneys showed a significant tubular dilation and interstitial inflammation. The levels of protein and mRNA expression in apoptosis, ER stress, autophagy-related protein and pro-fibrotic factors were also markedly increased in UUO mice (P <0.05). In contrast, SIL or LW1646 treatment was associated with attenuated tubular dilation, infiltration of inflammatory cells and collagen content in the obstructed kidney of the mice. The protein and mRNA expression levels of renal TGF-β1 were markedly decreased, and the protein expression levels of apoptosis, endoplasmic reticulum stress, and autophagy markers were also significantly downregulated by PDE5 inhibitors. In HK-2 cells, TGF-β1 induced increased expression levels of fibronectin and BiP, which was at least partially reversed by cGMP, a product of PDE inhibition. Additionally, PDE5 inhibitors were found to modulate aberrant levels of autophagy and apoptosis. ConclusionIn conclusion, PDE5 inhibitors, in particular, LW1646, can alleviate the progression of fibrosis by improving ER stress, apoptosis and autophagy as well as downregulating protein and mRNA expression of TGF-β1.
7.Preparation of 3D printed metoprolol tartrate chewable tablets and optimization of printing process
Shan-shan WANG ; Xiao-lu HAN ; En LIANG ; Cong-hui LI ; Chun-yan LIU ; Ming-yuan LI ; Zeng-ming WANG ; Peng YU ; Ai-ping ZHENG
Acta Pharmaceutica Sinica 2023;58(9):2811-2817
With the growing demand of personalized medicine for children, it is especially important to develop medicines for children. In this study, using metoprolol tartrate as model drug, we developed 3D printed chewable tablets suitable for children with automated dosage distribution using semi-solid extruded (SSE) 3D printing technology. Based on the quality by design concept, this study prepared a semi-solid material with good printability using gelatin as the substrate, constructed 3D models and printed tablets with the aid of computer-aided design. The printing parameters were optimized and determined as follows: print temperature of 35-37 ℃, print speed of 25 mm·s-1, fill rate of 15%, and number of outer profile layers of 2. Subsequently, the printing process and the quality uniformity of the tablets were verified, and a linear relationship between the dose and the number of model layers was obtained. Finally, 3D printed chewable tablets were superior in terms of appearance, dose accuracy and compliance compared with traditional split-dose commercially available tablets. In this study, 3D printed metoprolol tartrate chewable tablets with good performance were successfully prepared to address the personalized medication needs of pediatric patients.
8.Captopril related kidney damage: renal afferent arteriolar responses to angiotensin II and inflammatory signaling.
Su-Han ZHOU ; Qian HUANG ; Ying ZHOU ; Xiao-Xia CAI ; Yu CUI ; Qin ZHOU ; Jie GUO ; Shan JIANG ; Nan XU ; Jiang-Hua CHEN ; Ling-Li LI ; En-Yin LAI ; Liang ZHAO
Acta Physiologica Sinica 2022;74(1):125-133
Captopril can have nephrotoxic effects, which are largely attributed to accumulated renin and "escaped" angiotensin II (Ang II). Here we test whether angiotensin converting enzyme-1 (ACE1) inhibition damages kidneys via alteration of renal afferent arteriolar responses to Ang II and inflammatory signaling. C57Bl/6 mice were given vehicle or captopril (60 mg/kg per day) for four weeks. Hypertension was obtained by minipump supplying Ang II (400 ng/kg per min) during the second 2 weeks. We assessed kidney histology by periodic acid-Schiff (PAS) and Masson staining, glomerular filtration rate (GFR) by FITC-labeled inulin clearance, and responses to Ang II assessed in afferent arterioles in vitro. Moreover, arteriolar H2O2 and catalase, plasma renin were assayed by commercial kits, and mRNAs of renin receptor, transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) in the renal cortex, mRNAs of angiotensin receptor-1 (AT1R) and AT2R in the preglomerular arterioles were detected by RT-qPCR. The results showed that, compared to vehicle, mice given captopril showed lowered blood pressure, reduced GFR, increased plasma renin, renal interstitial fibrosis and tubular epithelial vacuolar degeneration, increased expression of mRNAs of renal TGF-β and COX-2, decreased production of H2O2 and increased catalase activity in preglomerular arterioles and enhanced afferent arteriolar Ang II contractions. The latter were blunted by incubation with H2O2. The mRNAs of renal microvascular AT1R and AT2R remained unaffected by captopril. Ang II-infused mice showed increased blood pressure and reduced afferent arteriolar Ang II responses. Administration of captopril to the Ang II-infused mice normalized blood pressure, but not arteriolar Ang II responses. We conclude that inhibition of ACE1 enhances renal microvascular reactivity to Ang II and may enhance important inflammatory pathways.
Angiotensin II/pharmacology*
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Animals
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Arterioles/metabolism*
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Captopril/pharmacology*
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Hydrogen Peroxide/pharmacology*
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Kidney
;
Mice
9.Application and clinical efficacy of ultrasound debridement method in residual burn wounds.
Ze Liang HE ; Jin LI ; Zhen Yang SUI ; Ju Lei ZHANG ; Liang En AN ; Ling Ling LIU ; Cheng Liang ZHANG ; Yuan Yuan YAO ; Shu Lin QIU ; Xiao Dong LI
Chinese Journal of Burns 2022;38(11):1034-1039
Objective: To investigate the application and clinical efficacy of ultrasound debridement method in residual burn wounds. Methods: A retrospective cohort study was conducted. From August 2017 to August 2021, 64 patients with residual burn wounds who met the inclusion criteria were admitted to the 980th Hospital of the Joint Logistic Support Force of PLA. According to the debridement method adopted for the residual wounds, the patients were divided into ultrasound debridement group (34 cases, 22 males and 12 females, aged (31±13) years) and traditional debridement group (30 cases, 19 males and 11 females, aged (32±13) years). After the corresponding debridement, the wounds of patients in the two groups were selected for stamp skin grafting or large skin grafting according to the wound site and skin donor status. For unhealed wounds after stage Ⅰ surgery, secondary debridement and skin grafting were be performed, with the wound debridement methods in the 2 groups being the same as those of stage Ⅰ, respectively. On postoperative day 3, drug-sensitive test was used to detect the bacteria in the wound and the positive rate of bacteria was calculate. On postoperative day 7, the survival rate of skin slices in wound and the incidence of subcutaneous hematoma were calculated. At discharge, wound healing time and debridement times of patients were counted, and the secondary debridement rate was calculated. Data were statistically analyzed with independent sample t test or chi-square test. Results: On postoperative day 3, the wounds in ultrasound debridement group were infected with Staphylococcus aureus in 2 cases and Pseudomonas aeruginosa in 2 cases, and the wounds in traditional debridement group were infected with Staphylococcus aureus in 5 cases, Pseudomonas aeruginosa in 3 cases, Acinetobacter baumannii in 1 cases, Klebsiella pneumoniae in 1 cases, and Enterobacter cloacae in 1 cases. The positive rate of bacteria of wound in ultrasound debridement group was significantly lower than that in traditional debridement group (χ2=5.51, P<0.05). On postoperative day 7, the survival rate of skin grafts in ultrasound debridement group was (92±5) %, which was significantly higher than (84±10) % in traditional debridement group (χ2=6.78, P<0.01); the incidence of subcutaneous hematoma in ultrasound debridement group was 17.6% (6/34), which was significantly lower than 40.0%( 12/30) in traditional debridement group, χ2=3.94, P<0.05. At discharge, the wound healing time in ultrasound debridement group was (11.0±2.0) d, which was significantly shorter than (13.0±3.1) d in traditional debridement group (t=3.81, P<0.01); the secondary debridement rate of wounds in ultrasound debridement group was 2.9% (1/34), which was significantly lower than 20.0% (6/30) in traditional debridement group (χ2=4.76, P<0.05). Conclusions: Ultrasound debridement method can significantly reduce the bacterial load of residual burn wounds, reduce postoperative hematoma formation, and promote the survival of skin grafts to shorten the course of disease of patients.
Male
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Female
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Humans
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Debridement/methods*
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Retrospective Studies
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Treatment Outcome
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Bacteria
;
Burns/microbiology*
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Hematoma
10.Visualization and application method of acupuncture-moxibustion knowledge of senile dementia in ancient books based on partial order structure.
En-Liang YAN ; Li-Ming LU ; Chun-Zhi TANG
Chinese Acupuncture & Moxibustion 2022;42(12):1421-1426
Acupuncture-moxibustion has affirmative curative effect in the prevention and treatment of senile dementia. Starting from the literature research, a visualization and application method of acupuncture-moxibustion knowledge of senile dementia in ancient books based on partial order structure is proposed. This method could extract and integrate the acupuncture-moxibustion knowledge of senile dementia contained in ancient books of traditional Chinese medicine, and establish a standardized, structured and visual knowledge graph. Applying this method to knowledge visual analysis and clinical auxiliary guidance could provide reference for combing the knowledge of ancient books of traditional Chinese medicine and transforming the knowledge of ancient books into clinical application.
Humans
;
Alzheimer Disease
;
Medicine, Chinese Traditional

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