1.Exploration of Traditional Chinese and Western Medicine in Prevention and Treatment of DKD Based on Mitochondrial Autophagy Mediated by PINK1/Parkin Signaling Pathway: A Review
Runsheng LIU ; Xiaodong ZHANG ; Zhaoqing LI ; Jing WANG ; Jinglu ZHANG ; Lixia JIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):302-313
Diabetic kidney disease (DKD) is one of the more common chronic kidney diseases,and its causes are complex. DKD is very easy to progress to end-stage renal disease,and the current therapeutic effect still needs to be improved. As an important excretive organ of the human body, the kidney has physiological functions such as discharging metabolic waste, regulating fluid balance, and maintaining the stability of the body's internal environment. These highly complex biochemical processes all depend on the energy support provided by mitochondria. Mitochondrial dysfunction is a key factor causing kidney injury, and the imbalance of mitochondrial homeostasis is an important link leading to mitochondrial dysfunction. The occurrence and development of DKD are often accompanied by the imbalance of mitochondrial homeostasis in renal cells. Mitochondrial autophagy, as a means of regulating mitochondrial homeostasis, is very important for the prevention and treatment of DKD. The PTEN-induced putative kinase 1 (PINK1)/Parkin pathway is one of the most classical pathways to regulate mitochondrial autophagy. Recent studies have found that some drugs can regulate the PINK1/Parkin signaling pathway to target mitochondrial homeostasis and exert renoprotective effects. In particular, traditional Chinese medicine has a significant effect on early and middle stage DKD by regulating PINK1/Parkin pathway-mediated mitochondrial autophagy. This article discussed the mechanism of PINK1/Parkin pathway in mitochondrial autophagy and DKD and reviewed the effect of PINK1/Parkin pathway-mediated mitochondrial autophagy on DKD. At the same time, it explored the therapeutic effect of traditional Chinese and western medicine on DKD mediated by PINK1/Parkin-mediated mitochondrial autophagy, aiming to broaden the ideas of traditional Chinese and western medicine for the prevention and treatment of DKD from the perspective of PINK1/Parkin regulating mitochondrial autophagy.
2.Exploration of Traditional Chinese and Western Medicine in Prevention and Treatment of DKD Based on Mitochondrial Autophagy Mediated by PINK1/Parkin Signaling Pathway: A Review
Runsheng LIU ; Xiaodong ZHANG ; Zhaoqing LI ; Jing WANG ; Jinglu ZHANG ; Lixia JIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):302-313
Diabetic kidney disease (DKD) is one of the more common chronic kidney diseases,and its causes are complex. DKD is very easy to progress to end-stage renal disease,and the current therapeutic effect still needs to be improved. As an important excretive organ of the human body, the kidney has physiological functions such as discharging metabolic waste, regulating fluid balance, and maintaining the stability of the body's internal environment. These highly complex biochemical processes all depend on the energy support provided by mitochondria. Mitochondrial dysfunction is a key factor causing kidney injury, and the imbalance of mitochondrial homeostasis is an important link leading to mitochondrial dysfunction. The occurrence and development of DKD are often accompanied by the imbalance of mitochondrial homeostasis in renal cells. Mitochondrial autophagy, as a means of regulating mitochondrial homeostasis, is very important for the prevention and treatment of DKD. The PTEN-induced putative kinase 1 (PINK1)/Parkin pathway is one of the most classical pathways to regulate mitochondrial autophagy. Recent studies have found that some drugs can regulate the PINK1/Parkin signaling pathway to target mitochondrial homeostasis and exert renoprotective effects. In particular, traditional Chinese medicine has a significant effect on early and middle stage DKD by regulating PINK1/Parkin pathway-mediated mitochondrial autophagy. This article discussed the mechanism of PINK1/Parkin pathway in mitochondrial autophagy and DKD and reviewed the effect of PINK1/Parkin pathway-mediated mitochondrial autophagy on DKD. At the same time, it explored the therapeutic effect of traditional Chinese and western medicine on DKD mediated by PINK1/Parkin-mediated mitochondrial autophagy, aiming to broaden the ideas of traditional Chinese and western medicine for the prevention and treatment of DKD from the perspective of PINK1/Parkin regulating mitochondrial autophagy.
3.Differential expression and molecular genetic characteristics of CD36 antigen in platelet donor database in Shaanxi province, China
Tianju WANG ; Jun QI ; Manni WANG ; Yuhui LI ; Lixia SHANG ; Le CHEN ; Xiaofang WANG
Chinese Journal of Blood Transfusion 2025;38(5):621-628
Objective: To screen the frequency of CD36 antigen expression in platelet donor database in Shaanxi province and analyze the molecular genetic characteristics of samples with CD36 antigen deficiency and low expression. Methods: A total of 525 platelet donors samples were randomly collected during May 2023. CD36-FITC monoclonal antibody was used for immunofluorescence labeling, and flow cytometry was applied to detect the expression of CD36 antigen on platelets. For samples with CD36 antigen deficiency on platelets, the expression of CD36 on monocytes was further detected. Samples with CD36 antigen deficiency and low expression were sequenced and analyzed. Results: Among the 525 blood samples, 99.24% (521/525) showed positive expression of CD36 antigen. There were differences in the expression intensity of CD36 antigen, with low expression accounting for 3.43% (18/525) and CD36 antigen deficiency accounting for 0.76% (4/525), all of which were type Ⅱ deficiency. The exon mutation frequency of CD36 type Ⅱ deficiency and low expression samples was 31.82% (7/22), and the exon mutation types were 121-1_126delGCAAGTT, 329-330delAC, 1142T>G, 1204-1246dupl 43bp, 1221G>A, and 1228-1239delATTGTGCCTATT. All four cases of CD36 type Ⅱ deficiency had a 121-6 T>C mutation in intron 3. All CD36 low expression samples had a mutation of 282-10A>G, and 121-6T>C mutation rate was 61.1%(11/18). Conclusion: There were differences in the expression of CD36 antigen in the platelet donor database in Shaanxi province, which may be caused by multiple molecular genetic variations. The frequency of CD36 antigen deficiency in Shaanxi was lower than that of Han, Zhuang and Yao populations in southern China. This study provides references for solving the CD36 antibody mediated transfusion reaction and auxiliary treatment of diseases caused by CD36 antigen deficiency in the future. It also provides a basis for investigating the molecular mechanisms of CD36 deficiency and low expression.
4.Cost-utility analysis of tislelizumab in the treatment of locally advanced or metastatic (non-)squamous NSCLC
Chunyan WANG ; Jing WU ; Lixia SHEN
China Pharmacy 2025;36(11):1370-1374
OBJECTIVE From the perspective of China’s healthcare system, to evaluate the cost-effectiveness of tislelizumab in patients with locally advanced or metastatic squamous or non-squamous non-small cell lung cancer (NSCLC) whose disease progresses or is intolerable after receiving platinum-containing dual chemotherapy in the past. METHODS Rationale-303 research data were used to construct a partitioned survival model. The model period was set to be 21 days and simulated to 120 months. Using quality-adjusted life year (QALY) as a health output index, the incremental cost-effectiveness ratio (ICER) was calculated by discounting cost and health output with a discount rate of 5%. Single-factor sensitivity analysis and probability sensitivity analysis were performed to verify the robustness of the basic analysis results. RESULTS Cost-utility analysis results showed that the ICER of tislelizumab group was 65 653.52 yuan/QALY, compared with docetaxel group. This means that the regimen of tislelizumab was more cost-effective than the docetaxel regimen when the willingness-to-pay threshold (WTP) was 3 times China’s gross domestic product (GDP) per capita in 2023 (268 200 yuan/QALY). The results of single-factor sensitivity analysis showed that the three parameters that had a greater impact on ICER were the prices of tislelizumab, docetaxel and pemetrexed. The results of the probabilistic sensitivity analysis showed that the probabilities of the above two treatment regimens being cost-effective were both 50% when the WTP threshold was approximately 65 000 yuan/QALY. The probability of tislelizumab regimen being cost- effective was 100% when the WTP threshold was ≥134 000 yuan/QALY. CONCLUSIONS From the perspective of China’s healthcare system, when taking 3 times China’s GDP per capita in 2023 as the WTP threshold, tislelizumab is cost-effective for patients with locally advanced or metastatic squamous or non-squamous NSCLC after receiving platinum-containing dual chemotherapy in the past, compared with docetaxel.
5.Clinical observation of Xiaoyin capsules combined with secukinumab in the treatment of moderate to severe plaque psoriasis
Quan GAN ; Beibei WANG ; Beibei SU ; Lixia WANG
China Pharmacy 2025;36(19):2428-2432
OBJECTIVE To evaluate the clinical efficacy and safety of Xiaoyin capsules combined with secukinumab in the treatment of moderate to severe plaque psoriasis. METHODS A retrospective study was conducted on 105 patients with moderate to severe plaque psoriasis who received treatment in the Dept. of Dermatology of Xinxiang Central Hospital from January 2021 to June 2024. According to the treatment plan, they were divided into conventional group(n=32), monoclonal antibody group(n=45), and combination group(n=28). The conventional group was given Calcipotriol ointment+Fluticasone propionate cream+Acitretin capsules; the monoclonal antibody group was treated with secukinumab injection in addition to the treatment of the conventional group; the combination group received oral administration of Xiaoyin capsules in addition to the treatment of the monoclonal antibody group. All patients received at least 12 weeks of treatment. The psoriasis area and severity index(PASI) score, PASI improvement rate, dermatology life quality index(DLQI) score, physician’s global assessment(PGA) score, patient’s global assessment(PtGA) score before and after treatment, and the incidence of adverse reactions during treatment were compared among the three groups. RESULTS Before treatment, there was no statistically significant difference in the above scores among the three groups(P>0.05). After treatment, the scores of all three groups of patients significantly decreased compared to before treatment (P<0.05); the total PASI score and erythema, scales, affected body surface area score, the total DLQI score and symptom perception, daily activity, social score, the PGA and PtGA scores of the combination group were significantly lower than the other two groups(P<0.05); PASI 50(the proportion of patients whose PASI score decreased by ≥50% from baseline, and so on), PASI 75, and PASI 90 were significantly higher than the other two groups(P<0.05); the total PASI score, erythema, and affected body surface area score of patients in the monoclonal antibody group were significantly lower than the conventional group(P<0.05), and PASI 75 was significantly higher than the conventional group(P<0.05). There was no statistically significant difference in the total incidence of adverse reactions among the 3 groups(P=0.637). CONCLUSIONS The combination of Xiaoyin capsules and secukinumab can significantly improve the skin lesions and quality of life in patients with moderate to severe plaque psoriasis, with good tolerability in the short term and no significant increasein the risk of serious adverse reactions.
6.Role of mesenchymal stem cells and their exosomes in the treatment of drug-induced liver injury
Guojing XING ; Longlong LUO ; Lifei WANG ; Shunna WANG ; Xiaofeng ZHENG ; Lixia LU ; Jiucong ZHANG
Journal of Clinical Hepatology 2024;40(3):633-638
The incidence rate of drug-induced liver injury (DILI) is increasing year by year with unknown mechanisms, and the treatment methods for DILI mainly include drugs, liver support systems, and liver transplantation, all of which have certain limitations. Therefore, the search for safer and more effective treatment methods has become a research hotspot at present. Studies have shown that mesenchymal stem cells and their exosomes can alleviate liver injury by reducing liver inflammation, promoting hepatocyte proliferation and regeneration, inhibiting the apoptosis of hepatocytes, improving oxidative stress, and regulating immunity. This article briefly reviews the role of mesenchymal stem cells and their exosomes in the treatment of DILI, so as to provide a reference for further research.
7.Randomized, Open, Parallel Controlled, Multi-center Study for Efficacy and Safety of Lianhua Qingke Tablets in Treatment of Acute Bronchitis in Children with Syndrome of Phlegm-heat Obstructing Lung
Nan LI ; Shaoyi GENG ; Xiaofang WANG ; Xiaowei ZHANG ; Lixia JIA ; Rongzhen KANG ; Xiangjun DU ; Lichun WU ; Linlin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):90-94
ObjectiveTo evaluate the efficacy and safety of Lianhua Qingke tablets in the treatment of acute bronchitis in children with the syndrome of phlegm-heat obstructing lung. MethodA randomized, open, parallel controlled, and multi-center clinical study was conduted. Children with acute bronchitis (syndrome of phlegm-heat obstructing lung) were randomly assigned to an observation group and a control group. The control group received routine basic treatment, and the observation group was treated with Lianhua Qingke Tablets on the basis of routine basic treatment. After 7 days of treatment, the clinical efficacy, TCM efficacy, time to symptom disappearance, time to cough disappearance, and clinical safety were compared between the two groups. ResultA total of 248 children were included (124 in the observation group and 124 in the control group). After 7 days of treatment, the total response rate in terms of clinical efficacy in the observation group was 96.8% (120/124), which was higher than that (90.3%, 112/124) in the control group (Z=-5.034, P<0.01). The total response rate in terms of TCM syndrome in the observation group was 97.6% (121/124), which was higher than that (93.5%, 116/124) in the control group (χ2=-5.326, P<0.01). The scores of physical signs and TCM symptoms in the observation group were lower than those in the control group at the time of taking medicine for 3 days and 7 days (P<0.01). The time to symptom disappearance and the time to cough disappearance in the observation group were shorter than those in the control group (P<0.01). Drug-related adverse reactions occurred in neither group. ConclusionLianhua Qingke tablets demonstrate a definite effect on acute bronchitis in children with the syndrome of phlegm-heat blocking lung. The tablets can significantly shorten the course of disease and relieve cough and TCM symptoms, with high safety, which is worthy of clinical application and promotion.
8.Correlation between DKK1 promoter methylation level and diabetic microangiopathopathy complicated with osteoporosis
Jianguo HUANG ; Xiaohui WANG ; Jiangjie WANG ; Jia LIU ; Lei FENG ; Lixia SUN ; Fuyuan LI
Chinese Journal of Endocrine Surgery 2024;18(1):125-129
Objective:To investigate the correlation between the promoter methylation level of Dickkopf-related protein 1 (DKK1) gene and diabetic microangiopaopathy complicated with osteoporosis.Methods:Patients with type 2 diabetes mellitus (T2DM) microangiopathopathy who were admitted to our hospital from Jan. 2019 to Dec. 2022 were collected as research objects, and divided into observation group (44 cases) and control group (58 cases) according to whether they were complicated with osteoporosis. Bone mineral density (BMD) of lumbar spine (L1-4) was measured, and bone metabolism indexes, including serum calcium, serum phosphorus, 25-hydroxy vitamin D3[25-hydroxy vitamin D3, 25- (OH) D3], PTH, C-terminal telopeptide of typeI collagen (CTX), procollagen of aminoterminal propeptide (PINP) and tartrate resistant acid phosphatase (TRACP) levels were detected; The promoter methylation level of DKK1 gene was determined.Results:The methylation level of DKK1 gene promoter in the observation group was 5.17%±0.73%, which was significantly higher than that in the control group (3.81%±0.61%), with statistical significance ( t=5.22, P<0.001). The 25- (OH) D3 level, PTH and lumbar bone density in the observation group were significantly lower than those in the control group, while the CTX and TRACP levels were significantly higher than those in the control group ( t was 5.58, 4.35, 4.12, 4.05 and 4.17, respectively, P<0.001). In all patients, the promoter methylation level of DKK1 gene was significantly positively correlated with CTX and TRACP ( r was 0.41 and 0.39, P was 0.006 and 0.027, respectively), and significantly negatively correlated with PTH and lumbar bone density ( r was -0.38 and -0.43, respectively). P=0.015 and 0.003, respectively). ROC curve analysis showed that the area under the curve of DKK1 methylation level to distinguish type 2 diabetes microangionopathy with and without osteoporosis was 0.841 (0.762-0.921), and the sensitivity and specificity were 86.4% and 72.4%, respectively. Conclusion:The methylation level of DKK1 gene promoter is associated with osteoporosis and bone metabolism in T2DM patients with microangiopathia.
9.Longitudinal extrauterine growth restriction in extremely preterm infants: current status and prediction model
Xiaofang HUANG ; Qi FENG ; Shuaijun LI ; Xiuying TIAN ; Yong JI ; Ying ZHOU ; Bo TIAN ; Yuemei LI ; Wei GUO ; Shufen ZHAI ; Haiying HE ; Xia LIU ; Rongxiu ZHENG ; Shasha FAN ; Li MA ; Hongyun WANG ; Xiaoying WANG ; Shanyamei HUANG ; Jinyu LI ; Hua XIE ; Xiaoxiang LI ; Pingping ZHANG ; Hua MEI ; Yanju HU ; Ming YANG ; Lu CHEN ; Yajing LI ; Xiaohong GU ; Shengshun QUE ; Xiaoxian YAN ; Haijuan WANG ; Lixia SUN ; Liang ZHANG ; Jiuye GUO
Chinese Journal of Neonatology 2024;39(3):136-144
Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.
10.Effect and mechanism of protein kinase N1 on the proliferation of mouse cardiomyocytes
Zonglei ZHAO ; Songge CHEN ; Suofeng SUN ; Lixia WANG
Journal of Xinxiang Medical College 2024;41(3):204-208
Objective To explore the effect and mechanism of protein kinase N1(PKN1)on the proliferation of mouse cardiomyocytes.Methods Two 1-day-old mice were anesthetized with isoflurane,and their cardiomyocytes were isolated and divided into the control group and the interference group.The cardiomyocytes in the interference group were transfected with PKN1 fragments,while the cardiomyocytes in the control group were transfected with control fragments.According to the random number table method,10 mice were divided into the normal group and the observation group,with 5 mice in each group.The mice in the observation group were injected with PKN1 adenovirus in situ in the heart,while the mice in the normal group were injected with empty adenovirus in situ in the heart.The Ki-67 positive expression in myocardial cells and tissues of mice in the four groups was detected by immunofluorescence assay,indicating the proliferation ability of cardiomyocytes.The PKN1 mRNA expression in cardiomyocytes of mice in the control group and interference group was measured by real-time fluorescence quan-titative polymerase chain reaction.The expression of PKN1 and cyclin D1 proteins in cardiomyocytes of mice in the control group and interference group was determined by Western blot.Results The positive expression rates of Ki-67 in myocardial cells of mice in the interference group was significantly lower than that in the control group(t=11.201,P<0.01);the positive expression rate of Ki-67 in myocardial tissue of mice in the observation group was significantly lower than that in the normal group(t=11.851,P<0.01).The relative expression level of PKN1 mRNA in cardiomyocytes of mice in the interference group was significantly lower than that in the control group(t=7.022,P<0.01).The relative expression levels of PKN1 and cyclin D1 proteins in cardiomyocytes of mice in the interference group were significantly lower than those in the control group(t=5.762,6.884;P<0.01).Conclusion The decreased expression of PKN1 in mouse cardiomyocytes can inhibit the expression of cyclin D1 protein,thereby restraining cardiomyocyte proliferation.

Result Analysis
Print
Save
E-mail