1.Prevention and Treatment of Asthma by Traditional Chinese Medicine Regulating PI3K/Akt Signaling Pathway: A Review
Yasheng DENG ; Yanping FAN ; Wenyue LI ; Yonghui LIU ; Zhaobing NI ; Jinjiang XU ; Haobin CHEN ; Qiuye WU ; Jiang LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):262-275
Asthma is a chronic inflammatory respiratory disease involving multiple cells and cellular components, characterized by recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing, significantly impacting patients' quality of life. The phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway, as a crucial hub in intracellular signaling, is widely involved in the regulation of cell growth, proliferation, survival, metabolism, and a series of pathophysiological processes. Its regulatory role in the pathological progression of asthma is particularly significant, specifically in promoting airway inflammation, mediating epithelial mesenchymal transition, accelerating airway remodeling, regulating cell autophagy, inducing mucus hypersecretion, and influencing immune response balance. This study analyzed potential molecular targets of the PI3K/Akt pathway, including activators such as cysteine proteinase inhibitor 1(CST1), found in inflammatory zone 1(FIZZ1) and free fatty acid receptor 1(FFAR1), and inhibitors such as human β-defensin-3(hBD-3), disintegrins, metalloproteinase 33(ADAM33) and interleukin-27(IL-27), and initially revealed the potential molecular mechanisms of traditional Chinese medicine(TCM) in asthma intervention. Based on this, the authors systematically summarized the efficacy and specific mechanisms of TCM monomers, compounds, and external treatments for asthma by regulating the PI3K/Akt signaling pathway through literature review and analysis, aiming at establishing a robust foundation for the wide application and advanced development of TCM in asthma treatment, offering innovative insights for clinical research and drug development of asthma.
2.Prevention and Treatment of Asthma by Traditional Chinese Medicine Regulating PI3K/Akt Signaling Pathway: A Review
Yasheng DENG ; Yanping FAN ; Wenyue LI ; Yonghui LIU ; Zhaobing NI ; Jinjiang XU ; Haobin CHEN ; Qiuye WU ; Jiang LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):262-275
Asthma is a chronic inflammatory respiratory disease involving multiple cells and cellular components, characterized by recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing, significantly impacting patients' quality of life. The phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway, as a crucial hub in intracellular signaling, is widely involved in the regulation of cell growth, proliferation, survival, metabolism, and a series of pathophysiological processes. Its regulatory role in the pathological progression of asthma is particularly significant, specifically in promoting airway inflammation, mediating epithelial mesenchymal transition, accelerating airway remodeling, regulating cell autophagy, inducing mucus hypersecretion, and influencing immune response balance. This study analyzed potential molecular targets of the PI3K/Akt pathway, including activators such as cysteine proteinase inhibitor 1(CST1), found in inflammatory zone 1(FIZZ1) and free fatty acid receptor 1(FFAR1), and inhibitors such as human β-defensin-3(hBD-3), disintegrins, metalloproteinase 33(ADAM33) and interleukin-27(IL-27), and initially revealed the potential molecular mechanisms of traditional Chinese medicine(TCM) in asthma intervention. Based on this, the authors systematically summarized the efficacy and specific mechanisms of TCM monomers, compounds, and external treatments for asthma by regulating the PI3K/Akt signaling pathway through literature review and analysis, aiming at establishing a robust foundation for the wide application and advanced development of TCM in asthma treatment, offering innovative insights for clinical research and drug development of asthma.
3.Effect and mechanism of embryonic intervention with Zuogui pill on the glucose tolerance in offsprings of pregnant rats with gestational diabetes mellitus
Min YANG ; Yujie WU ; Kainan SUN ; Yonghui WANG ; Chaoqun WANG ; Kaixia XU
China Pharmacy 2025;36(16):1981-1987
OBJECTIVE To explore the effect and mechanism of embryonic intervention with Zuogui pill on the glucose tolerance in offsprings of pregnant rats with gestational diabetes mellitus. METHODS Pregnant rats were randomly divided into blank group, model group, positive control group (insulin glargine), Zuogui pill low-, medium- and high-dose groups (4.725, 9.45, 18.9 g/kg). In addition to the blank group, streptozotocin was injected intraperitoneally to establish a gestational diabetes mellitus rat model. From day 6 to day 18 of pregnancy, each group was given relevant medicine and distilled water intragastrically, once a day. After 21 days of birth, the body weight and body length of offsprings were recorded, and the area under the curve (AUC) was calculated through a glucose tolerance test. After 22 days of birth, fasting blood glucose (FBG), fasting insulin (FINS) levels in serum, insulin sensitivity index (ISI), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured, and the morphological structure of pancreatic tissue was observed. The protein spectrum of pancreatic tissue was analyzed by tandem mass tag-based proteomics, and protein and mRNA expression levels of apolipoprotein A1(ApoA1), solute carrier family 27 member 1 (Slc27a1), kininogen 1(Kng1) and sodium/potassium-transporting ATPase subunit alpha 2 (Atp1a2), solute carrier family 7 member 5 (Slc7a5), solute carrier family 3 member 2 (Slc3a2), bile acid-coenzyme A: amino acid N- acyltransferase (Baat), eukaryotic translation initiation factor 2 subunit gamma (Eif2s3) were detected. RESULTS Compared with the model group, the body weight, body length and ISI of offsprings in the positive control group and Zuogui pill medium-dose group were significantly increased (P<0.05), while the glucose tolerance and islet cell proliferation were significantly improved, and the AUC, FBG, FINS and HOMA-IR were significantly decreased (P<0.05). There were 88 potential target proteins for the embryonic intervention of Zuogui pill in offsprings of pregnant rats with gestational diabetes mellitus,involving multiple pathways such as peroxisome proliferator-activated receptor (PPAR), cyclic guanosine monophosphate-protein kinase G (cGMP-PKG), fat digestion and absorption, and bile secretion. The proteins closely related to glucose metabolism and insulin resistance mainly included ApoA1, Slc27a1, Kng1, Atp1a2, Slc7a5, Slc3a2, Baat, and Eif2s3. Among them, compared with the model group, protein and mRNA expressions of Slc7a5, Slc3a2, and Baat in the pancreatic tissues of pregnant rat offsprings in the Zuogui pill medium-dose group were significantly up-regulated (P<0.05); protein and mRNA expressions of ApoA1, Slc27a1, Kng1, Atp1a2 and Eif2s3 were all significantly down-regulated (P<0.05). CONCLUSIONS The intervention of Zuogui pill in the embryonic period on offsprings of pregnant rats with gestational diabetes mellitus can improve their blood glucose levels and pancreatic pathological morphology. The mechanism may be related to the upregulation of the expressions of Slc7a5, Slc3a2, and Baat and the down-regulation of ApoA1, Slc27a1, Kng1, Atp1a2 and Eif2s3 expressions in the PPAR, cGMP-PKG, fat digestion and absorption, and bile secretion pathways.
4.Association between congenital hypothyroidism and in-hospital adverse outcomes in very low birth weight infants
Sha ZHU ; Jing XU ; Ranran SHI ; Xiaokang WANG ; Maomao SUN ; Shina LI ; Lingling GAO ; Yuanyuan LI ; Huimin WEN ; Changliang ZHAO ; Shuai LI ; Juan JI ; Cuihong YANG ; Yonghui YU
Chinese Journal of Pediatrics 2024;62(1):29-35
Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.
5.Trends and age-period-cohort analysis of leukemia incidence in Qidong from 1972 to 2021
Jian ZHU ; Yongsheng CHEN ; Jun WANG ; Yonghui ZHANG ; Lulu DING ; Yuanyou XU ; Yongfeng YAN ; Jianguo CHEN ; Hong CAI
Chinese Journal of Oncology 2024;46(10):961-967
Objective:To describe the epidemiological characteristics and trends of leukemia incidence in Qidong between 1972 and 2021, and provide guidelines for prevention and control measures and strategies.Methods:The cancer registry data was collected and analyzed on leukemia incidence during 1972—2021 in Qidong by sex, age and time. Crude incidence rate (CR), China age-standardized rate (ASRC), world age-standardized rate (ASRW), and average annual change percentage (AAPC) was calculated by Joinpoint software. Age-period-cohort (APC) model was used to analyze the influence of age, period and birth cohort on the changes in the incidence trend of leukemia patients.Results:From 1972 to 2021, there were 2 948 patients with leukemia in Qidong, accounting for 2.00% of all cancer new cases, CR of leukemia was 5.26/10 5, ASRC was 4.34/10 5, ASRW was 4.35/10 5. The truncated incidence of 35—64 years old was 5.29/10 5, the cumulative incidence rate between the ages of 0 and 74 years old was 0.40%, the cumulative risk was 0.40%. There were 1 608 male patients, the CR, ASRC, and the ASRW were 5.81/10 5, 4.88/10 5 and 4.85/10 5. The number of female patients were 1 340, and the CR, ASRC, and the ASRW were 4.71/10 5, 3.86/10 5 and 3.91/10 5, respectively. Temporal trends indicated significant upward trends in ASRC among both gender, males and females with AAPC values of 1.41% ( P<0.001), 1.15% ( P<0.001), and 1.73% ( P<0.001), respectively. The results of the APC model showed that the average net drift value of leukemia incidence in all age groups was 1.57% (95% CI, 1.24%-1.89%), and the highest value of local drift was 3.20% (95% CI, 1.63%-4.78%) in the 80~ years old group. The incidence of leukemia increased with age. With the passage of time, the risk of leukemia incidence increased gradually compared with the rate ratio of leukemia incidence (risk ratio [ RR], 1.00) in 1992—1996, the RR of leukemia incidence increased from 0.70 during 1972—1976 to 1.57 during 2017—2021. The later the cohort was born, the greater the risk of leukemia incidence compared with the relative risk of leukemia incidence ( RR, 1.00) in 1952—1956 cohort, the RR of leukemia incidence increased from 0.24 in the 1892—1896 cohort to 2.73 in the 2017—2021 cohort. Conclusions:The incidence of the leukemia has presented a rising trend in the past fifty years. Leukemia incidence increased with age, and the period and cohort effects on the risk of incidence increase. Further research is needed to investigate the risk factors related to leukemia.
6.Trends and age-period-cohort analysis of leukemia incidence in Qidong from 1972 to 2021
Jian ZHU ; Yongsheng CHEN ; Jun WANG ; Yonghui ZHANG ; Lulu DING ; Yuanyou XU ; Yongfeng YAN ; Jianguo CHEN ; Hong CAI
Chinese Journal of Oncology 2024;46(10):961-967
Objective:To describe the epidemiological characteristics and trends of leukemia incidence in Qidong between 1972 and 2021, and provide guidelines for prevention and control measures and strategies.Methods:The cancer registry data was collected and analyzed on leukemia incidence during 1972—2021 in Qidong by sex, age and time. Crude incidence rate (CR), China age-standardized rate (ASRC), world age-standardized rate (ASRW), and average annual change percentage (AAPC) was calculated by Joinpoint software. Age-period-cohort (APC) model was used to analyze the influence of age, period and birth cohort on the changes in the incidence trend of leukemia patients.Results:From 1972 to 2021, there were 2 948 patients with leukemia in Qidong, accounting for 2.00% of all cancer new cases, CR of leukemia was 5.26/10 5, ASRC was 4.34/10 5, ASRW was 4.35/10 5. The truncated incidence of 35—64 years old was 5.29/10 5, the cumulative incidence rate between the ages of 0 and 74 years old was 0.40%, the cumulative risk was 0.40%. There were 1 608 male patients, the CR, ASRC, and the ASRW were 5.81/10 5, 4.88/10 5 and 4.85/10 5. The number of female patients were 1 340, and the CR, ASRC, and the ASRW were 4.71/10 5, 3.86/10 5 and 3.91/10 5, respectively. Temporal trends indicated significant upward trends in ASRC among both gender, males and females with AAPC values of 1.41% ( P<0.001), 1.15% ( P<0.001), and 1.73% ( P<0.001), respectively. The results of the APC model showed that the average net drift value of leukemia incidence in all age groups was 1.57% (95% CI, 1.24%-1.89%), and the highest value of local drift was 3.20% (95% CI, 1.63%-4.78%) in the 80~ years old group. The incidence of leukemia increased with age. With the passage of time, the risk of leukemia incidence increased gradually compared with the rate ratio of leukemia incidence (risk ratio [ RR], 1.00) in 1992—1996, the RR of leukemia incidence increased from 0.70 during 1972—1976 to 1.57 during 2017—2021. The later the cohort was born, the greater the risk of leukemia incidence compared with the relative risk of leukemia incidence ( RR, 1.00) in 1952—1956 cohort, the RR of leukemia incidence increased from 0.24 in the 1892—1896 cohort to 2.73 in the 2017—2021 cohort. Conclusions:The incidence of the leukemia has presented a rising trend in the past fifty years. Leukemia incidence increased with age, and the period and cohort effects on the risk of incidence increase. Further research is needed to investigate the risk factors related to leukemia.
7.Evaluation of anticoagulant effect and predicted dose of low molecular weight heparin in hemodialysis by anti-Ⅹa factor activity
Zhenxing WANG ; Yonghui MAO ; Yuan WANG ; Peijie FU ; Xin DANG ; Lengnan XU
Chinese Journal of Preventive Medicine 2024;58(2):254-260
The purpose of this study was to explore the reasonable dose of low molecular weight heparin (LMWH) in hemodialysis (HD) and the strategy of preventing extracorporeal circuit coagulation (ECC). A retrospective case-control study included patients who used LMWH for anticoagulation during maintenance hemodialysis (MHD) in the Hemodialysis Center of Beijing Hospital from December 2020 to January 2021. Basic data such as weight, height, basic kidney disease, dialysis age and anti-Ⅹa factor activity before, during and after dialysis were collected. A total of 46 patients were enrolled in this study, including 5 patients in coagulation group (10.9%) and 41 patients in non-coagulation group (89.1%). The anti-Ⅹa factor activity reached its peak at 0.5 h after the start of HD. The level of anti-Ⅹa factor was incorporated into the receiver operating characteristic curve (ROC curve). The results showed that the area under the ROC curve (AUC) was 0.802 (95% confidence interval: 0.651-0.54, P=0.029), and the cutoff was 0.31 IU/ml (sensitivity 1, specificity 0.683). It is suggested that the body surface area should be used as the basis to estimate the anticoagulant dose of LMWH in HD, and the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml, which is of diagnostic value for ECC. In addition, the results of binary logistic regression analysis showed that dialysis age was an independent risk factor for ECC ( OR value 1.319, 95% CI 1.052-1.654, P=0.017). In summary, this study reveals that dialysis age may be a risk factor for ECC and that the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml can be used as a potential diagnostic cut-off point for ECC in HD patients, which provides a scientific basis for monitoring strategies to prevent blood coagulation in HD filters.
8.Evaluation of anticoagulant effect and predicted dose of low molecular weight heparin in hemodialysis by anti-Ⅹa factor activity
Zhenxing WANG ; Yonghui MAO ; Yuan WANG ; Peijie FU ; Xin DANG ; Lengnan XU
Chinese Journal of Preventive Medicine 2024;58(2):254-260
The purpose of this study was to explore the reasonable dose of low molecular weight heparin (LMWH) in hemodialysis (HD) and the strategy of preventing extracorporeal circuit coagulation (ECC). A retrospective case-control study included patients who used LMWH for anticoagulation during maintenance hemodialysis (MHD) in the Hemodialysis Center of Beijing Hospital from December 2020 to January 2021. Basic data such as weight, height, basic kidney disease, dialysis age and anti-Ⅹa factor activity before, during and after dialysis were collected. A total of 46 patients were enrolled in this study, including 5 patients in coagulation group (10.9%) and 41 patients in non-coagulation group (89.1%). The anti-Ⅹa factor activity reached its peak at 0.5 h after the start of HD. The level of anti-Ⅹa factor was incorporated into the receiver operating characteristic curve (ROC curve). The results showed that the area under the ROC curve (AUC) was 0.802 (95% confidence interval: 0.651-0.54, P=0.029), and the cutoff was 0.31 IU/ml (sensitivity 1, specificity 0.683). It is suggested that the body surface area should be used as the basis to estimate the anticoagulant dose of LMWH in HD, and the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml, which is of diagnostic value for ECC. In addition, the results of binary logistic regression analysis showed that dialysis age was an independent risk factor for ECC ( OR value 1.319, 95% CI 1.052-1.654, P=0.017). In summary, this study reveals that dialysis age may be a risk factor for ECC and that the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml can be used as a potential diagnostic cut-off point for ECC in HD patients, which provides a scientific basis for monitoring strategies to prevent blood coagulation in HD filters.
9.Selecting appropriate evaluation equations for assessing declining kidney function in aging individuals with disease conditions
Lengnan XU ; Congxia CHEN ; Ying SUN ; Xin LIU ; Aiqun CHEN ; Yonghui MAO
Chinese Journal of Geriatrics 2024;43(9):1155-1161
Objective:To compare the performance of 11 glomerular filtration rate(GFR)equations in Chinese elderly hospitalized patients using dynamic renal imaging as the reference standard.Methods:The retrospective study involved patients aged 60 years and older who were admitted to Beijing Hospital between January, 2017, and January 2020.Glomerular filtration rate(GFR)was assessed through dynamic renal imaging for all participants.Estimated GFR(eGFR)was calculated using various equations based on serum creatinine and/or cystatin C levels, including All Age Spectrum(FAS), Berlin Initiative Study(BIS), Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI), Modification of Diet in Renal Disease Study(MDRD), MDRD in China(MDRDc), and Xiangya..Results:A total of 691 patients, of which 383 were males, with an age range of 60 to 90 years(mean age 71.9±7.7 years), were included in the study.Among the different equations used to estimate glomerular filtration rate(GFR)in ml·min -1·1.73m -2, the smallest deviations were observed with FAScys(2.48), FAScr-cys(3.07), CKD-EPIcys(4.20), and BIScr-cys(7.42).Conversely, the most accurate estimations were found with BIScr-cys(10.38), FAScr-cys(11.94), FAScys(12.08), CKD-EPIcr-cys(13.21), and CKD-EPIcys(13.51).The highest P30 values, indicating the proportion of estimates within 30% of the true GFR, were achieved by FAScr-cys(68.97%), FAScys(68.96%), CKD-EPIcys(63.22%), and BIScr-cys(61.67%).The equations with the lowest root mean square errors were BIScr-cys(9.73), CKD-EPIcr-cys(10.98), FAScr-cys(11.27), CKD-EPIcys(11.52), and FAScys(11.53).Specifically, the FAS equation showed higher accuracy in men, while BIScr-cys and CKD-EPIcys were more accurate in women.Among patients with chronic kidney disease(CKD), the P30 values for BIScr-cys, FAScys, and FAScr-cys were 86.96%, 83.33%, and 80.95% respectively.Notably, for patients with mGFR ≥ 30 ml/min, MDRDc overestimated GFR the most, whereas for patients with mGFR<30 ml/min, Xiangya exhibited the most significant overestimation of GFR. Conclusions:Among the equations tested, BIScr-cys, FAScys, and FAScr-cys demonstrated the highest accuracy and are therefore recommended for use in Chinese elderly hospitalized patients.
10.Astaxanthin Repairs Pressure Injury by Alleviating Oxidative Stress and Inflammation
Yang CHEN ; Xinrun MA ; Yonghui WANG ; Bei GAO ; Zhenrong XU ; Yanhong GAO
Journal of Medical Biomechanics 2024;39(5):830-837
Objective To explore the effects of astaxanthin on pressure injury wounds.Methods In vitro experiment:Fibroblasts were treated with different concentrations of astaxanthin and their proliferation activity was detected by CCK-8 assay.Subsequently,fibroblasts were induced by hypoxia/reoxygenation,and the optimal concentration of astaxanthin was administered.Then the intracellular reactive oxygen species(ROS)level was detected by DHE fluorescent probes and the mRNA expression level of TNF-α,IL-1β,IL-6,IL-10,TGF-β was evaluated by RT qPCR.In vivo experiment:to construct a pressure injury model,two circular magnets were symmetrically adsorbed on both sides of the mouse skin for 5 hours everyday.Subsequently,equal amounts of physiological saline,low-dose astaxanthin(10 mg/kg),and high-dose astaxanthin(20 mg/kg)were administered by gavage in groups.Wound images were taken regularly.After 7-day treatment,wound healing rates were counted and wound tissues were collected for histopathological staining.Results In vitro,the fluorescence intensity of DHE in the astaxanthin groups were reduced dramatically.The relative mRNA expression level of TNF-α,IL-1β,IL-6 in the astaxanthin group declined,and the level of TGF-β and IL-10 mRNA increased significantly(P<0.05).In vivo,the wound healing rate and the level of TGF-β,IL-10 in high-dose astaxanthin group increased significantly.The ROS content and the level of TNF-α,IL-1β and IL-6 dropped markedly in astaxanthin groups(P<0.05).Conclusions Astaxanthin can significanlty alleviate oxidative stress,mitigate inflammation,thus exerting a protective effect on pressure injury wounds.

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