1.Interpretation of 2024 ESC guidelines for the management of elevated blood pressure and hypertension
Yu CHENG ; Yiheng ZHOU ; Yao LÜ ; ; Dongze LI ; Lidi LIU ; Peng ZHANG ; Rong YANG ; Yu JIA ; Rui ZENG ; Zhi WAN ; Xiaoyang LIAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):31-40
The European Society of Cardiology (ESC) released the "2024 ESC guidelines for the management of elevated blood pressure and hypertension" on August 30, 2024. This guideline updates the 2018 "Guidelines for the management of arterial hypertension." One notable update is the introduction of the concept of "elevated blood pressure" (120-139/70-89 mm Hg). Additionally, a new systolic blood pressure target range of 120-129 mm Hg has been proposed for most patients receiving antihypertensive treatment. The guideline also includes numerous additions or revisions in areas such as non-pharmacological interventions and device-based treatments for hypertension. This article interprets the guideline's recommendations on definition and classification of elevated blood pressure and hypertension, and cardiovascular disease risk assessment, diagnosing hypertension and investigating underlying causes, preventing and treating elevated blood pressure and hypertension. We provide a comparison interpretation with the 2018 "Guidelines for the management of arterial hypertension" and the "2017 ACC/AHA guideline on the prevention, detection, evaluation, and management of high blood pressure in adults."
2.Effects of Zuogui Jiangtang Yishen Formula in regulating the NLRP3/caspase-1/GSDMD signaling axis on pyroptosis in rats with diabetic kidney disease
Shujuan Hu ; Xuhua Li ; Yao Peng ; Lili Chen ; Rong Yu ; Yajun Peng
Digital Chinese Medicine 2025;8(3):379-388
Objective:
To investigate the effects of Zuogui Jiangtang Yishen Formula (左归降糖益肾方, ZGJTYSF) in regulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) signaling axis on pyroptosis in rats with diabetic kidney disease (DKD).
Methods:
Fifty male specific pathogen-free (SPF) grade Goto-Kakizaki (GK) rats (12 weeks old) were fed a high-fat diet for one month to establish an early DKD model. Model establishment was confirmed when fasting blood glucose (FBG) ≥ 11.1 mmol/L and urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g. The successfully modeled early DKD rats were randomly divided by random number table into five groups (n = 10 per group): model group; dapagliflozin group (1.0 mg/kg, by gavage, served as positive control); and low-, medium-, and high-dose of ZGJTYSF groups (4.9, 9.9, and 19.9 g/kg, respectively, by gavage). Age-matched male SPF Wistar rats (n = 10) served as control group. Rats in control and model groups were gavaged with equivalent volumes of distilled water. Treatment lasted 12 weeks. Changes in uACR, FBG, and renal function were observed in all groups. Hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining were used to observe renal histopathological changes. Immunohistochemistry was performed to detect the localization and expression of caspase-1, GSDMD, and NLRP3 in rat renal tissues. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was utilized to detect pyroptosis in renal tissues. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were applied to detect mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, interleukin (IL)-1β, and IL-18.
Results:
Compared with model group, all doses of ZGJTYSF showed reductions in FBG, with medium- and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12 (P < 0.05). For uACR, all doses of ZGJTYSF groups exhibited a decreasing trend, with high-dose of ZGJTYSF group being significantly lower than low- and medium-dose of ZGJTYSF groups at week 12 (P < 0.05) and showing no significant difference from dapagliflozin group (P > 0.05). No significant differences in renal function parameters (serum creatinine, blood urea nitrogen, and uric acid) were observed among groups (P > 0.05). Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group, with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group. Immunohistochemistry demonstrated significantly reduced expression of caspase-1, GSDMD, and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group (P < 0.05 or P < 0.01), while the differences in low- and medium-dose of ZGJTYSF groups were not statistically significant (P > 0.05). TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups (P < 0.01), indicating a marked reduction in pyroptotic cells. Molecular analysis revealed that compared with model group, both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 in renal tissues (P < 0.01), while low- and medium-dose of ZGJTYSF groups showed downward trends without statistical significance (P > 0.05).
Conclusion
ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis, thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.
3.Role of TGF-β/Smads signaling pathway in myocardial fibrosis of heart failure and research status of traditional Chinese medicine intervention
Yao-Hui HUO ; Jing ZHANG ; Li-Rong ZHOU ; Xiao-Gang ZHANG ; Yong-Ze GAO ; Li-Ming LIU ; Kai LIU
The Chinese Journal of Clinical Pharmacology 2024;40(3):444-448
During the progression of heart failure(HF),abnormal transduction of the transforming growth factor-β(TGF-β)/Smads signaling pathway is important mechanism of myocardial fibrosis(MF)in HF.TGF-β,a key factor in MF,is in an overexpression state in the process of MF in HF,and Smads is a major effector downstream of TGF-β.The TGF-β/Smads pathway induces abnormal proliferation of myofibroblasts,aggravates myocardial extracellular matrix deposition,and reduces the ability of the cardiac tissues to resist fibrosis,which plays a complex role in the pathogenesis of MF in HF.Traditional Chinese medicine(TCM)has the efficacy of unequivocal inhibiting myocardial collagen deposition,anti-MF,protecting the myocardium and improving cardiac function in the prevention and treatment of MF in HF and so on,and the TGF-β/Smads pathway is one of the key pathways through which TCM monomers,TCM combinations,and proprietary medicines can exert their cardioprotective effects on the HF.This paper reviews the existing experimental research results of TCM intervening in the TGF-β/Smads pathway for the treatment of MF in HF over the past 10 years,with a view to providing theoretical basis for the prevention and treatment of HF MF well as the development and of new drugs.
4.Effect of Shexiang Baoxin pill on cardiac angiogenesis in spontaneously hypertensive rats
Rong HUA ; Qing-Hai ZHANG ; Yi TANG ; Qian LI ; Yao-Yuan XIAO ; Lin-Lin LIU ; Ming-Xiang TANG
The Chinese Journal of Clinical Pharmacology 2024;40(8):1180-1183
Objective To explore the effect of Shexiang Baoxin pill on cardiac tissue angiogenesis in spontaneously hypertensive rats(SHR).Method Twenty 12 week old male SHR were randomly divided into experimental group and model group,with 12 week old male SD rats as the normal control group.The experimental group rats were orally administered with Shexiang Baoxin pill(45 mg·kg-1)daily,and their blood pressure was monitored using a non-invasive tail artery blood pressure gauge every four weeks.Eight weeks later,cardiac tissue was taken for platelet endothelial cell adhesion molecule-1(PECAM-1/CD31)immunofluorescence staining to observe CD31 expression level.Use protein blotting to detect the expression levels of myocardial endothelial growth factor(VEGF),myocardial endothelial growth factor receptor 2(VEGF-R2),basic fibroblast growth factor(bFGF)and phosphorylated protein kinase B(p-Akt)/protein kinase B(Akt)proteins.Result There was significant increase in blood pressure between the experimental group,model group and normal group at the same time point(all P<0.01),but there was no statistically significant difference in blood pressure changes between the experimental group and model group at the same time point(all P>0.05).The CD31 expression rates of the normal group,model group and experimental group were(3.79±0.84)%,(2.54±0.42)%and(3.56±0.49)%;VEGF levels were 0.95±0.10,0.73±0.08 and 0.94±0.15;VEGF-R2 levels were 0.85±0.10,0.61±0.14 and 0.80±0.10;bFGF levels were 0.84±0.04,0.51±0.21 and 0.74±0.14;p-Akt/Akt levels were 0.85±0.15,0.57±0.13 and 0.80±0.20,respectively.The differences between the normal group and the model group,as well as the experimental group and the model group,were statistically significant(all P<0.05).Conclusion Shexiang Baoxin pill can promote the neovascularization of microvessels in the heart tissue of spontaneously hypertensive rats,and its mechanism may be related to the activation of PI3K/Akt phosphorylation,upregulation of bFGF,VEGF and their receptor VEGF-R2 in myocardial tissue.
5.Bioequivalence study of pyrazinamide tablets in Chinese healthy subjects
Li-Bing YE ; Chong YAO ; Ying-Rong CHEN ; Lu-Yuan TONG ; Tao YANG ; Xiao LU ; Min XU ; Qiu-Yue JIN ; Shui-Xin YANG
The Chinese Journal of Clinical Pharmacology 2024;40(15):2236-2240
Objective To evaluate the bioequivalence and safety of two pyrazinamide tablets in healthy Chinese subjects.Methods An open,randomized,single-dose,two-sequence,two-cycle,double-cross trial design was used.All 48 healthy subjects(24 in fasting and 24 in fed trial)were randomized to receive a single oral dose of a 0.5 g pyrazinamide tablet(test or reference)per cycle.The plasma concentration of the drug was determined by liquid chromatography coupled to tandem mass spectrometry method.The pharmacokinetic parameters were calculated by WinNonlin v8.2,and the bioequivalence was evaluated by SAS 9.4.Results In the fasting group,the Cmax of the test and reference preparation of pyrazinamide tablets were(13.28±2.82)and(12.88±4.49)μg·mL-1,the AUC0-t were(139.17±26.58)and(138.63±28.92)h·μg·mL-1,the AUC0-∞ were(148.96±33.65)and(148.71±36.97)h·μg·mL-1 respectively.In the fed group,the Cmax of the test and reference preparation of pyrazinamide tablets were(11.89±1.96)and(11.99±1.92)μg·mL-1,the AUC0-t were(138.22±37.21)and(141.68±25.80)h·μg·mL-1,the AUC0-∞ were(152.20±32.41)and(151.04±28.05)h·μg·mL-,respectively.The 90%confidence intervals of Cmax,AUC0-t and AUC0-∞ geometric mean ratios of the test and reference preparation were all within 80.00%to 125.00%.The incidence of adverse events was 16.70%for both the test and reference preparation in the fasting group and 8.30%for both the test and reference preparation in the fed group,all of which were mild in severity.Conclusion The test and reference preparation of pyrazinamide tablets were bioequivalent,safe and well tolerated in healthy Chinese subjects under fasting and fed conditions.
6.Effect and Mechanism of Zuogui Jiangtang Yishen Prescription on Diabetic Kidney Disease in Rats via Regulation of MiRNA-27a/Wnt/β-catenin Pathway
Shujuan HU ; Xuhua LI ; Xiu LIU ; Yao PENG ; Lili CHEN ; Rong YU ; Yajun PENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):90-97
ObjectiveTo explore the protective effects and potential mechanism of Zuogui Jiangtang Yishen prescription (ZJYP) in Goto-Kakizaki (GK) rats with early-stage diabetic kidney disease (DKD). MethodFifty 12-week-old male GK rats were included in this study. DKD was induced after one month of high-fat feeding, with fasting blood glucose (FBG) ≥ 11.1 mmol·L-1 and urinary albumin/creatinine ratio (ACR) ≥ 30 mg·g-1 used as model criteria. After successful modeling, DKD rats were randomly divided into five groups (n=10 in each group): the model group, the western medicine group treated with dapagliflozin (1.0 mg·kg-1·d-1), low-, medium-, and high-dose ZJYP groups (4.9, 9.9, 19.9 g·kg-1·d-1 by gavage). Ten Wistar rats served as normal controls, with both the normal and model groups receiving physiological saline in the same volume as the treatment groups by gavage for 8 weeks. The urinary ACR, FBG, body weight, and liver and kidney functions of the rats were observed. Renal tissues were subjected to haematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining and examined under an electron microscope to observe pathological changes. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect miRNA-27a, Wnt, and β-catenin mRNA and protein expression levels in renal tissues. ResultCompared with the results in the normal group, the FBG levels in DKD rats of the model group increased significantly at 0, 2, 4, 6, and 8 weeks of drug intervention (P<0.05), and urinary ACR increased significantly at 0, 4, 8 weeks (P<0.05). Renal pathological staining and electron microscopy revealed an increase in mesangial cells and matrix, slight thickening of the basement membrane, and increased interstitial fibrosis and renal tubular atrophy in the model group. The mRNA expression levels of miRNA-27a, Wnt, and β-catenin were significantly higher in the model group than in the normal group (P<0.05). Renal Wnt and β-catenin protein levels were also significantly higher in the model group (P<0.05). After drug intervention, the FBG levels in the low-, medium-, and high-dose ZJYP groups showed a dose-dependent decrease compared with those in the model group at 6 and 8 weeks (P<0.05). The urinary ACR also showed a dose-dependent decrease in the low-, medium-, and high-dose ZJYP groups, but the differences were not statistically significant. There were no significant differences in liver function, renal function, renal index, or routine blood lipid test results among the low-, medium-, and high-dose ZJYP groups. Renal glomerular and tubular lesions were milder in the ZJYP groups and the western medicine group than in the model group, with similar pathological changes observed in the high-dose ZJYP group and the western medicine group. The renal mRNA levels of miRNA-27a, Wnt, and β-catenin were significantly lower in the high-dose ZJYP group (P<0.05), and renal Wnt and β-catenin protein levels were significantly lower in both the western medicine group and the high-dose ZJYP group compared with the levels in the model group (P<0.05). The Wnt and β-catenin protein levels were lower in the renal tissues of the low- and medium-dose ZJYP groups compared with the levels in the model group, but the differences were not statistically significant. ConclusionZJYP can effectively improve glucose metabolism and alleviate early damage in DKD rats, thereby delaying the progression of DKD. Its mechanism may be related to the inhibition of the miRNA-27a/Wnt/β-catenin signaling pathway in renal tissues.
7.Effects of electroacupuncture on motor function and related molecular mechanisms in mice with Parkinson's disease
Ling QI ; Yanan LI ; Yao WANG ; Xiaolei ZHANG ; Mengni HU ; Hanzhang LI ; Die XIAO ; Zhen RONG ; Jun MA
Journal of Beijing University of Traditional Chinese Medicine 2024;47(5):721-728
Objective To explore the effects of electroacupuncture on motor function in Parkinson's disease(PD)model mice and NLRP3 inflammasome-related proteins in the midbrain substantia nigra(SN).Methods C57BL/6 mice were assigned to three groups according to the random number table method:control group,model group,and electroacupuncture(EA)group,12 mice per group.The PD model was reproduced by intragastric administration of rotenone solution 10 mg/(kg·d).EA group was administered at the three selected points,"Fengfu"(GV16),"Taichong"(LR3),and"Zusanli"(ST36),with a treatment cycle of 2 weeks.The control and model groups took the same time synchronous fixation operation for the control variable.Behavioral scores and open field tests were used to detect the exercise ability of mice in each group.Tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the midbrain SN of mice in all groups were measured with an immunohistochemistry test.NLRP3 and cysteinyl aspartate specific proteinase-1(Caspase-1)protein expression levels in the midbrain SN of mice in the three groups were measured using Western blotting,and interleukin-1β(IL-1β)content was determined with an enzyme-linked immunosorbent assay.Results Compared to the control group,the behavioral scores of the mice in the model group were higher(P<0.01).Compared to the model group,the behavioral scores of the mice in the EA group were lower(P<0.01).Compared to the control group,the time ratio of the relative rest state of the mice in the model group(<100 mm/s)increased significantly(P<0.01),while the time ratio of the slow motion(100~200 mm/s)and time ratio of the fast motion(>200 mm/s)state decreased significantly(P<0.01).Compared to the model group,the time ratio spent in the relative rest state of mice in the EA group decreased significantly(P<0.01),while the time ratio of the slow motion state and time ratio of the fast motion state and movement rate increased significantly(P<0.01).Compared to the control group,the TH expression level decreased in the SN in the model group(P<0.01),while α-syn increased(P<0.01).Compared to the model group,the TH expression level in the EA group increased(P<0.05),while α-syn decreased(P<0.05).Compared to the control group,the protein expressions of NLRP3 and Caspase-1 in the SN of the model group increased(P<0.01);compared to the model group,the expressions of NLRP3 and Caspase-1 in the SN of the midbrain of mice decreased after EA treatment(P<0.01).Compared to the control group,IL-1β in the SN of the mouse midbrain increased in the model group(P<0.01).Compared to the model group,IL-1β decreased in the EA group(P<0.05).Conclusion This experiment shows that stimulation of EA in"Fengfu","Taichong",and"Zusanli"can effectively reduce abnormal aggregation of the PD marker α-syn,increase TH expression,and enhance the motor dysfunction of PD model mice.The molecular mechanism is related to the regulation of the expression of NLRP3,Caspase-1,and IL-1β of inflammasome-related pathways.
8.Short-term results of sleeve wrapping technique using remnant aortic wall in modified Bentall procedure
MENG Maolong ; Yao WANG ; Pingfan LU ; Huapeng LI ; Rong REN ; Wen ZHANG ; Fengjie CHEN ; Xianmian ZHUANG ; Xiang WANG ; Gang LI ; Hongwei GUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(02):283-287
Objective To evaluate the short-term results of sleeve wrapping technique using remnant aortic wall in modified Bentall procedure. Methods The patients undergoing modified Bentall procedure with the remnant aortic wall as a sleeve to cover the sewing area of composite valved graft and the aortic annulus for proximal hemostasis between March 2021 and March 2022 in Shenzhen Fuwai Hospital were enrolled. Short-term results were assessed by cardiopulmonary bypass time, aortic clamping time, mechanical ventilation time, ICU stay, postoperative hospital stay, effusion drainage on the first postoperative day, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), and follow-up results. Results A total of 14 patients were collected, including 12 males and 2 females, with a mean age of 55.33±10.57 years. There was no postoperative or follow-up death. Cardiopulmonary bypass time was 147.90±21.29 min, aortic clamping time was 115.70±15.23 min, mechanical ventilation time was 19.42±8.98 h, ICU stay was 99.08±49.42 h, and postoperative hospital stay was 16.33±2.74 d. Thoracic drainage volume was 333.33±91.98 mL on the first postoperative day. Only 2 patients required blood transfusion (4.5 U and 2 U, respectively). During the follow-up of 6.17±3.69 months, there was no death, no aortic or valve-related complications. There was statistical difference in the LVEDD between preoperation and before discharge after surgery (P<0.001), and between half a year after surgery and before discharge after surgery (P<0.001). There was a little decrease of LVEF before discharge after surgery compared with preoperative LVEF, but there was no statistical difference (P=0.219). There was no statistical difference in the LVEF half a year after operation compared with that before operation (P=1.000). Conclusion Sleeve wrapping technique using remnant aortic wall in modified Bentall procedure has good short-term results. This modification may be a simple, effective way in controlling proximal bleeding.
9.Identification of cajanonic acid A metabolites in rats by UPLC-Q-TOF-MS/MS
Yao CHENG ; Yu-juan BAN ; Rui CHEN ; Li ZHANG ; Ke-rong HU ; Jing HUANG
Acta Pharmaceutica Sinica 2024;59(5):1382-1390
This research established a simple, rapid and sensitive ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) method to investigate the metabolic profiles of cajanonic acid A (CAA) in rats. After intragastric administration of CAA (30 mg·kg-1) to rats, the biological samples were detected by UPLC-Q-TOF-MS/MS. Relevant data was collected and processed, the accurate mass and MS2 spectra of the metabolites were compared with the parent compound. As a result, a total of 23 metabolites were detected, including 15 in urine, 11 in bile, 11 in feces, and 9 in plasma. The major metabolic pathways related to CAA included dehydrogenation, reduction, hydroxylation, methylation and glucuronide conjugation. This experiment was approved by Animal Ethics Committee of Guizhou Medical University (approval number: 1603137).
10.Association between job burnout, depressive symptoms, and insomnia among employees in electronic manufacturing industry
Xiaoyi LI ; Yao GUO ; Rong ZHAO ; Xiaodong JIA ; Jin WANG ; Huiqing CHEN ; Xiaoman LIU
Journal of Environmental and Occupational Medicine 2024;41(11):1205-1212
Background The high-quality development of manufacturing in China has spurred industrial transformation and upgrading, placing higher demands on the skills of employees in the electronic manufacturing industry. This situation may induce psychological health problems such as job burnout and depressive symptoms in the employees, and also lead to insomnia, which has become a public health problem that urgently needs attention and solution. Objective To investigate the relationship between job burnout, depressive symptoms, and insomnia among employees in the electronic manufacturing industry. Methods A total of

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