Objective: To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.

Objective: This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively. Methods: The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model. Results: Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group. Conclusion This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.

OBJECTIVE: To investigate the relevance ratio of osteoporosis and bone mass of middle aged and elderly people in Beijing communities, in order to understand occurrence and development trend of abnormality of bone mass in high-risk population from community. METHODS: Based on the method of cross-sectional investigation, the information data of 1 540 middle-aged and elderly people from 10 communities were collected, including 415 males and 1 125 females, aged from 45 to 80 years old with the average of (63.02±7.15) years old; the height was (161.34±7.24) cm, the weight was (65.90±10.19) kg, body mass index was (25.29±3.32) kg /m2. Bone mineral density (BMD) of lumbar vertebrae (L RESULTS: The level of β-CTX was(0.27±0.12) ng /ml, procollanen type 1 N-terminal propeptide(P1NP) was(51.03± 22.36) ng /ml, 25(OH) D3 was (16.68±6.24) ng /ml, serum calcium was(2.34±0.09) mmol / L, blood phosphorus was (1.43± 0.37) mmol / L, and blood magnesium was (0.94±0.07) mmol / L, alkaline phosphatase was (79.28±20.48) U/ L, parathyroid hormone was (3.09±1.60) pmol / L, osteocalcin was (13.29±6.65) ng /ml. Except for blood magnesium, the other indexes had significant differences between different sex groups( CONCLUSION There are obvious differences in relevance ratio of osteoporosis and low bone mass among different sites. It is suggested that the clinical diagnosis of osteoporosis should be combined with bone mineral density and bone metabolic markers. With the increasing prevalence of osteoporosis among middle aged and elderly people in Beijing community, continuous follow-up research based on community primary health care units could promote early examination, early diagnosis, and early treatment of middle aged and elderly people at high risk of osteoporosis in community.
Absorptiometry, Photon ; Aged ; Aged, 80 and over ; Beijing/epidemiology* ; Bone Density ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis/epidemiology*

OBJECTIVE: To evaluate the clinical effect of acupuncture on smoking cessation and withdrawal symptoms and to explore the influence factors of acupuncture on smoking cessation. METHODS: A total of 500 subjects with tobacco dependence were randomized into an acupuncture group, an auricular therapy group, an acupuncture plus auricular therapy group, a TENS group and a nicotine replacement therapy group (NRT group), 100 cases in each one. In the acupuncture group, acupuncture was applied at Baihui (GV 20), Lieque (LU 7), Hegu (LI 4) and Zusanli (ST 36). The treatment was given 5 times a week, once a day in the first 2 weeks. The treatment was given once every 2 days in the week 3 and 4, 3 times a week, and twice a week, once every 3 days in the week 5 to 8. In the auricular therapy group, the ear point pressure therapy was used at shenmen (TF), neifenmi (CO), pizhixia (AT) and jiaogan (AH), 3 times a week. In the acupuncture plus auricular therapy group, acupuncture and auricular therapy were adopted with the same points and manipulation as the previous two groups. Acupuncture was given 3 times a week and the auricular therapy was given twice a week. In the TENS group, SDZ-Ⅱ B type electric acupuncture apparatus was used to stimulate Lieque (LU 7) and Zusanli (ST 36), once a day. In the NRT group, the nicotine patch was used on the chest, back and the upper arms of the subjects, once a day. The duration of treatment was 8 weeks as one course in every group. Afterwards, the 16-week follow-up was conducted. The time-point withdrawal rate was evaluated by the level of urine cotinine in 8 weeks of treatment and in the follow-up in the subjects of 5 groups. The persistent withdrawal rate was evaluated by the self-report of the subjects in 8 weeks of treatment as well as in the follow-up in the 5 groups. The withdrawal effect, the score of the fagerstrom test for nicotine dependence (FTND) and the score of the heaviness of smoking index (HSI) were compared among the groups. Twenty indexes were selected as the potential influence factors, the 72 h withdrawal rate based on the level of urine cotinine in 8 weeks of treatment and in the follow-up was taken as the dependent variable. Using the two categories of Logistic regression analysis, the influence factors of therapeutic effect of acupuncture were screened for smoking cessation. RESULTS: After 8 weeks of treatment, the time-point withdrawal rate in the subjects among the groups was NRT group > acupuncture plus auricular therapy group > auricular therapy group > acupuncture group > TENS group. In the follow-up, the time-point withdrawal rate was acupuncture plus auricular therapy group > NRT group > acupuncture group > TENS group > auricular therapy group, but without statistical significance in comparison (>0.05). After 8 weeks of treatment, the persistent withdrawal rate in the subjects among the groups was auricular therapy group > TENS group > acupuncture group > acupuncture plus auricular therapy group > NRT group. In the follow-up visit, the persistent withdrawal rate was auricular therapy group > TENS group > acupuncture plus auricular therapy group > acupuncture group > NRT group. The result in the auricular therapy group was better than all of the other 4 groups (<0.05). Except in the follow-up visit, FTND score in the acupuncture group was lower than the auricular therapy group (<0.05), FTND score and HSI score were not different significantly in statistics among the groups either in 8 weeks of treatment or in the follow-up (>0.05). The regression analysis showed that the factors, i.e. nationality, educational background, drinking frequency, pre-treatment FTND score, pre-treatment HSI score and smoking cessation for physical reason in family, were correlated significantly with the withdrawal result after 8-week treatment (<0.05). The factors, i.e. education background, smoking age, pre-treatment FTND score and different therapeutic methods, were correlated significantly with the withdrawal result in the follow-up (<0.05). CONCLUSION Acupuncture combined with auricular therapy effectively reduce nicotine dependence and smoking intensity and relieve withdrawal symptoms. There are many factors that affect the withdrawal effect in smoking cessation. Hence, the influence factors in smoking cessation with acupuncture should be clearly determined so as to develop the individual regimen for smoking cessation and improve the clinical therapeutic effect of acupuncture on smoking cessation.
Acupuncture Therapy ; Humans ; Smoking ; Smoking Cessation ; Tobacco Use Cessation Devices ; Treatment Outcome