1.Mechanism of Qishen Yiqi Dropping Pills in regulating gut microbiota and ROS/TXNIP/NLRP3 signaling pathway to improve chronic heart failure in rats
Lifei LYU ; Tingting ZHU ; Fan DING ; Yingdong LU ; Xiangning CUI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):354-369
Objective:
This study explored the regulatory effects of QiShen Yiqi Dropping Pills (QSYQ) on chronic heart failure (CHF) in rats and their related mechanisms based on the gut microbiota and reactive oxygen species (ROS)/thioredoxin interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) signaling pathway.
Methods:
Sixty-five SPF-grade male SD rats were used to establish a CHF model through subcutaneous multiple injections of isoproterenol (ISO) combined with exhaustion and food control methods. The modeled rats were randomly divided into model, captopril (5.30 mg/kg), and QSYQ low-, medium-, and high-dose groups (0.08, 0.16, and 0.32 g/kg, respectively), with 11 rats per group, plus a blank group of seven rats. The medication groups were given corresponding drugs by gavage, whereas the blank and model groups were administered an equivalent volume of purified water continuously for four weeks. Rat heart function was assessed via transthoracic echocardiography, and myocardial tissue pathology changes were observed through hematoxylin and eosin staining. Serum levels of brain natriuretic peptide (BNP), lipopolysaccharide (LPS), interleukin-18 (IL-18), and interleukin-1β (IL-1β) were measured using an enzyme-linked immunosorbent assay. Automated biochemical analyzers were used to determine creatine kinase (CK), lactate dehydrogenase (LDH), and MB isoenzyme of creatine kinase (CK-MB) content. Myocardial ROS levels were examined using flow cytometry; myocardial TXNIP and NLRP3 expression were detected using immunohistochemistry. Real-time qPCR and Western blotting were used to examine myocardial mRNA and protein expression of TXNIP, NLRP3, apoptosis-related spot-like protein (ASC), caspase-1, and IL-1β, as well as myocardial thioredoxin (Trx) and colonic tight junction proteins (zonula occludens-1, ZO-1), occludin, and claudin-5. Differences in the gut microbiota of the blank, model, and QSYQ high-dose groups were determined using high-throughput 16S rDNA sequencing.
Results:
Compared to the blank group, the model group exhibited significantly reduced left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01); increased serum BNP, LPS, IL-18, and IL-1β (P<0.01) levels; increased CK, LDH, and CK-MB (P<0.01) contents; visible myocardial tissue fibrous edema, wavy appearance, cytoplasmic loosening, round vacuolar degeneration, local tissue fibrous dissolution replaced by proliferative connective tissue, accompanied by inflammatory cell infiltration; significantly increased myocardial ROS levels (P<0.01); and significantly increased myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly increased (P<0.05, P<0.01, respectively), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly decreased (P<0.01). Compared to the model group, the QSYQ high-dose group showed the most significant changes (P<0.05, P<0.01), with significant increases in LVEF and LVFS (P<0.01); significant decreases in serum BNP, LPS, IL-18, and IL-1β levels (P<0.01); significant reductions in CK, LDH, and CK-MB content (P<0.01); improved myocardial tissue damage; significantly decreased myocardial ROS levels (P<0.01); and significantly reduced myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly decreased (P<0.05, P<0.01), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly increased (P<0.01). 16S rDNA sequencing results confirmed that the gut microbiota of rats changed after modeling and drug intervention, with significant differences in both α- and β-diversity. Compared to the blank group, at the family level, the abundance of Oscillospiraceae decreased (P<0.05), whereas the abundance of Lactobacillaceae increased. At the species level, the abundance of Segatella copri and Treponema succinifaciens increased, whereas the abundance of Kineothrix alysoides (P<0.05), Ruminococcus callidus, and Prevotellamassilia timonensis decreased. Compared to the model group, at the family level, the abundance of Oscillospiraceae increased (P<0.05) in the QSYQ high-dose group, whereas the abundance of Lactobacillaceae decreased. At the species level, the abundance of Segatella copri and Treponema succinifaciens decreased, whereas the abundance of Kineothrix alysoides increased (P<0.05).
Conclusion
QSYQ can regulate the relative abundance of symbiotic bacteria Kineothrix alysoides in the intestines, reduce serum LPS levels, inhibit the ROS/TXNIP/NLRP3 signaling pathway, and improve inflammatory responses, thereby exerting therapeutic effects on CHF.
2.Clinical Comprehensive Evaluation of Guanxinjing Capsules in Treating Angina Pectoris of Coronary Heart Disease with Syndrome of Qi Deficiency and Blood Stasis in "6+1" Dimensions
Mengmeng WANG ; Xin CUI ; Jian LYU ; Yanming XIE ; Lianxin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):120-128
ObjectiveTo systematically review the available studies about Guanxinjing capsules in treating angina pectoris of coronary heart disease (syndrome of Qi deficiency and blood stasis), evaluate the evidence quality and comprehensive value of Guanxinjing capsules in 6+1 dimensions involving 9 aspects, and clarify the clinical positioning and advantages of this medicine. MethodsA qualitative combined with quantitative evaluation method was adopted, involving clinical medicine, epidemiology, evidence-based medicine, and pharmacoeconomics. Through public data collection, questionnaire surveys, real-world data collection, and literature comprehensive evaluation, an evaluation system involving 9 aspects in 6+1 dimensions was constructed for Guanxinjing capsules. Experts assigned weights to the criterion layer and indicator layer, and the multi-criteria decision analysis (MCDA) model and CSC (V2.0) were employed to measure each dimension and reveal the clinical value of Guanxinjing capsules. Results①The evaluation results showed that Guanxinjing capsules are safe. According to the adverse reactions in the instructions, the systematic evaluation and meta-analysis of clinical safety, and the data collected by the National Center for Adverse Drug Reaction Monitoring, the adverse reactions of Guanxinjing capsules mainly include chest tightness, dyspnea, dizziness, and digestive system-related symptoms, with a standardized score of 0.75 points, which suggests good safety. ②The meta-analysis results suggest that according to the same efficacy standards, the effectiveness of Guanxinjing capsules alone and Guanxinjing capsules combined with conventional Western medicine or Chinese patent medicines is higher than that of conventional Western medicine or the Chinese patent medicine Shenshao capsules alone in treating coronary heart disease. The standardized score of effectiveness is 0.57, which indicates that the effectiveness still requires evidence support. ③With the individual disposable income in 2020 as the expected payment assumption threshold, compared with conventional treatment alone, combining Guanxinjing capsules with conventional treatment is cost-effective and economical for the patients with angina pectoris of coronary heart disease under certain conditions (higher than 106.91 yuan), which suggests good economy. ④At present, 3 patents for the invention of Guanxinjing capsules have been approved, covering multiple fields such as clinical innovation, service system innovation, and industrial development, which implies good innovation. ⑤In addition, the questionnaire surveys for medical staff involve five different dimensions, and the statistical scores and evaluation results show good suitability of Guanxinjing capsules. ⑥The reimbursement rate of Guanxinjing capsules by residents is high. The sampling survey results show that Guanxinjing capsules are fully equipped in hospitals across China and have good accessibility. ⑦Derived from the theory of activating blood and resolving stasis proposed by Wang Qingren, a famous physician in the Qing Dynasty, Guanxinjing capsules integrate multiple therapies such as replenishing Qi, nourishing Yin, and aromatic warming and unblocking. According to the analysis data in the "6+1" dimensions, the clinical comprehensive evaluation score of Guanxinjing capsules for angina pectoris of coronary heart disease (syndrome of Qi deficiency and blood stasis) was 0.73. ConclusionThe results of comprehensive evaluation of each dimension and clinical value suggest that Guanxinjing capsules in treating angina pectoris of coronary heart disease (syndrome of Qi deficiency and blood stasis) have sufficient clinical evidence, good safety, suitability, and accessibility. It is recommended that Guanxinjing capsules can be included in the documents of basic clinical medication management in accordance with the established procedure.
3.Pathogenesis and Treatment Based on Syndrome Differentiation of Traditional Chinese Medicine for Cough Variant Asthma: A Review
Jingshu LUO ; Mingxia YU ; Mingsheng LYU ; Hongsheng CUI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):125-134
Cough variant asthma (CVA) is a special type of asthma and the most common cause of chronic cough in China. It has a relatively high incidence, seriously affects patients' quality of life, and in some cases may even progress to typical asthma, posing an important challenge in the field of health economics. At present, first-line treatment in Western medicine mainly consists of inhaled corticosteroids combined with bronchodilators. However, there remain many problems such as poor efficacy in some patients, frequent relapse after drug withdrawal, and poor compliance, making it urgent to improve treatment strategies. In-depth research on the pathogenesis is helpful for a comprehensive understanding and prevention of CVA. The pathogenesis of CVA is complex and involves multiple pathophysiological links. While similar to typical asthma, it still presents some differences. Traditional Chinese medicine (TCM) has unique advantages in the treatment of CVA. Guided by the theory of syndrome differentiation and treatment, TCM can not only improve the clinical symptoms of CVA but also prevent recurrence. In recent years, with the continuous deepening of research on the pathogenesis of CVA and on its treatment with TCM based on syndrome differentiation, related academic achievements have been updated year by year. A review of literature in China and abroad shows that the current pathogenesis of CVA can be summarized into six aspects: airway inflammation, airway remodeling, airway hyperresponsiveness, cough hypersensitivity, genetic factors, and imbalance of intestinal flora. TCM often differentiates and treats CVA from four perspectives: cause, disease location, disease nature, and disease tendency. This paper systematically summarizes the progress in the study of CVA pathogenesis, comprehensively collates the experience and clinical research evidence on its treatment with TCM based on syndrome differentiation, and discusses the problems existing in current research. On this basis, it puts forward suggestions and prospects for future research and development of TCM in the treatment of CVA, with a view to providing a theoretical basis and therapeutic approaches for its prevention and treatment.
4.Effect of ureteral wall thickness at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy
Wei PU ; Jian JI ; Zhi-Da WU ; Ya-Fei WANG ; Tian-Can YANG ; Lyu-Yang CHEN ; Qing-Peng CUI ; Xu XU ; Xiao-Lei SUN ; Yuan-Quan ZHU ; Shi-Cheng FAN
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1077-1081
Objective To investigate the effect of varying ureteral wall thickness(UWT)at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy(URL).Methods The clinical data of 164 patients with ureteral stones in our hospital were retrospectively analyzed.According to different UWT,the patients were divided into the mild thickening group(84 cases,UWT<3.16 mm),the moderate thickening group(31 cases,UWT 3.16 to 3.49 mm),and the severe thickening group(49 cases,UWT>3.49 mm),and the differences of clinical related indicators among the three groups were compared.Results The incidence of postoperative renal colic and leukocyte disorder in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,and the differences were statistically significant(P<0.05).The postoperative catheterization time in the mild thickening group and the moderate thickening group were shorter than that in the severe thickening group,and the incidences of secondary lithotripsy,residual stones and stone return to kidney in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,with statistically significant differences(P<0.05).The length of hospital stay and hospitalization cost in the mild thickening group and the moderate thickening group were shorter/less than those in the severe thickening group,with statistically significant differences(P<0.05).Conclusion With the increase of UWT(especially when UWT>3.49 mm),the incidence of postoperative complications and hospitalization cost of URL increase to varying degrees,and the surgical efficacy decreases.In clinical work,UWT measurement holds potential value in predicting the surgical efficacy and complications of URL.
5.Treadmill exercise up-regulates BDNF/TrkB-CREB pathway to improve anxiety-like behavior in neuropathic pain rats
Xiaoge WANG ; Jinyu BAO ; Shuai YANG ; Yihang LYU ; Weidong ZANG ; Cui LI
Acta Laboratorium Animalis Scientia Sinica 2024;32(9):1149-1159
Objective To investigate the effects of low-to-moderate intensity treadmill exercise on pain and anxiety-like behaviors in rats with chronic constriction injury of the sciatic nerve(CCI),and to explore the neural mechanism of the exercise-related brain-derived neurotrophic factor(BDNF)/tropomyosin receptor kinase B(TrkB)-cAMP-response element binding protein(CREB)pathway in relieving pain and anxiety behaviors in CCI rats.Methods Thirty-two D rats were divided randomly into four groups:sham group,CCI group,sham+exercise(Sham+Exe)group,and CCI+exercise(CCI+Exe)group.Rats in the exercise groups underwent treadmill training for 4 weeks.The paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)were measured before and at different time points after the operation.The elevated plus maze(EPM)and open field test(OFT)were used to evaluate anxiety-like behaviors in the rats.mRNA and protein expression levels of BDNF,TrkB,and CREB in the hippocampus were detected by real-time quantitative reverse transcription PCR and Western Blot,respectively.Results(1)The PWT and PWL on the operative side of the rats were significantly lower in the CCI compared with the sham group at 7,14,21,28,and 35 days after the operation(P<0.001).The PWT on the ipsilateral side was significantly increased in the CCI+Exe group after 21 days compared with the CCI group(P<0.05),and the PWL on the ipsilateral side increased significantly after 14 days(P<0.05).(2)The EPM result showed that rats in the CCI group spent a significantly lower proportion of time in the open arms(P<0.001)and significantly more time in the closed arms compared with the sham group(P<0.01).Rats in the CCI+Exe group spent significantly more time in the open arms than the CCI group(P<0.05).(3)The OFT result showed that rats in the CCI group spent a significantly lower proportion of time in the central area of the open field compared with the sham group(P<0.001),while the percentage of time was significantly increased in the CCI+Exe group compared with the CCI group(P<0.05).(4)BDNF,TrkB,and CREB mRNA and protein levels in the hippocampus were significantly lower in the CCI group compared with the sham group(P<0.05,P<0.01).Four-week treadmill exercise increased the mRNA and protein expression levels of BDNF,TrkB,and CREB in the hippocampus of CCI rats(P<0.05).Conclusions Four weeks of treadmill exercise alleviates mechanical and thermal hyperalgesia and anxiety induced by chronic pain in CCI rats.Up-regulation of the BDNF/TrkB-CREB pathway may be one of the mechanisms by which exercise relieves chronic pain and improves anxiety.
6.A study on the impact of organizational capacity on organizational performance in Beijing's community health service centers:A qualitative comparative analysis based on fuzzy sets
Bo LYU ; Cheng-Sen CUI ; Kai MENG
Chinese Journal of Health Policy 2024;17(10):31-38
Objective:To explore the impact of organizational capacity on organizational performance in community health centers(CHCs),and to provide a scientific basis for improving the organizational performance of CHCs.Methods:Randomly select one administrative district from each of the four functional zones in Beijing,and all the 66 CHCs in the four administrative districts were chosen as sample cases.Fuzzy set qualitative comparative analysis(fsQCA)was used to explore the effect of nine secondary competencies of organizational competence segmentation on high and low organisational performance in CHCs.Results:There are three groupings of high and low performing CHCs,and the strengthening of medical service capacity,public health capacity,decision-making capacity,normative capacity and learning capacity play a universal role in improving the organizational performance of CHCs.Conclusions:The performance of community health service centres is the result of a variety of elements linked to each other,and multiple paths can enable them to achieve high organizational performance,community health service centres can be combined with their own advantages of differentiated development,and lower-performing community health service centres can give priority to the development of medical service capacity and learning capacity to promote the rapid improvement of organizational performance.
7.Clinical manifestation, muscular imaging and pathological characteristics of anti-signal recognition particle positive immune-mediated necrotizing myopathy
Shiyao LI ; Qianqian QU ; Xianzhao ZHENG ; Xiaoli MA ; Wenhao CUI ; Dan LI ; Zheng LYU ; Jiongbo ZHAO ; Jiaxuan WANG ; Cong HU ; Haidong LYU
Chinese Journal of Neurology 2024;57(9):1000-1008
Objective:To analyze the clinical characteristics, muscle imaging and pathological features of patients with anti-signal recognition particle positive immune-mediated necrotizing myopathy (SRP-IMNM).Methods:Nine patients with SRP-IMNM were collected in the Neuromuscular Disease Center of Jiaozuo People′s Hospital from May 2018 to May 2023, who were confirmed by skeletal muscle pathology and myositis-specific autoantibodies detection, and their clinical manifestations, muscle imaging and muscle pathology characteristics were systematically summarized.Results:Among the 9 patients with SRP-IMNM, there were 7 females and 2 males. The age of onset ranged from 18 to 59 years. All the patients presented proximal muscle weakness. Seven patients experienced neck weakness, and dysphagia was present in 5 patients. Laboratory examinations showed elevated serum creatine kinase levels in all 9 patients (1 866-6 725 U/L). Eight patients were combined with other antibodies positivity, except for anti-SRP antibody. Among them, 7 patients were combined with anti-Ro-52 antibody positivity, 4 patients combined with anti-Ro-52 antibody positivity alone, and 3 patients combined with 3 or more positive antibodies simultaneously. Those patients who presented with interstitial lung disease and cardiac involvement were all combined with other antibodies positivity. Seven patients completed thigh muscle magnetic resonance imaging (MRI), which showed diffuse skeletal muscle oedema, partial muscle atrophy and fatty replacement, primarily affecting the posterior thigh muscle group. Two patients underwent shank muscle MRI. The soleus involvement was evident, while the tibialis anterior muscle and gastrocnemius muscles were involved in 1 patient. All 9 patients showed varying degrees of scattered muscle fiber necrosis and regeneration on muscle biopsies. In 1 patient, a small amount of inflammatory cell infiltration was observed. Pipestem capillaries were observed in 4 patients. Immunohistochemical staining revealed a small number of CD68-positive lymphocytes in 8 patients. Additionally, 5 patients showed upregulation of major histocompatibility complex Ⅰ expression on the muscle fiber membrane, while 6 patients showed deposition of membrane attack complex (C5b-9) on non-necrotic muscle fibers and capillaries. P62 staining showed homogeneous fine-granular in sarcoplasm in 6 patients.Conclusions:In addition to proximal muscle weakness, patients with SRP-IMNM often experience neck weakness and dysphagia. Those with multiple antibodies are more likely to develop interstitial lung disease and cardiac involvement. SRP-IMNM patients have diffuse oedema in the affected muscles, and the posterior thigh muscles are more prone to atrophy and fatty tissue formation. C5b-9 deposition and pipestem capillaries are significant pathological features of SRP-IMNM, which provide additional evidence for clinical diagnosis.
8.Analysis of incidence and mortality of breast cancer in tumor registration areas of Shanxi Province in 2019
Zhaohui MA ; Ling CAO ; Licheng LYU ; Xuerong GUO ; Wangfei CUI ; Xinchen WANG ; Ruifeng ZHANG ; Yongzhen ZHANG
Cancer Research and Clinic 2024;36(9):659-663
Objective:To investigate the incidence and mortality of breast cancer in tumor registration areas of Shanxi Province in 2019.Methods:A cross-sectional study was conducted. The tumor registration data reported by 13 tumor registration areas in Shanxi Province in 2019 were collected, and the overall incidence and mortality of breast cancer were analyzed. The stratified analysis was conducted by gender and region, and the incidence, mortality, accumulation rate (0-74 years old), age-specific incidence rate, age-specific mortality rate, Chinese population standardized rate and world population standardized rate were calculated. The standard population was based on the 2000 China population census standard population composition and Segi world standard population composition.Results:In 2019, there were 871 new cases of breast cancer in the tumor registration areas of Shanxi Province, with an incidence rate of 17.83/100 000, and 202 deaths, with a mortality rate of 4.13/100 000. The age-specific incidence of breast cancer was at a low level in 0-25 years old, it increased rapidly after 30 years old, and reached a peak in people aged 60 years old. The age-specific mortality showed a slow rising trend with the increase of age, and increased rapidly in people over 75 years old. The age-specific incidence and mortality of breast cancer in female were higher than those in male. Although the general trend of change concerning urban and rural age-specific incidence was similar, the trend of change concerning urban and rural age-specific mortality had their own characteristics. In 4 urban tumor registration areas, the highest male and female Chinese population standardized incidence rates were found in Yuci District of Jinzhong City (0.62/100 000) and Yangquan City (41.86/100 000). Male Chinese population standardized mortality rate was 0/100 000, and the highest female Chinese population standardized mortality rate was found in Yangquan City (12.62/100 000). In 9 rural tumor registration areas, the highest male and female Chinese population standardized incidence rates were found in Jishan County (2.59/100 000) and Pingding County (36.42/100 000). The highest Chinese population standardized mortality rates were found in Yuanqu County (0.89/100 000) and Jishan County (4.82/100 000).Conclusions:Women, urban area people and middle-aged and elderly people are the foci of breast cancer prevention and control in Shanxi Province.
9.Clinical efficacy of 1 565 nm non-ablative fractional laser in androgenetic alopecia
Yi CHENG ; Yaping XU ; Lijing LYU ; Yu CUI ; Yan ZHANG ; Caixia HU
Tianjin Medical Journal 2024;52(9):936-939
Objective To investigate the clinical efficacy and safety of 1 565 nm non-ablative fractional laser combined with topical minoxidil and oral finasteride in the treatment of patients with androgenetic alopecia(AGA).Methods Seventy-five male AGA patients with Norwood-Hamilton classification grade Ⅱ-Ⅲ,were randomly assigned into three groups:the control group 1,the control group 2 and the experimental group,with 25 cases in each group.Patients in the control group 1 received topical 5%minoxidil(1 mL,twice daily).Patients in the control group 2 were treated with both topical 5%minoxidil and oral finasteride(1 mg,once daily).Patients in the experimental group received a combined therapy of 1 565 nm non-ablative fractional laser in addition to topical 5%minoxidil and oral finasteride.Hair overall efficacy was evaluated using a 7-point rating scale after 24 weeks of treatment.Hair diameter and density were measured using a dermoscope.Patient satisfaction was assessed post-treatment,and adverse reactions were recorded.Results The overall efficacy of hair in the experimental group was superior to the control group 1 and the control group 2.There were no significant differences in hair density and hair diameter before treatment between the three groups(P>0.05).After treatment,hair diameter and density increased in all three groups compared to baseline values(P<0.05),and the hair diameter and hair density of the experimental group were higher than those of the control group 1 and the control group 2(P<0.05).Patient satisfaction in the experimental group was higher than that in the control group 1 and the control group 2(P<0.05).Patients in the experimental group experienced tolerable pain and burning sensations during laser treatment,and the symptoms were self-alleviated within a few hours.There were no serious adverse reactions reported in any group.Conclusion The combination therapy of 1 565 nm non-ablative fractional laser,5%minoxidil,and finasteride demonstrates significantly better efficacy in the treatment of AGA than minoxidil and finasteride alone drug therapy.
10.Application Progress of Drug Crystal form in Clinical and Crystallization Process
Chunyan LYU ; Xiaoqing HOU ; Wenyu CUI ; Wenjun ZHANG ; Wenqian WANG ; Rui HAN
Herald of Medicine 2024;43(8):1296-1302
The difference in the crystal form of the drug leads to different solubility and stability,affecting drug's the clinical efficacy and bioavailability.Therefore,in recent years,drug crystal forms have received more and more attention from researchers.By reviewing and sorting out relevant literature,this paper summarizes the research progress of drug crystallization theory in recent years from the aspects of influencing factors of drug crystal form,identification and control of drug crystal form,drug crystal form evaluation methods,and applications,aiming to provide a reference for drug crystal form control and process screening.


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