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.Rheumatic diseases and portal hypertension
Li SHEN ; Weijia DUAN ; Tingting LYU ; Jidong JIA
Journal of Clinical Hepatology 2025;41(5):812-816
Rheumatic diseases are a group of chronic disorders characterized by abnormalities in the immune system, while portal hypertension occurs due to increased blood flow or heightened resistance in the portal venous system or obstruction of hepatic venous outflow. Both rheumatic diseases and their medications can lead to noncirrhotic portal hypertension. The hypercoagulable state associated with rheumatic diseases can result in thrombosis within the portal and hepatic venous systems, and damage to the intrahepatic portal system and hepatic sinusoidal endothelial system can lead to porto-sinusoidal vascular disease and hepatic sinusoidal obstruction syndrome. Moreover, drugs used for the treatment of rheumatic diseases may cause liver parenchymal injury, which further leads to liver fibrosis and cirrhosis, or they may damage the hepatic vascular endothelium and thus cause noncirrhotic portal hypertension. This article elaborates on the mechanisms and characteristics by which common rheumatic diseases and their therapeutic agents lead to portal hypertension, in order to provide insights and assistance for clinical diagnosis, treatment, and follow-up monitoring.
3.Efficacy of pudendal nerve modulation in the treatment of female pudendal neuralgia
Ziqin ZHOU ; Xin SONG ; Yinjun GU ; Tingting LYU ; Weilin FANG ; Jin HUANG ; Jianwei LYU ; Zhikang CAI ; Zhong WANG
Journal of Modern Urology 2025;30(5):395-399
Objective: To investigate the clinical efficacy and safety of pudendal nerve modulation (PNM) in the treatment of female pudendal neuralgia (PN),so as to promote the clinical application of this technique. Methods: A retrospective analysis was conducted on 20 female PN patients who failed conservative treatment at Gongli Hospital during Nov.2020 and Oct.2023.All patients underwent simultaneous PNM and sacral nerve modulation (SNM) with the assistance of 3D printing navigation.Dual-stage test electrodes for PNM and SNM were implanted,followed by alternate therapeutic trial for each modality.Secondary conversion rates and longitudinal outcomes,including visual analogue score (VAS),patient health questionnaire-9 (PHQ-9),and quality of life (QoL) scores were compared preoperatively,post-stage Ⅰ,and at 3,6,and 12 months post-stage Ⅱ. Results: All operations were successful.After the trial phase,the secondary conversion rate for PNM was significantly higher than that for SNM; 16 patients (16/20,80%) chose the second-phase PNM implantation surgery,3 (3/20,15%) chose second-phase SNM implantation,and 1 (1/20,5%) had electrodes removed due to ineffective results from both trials.Further assessment revealed that the improvements in VAS,PHQ-9,and QoL scores for PNM patients were significantly better than those for SNM patients after the first phase of surgery and at 3,6 and 12 months after the second-phase conversion (P<0.05).No complications such as electrode migration or infection were observed during the follow-up of 12-15 months. Conclusion: PNM provides more effective relief of pain symptoms and improvements in depressive states for female PN patients compared to SNM.With the assistance of 3D printing navigation,the operation is simple and safe,and offers stable therapeutic effects.It is worthy of clinical promotion and application.
4.New insights into translational research in Alzheimer's disease guided by artificial intelligence, computational and systems biology.
Shulan JIANG ; Zixi TIAN ; Yuchen YANG ; Xiang LI ; Feiyan ZHOU ; Jianhua CHENG ; Jihui LYU ; Tingting GAO ; Ping ZHANG ; Hongbin HAN ; Zhiqian TONG
Acta Pharmaceutica Sinica B 2025;15(10):5099-5126
Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.
5.Platelet-rich plasma in the treatment of interstitial cystitis/bladder pain syndrome:a single-center prospective study
Jin HUANG ; Rong LYU ; Wenjun MENG ; Tingting LYU ; Weilin FANG ; Jianwei LYU
Journal of Modern Urology 2025;30(12):1043-1048
Objective To investigate the clinical efficacy of platelet-rich plasma (PRP) therapy for interstitial cystitis/bladder pain syndrome (IC/BPS). Methods This single-center prospective study involved 97 IC/BPS patients treated in our hospital during Sep.2023 and Apr.2025, who underwent transurethral bladder injection of PRP. The injections were administered once a month for four sessions. The global response assessment (GRA) score,24-hour urinary frequency, maximum single voiding volume, visual analogue scale (VAS) score, O'Leary score, pelvic pain, urgency and frequency (PUF) score, and Zung self-rating anxiety scale (SAS) score were analyzed. Results All 97 patients completed four injections. The GRA score,24-hour urinary frequency, VAS score, O'Leary score and PUF score were improved significantly after treatment (P<0.007). Intraoperative bladder capacity with significant improvement were observed after the first injection (P<0.01), and the maximum urine output were observed after the fourth injection (P<0.007). The SAS score was not significantly improved. Conclusion Repeated PRP injections can effectively alleviate bladder pain, improve frequent and urgent urination symptoms, and increase the bladder capacity.
6.Summary of the 19 th Chinese Symposium of Burns and Wounds
Yanling LYU ; Yu MO ; Guangping LIANG ; Gaoxing LUO ; Yizhi PENG ; Dan SUN ; Kaizhen QIU ; Luyao WU ; Tingting LI ; Zhixin LIU
Chinese Journal of Burns 2024;40(7):699-700
The 19 th Chinese Symposium of Burns and Wounds was successfully held in Foshan of Guangdong Province from June 20 th to 22 nd in 2024. There were more than 700 delegates attending the academic event. The theme of the congress was expansion, integration and standardization, which could promote academic exchanges, multi-disciplinary fusion, and standardization of clinical treatment of burns and wounds. A total of nearly 200 famous experts and scholars had their speeches on the two-day keynote forum and special academic seminars including critical care, wound repair, scar prevention and treatment, rehabilitation nursing, and disciplinary integration sessions. The congress ended successfully with abundant fruits and friendship.
7.Exploring the feasibility of endoscopic surgery by gastrointestinal surgeons: surgeon′s perspective
Jun LUO ; Bei LI ; Ying YU ; Tingting HUANG ; Lan CHEN ; Meiwen HE ; Shaowei XIONG ; Mingxuan ZHU ; Zhanlong SHEN ; Guoqing LYU
Chinese Journal of Digestive Surgery 2024;23(8):1123-1126
Due to traditional professional divisions, the practice of endoscopy by gastro-intestinal surgeons in China remains controversial. However, with the evolution of treatment philo-sophies, medical technology, and equipment advancements, a trend of integration between tradi-tional surgery and endoscopy is emerging. Gastrointestinal surgeons performing endoscopy can maxi-mize patient benefits, and they naturally possess advantages in conducting endoscopic procedures. It is recommended to further establish entry thresholds for surgeons to perform endoscopy, provide standardized endoscopic training for surgeons, and coordinate efforts at the administrative depart-ment. With the support of artificial intelligence, more patients can receive minimally invasive, indivi-dualized, and precise treatments.
8.Clinical features and risk factors for invasive fungal sinusitis after allogeneic hematopoietic stem cell transplantation
Haixia FU ; Jiajia LI ; Yuanyuan ZHANG ; Yuqian SUN ; Xiaodong MO ; Tingting HAN ; Jun KONG ; Meng LYU ; Wei HAN ; Huan CHEN ; Yuhong CHEN ; Fengrong WANG ; Chenhua YAN ; Yao CHEN ; Jingzhi WANG ; Yu WANG ; Lanping XU ; Xiaojun HUANG ; Xiaohui ZHANG
Chinese Journal of Hematology 2024;45(1):22-27
Objective:To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT.Methods:Nineteen patients with IFR after allo-HSCT at Peking University People’s Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) .Results:Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10–59) years. The median IFR onset time was 68 (9–880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation ( P=0.021) , hemorrhagic cystitis after transplantation ( P=0.012) , delayed platelet engraftment ( P=0.008) , and lower transplant mononuclear cell count ( P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively ( P<0.01) . Conclusion:Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.
9.The effect of glucose-6-phosphate dehydrogenase deficiency on allogeneic hematopoietic stem cell transplantation in patients with hematological disorders
Jia WANG ; Haixia FU ; Yuanyuan ZHANG ; Xiaodong MO ; Tingting HAN ; Jun KONG ; Yuqian SUN ; Meng LYU ; Wei HAN ; Huan CHEN ; Yuhong CHEN ; Fengrong WANG ; Chenhua YAN ; Yao CHEN ; Jingzhi WANG ; Yu WANG ; Lanping XU ; Xiaojun HUANG ; Xiaohui ZHANG
Chinese Journal of Hematology 2024;45(2):121-127
Objectives:To determine the effect of glucose-6-phosphate-dehydrogenase (G6PD) deficiency on patients’ complications and prognosis following allogeneic stem cell hematopoietic transplantation (allo-HSCT) .Methods:7 patients with G6PD deficiency (study group) who underwent allo-HSCT at Peking University People's Hospital from March 2015 to January 2021 were selected as the study group, and thirty-five patients who underwent allo-HSCT during the same period but did not have G6PD deficiency were randomly selected as the control group in a 1∶5 ratio. Gender, age, underlying diseases, and donors were balanced between the two groups. Collect clinical data from two patient groups and perform a retrospective nested case-control study.Results:The study group consisted of six male patients and one female patient, with a median age of 37 (range, 2-45) years old. The underlying hematologic diseases included acute myeloid leukemia ( n=3), acute lymphocytic leukemia ( n=2), and severe aplastic anemia ( n=2). All 7 G6PD deficiency patients achieved engraftment of neutrophils within 28 days of allo-HSCT, while the engraftment rate of neutrophils was 94.5% in the control group. The median days of platelet engraftment were 21 (6–64) d and 14 (7–70) d ( P=0.113). The incidence rates of secondary poor graft function in the study group and control group were 42.9% (3/7) and 8.6% (3/35), respectively ( P=0.036). The CMV infection rates were 71.4% (5/7) and 31.4% (11/35), respectively ( P=0.049). The incidence rates of hemorrhagic cystitis were 57.1% (4/7) and 8.6% (3/35), respectively ( P=0.005), while the bacterial infection rates were 100% (7/7) and 77.1% (27/35), respectively ( P=0.070). The infection rates of EBV were 14.3% (1/7) and 14.3% (5/35), respectively ( P=1.000), while the incidence of fungal infection was 14.3% (1/7) and 25.7% (9/35), respectively ( P=0.497). The rates of post-transplant lymphoproliferative disease (PTLD) were 0% and 5.7%, respectively ( P=0.387) . Conclusions:The findings of this study indicate that blood disease patients with G6PD deficiency can tolerate conventional allo-HSCT pretreatment regimens, and granulocytes and platelets can be implanted successfully. However, after transplantation, patients should exercise caution to avoid viral infection, complications of hemorrhagic cystitis, and secondary poor graft function.
10.Clinical analysis of allogeneic hematopoietic cell transplantation in 9 patients with hematological malignancies complicated by Gilbert’s syndrome
Xiaolu ZHU ; Jingzhi WANG ; Meng LYU ; Tingting HAN ; Fengmei ZHENG ; Yuhong CHEN ; Yuanyuan ZHANG ; Huan CHEN ; Xiaohui ZHANG ; Lanping XU ; Xiaojun HUANG ; Yu WANG
Chinese Journal of Hematology 2024;45(9):851-855
From January 1, 2013, to March 1, 2024, nine patients with hematological malignancies complicated by Gilbert’s syndrome in Peking University People’s Hospital underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patients comprised seven male and two female cases, with a median age of 38 (13-60) years old. Among them, three cases were acute myeloid leukemia, three cases were acute lymphocytic leukemia, two cases were myelodysplastic syndrome, and one case was chronic myelomonocytic leukemia. None of the patients had viral hepatitis. Of the nine cases, seven cases received the Bu-Cy+ATG regimen, while the other two cases received the TBI-Cy+ATG regimen (Bu, busulfan; Cy, cyclophosphamide; ATG, antithymocyte immunoglobulin; and TBI, total body irradiation). All patients achieved neutrophil engraftment, and eight received platelet engraftment. The median total bilirubin level was 45.4 (22.5-71.2) μmol/L before transplantation and 22.0 (18.0-37.2) μmol/L on -1d of preconditioning. The total bilirubin level on +20d after the transplantation of eight patients decreased compared with the baseline level before transplantation. Moreover, one patient had a transient increase in the total bilirubin level on +5d after transplantation, which was considered to be attributed to the toxicity of Bu. No patients were complicated by hepatic veno-occlusive disease. The median follow-up time was 739 (42-2 491) days. During the follow-up period, one patient died of recurrence, and the remaining eight patients had disease-free survival events.


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