1.Mechanism of Xinnao shutong capsule alleviating cerebral ischemia-reperfusion injury in rats by regulating ferroptosis
Huani LI ; Changhe LIU ; Xiaoyan GUO ; Xin ZHONG ; Wei ZHANG ; Wenjing GE
China Pharmacy 2025;36(3):306-311
OBJECTIVE To study the mechanism of Xinnao shutong capsule alleviating cerebral ischemia reperfusion injury (CIRI) in rats by regulating the ferroptosis pathway. METHODS SD rats were randomly divided into sham operation group, model group, Xinnao shutong low-dose, high-dose group (220, 440 mg/kg), Ginkgo biloba leaves extract group (positive control, 150 mg/kg). Each group of rats was orally administered with the corresponding medication/normal saline for 7 consecutive days. Transient occlusion of the middle cerebral artery was adopted to induce the CIRI model; the samples were taken 24 h after the operation; the cerebral infarction area of rats was detected, and the cerebral infarction rate was calculated. The pathological changes of brain tissues were observed, and the levels of lipid peroxide (LPO), malondialdehyde (MDA) and glutathione (GSH) in cerebral tissue were detected; mRNA and protein expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase 1(HO-1) and glutathione peroxidase 4 (GPX4) were all detected in cerebral tissue of rats. RESULTS Compared with model group, the cerebral infarction rate, the content of total iron in cerebral tissue and serum level of LPO (except for Ginkgo biloba leaves extract group and Xinnao shutong low-dose group) were all decreased significantly in G. biloba leaves extract group and Xinnao shutong groups (P<0.05 or P<0.01); the serum level of GSH, the protein and mRNA expressions of Nrf2, HO-1 and GPX4 were all increased significantly (P<0.05 or P<0.01). The pathological damage to brain tissue was reduced, the number of nerve cells increased, the edema was alleviated, and the nuclear membrane was flattened. CONCLUSIONS Xinnao shutong capsule can inhibit ferroptosis and reduce CIRI, the mechanism of which may be associated with the activation of the Nrf2/HO-1/GPX4 signaling pathway.
2.PENG Peichu's Experience in Staged Differentiation and Treatment of Prostate Cancer
Xinyu XU ; Yu PENG ; Wenjing ZHU ; Jing ZHAI ; Dongya SHENG ; Mingyang WANG ; Yiqun SHAO ; Boyang LI ; Qi ZHONG
Journal of Traditional Chinese Medicine 2024;65(7):678-683
This paper summarized Professor PENG Peichu's experience in the differentiation and treatment of prostate cancer in three phases and four stages. It is considered that prostatic cancer is categorized into root deficiency and branch excess, with depletion of healthy qi as the root, and the accumulation of cancer toxin as the minifestation. Clinical diagnosis and treatment of prostatic cancer can be divided into three phases and four stages according to the exuberance and decline of pathogenic and healthy qi and the changes of deficiency and excess of yin and yang. In the initial accumulation phase of cancer toxin (yang excess stage), the key pathogenesis is the accumulation of dampness, heat and static blood, and internal generation of cancer toxin, and the treatment should be resolving toxins, fighting cancer and dispelling yang excess. In the phase of healthy qi deficiency and toxin accumulation (yin deficiency stage), with the lung and kidney yin deficiency, dampness, heat and static toxin accumulation as the key pathogenesis, the treatment should be centered on mutual generation between metal and water to nourish kidney yin, supplemented with the method of clearing heat and draining dampness, activating blood and resolving toxins, for which self-made Nanbei Formula(南北方)is usually used. In the phase of yang deficiency and cold stagnation (yang deficiency stage and yin excess stage), with the spleen and kidney yang deficiency, cold dampness stagnation, static heat and toxin accumulation as the key pathogenesis, the treatment should be warming and tonifying spleen and kidney to dissipate cold accumulation; for deficiency of both yin and yang, and excess pathogen obstruction, modified Yanghe Decoction(阳和汤) is recommended, while for yang deficiency, cold congealing and blood stasis, self-made Wenshen Sanjie Formula(温肾散结方) can be used, and for cold dampness binding with cancer toxin, and cold complex with heat, self-made Quanan Formula (泉安方) is advised.
3.Differential expression of inflammatory proteins in diabetic skin ulcers and ordinary skin ulcers
Wu XIONG ; Youyuan HE ; Xi ZHANG ; Jianda ZHOU ; Jia CHEN ; Xiaoling ZOU ; Sijia ZHAO ; Xingxing ZHONG ; Yutan CAO ; Wenjing QU
Journal of Chinese Physician 2024;26(3):331-336
Objective:To study and screen the differential expression of inflammatory proteins in diabetes skin ulcers and common skin ulcers, so as to provide experimental basis for further research on anti-inflammatory and healing drug targets of diabetes skin ulcers.Methods:The tissues of 11 patients with diabetes skin ulcer, 12 patients with common skin ulcer and 11 patients with normal skin were collected from the First Hospital of Hunan University of Chinese Medicine. The levels of inflammatory protein Toll like receptor 4 (TLR4), nuclear factor κB (NF-κB), pro-inflammatory factor interferon -γ (IFN -γ), tumor necrosis factor - α (TNF -α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1β (IL-1β), macrophage chemotactic protein-1 (MCP-1), anti-inflammatory factors epidermal growth factor (EGF), interleukin-4 (IL-4), and interleukin-10 (IL-10) were detected in three groups of tissues using enzyme-linked immunosorbent assay (ELISA).Results:Compared with normal tissues, the concentrations of TLR4, NF-κB, IFN -γ, TNF -α, IL-1β, IL-6, IL-8, MCP-1 and EGF in common ulcer skin tissues and diabetes ulcer tissues were higher, and the concentrations of IL-10 were lower, with statistically significant differences (all P<0.05); Compared with the normal tissue, the concentration of IL-4 in diabetes ulcer tissue was lower, the difference was statistically significant ( P<0.05); Compared with ordinary ulcer skin tissue, the concentrations of TLR4, NF-κB and MCP-1 in diabetes ulcer tissue were higher, and the concentrations of IL-4 were lower, with statistically significant differences (all P<0.05). Conclusions:The skin ulcer in diabetes patients will have inflammatory reaction, and high glucose promotes the inflammatory reaction of skin ulcer, which may be related to the abnormal expression of TLR4, NF-κB, MCP-1 and IL-4. TLR4/NF-κB signal pathway and inflammatory factors MCP-1 and IL-4 may be the target of the inflammation regulation of diabetes skin ulcer.
4.Investigation of microorganism contamination in the whole production chain of three kinds of TCM formula granules
Wenjing LI ; Yanfei ZHONG ; Huanmin ZHU
Drug Standards of China 2024;25(3):265-272
Objective:The contaminated microorganisms in the whole production process of Yujin,mulberry leaf and cicada were investigated,and a database was established to explore the microbial key control points and control measures in the production process of traditional Chinese medicine(TCM)formula granules,in order to provide demonstration research for enterprises,provide basis for formulating standards and improving production processes,and fill the blank of the whole.Methods:The raw materials,intermediate products and final products of three kinds of TCM formula particles were analyzed according to the Chinese Pharmacopoeia 2020,and the supporting mi-croorganisms were identified by mass spectrometry technology.The degree of exogenous polluting microorganisms from raw materials to finished products of TCM formula particles and the types of microorganisms easily contamina-ted were analyzed and studied.Results:The raw materials(TCM decoction pieces)of the three TCM formulations granules had serious microbial pollution,and the thermostable bacillus of the raw materials could still be detected in the intermediate products and final products even after the process treatment,and the total number of aerobic bacte-ria in some batches exceeded the limit.Enterococcus faecium from human and animal intestines was also detected in intermediate products and finished products.Conclusion:①Strengthening the control of microbial contamination of TCM decoction pieces is conducive to reducing the microbial load of final products;②There are risks of spore microorganism contamination in the production technology of 3 kinds of formula granuleshas,and the production process parameters should be optimized to reduce the microbial load;③Pharmaceutical companies need to strength-en the whole process of product control to reduce the risk of microbial contamination.
5.Efficacy-driving Mechanism of Danhong Injection for Stable Angina Pectoris Based on Composition-activity Relationship of Target Modules
Siwei TIAN ; Wenjing ZONG ; Jun LIU ; Wei YANG ; Qikai NIU ; Siqi ZHANG ; Jing'ai WANG ; Huamin ZHANG ; Zhong WANG ; Bing LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):121-128
ObjectiveTo explore the efficacy-driving mechanism of Danhong injection (DHI) in the treatment of stable angina pectoris (SAP) based on the composition-activity relationship of target modules and clarify the pharmacological effects of DHI. MethodAccording to the angina frequency (AF) in the Seattle Angina Questionnaire (SAQ) that was obtained in the previous clinical trial, the patients before and after DHI treatment were grouped based on efficacy. The transcriptomic data of the patients before treatment and in the best efficacy group 30 days post-treatment were selected as the data source, and then weighted gene co-expression network analysis (WGCNA) was employed to construct the co-expression network. Relevant modules in the network were identified and associated with clinical features. In addition, the On-modules (Z value below 0) were identified by Zsummary. The topological indicators such as density, centrality, and clustering coefficient were adopted to explore the dynamics of DHI efficacy at the network level and module level, respectively. In addition, the driver genes were screened by the personalized network control (PNC) algorithm. Finally, rat H9C2 cells were used to establish the model of hypoxia/reoxygenation (H/R), which was used to confirm the potential therapeutic target of DHI for SAP and provide a scientific basis for revealing the therapeutic mechanism of DHI. ResultWe identified 19 modules in the best efficacy group of DHI for SAP, and the comparison between day 0 and day 30 revealed 12 On-modules. The changes of network topological indicators at the network and module levels confirmed the correlation between the best efficacy of DHI treatment and topological dynamics. Finally, the driver genes, Klotho and fibroblast growth factor 22 (FGF22), in DHI treatment of SAP were verified by the H9C2 cell model of H/R. ConclusionBased on clinical transcriptome data, this study determined the composition-activity relationship of target modules of DHI for SAP, which provided a scientific basis for deciphering the efficacy-driven mechanism of DHI for SAP.
6.Electrophysiological characteristics and clinical significance of unilateral tinnitus with normal hearing threshold
Wenjing WU ; Zhendong JIANG ; Fazhang LAN ; Ya HE ; Cheng ZHONG
Journal of Army Medical University 2024;46(17):2016-2020
Objective To investigate the electrophysiological characteristics and clinical significance of unilateral tinnitus with normal hearing threshold.Methods A total of 34 patients with normal hearing but unilateral tinnitus admitted to our department from May 2022 to February 2023 were recruited as the study subjects.Pure tone hearing threshold detection,distortion product otoacoustic emission(DPOAE),auditory brainstem response(ABR)detection and extended high-frequency pure tone audiometry were performed on both ears(affected side and healthy side)of every patient.The data of the affected side group and those of healthy side group were compared.Results The Ⅰ-wave latency of ABR was significantly shorter(1.60 vs 1.73 ms,P=0.018),and its amplitude was obviously decreased(0.19 vs 0.23 μV,P=0.003)in the affected side group when compared with the healthy side group.In the affected group(34 ears),there were 18 ears(52.94%)having amplitude of wave Ⅲ greater than that of wave Ⅴ,while in the healthy group,no such difference in the amplitude between wave Ⅲ and wave Ⅴ was observed.There was statistical significance between the 2 groups(Chi-square=24.480,P<0.001).In the 12.5,14.0,16.0,18.0 and 20.0 kHz conditions,the average hearing threshold of extended high-frequency audiometry was all significantly higher in the affected side group than the healthy group(P<0.05).Conclusion For subjective tinnitus patients with normal hearing threshold,ABR examination is helpful in preliminarily determining whether there are hidden functional changes in the auditory pathway.Decreased Ⅰ-wave amplitude,shortened Ⅰ-wave latency,and wave Ⅲ amplitude greater than wave Ⅴ amplitude can be used as objective reference indicators.
7.Relationship Between NLRP3 Inflammatory Corpuscles and Chronic Atrophic Gastritis Based on "Spleen-mitochondrion Correlation"
Xiujuan LI ; Liqun LI ; Chaobei MA ; Yuyan WANG ; Wenjing FU ; Furong LIU ; Huanying ZHONG ; Lijian LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(17):267-273
Chronic atrophic gastritis (CAG) is a common and intractable disease in the digestive system characterized by the reduction or disappearance of gastric mucosal glands. The intestinal metaplasia or dysplasia in CAG is called precancerous lesion, which greatly increases the risk of cancerization. Dysactivation of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammatory corpuscles can release a large number of inflammatory factors, induce inflammatory cascade reactions, and participate in the process of many diseases. As reported, the dysactivation of NLRP3 inflammatory corpuscles can cause long-term chronic inflammatory infiltration of gastric mucosa and induce the development of CAG. Mitochondrial dysfunction plays an important role in the activation of NLRP3 inflammatory corpuscles. The accumulation of reactive oxygen species (ROS) produced by mitochondrial dysfunction is the key to activating NLRP3 inflammatory corpuscles. Professor LIU Youzhang put forward the theory of "spleen-mitochondrion correlation", which holds that the spleen mainly transports water and grains, generates qi and blood, transports nutrients to the whole body, and supplies energy and materials needed by the body. Adenosine triphosphate (ATP) generated by mitochondria through the circulation of tricarboxylic acid is the main energy source of the human body. The view that both of them serve as human energy processing plants coincides in terms of physiology. Pathologically, spleen deficiency is associated with mitochondrial oxidative phosphorylation dysfunction. Pathological products such as dampness, turbidity, phlegm, and blood stasis due to failure in transportation because of spleen deficiency are consistent with metabolites generated by mitochondrial dysfunction. Based on the theory of "spleen-mitochondrion correlation", this study discussed the pathogenesis of CAG in traditional Chinese medicine (TCM), analyzed the relationship between NLRP3 inflammatory corpuscles and the pathogenesis of CAG, and proposed that the activation of NLRP3 inflammatory corpuscles by mitochondrial dysfunction was the modern biological basis of the pathogenesis of spleen deficiency in CAG. The spleen-strengthening method may be related to improving the mitochondrial function and inflammatory response of patients with CAG and alleviating the damage of gastric mucosa, providing a new idea for TCM in the prevention and treatment of CAG.
8.Application of 4DCT-based lung functional imaging in radiotherapy for lung cancer
Wenjing ZHONG ; Ying LI ; Haixia CUI
Chinese Journal of Radiation Oncology 2023;32(5):481-487
Radiation pneumonia is a side effect that cannot be ignored in the current radiation therapy for lung cancer. At present, there are studies and reports of the introduction of functional imaging technology into lung cancer radiotherapy plans, in which 4DCT has better application prospects in radiotherapy for lung cancer because of its advantages of simple operation, high spatial resolution and no additional cost, etc. Compared with single-photon emission computed tomography (SPECT)-CT, positron emission tomography (PET)-CT, MRI has a better application prospect in radiotherapy of lung cancer. The use of 4DCT to obtain the patient's lung function status can predict radiation pulmonary toxicity and assist clinicians to deliver prompt interventions. Moreover, it can help carry out radiotherapy for functional lung avoidance, mitigate the damage of normal lung tissues, and alleviate chest toxicity, which may have wider application value in the future. In this article, research progress on functional lung imaging algorithms based on 4DCT and the application of radiation therapy for lung cancer was reviewed.
9.Doxycycline-moxifloxacin sequential therapy for Mycoplasma genitalium urethritis/cervicitis: a clinical observation
Sai LI ; Huazhong XUE ; Shuwen ZHANG ; Juan JIANG ; Shuzhen QI ; Yuanyuan ZHAO ; Jinping ZHANG ; Zhong SHA ; Wenjing LE ; Biwei WANG ; Shixuan ZHAO ; Xiaofeng ZHU ; Xiaohong SU
Chinese Journal of Dermatology 2022;55(12):1092-1095
Objective:To investigate outcomes and safety of doxycycline-moxifloxacin sequential regimen in the treatment of Mycoplasma genitalium urethritis/cervicitis. Methods:From June 2019 to December 2020, patients with Mycoplasma genitalium urethritis/cervicitis confirmed by nucleic acid amplification testing were successively recruited at Department of Sexually Transmitted Diseases, Hospital of Dermatology, Chinese Academy of Medical Sciences, and received sequential therapy with oral doxycycline for 7 days followed by oral moxifloxacin for 7 days. Clinical and/or etiological assessment was conducted 2 to 3 weeks after the end of treatment. Fisher′s exact test was used to analyze factors influencing the treatment outcome. Results:Totally, 36 eligible subjects were enrolled, including 30 males and 6 females. Among them, 18 (50%) patients completed post-treatment etiological assessment, which showed that 12 achieved microbiological cure, and treatment failures occurred in 6; another 18 patients achieved clinical cure. The overall response rate to doxycycline-moxifloacin sequential therapy was 83.3% (30/36, 95% confidence interval[ CI]: 70.5%, 96.1%) . The treatment outcome showed no significant association with the patients′ age, gender, marital status, number of sexual partners in the past 1 month, history of sexually transmitted diseases, history of antibiotic use in the past 1 month, or co-infections (all P > 0.05) . Conclusion:The efficacy of doxycycline-moxifloacin sequential regimen is limited in the treatment of Mycoplasma genitalium infections in Nanjing area, and clinicians should be alerted to the possibility of treatment failure in clinical practice.
10.Heritability and genetic correlation of body mass index and coronary heart disease in Chinese adult twins
Yu′e XI ; Wenjing GAO ; Xuanming HONG ; Jun LYU ; Canqing YU ; Shengfeng WANG ; Tao HUANG ; Dianjianyi SUN ; Chunxiao LIAO ; Yuanjie PANG ; Zengchang PANG ; Min YU ; Hua WANG ; Xianping WU ; Zhong DONG ; Fan WU ; Guohong JIANG ; Xiaojie WANG ; Yu LIU ; Jian DENG ; Lin LU ; Weihua CAO ; Liming LI
Chinese Journal of Preventive Medicine 2022;56(7):940-946
Objective:To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation.Methods:Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD.Results:A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95% CI: 0.49-0.55) and 0.76 (95% CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD ( rA=0.10, 95% CI:0.02-0.17). Conclusion:In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

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