1.Proteomics and Network Pharmacology Reveal Mechanism of Xiaoer Huatan Zhike Granules in Treating Allergic Cough
Youqi DU ; Yini XU ; Jiajia LIAO ; Chaowen LONG ; Shidie TAI ; Youwen DU ; Song LI ; Shiquan GAN ; Xiangchun SHEN ; Ling TAO ; Shuying YANG ; Lingyun FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):69-79
ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough (AC) by Xiaoer Huatan Zhike granules (XEHT) based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin (OVA) and 100 mg aluminum hydroxide, a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model, low-, medium- and high-dose (1, 5, 20 g·kg-1, respectively) XEHT, and sodium montelukast (1 mg·kg-1) groups (n=6), and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage, and those in the blank and model groups received the same volume of normal saline by gavage, 1 time·d-1. After 10 consecutive days of drug administration, the guinea pigs were stimulated by 1% OVA nebulization, and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA) in the bronchoalveolar lavage fluid (BALF) and immunoglobulin G (IgG) and immunoglobulin A (IgA) in the serum. Immunohistochemistry (IHC) was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6, interleukin-1β (IL-1β), and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group, the model group showed increased coughs (P<0.01), elevated levels of CRP, TNF-α, IL-6, and MDA and lowered level of SOD in the BALF (P<0.05, P<0.01), elevated levels of IgA and IgG in the serum (P<0.05, P<0.01), congestion of the lung tissue and infiltration of inflammatory cells, increased expression of IL-6 and TNF-α (P<0.01), large areas of low electron density edema in type Ⅱ epithelial cells, obvious swelling and vacuolization of the organelles, karyopyknosis or sparse and dissolved chromatin, and up-regulated mRNA levels of IL-6, IL-1β, and TNF-α (P<0.01). Compared with the model group, the drug administration groups showed reduced coughs (P<0.01), lowered levels of CRP, TNF-α, IL-6, and MDA and elevated level of SOD in the BALF (P<0.05, P<0.01), alleviated lung tissue congestion, inflammatory cell infiltration, and type Ⅱ epithelial cell injury, and decreased expression of IL-6 and TNF-α (P<0.01). In addition, the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG (P<0.05, P<0.01). The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6, IL-1β, and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α (P<0.05, P<0.01). Phospholipase D, mammalian target of rapamycin (mTOR), and epidermal growth factor receptor family of receptor tyrosine kinase (ErbB) signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D, mTOR, and ErbB signaling pathways.
2.Optimization of Processing Technology of Honey Bran-fried Rosae Laevigatae Fructus and Analysis of Its Mechanism in Treatment of Ulcerative Colitis
Bin LIU ; Lingyun ZHONG ; Hongbing LUO ; Qi DENG ; Fuyu XU ; Simin ZHONG ; Ying ZHOU ; Xide YE ; Feipeng GONG ; Yuncheng GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):216-224
ObjectiveTo optimize the processing technology of honey bran-fried Rosae Laevigatae Fructus(h-RLF), formulate relevant quality standards, and explore its improving effect and mechanism on mice with ulcerative colitis(UC) induced by dextran sodium sulfate(DSS). MethodsTaking the content of polysaccharides and water-soluble extract as the indexes, L9(34) orthogonal test was used to optimize parameters of the amount of honey bran, frying time and frying temperature. The quality of 15 batches of h-RLF decoction pieces was evaluated according to the optimized process, and the inspection limit standard was preliminarily drawn up. Eighty SPF male Kunming mice were randomly divided into 8 groups, including the blank group, model group, mesalazine group(0.13 g·kg-1), RLF group(3.77 g·kg-1), bran-fried RLF group(3.77 g·kg-1), h-RLF low, medium and high dose groups(1.89, 3.77, 7.54 g·kg-1), with 10 mice in each group. The mice in the blank group were free to drink pure water, and the other groups were free to drink 3% DSS solution for 7 days to prepare UC mouse model. Each treatment group was given corresponding drugs by intragastric administration, and the blank and model groups were given equal volume of normal saline. The body weight of mice was recorded daily and the disease activity index(DAI) was calculated. After the administration, the colon tissues of mice were collected to observe the pathological changes by hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor(TNF)-α, interleukin(IL)-1β, IL-6 and IL-10 in the colon of mice were detected by enzyme-linked immunosorbent assay(ELISA). Western blot was used to detect the expression levels of phosphorylation nuclear transcription factor-κB p65(p-NF-κB p65), Toll-like receptor 4(TLR4), p-p38 mitogen-activated protein kinase(p-p38 MAPK), p-extracellular signal-regulated kinase(p-ERK) and p-c-Jun N-terminal kinase(p-JNK) proteins in colon tissues. ResultsThe optimum processing technology of h-RLF was 20 g honey bran per 100 g RLF, and stir-frying at 200 ℃ for 8 min. The limit standard under the examination of h-RLF was preliminarily formulated as follows:the polysaccharide content should not be less than 25% based on anhydrous glucose(C6H12O6), the content of water-soluble extract should not be less than 38%, the moisture content should not be more than 12.0%, the total ash content should not be more than 5.0%, and the acid-insoluble ash content should not be more than 1.0%. The cluster heat map analysis showed that the quality of RLF from Huanggang, Hubei province was better. Animal experiments showed that compared with the blank group, the DAI score of the model group was significantly increased, the levels of TNF-α, IL-1β and IL-6 in the colon tissue were significantly increased, the IL-10 level was significantly decreased, the colonic mucosa was seriously damaged, accompanied by a large number of inflammatory cell infiltration, tissue congestion and a significant reduction in glands, and the expression levels of p-NF-κB p65, TLR4, p-p38 MAPK, p-ERK and p-JNK proteins were significantly increased(P<0.01). Compared with the model group, each administration group could alleviate the symptoms of colonic ulcer, the structure of colonic crypt was basically intact, and the glands were arranged in an orderly manner. Among them, the high-dose group of h-RLF had a better effect, which could significantly reduce the DAI score and the levels of TNF-α, IL-1β and IL-6 in colon tissue(P<0.01), and significantly increase the level of IL-10(P<0.01), alleviate the colonic mucosal injury, and effectively inhibit the expression levels of p-NF-κB p65, TLR4, p-p38 MAPK, p-ERK and p-JNK proteins(P<0.01). ConclusionThe key parameters of the processing technology of h-RLF are determined, and the optimized technology is stable and feasible. The established quality standard is simple and reliable, and can be used for the quality control. h-RLF can effectively alleviate DSS-induced UC, and its mechanism may be related to inhibiting the activation of NF-κB/TLR4/MAPK pathway.
3.The Association between Ophthalmic Artery Doppler Variables and the Severi-ty of Pre-eclampsia:a Meta-analysis
Li DAI ; Xiaohong WEI ; Lingyun LIAO ; Yangxue YIN ; Qin XU ; Shuangshuang XIE ; Rong ZHOU
Journal of Practical Obstetrics and Gynecology 2024;40(2):153-158
Objective:To investigate the association between the Doppler variables of the ophthalmic artery with the severity of preeclampsia(PE).Methods:Systematic literature was searched between January 1995 and March 2023 in PubMed,Web of Science,Embase,and the Cochrane Library.Studies comparing ophthalmic artery Doppler variables,including peak systolic velocity(PSV),end-diastolic velocity(EDV),resistive index(Rl),pulsa-tility index(PI),and peak ratio(PR,the ratio of the flow velocity of the second peak to that of the initial peak)in patients with PE,severe preeclampsia(sPE),and healthy pregnant women were included.The random-effects model was adopted as the method of pooled analysis,and the I2value was used to assess heterogeneity.The pooled standardized mean difference(SMD)with 95%confidence interval(CI)was used to estimate the associa-tion between ophthalmic artery Doppler variables and PE patient's characteristics.Results:Eight retrospective studies were eventually included in this Meta-analysis.Our pooled results suggested that compared with PE ca-ses,sPE patients had lower PI levels(SMD-0.56,95%CI-0.92~-0.20,P=0.000),higher EDV levels(SMD 0.47,95%CI 0.12~0.83,P=0.028)and higher PR levels(SMD0.96,95%CI 0.13~1.78,P=0.023).Howev-er,there was no significant difference between PE and sPE patients about the PSV and RI(P=0.361,P=0.626).Conclusions:This review demonstrates that ophthalmic artery Doppler variables(PI,EDV and PR)could be useful for predicting PE and PE development(especially in identifying sPE),which in turn may help the practitioner in the management of these complicated cases and in taking early necessary precautions.
4.Research progress of immune checkpoint inhibitor associated pneumonia in non-small cell lung cancer and integrated TCM and Western medicine treatment
Jingtao ZHANG ; Zichen LIU ; Lingyun JI ; Fei XU
Chinese Journal of Immunology 2024;40(1):213-219
Immune checkpoint inhibitors(ICIs)mainly including the CTL antigen 4(CTLA-4)and PD-1/PD-L1,which would offer a notable clinical benefit for non-small cell lung cancer(NSCLC)patients.By strengthening the antitumor immune re-sponse of the body,ICIs lead to immune-related adverse events(irAEs),including checkpoint inhibitor pneumitis(CIP).Although the clinical incidence of CIP is relatively low,some serious cases may prolong or terminate of immunotherapy,even life threateing.This article tries to summarize the clinical manifestations,pathological characteristics,biological mechanism,susceptible population,diagnosis and differential diagnosis,and integrated traditional Chinese and Western medicine treatment of CIP,in order to understand CIP more clearly.
5.Exploration on Syndrome Differentiation Thinking for Stress Sensitization-induced Depression from the Perspective of"Deficient Qi with Stagnation and Heat"
Xu CHEN ; Jing CAO ; Qianlin JIA ; Lingyun XI ; Yang BAI ; Haoyu PANG ; Xia HONG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(1):11-14
TCM proposes that the core pathological mechanism of depression is"deficient qi with stagnation and heat",with the following pathogenic characteristics and evolution patterns:"deficient qi"as the nature,and deficiency in nature is in spleen,and deficiency in superficiality is in brain;"stagnation"is the superficiality,and qi stagnation,phlegm stagnation,and blood stagnation are in the brain collaterals;"heat"fires the brain collaterals,depression raised the heat,and excessive heat accumulated to stagnation.Based on the understanding of the pathogenesis of depression caused by stress sensitization in modern medicine,this article explored the potential association between this mechanism and the core pathogenesis of"deficient qi with stagnation and heat".It proposed that tonifying deficiency,promoting circulation,and clearing heat are the basic treatment principles for depression.By inhibiting inflammatory reactions and improving the stress sensitization state of neurons and glial cells,TCM compound formulas can exert multi-target and multi-dimensional therapeutic characteristics.
6.Origin,Processing Method and Quality Standard of Fermentum Rubrum: A Review
Fuyu XU ; Hongbing LUO ; Lingyun ZHONG ; Songhong YANG ; Qi DENG ; Bin LIU ; Simin ZHONG ; Ying ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):267-274
Fermentum Rubrum(FR) is a kind of traditional Chinese medicine with dual-use functions of medicine and food, which has been used for more than 1 000 years. By referring to the ancient herbal classics and modern laws and regulations, the author sorted out the origin of FR, sorted out the development of processing, and analyzed the problems existing in the quality standard, aiming to provide a basis for further research and development of FR. There are many theories about the origin of FR. After summarizing and sorting out the relevant literature, three viewpoints are mainly drawn, including Han dynasty origin theory, Wei and Jin origin theory and Tang dynasty origin theory. After synthesizing the views of various schools, it is believed that the origin of FR should be no later than the Eastern Han dynasty. FR is made from rice by fermentation, which has the effect of strengthening the spleen, eliminating food, promoting blood circulation and removing stasis after fermentation. Although the natural fermentation in ancient times has been able to pay attention to the influence of temperature, humidity and strain on the quality of FR, due to the low level of science and technology, there are still problems such as complicated and cumbersome process, large workload and high labor cost. To the pure fermentation in modern times, the fermentation processing method of FR has been evolved, gradually improved and perfected. However, due to the lack of standardized research, there is no unified standard for the fermentation process of FR in various regions, and the quality standard lags behind seriously, which leads to the unstable product quality on the market. Among the 15 specifications for the preparation of FR, only 6 have been published in the past 5 years, and most of them have not been revised in a timely manner, and some of them have not been included in the updated version. Based on this, it is recommended to carry out a systematic study on processing technology of FR, and the best process is selected to accelerate the revision and improvement of its standardization, so as to improve the quality of FR sold in the market and promote its stable and sustainable development.
7.Analysis of the epidemic characteristics and disease burden of hospitalized children with viral myocarditis in China from 2016 to 2021
Luci HUANG ; Wei SHAO ; Lingyun GUO ; Yiliang FU ; Fei LI ; Hui XU ; Guoshuang FENG ; Lu GAO ; Zhengde XIE ; Yue YUAN ; Gang LIU ; Xiangpeng CHEN
Chinese Journal of Experimental and Clinical Virology 2024;38(4):432-438
Objective:This study aimed to provide basic data for the prevention, diagnosis and treatment of pediatric viral myocarditis (VMC) in China through analyzing the epidemic characteristics and disease burden of pediatric inpatients with VMC from 2016 to 2021.Methods:We performed a descriptive statistical analysis to the age, genders, seasons, regions and hospitalization cost and days of pediatric VMC inpatients and the death. All of the information was obtained from 27 Children′s hospitals or Maternal and Child Health hospitals of 23 provinces of China from 2016 to 2021.Results:A total of 7 647 599 cases including 1 646 VMC inpatients were admitted into our study. The annual numbers of hospitalizations were 173, 227, 313, 301, 295 and 337, with the hospitalized constituent ratios being 14.9/100 000, 17.9/100 000, 23.0/100 000, 20.5/100 000, 26.5/100 000 and 26.4/100 000 from 2016 to 2021. In recent 6 years, the proportion of VMC hospitalizations had increased yearly ( P<0.001), and had associated with the onset age ( P<0.001). Aged 12-≤18 years owned the highest hospitalized constituent ratio. The Northeast of China owned the largest number of VMC inpatients, and the East second to it. Among the 1 646 VMC children, there were 68 deaths, with the hospitalized case fatality rate of 4.13%. There were no significant differences between genders, age, seasons, years and fatality rate of VMC inpatients. For the diseases burden, the median of hospitalization days of all VMC inpatients was 10 days (IQR 6, 21), and the median of hospitalization cost was 1 1 842.3 RMB (IQR 6 969.22, 19 714.78). The median of hospitalization days of deceased VMC children was only 1 day (IQR 1, 3), the median cost could be 8 874.03 RMB (IQR 5 277.94, 5 6 151.59). Conclusions:In this study, we found that proportion of hospitalization of VMC children increased year by year, adolescence might be a risk factor of VMC. The fatality of VMC inpatients could be up to 4.13%, and the death led to a huge economic burden of society, family and individuals.
8.Discussion on the Effects of Baitouweng Decoction on Improving Intestinal Mucosal Healing in Mice with Ulcerative Colitis Based on RIPK1/RIPK3/MLKL Signaling Pathway
Jiansheng HU ; Wen WANG ; Xueliang YANG ; Lingyun XU ; Xinying ZHANG ; Hongbo SU ; Yongli ZHANG ; Shumei LIN ; Linmei SUN
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(7):106-112
Objective To explore the effects and mechanism of Baitouweng Decoction in intestinal mucosal healing in mice with ulcerative colitis(UC)based on RIPK1/RIPK3/MLKL signaling pathway.Methods Totally 30 C57BL/6 male mice were randomly divided into control group,model group,Baitouweng Decoction group,infliximab group and combination group(Baitouweng Decoction+infliximab),with 6 mice in each group.A mouse model of UC was established by free administration of 3.5%sodium gluconate sulfate solution for 7 days.After modeling,Baitouweng Decoction group was given 8 g/kg Baitouweng Decoction solution by gavage daily,while the infliximab group was given 5 mg/kg infliximab intraperitoneal injection,the combination group was given synchronous gastric and intraperitoneal injection,while the control group and model group were given equal volume of normal saline by gavage for 7 consecutive days.The body mass of mice was recorded daily,fecal characteristics were observed,and disease activity index(DAI)score was performed,colon length was measured after intervention,ELISA was used to detect the contents of serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α),RT-qPCR was used to detect mRNA expressions of RIPK1,RIPK3 and MLKL in colon tissue,Western blot and immunofluorescence staining were used to detect the expressions of RIPK1,RIPK3 and MLKL protein in colon tissue.Results Compared with the control group,the model group mice showed a decrease in body mass(P<0.01),an increase in DAI score(P<0.01),a shortened colon length(P<0.01),and an increase in serum IL-6 and TNF-α content(P<0.01);colonic mucosal was destructed,with disappearance of crypts and glandular structures,extensive infiltration of inflammatory cells,and increased pathological score of colon tissue(P<0.01);the mRNA and protein expressions of RIPK1,RIPK3 and MLKL in colon tissue increased(P<0.01,P<0.05).Compared with the model group,the body mass of mice in each treatment group increased(P<0.01),and the DAI score decreased(P<0.01),colon length increased(P<0.01),and the contents of serum IL-6 and TNF-α decreased(P<0.05,P<0.01);the destruction of the colonic mucosal barrier was reduced,the pathological score of colon tissue was reduced(P<0.05);the expressions of RIPK1,RIPK3 and MLKL mRNA and protein in colon tissue decreased(P<0.05,P<0.01).Conclusion Baitouweng Decoction can alleviate intestinal mucosal damage and inflammation in UC mice,and its mechanism may be related to the inhibition of the RIPK1/RIPK3/MLKL signaling pathway.
9.Guidelines for Psychological Rehabilitation Intervention Combined Integrated Traditional Chinese and Western Medicine After Radical Surgery for Early and Middle Stage Colorectal Cancer
Yufei YANG ; Lili TANG ; Lingyun SUN ; Ying PANG ; Zixu WANG ; Qiuli YANG ; Yun XU ; Haibo ZHANG ; Peng SHU ; Yutong FEI ; Rongyan PENG ; Jiaxi LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(21):10-23
In recent years, the incidence of colorectal cancer has been rising in China, and with the promotion of early screening and early diagnosis, most colorectal cancers are able to achieve long-term survival through timely diagnosis and treatment. Nevertheless, 30%-70% of patients with early to mid-stage colorectal cancer after radical surgery still have psychological problems such as anxiety, depression, and fear of recurrence and metastasis, and they hope to seek help from traditional Chinese medicine(TCM) treatment. In order to further standardize the integrated traditional Chinese and western medicine psychological rehabilitation interventions of stage Ⅰ-Ⅲ colorectal cancer after radical surgery, and to improve the diagnosis and treatment level, under the support of the pilot project of clinical collaboration between Chinese and western medicine for major and difficult diseases of National Administration of TCM, experts in oncology, integrated Chinese and western medicine, psychology, surgery, nursing, evidence-based medicine and other disciplines from 10 units nationwide participated in the work, led by Xiyuan Hospital,China Academy of Chinese Medical Sciences and Beijing Cancer Hospital. Based on the methodology and process of guideline development of the World Health Organization Handbook for Guideline Development and the Regulations for Group Standards of China Association of Chinese Medicine, the Guidelines for Psychological Rehabilitation Intervention Combined Integrated Traditional Chinese and Western Medicine After Radical Surgery for Early and Middle Stage Colorectal Cancer have been developed according to the current best evidence, extensive consultation with clinical experts and following the situation of current clinical practice. The guideline provides the psychological characteristics, the needs and willingness to accept psychological rehabilitation, the interventions for psychological rehabilitation, evaluation of efficacy, follow-up review, educational guidance and others of patients with stage Ⅰ-Ⅲ colorectal cancer after radical surgery. It can provide guidance for TCM(integrated Chinese and western medicine) clinicians and psychologists engaged in the psychological rehabilitation of integrated Chinese and western medicine oncology, especially for doctors in primary medical institutions.
10.Therapeutic effects of Chinese herbal medicines for treatment of urolithiasis: A review.
Chen JIANG ; Lingyun WANG ; Yang WANG ; Rongjia XU ; Hongtao YANG ; Jibin PENG
Chinese Herbal Medicines 2023;15(4):526-532
Urolithiasis is a common and complex disease of the urinary system, which can cause urinary tract blockage, urinary tract infection, and even damage to urinary system-related tissues. Although urolithiasis can be cured, its high recurrence rate and the development of chronic kidney disease in some patients have drawn the attention of nephrologists. Although the application of extracorporeal lithotripsy, percutaneous nephrolithotomy and other minimally invasive techniques have made the treatment of urolithiasis more efficient, pharmacotherapy plays an indispensable role in reducing their morbidity and recurrence rates. Traditional Chinese medicine (TCM) has been used for treatment and prevention of urolithiasis in developing countries for centuries, known for its unquestionable efficacy and safety. This article reviews the progress of clinical trials and pharmacological studies on the treatment of urolithiasis with Chinese herbal medicines (CHMs). The mechanism of CHMs in the treatment of urolithiasis mainly involve preventing further growth and aggregation of urolithiasis, reducing the PH of urine, promoting calculus dissolution. Furthermore, some CHMs can increase urine output, relax smooth muscles, and promote the removal of calculus. These findings provide new treatment strategies and options for urolithiasis and secondary kidney damage.

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