1.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
2.Monitoring results of mosquito-ovitraps placed in different orientations in multi-storey residential areas
Caixiong LIU ; Bin GE ; Haibing ZHANG ; Lin WANG ; Tao YANG ; Yujiao WEI ; Haiying XIE ; Yu ZHANG ; Hongxia LIU ; Juntao SHEN
Shanghai Journal of Preventive Medicine 2025;37(2):109-113
ObjectiveTo find out whether there is any difference in the monitoring results of mosq-ovitraps placed in different orientations in multi-storey residential areas, so as to provide a scientific basis for routine and emergency monitoring of Aedes albopictus with mosq-ovitraps in residential areas. MethodsFrom July 6th to October 26th 2023, one mosquito ovitrap was set up in each of the 4 orientations of east, south, west and north around the buildings in a multi-storey residential area in Jinhui Town, Fengxian District, Shanghai. Data was collected and recorded 72 hours after placement. The chi-square test was used to compare the mosquito ovitrap indices (MOIs) of two independent samples, and the Kruskal⁃Wallis H test was used to compare the MOIs of multiple independent samples. ResultsAfter 16 weeks of surveillance, 997 mosquito ovitraps were recovered, of which 211 were positive, with the mosquito ovitrap index (MOI) of 21.16% and the Aedes albopictus density index of 1.03 mosquitoes·ovitrap-1. The MOIs were higher in September (24.22%) and October (23.96%), and the MOIs in the west, south and north within the two months were all above 20.00%. From July to October, the MOIs in the east, west, south and north were 20.70%, 22.20%, 25.50% and 16.20%, respectively, and the difference in MOIs among the 4 orientations was not statistically significant (χ2=6.647, P=0.084). Stratified analysis by month showed that in August, the south side of the multi-storey residential areas had the highest MOI (31.30%), the north side had the lowest MOI (1.30%), and there was a statistically significant difference in MOI in the east, west, south and north (χ2=25.986, P<0.001). In October, the MOI in the west was the highest (33.30%) and the MOI in the east was the lowest (6.30%), the difference in MOIs of the 4 orientations was statistically significant (χ2=12.007, P=0.007). The MOIs in the south side of the building in the outskirts of the residential area from the 1st week in July to the 4th week in October was lower (19.20%) than that in the south side of the inner building (31.70%), and the difference in MOI was statistically significant (χ2=5.118, P=0.024). ConclusionThe study of MOI in different orientations in a multi-storey residential area is a preliminary exploration based on field work, and the results show that there is a difference in MOIs in different orientations during the peak breeding period of mosquitoes. Further indicators such as temperature, humidity and wind speed in different orientations can be collected to explore the influencing factors of MOIs.
3.Research progress on association between shift work and cardiometabolic risk in nurses
Meng FAN ; Yajuan YANG ; Fangbiao TAO ; Xiaoyan WU
Journal of Environmental and Occupational Medicine 2025;42(4):512-516
Cardiometabolic disease is one of the leading causes of morbidity and mortality in adults. In recent years, the prevalence of cardiometabolic disease has increased year by year, becoming a major problem in the global disease burden. The occurrence and development of cardiometabolic risk are affected by many factors. Shift work as an occupational hazard has been widely concerned. Nurses are a typical population for shift work, but few studies have looked at the association between their shift work and cardiometabolic risk. This article reviewed the current situation of cardiometabolic risk and the research progress on the association between shift work and cardiometabolic risk among nurses. The results showed that cardiometabolic risk is prevalent in the nurse population. Shift work is associated with cardiometabolic risks such as metabolic syndrome, cardiovascular disease, diabetes, and dyslipidemia, and is mediated by circadian rhythm disorder, hormone secretion disorder, and stress response. However, the causal relationship between shift work and cardiometabolic risk is still unclear, and further prospective cohort studies should be conducted to improve the understanding of the impact of shift work on cardiometabolic risk in order to improve the cardiometabolic health status of nurses.
4.Study on the safety and pharmacological effect on improving dyspepsia of Shuangshu decoction in rats
Xinyuan CHEN ; Changzhou XIONG ; Jiongfen LI ; Kangyi YU ; Huan XU ; Yingxia WANG ; Dan LIAO ; Junyu TAO ; Ziyi YANG ; Caizhi LIN
China Pharmacy 2025;36(9):1059-1064
OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia (FD) in rats. METHODS In safety test, 40 rats were divided into blank control group, Shuangshu decoction low-dose, medium- dose and high-dose groups [108, 216, 324 g/(kg·d), calculated by raw medicine, the same applies below]; they were given relevant medicine intragastrically, for continuous 14 days. The mortality and toxic reactions of rats were recorded, and the organ indexes of the liver, kidney, spleen, lung and heart of rats were calculated; the pathological morphological changes in the liver, kidney, spleen, lung, heart, stomach, duodenum, and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded, and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed, and blood routine and serum biochemical indicators were measured, in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group, model group, and Shuangshu decoction low-, medium-, and high-dose groups (9.45, 18.9, 37.8 g/kg), with 10 rats in each group. Except for blank control group, rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide (3.5 mg/kg). Rats in each group were administered the corresponding drug solution/normal saline intragastrically, once a day, for 14 consecutive days. After the last medication, fecal moisture content, intestinal propulsion rate, gastric emptying rate and serum level of motilin were all detected, and interstitial cell of Cajal (ICC) ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group, and no significant difference was found in organ coefficient, routine blood and serum biological index, compared to blank control group (P>0.05); no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that, compared with the blank control group, the fecal moisture content, gastric emptying rate, intestinal propulsion rate, and serum motilin levels in the model group were significantly decreased (P<0.05); in the colonic tissue, the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae, and the endoplasmic reticulum was dilated. Compared with model group, the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators (P< 0.05); additionally, there was a large number of mitochondria in the ICC of the colonic tissue, with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats; its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion, as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.
5.A Case Report of Pachydermoperiostosis by Multidisciplinary Diagnosis and Treatment
Jie ZHANG ; Yan ZHANG ; Li HUO ; Ke LYU ; Tao WANG ; Ze'nan XIA ; Xiao LONG ; Kexin XU ; Nan WU ; Bo YANG ; Weibo XIA ; Rongrong HU ; Limeng CHEN ; Ji LI ; Xia HONG ; Yan ZHANG ; Yagang ZUO
JOURNAL OF RARE DISEASES 2025;4(1):75-82
A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in
6.Para-aortic lymph node dissection with or without nerve-sparing in gynecological malignancies
Qiang WEN ; Yuyang ZHU ; Haifei ZHOU ; Li YANG ; Feng SHAO ; Tao ZHU ; Zhuyan SHAO
Journal of Gynecologic Oncology 2025;36(1):e9-
Objective:
Para-aortic lymph node dissection (PALND) is a widely used treatment that causes many complications. This study is to evaluate the efficacy and safety of nerve-sparing para-aortic lymph node dissection (NSPALND) by comparing it with conventional PALND in gynecological malignancies and to prove whether locating the superior hypogastric plexus (SHP) can help reveal the para-aortic nerves.
Methods:
This is a retrospective study of the patients who underwent para-aortic lymphadenectomy from January 2020 to December 2022 at Zhejiang Cancer Hospital. All of them were divided into NSPALND and PALND groups according to whether or not nervesparing was performed. The surgical, functional and oncological outcomes were evaluated.
Results:
There were 43 patients enrolled, of which, 20 patients underwent NSPALND and 23 patients underwent PALND. The para-aortic nerves were successfully revealed by locating the SHP in all 20 cases of NSPALND. The post-operative anal exhaust time in the NSPALND group was significantly shorter than that in the PALND group (2.5 vs. 4 days, p=0.006), and the incidence of acute intestinal obstruction in the NSPALND group was significantly lower than that in the PALND group (10% vs. 39%, p=0.029). There was no difference between the two groups in terms of catheterization duration, urinary retention, dysuria, as well as the number of lymph nodes removed and the para-aortic recurrence rate.
Conclusion
NSPALND can significantly reduce the rate of acute intestinal obstruction and improve post-operative intestinal function. Locating the SHP and using it as an anatomical landmark to reveal the para-aortic nerves is feasible. Its exact clinical value needs to be further studied.
7.Treatment of Hyperuricemia and Gouty Arthritis by Buyang Huanwu Tongfeng Decoction via Inhibition of PPAR-γ/NF-κB/AGEs/RAGE Pathway Based on Network Pharmacology
Yue CAO ; Wanmei YAO ; Tao YANG ; Man YANG ; Ruimin JIA ; Rongrong LU ; Xue FENG ; Biwang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):182-192
ObjectiveThis paper aims to investigate the potential molecular biological mechanism of Buyang Huanwu Tongfeng decoction in treating hyperuricemia and gouty arthritis by network pharmacology and molecular docking technology and preliminarily verify the mechanism through animal experiments. MethodsThe active ingredients and targets in the Buyang Huanwu Tongfeng decoction were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and ETCM databases. The DisGeNET and GeneCards databases were utilized to acquire disease targets associated with hyperuricemia and gouty arthritis. These disease targets were then intersected with drug targets to identify key targets. The R language ClusterProfiler package and Python were employed for conducting gene ontology(GO) enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis. The regulatory network diagram of the drug-key target-function-pathway was visualized using Cytoscape 3.9.1 software, and the protein-protein interaction (PPI) network for key targets was depicted. Finally, the hub gene was determined through topological analysis. Auto Dock, PyMOL, and other software were used for molecular docking to explore the possible therapeutic mechanism of Buyang Huanwu Tongfeng decoction for hyperuricemia and gouty arthritis. In animal experiments, a composite rat model of hyperuricemia induced by intraperitoneal injection of oteracil potassium combined with gouty arthritis induced by the modified Coderre method was established. Through hematoxylin-eosin(HE) staining, uric acid test, enzyme linked immunosorbent assay(ELISA), Western blot, and real-time polymerase chain reaction(Real-time PCR), the molecular mechanism and key targets of Buyang Huanwu Tongfeng decoction for treating hyperuricemia and gouty arthritis were observed. ResultsAfter screening and removing duplicate values, 76 active ingredients and 15 key targets were finally obtained. GO enrichment analysis yielded that the treatment of hyperuricemia and gouty arthritis with Buyang Huanwu Tongfeng decoction was significantly associated with acute inflammatory response, astrocyte activation, regulation of interleukin (IL)-8 production, nuclear receptor activity, and binding of growth factor receptor. KEGG pathway enrichment analysis obtained that the key target genes were significantly associated with the IL-17 signaling pathway, advanced glycosylation end/receptor of advanced glycation endproducts(AGE/RAGE) signaling pathway, anti-inflammatory, and other pathways. PPI network indicated that albumin(ALB), peroxisome proliferator-activated receptor-γ (PPAR-γ), IL-6, IL-1β, and C-reactive protein(CRP) were the key protein targets. The molecular docking results showed that ALB had the strongest binding force with beta-carotene (β-carotene). Biochemical results showed that blood uric acid decreased in the Buyang Huanwu Tongfeng decoction groups. HE staining results showed that the low-dose (7.76 g·kg-1·d-1), medium-dose (15.53 g·kg-1·d-1), and high-dose (31.05 g·kg-1·d-1) groups of Buyang Huanwu Tongfeng decoction had different degrees of remission, and the remission of the high-dose group was the most obvious. Fibroblastic tissue hyperplasia in synovial joints accompanied with inflammatory cell infiltration, as well as inflammatory cell infiltration in renal tissue of the high-dose group was significantly reduced, followed by the medium-dose and low-dose groups, and the expression of ALB, PPAR-γ, IL-6, IL-1β, and CRP was down-regulated to different degrees. ConclusionBy regulating the targets such as ALB, PPAR-γ, IL-6, IL-1β, and CRP, inhibiting the PPAR-γ/nuclear transcription factor (NF)-κB pathway, and reducing AGEs/RAGE-mediated inflammation, Buyang Huanwu Tongfeng decoction exerts anti-inflammatory and analgesic effects and activates blood circulation and diuresis in the treatment of hyperuricemia and gouty arthritis.
8.Rapid Identification of Different Parts of Nardostachys jatamansi Based on HS-SPME-GC-MS and Ultra-fast Gas Phase Electronic Nose
Tao WANG ; Xiaoqin ZHAO ; Yang WEN ; Momeimei QU ; Min LI ; Jing WEI ; Xiaoming BAO ; Ying LI ; Yuan LIU ; Xiao LUO ; Wenbing LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):182-191
ObjectiveTo establish a model that can quickly identify the aroma components in different parts of Nardostachys jatamansi, so as to provide a quality control basis for the market circulation and clinical use of N. jatamansi. MethodsHeadspace solid-phase microextraction-gas chromatography-mass spectrometry(HS-SPME-GC-MS) combined with Smart aroma database and National Institute of Standards and Technology(NIST) database were used to characterize the aroma components in different parts of N. jatamansi, and the aroma components were quantified according to relative response factor(RRF) and three internal standards, and the markers of aroma differences in different parts of N. jatamansi were identified by orthogonal partial least squares-discriminant analysis(OPLS-DA) and cluster thermal analysis based on variable importance in the projection(VIP) value >1 and P<0.01. The odor data of different parts of N. jatamansi were collected by Heracles Ⅱ Neo ultra-fast gas phase electronic nose, and the correlation between compound types of aroma components collected by the ultra-fast gas phase electronic nose and the detection results of HS-SPME-GC-MS was investigated by drawing odor fingerprints and odor response radargrams. Chromatographic peak information with distinguishing ability≥0.700 and peak area≥200 was selected as sensor data, and the rapid identification model of different parts of N. jatamansi was established by principal component analysis(PCA), discriminant factor alysis(DFA), soft independent modeling of class analogies(SIMCA) and statistical quality control analysis(SQCA). ResultsThe HS-SPME-GC-MS results showed that there were 28 common components in the underground and aboveground parts of N. jatamansi, of which 22 could be quantified and 12 significantly different components were screened out. Among these 12 components, the contents of five components(ethyl isovalerate, 2-pentylfuran, benzyl alcohol, nonanal and glacial acetic acid,) in the aboveground part of N. jatamansi were significantly higher than those in the underground part(P<0.01), the contents of β-ionone, patchouli alcohol, α-caryophyllene, linalyl butyrate, valencene, 1,8-cineole and p-cymene in the underground part of N. jatamansi were significantly higher than those in the aboveground part(P<0.01). Heracles Ⅱ Neo electronic nose results showed that the PCA discrimination index of the underground and aboveground parts of N. jatamansi was 82, and the contribution rates of the principal component factors were 99.94% and 99.89% when 2 and 3 principal components were extracted, respectively. The contribution rate of the discriminant factor 1 of the DFA model constructed on the basis of PCA was 100%, the validation score of the SIMCA model for discrimination of the two parts was 99, and SQCA could clearly distinguish different parts of N. jatamansi. ConclusionHS-SPME-GC-MS can clarify the differential markers of underground and aboveground parts of N. jatamansi. The four analytical models provided by Heracles Ⅱ Neo electronic nose(PCA, DFA, SIMCA and SQCA) can realize the rapid identification of different parts of N. jatamansi. Combining the two results, it is speculated that terpenes and carboxylic acids may be the main factors contributing to the difference in aroma between the underground and aboveground parts of N. jatamansi.
9.Shentong Zhuyutang Regulates SIRT1/Nrf2 Pathway to Ameliorate Intervertebral Disc Degeneration in Rats
Jiajun HUANG ; Diyou WU ; Guangyi TAO ; Yu ZHAO ; Junqing HUANG ; Bin YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):29-39
ObjectiveTo study the effect and mechanism of Shentong Zhuyutang in treating intervertebral disc degeneration (IDD) in rats. MethodsIn the cell experiment, male rats were administrated with normal saline or low-, medium-, and high-dose (3.38, 6.75,13.5 g·kg-1, respectively) Shentong Zhuyutang by gavage, respectively, and serum samples were collected after 7 days of continuous administration. Another 10 male rats were selected for the isolation of nucleus pulposus cells. The cell model of IDD was established by treatment with interleukin (IL)-1β. The modeled cells were then treated with Shentong Zhuyutang-containing serum and the ferroptosis inhibitor ferrostatin-1 (Fer-1), respectively, to investigate the effects of Shentong Zhuyutang-containing serum on the proliferation and ferroptosis of nucleus pulposus cells. To study the role of silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) in the regulation of ferroptosis in nucleus pulposus cells by Shentong Zhuyutang-containing serum, this study treated the cells with the SIRT1 inhibitor Ex 527 and the Nrf2 inhibitor ML385, respectively, in addition to the treatment with IL-1β and high-dose Shentong Zhuyutang-containing serum. The cell-counting kit-8 (CCK-8) assay and EdU staining were employed to measure the cell viability and proliferation, respectively. The Fe2+, glutathione (GSH), and malondiadehyde (MDA) levels were measured by colorimetric assay. Western blot was employed to determine the protein levels of glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family 4 (ACSL4), Collagen Ⅱ, Aggrecan, SIRT1, and Nrf2. Immunofluorescence was used detect SIRT1 expression. In the animal experiment, male rats were treated with anulus puncture for the modeling of IDD. Rats were randomly assigned into sham operation, model, Shentong Zhuyutang-containing serum (13.5 g·kg-1), and positive control (nimesulide dispersible tablets, 0.18 mg·kg-1) groups. Rats in the drug intervention groups were administrated with corresponding agents at 1 mL·kg-1, and those in the sham operation and model groups were administrated with equal volumes of normal saline, once daily for 28 consecutive days. At the end of the last administration, the histopathological changes in the intervertebral discs of rats were observed by hematoxylin-eosin staining and scored by the Masuda method. Western blot was employed to determine the protein levels of SIRT1, Nrf2, GPX4, and Collagen Ⅱ in the nucleus pulposus tissue. ResultsCompared with the control group, the IL-1β group of nucleus pulposus cells showed elevated levels of Fe2+, MDA, and ACSL4 (P<0.05), decreased cell viability, lowered GSH level, and down-regulated protein levels of GPX4, Collagen Ⅱ, and Aggrecan (P<0.05). Shentong Zhuyutang-containing serum and Fer-1 reversed the effects of IL-1β on the viability and ferroptosis of nucleus pulposus cells and up-regulated the protein levels of Collagen Ⅱ and Aggrecan in nucleus pulposus cells (P<0.05). Compared with the control group, the IL-1β group showcased down-regulated expression of Sirt1 and Nrf2 in nucleus pulposus cells (P<0.05). Compared with the IL-1β group, the high-dose Shentong Zhuyutang-containing serum+IL-1β group showed up-regulated expression of SIRT1 and Nrf2 in nucleus pulposus cells (P<0.05). Compared with the high-dose Shentong Zhuyutang-containing serum+IL-1β group, the ML385 group showed down-regulated protein levels of Nrf2 and GPX4, lowered GSH level, and elevated Fe2+ and MDA levels (P<0.05). In addition, the Ex 527 group showed down-regulated protein levels of SIRT1, Nrf2, and GPX4 (P<0.05). The results of the animal experiment showed that compared with the sham operation group, the model group had severe degeneration of the intervertebral disc tissue with increased pathological score, up-regulated protein level of ACSL4 (P<0.05), and down-regulated protein levels of SIRT1, Nrf2, GPX4, and Collagen Ⅱ (P<0.05). Compared with the model group, the Shentong Zhuyutang group showed alleviated IDD with declined pathological score, down-regulated protein level of ACSL4 (P<0.05), and up-regulated protein levels of SIRT1, Nrf2, GPX4, and Collagen Ⅱ (P<0.05). ConclusionShentong Zhuyutang may activate the SIRT1/Nrf2 signaling pathway to inhibit the ferroptosis of nucleus pulposus cells, thereby delaying the process of IDD in rats.
10.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.

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