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.Next-generation antifungal drugs: Mechanisms, efficacy, and clinical prospects.
Xueni LU ; Jianlin ZHOU ; Yi MING ; Yuan WANG ; Ruirui HE ; Yangyang LI ; Lingyun FENG ; Bo ZENG ; Yanyun DU ; Chenhui WANG
Acta Pharmaceutica Sinica B 2025;15(8):3852-3887
Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.
3.Lung ultrasound for guiding mechanical ventilation in preterm infants with respiratory distress syndrome
Xinyue DAO ; Lingyun BAO ; Kun DU
Chinese Journal of Perinatal Medicine 2025;28(11):944-949
Objective:To evaluate lung ultrasound (LUS) for dynamic monitoring during invasive mechanical ventilation in preterm infants with neonatal respiratory distress syndrome (NRDS) and characterize LUS features before and after ventilation.Methods:This retrospective cohort study enrolled 110 NRDS preterm infants requiring invasive mechanical ventilation within 24 hours of admission at Kunming Children's Hospital from August 2019 to June 2022. Patients were divided into control ( n=61, pre-LUS era from August 2019 to May 2021) and LUS groups ( n=49, LUS era from June 2021 to June 2022). LUS manifestations before and after ventilation were systematically analyzed, with intergroup comparisons of complications (pneumothorax, pulmonary hemorrhage, pulmonary consolidation), ventilation duration, weaning proportions within specific timeframes, and weaning failure rates using two independent t-tests, rank-sum tests, Chi square tests (Fisher's exact test) with Bonferroni correction. Results:(1) Pre-ventilation LUS showed snowflake sign in 95.9% (47/49) and ground-glass opacity in 4.1% (2/49) of infants. Post-ventilation alveolar recruitment manifested as an abrupt reduction of the snowflake sign with complete resolution by 12 hours, while ground-glass opacity demonstrated an initial increase followed by gradual decrease, with subsequent emergence of A-lines after 12 hours of ventilation. (2) The LUS group showed a higher detection rate of pulmonary consolidation compared to the control group assessed by chest X-ray [65.3% (32/49) vs. 14.8% (9/61), χ2=29.70, P=0.001]. (3) The LUS group demonstrated higher weaning proportion within 24 hours [22.4% (11/49) vs. 0.0% (0/61)], and lower proportion beyond 72 hours [40.8% (20/49) vs. 67.2% (41/61)] (Bonferroni-corrected, both P<0.008). (4) Ventilation duration was significantly shorter in the LUS group [54.0 (25.0-128.5) vs. 107.5 (52.3-143.8) hours, Z=-2.85, P=0.004] with comparable weaning failure rates [10.2% (5/49) vs. 9.8% (6/61), χ2<0.01, P>0.999]. Conclusion:LUS patterns differ significantly pre- and post-ventilation in NRDS infants, enabling dynamic monitoring of pulmonary changes during mechanical ventilation to facilitate treatment adjustment and timely extubation.
4.Prognostic value of PRMT2,TRAF2 and metastasis-related gene in renal clear cell carcinoma
Lingyun DU ; Yaowu WANG ; Nan REN
Tianjin Medical Journal 2025;53(5):492-497
Objective To analyze the correlation between expression levels of protein arginine methyltransferase 2(PRMT2),TNF receptor associated factor 2(TRAF2)and metastasis-related genes in clear cell renal cell carcinoma(ccRCC)and their evaluation value for prognosis.Methods A total of 110 patients with ccRCC were selected.The expression levels of PRMT2,TRAF2 protein and mRNA,and the expression of metastasis-related genes[N-cadherin(N-cad),E-cadherin(E-cad),vascular endothelial growth factor A(VEGFA),vascular endothelial growth factor C(VEGFC)]were detected in cancer tissue and paracancer tissue.Pearson correlation analysis was used to analyze the correlation between PRMT2,TRAF2 mRNA and metastasis-related genes,and the effect of PRMT2 and TRAF2 expression on the prognosis of ccRCC patients.Results The mRNA expression levels of PRMT2,TRAF2,N-cad,VEGFA and VEGFC were higher in ccRCC cancer tissue than those in adjacent tissue,and E-cad was lower in ccRCC cancer tissue than that in adjacent tissue(P<0.01).PRMT2 and TRAF2 mRNA were positively correlated with N-cad,VEGFA and VEGFC mRNA expression,and negatively correlated with E-cad mRNA expression in cancer tissue(P<0.01).The positive rates of PRMT2 protein and TRAF2 protein in ccRCC cancer tissue were higher than those in adjacent tissue(P<0.01).The positive rates of PRMT2 and TRAF2 protein in TNM stage III cancer tissue were higher than those in TNM stage I-II cancer tissue(P<0.05).The 3-year progression-free survival rate of the PRMT2 and TRAF2 positive group was lower than that of the negative group(P<0.05).TNM stage III,PRMT2 positive and TRAF2 positive were risk factors affecting the progression-free survival prognosis of ccRCC patients(P<0.05).Conclusion The expression levels of PRMT2 and TRAF2 are up-regulated in ccRCC,which are related to the expression of metastasis-related genes and TNM stage of tumor,and can be used as the marker for evaluating the prognosis of ccRCC.
5.A case report of relapsed and refractory multiple myeloma with multifocal extramedullary infiltration and pulmonary adenocarcinoma
Fang DU ; Lingyun ZHOU ; Jiao CHEN ; Danbo LIU ; Hongxian XIANG ; Haifei CHEN
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(1):122-128
Multiple myeloma(MM)remains an incurable disease,with most patients experiencing multiple relapses before ultimately progressing to refractory stage.Extramedullary infiltration is a common manifestation of relapse.However,distinguishing synchronous multifocal extramedullary infiltration from secondary malignancies poses significant diagnostic challenges.This study presents a case of relapsed refractory MM with multifocal extramedullary infiltration,diagnosed as coexistence of multiple myeloma extramedullary infiltration and pulmonary adenocarcinoma through multidisciplinary team(MDT)collaboration.Such coexistence is exceedingly rare in clinical practice and introduces substantial complexity in diagnosis and treatment planning.Through a comprehensive case report and literature review,this paper explores the diagnostic and therapeutic approaches to managing multifocal extramedullary infiltration coexisting with secondary malignancies in MM,highlighting the pivotal role of MDT in achieving precise diagnosis and optimizing patient outcomes.
6.Prognostic value of PRMT2,TRAF2 and metastasis-related gene in renal clear cell carcinoma
Lingyun DU ; Yaowu WANG ; Nan REN
Tianjin Medical Journal 2025;53(5):492-497
Objective To analyze the correlation between expression levels of protein arginine methyltransferase 2(PRMT2),TNF receptor associated factor 2(TRAF2)and metastasis-related genes in clear cell renal cell carcinoma(ccRCC)and their evaluation value for prognosis.Methods A total of 110 patients with ccRCC were selected.The expression levels of PRMT2,TRAF2 protein and mRNA,and the expression of metastasis-related genes[N-cadherin(N-cad),E-cadherin(E-cad),vascular endothelial growth factor A(VEGFA),vascular endothelial growth factor C(VEGFC)]were detected in cancer tissue and paracancer tissue.Pearson correlation analysis was used to analyze the correlation between PRMT2,TRAF2 mRNA and metastasis-related genes,and the effect of PRMT2 and TRAF2 expression on the prognosis of ccRCC patients.Results The mRNA expression levels of PRMT2,TRAF2,N-cad,VEGFA and VEGFC were higher in ccRCC cancer tissue than those in adjacent tissue,and E-cad was lower in ccRCC cancer tissue than that in adjacent tissue(P<0.01).PRMT2 and TRAF2 mRNA were positively correlated with N-cad,VEGFA and VEGFC mRNA expression,and negatively correlated with E-cad mRNA expression in cancer tissue(P<0.01).The positive rates of PRMT2 protein and TRAF2 protein in ccRCC cancer tissue were higher than those in adjacent tissue(P<0.01).The positive rates of PRMT2 and TRAF2 protein in TNM stage III cancer tissue were higher than those in TNM stage I-II cancer tissue(P<0.05).The 3-year progression-free survival rate of the PRMT2 and TRAF2 positive group was lower than that of the negative group(P<0.05).TNM stage III,PRMT2 positive and TRAF2 positive were risk factors affecting the progression-free survival prognosis of ccRCC patients(P<0.05).Conclusion The expression levels of PRMT2 and TRAF2 are up-regulated in ccRCC,which are related to the expression of metastasis-related genes and TNM stage of tumor,and can be used as the marker for evaluating the prognosis of ccRCC.
7.A case report of relapsed and refractory multiple myeloma with multifocal extramedullary infiltration and pulmonary adenocarcinoma
Fang DU ; Lingyun ZHOU ; Jiao CHEN ; Danbo LIU ; Hongxian XIANG ; Haifei CHEN
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(1):122-128
Multiple myeloma(MM)remains an incurable disease,with most patients experiencing multiple relapses before ultimately progressing to refractory stage.Extramedullary infiltration is a common manifestation of relapse.However,distinguishing synchronous multifocal extramedullary infiltration from secondary malignancies poses significant diagnostic challenges.This study presents a case of relapsed refractory MM with multifocal extramedullary infiltration,diagnosed as coexistence of multiple myeloma extramedullary infiltration and pulmonary adenocarcinoma through multidisciplinary team(MDT)collaboration.Such coexistence is exceedingly rare in clinical practice and introduces substantial complexity in diagnosis and treatment planning.Through a comprehensive case report and literature review,this paper explores the diagnostic and therapeutic approaches to managing multifocal extramedullary infiltration coexisting with secondary malignancies in MM,highlighting the pivotal role of MDT in achieving precise diagnosis and optimizing patient outcomes.
8.Lung ultrasound for guiding mechanical ventilation in preterm infants with respiratory distress syndrome
Xinyue DAO ; Lingyun BAO ; Kun DU
Chinese Journal of Perinatal Medicine 2025;28(11):944-949
Objective:To evaluate lung ultrasound (LUS) for dynamic monitoring during invasive mechanical ventilation in preterm infants with neonatal respiratory distress syndrome (NRDS) and characterize LUS features before and after ventilation.Methods:This retrospective cohort study enrolled 110 NRDS preterm infants requiring invasive mechanical ventilation within 24 hours of admission at Kunming Children's Hospital from August 2019 to June 2022. Patients were divided into control ( n=61, pre-LUS era from August 2019 to May 2021) and LUS groups ( n=49, LUS era from June 2021 to June 2022). LUS manifestations before and after ventilation were systematically analyzed, with intergroup comparisons of complications (pneumothorax, pulmonary hemorrhage, pulmonary consolidation), ventilation duration, weaning proportions within specific timeframes, and weaning failure rates using two independent t-tests, rank-sum tests, Chi square tests (Fisher's exact test) with Bonferroni correction. Results:(1) Pre-ventilation LUS showed snowflake sign in 95.9% (47/49) and ground-glass opacity in 4.1% (2/49) of infants. Post-ventilation alveolar recruitment manifested as an abrupt reduction of the snowflake sign with complete resolution by 12 hours, while ground-glass opacity demonstrated an initial increase followed by gradual decrease, with subsequent emergence of A-lines after 12 hours of ventilation. (2) The LUS group showed a higher detection rate of pulmonary consolidation compared to the control group assessed by chest X-ray [65.3% (32/49) vs. 14.8% (9/61), χ2=29.70, P=0.001]. (3) The LUS group demonstrated higher weaning proportion within 24 hours [22.4% (11/49) vs. 0.0% (0/61)], and lower proportion beyond 72 hours [40.8% (20/49) vs. 67.2% (41/61)] (Bonferroni-corrected, both P<0.008). (4) Ventilation duration was significantly shorter in the LUS group [54.0 (25.0-128.5) vs. 107.5 (52.3-143.8) hours, Z=-2.85, P=0.004] with comparable weaning failure rates [10.2% (5/49) vs. 9.8% (6/61), χ2<0.01, P>0.999]. Conclusion:LUS patterns differ significantly pre- and post-ventilation in NRDS infants, enabling dynamic monitoring of pulmonary changes during mechanical ventilation to facilitate treatment adjustment and timely extubation.
9.The curative effect and mechanism of magnetic hyperthermia in the treatment of knee osteoarthritis
Fei GAO ; Longlong DU ; Tong WANG ; Xuefeng LI ; Yuke ZHONG ; Qimeng GAO ; Rui CHEN ; Puwei YUAN ; Lingyun ZHAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(5):784-793
【Objective】 We combined the concept of traditional medicine with magnetic induction technology, originally brought up the research concept of magnetic hyperthermia to cure KOA, explored the mechanism and constructed a new treatment of KOA with modern medical features. 【Methods】 Through establishing a primary KOA model in rats and constructing ferrimagnetic vortex domain iron oxide nanorings (FVIOs) as a platform for highly efficient magnetic hyperthermia agent, the lesions of KOA were heated accurately under the low-intensity magnetic field. We confirmed the curative effect through the results of pain perception, histopathology, knee joint morphology and microscopic bone structure and the content of serum inflammatory factor, to study the therapeutic mechanism of magnetic hyperthermia for KOA. 【Results】 Compared with the model group, the recovery of mechanical pain threshold after magnetic hyperthermia improved by approximately 48.9%; the degree of hyperemia and edema of joint capsule and synovial tissue and the wear degree of joint cartilage surface, were significantly reduced; the Mankin and OARSI scores decreased by about 33% and 20%, respectively; the MicroCT results indicated that the degree of hardening of the subchondral bone also improved; the expression of inflammatory factors in the serum was reduced. 【Conclusion】 In this study, we utilized the FVIOs as a high-efficiency magnetic hyperthermia platform for the treatment of KOA. The efficacy of magnetic hyperthermia on KOA is clarified, and the mechanism is related to the inhibition of inflammatory factors.
10.An investigation of bacillary dysentery outbreaks in three schools in Ankang
Chinese Journal of School Health 2021;42(6):922-924
Objective:
To investigate risk factors and epidemiological characteristics of bacillary dysentery outbreaks in three schools, and to provide scientific basis for the prevention and control of the epidemic in the future.
Methods:
Case definition was established. All suspected, possible and confirmed cases of all students and faculty members from 3 schools (A, B, C) were selected for epidemiological investigation. Control group was used for case-control analysis, and relevant samples were collected for laboratory testing.
Results:
A total of 132 cases were found in 3 schools, all of which were from students, with the incidence rate of 17.74%. The morbidity in kindergarten A was 20.00%, in center primary school B it was 21.74%, and in junior middle school C it was 11.61%. Cohort studies and casecontrol studies suggested that schools are exposed places and that washing hands with raw water in schools was possible risk factor [OR(95%CI) =4.50(1.01-20.11)]. Nine stool samples were tested in laboratory, among which 8 were positive for Shigella(88.99%), and Shigella was detected in the end nodes of school s pipeline network, the water samples from canteen bucket, and the floor drains of sewer pipe.
Conclusion
The bacillary dysentery outbreaks in 3 schools was caused by Shigella, which may be due to fecal contamination of domestic water in 3 schools before the start of the school year. It is suggested to strengthen the management of centralized water supply and construction in rural areas, intensify the supervision at all levels, and sanitation and disinfection before school opens at all levels.


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