This study aims to investigate the effects and mechanisms of the effective-compounds of Jinshui Huanxian formula (ECC-JHF) in improving pulmonary fibrosis. Animal experiments were approved by the Ethics Committee of the Animal Experiment Center of Henan University of Chinese Medicine (approval number: IACUC-202306012). The mouse model of pulmonary fibrosis was induced using bleomycin (BLM). Hematoxylin-eosin (H&E) staining was used to detect the histopathological changes of lung tissues. Masson staining was used to assess the degree of fibrosis in lung tissues. Immunofluorescence (IF) and real-time quantitative PCR (qPCR) were performed to measure the expression of collagen type I (COL I), α-smooth muscle actin (α-SMA), fibronectin (FN), interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) in lung tissues. Flow cytometry (FCM) was employed to detect the proportion of M1 and M2 macrophages in the bronchoalveolar lavage fluid (BALF) of mice. IF and qPCR were also used to detect the expression of lipase family member N (LIPN) in lung tissues. Free fatty acid assay kit was used to detect the level of free fatty acids in lung tissue. Bone marrow-derived macrophages (BMDMs) were treated with interleukin-4 (IL-4) to induce M2 polarization. FCM was used to measure the proportion of CD206⁺ M2 macrophages. IF was utilized to detect LIPN expression and lipid droplet decomposition. The results showed that in BLM-induced pulmonary fibrosis mice, ECC-JHF significantly attenuated BLM-induced alveolar inflammation and collagen deposition, inhibited fibroblast activation in lung tissues, and decreased the proportion of M2 macrophages in BALF. It also significantly suppressed LIPN expression and free fatty acid level in lung tissues. In the IL-4 induced BMDMs M2 polarization model, ECC-JHF significantly inhibited the proportion of CD206⁺ M2 macrophages, down-regulated the expression of LIPN, and blocked lipid droplet catabolism. These results suggest that ECC-JHF may alleviate bleomycin-induced pulmonary fibrosis by inhibiting lipid droplet decomposition and M2 macrophage polarization.

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

Asthma, a chronic inflammatory airway disease with a high global prevalence, has a complex pathogenesis, in which airway remodeling plays a key role in the chronicity of the disease. Airway remodeling involves a series of pathophysiological changes, including airway epithelial damage, proliferation of mucous glands and goblet cells, subepithelial fibrosis, proliferation and migration of airway smooth muscle cells, and epithelial-mesenchymal transition. These complex pathological changes significantly increase airway resistance and responsiveness, forming an important pathological basis for refractory asthma. Currently, the regulatory mechanisms of airway remodeling focus on signaling pathways and regulatory targets. The signaling pathways include phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), nuclear factor-κB(NF-κB), transforming growth factor-β1(TGF-β1)/Smads, and mitogen-activated protein kinase(MAPK). The regulatory targets include microRNAs(miRNAs), competing endogenous RNAs(ceRNAs), long non-coding RNAs(lncRNAs), and circular RNAs(circRNAs). Key proteins involved in these processes include TGF-β1, silencing information regulator 2-related enzyme 1(SIRT1), chitinase 3-like protein 1(YKL-40), and adenosine deaminase-metalloproteinase 33(ADAM33). In recent years, the potential of traditional Chinese medicine in the treatment of asthma has become increasingly evident. Its active ingredients, extracts, and complexes can inhibit airway remodeling in asthma through multiple pathways, demonstrating a variety of effects, including anti-inflammatory actions, inhibition of smooth muscle cell proliferation and migration, regulation of epithelial-mesenchymal transition, attenuation of fibrosis and basement membrane thickening, reduction of mucus secretion, inhibition of vascular remodeling, modulation of immune imbalance, and antioxidative stress. This paper aims to provide an in-depth analysis of the pathogenesis and therapeutic targets of asthma, offering theoretical support and innovative strategies for clinical research and drug development in the treatment of asthma.
Asthma/pathology* ; Humans ; Airway Remodeling/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Signal Transduction/drug effects* ; Medicine, Chinese Traditional ; Transforming Growth Factor beta1/metabolism*

Widespread utilization of glyphosate has led to environmental residues,posing potential threats to ecological systems and human health.Traditional methods for detection of glyphosate are limited by specialized equipment and operational techniques,resulting in inefficient responses.Therefore,it is urgent to develop a convenient,sensitive and accurate detection method for detection of glyphosate.Herein,a new naphthalenesulfonamide-based"Turn-on"fluorescent probe was synthesized using 2-chloroaniline and dansyl chloride as raw materials through a one-step process,which showed a good linear relationship between the glyphosate concentration in concentration range of 0.003-70 μmol/L and the fluorescence intensity(R2=0.995),with a detection limit of 2.73 nmol/L(S/N=3).Analytical techniques such as nuclear magnetic resonance(NMR)spectroscopy and high-resolution mass spectrometry(HRMS)were used to investigate the interaction mechanism between the fluorescent probe and glyphosate.The results indicated that a nucleophilic substitution reaction occurred between the probe and the secondary amine(—NH—)of glyphosate,inducing a photoinduced electron transfer(PET)effect which enhanced the fluorescence intensity by 11.2 times.The probe showed good anti-interference ability towards coexisting metal ions,anions and pesticides in water.When applied to determination of glyphosate in the samples such as tap water,river water(Xiangxi River Reservoir),soil,soybeans,and corn,the spiking recoveries ranged from 94.7％to 109.9％,demonstrating the high accuracy and broad applicability of this detection method.A portable test strip based on this fluorescent probe was developed for rapid semi-quantitative analysis of glyphosate.The developed method was rapid,sensitive,and portable,providing theoretical and technical support for on-site measurement of environmental contaminants.

Objective To explore the predictive value of automated breast ultrasound(ABUS)features combined with Ki-67 in predicting pathological complete response(pCR)after neoadjuvant chemotherapy(NAC)in triple-negative breast cancer(TNBC).Methods A retrospective analysis was conducted on 127 female TNBC patients treated at Xijing Hospital,Air Force Medical University from March 2019 to December 2023.All patients underwent NAC and surgical treatment after ABUS examination.Based on postoperative pathological results,patients were divided into pCR group(n=60)and non-pathological complete response(npCR)group(n=67).Differences in various parameters before NAC were compared between the two groups.LASSO regression was used to identify independent factors influencing pCR after NAC in TNBC patients,and a predictive model was constructed using multivariate logistic regression.The prediction model was internally validated using the Bootstrap method(1000 resamples).The discriminative ability of the model was evaluated using receiver operating characteristic(ROC)curves,and the area under the curves(AUCs)of different prediction models were compared using De-long's test.The accuracy of the model was assessed using calibration curves,and the clinical benefit of the model was evaluated using clinical decision curve analysis(DCA).Results Significant differences were observed between two groups in terms of age,Ki-67,menopausal status,tumor type,posterior echo,coronal plane convergence sign,coronal plane skip sign,and coronal plane white wall sign before NAC(P<0.05).LASSO regression analysis showed that Ki-67,coronal plane convergence sign,and coronal plane white wall sign were independent influencing factors of pCR after NAC in TNBC patients(P<0.05).The AUC of the multivariate logistic regression model based on Ki-67 was 0.733(95%CI 0.646-0.819),the AUC of ABUS model was 0.777(95%CI 0.695-0.858),and the AUC of ABUS combined with Ki-67 model was 0.816(95%CI 0.741-0.890).De-long's test showed that the AUC of the combined model was higher than those of ABUS feature model and Ki-67 model,with statistically significant differences(P<0.05).There was no significant difference in the AUC between ABUS feature model and Ki-67 model(P=0.40).Hosmer-Lemeshow test indicated that the combined model had a good fit(P=0.304).Internal validation results showed that the combined model had a good stability with a consistency index(C-index)of 0.820(95%CI 0.726-0.879).The calibration curve demonstrated good consistency between the predicted and actual probabilities of the combined prediction model,and the DCA curve indicated that the model had favorable clinical benefit.Conclusion The combined ABUS feature and Ki-67 model can be used to predict the probability of pCR after NAC in TNBC patients,providing a reference for the formulation of clinical treatment plans in TNBC patients.

OBJECTIVE: To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA. METHODS: A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children's Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, i.e., 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children's Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00). RESULTS: There was a statistically significant difference in the gender and age distribution between the two groups of children (P < 0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes (P > 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children's samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. CONCLUSION DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.
Humans ; Arthritis, Juvenile/blood* ; Female ; Male ; Child ; Methotrexate/therapeutic use* ; Child, Preschool ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Transcriptome ; Adolescent ; RNA/genetics* ; Signal Transduction ; Gene Expression Profiling

Objective To explore the role of pulmonary surfactant(PS)combined with budesonide in improving oxygenation and clinical outcomes of neonatal acute respiratory distress syndrome(ARDS).Methods The present study is a historically controlled trial.Infants with ARDS requiring mechanical ventilation and PS replacement therapy were collected from the neonatal unit of Southwest Medical University.Those from January 2022 to November 2022 were set as intervention group(PS+ budesonid,n=35),treated with intratracheal instillation of a mixed suspension of budesonide(0.25 mg/kg)and PS(200 mg/kg),and continuous budesonide nebulization(0.25 mg/kg,twice per day)until withdrawal,then compared with a historical cohort,who just received intratracheal instillation of PS(200 mg/kg)(January 2020-December 2021,PS group,n=35).Baseline data such as gender,mode of delivery,1 min and 5 min Apgar score,birth weight,gestational age,time of onset,and cause of onset were recorded in both groups.The oxygenation and clinical outcomes of infants were compared between the two groups,including:(1)Arterial blood gas analysis indicators,such as partial pressure of oxygen(PaO2)and oxygenation index(OI)before treatment and at 6,12 and 24 hours of treatment;(2)Clinical observation and evaluation indicators,such as the time to withdrawal,duration of oxygen supplementation,length of stay,improvement of the radiological images of the lungs at 72 h of treatment,and repeated PS use;(3)Blood chemistry indicators,such as white blood cell(WBC),neutrocyte(NEU),procalcitonin(PCT)before treatment and at 3 and 7 days of treatment;and(4)Observation indicators of complications,weight growth,and mortality outcomes,such as the incidences of intracranial hemorrhage,gastrointestinal hemorrhage,neonatal necrotizing enterocolitis(NEC),and hyperglycemia,weight growth,and fatality rate.Results The differences in baseline data between the two groups were not statistically different(P＞0.05).The levels of PaO2 of the two groups were increased after treatment for different time periods,while the levels of OI were decreased(P＜0.001),and the levels of above indexes changed more significantly in PS+budesonide group than those in PS group(P＜0.05).The time to withdrawal,duration of oxygen supplementation,and length of stay in PS+budesonide group were shorter than those in PS group;the radiological images of the lungs showed that the pulmonary inflammation absorption was significantly better in PS+ budesonide group than that in PS group,while no significant difference between the two groups of infants with repeated PS use.The NEU was significantly higher in PS+budesonide group than in PS group at 3 d and 7 d of treatment(P＜0.001);and at 3 days of treatment,the PCT levels were significantly lower in PS+budesonide group than that in PS group(P＜0.05).The incidences of intracranial hemorrhage,gastrointestinal hemorrhage,NEC,hyperglycemia,weight growth,and fatality rate were not significantly different between the two groups(P＞0.05).Conclusion The use of budesonide in addition to surfactant may improve the oxygenation of neonates with ARDS,improve the inflammatory infiltrates in lungs,shorten the duration of mechanical ventilation and oxygen supplementation,and without short-term complications associated with budesonide use.

Objective:To evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.Methods:The patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.Results:After randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05). Conclusions:When used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.

The growth of three plague phages from Qinghai Plateau in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,PTB5,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were detected through a micromethod based on the OmniLogTM microbial identification system and by the drop method,to provide a scientific basis for future ecological studies and classification based on the host range.For plague vaccine strains EV76 and 614F,successful phage infection and subsequent phage growth were observed in the host bacte-rium.Diminished bacterial growth and respiration and a concomitant decrease in color were observed with the OmniLogTM mi-crobial identification system at 33 ℃ for 48 h.Yersinia pseudotuberculosis PTB5 was sensitive to Yersinia pestis phage 476,but Yersinia pseudotuberculosis PST5 was insensitive to phage 087 and 072204.Three strains of non-Yersinia pestis(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were insensitive to Yersinia pestis pha-ges 087,072204,and 476 showed similar growth curves.The growth of phages 476 and 087,as determined with the drop method,in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersin-ia enterocolitica 52302-2)showed the same results at 37 ℃,on the basis of comparisons with the OmniLogTM microbial i-dentification system;in contrast,phages 072204 did not show plaques on solid medium at 37 ℃ with plague vaccine strains EV76 and 614F.Determination based on the OmniLogTM detection system can be used as an alternative to the traditional determination of the host range,thus providing favorable application val-ue for determining the interaction between the phage and host bacteria.

Objective:To evaluate the long-term outcomes and prognostic factors of locally advanced gastric cancer with serosa-invasion.Methods:This study is a retrospective cohort study. The clinical and pathological data of 495 patients with locally advanced gastric cancer with serosa-invasion who underwent laparoscopic radical gastrectomy in Department of General Surgery, the First Hospital Affiliated to Army Medical University from October 2012 to October 2018 was analyzed retrospectively. There were 356 males and 139 females with an age ( M(IQR)) of 59 (16) years (range: 18 to 75 years). Observation indicators included postoperative results and long-term prognosis. The survival curve was drawn by the Kaplan-Meier method. Univariate and multivariate prognostic analysis was performed using the Cox proportional hazards model. Results:Among the 495 patients, a total of 57 patients (11.5%) were lost to follow-up, with a follow-up time of 89 (40) months (range: 23 to 134 months). The 5-year disease-free survival rate (DFS) and the 5-year overall survival rate (OS) were 56.0% and 58.2%, respectively. The 5-year DFS for patients with stage ⅡB, ⅢA, ⅢB, ⅢC were 71.2%, 60.5%, 51.6%, 33.3%, respectively. The 5-year OS for patients with stage ⅡB, ⅢA, ⅢB, ⅢC were 71.2%, 62.2%, 54.1%, 39.3%, respectively. Multivariate analysis showed that age >65 years (DFS: HR=1.402, 95% CI: 1.022 to 1.922, P=0.036; OS: HR=1.461, 95% CI: 1.057 to 2.019, P=0.022), lymph node dissection number less than 25 (DFS: HR=1.348, 95% CI: 1.019 to 1.779, P=0.036; OS: HR=1.376, 95% CI: 1.035 to 1.825, P=0.028), pathological stage Ⅲ (DFS: HR=2.131, 95% CI: 1.444 to 3.144, P<0.01; OS: HR=2.079, 95% CI: 1.406 to 3.074, P<0.01), and no postoperative chemotherapy (DFS: HR=3.127, 95% CI: 2.377 to 4.113, P<0.01; OS: HR=3.768, 95% CI: 2.828 to 5.020, P<0.01) were independent prognostic factors for the decrease in DFS and OS rates. Conclusions:Laparoscopic radical gastrectomy for locally advanced gastric cancer with serosa-invasion could achieve satisfactory long-term oncological outcomes. More lymph node dissection and standardized postoperative adjuvant chemotherapy are expected to further improve the prognosis of patients with locally advanced gastric cancer with serous invasion after laparoscopic radical surgery.