Acute lung injury(ALI) is a critical clinical condition primarily characterized by refractory hypoxemia and infiltration of inflammatory cells in lung tissue, which can progress into a more severe form known as acute respiratory distress syndrome(ARDS). Immune cells and inflammatory cytokines play important roles in the progression of the disease. Due to its unclear pathogenesis and the lack of effective clinical treatments, ALI is associated with a high mortality rate and severely affects patients' quality of life, making the search for effective therapeutic agents particularly urgent. Ginseng Radix et Rhizoma, the dried root of the perennial herb Panax ginseng from the Araliaceae family, contains active ingredients such as saponins and polysaccharides, which possess various pharmacological effects including anti-tumor activity, immune regulation, and metabolic modulation. In recent years, studies have shown that ginsenosides exhibit notable effects in reducing inflammation, ameliorating epithelial and endothelial cell injury, and providing anticoagulant action, indicating their comprehensive role in alleviating lung injury. This review summarizes the pathogenesis of ALI and the molecular mechanisms through which ginsenosides act at different stages of ALI development. The aim is to provide a scientific reference for the development of ginsenoside-based drugs targeting ALI, as well as a theoretical basis for the clinical application of Ginseng Radix et Rhizoma in the treatment of ALI.
Ginsenosides/pharmacology* ; Humans ; Acute Lung Injury/immunology* ; Animals ; Panax/chemistry* ; Drugs, Chinese Herbal

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

AIM To investigate the tumor-suppressive mechanism of Guiqi Yiyuan Extract combined with cisplatin in Lewis lung cancer mice.METHODS Ten intact C57BL/6J mice were assigned to the blank group.Sixty additional mice were developed into Lewis lung cancer models bearing transplanted tumor and subsequently allocated into the model group,the cisplatin group(5 mg/kg),the high-dose Guiqi Yiyuan Extract group(6.6 g/kg),and the low-dose,medium-dose and high-dose Guiqi Yiyuan Extract combined with cisplatin group(1.6,3.3,6.6 g/kg+5 mg/kg),with 10 mice in each group.Mice in the blank and model groups received saline via daily gavage,while treatment groups were administered Guiqi Yiyuan Extract orally(once daily),and cisplatin injection intraperitoneally(once every other day).After 14 days of drug administration,mice were euthanized for endpoint analysis.The following assessments were conducted:general health status and body weight changes monitored throughout the study period;tumor excision and weighing for inhibition rate calculation;histopathological examination of tumors via hematoxylin-eosin(HE)staining;serum quantification of IL-1 β,IL-18 and HMGB1 by ELISA;ultrastructural analysis of tumor cell death using transmission electron microscopy(TEM);spatial localization of TXNIP and GSDMD-N in tumor sections via immunofluorescence(IF);and Western blot detection of TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD,GSDMD-N protein expressions in tumor tissues.RESULTS Compared to the model group,the cisplatin group and all combination therapy groups exhibited significant reduction in tumor weight(P＜0.05)and increased tumor suppression rate;enhanced tumor tissue necrosis with characteristic pyroptotic morphology;elevated serum levels of IL-1β,IL-18 and HMGB1(P＜0.05);and upregulated expressions of pyroptosis-associated proteins TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD and GSDMD-N(P＜0.05).The high dose combination group demonstrated optimal therapeutic efficacy(P＜0.05).CONCLUSION Guiqi Yiyuan Extract enhances cisplatin sensitivity,demonstrating synergistic anti-tumor effects in Lewis lung carcinoma-bearing mice.This combinatorial therapeutic effect likely involves modulation of the TXNIP/NLRP3/Caspase-1/GSDMD pathway.

AIM To investigate the tumor-suppressive mechanism of Guiqi Yiyuan Extract combined with cisplatin in Lewis lung cancer mice.METHODS Ten intact C57BL/6J mice were assigned to the blank group.Sixty additional mice were developed into Lewis lung cancer models bearing transplanted tumor and subsequently allocated into the model group,the cisplatin group(5 mg/kg),the high-dose Guiqi Yiyuan Extract group(6.6 g/kg),and the low-dose,medium-dose and high-dose Guiqi Yiyuan Extract combined with cisplatin group(1.6,3.3,6.6 g/kg+5 mg/kg),with 10 mice in each group.Mice in the blank and model groups received saline via daily gavage,while treatment groups were administered Guiqi Yiyuan Extract orally(once daily),and cisplatin injection intraperitoneally(once every other day).After 14 days of drug administration,mice were euthanized for endpoint analysis.The following assessments were conducted:general health status and body weight changes monitored throughout the study period;tumor excision and weighing for inhibition rate calculation;histopathological examination of tumors via hematoxylin-eosin(HE)staining;serum quantification of IL-1 β,IL-18 and HMGB1 by ELISA;ultrastructural analysis of tumor cell death using transmission electron microscopy(TEM);spatial localization of TXNIP and GSDMD-N in tumor sections via immunofluorescence(IF);and Western blot detection of TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD,GSDMD-N protein expressions in tumor tissues.RESULTS Compared to the model group,the cisplatin group and all combination therapy groups exhibited significant reduction in tumor weight(P＜0.05)and increased tumor suppression rate;enhanced tumor tissue necrosis with characteristic pyroptotic morphology;elevated serum levels of IL-1β,IL-18 and HMGB1(P＜0.05);and upregulated expressions of pyroptosis-associated proteins TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD and GSDMD-N(P＜0.05).The high dose combination group demonstrated optimal therapeutic efficacy(P＜0.05).CONCLUSION Guiqi Yiyuan Extract enhances cisplatin sensitivity,demonstrating synergistic anti-tumor effects in Lewis lung carcinoma-bearing mice.This combinatorial therapeutic effect likely involves modulation of the TXNIP/NLRP3/Caspase-1/GSDMD pathway.

Objective:To explore the prevalence and independent associated factors of vascular calcification (VC) in non-dialysis chronic kidney disease (CKD) patients of stage 3-5.Methods:It was a single-center cross-sectional observational study. Non-dialysis stage 3-5 CKD patients ≥18 years old who were admitted to the Department of Nephrology, the First Affiliated Hospital of Sun Yat-sen University from May 1, 2022 to December 31, 2022 with VC evaluation were enrolled. The patients' general information, laboratory examination and imaging data were collected. Coronary artery calcification (CAC), thoracic aorta calcification (TAC), abdominal aorta calcification (AAC), carotid artery calcification and aortic valve calcification (AVC) were evaluated by cardiac-gated electron-beam CT (EBCT) scans, lateral lumbar x-ray, cervical macrovascular ultrasound and echocardiography, respectively. The differences in clinical data and the prevalence of VC at different sites of patients with different CKD stages were compared, and the prevalence of VC at different sites of patients in different age groups [youth group (18-44 years old), middle-aged group (45-64 years old) and elderly group (≥65 years old)] and patients with or without diabetes were compared. Multivariate logistic regression analysis was used to analyse the independent associated factors of VC for different areas.Results:A total of 206 patients aged (51±14) years were included, including 129 (62.6%) males. There were 44 patients with CKD stage 3 (21.4%), 51 patients with CKD stage 4 (24.8%), and 111 patients with CKD stage 5 (53.9%). CKD was caused by chronic glomerulonephritis [104 cases (50.5%)], diabetic kidney damage [35 cases (17.0%)], hypertensive kidney damage [29 cases (14.1%)] and others [38 cases (18.4%)]. Among 206 patients, 131 (63.6%) exhibited cardiovascular calcification, and the prevalence of CAC, TAC, AAC, carotid artery calcification, and AVC was 37.9%, 43.7%, 37.9%, 35.9% and 9.7%, respectively. The overall prevalence of VC in young, middle-aged and elderly patients was 24.6%, 73.6% and 97.4%, respectively. With the increase of age, the prevalence of VC in each site gradually increased, and the increasing trend was statistically significant (all P<0.001). The overall prevalence of VC in CKD patients with diabetes was 92.5% (62/67), and the prevalence of VC at each site in the patients with diabetes was significantly higher than that in the patients without diabetes (all P<0.001). Multivariate logistic regression analysis revealed that age (every 10 years increase, OR=2.51, 95% CI 1.77-3.56, P<0.001), hypertension ( OR=5.88, 95% CI 1.57-22.10, P=0.009), and diabetes ( OR=4.66, 95% CI 2.10-10.35, P<0.001) were independently correlated with CAC; Age (every 10 years increase, OR=6.43, 95% CI 3.64-11.36, P<0.001) and hypertension ( OR=6.09, 95% CI 1.33-27.84, P=0.020) were independently correlated with TAC; Female ( OR=0.23, 95% CI 0.07-0.72, P=0.011), age (every 10 years increase, OR=3.90, 95% CI 2.42-6.29, P<0.001), diabetes ( OR=5.37, 95% CI 2.19-13.19, P<0.001) and serum magnesium ( OR=0.01,95% CI 0-0.35, P=0.014) were independently correlated with AAC. Moreover, age and diabetes were independently correlated with carotid artery calcification, AVC and overall VC Conclusions:The prevalence of VC in non-dialysis CKD patients of stage 3-5 is 63.59%, of which CAC reaches 37.9%, TAC is the most common one (43.7%), while AVC is the least one (9.7%). Age and diabetes are the independent associated factors for VC of all sites except TAC, while hypertension is an independent associated factor for both CAC and TAC.

The present study identified chemical constituents of Honghua Xiaoyao Tablet (HXT) and explored its biological connotation and characteristics on the premenstrual syndrome (PMS) treatment from the "disease-syndrome-symptom" association network. UHPLC-Q Exactive Orbitrap HRMS technology was applied to analyze the chemical constituents in HXT. According to the composition principles, the compatible herbs of HXT were divided into the Shugan Jieyu group, Huoxue Tiaojing group and Yiqi Jianpi group. The candidate targets of the corresponding prescriptions of HXT efficacy groups were collected from the Pharmmapper database and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0. The gene set related to the clinical symptoms included in Traditional Chinese and Western Medicine diagnosis and treatment standards were obtained from SoFDA, GeneCards, DisGeNET, MalaCards and literature published. The "HXT candidate targets-PMS (liver depression, Qi stagnation, and blood stasis syndrome) genes" network was constructed based on the gene interaction information, and further, the core network targets were screened out by topological characteristics of calculating network, and the functional exploration was carried out based on Kyoto Encyclopedia of Genes and Genomes (KEGG) for exploring the therapeutic advantages in PMS treatment of HXT efficacy groups, which were further verified experimentally in vitro. A total of 109 components from HXT were identified, including 20 components from Shugan Jieyu group enriched in the neurological system, estrogen regulation, and "immune-inflammation" related pathways, 77 components from Huoxue Tiaojing group enriched in the blood-circulation system, "immune-inflammation" and estrogen regulation related pathways and 30 components from Yiqi Jianpi group regulating immune inflammation, digestive system, and hormone levels. The biochemical indicator detection demonstrated that both the levels of 5-HT and DA in the hypothalamus tissues and the levels of E₂, NO, VEGF and RLN in the uterine tissues of PMS model rats were lower than those in controls, which the levels of OT, PROG, IL-6, IL-1β and TNF-α in the uterine tissues were increased in PMS group, which were all reversed by the administration of HXT, indicating that this prescription may regulate the synthesis and secretion of estrogen, intervene in neurotransmitter synthesis and signal transduction, reverse the imbalance of "immune-inflammation", and regulate digestive system function through various biological pathways, exerting the liver-smoothing, Qi-regulating, blood-activating and spleen-tonifying comprehensive effects, leading to alleviating the "neuroendocrine-endocrine-immune" system and blood-circulation disorders. The relevant results may provide a reference for clarifying the advantages and efficacy of HXT in treating PMS with liver stagnation, Qi stagnation, and blood stasis syndrome, and exploring its therapeutic advantages. The animal experiment of this study was approved by the Ethics Committee of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (approval number: 2023B248).

Objective:To summarize the clinical and pathological characteristics, treatment methods, and prognosis of papillary renal neoplasm with reverse polarity (PRNRP).Methods:The clinical and pathological data of six pathologically confirmed PRNRP patients admitted to Renji Hospital affiliated with Shanghai Jiaotong University School of Medicine from August 2022 to August 2023 were retrospectively analyzed. Among them, three were male and three were female, with an average age of (55.3±10.5) years old. All six cases were incidentally discovered during health examinations. Preoperative contrast-enhanced CT scans showed tumors with cortical phase manifestations of uneven enhancement, avascularity, and indistinct borders, with CT values of (85.6±18.7) HU. In the corticomedullary phase, the CT values showed mild elevation, with an average of (94.3±4.7) HU. In the delayed phase, the tumor boundaries were clear, and the enhancement degree was significantly lower than that of the surrounding renal cortex and medulla, with a tumor CT value of (86.3±11.9) HU. The pseudocapsule of the tumor was not clearly displayed on contrast-enhanced CT scans. All cases underwent partial nephrectomy, including two cases of robot-assisted laparoscopic partial nephrectomy and four cases of laparoscopic partial nephrectomy.Results:Postoperative pathological measurements revealed a maximum tumor diameter ranging from 6 to 15 mm, with an average diameter of (11.0±3.5) mm. All six cases were classified as pT 1aN 0M 0 stage. Microscopically, the tumors exhibited branching papillary structures with eosinophilic cytoplasm, and the tumor cells displayed low-grade nuclei located at the top of the cytoplasm and away from the basal membrane. Immunohistochemical analysis showed diffuse strong positivity for GATA3 and CK7, while CA-Ⅸ expression was negative. The median follow-up time after surgery was 10(9, 13) months, and no tumor recurrence or metastasis was observed. Conclusions:PRNRP is a rare, low-grade malignant papillary renal tumor. Contrast-enhanced CT scan has characteristic features of avascularity. Pathological morphological features are low-grade nuclei located at the top of the cytoplasm and far away from the basal membrane, forming a "reverse polarity". The immunophenotype shows positive expression of GATA3 and CK7. Partial nephrectomy is the recommended treatment approach, and the postoperative prognosis is favorable.

This study aims to identify the novel biomarkers of cold-dampness syndrome(RA-Cold) of rheumatoid arthritis(RA) by gene set enrichment analysis(GSEA), weighted gene correlation network analysis(WGCNA), and clinical validation. Firstly, transcriptome sequencing was carried out for the whole blood samples from RA-Cold patients, RA patients with other traditional Chinese medicine(TCM) syndromes, and healthy volunteers. The differentially expressed gene(DEG) sets of RA-Cold were screened by comparison with the RA patients with other TCM syndromes and healthy volunteers. Then, GSEA and WGCNA were carried out to screen the key DEGs as candidate biomarkers for RA-Cold. Experimentally, the expression levels of the candidate biomarkers were determined by RT-qPCR for an independent clinical cohort(not less than 10 cases/group), and the clinical efficacy of the candidates was assessed using the receiver operating characteristic(ROC) curve. The results showed that 3 601 DEGs associated with RA-Cold were obtained, including 106 up-regulated genes and 3 495 down-regulated genes. The DEGs of RA-Cold were mainly enriched in the pathways associated with inflammation-immunity regulation, hormone regulation, substance and energy metabolism, cell function regulation, and synovial pannus formation. GSEA and WGCNA showed that recombinant proteasome 26S subunit, ATPase 2(PSMC2), which ranked in the top 50% in terms of coefficient of variation, representativeness of pathway, and biological modules, was a candidate biomarker of RA-Cold. Furthermore, the validation results based on the clinical independent sample set showed that the F1 value, specificity, accuracy, and precision of PSMC2 for RA-Cold were 70.3%, 61.9%, 64.5%, and 81.3%, respectively, and the area under the curve(AUC) value was 0.96. In summary, this study employed the "GSEA-WGCNA-validation" integrated strategy to identify novel biomarkers of RA-Cold, which helped to improve the TCM clinical diagnosis and treatment of core syndromes in RA and provided an experimental basis for TCM syndrome differentiation.
Humans ; Arthritis, Rheumatoid/drug therapy* ; Biomarkers/metabolism* ; Medicine, Chinese Traditional ; Gene Expression Profiling/methods* ; Computational Biology ; Gene Regulatory Networks ; ATPases Associated with Diverse Cellular Activities/therapeutic use* ; Proteasome Endopeptidase Complex/therapeutic use*

OBJECTIVE: The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model. METHODS: Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model. RESULTS: On the 10th day after inoculation, hCD45⁺ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3⁺ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks. CONCLUSION Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.
Humans ; Animals ; Mice ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Heterografts ; Bone Marrow ; Disease Models, Animal ; T-Lymphocytes ; Mice, SCID

Objective:To explore the difference of the vessel and plaque characteristics, myocardial perfusion and cardiac function between patients with ischemia with non-obstructive coronary artery disease (INOCA) and obstructive coronary artery disease (CAD).Methods:From July 2021 to June 2022, 101 patients with angina were referred to dynamic computed tomography myocardial perfusion (CTP) and coronary computed tomography angiography (CCTA) and retrospectively included in our hospital. Based on the results of CTP and CCTA, patients were divided into INOCA (27 cases), moderate obstructive CAD (26 cases) and severe obstructive CAD (48 cases). The anatomical coronary artery stenosis, plaque characteristics and myocardial perfusion features of all patients were analyzed. Furthermore, left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were obtained on full-phase reconstruction CCTA image by using Medis Suite 3.2 postprocessing software. Multigroup analysis used one way ANOVA or Kruskal Wallis H test. Results:Patients with INOCA were younger than patients with moderate and severe obstructive CAD ( P<0.001). INOCA patients (7.4%, 2/27) had lower rate of positive remodeling than both moderate (57.7%, 15/26, P<0.001) and severe obstructive CAD patients (33.3%, 16/48, P=0.017). The percentage of ischemic myocardium volume in patients with INOCA were similar with those in patients with severe CAD (all P>0.05), but significantly higher than those in patients with moderate CAD (all P<0.05). No significant difference in terms of GLS was detected between patients with INOCA [-17.4% (-21.6%, -11.6%)] and severe CAD [-17.6% (-21.9%, -14.8%), P=0.536], however, patients both with INOCA and severe CAD also had higher GLS than patients with moderate obstructive CAD [-22.3% (-29.8%, -19.0%), all P<0.05]. Conclusions:Based on"one-stop-shop"CTP combined with CCTA imaging, early cardiac functional changes including abnormal myocardial perfusion and myocardial strain in INOCA patients were similar to those in patients with severe obstructive CAD and more severe than those in patients with moderate obstructive CAD.