ObjectiveTo investigate the intervention effects of modified Linggui Zhugan Tang （LGZGT） on patients with obstructive sleep apnea-hypopnea syndrome （OSAHS） of the spleen deficiency and dampness obstruction with blood stasis type， reveal its possible mechanisms， and provide a theoretical basis for the clinical treatment of OSAHS with traditional Chinese medicine （TCM）. MethodsEighty OSAHS patients with spleen deficiency and dampness obstruction with blood stasis were randomly assigned to a control group and an observation group （1∶1） using a random number table， with 40 patients in each group. The control group received standard basic treatment combined with oral Doxofylline tablets， while the observation group received standard basic treatment combined with modified LGZGT. Serum levels of macrophage migration inhibitory factor （MIF）， microRNA-223 （miR-223）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of MIF， miR-223， and IL-18 were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. After two months of treatment， the total clinical efficacy， apnea-hypopnea index （AHI）， lowest nocturnal oxygen saturation （LSpO₂）， body mass index （BMI）， TCM syndrome scores， and expression levels of MIF， miR-223， and IL-18 before and after treatment were compared between the two groups. Correlations between MIF， miR-223， IL-18 and AHI and LSpO₂ were also analyzed. ResultsCompared with the control group， the observation group showed a significantly higher total clinical effective rate （P<0.01， Z=-3.49）. Within the control group， no significant changes were observed in AHI， LSpO₂， BMI， TCM syndrome scores， or MIF， miR-223， IL-18 levels and their mRNAs after treatment. In the observation group， AHI， BMI， TCM syndrome scores， and MIF and IL-18 levels and their mRNAs decreased significantly， while LSpO₂ increased significantly （P<0.01）. After treatment， compared with the control group， the observation group exhibited significantly lower AHI， BMI， TCM syndrome scores， and MIF and IL-18 levels and their mRNAs， and significantly higher LSpO₂ （P<0.01）. Correlation analysis showed that MIF and IL-18 were positively correlated with AHI （P<0.01） and negatively correlated with LSpO₂ （P<0.01）， whereas miR-223 was negatively correlated with AHI （P<0.01） and positively correlated with LSpO₂ （P<0.01）. ConclusionModified LGZGT may improve OSAHS of the spleen deficiency and dampness obstruction with blood stasis type by reducing airway inflammatory factors， alleviating airway inflammation， relieving airway edema and stenosis， and improving airway obstruction.

The randomized controlled trials (RCTs) regarding acupuncture direction published from January 1st, 2013, to November 7th, 2023 were searched in China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP Chinese Journal Database. As a result, 21 RCTs were included. The problems identified included conceptual misunderstandings regarding acupuncture direction, incomplete selection strategies, confounding research factors, and inaccuracies in reporting. Based on the findings, four strategic approaches for enhancing therapeutic efficacy through acupuncture direction were summarized: aligning needle direction with the meridian pathway, directing the needle toward the lesion site, orienting the needle toward adjacent acupoints, and targeting special anatomical structures. Two additional strategies were proposed for optimizing the procedure: simplifying acupuncture operations and directing the needle toward safe anatomical sites. Recommendations were made to improve the rationality of research factor settings and the completeness of acupuncture operation reporting. Furthermore, three methods for reporting acupuncture direction were discussed: reporting the tip-pointed position, reporting the insertion angle and orientation, and reporting azimuth and polar angles, aiming to promote greater standardization and completeness in acupuncture practice and reporting.
Acupuncture Therapy/standards* ; Humans ; Acupuncture Points ; Randomized Controlled Trials as Topic ; Meridians

Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

Geniposidic acid(GA), a natural iridoid, exists in the roots, stems, leaves, flowers, bark, fruits, and seeds of medicinal plants of Rubiaceae, Eucommiaceae, and Plantaginaceae. Modern pharmacological studies have revealed that GA has multiple pharmacological activities, including organ-protective, anti-inflammatory, antioxidative, anti-osteoporosis, anti-neurodegenerative, and anti-cardiovascular effects. GA can enhance cell/organism defenses by upregulating key anti-inflammatory and antioxidant cytokines, while downregulating key node proteins in pro-inflammatory signaling pathways such as AhR and TLR4/MyD88, thereby exerting pharmacological effects such as organ protection. Pharmacokinetic investigations have suggested that after oral administration, GA can be distributed in multiple organs(kidney, liver, heart, spleen, lung, etc.). In addition, the pharmacokinetic behavior of GA could be significantly altered under disease conditions, as demonstrated by a marked increase in systematic exposure. This article comprehensively summarizes the reported pharmacological activities and mechanisms and systematically analyzes the pharmacokinetic characteristics and key parameters of GA, with the aim of providing a theoretical basis and scientific reference for the precise clinical application of GA-related Chinese patent medicines, as well as for the investigation and development of innovative drugs based on GA.
Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Iridoid Glucosides/chemistry* ; Plants, Medicinal/chemistry* ; Anti-Inflammatory Agents/pharmacology*

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective : To explore whether chrysophanol(CHR) affects macrophage polarization by promoting mitochondrial biosynthesis through AMPK/PGC-1α pathway. Methods : The molecular docking and binding ability of CHR with AMPK and PGC-1α were predicted by Autodock vina software. Human monocytes(THP-1) were induced to M0 macrophages by phorbol myristate acetate(PMA), and to M1 macrophages by lipopolysaccharide(LPS) combined with interferon-γ(IFN-γ), which were set as Control group. M1 macrophages treated with CHR were set as CHR group. M1 macrophages treated with CHR combined with AMPK inhibitor(Compound C) were set as CHR+Compound C group. The mRNA expression levels of M1 macrophage markers(iNOS, CD86) and mitochondrial biosynthesis related genes(PGC-1α, NFR-1, TFAM) were detected by Quantitative real time polymerase chain reaction(qRT-PCR). The expression level of M1 macrophage marker iNOS was detected by immunofluorescence. The protein expression levels of AMPK, p-AMPK and PGC-1α were detected by Western blot. Results : The docking results showed that the binding energies of CHR with AMPK and PGC-1α were-8.4 kcal/mol and-7.4 kcal/mol, respectively. qRT-PCR results showed that the in vitro model of M1 macrophages was successfully established. Compared with the Control group, CHR treatment significantly increased the mRNA expression of mitochondrial biosynthesis-related genes PGC-1α, NFR-1, and TFAM(P<0.001). Compared with CHR treatment group, CHR combined with Compound C treatment significantly decreased the mRNA expression levels of mitochondrial biosynthesis-related genes PGC-1α, NFR-1, and TFAM(P<0.05). Immunofluorescence results showed that CHR treatment inhibited the protein expression of iNOS compared with the Control group(P<0.001). Compared with CHR treatment group,CHR combined with Compound C treatment reversed the inhibitory effect of CHR on i NOS protein expression(P<0.05). Western blot results showed that compared with the Control group,the CHR treatment group had significant increase in the protein expression levels of p-AMPK and PGC-1α(P<0.001).Compared with CHR treatment group,CHR combined with Compound C treatment significantly decreased the protein expression levels of p-AMPK and PGC-1α(P<0.05). Conclusion Chrysophanol may inhibit macrophage polarization to M1 by activating AMPK/PGC-1α signaling pathway to promote mitochondrial biosynthesis.

Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

OBJECTIVE: To screen factors affecting the prognosis of chronic myeloid leukemia (CML) patients, and construct a nomogram model for event-free survival (EFS). METHODS: To screen out meaningful variables by univariate and multivariate Cox regression analysis in CML patients, and construct a nomogram model using R software. The nomogram was validated using consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, decision curve analysis (DCA), and risk stratification analysis. RESULTS: This study analyzed data from 116 CML patients. Univariate and multivariate Cox regression analysis demonstrated that age, peripheral blood basophil percentage, BCR-ABL1 ^IS at 3 months, and red blood cell distribution width (RDW) were independent prognostic factors of EFS. Subsequently, a nomogram was constructed based on the above predictors. The C-index of the nomogram was 0.733(95%CI : 0.676-0.790). The AUC values for predicting 1-, 3-, and 5-year EFS rate were 0.765, 0.855, and 0.827, respectively. The results of the calibration curve and DCA curve showed that the predictive model had good consistency, as well as strong clinical utility. The patients were stratified into high-risk group and low-risk group based on the total score of the model, there was a significant difference in EFS between the two groups (P < 0.001). CONCLUSION Age, peripheral blood basophil percentage, BCR-ABL1 ^IS at 3 months, and RDW were associated with the prognosis of CML patients. The nomogram model constructed in this study can accurately predict the prognostic status of CML patients, but its widespread application still requires external and prospective validation.
Nomograms ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality* ; Proportional Hazards Models ; Erythrocyte Indices ; Risk Assessment/methods* ; Fusion Proteins, bcr-abl/genetics* ; Basophils ; Leukocyte Count ; Humans

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies