1.Research progress on the mechanism of traditional Chinese medicine intervening in osteoarthritis by modulating the inflammatory microenvironment
Zuo WANG ; Yuxin LIU ; Yuxin QIAO ; Zhengyu YANG ; Ru WANG ; Wenbin LIAO ; Yan GAO ; Jiayi FENG ; Guohua LI
China Pharmacy 2026;37(6):823-828
The inflammatory microenvironment is closely associated with the initiation and progression of osteoarthritis (OA), specifically manifesting as macrophage activation, dysregulation of inflammatory cytokines, and redox imbalance. Following an overview of the pathological characteristics of the OA inflammatory microenvironment, this paper reviews the research progress on the mechanism of traditional Chinese medicine (TCM) intervening in OA by modulating the inflammatory microenvironment. It has been found that TCM monomers/active ingredients (such as total alkaloids from Strychnos nux-vomica , quercetin, triptolide, etc.), herb pairs (e.g. Angelica pubescens - Gentiana macrophylla , Carthami Flos-Lycopodii Herba), and TCM formulas (such as Zhuanggu jianxi formula, Duhuo jisheng decoction and Rongjin niantong formula, etc.) can inhibit macrophage activation, reduce the release of proinflammatory cytokines and the generation of reactive oxygen species by inhibiting multiple signaling pathways, including nuclear factor-κB, Wnt/ β -catenin, and mitogen-activated protein kinase, thereby alleviating the articular inflammatory microenvironment, restoring local joint homeostasis, and slowing the progression of OA.
2.Zuoguiwan Mitigates Oxidative Stress in Rat Model of Hyperthyroidism Due to Kidney-Yin Deficiency via DRD4/NOX4 Pathway
Ling LIN ; Qianming LIANG ; Changsheng DENG ; Li RU ; Zhiyong XU ; Chao LI ; Mingshun SHEN ; Yueming YUAN ; Muzi LI ; Lei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):43-51
ObjectiveTo decipher the mechanism by which Zuoguiwan (ZGW) treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 (DRD4)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone (0.35 mg·kg-1). After successful modeling, the rats were randomized into model, methimazole (positive control, 5 mg·kg-1), low-, medium-, and high-dose (1.85, 3.70, 7.40 g·kg-1, respectively) ZGW, and normal control groups. After 21 days of continuous gavage, the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones [triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH)], renal function indexes [serum creatine (Scr) and blood urea nitrogen (BUN)], energy metabolism markers [cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)], and oxidative stress-related factors [superoxide dismutase (SOD), malondialdehyde (MDA), and NADPH)] were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was employed to analyze the expression of DRD4, NOX4, mitochondrial respiratory chain complex proteins [NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) and cytochrome C oxidase subunit 4 (COX4)], and inflammation-related protein [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), p38 mitogen-activated protein kinase (MAPK)] pathway in the renal tissue. ResultsCompared with the normal group, the model group showed mental malaise, body weight decreases (P<0.01), inflammatory cell infiltration in the renal tissue, a few residual parotid glands in the thyroid, elevations in serum levels of T3, T4, Scr, BUN, cAMP, cAMP/cGMP, MDA, and NADPH (P<0.01), down-regulation in protein levels of TSH, SOD, and DRD4 (P<0.05, P<0.01), and up-regulation in expression of NOX4, p-p38 MAPK/p38 MAPK, and inflammatory factors (P<0.01). Compared with the model group, ZGW increased the body weight (P<0.05, P<0.01), reduced the infiltration of renal interstitial inflammatory cells, restored the thyroid structure and follicle size, lowered the serum levels of T3, T4, Scr, BUN, cAMP, cAMP/cGMP, MDA and NADPH (P<0.05, P<0.01), up-regulated the expression of TSH, SOD and DRD4 (P<0.05, P<0.01), and down-regulated the expression of NOX4, p-p38 MAPK/p38 MAPK, and inflammatory factors (P<0.05, P<0.01). Moreover, high-dose ZGW outperformed methimazole (P<0.05). ConclusionBy activating DRD4, ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway, reduce oxidative stress and inflammatory response, thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.
3.Electroacupuncture Ameliorates NLRP3-mediated Pyroptosis in Spinal Cord Injury Rats by Reshaping The Gut Microbiota
Yin-Jie CUI ; Hong-Ru LI ; Jing-Yi LIU ; Hai-Lin DU ; Shu-Wen LIU ; Yuan YANG ; Chen-Guang ZHENG ; Jian-Qin XIANG ; Xiao-Juan SONG
Progress in Biochemistry and Biophysics 2026;53(5):1132-1153
ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.
4.Electroacupuncture Ameliorates NLRP3-mediated Pyroptosis in Spinal Cord Injury Rats by Reshaping The Gut Microbiota
Yin-Jie CUI ; Hong-Ru LI ; Jing-Yi LIU ; Hai-Lin DU ; Shu-Wen LIU ; Yuan YANG ; Chen-Guang ZHENG ; Jian-Qin XIANG ; Xiao-Juan SONG
Progress in Biochemistry and Biophysics 2026;53(5):1132-1153
ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.
5.Effects of coal mine dust on lung function in rats
LIU Yang ; LI Meng ; LU Liyuan ; WANG Ru ; YANG He ; ZHANG Huifang
Journal of Preventive Medicine 2025;37(1):96-101
Objective:
To explore the impacts of coal mine dust on lung function in rats, so as to provide the basis for the early prevention and treatment of coal worker's pneumoconiosis.
Methods:
Seventy-two SPF-grade 8-week-old male Sprague-Dawley rats were randomly divided into the coal dust group, the coal-silica dust group, the silica dust group and the control group. The rats in the first three groups of rats were administered 1 mL corresponding dust suspension into the lungs using non-exposure tracheal instillation, while the rats in the control group were administered 1 mL normal saline. Respiratory rate (f), forced vital capacity (FVC), peak expiratory flow (PEF) and dynamic pulmonary compliance (Cdyn) were measured at 1, 3 and 6 months after dust exposure. Lung tissues were collected to measure reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels using corresponding ELISA kits and ATP assay kits, respectively. The relative mRNA expressions of peroxisome proliferators-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (TFAM) were detected using real-time fluorescent quantitative polymerase chain reaction assay. The relative protein expressions of PGC-1α and TFAM were detected using Western blotting.
Results:
There was no interaction between dust type and exposure duration on f (P>0.05), but there were interactions on FVC, PEF and Cdyn (all P<0.05). Compared with the control group at 6 months after dust exposure, the f of the rats in the silica dust group were increased, while the FVC and PEF of the rats in the coal-silica dust and silica dust groups were decreased, and Cdyn of the rats in the coal dust, coal-silica dust and silica dust groups were decreased (all P<0.05). There were interactions between dust type and exposure duration on ROS and ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM (all P<0.05). Compared with the control group at 3 and 6 months after dust exposure, the ROS levels in the rats in the coal dust, coal-silica dust and silica dust groups were increased, while the ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM were decreased (all P<0.05).
Conclusion
The lung function impairment in rats caused by different types of coal mine dust is related to PGC-1α-mediated mitochondrial biogenesis dysfunction, which leads to increased ROS levels, decreased ATP and TFAM levels.
6.The significance of preoperative neck enhanced multidetector computed tomography in predicting the recurrent veins and classifying their courses of the submental flap reflux vein for repair in pharyngeal cancer
Qian SHI ; Jugao FANG ; Qi ZHONG ; Lizhen HOU ; Hongzhi MA ; Ling FENG ; Shizhi HE ; Meng LIAN ; Yanming ZHAO ; Ru WANG ; Yunxia LI ; Xixi SHEN ; Yifan YANG ; Lingwa WANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(10):1208-1214
Objective:To evaluate preoperative high-resolution thin-layer cervical enhanced CT used to predict the venous route of the submental flap reflux vein and its relationship with adjacent structures in order to guide the anatomical understanding and protection of submental flap in pharyngeal cancer surgery.Methods:Sixty consecutive patients with pharyngeal cancer who underwent submental flap repair surgery in our department from March 2022 to December 2024, as well as 60 patients who were accepted neck dissection suffering other cancers, were selected. Before surgery, high-resolution cervical enhanced CT scans were performed, and the position of the transverse section of the facial vein in the venous phase horizontal image gradually variation tendency was focused layer by layer. The direction and adjacent relationship of the submental flap reflux veins were determined and recorded. Combined with 60 patients with other head and neck tumors who underwent neck dissection in our department during the same period (a total of 120 cases, 240 sides), the classification and management of the draining veins of Fang′s mental flap were conducted. Type Ⅰ mainly drains into the internal jugular vein; Type Ⅱ mainly drains into the external jugular vein and Type Ⅲ mainly drains into the anterior jugular vein (often accompanied by an external jugular draining branch). The status and proportion of venous drainage were analyzed.Results:Vascular predictive coincidence rate was 98.3% (59/60) among the 60 patients with pharyngeal cancer. Only one patient was predicted to have a simple return to the external jugular vein. However, during the operation, in addition to the main return to the external jugular vein, a small portion also returned to the internal jugular vein. Submental flap reflux vessels were classified into three types based on intraoperative submental flap venous return in 60 cases of laryngopharyngeal cancer, in conjunction with the analysis of venous return patterns from 240 cervical CT scans. Type Ⅰ mainly refluxed to the internal jugular vein, accounting for 42.1%. Type Ⅱ mainly refluxed to the external jugular vein (47.9%). Type Ⅲ mainly refluxed to the anterior jugular vein (10.0%). The total detection rate of CT reading of 240 venous reflux was 98.7% (237/240). Vascular predictive coincidence rate was 97.9%(235/240).Conclusion:The detailed analysis of submental venous return vessels can accurately predict the direction of reflux veins and its surrounding areas by preoperative high-resolution enhanced CT scan. This provides reliable guidance for the anatomy and protection of the submental flap reflux veins during surgery.
7.Efficacy comparison of subsequent treatment modalities for locally advanced hypopharyngeal cancer with partial response to neoadjuvant chemotherapy
Ru WANG ; Zheng LI ; Jugao FANG ; Junfang XIAN ; Qi ZHONG ; Yang ZHANG ; Lizhen HOU ; Hongzhi MA ; Ling FENG ; Shizhi HE ; Qian SHI ; Yifan YANG ; Haiyang LI ; Lingwa WANG ; Xinyu LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(10):1223-1231
Objective:To compare the survival outcomes of different subsequent treatment regimens in patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) who achieved partial response (PR) after neoadjuvant chemotherapy based on the gross tumor volume regression rate (GTVRR).Methods:This retrospective study included patients with locally advanced HPSCC treated at the Department of Head and Neck Surgery, Beijing Tongren Hospital, from January 2011 to December 2023. The cohort included 135 males and 3 females, aged from 35 to 77 years. All patients received 2-3 cycles of TPF regimen (paclitaxel+cisplatin+5-fluorouracil) neoadjuvant chemotherapy. Subsequent treatments included concurrent chemoradiotherapy or surgery combined with postoperative adjuvant radiotherapy. The impacts of different subsequent treatment modalities on the survivals and prognoses of patients were compared based on GTVRR thresholds of 50% and 70%. The χ 2 test was used to analyze influencing factors; survival analysis and intergroup comparisons were performed using the Kaplan-Meier method and Log-rank test; prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results:The 5-year OS and PFS rates were 56.5% and 47.9%, respectively, while, the 10-year OS and PFS rates were 25.8% and 21.2%, respectively. The median OS was 75 months, and the median PFS was 48 months. The laryngeal function preservation rate for the entire cohort was 83.3%. The patients who underwent surgery combined with postoperative radiotherapy had significantly better OS and PFS outcomes than those treated with concurrent chemoradiotherapy ( P<0.05). Stratification based on GTVRR revealed that the surgery plus postoperative radiotherapy regimen was particularly effective for PR patients with a GTVRR of 30%-70%, showing significantly better OS and PFS compared to the concurrent chemoradiotherapy group ( P<0.05). Conclusion:The optimal subsequent treatment for PR-HPSCC may be surgery-based comprehensive treatment, particularly for patients with a GTVRR of 30%-70%. This study offers valuable insights for the stratified treatment of HPSCC, which could contribute to improving overall patient prognosis.
8.Application value of low-temperature plasma bipolar forceps in thyroid cancer surgery
Lingzhao MENG ; Xiaopeng QU ; Pengyu TAO ; Fan YANG ; Yuansheng RAO ; Ru WANG ; Jugao FANG
Journal of Capital Medical University 2025;46(3):553-558
Objective To explore the application value of low-temperature plasma bipolar forceps in open thyroid cancer surgery.Methods The clinical data of 30 patients with differentiated thyroid cancer treated with low-temperature plasma bipolar forceps by our team from May 2021 to October 2024 were retrospectively analyzed.And 30 patients with differentiated thyroid cancer treated with monopolar electrocautery+ultrasonic scalpel were selected as the control group.The surgical procedures for both groups were thyroid lobectomy,isthmus resection+ipsilateral level Ⅵ lymph node dissection.The age,gender,body mass index(BMI),tumor TNM stage,operation time,intraoperative blood loss,48 h postoperative drainage volume,and surgical complications of the two groups were compared.Results There were no significant differences in age,gender,BMI,and tumor TNM stage between the two groups.The operation time,intraoperative blood loss,48 h postoperative drainage volume,and the incidence of postoperative transient hypoparathyroidism in the low-temperature plasma bipolar forceps group were significantly less than those in the control group(P<0.05).There were no occurrences of postoperative subcutaneous hematoma,permanent recurrent laryngeal nerve palsy,and permanent hypoparathyroidism in both groups.Conclusion In thyroid cancer surgery,low-temperature plasma bipolar forceps can not only achieve fine detailed operations,but also effectively protect the blood supply of the recurrent laryngeal nerve,superior laryngeal nerve,and parathyroid glands.It has less trauma and a faster postoperative recovery,and is worthy of clinical promotion and application.
9.Clinicopathological significance of USP9X and PD-L1 expression in pulmonary sarcomatoid carcinoma
Yang YANG ; Qian LIU ; Yi RU ; Shasha ZHANG ; Biao LIU
Chinese Journal of Clinical and Experimental Pathology 2025;41(6):746-750
Purpose To investigate the expression of ubiquitin-specific protease 9X(USP9X)and programmed cell death ligand 1(PD-L1)in pulmonary sarcomatoid carcinoma(PSC),and to assess their clinicopathological signif-icance.Methods Immunohistochemical staining was performed on 48 PSC specimens using the EnVision two-step method to detect USP9X and PD-L1 expression.The relationships between their expressions levels and clinicopathologi-cal parameters were analyzed.Results USP9X was positively expressed in 81.3%(39/48)of PSC cases,and the USP9X positivity rate was significantly higher in lymph node-negative tumors compared with lymph node-positive tumors(P<0.05).PD-L1 expression was observed in 70.8%(34/48)of cases,with a significantly higher positivity rate in male patients than in female patients(P<0.01).Correlation analysis showed a significant positive association between USP9X and PD-L1 expression in PSC(P<0.05).Conclusion Both USP9X and PD-L1 are highly expressed in PSC,and their expression levels are significantly positively correlated.Combined detection of USP9X and PD-L1 may aid in predicting the efficacy of immunotherapy in PSC.
10.Effect of fasting blood glucose on coronary fractional flow reserve in patients with borderline coronary artery disease
Yi-wen ZHANG ; Ya-dong LIU ; Meng-xiao WANG ; Yi-ru WANG ; Yun-peng YANG ; Yun-fang SU ; Ji-xin ZHI
Chinese Journal of Interventional Cardiology 2025;33(5):272-277
Objective To explore the correlation between fasting blood glucose(FBG)level and fractional flow reserve(FFR)in patients with borderline coronary artery disease,and to clarify its potential influence on FFR measurement.Methods From August 2020 to August 2023,the data of 135 patients with coronary atherosclerotic heart disease who received coronary angiography and FFR evaluation in the Fourth Affiliated Hospital of Harbin Medical University were retrospectively collected.According to the exclusion and inclusion criteria,85 cases of borderline diseased vessels of single coronary artery with stenosis degree of 50%-80%were screened out,and they were divided into FBG≥6.1 mmol/L group(47 cases)and FBG<6.1 mmol/L group(38 cases).The baseline data,angiographic and functional indexes of the two groups were compared,and the correlation between FBG and FFR was analyzed.Results Compared with the FBG<6.1 mmol/L group,the FBG≥6.1 mmol/L group had a higher proportion of FFR negative results(72.3%vs.23.7%,P<0.001),and the FFR measurement values were generally increased[0.84(0.80,0.90)vs.0.75(0.68,0.80),P<0.001],with statistically significant differences.Pearson correlation analysis was performed on all lesions,and FFR>0.80(negative result)was positively correlated with FBG≥6.1 mmol/L(r=0.484,P<0.001).Conclusions Among the patients with borderline coronary artery disease(50%-80%stenosis)included in this study,FBG≥6.1 mmol/L is significantly correlated with FFR>0.80.For patients with borderline coronary lesions with elevated FBG,the influence of blood glucose factors should be carefully considered in clinical interpretation of FFR results.


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