ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P0.01）， significantly decreased fractional shortening （FS） （P0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P0.05， P0.01）， significantly increased FS （P0.05， P0.01）， significantly decreased LVDD and LVDS （P0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P0.01）， and significantly decreased BV at high， medium， and low shear rates （P0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P0.05， P0.01）， while HDL levels were significantly decreased （P0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P0.05， P0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P0.05， P0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P0.05， P0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P<0.01）， significantly decreased fractional shortening （FS） （P<0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P<0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P<0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P<0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P<0.05， P<0.01）， significantly increased FS （P<0.05， P<0.01）， significantly decreased LVDD and LVDS （P<0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P<0.01）， and significantly decreased BV at high， medium， and low shear rates （P<0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P<0.05， P<0.01）， while HDL levels were significantly decreased （P<0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P<0.05， P<0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P<0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P<0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P<0.05， P<0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P<0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P<0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P<0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P<0.05， P<0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

ObjectiveTo evaluate the anti-inflammatory activity of the novel magnolol ester derivative YW and to investigate its effects on chondrocyte senescence and preliminary mechanisms. MethodsMagnolol and p-methylbenzoic acid were used as raw materials to synthesize the magnolol ester derivative YW （Molecular Formula： C₂₆H₂₄O₃， Molecular Weight： 384.17， HPLC Purity >96%） via DCC/DMAP-catalyzed esterification. Cytotoxicity was assessed using the CCK-8 assay. A lipopolysaccharide （LPS）-induced RAW264.7 macrophage activation model and an interleukin-1β （IL-1β）-induced rat primary chondrocyte model were established. The release and mRNA expression of inflammatory factors including nitric oxide （NO）， IL-1β， tumor necrosis factor-alpha （TNF-α）， and IL-6 were detected by enzyme-linked immunosorbent assay （ELISA）， Griess reagent method， and quantitative real-time PCR （RT-qPCR）. The expression of senescence markers such as inducible nitric oxide synthase （iNOS）， pro-interleukin-1β （pro-IL-1β）， lysine acetyltransferase 7 （KAT7）， cyclin-dependent kinase inhibitor 1A （p21）， and cyclin-dependent kinase inhibitor 2A （p16）， as well as proteins related to chondrocyte extracellular matrix synthesis and catabolism， were analyzed by Western blot （WB）. Molecular docking was performed using Discovery Studio 2019 to validate target binding. ResultsYW exhibited no significant cytotoxicity at concentrations ≤20 μmol/L. YW concentration-dependently inhibited LPS-induced macrophage inflammatory cytokine release， significantly downregulated iNOS， Pro-IL-1β protein， and inflammatory cytokine mRNA expression （P<0.01）. YW stably bound to KAT7 protein （binding energy： -94.2 kcal/mol）； YW downregulated KAT7 and aging marker protein expression in naturally aged and IL-1β-induced chondrocyte models （P<0.01）； YW regulated chondrocyte matrix synthesis and catabolic protein expression in IL-1β-induced chondrocytes （P<0.01）. ConclusionYW inhibits macrophage activation and inflammatory cytokine release while downregulating KAT7 and senescence marker protein expression in chondrocytes， thereby blocking chondrocyte senescence.

ObjectiveTo investigate the protective effect of magnolol ester derivative YW against cisplatin （Cis）-induced acute kidney injury （AKI） and to explore its effect and preliminary mechanisms on Cis-induced AKI. MethodsThe research group designed and synthesized the magnolol ester derivative YW using magnolol as the parent core. Molecular docking was employed to predict the binding interaction between YW and lysine acetyltransferase 7 （KAT7）. A Cis-induced AKI model was established in C57BL/6J mice. Mice were divided into the normal control group， model group， YW low/medium/high dose groups （17.5， 35， 70 mg/kg）， and the positive control amifostine group. Renal function was assessed by measuring serum creatinine （Scr） and blood urea nitrogen （BUN） levels. Pathological changes were evaluated via HE staining and scoring of kidney tissues. Protein expression levels of kidney injury molecule 1 （KIM-1）， lysine acetyltransferase 7 （KAT7）， and cyclin-dependent kinase inhibitor 1A （p21） in kidney tissues were detected by Western blot （WB）. HK-2 cells were treated with different concentrations of YW； cell viability was measured by CCK-8 assay. WB was used to detect the expression levels of the renal injury marker KIM-1， KAT7， and its downstream protein p21. Cellular senescence was assessed by senescence-associated β-galactosidase （SA-β-Gal） staining. ResultsYW could stably bind to KAT7. In vivo experiments showed that， compared with the model group， all YW dose groups， especially the medium and high doses， significantly reduced the elevated levels of Scr and BUN in AKI mice （P<0.001） and effectively ameliorated renal histopathological damage. YW significantly downregulated the protein expression levels of KIM-1， KAT7， and p21 in kidney tissues （P<0.05）. Concentrations of YW≤10 μmol/L had no significant effect on HK-2 cell viability. YW inhibited the Cis-induced decline in HK-2 cell viability （P<0.05）， suppressed the Cis-induced upregulation of KIM-1， KAT7， and p21 proteins （P<0.05）， and significantly decreased the percentage of SA-β-Gal-positive cells （P<0.01）. ConclusionYW suppresses the expression of KAT7 and p21 proteins and inhibits the decline in HK-2 cell viability in cisplatin-induced AKI， significantly mitigates HK-2 cell senescence， and improves renal function， providing preliminary experimental evidence for developing AKI treatment strategies based on structural optimization of natural products.

Hepatic encephalopathy is a difficult and critical disease with rapid progression and limited treatment methods in the field of liver disease， and it is urgently needed to make breakthroughs in its pathogenesis. Selection of appropriate prevention and treatment strategies is of great importance in delaying disease progression and reducing the incidence and mortality rates. This article reviews the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine， proposes a new theory of “turbid toxin pathogenesis”， analyzes the scientific connotations of “turbid”， “toxin”， and the theory of “turbid toxin pathogenesis”， and constructs the “four-step” prevention and treatment strategies for hepatic encephalopathy， thereby establishing the new clinical prevention and treatment regimen for hepatic encephalopathy represented by “four prescriptions and two techniques” and clarifying the effect mechanism and biological basis of core prescriptions and techniques in the prevention and treatment of hepatic encephalopathy， in order to provide a reference for the prevention and treatment of hepatic encephalopathy.

Background/Aims: Distal mean nocturnal baseline impedance (MNBI) measuring via pH-impedance may be valuable in diagnosing patients with suspected laryngopharyngeal reflux (LPR). However, its wide adoption is hindered by cost and invasiveness. This study investigates whether baseline impedance measured during high-resolution impedance manometry (HRIM-BI) can predict pathological MNBI. Methods: A cross-sectional study in Taiwan included 74 subjects suspected of LPR, who underwent HRIM (MMS) and pH-impedance testing (Diversatek), after stopping proton pump inhibitors for more than 7 days. Subjects with grade C or D esophagitis or Barrett’s esophagus were excluded. The cohort was divided into 2 groups: those with concomitant typical reflux symptoms (CTRS, n = 28) and those with isolated LPR symptoms (ILPRS, n = 46). HRIM-BI measurements focused on both distal and proximal esophagi. Pathological MNBI was identified as values below 2065 Ω, measured 3 cm above the lower esophageal sphincter. Results: In all subjects, distal HRIM-BI values correlated weakly with distal MNBI(r = 0.34-0.39, P < 0.005). However, in patients with ILPRS, distal HRIM-BI corelated moderately with distal MNBI(r = 0.43-0.48, P < 0.005). The areas under the receiver operating characteristic curve was 0.78 (P = 0.001) with a sensitivity of 0.83 and a specificity of 0.68. No correlation exists between distal HRIM-BI and distal MNBI in patients with CTRS, and between proximal HRIM-BI and proximal MNBI in both groups. Conclusions Distal HRIM-BI from HRIM may potentially predict pathological MNBI in patients with ILPRS, but not in those with CTRS. Future outcome studies linked to the metric are warranted.

Objective To explore the role of SLIT-ROBO Rho GTPase-activating protein 2(srGAP2)in spinal motor neuron degeneration in amyotrophic lateral sclerosis(ALS).Methods Applied bioinformatics analysis to investigate the expression changes of srGAP2 in the spinal cord of human superoxide dismutase 1(hSOD1)mutant ALS transgenic mice.hSOD1 G93A mutant ALS transgenic mice were selected for animal experimental validation,with littermate wild type(WT)mice serving as the control group.A total of 36 pairs were divided into four groups,namely the pre-onset stage,early-onset stage,mid-onset stage,and late-onset stage.The expression changes and cellular localization of srGAP2 in the spinal cord of ALS mice were detected by Real-time PCR,Western blotting and immunofluorescent double-label staining.The hSOD1G93A mutant NSC34 motor neuron-like cell model was established,and in vitro experiments were carried out to detect the changes in srGAP2 expression,and the effects of srGAP2 over-expression on the viability of hSOD1G93A mutant NSC34 cells and the growth of cell protrusions.Results Bioinformatics analysis revealed abnormally low expression of srGAP2 in the spinal cord of hSOD1 mutant ALS mice.Animal experiments verified that compared with the WT mice,the expression of srGAP2 was reduced at both mRNA level and protein level in the spinal cord of hSOD1G93A mutant ALS transgenic mice at early-onset,mid-onset and late-onset stages.Compared with the WT mice,srGAP2 integral absorbance(IA)values in srGAP2+/NeuN+double-positive cells in the anterior horn of the spinal cord of hSOD1G93A mutant ALS transgenic mice were lower,srGAP2 IA values in srGAP2+/GFAP+double-positive cells were higher;Compared with the hSOD1WT NSC34 cells,the expression of srGAP2 was reduced at both mRNA level and protein level in hSOD1G93A mutant NSC34 cells.Over-expression of srGAP2 elevated the viability of hSOD1G93A mutant NSC34 cells,and up-regulated the expression level of synapse-related protein β Ⅲ-tubulin and growth associated protein 43(GAP43).Conclusion Low expression of srGAP2 is closely associated with the progression of ALS,while over-expression of srGAP2 can promote outgrowth of cell protrusions and exert a protective effect on spinal motor neurons in ALS.

This study established a high performance liquid chromatography(HPLC) fingerprint of Chuanxiong Rhizoma from different producing areas and screened its potential differential components for producing areas by chemometrics. Furthermore, the content of the above differential components in Chuanxiong Rhizoma from different producing areas was measured and compared. Then, the geoherbalism markers(geo-markers) that can be used to distinguish Dao-di and non-Dao-di Chuanxiong Rhizoma were excavated by chemometrics. In fingerprint studies, a total of 27 common peaks were determined, and the fingerprint similarity for 37 batches of Chuanxiong Rhizoma samples from different producing areas was above 0.968. The orthogonal partial least squares-discriminant analysis(OPLS-DA) was capable of distinguishing Chuanxiong Rhizoma from Sichuan and from three other provinces, as well as Dao-di Chuanxiong Rhizoma(from Dujiangyan) and non-Dao-di Chuanxiong Rhizoma(from other producing areas) in Sichuan province. Meanwhile, 14 potential differential components in Chuanxiong Rhizoma from different provinces and 16 potential differential components in Chuanxiong Rhizoma from different producing areas in Sichuan were screened by the variable importance in projection(VIP) analysis under OPLS-DA. The reference standards were used to identify 10 potential differential components in the common peaks, and subsequent content determination verified that the content of the above 10 potential differential components was different among different producing areas. Then, the OPLS-DA and VIP analysis were performed with the content of the 10 potential differential components as variables. The results showed that Z-ligustilide, chlorogenic acid, and the ratio of butylidenephthalide/senkyunolide A were the geo-markers that can distinguish Chuanxiong Rhizoma from Sichuan and Chuanxiong Rhizoma from Shaanxi, Hebei, and Jiangxi, while Z-ligustilide, n-butylphthalide, and the ratios of Z-ligustilide/senkyunolide A and butylidenephthalide/senkyunolide A were the geo-markers that can distinguish Dao-di Chuanxiong Rhizoma(from Dujiangyan) and non-Dao-di Chuanxiong Rhizoma(from other producing areas) in Sichuan province. This study elucidated the differences in material basis of Dao-di and non-Dao-di Chuanxiong Rhizoma based on fingerprinting and content determination combined with chemometrics, which provides a reference for the study of material basis of Dao-di traditional Chinese medicine.
Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Chemometrics/methods* ; Quality Control

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

Background/Aims: Distal mean nocturnal baseline impedance (MNBI) measuring via pH-impedance may be valuable in diagnosing patients with suspected laryngopharyngeal reflux (LPR). However, its wide adoption is hindered by cost and invasiveness. This study investigates whether baseline impedance measured during high-resolution impedance manometry (HRIM-BI) can predict pathological MNBI. Methods: A cross-sectional study in Taiwan included 74 subjects suspected of LPR, who underwent HRIM (MMS) and pH-impedance testing (Diversatek), after stopping proton pump inhibitors for more than 7 days. Subjects with grade C or D esophagitis or Barrett’s esophagus were excluded. The cohort was divided into 2 groups: those with concomitant typical reflux symptoms (CTRS, n = 28) and those with isolated LPR symptoms (ILPRS, n = 46). HRIM-BI measurements focused on both distal and proximal esophagi. Pathological MNBI was identified as values below 2065 Ω, measured 3 cm above the lower esophageal sphincter. Results: In all subjects, distal HRIM-BI values correlated weakly with distal MNBI(r = 0.34-0.39, P < 0.005). However, in patients with ILPRS, distal HRIM-BI corelated moderately with distal MNBI(r = 0.43-0.48, P < 0.005). The areas under the receiver operating characteristic curve was 0.78 (P = 0.001) with a sensitivity of 0.83 and a specificity of 0.68. No correlation exists between distal HRIM-BI and distal MNBI in patients with CTRS, and between proximal HRIM-BI and proximal MNBI in both groups. Conclusions Distal HRIM-BI from HRIM may potentially predict pathological MNBI in patients with ILPRS, but not in those with CTRS. Future outcome studies linked to the metric are warranted.