Introduction:  Benzodiazepines are a class of sedative-hypnotic drugs often used by people suffering from anxiety, sleep disorders, stress reactions, panic disorders, obsessive-compulsive disorders, and mania due to their anticonvulsant, anxiolytic, and muscle relaxant properties [1,2]. Between the year 1996 to 2013, the percentage of US adults filling benzodiazepine prescriptions rose from 8.1 million to 13.5 million (67% increase), and the cumulative quantity of benzodiazepines served over the years surged by 140% [3]. However, this rise in treatment using benzodiazepines heavily contributed to an increase in the number of cases of benzodiazepine overdose-related deaths, from 0.58 to 3.07 per 100,000 adults. This value soon reached a plateau in early 2010 but continued to increase among the elderly and the Hispanic and African American communities [3]. It is worth noting that nearly 75% of these deaths were not caused by benzodiazepines alone but by the added effects of alcohol, opioids, or amphetamines [3].In mention to its relation with age, the use and misuse of benzodiazepines vary, with individuals between the ages of 50 to 64 years having the highest prescription-based use, whereas young adults of ages 18 to 25 years presented with the highest statistics for non-prescription based use, highlighting the misuse and abuse of benzodiazepines, according to a study conducted in the United States [4].Overdoses induced by benzodiazepines rarely present as an emergency and are often aggravated further by additional ingestion of other drugs [5]. In people with long-term benzodiazepine use, immediate retirement from the drug may induce a severe withdrawal syndrome, resulting in anxiety, confusion, sleep disorders, and in extreme cases, seizures [6]. The most widely used benzodiazepine, Alprazolam, has much greater side effects from withdrawal, including mania, psychosis, delirium, and hyperadrenergic states [7]. Furthermore, tapering of benzodiazepines has been linked to Takotsubo cardiomyopathy [8].This article reports a case regarding a Pakistani patient with no previous history of drug abuse that voluntarily overdosed on benzodiazepines (Alprazolam) alone and was later diagnosed with hypoxic-ischemic (anoxic) encephalopathy.Case Presentation:A 32-year-old Pakistani male was presented to the emergency department in an unconscious and gasping condition. His mother had found him in an unresponsive, comatose state. The patient had a history of epilepsy, anxiety, and depression. The remainder of his past medical history was unremarkable, and any admissions made during childhood had no recrudesce in adulthood.At the emergency department, the patient suffered multiple seizure episodes, and remained unconscious, maintaining a GCS of 3/15. Upon physical examination, unresponsive bilateral pinpoint pupils were noted; the neck of the patient was found to be supple, and the bilateral plantar reflexes were normal, suggesting active involuntary movement. His abdomen was soft and nontender, and his chest was found to be unremarkable.On the first day of admission, a complete blood count revealed a low hemoglobin count of 12.9 g/dl, leukocytosis (white blood cell count of 14.0 x 10^9/L), neutrophilia (neutrophil at 93%), hyperglycemia (glucose concentration at 93 mg/dl) and hyperproteinemia (proteins: 66.1 mg/dl), while displaying a minor decrease in the hematocrit levels. The test for plasma lactate levels was normal, resting at 15.5; however, lactate dehydrogenase levels produced a low result of 21 U/L (the normal range is 135 – 225 U/L). The above-mentioned laboratory investigations have been summarized in Table 1. Arterial blood gases revealed high anion gap metabolic acidosis. On the second day of admission, a urine test revealed a positive result for benzodiazepine overdose (>200 ng/ml) while testing negative for amphetamines, cannabinoids, barbiturates, and cocaine metabolites, as mentioned in Table 2.  Enzyme-linked immunosorbent assay for human immunodeficiency virus (HIV) antibodies and tests for the presence of Hepatitis B and C virus revealed negative results. The gram stain showed no organisms. On the fifth day, a test for C-reactive protein (CRP) revealed a CRP of 15.62 mg/l (normal range is less than 6), suggesting the presence of an inflammation reaction. His respiratory examination displayed acute hypercapnic respiratory failure (type II).A CT scan, which was also conducted on the first day, revealed no intraparenchymal hemorrhage, cerebral edema, or midline shift. Grey and white matter differentiation were intact, and the basal ganglia and thalami showed normal density. This was viewed through multiple axial images obtained from the base up to the vertex of the skull without intravascular contrast.Initial treatment for hypercapnic respiratory failure and seizures was initiated, as these were the presenting symptoms when our patient had arrived in the ER. He was intubated, aided by a pressure-synchronized intermittent mandatory ventilation (P-SIMV) mode ventilator, and transferred to the ICU for intensive care and monitoring. The patient was administered anti-inflammatory glucocorticoids, intravenous lactam antibiotics (meropenem, and tazobactam with piperacillin), levetiracetam for the treatment of seizures, and half normal saline with 2 amps of KCL at 75 ml/hr via a nasogastric tube as an immediate course of treatment.On the third day, the patient had self-extubated but maintained an oxygen saturation of 99% and was supplied with 5 L/min oxygen via facemask at a respiratory rate of 22/min. The patient’s GCS topped 15/15, and reintubation was considered unnecessary. The patient was drowsy, but was physically responsive and fully capable of conversing with the consultant. On this day the patient was diagnosed with benzodiazepine poisoning. The patient admitted to intentionally overdosing on Alprazolam, a type of benzodiazepine, with suicidal intentions, despite not having any history of using the drug or any other illicit substances previously. He was later diagnosed with major depressive disorder by the neurologist that overlooked the case.Further in regards to the patient’s condition, anion gaps returned to normal, and no further seizures occurred. The patient remained fatigued, but mobilization out of bed was prescribed. The patient had a physiotherapy session in which chest physiotherapy was conducted. The patient was kept in an ICU setting for another day before being transferred to a normal monitoring setup.In regards to the radiological tests taken following the initial CT scan, an echocardiography, electroencephalography (EEG) and a general abdomen ultrasound were taken on the third day. Echocardiography revealed atypical septal motion and an ejection fraction of 55%; however, all other findings were normal, with an absence of thrombi or pericardial effusions. EEG reported fast beta activity of 15-18 Hz in the background rhythm and muscle stiffness due to ventilation; however, photic stimulation was normal, and no focal or generalized epileptic discharges were noted. Since idiopathic epilepsy appears normal on an interictal EEG, the technician had advised that a diagnosis be made after clinical correlation. The abdominal ultrasound showed a slightly altered texture with raised echogenicity of the liver; however, the rest of the abdomen was unremarkable. On the fifth and sixth days of admission, a brain MRV/DWI and MRA were conducted to accurately view the condition of the brain. MRA revealed a comparatively attenuated right vertebral artery with normal hyperintensity within the right and left vertebral, basilar, and bilateral posterior cerebral arteries. No evidence of stenosis or abnormal dilation of the hyperintense arteries was seen. The MRV presented evidence of bilateral symmetrical abnormal signal intensity areas seen in the basal ganglia, predominantly in the globus pallidus, which appears hyperintense on T2/FLAIR images while showing restriction on the DWI images. The superior sagittal, inferior sagittal, transverse, and straight sinuses appeared unremarkable, and no venous segment filling was detected to show signs of thrombosis. Another MRV, which was taken 24 hours after the first one, presented the Dural sinuses as normal. The MRI, MRA, and MRV imaging, with DWI protocol, demonstrates ischemic hypoxic insult involving bilateral globus pallidus, which was later understood to be linked to the benzodiazepine intoxication.Upon gaining consciousness, the patient admitted to intentionally overdosing on Alprazolam with suicidal intentions, despite not having any history of using the drug or any other illicit substances previously. He was later diagnosed with major depressive disorder by the neurologist that overlooked the case.On the final day, the patient possessed the following vitals: blood pressure of 130/80, a pulse of 76/min, respiratory rate of 21/min, and oxygen saturation of 99% in the absence of oxygen support. The abdomen, respiratory and cardiovascular examinations were completely normal. The patient had fully gained consciousness, was well-oriented in time, place, and person, and held a GCS of 15/15, with an attenuated right vertebral artery under CNS findings. He was discharged after staying at the hospital for 6 days and was instructed to return for a follow-up after 1 week.During the follow-up, the patient presented with no cognitive deterioration and was completely responsive and healthy. The patient presented with no personality changes and sustained a GCS of 15/15.

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Primary breast lymphoma (PBL) is a rare form of extranodal lymphoma defined by the presence of a primary lesion within the breast with or without regional nodal involvement, but no other extra-mammary sites of involvement. Bilateral PBL is even more rare with very few cases reported in the literature. Herein, we

Maxillary molar root amputation: Case report with a 14-year follow-up and updated mini reviewKey Clinical Message : Root resection is performed to create a maintainable furcation area in teeth with advanced periodontitis. However, the long-term feasibility of this treatment remains controversial. We present a case in which distal root resection in a maxillary molar successfully preserved the form and function of the dentition for approximately 14 years.Keywords : Periodontitis, Furcation defect; long-term; Prognosis, Molar teeth

FH mutation associated uterine leiomyomas: A Case Report and Literature Review

Aim: To examine and understand the work processes of AMS teams across two hospitals that use the same digital intervention, and to identify the challenges and enablers to effective AMS in each setting. Methods: Employing a contextual inquiry approach informed by the Systems Engineering Initiative for Patient Safety (SEIPS) model, observations and semi-structured interviews were conducted with AMS team members (n=15) in two Australian hospitals. Qualitative data analysis was conducted, mapping themes to the SEIPS framework. Results: Both hospitals utilised similar systems, however, they displayed variations in AMS processes, particularly in post-prescription review, interdepartmental AMS meetings, and the utilisation of digital tools. An antimicrobial dashboard was available at both hospitals but was utilised more at the hospital where the AMS team members were involved in the dashboard’s development, and there were user champions. At the hospital where the dashboard was utilised less, participants were unaware of key features, and interoperability issues were observed. Establishing strong relationships between the AMS team and prescribers emerged as key to effective AMS at both hospitals. However, organisational and cultural differences were found, with one hospital reporting insufficient support from executive leadership, increased prescriber autonomy, and resource constraints. Conclusion: Organisational and cultural elements, such as executive support, resource allocation, and interdepartmental relationships, played a crucial role in achieving AMS goals. System interoperability and user champions further promoted the adoption of digital tools, potentially improving AMS outcomes through increased user engagement and acceptance.

To analyze images in various fields of science and technology, it is often necessary to count observed objects and determine their parameters. This can be quite labor-intensive and time-consuming. This article presents DLgram, a universal, user-friendly cloud service that is developed for this purpose. It is based on deep learning technologies and does not require programming skills. The user labels several objects in the image and uploads it to the cloud where the neural network is trained to recognize the objects being studied. The user receives recognition results which, if necessary, can be corrected, errors removed, or missing objects added. In addition, it is possible to carry out mathematical processing of the data obtained to get information about the sizes, areas, and coordinates of the observed objects. The article describes the service features and discusses examples of its application. The DLgram service allows to reduce significantly the time spent on quantitative image analysis, reduce subjective factor influence, and increase the accuracy of analysis.

Once batteries reach their end-of-life (EoL), they are expected to be collected, dismantled, and shredded into black mass (BM) which includes wealth amounts of critical metals. BM can be regarded as a kind of urban mines, where recyclers extract critical metals and reintroduce them into new battery manufacturing. Focusing on the BM, this article discussed the necessity of BM recovery and current recycling situations. Although the benefits of recycling are commonly agreed upon, there remain still many challenges and issues to overcome. The BM market is still in its infancy, relevant regulatory frameworks need to be updated with the widespread use and advancement of lithium-ion batteries (LIBs). Current BM-producing and processing technologies still have room for large improvements in terms of economic feasibility and sustainability that in the end requires efforts from both researchers and industrial stakeholders with growing interests and patient engagements.

This paper proposes a dynamic programming approach targeted to solve a natural resource problem of water storage management for irrigation in an environmentally and socially sustainable way. The problem we examine in our formulation, which deals with the control of water storage in tanks, incorporates assumptions that are milder compared to those previously discussed in the literature concerning similar approaches. Specifically, we consider a time periodic optimal control problem whose performance functional to be maximized merely satisfies a contraction assumption (in the sense of Boyd and Wong) weaker than the one usually considered in the pertinent literature. By using an appropriate fixed point theorem, a time periodic value function can be constructed to enable the definition of optimal feedback control strategies. After showing the insufficiency of Banach contraction frameworks, and proving the underlying auxiliary mathematical results, we show our main result under conditions that are weaker than the previous related ones. Simulation results illustrate the performance of our approach.

Recommendations for müllerian anomalies classificationSi Su1,2, Lan Zhu1*1 Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Obstetric and Gynecologic Diseases, Beijing, China2 Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China*Corresponding Author: Lan Zhu, MD, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Obstetric and Gynecologic Diseases, No. 1 Shuaifuyuan, Dongcheng District, 100730, Beijing, China ([email protected])The word count for the main text: 506.In 2021, a new müllerian Anomalies Classification was proposed by American Society for Reproductive Medicine (ASRM 2021), 1 which was based on the American Fertility Society (AFS) 1988 2 and combined the benefits of existing classifications. However, mullerian anomalies is a group of complex diseases with various manifestations. And no consensus has been reached about the classification and diagnosis in clinical practice. The purpose of this study is to test the clinical application value of this new classification through the analysis of the cases from Peking Union Medical College Hospital in the past 20 years, and put forward valuable recommendations.A retrospective study was conducted using clinical data of hospitalized patients from January 2003 to December 2022 from Peking Union Medical College Hospital. Inclusion criteria included patients with 46, XX karyotype, diagnosed of müllerian anomalies, and clearly identified alterations of the uterus, cervix, and vagina. Clinical data of patients were collected through the hospital information system, and classification was performed based on the ASRM 2021. SPSS 25.0 version was used for data analysis.2671 patients were included, with an average visiting age of 28.9±10.0 years. The most common is septate uterus with 1144 cases (42.8%), followed by MRKH syndrome (20.4%), Herlyn-Werner-Wunderlich syndrome (HWWS) (10.4%), unicornuate uterus (7.4%), cervical agenesis (6.5%), uterus didelphys (5.6%), bicornuate uterus (2.9%), longitudinal vaginal septum (without uterine malformation) (2.0%), transverse vaginal septum (1.2%), complex anomalies (0.5%) and other anomalies (0.3%) (Table 1). It should be emphasized that HWWS was taken as an independent classification for statistical analysis, with reference to the clinical definition (uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis).3,4 13 cases of complex anomalies were identified and 8 cases that could not be classified were classified as other anomalies (Supplement table 1).ASRM 2021 was proposed based on the AFS 1988, which is the most widely used classification in the past 30 years. We found ASRM 2021could distinguish most clinical patients well, but there are still some shortcomings. First, the classification of patients with uterine malformations and longitudinal/transverse/oblique vaginal septum is not clear. We recommend that patients with longitudinal vaginal septum and uterine anomalies should be classified into the uterine anomalies respectively, while others without uterine anomalies should be included in longitudinal vaginal septum. All transverse vaginal septum should be included in transverse vaginal septum, because the symptoms of transverse septum are prominent. A new type of HWWS should be added. Because the obstructive symptom is prominent. Second, we found several cases of complex anomalies. For these patients, multidisciplinary and individualized treatment should be carried out. The anomalies we found that are not currently classified include T-shaped uterus, congenital vaginal stenosis, and accessory and cavitated uterine masses (ACUM). With the deeper insight into this field, there may be a better way to classify them. The limitation of this study is that as a single-center retrospective study, there could be statistical biases.In conclusion, we put forward following suggestions for ASRM 2021 classification: 1) Minimize overlaps of classification and add a type of HWWS; 2) Update complex anomalies timely; 3) Add other anomalies classification.

Should we stay or should we go – the ever-growing role of Twitter (X) in Neuroscience dissemination and a quandary of conscience for a field.Kenneth A. Foxe and John J. Foxe

The Janzen-Connell hypothesis is one of the most important hypotheses in ecology, but is mostly tested indirectly without accounting for the underlying plant-associated organisms, or only for highly host-specific organisms. Advances in massive sequencing allow to sample, for example, the fungi communities associated with different plant species, and spatial analysis can reveal spatial patterns in the number of organisms (species) shared by plant species and their neighbours. We show how combining these tools provides new perspectives for testing the Janzen Connell hypothesis. We illustrate our approach using a natural experiment in two fully-mapped Mediterranean forest plots, where the dominant dry- and fleshy-fruited species have distinctly different seed deposition patterns, leading to contrasting expectation about the emerging spatial structures. Our analysis confirmed these expectations and provided deep insights into how the neighbourhood load of plant-associated fungi and herbivorous insects changes during plant ontogeny and how seed dispersal mechanisms modulates Janzen-Connell effects.

Background and Purpose: Traumatic brain injury (TBI) imposes life-long physical, psychological, and financial burdens on affected individuals. The current study investigated the effects of chronic nicotine exposure via E-cigarette (E-cig) on TBI-associated behavioral and biochemical changes. Experimental Approach: Adult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E-cigarette (E-Cig) vapor for six weeks. The effects of chronic nicotine exposure on sensorimotor functions, locomotion, and sociability were evaluated by nesting, open field, and social approach, respectively. Immunoblots were performed to assess changes of mature brain-derived neurotrophic factor (mBDNF) and associated downstream signaling proteins (p-Akt and p-Erk). Histological analyses of the cortex were performed to evaluate the effects of chronic nicotine exposure on Microglia-mediated neuroinflammation. Key Results: Post-injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histology analysis revealed that chronic nicotine exposure increased the survival of cortical neurons in the perilesion cortex. Immunoblots of cortical tissue revealed that chronic nicotine exposure significantly upregulated mBDNF expression, P-Erk, and p-Akt in the perilesion cortical tissue of CCI mice. Additional IF microscopy revealed elevated mBDNF and p-Akt expression was predominantly localized in cortical neurons of CCI mice. Furthermore, immunolabeling of Iba1 showed that chronic nicotine exposure attenuates microglia-mediated chronic neuroinflammation in the perilesional cortex of CCI mice. Conclusions and Implications: Post-injury chronic nicotine exposure via vaping facilitates sensorimotor function recovery by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signaling. Results from this study support the neuroprotective properties of nicotine, further investigation is needed due to its highly addictive nature.

Introduction Oral propranolol is a first-line treatment for infantile hemangiomas (IH). This study aims to describe the results of treating IH with propranolol only or initial propranolol therapy followed by laser therapy, surgical excision, corticosteroid therapy, or a second cycle of propranolol. Methods Our patient population included pediatric patients (<18 years of age) diagnosed with IH at Monroe Carell Junior Children’s Hospital at Vanderbilt University Medical Center between August 2009 to July 2017. Patient demographics, IH clinical features, and treatment data were extracted from the electronic medical record. Results Three hundred forty patients with IH were included in this study, with a prevalence of focal lesions (71%) and a total of 279 (82%) IH located on the head/neck. Lesions of the head had a statistically significant association with PHACE syndrome (p<0.001). Most patients initiated propanolol treatment before the age of 6 months (71%), with continuation for ≥6 months (69%). Upon discontinuation of propranolol, 14 (4%) patients required a second cycle of propranolol for regrowth. After controlling for IH location, patients with a family history of hemangiomas or cardiac abnormalities were 3.6 times more likely to need a second round of propranolol treatment (OR, 3.6; 95% Confidence Interval 1.14-11.19) (P=0.03). Conclusion The study confirms propranolol’s effectiveness and safety, reinforcing the need for early intervention and close monitoring following treatment termination to prevent regrowth. Ultimately, this research contributes to advancing the understanding and treatment of IH, aiming to optimize patient outcomes and reduce morbidity.

Nutrient deficiency, excitotoxic injury, and oxidative stress caused by cerebral ischemia/reperfusion injury are important inducing factors of mitophagy and ferroptosis in neurons. Ferroptosis is an iron-dependent mode of cell death usually accompanied by a large accumulation of iron ions and lipid peroxides. Mitophagy is one of the forms of selective autophagy, which can maintain mitochondrial and cellular homeostasis by eliminating dysfunctional mitochondria. Mitophagy and ferroptosis are closely related to the pathological mechanism of ischemia/reperfusion injury. However, the function and mechanism of mitophagy in regulating ferroptosis are only beginning to be understood, and the relationship between mitophagy and ferroptosis after cerebral ischemia/reperfusion has not been elucidated. This article reviews the mechanism pathways of mitophagy and ferroptosis after cerebral ischemia/reperfusion, especially discusses the common regulatory factors of mitophagy and ferroptosis in cerebral reperfusion injury, and focuses on the therapeutic potential of mitophagy in regulating ferroptosis, in order to provide ideas for targeted treatment of cerebral ischemia/reperfusion injury.

Cartilage is frequently used as scaffolds for repairing and reconstructing body surface organs. However, after successful plastic surgery, transplanted cartilage scaffolds often exhibit deformation and absorption over time. To enhance the shapping stability of cartilage scaffolds and improve patients’ satisfaction after reconstructions, we employed the ear folding models in New Zealand rabbit to confirm whether the 1064nm Nd:YAG laser could promote cartilage reshapping. There was an increase in collagen and aromatase (Cyp19) expression within the ear cartilage after laser treatment. Moreover, we have discovered that the Cyp19 inhibitor can suppress the shaping effect of the laser on cartilage, as well as the expression of collagen and Cyp19. The overall findings suggest that treatment with 1064nm Nd:YAG laser irradiation can enhance estrogen levels in local cartilage tissues by upregulating Cyp19 expression in chondrocytes through photobiomodulation, thereby promoting the proliferation and collagen secretion of chondrocytes to improve cartilage reshaping and stability.

Background: Starting from May 31 st, 2023, the local transmission of monkeypox (Mpox) in mainland China began in Beijing. Till now, the transmission characteristics have not been explored. Method: Based on the daily Mpox incidence data in the first three weeks of Beijing (from May 31 st to June 21 st, 2023) , we employed the instant-individual heterogeneity transmission model to simultaneously calculate the effective reproduction number ( R e) and the degree of heterogeneity ( k) of the Beijing epidemic. We additionally simulated the monthly infection size in Beijing from July to September and compared with the reported data to project subsequent transmission dynamics. Results: We estimated R e to be 1.68 [95% HPD:1.12, 2.41], and k to be 2.57 [95% HPD: 0.54, 83.88], suggesting the transmission of Mpox in Beijing was supercritical and didn’t have considerable transmission heterogeneity. We projected that R e fell in the range of 0.95 to 1.0 from July to September, highlighting more efforts needed to further reduce the Mpox transmissibility. Conclusion: Our findings revealed supercritical and homogeneous transmission of the Mpox epidemic in Beijing. Our results may provide reference for understanding and predicting of the on-going Mpox transmission in other regions of China and assess the effect of control measures.

Background and purpose: Bardoxolone methyl (2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid methyl ester, CDDO-Me) is a potent activator of nuclear factor erythroid 2-related factor (Nrf)2, which induces anti-oxidative-associated genes. CDDO-Me is known to exert protective effects against chronic inflammatory diseases in the kidney and lungs. However, its pharmacological effects on non-alcoholic steatohepatitis (NASH) caused by fat accumulation remain unknown. In this study, we examined the hepatoprotective effects of CDDO-Me in a diet-induced NASH mouse model, and elucidated its pharmacological mechanisms using RNA-seq analysis. Experimental approach: CDDO-Me was orally administered to mice fed a choline-deficient, L-amino acid-defined, high-fat diet, and histological, biochemical, and transcriptome analyses were performed on the livers of mice that developed NASH. Key results: CDDO-Me administration induced the expression of antioxidant genes and cholesterol transporters downstream of Nrf2 and significantly improved the symptoms of NASH. Whole-transcriptome analysis revealed that CDDO-Me inhibited the inflammatory pathway that leads to phagocyte recruitment, in addition to activating the Nrf2-dependent pathway. Among inflammatory pathways, CC chemokine ligand (CCL)3 and CCL4 in the downstream of NF-B, which are associated with the recruitment of macrophages expressing CC chemokine receptor (CCR)1 and CCR5, were released into blood in NASH mice. In contrast, CDDO-Me directly inhibited the expression of CCL3-CCR1 and CCL4-CCR5 in macrophages. Conclusions and Implications: Overall, this study revealed the potent hepatoprotective effect of CDDO-Me in a NASH mouse model, and demonstrated that its pharmacological effects were closely associated with the reduction of macrophage infiltration through CCL3-CCR1 and CCL4-CCR5 inhibition, in addition to Nrf2-mediated hepatoprotective effects.