Lymphoepithelioma-Like Intrahepatic Cholangiocarcinoma Associated with Epstein-Barr Virus and Hepatitis Virus: Case Report and a Literature Review.

Background: Lymphoepithelioma-like carcinoma of the liver is a rare primary malignancy of the liver. The identification of lymphoepithelioma-like cholangiocarcinoma is very limited as there are currently very few reports of such cases. Although previous studies have reported the lymphoepithelioma-like cholangiocarcinoma pathologic features, few studies have revealed the clinic features, imaging characteristics, and clinical course and outcomes. This study was analyzed from multiple aspects such as contrast-enhanced ultrasound, magnetic resonance imaging, and pathological characteristics, aiming to improve the comprehensive understanding of this rare subtype of disease. Case Presentation: A 43-year-old female with a history of hepatitis B for over 20 years presented with a lesion found in the right lobe of her liver. After discussion by a multidisciplinary team (MDT), malignant tumors cannot be excluded based on contrast-enhanced ultrasound and MRI. Thus, we decided to perform surgery for the patient. Postoperative pathology confirmed lymphoepithelioma-like intrahepatic cholangiocarcinoma. After 3 months of follow-up, the patient was still alive and no recurrence was observed. Conclusion: The purpose of this article is to describe a rare case of lymphoepithelioma-like intrahepatic cholangiocarcinoma and analyze its contrast-enhanced ultrasound and contrast-enhanced MRI features, which will be helpful for physicians in diagnosing this disease. From the perspective of CEUS, the wedge-shaped highly enhanced area around the lesion in the arterial phase appears to be inflammatory but looks malignant based on the extremely fast washout. The lesion showed a low signal on T1WI, a high signal on T2WI and DWI, and an abnormal perfusion shadow can be seen behind the lesion. In particular, this subtype of cholangiocarcinoma has a good prognosis, the clinician should improve the recognition of the disease to strive for early diagnosis and therapy.

Endothelial DR6 in blood-brain barrier malfunction in Alzheimer's disease.

The impairment of the blood-brain barrier (BBB) has been increasingly recognised as a critical element in the early pathogenesis of Alzheimer's disease (AD), prompting a focus on brain endothelial cells (BECs), which serve as the primary constituents of the BBB. Death receptor 6 (DR6) is highly expressed in brain vasculature and acts downstream of the Wnt/ß-catenin pathway to promote BBB formation during development. Here, we found that brain endothelial DR6 levels were significantly reduced in a murine model of AD (APPswe/PS1dE9 mice) at the onset of amyloid-ß (Aß) accumulation. Toxic Aß25-35 oligomer treatment recapitulated the reduced DR6 in cultured BECs. We further showed that suppressing DR6 resulted in BBB malfunction in the presence of Aß25-35 oligomers. In contrast, overexpressing DR6 increased the level of BBB functional proteins through the activation of the Wnt/ß-catenin and JNK pathways. More importantly, DR6 overexpression in BECs was sufficient to rescue BBB dysfunction in vitro. In conclusion, our findings provide new insight into the role of endothelial DR6 in AD pathogenesis, highlighting its potential as a therapeutic target to tackle BBB dysfunction in early-stage AD progression.

Indocyanine Green Fluorescence Imaging in the Surgical Management of Skin Squamous Cell Carcinoma.

Introduction: Indocyanine green (ICG) fluorescence imaging has been used in the resection surgery and sentinel lymph node biopsy of many tumors. The aim of the present study is to verify the feasibility and effectiveness of ICG fluorescence imaging used for guiding the biopsy and resection of skin squamous cell carcinoma (SSCC). Methods: Sixty patients were enrolled, including 18 patients of suspected SSCC and 42 patients of diagnosed SSCC on admission. The ICG fluorescence imaging-guided skin biopsy was performed preoperatively in the 18 cases of suspected SSCC. Fifty-three patients underwent ICG fluorescence imaging-guided radical excision. Results: The results showed that 138 skin tissue samples in 60 patients with preoperative or intraoperative ICG fluorescence imaging-guide biopsy were collected. For a total number of 138 biopsies, 122 specimens were squamous cell carcinoma, and the accuracy rate was 88.4%, which was significantly higher than that of the group without preoperative ICG fluorescence imaging (41/62, 66.1%, P < 0.05). Fifty-three patients underwent surgery guided with ICG fluorescence imaging. Residual fluorescent signals in 24 patients were intraoperatively found and the excision was then expanded until the signals disappeared. Follow-up to November 2022, 12 patients died, of which 5 cases died from the tumor recurrence, and the others died due to advanced ages or other reasons. The recurrence rate was 9.4%, which was not significantly different from that of the group received routine radical resection (4/35, 11.4%, P > 0.05). Moreover, sentinel lymph nodes were successfully detected under ICG fluorescence imaging in the 4 patients with suspected lymph node metastases, and the location of lymph nodes can be precisely identified. Conclusion: ICG fluorescence imaging technique can guide the pathology biopsy to improve the accuracy of pathological examination, and help to identify the boundaries of tumor tissues and sentinel lymph nodes to resect tumor radically during operation.

Protective effect of liraglutide on the myocardium of type 2 diabetic rats by inhibiting polyadenosine diphosphate-ribose polymerase-1.

BACKGROUND: In recent years, studies have found that the occurrence and development of diabetic cardiomyopathy (DCM) is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1 (PARP-1) activity. PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress, the inflammatory response, apoptosis and myocardial fibrosis. AIM: To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats, further clarified the protective effect of liraglutide on the heart, and provided a new option for the treatment of DCM. METHODS: Forty healthy male SD rats aged 6 wk were randomly divided into two groups, a normal control group (n = 10) and a model group (n = 30), which were fed an ordinary diet and a high-sugar and high-fat diet, respectively. After successful modeling, the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group (further divided into a high-dose group and a low-dose group). The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention. Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles. Intact heart tissue was dissected, and its weight was used to calculate the heart weight index. Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry. RESULTS: The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group, and those in the intervention group were decreased compared with those in the model group, with a more obvious decrease observed in the high-dose group (P < 0.05). In the model group, myocardial fibers were disordered, and inflammatory cells and interstitial fibrosis were observed. The cardiomyopathy of rats in the intervention group was improved to different degrees, the myocardial fibers were arranged neatly, and the myocardial cells were clearly striated; the improvement was more obvious in the high-dose group. Compared with the normal control group, the expression of PARP-1 in myocardial tissue of the model group was increased, and the difference was statistically significant (P < 0.05). After liraglutide intervention, compared with the model group, the expression of PARP-1 in myocardial tissue was decreased, and the reduction was more obvious in the high-dose group (P < 0.05) but still higher than that in the normal control group. CONCLUSION: Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.

The associations between diode laser (810 nm) therapy and chronic wound healing and pain relief: Light into the chronic wound patient's life.

Chronic wounds have become one of the major issues in medicine today, the treatments for which include dressing changes, negative pressure wound therapy, hyperbaric oxygen, light irradiation, surgery and so forth. Nevertheless, the application of diode lasers in chronic wounds has rarely been reported. This retrospective cohort study aimed to evaluate the therapeutic effect of diode laser (810 nm) irradiation on chronic wounds. Eighty-nine patients were enrolled in the study. The control group (41 patients) received traditional dressing change therapy, while the diode laser treatment group (48 patients) were patients received additional treatment with diode laser (810 nm) irradiation for 10 min at each dressing change. Wound healing time was compared between two groups, while the pain relief index was creatively introduced to evaluate the effect of relieving wound pain, which was calculated by the difference in pain scores between the first and last dressing changes divided by the number of treatment days. The wound healing time of the diode laser treatment group was 22.71 ± 8.99 days, which was significantly shorter than that of the control group (37.44 ± 23.42 days). The pain relief index of the diode laser treatment group was 0.081 ± 0.055, which was significantly increased compared with that of the control group (0.057 ± 0.033). Our findings suggest that diode laser irradiation has the potential to promote healing in chronic wounds and relieve wound pain.

Directly targeting ASC by lonidamine alleviates inflammasome-driven diseases.

BACKGROUND: Dysregulated activation of the inflammasome is involved in various human diseases including acute cerebral ischemia, multiple sclerosis and sepsis. Though many inflammasome inhibitors targeting NOD-like receptor protein 3 (NLRP3) have been designed and developed, none of the inhibitors are clinically available. Growing evidence suggests that targeting apoptosis-associated speck-like protein containing a CARD (ASC), the oligomerization of which is the key event for the assembly of inflammasome, may be another promising therapeutic strategy. Lonidamine (LND), a small-molecule inhibitor of glycolysis used as an antineoplastic drug, has been evidenced to have anti-inflammation effects. However, its anti-inflammatory mechanism is still largely unknown. METHODS: Middle cerebral artery occlusion (MCAO), experimental autoimmune encephalomyelitis (EAE) and LPS-induced sepsis mice models were constructed to investigate the therapeutic and anti-inflammasome effects of LND. The inhibition of inflammasome activation and ASC oligomerization by LND was evaluated using western blot (WB), immunofluorescence (IF), quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) in murine bone marrow-derived macrophages (BMDMs). Direct binding of LND with ASC was assessed using molecular mock docking, surface plasmon resonance (SPR), and drug affinity responsive target stability (DARTS). RESULTS: Here, we find that LND strongly attenuates the inflammatory injury in experimental models of inflammasome-associated diseases including autoimmune disease-multiple sclerosis (MS), ischemic stroke and sepsis. Moreover, LND blocks diverse types of inflammasome activation independent of its known targets including hexokinase 2 (HK2). We further reveal that LND directly binds to the inflammasome ligand ASC and inhibits its oligomerization. CONCLUSIONS: Taken together, our results identify LND as a broad-spectrum inflammasome inhibitor by directly targeting ASC, providing a novel candidate drug for the treatment of inflammasome-driven diseases in clinic.

Global morbidity and mortality of lower respiratory infections: A population -based study.

BACKGROUND: This study provides a comprehensive, comparative and updated estimates of temporal patterns of lower respiratory infections (LRIs) globally over the past three decades. METHODS: The data on morbidity and mortality of patients with LRIs at the global, regional and national levels were retrieved from the Global Burden of Disease (GBD) 2019 study. RESULTS: Globally, the incident cases of LRIs increased from 414,342,866 [95% uncertainty interval (UI):383,529,625 to 449, 086,938]in 1990 to 488,902,504(95% UI: 457,572,987 to 522,635,542)in 2019 with the age standardized incidence rate (ASIR) decreased from 8,276/100,000 persons (95% UI: 7,727 to 8,892) to 6,295/100,000 persons (95% UI: 5,887 to 6,737) between 1990 and 2019. Number of LRIs deaths were 2,493,200 (95% UI: 2,268,184 to 2,736,184) in 2019, a decrease of 24.9% (95% UI: -34.4 to -15.4) in the past 30 years. Meanwhile, the age-standardized death rate (ASDR) declined also from 67/100,000 persons (95% UI: 61 to 73) in 1990 to 34/100,000 persons (95% UI: 31 to 38) in 2019. Moreover, the numbers and age-standardized rates per 100,000 persons of morbidity and mortality varied widely by age, sex, Socio-Demographic Index (SDI) quintiles, and geographical locations in 2019. CONCLUSION: LRIs remain a major public health concern . Some differences in age, sex, SDI quintiles, and geographical locations contribute to LRIs-related global health policy development and health system resource optimization.

Emergence of a Carbapenem-Resistant Klebsiella pneumoniae Isolate Co-harbouring Dual bla NDM- 6 -Carrying Plasmids in China.

The widespread emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) with limited therapeutic options has become a global concern. In this study, a K. pneumoniae strain called KP2e was recovered from a human case of fatal septic shock in a Chinese hospital. Polymerase chain reaction and sequencing, antimicrobial susceptibility testing, conjugation experiments, S1 nuclease-pulsed field gel electrophoresis/southern blot, whole genome sequencing and comparative genomics were performed to investigate the phenotypic and molecular characteristics of this isolate. KP2e possessed the NDM-6-encoding gene and exhibited resistance to almost all ß-lactams except for monobactam. This strain belonged to sequence type 4024, the complete genome of which was composed of one chromosome and three plasmids. Furthermore, bla NDM-6 coexisted on two self-transmissible plasmids, which were assigned to types IncFIB and IncN. A structure of IS26-composite transposon capturing an identical Tn125 remnant (ΔISAba125-bla NDM-6 -ble MBL -trpF-dsbC-cutA-groES-ΔgroEL) was identified in the two plasmids, and this conserved bla NDM -surrounding genetic context was similar to that of few IncN plasmids found in other regions of China. Our research appears to be the first description of a clinical strain that emerged co-harbouring dual bla NDM -carrying plasmids, and the first report of NDM-6-positive CRKP in China. These findings demonstrated that IncN is a key medium in the evolution and expanding dissemination of bla NDM genes among various species, which indicates that close monitoring and rapid detection of bla NDM -harbouring plasmids is necessary.

TRIOL Inhibits Rapid Intracellular Acidification and Cerebral Ischemic Injury: The Role of Glutamate in Neuronal Metabolic Reprogramming.

As one of the key injury incidents, tissue acidosis in the brain occurs very quickly within several minutes upon the onset of ischemic stroke. Glutamate, an excitatory amino acid inducing neuronal excitotoxicity, has been reported to trigger the decrease in neuronal intracellular pH (pHi) via modulating proton-related membrane transporters. However, there remains a lack of clarity on the possible role of glutamate in neuronal acidosis via regulating metabolism. Here, we show that 200 µM glutamate treatment quickly promotes glycolysis and inhibits mitochondrial oxidative phosphorylation of primary cultured neurons within 15 min, leading to significant cytosolic lactate accumulation, which contributes to the rapid intracellular acidification and neuronal injury. The reprogramming of neuronal metabolism by glutamate is dependent on adenosine monophosphate-activated protein kinase (AMPK) signaling since the inhibition of AMPK activation by its selective inhibitor compound C significantly reverses these deleterious events in vitro. Moreover, 5α-androst-3ß,5α,6ß-TRIOL (TRIOL), a neuroprotectant we previously reported, can also remarkably reverse intracellular acidification and alleviate neuronal injury through the inhibition of AMPK signaling. Furthermore, TRIOL remarkably reduced the infarct volume and attenuated neurologic impairment in acute ischemic stroke models of middle cerebral artery occlusion in vivo. In summary, we reveal a novel role of glutamate in rapid intracellular acidification injury resulting from glutamate-induced lactate accumulation through AMPK-mediated neuronal reprogramming. Moreover, inhibition of the quick drop in neuronal pHi by TRIOL significantly reduces the cerebral damages, suggesting that it is a promising drug candidate for ischemic stroke.

The Value of Ultrasonography in Predicting Acute Gangrenous Cholecystitis.

Acute cholecystitis is a common clinical inflammatory lesion of the gallbladder. With the aggravation of inflammation, ischemic, necrosis, and even acute gangrenous cholecystitis occur in the gallbladder. At the same time, a variety of complications appear, seriously affecting the prognosis of patients. It is recommended that ultrasound can be utilized as the first choice for the diagnosis of acute cholecystitis, due to its fastness, convenience, non-radiation, and low cost. Here, we summarize the latest progress that can predict acute gangrenous cholecystitis in ultrasound, thus assisting us in identifying patients with high risk of gangrene in early stage, and treating these patients in time.

Current Perspectives on the Unique Roles of Exosomes in Drug Resistance of Hepatocellular Carcinoma.

As a common malignant tumor worldwide, the prognosis of hepatocellular carcinoma (HCC) remains unsatisfactory, even though treatment methods have improved. Despite the developments in traditional chemotherapy and emerging targeted immunotherapy, the problem of recurrence and metastasis of HCC and adverse effects on survival and prognosis are still serious. Drug resistance is a daunting challenge that impedes HCC treatment. Exosomes, a class of extracellular vesicles ranging in size from 30 to 100 nm, have been the focus of recent studies. Exosomes can activate various signaling pathways and regulate the tumor microenvironment with their cargo, which includes functional lipids, proteins, and nucleic acids. Thus, they change the phenotype of recipient cells via exosome-mediated communication. Exosomes secreted by tumors or stromal cells can also transfer drug-resistant traits to other tumor cells. However, their effects on drug resistance in HCC are not completely understood. In this review, we summarize and discuss the underlying relationship between exosomes and drug resistance in HCC. In addition, we also show that exosomes may act as candidate biomarkers for predicting and monitoring drug responses and as potential targets or vectors to reverse the drug resistance of HCC.

Undifferentiated pleomorphic sarcoma of the pancreas: a rare case report and literature review.

BACKGROUND: Primary undifferentiated pleomorphic sarcoma (UPS) of the pancreas is an exceedingly rare malignant tumor, with only 15 cases have been reported in the medical literature. At present, clinicians have poor recognition of the tumor, the epidemiology, diagnosis, and treatment of this disease have yet not been established. CASE PRESENTATION: In this report, we depict the clinical and imaging characteristics of a 37-year-old man presenting with a primarily cystic UPS. The patient complained of epigastric pain and distention over 20 days. Abdominal CT and pancreatic magnetic resonance imaging revealed cystic and cystic solid masses in the pancreatic body and tail. An abdominal ultrasound echogram revealed the mass in the body of the pancreas to be cystic with separation echo inside, and the wall was thick, not smooth. Besides, a hypoechoic mass was seen in the tail area of the pancreas with an inhomogeneous echoic pattern, containing small patches of no echo zone in the central. Microscopically, spindle fibroblast-like cells are arranged in a characteristic storiform pattern with pleomorphic and multinucleated cells. Immunohistochemically, tumor cells were positive for CD68 and vimentin. Seven months postoperatively, he was diagnosed with pulmonary lymph node metastasis and died 5 months later. Combined with this case report, we also reviewed the literature regarding UPS of the pancreas. CONCLUSIONS: As we know, this is the first report on ultrasonography findings of pancreatic UPS. Despite there are no distinctive manifestation of UPS, a solid cystic lesion on ultrasonography or a hypodense area in the lesion on T2-weighted imaging, should be considered for differential diagnosis with pancreatic UPS. We believe this article may add some ideas into the diagnosis and therapy of patients with this tumor.

Nerve root magnetic stimulation improves locomotor function following spinal cord injury with electrophysiological improvements and cortical synaptic reconstruction.

Following a spinal cord injury, there are usually a number of neural pathways that remain intact in the spinal cord. These residual nerve fibers are important, as they could be used to reconstruct the neural circuits that enable motor function. Our group previously designed a novel magnetic stimulation protocol, targeting the motor cortex and the spinal nerve roots, that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury. Here, we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury. Rats underwent surgery to clamp the spinal cord at T10; three days later, the rats were treated with repetitive magnetic stimulation (5 Hz, 25 pulses/train, 20 pulse trains) targeting the nerve roots at the L5-L6 vertebrae. The treatment was repeated five times a week over a period of three weeks. We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord. In addition, the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex. Overall, the results suggest that nerve root magnetic stimulation may be an effective, noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.

Percutaneous Transhepatic Gallbladder Drainage Combined with Laparoscopic Cholecystectomy Versus Emergency Laparoscopic Cholecystectomy for the Treatment of Moderate Acute Cholecystitis: A Meta-Analysis.

Background: We compared the clinical outcomes of laparoscopic cholecystectomy (LC) after percutaneous transhepatic gallbladder drainage (PTGBD) with those of emergency LC (ELC) in patients with moderate acute cholecystitis (AC) as per the Tokyo Guidelines. Methods: A meta-analysis of clinical comparative studies investigating the efficacy of PTGBD combined with LC (PTGBD + LC) versus ELC for moderate AC patients was performed. Results: The PTGBD + LC group had a shorter operative time (mean difference [MD] = -25.02 minutes; 95% confidence interval [95% CI] -35.50 to -14.54; P < .00001), less intraoperative bleeding (MD = -33.38 mL; 95% CI -45.43 to -21.33; P < .00001), shorter postoperative hospital stay (MD = -2.37 days; 95% CI -3.30 to -1.44; P < .00001), lower conversion rate (odds ratio [OR] 0.23; 95% CI 0.11-0.48; P < .0001), and lower total postoperative morbidity (OR 0.26; 95% CI, 0.10-0.67; P = .005) compared with the ELC group. There was no significant difference in total hospital stay (MD = 1.71 days; 95% CI -0.17 to 3.60; P = .08) and the incidence of bile leak (OR 0.30; 95% CI 0.07-1.29; P = .11). Conclusions: Compared with ELC, LC after PTGBD can effectively reduce the difficulty of operation, total postoperative morbidity, and conversion rate, and shorten the postoperative hospital stay and operative duration in patients with moderate AC as per the Tokyo Guidelines. In clinical practice, it is necessary to formulate individualized treatment plans based on the condition and willingness of the patients.

The impact of transthoracic echocardiography on the short-term prognosis of elderly patients in the intensive care unit: a retrospective analysis based on the MIMIC-III database.

BACKGROUND: Elderly patients in the intensive care unit (ICU) often suffer from cardiac function impairment. Real-time monitoring of cardiac function and structural changes has important clinical significance. Transthoracic echocardiography (TTE) is a convenient, intuitive, and non-invasive real-time examination of the heart, and it has been widely used for intensive care patients. This study aims to analyze the impact of TTE on the prognosis of elderly patients in ICU. METHODS: Data from elderly patients in the ICU was obtained from the MIMIC-III 1.4 database, and they were divided into a TTE examination group and a non-TTE examination group. The baseline data of the two groups were compared, and multiple regression analysis, propensity score (PS), compatibility analysis, and other methods were used to analyze the influence of TTE on the prognosis of elderly patients in ICU. RESULTS: A total of 8,952 elderly cases were included, comprising 3,280 cases (36.6%) in the TTE group and 5,672 cases (63.4%) in the non-TTE group. The SAPS score (20.34±5.34 vs. 18.74±5.2, t=13.889, P<0.001) and SOFA score (5.10±3.38 vs. 3.82±2.81, t=19.250, P<0.001) of patients in the TTE group were higher than those of non-TTE group. The rate of patients in the TTE group receiving mechanical ventilation (52.10% vs. 34.80%) and vasoactive drugs (29.30% vs. 15.00%) was significantly higher than that in the non-TTE group. In the PS score compatibility cohort, the 28-day mortality rate of patients in the TTE group was 23.4%, and the 28-day mortality rate of patients in the non-TTE group was 28.7%. The adjusted odd ratio (OR) value was 0.76 (95% CI: 0.65-0.87, P<0.001). Analysis of secondary endpoints showed that patients in the TTE group did not use mechanical ventilation and hypertension drugs for a longer period of time than those in the non-TTE group, and the TTE group patients had significantly more fluid input in the first three days after admission to the ICU than in the non-TTE group. CONCLUSIONS: TTE examination can reduce the 28-day mortality risk of elderly critically ill patients.

Current perspectives on exosomes in the diagnosis and treatment of hepatocellular carcinoma (review).

The prognosis of hepatocellular carcinoma (HCC), a malignant tumor, is poor. Tumor recurrence and metastasis are the major challenges for the treatment of HCC. Various studies have demonstrated that exosomes, which are loaded with various biomolecules including nucleic acids, lipids, and proteins are involved in the recurrence and metastasis of HCC. Additionally, exosomes mediate various biological processes, such as immune response, cell apoptosis, angiogenesis, thrombosis, autophagy, and intercellular signal transduction. In cancer, exosomes regulate cancer cell differentiation, development, and drug resistance. Circular RNAs, microRNAs, and proteins in the exosomes can serve as early diagnostic and prognostic markers for HCC. As exosomes are characterized by low immunogenicity and high stability in the tissues and circulation, they can be used to deliver the drugs in cancer therapies.

Autologous scalp skin grafting to treat toxic epidermal necrolysis in a patient with a large skin injury: A case report.

BACKGROUND: Toxic epidermal necrolysis (TEN) is often associated with skin wounds affecting large areas. Healing of this type of wound is difficult because of pressure, infection and other factors. It can increase the length of hospital stay and result in wound sepsis and even death. CASE SUMMARY: A 49-year-old woman developed a skin lesion covering 80% of the total body surface area after using a kind of Chinese medicinal ointment on a burn wound on her back; she developed life-threatening wound sepsis and septic shock. Methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa and other bacteria were cultured from wound tissue, deep venous catheter and blood samples. Imipenem cilastatin sodium, tigecycline and teicoplanin were used for anti-infection therapy. Finally, the patient was transferred to the burn department because of severe wound sepsis. In the burn intensive care unit, pain-free dressing changes and autologous scalp skin grafting were performed to heal the wound in addition to reasonable and effective antibacterial treatment according to microbial susceptibility test results. After three operations within 2 wk, the wound healed and sepsis resolved. CONCLUSION: TEN patients with large areas of skin injury may develop wound infection and life-threatening wound sepsis. Autologous scalp skin grafting may be beneficial for rapid wound healing and reducing the risk of sepsis in TEN patients, and it leaves no scar at the donor site.

Role of chemokines in hepatocellular carcinoma (Review).

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide, with an unsatisfactory prognosis, although treatments are improving. One of the main challenges for the treatment of HCC is the prevention or management of recurrence and metastasis of HCC. It has been found that chemokines and their receptors serve a pivotal role in HCC progression. In the present review, the literature on the multifactorial roles of exosomes in HCC from PubMed, Cochrane library and Embase were obtained, with a specific focus on the functions and mechanisms of chemokines in HCC. To date, >50 chemokines have been found, which can be divided into four families: CXC, CX3C, CC and XC, according to the different positions of the conserved N­terminal cysteine residues. Chemokines are involved in the inflammatory response, tumor immune response, proliferation, invasion and metastasis via modulation of various signaling pathways. Thus, chemokines and their receptors directly or indirectly shape the tumor cell microenvironment, and regulate the biological behavior of the tumor. In addition, the potential application of chemokines in chemotaxis of exosomes as drug vehicles is discussed. Exosomes containing chemokines or expressing receptors for chemokines may improve chemotaxis to HCC and may thus be exploited for targeted drug delivery.

SMARCB1 Promotes Ubiquitination and Degradation of NR4A3 via Direct Interaction Driven by ROS in Vascular Endothelial Cell Injury.

Nuclear receptor subfamily 4 group A member 3 (NR4A3) protects the vascular endothelial cell (VEC) against hypoxia stress, whose expression is primarily reported to be governed at a transcriptional level. However, the regulation of NR4A3 in the protein level is largely unknown. Here, we report that NR4A3 protein abundance is decreased immensely in VEC injury induced by reoxygenation after oxygen-glucose deprivation (OGD-R), which is significantly blocked by the administration of the antioxidative steroid TRIOL. Moreover, the notable improvement of NR4A3 and the alleviation of pulmonary endothelial barrier hyperpermeability induced by acute hypobaric hypoxia in cynomolgus monkeys are also observed after TRIOL administration. The overproduction of reactive oxygen species (ROS) decreases NR4A3 protein abundance in VEC under OGD-R condition, which is reversed by TRIOL and N-acetylcysteine (NAC). TRIOL dose-dependently increases the NR4A3 protein level by inhibiting ubiquitination and ubiquitin proteasome system- (UPS-) mediated degradation rather than promoting its transcription. Using yeast two-hybrid screening, we further identify the interaction between NR4A3 and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), and the DNA-binding domain of NR4A3 is required for this interaction. Knockdown of SMARCB1 reduces ubiquitination and degradation of NR4A3, suggesting the proubiquitylation effect of this interaction which is enhanced by ROS in VEC injury induced by OGD-R. In summary, our study here for the first time reveals a posttranslational regulation in SMARCB1-mediated NR4A3 protein degradation which is driven by ROS, providing further understanding of the impaired regulation of NR4A3-mediated prosurvival pathways under pathological condition in VEC.