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Abstract: Sepsis-induced myocardial dysfunction commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. This study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. In addition, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NOD-like receptor protein-3 (NLRP3) upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for sepsis-induced myocardial dysfunction therapy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Studies show that vertebral fractures could predict the risk of hip fractures. We aimed to evaluate the potential benefits of whether the timing of vertebroplasty (VP) for vertebral fracture associated with the risk of hip fracture for hip replacement.We identified 142,782 patients from the Taiwan National Health Insurance Database with thoracolumbar vertebral fracture (International Classification of Diseases, Ninth Revision, Clinical Modification:805.2-805.9) who were followed up from 2000 to 2013. These patients were divided into those who underwent VP (VP group) (International Classification of Diseases, Ninth Revision, Clinical Modification : 78.49) within 3 months and those who did not (non-VP group). After adjusting for the confounding factors, the Cox proportional hazards analysis was used to estimate the effect of early VP on reducing the risk of hip fracture. The difference in the risk of hip replacement, between the VP group and non-VP group was estimated using the Kaplan-Meier method with the log-rank test.In the 14-year follow-up, the cumulative incidence rate of hip replacement in the VP group was lower than that in the non-VP group (0.362% and 0.533%, respectively, long-rank P < .001). There was a significant difference between the 2 groups since the first-year follow-up.Our study showed that early VP performed to avoid progression of the kyphotic changes following thoracolumbar vertebral fracture may reduce the risk of hip fracture. These results, obtained from retrospective data, indicate that a prospective study is warranted.

Background and Purpose- Pontine autosomal dominant microangiopathy and leukoencephalopathy, a recently defined subtype of cerebral small vessel disease, is associated with mutations in COL4A1 (collagen type IV alpha 1 chain) 3' untranslated region. We here describe a pontine autosomal dominant microangiopathy and leukoencephalopathy pedigree with COL4A1 mutation presenting both pontine and cervical spinal cord involvement. Methods- For the diagnostic purpose, brain and spinal magnetic resonance imaging scanning, skin biopsy, and whole-exome sequencing were performed on the patients in the pedigree. Suspected pathogenic variants were further confirmed by cosegregation analysis using Sanger sequencing in the family members. Results- We identified a mutation located at the binding site of miR-29 (microRNA-29) in 3' untranslated region of COL4A1(c.*32G>A). The pontine autosomal dominant microangiopathy and leukoencephalopathy patients in this pedigree carried this variant, whereas other healthy family members but one did not. Magnetic resonance imaging showed lesions in the pons, white matter, and cervical spinal cord. Skin biopsy revealed thickened basal lamina in vessels. Conclusions- For the first time, we reported cervical spinal involvement in pontine autosomal dominant microangiopathy and leukoencephalopathy and expanded the clinical spectrum of this disease.

Rationale: Littoral cell angioma (LCA) is a rare primary vascular neoplasm of the spleen. It can be benign or malignant. Pathology and immunohistochemistry are the gold standards for the diagnosis of LCA. Therefore, splenectomy is recommended for the purpose of diagnosis and treatment, and subsequent follow-up is necessary. There are limited reports about LCA. Here, we present a case of a female patient with LCA undergoing laparoscopic splenectomy in order to provide clinical experience in LCA treatment., Patient Concerns: A 32-year-old female attended the outpatient Department of Hepatobiliary Surgery for follow-up of hepatic hemangiomas. The patient presented with intermittent abdominal distension, which was slightly under no obvious inducement., Diagnosis: Physical examination found no signs of abdominal tenderness and rebound tenderness, and liver and spleen were impalpable. The contrast-enhanced computed tomography (CT) showed multiple space-occupying lesions in the spleen, mottled low-density lesions, multiple hypoattenuating nodules with no contrast enhancement on the arterious phase. Delayed contrast-enhanced helical CT scan displayed incomplete filling of hypodense splenic lesions., Interventions: Given that it was uncertain whether it was a benign or a malignant tumor, a laparoscopic total splenectomy was performed., Outcomes: The final pathological diagnosis was LCA. Her postsurgical course was uneventful, and no surgery-related complications were found. No signs of recurrence were observed in the 16 months after the operation., Lessons: LCA was a rare primary vascular neoplasm of the spleen, and laparoscopic splenectomy for LCA was safe and feasible, and postoperative course was uneventful. However, regular follow-up and long-time monitoring after splenectomy for LCA is recommended because of its potential malignant biological behavior.

Rationale: Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare and are difficult to diagnose preoperatively.We report a case of PHNET diagnosed preoperatively and successfully resected using associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)., Patient Concerns: A 72-year-old woman was admitted to our hospital for a hepatic mass, which was incidentally identified during a routine health checkup. The patient has no other obvious symptoms of discomfort., Diagnoses: Physical examination revealed a palpable mass in the right upper quadrant of her abdomen. Dynamic contrast-enhanced abdominal computed tomography (CT) showed a low-density mass measuring 13 × 7 × 6 cm in both, the right and left hepatic lobes. F-fluorodesoxyglucose positron emission tomography (F-FDG PET) and fused PET/CT showed increased uptake by the mass, which was indicative of a hepatic tumor., Interventions: We use a novel ALPPS surgical procedure to safely and radically remove primary neuroendocrine tumors., Outcomes: No postoperative bleeding and bile leakage were reported, and the patient recovered uneventfully.The patient was followed-up for a year without recurrence., Lessons: PHNETs are rare tumors, and confirming the diagnosis using the best possible preoperative examination is important. An optimal treatment plan is selected based on the patient's condition to ensure a favorable prognosis. Tumors too large to undergo surgical removal can be resected using the ALPPS procedure, as described in this case report.

This study aims to compare the effect of Philips' Brilliance 64-slice and 256-slice (multislice) computed tomography on effective doses when changing the operating parameters for simulated examinations of patients' spine tumors, including changes in pitch, tube voltage (kV), and effective tube current-time product (mA s). This study considers the possibility of using other probable operating conditions to reduce patients' effective doses. The absorbed doses to organs and skin are measured by taking data from thermoluminescent dosimeters (GR-200 and GR-200F) in relevant positions on the anthropomorphic Rando phantom. We also used an American College of Radiology computed tomography accreditation phantom to experiment with image spatial resolution under various scan conditions in order to achieve results over 5 line pairs per cm, the analytical capability required to meet diagnostic needs. The results show that, in general, when we change the pitch, effective tube current-time product, and tube voltage, the effective doses from 256-slice computed tomography exceed those from 64-slice computed tomography.

Objective: We investigated the efficacy of plasma exchange (PE) in antiphospholipid antibody (aPL)-positive patients with a spontaneous intracerebral hemorrhage (ICH) and high D-dimer levels., Materials and Methods: From May 2013 to May 2016, we evaluated 32 patients who were below the age of 50 and presented with spontaneous ICH. Five patients were positive for aPL antibody and 3 had a higher level of D-dimer. These 3 patients underwent 5 sessions of PE using fresh frozen plasma as replacement fluid. We analyzed the days postadmission until PE-start, the days of intensive care unit (ICU) hospitalization, D-dimer series, Glasgow Coma Scale (GCS) scores, and modified Rankin scale (mRS) scores. D-dimer levels and GCS scores were recorded at both pre-PE and post-PE stages. The mRS scores were recorded at pre-PE stage and 3 months post-PE., Results: The mean postadmission period until PE-start was 8.33 days. The mean ICU hospitalization was 17.33 days. The D-dimer level pre-PE ranged from 2.34 to 5.44 mg/L fibrinogen equivalent unit (FEU). The D-dimer level post-PE ranged from 1.05 to 3.30 mg/L FEU. The amount of decline of the D-dimer level between pre-PE and post-PE ranged from 0.65 to 2.14 mg/L FEU. The GCS score pre-PE was between 7 and 8. The highest post-PE GCS score was 14. The improved GCS scores post-PE ranged from 3 to 6. The improved mRS scores of 3 months post-PE ranged from 3 to 4., Conclusions: The concurrent presence of positive aPL and a higher D-dimer level may worsen the neurological outcome of patients with a spontaneous ICH. Aggressive PE is effective for the treatment of such patients, decreasing the extent of the ICU hospitalization.

Rationale: Urethral hemangiomas commonly occur in men or elderly women. We presented a rare case of urethral hemangioma in a prepubertal female patient., Patients Concerns: An 8-year-old girl had the complaints of bloody staining of clothing, a foul perineal odor, and urethral pain. She was brought to our genitourinary outpatient department for survey and a single, 1-cm compressible reddish nodule at the 10-2 o'clock position in the distal urethra was found., Diagnoses: Urethral hemangioma in a prepubertal girl was diagnosed after excision of the urethral nodule., Interventions: Excision with 8 "stay" sutures in the protruding urethral mucosa was performed., Outcomes: Normal micturition without symptom recurrence was noted at the 3-month follow-up., Lessons: Urethral hemangioma is also found in prepubertal female patient. Increased physician awareness and early recognition of a urethral hemangioma can avoid unnecessary examinations and patient anxiety. The procedure of excision with 8 "stay" sutures in the protruding urethral mucosa facilitates mobilization from the distal urethra and provides a good surgical view of abnormal proliferative blood vessels. Therefore, the lesion can be removed as clean as possible.

Tumor control rates of pituitary adenomas (PAs) receiving adjuvant CyberKnife stereotactic radiosurgery (CK SRS) are high. However, there is currently no uniform way to estimate the time course of the disease. The aim of this study was to analyze the volumetric responses of PAs after CK SRS and investigate the application of an exponential decay model in calculating an accurate time course and estimation of the eventual outcome.A retrospective review of 34 patients with PAs who received adjuvant CK SRS between 2006 and 2013 was performed. Tumor volume was calculated using the planimetric method. The percent change in tumor volume and tumor volume rate of change were compared at median 4-, 10-, 20-, and 36-month intervals. Tumor responses were classified as: progression for >15% volume increase, regression for ≤15% decrease, and stabilization for ±15% of the baseline volume at the time of last follow-up. For each patient, the volumetric change versus time was fitted with an exponential model.The overall tumor control rate was 94.1% in the 36-month (range 18-87 months) follow-up period (mean volume change of -43.3%). Volume regression (mean decrease of -50.5%) was demonstrated in 27 (79%) patients, tumor stabilization (mean change of -3.7%) in 5 (15%) patients, and tumor progression (mean increase of 28.1%) in 2 (6%) patients (P = 0.001). Tumors that eventually regressed or stabilized had a temporary volume increase of 1.07% and 41.5% at 4 months after CK SRS, respectively (P = 0.017). The tumor volume estimated using the exponential fitting equation demonstrated high positive correlation with the actual volume calculated by magnetic resonance imaging (MRI) as tested by Pearson correlation coefficient (0.9).Transient progression of PAs post-CK SRS was seen in 62.5% of the patients receiving CK SRS, and it was not predictive of eventual volume regression or progression. A three-point exponential model is of potential predictive value according to relative distribution. An exponential decay model can be used to calculate the time course of tumors that are ultimately controlled., Competing Interests: The authors report no conflicts of interest.

Introduction: The fatal type of antiphospholipid syndrome is a rare but life-threating condition. It may be triggered by surgery or infection. Endoscopic transnasal-transsphenoidal surgery is a common procedure for pituitary tumor. We report a catastrophic case of a young woman died of fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery., Methods and Result: A 31-year-old woman of a history of stroke received endoscopic transnasal-transsphenoidal surgery for a pituitary tumor. The whole procedure was smooth. However, the patient suffered from acute delirium on postoperative day 4. Then, her consciousness became comatose state rapidly with dilatation of pupils. Urgent magnetic resonance imaging of brain demonstrated multiple acute lacunar infarcts. The positive antiphosphoipid antibody and severe thrombocytopenia were also noted. Fatal antiphospholipid syndrome was diagnosed. Plasma exchange, corticosteroids, anticoagulant agent were prescribed. The hemodynamic condition was gradually stable. However, the consciousness was still in deep coma. The patient died of organ donation 2 months later., Conclusion: If patients have a history of cerebral stroke in their early life, such as a young stroke, the APS and higher risk of developing fatal APS after major surgery should be considered. The optimal management of APS remains controversial. The best treatment strategies are only early diagnosis and aggressive therapies combing of anticoagulant, corticosteroid, and plasma exchange. The intravenous immunoglobulin is prescribed for patients with refractory APS., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Meningioma is the most common benign brain lesion in adults. Conservative treatment is suggested if there is no obvious neurological symptom or mass effect, but cerebral metastases require aggressive therapy. Single dural-based metastatic carcinoma mimicking meningioma is uncommon. Here is a case of clinical dilemma between meningioma and metastatic carcinoma mimicking meningioma. A woman with a history of invasive ductal carcinoma of the breast presented with headache and blurred vision. Brain computed tomography and magnetic resonance imaging (MRI) both gave the impression of meningioma. After surgical resection of the brain lesion, histopathology revealed that it was a metastatic lesion from the breast. This report discussed the optimal management of single dural-based metastatic carcinoma mimicking meningioma.

The hexokinase inhibitor 3-bromopyruvate (3-BrPA) can inhibit glycolysis in tumor cells to reduce ATP production, resulting in apoptosis. However, as 3-BrPA is an alkylating agent, its cytotoxic action may be induced by other molecular mechanisms. The results presented here reveal that 3-BrPA-induced apoptosis is caspase independent. Further, 3-BrPA induces the generation of reactive oxygen species in MDA-MB-231 cells, leading to mitochondria-mediated apoptosis. These results suggest that caspase-independent apoptosis may be induced by the generation of reactive oxygen species. In this study, we also demonstrated that 3-BrPA induces apoptosis through the downregulation of myeloid cell leukemia-1 (Mcl-1) in MDA-MB-231 breast cancer cells. The results of Mcl-1 knockdown indicate that Mcl-1 plays an important role in 3-BrPA-induced apoptosis. Further, the upregulation of Mcl-1 expression in 3-BrPA-treated MDA-MB-231 cells significantly increases cell viability. In addition, 3-BrPA treatment resulted in the downregulation of p-Akt, suggesting that 3-BrPA may downregulate Mcl-1 through the phosphoinositide-3-kinase/Akt pathway. These findings indicate that 3-BrPA induces apoptosis in breast cancer cells by downregulating Mcl-1 through the phosphoinositide-3-kinase/Akt signaling pathway.

Endothelial dysfunction is thought to be a major cause of vascular injury in smokers. Ghrelin is a recently discovered peptide that plays a modulatory role in atherosclerosis. However, it is unknown how ghrelin regulates nicotine-induced vascular cell adhesion molecule-1 (VCAM-1) expression. We examined nicotine-induced VCAM-1 expression in human umbilical vein endothelial cells pretreated with ghrelin and detected the activity of protein kinase C (PKC), p38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor (NF)-kappaB. Our study showed that ghrelin inhibited nicotine-induced VCAM-1 expression in human umbilical vein endothelial cells in a concentration-dependent and time-dependent way. We also found that ghrelin inhibited nicotine-induced PKC, p38 MAPK, and NF-kappaB activation. The results suggest that ghrelin inhibits nicotine-induced VCAM-1 expression, and PKC, p38 MAPK, and NF-kappaB play active roles in that process. Exogenous ghrelin may provide a possible approach for preventing or reversing atherosclerosis in smokers.

Resting-state functional MRI and structural MRI were used to study correlations of spontaneous activity and gray matter density between the left and right primary sensorimotor areas in pianists and nonmusicians. Functional MRI analysis showed significant correlation of spontaneous activity between the left and right primary sensorimotor area in both groups; however, there was no between-group difference. Structural MRI analysis showed significant correlation in gray matter density between the left and right sensorimotor areas in nonmusicians (r=0.65, P=0.001), but not in pianists (r=0.07, P=0.78), with a significant between-group difference (P=0.035). The lack of correlation of gray matter density between the left and right sensorimotor areas might be the basis of bimanual coordination of the pianists.

Gabapentin and pregabalin have been demonstrated, both in animal pain models and clinically, to be effective analgesics particularly for the treatment of neuropathic pain. The precise mechanism of action for these two drugs is unknown, but they are generally believed to function via initially binding to the alpha2delta subunit of voltage-gated Ca2+ channels. In this study, we used a pharmacological approach to test the hypothesis whether high affinity interactions with the alpha2delta subunit alone could lead to attenuation of neuropathic pain in rats. The anti-allodynic effects of gabapentin and pregabalin, along with three other compounds--(L)-phenylglycine, m-chlorophenylglycine and 3-exo-aminobicyclo[2.2.1]heptane-2-exo-carboxylic acid (ABHCA)--discovered to be potent alpha2delta ligands, were tested in the rat spinal nerve ligation model of neuropathic pain. Gabapentin (Ki = 120 nM), pregabalin (180 nM) and (L)-phenylglycine (180 nM) were shown to be anti-allodynic, with respective ED50 values of 230, 90 and 80 micromol/kg (p.o.). (L)-Phenylglycine was as potent as pregabalin and equi-efficacious in reversing mechanical allodynia. In contrast, two ligands with comparable or superior alpha2delta binding affinities, m-chlorophenylglycine (Ki = 54 nM) and ABHCA (150 nM), exhibited no anti-allodynic effects at doses of 30-300 micromol/kg (p.o.), although these compounds achieved substantial brain levels. The data demonstrate that, at least in the rat spinal nerve ligation model of neuropathic pain, (L)-phenylglycine has an anti-allodynic effect, but two equally potent alpha2delta subunit ligands do not. These results suggest that additional mechanisms, besides alpha2delta interactions, may contribute to the effects of compounds like gabapentin, pregabalin and (L)-phenylglycine in neuropathic pain.

Metabotropic glutamate receptors (mGluRs) have previously been shown to play a role in pain transmission during inflammatory or neuropathic pain states. However, the role of mGluR5 in post-operative pain remains to be fully investigated. The present study was conducted to characterize analgesic activity of 2-methyl-6-(phenylethynyl)-pyridine (MPEP) in the skin-incision-induced post-operative pain model in rats. MPEP is a potent and selective mGluR5 antagonist with high affinity (K(i)=6.3+/-0.9 nM) in rat cortex using [(3)H]-MPEP as a radioligand, while not competing with the mGluR1-selective radioligand [(3)H]-R214127 (K(i)>10,000 nM) in rat cerebellum. Post-operative pain was examined 2 h following surgery using weight-bearing (WB) difference between injured and uninjured paws as a measure of non-evoked pain. In this model, MPEP, as morphine, showed dose-dependent effects and full efficacy after systemic administration (ED(50)=15 mg/kg, i.p. for MPEP, ED(50)=1.3 mg/kg, s.c. for morphine). In addition, intrathecal (i.t.) and intracerebroventricular (i.c.v.) MPEP reduced WB difference (ED(50)=65 microg/rat i.t. and ED(50)=200 microg/rat i.c.v.). Interestingly, intraplantar (i.pl.) injection of MPEP either before or after surgery induced a similar reduction in WB difference (ED(50)=90 microg/rat, i.pl.) while contralateral i.pl. MPEP injection did not produce any effect. These results demonstrate that both peripheral and central mGluR5 receptors play a role in nociceptive transmission observed during post-operative pain. In addition, the data suggest that mGluR5 antagonists could offer a new therapeutic approach to the treatment of post-operative pain.

Background and Purpose: Silent cerebral infarction is often found on computed tomographic scan in patients with asymptomatic carotid stenosis, but its relation to the arterial stenosis is uncertain., Methods: We compared computed tomographic scans and carotid Doppler in 115 patients with asymptomatic carotid stenosis, 203 with carotid transient ischemic attacks and carotid stenosis, and 63 with transient ischemic attacks but without carotid stenosis. There was no group with normal carotid arteries for comparison., Results: Lesions seen on CT scan were most common in the transient ischemic attack with carotid stenosis group (47%) compared with the other groups (30%, 19%) (p less than 0.001). Cerebral infarcts ipsilateral to the carotid stenosis were found in 10% of patients with mild (35-50%) stenosis, 17% in moderate (50-75%) stenosis, and 30% with severe (greater than 75%) carotid stenosis (p less than 0.001). In patients with asymptomatic carotid stenosis, 68% of infarcts were ipsilateral to the stenosis; in those with transient ischemic attacks and carotid stenosis, 86% of infarcts were ipsilateral to the stenosis., Conclusions: The more severe the carotid stenosis, the higher the incidence of cerebral infarction ipsilateral to the stenosis. This finding applied to central infarcts as well as to peripheral infarcts in both symptomatic and asymptomatic patients. Silent cerebral infarction may be an indication for carotid endarterectomy in asymptomatic patients.

Background and Purpose: We sought to determine the risks of stroke, myocardial ischemia, and vascular death in patients with asymptomatic carotid stenosis., Methods: Six hundred ninety-six patients with asymptomatic carotid stenosis referred to the Doppler laboratory were followed prospectively for a mean time of 41 months. These patients were studied both clinically and by carotid Doppler ultrasound, including evaluation of the effect of stroke risk factors., Results: Transient ischemic attacks occurred in 75 patients and stroke in 29, while 132 had ischemic cardiac events. Five patients died from stroke and 59 from cardiac causes. Annual stroke rate was 1.3% in patients with carotid stenosis less than or equal to 75% and 3.3% in those with stenosis greater than 75%. Ipsilateral stroke rate was 2.5% in patients with greater than 75% carotid stenosis. Annual cardiac event rate was 8.3% and death rate 6.5% in patients with severe carotid stenosis., Conclusions: With carotid stenosis less than or equal to 75%, the stroke rate is negligible (1.3% annually) whereas the combined risk of cardiac ischemia and vascular death is as high as 9.9%. With stenosis greater than 75%, combined transient ischemic attack and stroke rate is 10.5% per year, with 75% of events ipsilateral to the stenosed artery.

Using Doppler ultrasonography, we evaluated the frequency and severity of carotid artery stenosis in 261 patients with carotid ischemic strokes, 813 patients with carotid transient ischemic attacks, 500 patients with asymptomatic neck bruits, and 500 controls. Most patients with strokes and transient ischemic attacks had no associated carotid artery disease (55% and 64%, respectively), and such patients without neck bruits were even more likely to be without carotid artery disease (69% and 77%, respectively). Carotid stenosis was more frequent and more likely to be severe in symptomatic than in asymptomatic patients (p less than 0.0002), even after adjusting for age and sex. Carotid stenosis is present in only a minority of patients with strokes and transient ischemic attacks, especially if neck bruits are absent, and the cause of the ischemic cerebral events in most of these patients remains unexplained.