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Abstract: The variant single nucleotide polymorphism rs8104571 has been associated with poor outcomes following traumatic brain injury (TBI) and is most prevalent in those of African ancestry. This single nucleotide polymorphism (SNP) resides within a gene coding for the TRPM4 protein, which complexes with SUR1 protein to create a transmembrane ion channel and is believed to contribute to cellular swelling and cell death in neurological tissue. Our study evaluates the relationship between circulating TRPM4 and SUR1, rs8104571 genotype, and clinical outcome in TBI patients. Trauma patients with moderate to severe TBI were included in this retrospective study. rs8104571 genotyping and admission plasma TRPM4 and SUR1 quantification was performed with real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Adequate plasma for TRPM4 and SUR1 ELISA quantification was available for 289 patients, 54 of whom were African American (AA). Plasma TRPM4 concentration was increased in those with a variant rs8104571 allele compared to wild type when controlling for demographics and injury characteristics in the overall cohort (P = 0.04) and within the AA subgroup (P = 0.01). There was no significant association between plasma TRPM4 or SUR1 and clinical outcome (each P > 0.05). Plasma TRPM4 abundance increased with acute kidney injury severity (P = 0.02). The association between increased plasma TRPM4 and variant rs810457 supports an underlying mechanism involving increased neuroinflammation with a subsequent increase in the leakage of TRPM4 from the central nervous system into circulation. Alternative sources of plasma TRPM4 including the kidney cannot be excluded and may play a significant role in the pathophysiology of trauma as well., Competing Interests: Funding and Conflicts of Interest: This research was supported by the National Institute of General Medical Sciences of the National Institutes of Health (T32GM008792). Additional funding was provided by the William Stamps Farish Fund, the Howell Family Foundation, and the James H. "Red" Duke Professorship. Dr. Cox reports additional support from the National Institutes of Health; Department of Defense-Medical Technology Enterprise Consortium; State of Texas Emerging Technology Fund; Generate Life Sciences, Inc.; Athersys, Inc.; Celgene Cellular Therapeutics; Cellvation, Inc.; Cellularity, Inc.; Hope Biosciences, Inc.; The Bentsen Foundation; Mission Connect; Let's Cure CP; Ladybug Foundation; Evelyn Griffin Foundation; Glassell Family Foundation; The George and Cynthia Mitchell Foundation; Grace R. Walls Endowment; Brown Foundation; Cellvation, Inc.; Coagulex, Inc.; EMIT Corporation. No other authors report funding or conflicts of interest., (Copyright © 2024 by the Shock Society.)

Loss of estrogen receptor/progesterone receptor (ER/PR) in endometrial cancer (EC) is associated with tumor progression and poor outcomes. Elevated pretreatment cancer antigen 125 (CA 125) level is a risk factor for lymph node metastasis (LNM). We evaluated whether the combination of ER/PR expression and CA 125 level could be used as a biomarker to predict LNM. We retrospectively investigated patients with endometrioid EC who underwent complete staging surgery during January 2015 to December 2020. We analyzed ER/PR status using immunohistochemical staining, and quantified its expression using the sum of both ER/PR H -scores. Receiver operating characteristic curves were used to identify optimal cutoff values of H -score and CA 125 levels for predicting LNM. A nomogram for predicting LNM was constructed and validated by bootstrap resampling. In 396 patients, the optimal cutoff values of the ER/PR H -score and CA 125 were 407 (area under the receiver operating characteristic curve: 0.645, P =0.001) and 40 U/mL (area under the receiver operating characteristic curve: 0.762, P <0.001), respectively. Multivariate analysis showed that CA 125 ≥40 UmL (odds ratio: 10.02; 95% CI: 4.74-21.18) and ER/PR H -score <407 (odds ratio: 4.20; 95% CI: 1.55-11.32) were independent predictors. An LNM predictive nomogram was constructed using these 2 variables and our model yielded a negative predictive value and negative likelihood ratio of 98.3% and 0.14, respectively. ER/PR expression with pretreatment CA 125 levels can help estimate LNM risk and aid in decision-making regarding the need for lymphadenectomy in patients with endometrioid EC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 by the International Society of Gynecological Pathologists.)

Rationale: Vulvar melanoma is a rare and aggressive tumor with a high risk of local recurrence and distant metastasis. The prognosis is poor with a 5-year overall survival rate of only 46.6%. Management of vulvar melanoma remains a clinical challenge. Recent evidences have shown that immune checkpoint inhibitors are effective in the treatment of vulvar melanoma., Patient Concerns and Diagnoses: A 63-year-old woman with vulvar malignant melanoma suffered inguinal lymph node metastasis after vulvectomy and chemotherapy. She underwent inguinal lymph node dissection and inguinal radiotherapy. The tumor progressed again and she received immunotherapy., Interventions: The tumor progressed again, and she was admitted to our hospital and received toripalimab combined with apatinib and abraxane., Outcomes: After 6 cycles of immunotherapy, the efficacy achieved partial remission. And with toripalimab as maintenance therapy, the patient achieved durable antitumor efficacy and good safety., Lessons: In this rare case, the patient with metastatic vulvar malignant melanoma had durable antitumor efficacy and good safety when receiving toripalimab., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: New hypoglycemic agents include sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide 1 receptor agonists (GLP1RAs), and dipeptidyl peptidase-4 inhibitors (DPP4is). The association between each class of these new hypoglycemic drugs and the risks of various digestive system diseases is unknown. We aimed to explore this relationship by performing a meta-analysis., Methods: We included large randomized trials of SGLT2is, GLP1RAs, and DPP4is. Outcomes of interest were 91 kinds of digestive diseases including 75 kinds of gastrointestinal disorders and 16 kinds of hepatobiliary disorders. Meta-analysis was done to generate pooled risk ratio (RR) and 95% confidence interval (CI). Subgroup analysis was conducted according to 3 different drug classes., Results: We included 21 large trials in this meta-analysis. Compared with placebo, GLP1RAs were associated with the higher risks of gastric ulcer hemorrhage (RR 2.68, 95% CI 1.07-6.68; Pdrug = .035; I2 = 0), pancreatitis (RR 1.48, 95% CI 1.02-2.15; Pdrug = .041; I2 = 0), cholangitis acute (RR 5.96, 95% CI 1.04-34.08; Pdrug = .045; I2 = 0), and cholecystitis acute (RR 1.52, 95% CI 1.08-2.15; Pdrug = .017; I2 = 1.5%), but were not significantly associated with the occurrences of the other 87 kinds of digestive diseases (Pdrug ranged from .064 to .999). SGLT2is versus placebo were not significantly associated with the occurrences of 91 kinds of digestive diseases (Pdrug ranged from .077 to .995). DPP4is versus placebo were not significantly associated with the occurrences of 91 kinds of digestive diseases (Pdrug ranged from .085 to .999)., Conclusions: Neither SGLT2is nor DPP4is are associated with the occurrences of various kinds of digestive diseases, whereas GLP1RAs are associated with the higher risks of 4 kinds of digestive diseases, namely, gastric ulcer hemorrhage, pancreatitis, cholangitis acute, and cholecystitis acute. These findings seem to suggest that GLP1RAs are not applicable for patients at high risk of 4 specific digestive diseases, whereas SGLT2is and DPP4is are safe for patients susceptible to digestive diseases. However, our findings require to be further verified by future studies with sufficient statistical power., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Perihippocampal failure is a rare clinical scenario in brain metastatic cancer patients following hippocampal-avoidance (HA) whole-brain radiotherapy (HA-WBRT). The clinical features have not been fully identified because clinical data on intracranial failure after HA-WBRT are limited. It is thus necessary to accumulate clinical data.We retrospectively analyzed cancer patients with brain metastases who were diagnosed between January 2014 and September 2020 at a regional referral hospital. The medical records of patients who underwent HA-WBRT were reviewed. The clinical features of intracranial recurrence were described. Dosimetry parameters were compared in terms of deviation from the recommended protocol of the Radiation Therapy Oncology Report 0933.Twenty-four eligible patients with brain metastases who underwent HA-WBRT were identified; 13 (54%) were male. Seventeen patients (71%) had lung cancer, 6 (25%) had breast cancer, and 1 (4%) had liver cancer. The median overall survival was 12 months. Three patients developed intracranial failure during clinical follow-up, and 2 relapsed with intracranial failure in the perihippocampal region at 13 and 22 months, respectively. The perihippocampal failure rate was about 8%. One patient with small cell lung cancer received HA-prophylactic cranial irradiation; the minimum and maximum doses to the hippocampi were 6.8 and 10.7 Gy, respectively. Another patient with brain metastases from lung adenocarcinoma received HA-WBRT; the minimum and maximum doses to the hippocampi were 5.4 and 10.6 Gy, respectively.We reported unusual cases of intracranial failure in the perihippocampal region following HA-WBRT. Perihippocampal failure could be attributed to an under-dose of radiation partially or be resulted from aggressiveness of cancer per se. Further research on this topic is encouraged., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The distinction between solitary inflammatory lesion and solitary lung cancer remains a challenge because of their considerable overlapping computed tomography (CT) imaging features., Purpose: This study aimed to verify whether spectral CT parameters can differentiate solitary lung cancer from solitary inflammatory lesions and to find their correlations with lesion size., Methods: A total of 78 patients with solitary lung lesions were included in our study. All of them underwent enhanced CT scans with Gemstone Spectral Imaging (GSI) mode, which was one of the dual-energy imaging technologies. According to maximum diameter (Dmax) of the lesion, regions of interest were collected and divided into inflammatory (group I: <3 cm [IA], n = 17; ≥3 cm [IB], n = 14) and cancer groups (group II: <3 cm [IIA], n = 20; ≥3 cm [IIB], n = 27). Computed tomography values (HU40keV, HU70keV), effective atomic number (Zeff), iodine concentration (IC), normalized IC (NIC), and spectral curve slopes (λ30, λ40) of each region of interest were calculated. The NIC was defined as the IC ratio of the lesion to the descending aorta. Mann-Whitney U test was used for intergroup (I vs II, IA vs IIA, IB vs IIB) and intragroup (IA vs IB, IIA vs IIB) comparisons, and receiver operating characteristic curve analysis was performed. Correlation analysis was applied to find the relationship between Dmax and GSI parameters., Results: No significant correlation was found between GSI parameters and Dmax in the inflammatory group, whereas inverse correlations were found in the cancer group. Gemstone spectral imaging parameters (except HU70keV) of group IIA were significantly higher than those of group IIB. There were significant differences in HU40keV, IC, NIC, λ30, and λ40 between groups IB and IIB under both arterial and venous phase (P values < 0.05), whereas the area under the curve for λ30 under venous phase was largest, and sensitivity and specificity were 96.32% and 85.71%, respectively. However, only HU40keV and HU70keV values under the arterial phase of IIA were significantly higher than those of IA., Conclusions: Quantitative parameters of GSI demonstrated an inverse correlation with the lesion size of solitary lung cancer, and GSI parameters can be new ways to differentiate solitary lung cancer from solitary inflammatory lesions., Competing Interests: The authors declare no conflict of interest. The research is partially supported by Planning Project Grand (3502Z20174012) and Guiding Project Grand (3502Z20199040) from the Xiamen Municipal Bureau of Science and Technology (CN)., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Palliative care in rural areas can be difficult to assess and, often is of lower quality compared to more densely populated regions. A program of multicenter palliative care discussion forum via tele-videoconference may be a promising tool for exchanging valuable experience and constructing a comprehensive hospice care system in Taiwan and China.The multicenter palliative care discussion forum began 1997 and 2010 in Taiwan and China, respectively. In every forum, 1 to 2 cases were presented by multiple field specialists, and multi-dimensional problems were discussed. All of these case reports and reference materials from the forums were analyzed.The conference discussed 199 and 143 cases in Taiwan and China, including 172 and 143 cancer patients. The most common mentioned symptom was pain (66.3% in Taiwan, 96.95% in China). As time went on, the rate of discussion in pain management issues decreased, but the social and psycho-spiritual issues increased in Taiwan. After some major legal and social changes, the discussion of ethical issues increased rapidly. In China, the trends and ranking in discussion of nonpain management issues stabilized and showed most frequently in psycho-spiritual issues, followed by social, ethical and legal issues.Sharing palliative experience via tele-videoconferences is an effective tool to improve the quality of care, and also saves a significant amount of time and expense. Experts in different professions from different hospitals should discuss any palliative problems, share their valuable experience, and ponder a comprehensive hospice care., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To compare image quality and radiation dose of split-filter TwinBeam dual-energy (SF-TBDE) with those of single-energy images (SECT) in the contrast-enhanced chest computed tomography (CT)., Methods: Two hundred patients who underwent SF-TBDE (n = 100) and SECT (n = 100) contrast-enhanced chest scanning were retrospectively analyzed. The contrast-to-noise ratio (CNR) and figure of merit (FOM)-CNR of 5 structures (lung, aorta, pulmonary artery, thyroid, and erector spinae) were calculated and subjectively evaluated by 2 independent radiologists. Radiation dose was compared using volume CT dose index and size-specific dose estimate., Results: The CNR and FOM-CNR of lung and erector spinae in SF-TBDE were higher than those of SECT (P < 0.001). The differences in the subjective image quality between the 2 groups were not significant (P = 0.244). Volume CT dose index and size-specific dose estimate of SF-TBDE were lower than those of SECT (6.60 ± 1.56 vs 7.81 ± 3.02 mGy, P = 0.001; 9.25 ± 1.60 vs. 10.55 ± 3.54; P = 0.001)., Conclusions: The SF-TBDE CT can provide similar image quality at a lower radiation dose compared with SECT., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) is an emerging technique in the area of minimally invasive surgery. Vaginal leiomyoma is a rare benign tumor, with only a few cases being reported in the literature. we demonstrate a novel approach for excision of a vaginal leiomyoma via vNOTES. To ensure reproducibility and replicability akin to a standardized procedure, we have provided a step-by-step video description of the use of vNOTES for upper anterior vaginal myomectomy., Patient Concerns: A 35-year-old female (G2P0A2) presented with a tumor in the upper anterior vaginal wall, which gradually increased in size., Diagnosis: A vaginal examination revealed a swollen area approximately 3-cm in diameter on the upper anterior vaginal wall. The swelling was mobile and solid. All other vitals were normal. Transvaginal ultrasound detected a 3.0 × 3.4 cm hypoechogenic mass on the superior vaginal wall, and a preoperative diagnosis of the vaginal tumor was confirmed., Interventions: The upper vaginal leiomyoma treated using transvaginal natural orifice transluminal endoscopic surgery., Outcomes: The procedure lasted for 20 min, and the postoperative course was uneventful., Conclusions: vNOTES can be a promising alternative to traditional vaginal surgery for upper vaginal disease due to advantages such as excellent exposure, easy access and precise suturing. However, more studies are needed to assess its long-term efficacy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Non-specific chronic low back pain (LBP) is a debilitating disease that profoundly impacts patients' daily physical function and quality of life. Gua sha therapy, as an easy-to-use and noninvasive complementary modality, has been widely used clinically in patients with non-specific chronic LBP. The aim of this study is to test the potential benefits and harms of gua sha therapy on patients with non-specific chronic LBP., Methods: Ten English databases, 3 Korean databases, 6 Chinese databases, 1 Japanese database, and 2 Brazilian databases will be searched from their inception to September 2019. Randomized controlled trials will be included if gua sha therapy was used as the sole treatment or as a part of combination therapy with other treatments in patients with non-specific chronic LBP. Two reviewers will independently extract the data and assess the methodological quality using the Cochrane criteria for risk of bias. The meta-analysis will be performed using Review Manager 5.3 software., Results: The findings of this systematic review will be published in a peer-reviewed journal., Conclusion: This systematic review will provide more evidence regarding the clinical usage of gua sha therapy for non-specific chronic LBP., Trial Registration Number: CRD42019134567.

Background: Equipping undergraduate nursing students with sufficient competence in evidence-based practice (EBP) is essential to meeting future practice needs. Integrating necessary EBP knowledge and skills systematically into the formal curriculum allows students to obtain better learning experience and outcomes. However, in Taiwan, a systematic nursing curriculum that integrates EBP concepts across the 4-year nursing baccalaureate program has not yet been developed. Moreover, engaging students in the clinical application of evidence remains a key challenge facing nursing education., Purpose: This study aimed to construct an EBP undergraduate nursing curriculum and develop clinical scenarios that support EBP teaching., Methods: Three cycles of action research, incorporating both focus group interviews and questionnaire surveys, were applied to construct and evaluate the appropriateness and feasibility of the EBP nursing curriculum and relevant teaching strategies., Results: An EBP nursing curriculum was constructed that integrates the three levels of learning objectives and corresponding learning outcomes, teaching content, and learning activities. Scenario activities were developed to familiarize students with the EBP process and to maximize their learning with regard to the clinical application of evidence. Next, a preliminary evaluation showed the appropriateness and feasibility of the developed curriculum, which was shown to foster the EBP competency of students and increase their confidence and positive attitudes toward EBP., Conclusions/implications for Practice: A systematic EBP bachelor nursing curriculum with effective pedagogical strategies was developed. The associated process and the elicited information may offer a valuable reference for other nursing schools.

Introduction: Severe trauma is accompanied by endothelial glycocalyx disruption, which drives coagulopathy, increasing transfusion requirements and death. This syndrome has been termed endotheliopathy of trauma (EOT). Some have suggested EOT results from endothelial cellular damage and apoptosis. Endothelial microvesicles (EMVs) represent cellular damage. We hypothesized that EOT is associated with endothelial damage and apoptosis resulting in an increase in circulating EMVs., Methods: Prospective, observational study enrolling severely injured patients. Twelve patients with EOT, based on elevated Syndecan-1 levels, were matched with 12 patients with lower levels, based on Injury Severity Score (ISS), abbreviated injury scale profile, and age. Thrombelastography and plasma levels of biomarkers indicative of cellular damage were measured from blood samples collected on admission. EMVs were determined by flow cytometry using varied monoclonal antibodies associated with endothelial cells. Significance was set at P < 0.05., Results: Admission physiology and ISS (29 vs. 28) were similar between groups. Patients with EOT had higher Syndecan-1, 230 (158, 293) vs. 19 (14, 25) ng/mL, epinephrine, and soluble thrombomodulin levels. Based on thrombelastography, EOT had reductions in clot initiation, amplification, propagation and strength, and a greater frequency of transfusion, 92% vs. 33%. There were no differences in EMVs irrespective of the antibody used. Plasma norepinephrine, sE-selectin, sVE-cadherin, and histone-complexed DNA fragments levels were similar., Conclusion: In trauma patients presenting with EOT, endothelial cellular damage or apoptosis does not seem to occur based on the absence of an increase in EMVs and other biomarkers. Thus, this suggests endothelial glycocalyx disruption is the underlying primary cause of EOT.

Living donor liver transplantation has advantages over deceased organ liver transplantation. However, the living liver donor candidates must be carefully assessed before surgery. Candidates may be excluded for various reasons. The purpose of this study was to evaluate the psychological profiles of excluded living liver donor candidates according to the reason for exclusion.A descriptive and cross-sectional study was conducted. Donor candidates were invited to participate if they were at least 20 years of age, related biologically or by marriage to the recipient (within 5 degrees), and had undergone living donor evaluation. Among the 338 participants recruited from August 2013 to December 2015, 116 were excluded for the following reasons: a medical condition (n = 35), failure to be chosen (n = 63), or withdrawal from the selection process (n = 18). The psychological profiles of these 3 exclusion groups were evaluated.There were no significant group differences in age, sex, education level, religion, marital status, and consanguinity (P > .05). The withdrawal group had fewer recipients with an hepatitis B virus infection than did the other groups (χ = 9.28, P = .01). Additionally, compared with the unchosen group, the withdrawal group had lower intimacy with the recipient (F = 5.32, P = .006) and higher ambivalence (F = 5.53, P = .005). In terms of family relationship parameters, the withdrawal group had lower family cohesion than the medical condition and unchosen groups (F = 4.44, P = .01), lower family expressiveness than the medical condition group (F = 3.76, P = .03), and higher family conflict than the medical condition and unchosen groups (F = 7.05, P = .001). The withdrawal group also had lower emotional social support than the medical condition group (F = 3.55, P = .03). There were no significant group difference in motivation, expectations, donation-related concerns, informational social support, value social support, instrumental social support, and health-related quality of life.The living donor candidates who withdrew from the selection process had obvious ambivalence, poorer family relationships, and insufficient emotional social support. The transplantation team should respect the autonomy of the candidate's decision and mitigate the impact of the donation decision on living liver donor candidates.

Background: The efficient and safe oral feeding of preterm infants, an essential criterion for hospital discharge, is affected by neurodevelopmental maturation. However, the timing of initiating oral feeding and its relation to maturation, feeding performance, and physiological responses are unclear., Purpose: The aim of this study was to determine the effect of a 1-week delay in the initiation of oral feeding on feeding performance, transition time, weight gain, and cardiorespiratory responses in preterm infants., Methods: In this randomized controlled trial, 40 infants with a gestational age at birth of less than 32 weeks were recruited. The control group (n = 18) began oral feeding when the infants were physiologically stable, whereas the experimental group (n = 22) began oral feeding 1 week later. Infant feeding performance, heart rate, and oxygen saturation were measured before, during, and after feeding on the first day of oral feeding and 3 days later. Daily weight gain was calculated by measuring body weight every morning, and transition time was calculated by counting the number of days from the initiation of oral feeding to the termination of tube feeding., Results: There were no significant differences between the two groups in terms of feeding performance, weight gain, or postmenstrual age at the completion of full oral feeding. The transition time was significantly shorter in the experimental group than in the control group. More infants in the control group experienced episodes of oxygen desaturation during feeding than in the experimental group., Conclusions/implications for Practice: For infants with a postmenstrual age of greater than 32 weeks who are ready to initiate oral feeding, postponing oral bottle feeding for 1 week may be considered as an intervention to reduce physiological distress.

The treatment of advanced triple-negative breast cancer, which failed in first-line or second-line therapy, is a significant challenge. We conducted this retrospective study to explore the efficacy and safety of apatinib and capecitabine as the third-line treatment for advanced triple-negative breast cancer.This retrospective study involved 44 advanced triple-negative breast cancer patients who failed in first-line or second-line therapy in Tangshan People's Hospital from January 2016 to February 2017. Twenty-two patients received apatinib and capecitabine, while 22 patients were treated with capecitabine monotherapy as third-line therapy. The progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events were compared between 2 groups.The apatinib and capecitabine group exhibited a higher PFS than capecitabine group (P = .001). Meanwhile, ORR and DCR in apatinib and capecitabine group were better than in capecitabine group (P = .042; .016). The 2 groups showed no significant difference in adverse events except degree I-II bleeding (P = .021). Both the apatinib and capecitabine and the capecitabine regimens revealed good tolerability.The apatinib and capecitabine regimen can achieve a better efficacy and similar serious adverse events compared with capecitabine regimen as the third-line treatment for advanced triple-negative breast cancer.

Background: Progressive hemorrhagic injury (PHI) is common in patients with severe traumatic brain injury (TBI) and is associated with worse outcomes. PHI pathophysiology remains poorly understood and difficult to predict. We performed an exploratory analysis aimed at identifying markers in need of further investigation to establish their predictive value in PHI following TBI., Methods: We performed a retrospective chart review of prospectively collected data from 424 highest-level activation trauma patients from January 2012 through December 2013. Patients with severe TBI, defined as head acute injury scale (AIS) score ≥3 and intracranial hemorrhage (ICH) on initial CT, were included. Stable hemorrhage (SH) and PHI was determined by measuring ICH expansion on repeat CT within 6 h. Of 424 patients evaluated, 72 met inclusion criteria. Twenty-five patients had repeated samples available and were dichotomized into SH (n = 6, 24%) and PHI (n = 19, 76%). Levels of plasminogen, urokinase and tissue plasminogen activators (uPA, tPA), plasminogen activator inhibitor-1, α2-antiplasmin (α2AP), and D-Dimers (DD) were measured upon admission and 2, 4, and 6 h later., Results: Longitudinal models identified tPA and DD as positively associated and α2AP inversely associated with PHI. High DD levels are strongly associated with developing PHI over time. Using the full TBI cohort of N = 72, receiver operating curve analysis provided a cutoff of 3.04 μg/mL admission DD to distinguish SH from PHI patients., Conclusion: Our findings support a relationship between markers of fibrinolysis in polytrauma patients with severe TBI and PHI, warranting further investigation into the potential for novel, predictive biomarkers.

Background: Alpha-fetoprotein (AFP) is an important marker for hepatocellular carcinoma, and the detection of serum AFP is currently the principle method for the diagnosis of hepatocellular carcinoma. The prevalence of gastric cancer (GC) with high level of serum AFP is extremely rare, but has unique clinical features., Case Summary: We herein present a rare case with GC and high level of serum AFP. A 64-year-old Chinese female underwent gastrectomy was diagnosed as gastric adenocarcinoma and the pathological stage was T1bN0M0, IA. With the progression of disease, the tumor widely metastasized and the serum AFP level increased progressively with the highest level of 3396 ng/mL. She successively entered into 3 lines palliative systematic chemotherapy and fourth-line targeted therapy of apatinib, a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. Although previous studies suggested that the prognosis of this special type of GC was poor, this patient lived for 22 months after tumor transfer. Apatinib kept her progression-free survival for 5 months, and the overall survival was 4.5 years., Conclusion: So, we speculate that maybe we can focus apatinib on serum AFP elevated GC patients.

Background: Synaptic mechanisms and neuronal oscillations have been proposed to be responsible for neuropathic pain formation. Many studies have also highlighted the important role of electrical synapses in synaptic plasticity and in neuronal oscillations. Thus, electrical synapses may contribute to neuropathic pain generation. However, previous studies have primarily focused on the role of chemical synapses, while ignoring the role of electrical synapses, in neuropathic pain generation., Methods: The authors adopted microinjection, RNA interference techniques, and behavioral tests to verify the link between connexin 36 (Cx36) and neuropathic pain. They also studied the selective Cx36 blocker mefloquine in rat chronic constriction injury and spared nerve injury model of neuropathic pain. Electrophysiologic recordings were used to further confirm the behavioral data., Results: The authors found that Cx36, which constitutes the neuron-neuron electrical synapses, was up-regulated in the anterior cingulate cortex after nerve injury (n = 5). Meanwhile, Cx36-mediated neuronal oscillations in the gamma frequency range (30 to 80 Hz) (n = 7 to 8) and the neuronal synaptic transmission (n = 13 to 19) were also enhanced. Neuropathic pain was relieved by disrupting Cx36 function or expression in the anterior cingulate cortex. They also found that mefloquine, which are clinically used for treating malaria, affected gamma oscillations and synaptic plasticity, leading to a sustained pain relief in chronic constriction injury and spared nerve injury models (n = 7 to 12)., Conclusion: The electrical synapses blocker mefloquine could affect gamma oscillations and synaptic plasticity in the anterior cingulate cortex and relieve neuropathic pain. Cx36 may be a new therapeutic target for treating chronic pain.

Background: The effects of general anesthetics on the hypothalamus-pituitary-adrenal axis and cortisol release in children are poorly characterized. Normal, daily fluctuation of cortisol levels complicates assessment of these effects. This study aimed to characterize the effects of etomidate compared with propofol on the normal cortisol secretory pattern in children undergoing urologic surgery by using a salivary cortisol assay., Methods: In this prospective, randomized, double-blind, controlled study, we recruited 80 children aged 3 to 12 years assigned ASA physical status I who were scheduled for urologic surgery and 11 healthy child volunteers. Before surgery, cortisol levels of the 11 volunteers and 15 study patients were tested from 7:00 AM to 9:00 PM every hour for 1 day. The study patients were then randomly allocated into an etomidate group and a propofol group, receiving etomidate 0.3 mg/kg (n = 38) or propofol 2 mg/kg (n = 39) and midazolam 0.1 mg/kg, fentanyl 2 μg/kg, and rocuronium 0.6 mg/kg for induction, respectively. The cortisol levels of the patients were assessed continuously for 2 days postoperatively., Results: The cortisol levels of the etomidate group were continuously and significantly lower than those of the propofol group from the time of discharge from the postanesthesia care unit (approximately 2:00 PM) until 8:00 AM the next morning (all P < 0.0001) and were significantly lower than before surgery at the same time points (all P < 0.0001). Except at 11:00 AM just before the operation, no significant differences in cortisol levels were detected before and after the operation in the propofol group (P max = 0.476, P min = 0.002). Also, no significant differences in clinical outcomes were detected between the 2 groups undergoing surgery (all P > 0.070)., Conclusions: Compared with propofol, a single induction dose of etomidate suppressed postoperative cortisol levels in healthy children undergoing urologic surgery. This suppression lasted approximately 24 hours and was not associated with any changes in clinical outcomes.

Tumor necrosis factor-alpha (TNF-α) has been demonstrated to have a close relationship with inflammation in the body. Although most researchers confirmed that TNF-α can have an effect on the expression of osteoblast specific genes, they had not elucidated the regulation of inflammatory factors in osteogenic gene expression during the process of bone marrow mesenchymal stem cells (BMMSCs) differentiating to osteoblast. The aim of this study was to investigate the effect of TNF-α at different concentrations on osteogenetic differentiation of BMMSCs. In this study, BMMSCs proliferation was analyzed by using cell counting kit-8 assay, cell osteogenic differentiation was evaluated by means of alkaline phosphatase activity assay and Von Koaas staining and the messenger RNA (mRNA) expression of bone morphogenetic proteins-2 (BMP-2) and drosophila mothers against decapentaplegic protein 1 (Smad1) was measured through real-time polymerase chain reaction. The results indicated that a low concentration of TNF-α at short-term promotes the osteogenetic differentiation of BMMSCs and increases the mRNA expression of BMP-2 and Smad1, but inhibits the osteogenetic differentiation of BMMSCs and the expression of BMP-2 and Smad1 at long term. In addition, regardless of a short or long time, a high concentration of TNF-α inhibits the osteogenetic differentiation of BMMSCs and the expression of Smad1, but results in a high expression of BMP-2.

Justicidin A (JA) is one of the methanol extracts of Justicia procumbens and was reported to induce apoptosis and inhibit the proliferation of human colon cancer cells. Using bladder cancer as a paradigm, this study was designed to identify the novel molecular basis underlying the antiangiogenic activities of JA and its potential in cancer therapy. Human bladder cancer cell lines (TSGH8301 and RT4) and immortalized uroepithelial cell lines (E6 and E7) were chosen to investigate the efficacy of JA in cell proliferation, apoptosis, and angiogenesis in vitro. The biological effects of JA treatment in vivo were examined using a xenograft tumor model in SCID mice. JA showed a dose-dependent and time-dependent inhibition of cell proliferation on TSGH8301 cancer cells, with IC50 values determined to be 0.44 μmol/l. Of interest, TSGH8301 cancer cells were more sensitive to JA than E7 immortalized uroepithelial cells, especially at lower concentrations. We further showed that JA inhibited the autocrine production of angiogenic factors and matrix-degrading enzymes in vitro and microvessel density in SCID mice in vivo (P< 0.01). Both differential cytotoxicity and angiogenesis inhibition of JA were confirmed by SCID mice experiments. Together, JA showed antiangiogenesis in vitro and in vivo through pleiotropic positive and negative regulators of angiogenesis molecules. The current investigation supports the potential of JA as an alternative chemoprevention agent for human bladder cancer.

Rodent models of hemorrhagic shock are paramount to our understanding of the pathophysiology of this disease, the effects on coagulation and in exploring the utility of resuscitative methods for managing patients in shock. These models usually require serial blood sampling during experimentation. The lack of standardized practices for these experimental models has resulted in technical variability, discordance in the literature, and incomparable results on blood coagulation analysis between researchers, hindering substantial progress in the field of hemorrhagic shock. The aim of this study was to define the effects of cardiac puncture versus arterial catheterization on coagulation in a rat model to provide data supporting standardization of one practice over another. Blood was collected from anesthetized rats via cardiac puncture or femoral artery catheterization and hemostatic potential analyzed by thrombelastography and calibrated automated thrombography. Our data show that blood collected via cardiac puncture demonstrated hypercoagulability as indicated by faster rates of clot formation and thrombin generation, increased overall clot strength, and a greater thrombin-generating capacity when compared with blood collected via femoral artery catheter. We conclude that blood collection methods have a profound effect on hemostatic potential, and standardization of these practices is necessary to define the effects of shock on coagulation in rodents.

Introduction: Recent data have associated improved survival after hemorrhagic shock with the early use of plasma-based resuscitation. Our laboratory has shown that FFP5 has decreased hemostatic potential compared with freshly thawed plasma (FFP0). We hypothesized that FFP5 would increase bleeding and mortality compared with FFP0 in a rodent bioassay model of uncontrolled liver hemorrhage., Methods: Hemostatic potential of plasma was assessed with the Calibrated Automated Thrombogram (CAT) assay. Rats underwent isovolemic hemodilution by 15% of blood volume with the two human plasma groups (FFP0 and FFP5) and two controls (sham and lactated Ringers). A liver injury was created by excising a portion of liver resulting in uncontrolled hemorrhage. Rats that lived for 30 minutes after liver injury were resuscitated to their baseline blood pressure and followed for 6 hours. Hemostasis was assessed by thromboelastography., Results: Hemostatic potential of FFP5 decreased significantly in all areas measured in the CAT assay as compared with FFP0 (p < 0.01). In the FFP5 group, overall survival was 54%, compared with 100% in the FFP0 and sham group (p = 0.03). For animals that survived 30 minutes and were resuscitated, there was no difference in bleeding and/or coagulopathy between groups. Irrespective of treatment, animals that died after resuscitation demonstrated increased intraperitoneal fluid volume (14.85 mL ± 1.9 mL vs. 7.02 mL ± 0.3 mL, p < 0.001)., Conclusion: In this model of mild preinjury hemodilution with plasma, rats that received FFP5 had decreased survival after uncontrolled hemorrhage from hepatic injury. There were no differences in coagulation function or intraperitoneal fluid volume between the two plasma groups.

Background: The purpose of this study is to evaluate bowel-cleansing methods for colonic preparation, based on the findings of PET-computed tomographic (CT) scans., Methods: A total of 175 patients were enrolled in this study. Patients with medical histories of colorectal cancer, abdominal operation, or abdominal malignancies were excluded from this study. The patients were divided into three groups according to the three kinds of bowel-cleansing methods used: (i) no laxatives or dietary restriction (control group), (ii) dietary restriction (low-residue diet), and (iii) a combination of contact laxatives (Dulcolax) and dietary restriction (low-residue diet). Colonic standardized uptake value data were recorded. The hot spots that influenced the interpretation of images or the localization of true lesions were classified as positive (+), whereas data that did not influence clinical diagnosis were classified as negative (-)., Results: In the first group, 22.2% of the patients with positive colonic hot spots were detected in whole-body PET-CT scans. In the second group, a 34.9% positive rate of colonic hot spots was visible. In the third group, a 73.5% positive rate was detected. The positive rate in the third group is significantly higher than the percentages detected in the first and the second groups (P<0.01)., Conclusion: The findings indicated that a low-residue diet is not beneficial to colonic preparation. Moreover, contact laxatives cause diagnostic confusion when PET-CT images are interpreted. Therefore, although PET-CT scans are capable of adding precision to functional imaging, and to focal localization, the researchers concluded that avoiding contact laxatives is necessary to decrease intestinal artifacts.

Purpose: To evaluate the effect of using tailored individual doses of radioiodine (¹³¹I) and fine tuning using low-dose antithyroid drug (ATD) in the treatment of Graves' disease, and an attempt to establish a therapeutic strategy that can keep both high rate of euthyroidism and low incidence of hypothyroidism., Methods: The dose of radioiodine was calculated using the calculated dose formula, and low-dose ATD was used as a way of fine tuning during follow-up. The intended dose of radioiodine was modified according to the patient's age at radioiodine therapy, thyroid size, and duration of hyperthyroidism before radioiodine therapy in the study group; it was set as 2.96 MBq/g of thyroid in the control group. Twenty patients with Graves' disease were nonrandomly assigned to the control group and 98 patients with Graves' disease to the study group. The outcomes, which included euthyroidism, hypothyroidism, and persistent hyperthyroidism, were determined according to the patients' states at the end of follow-up., Results: In the study group, 74 patients (75.5%) achieved the euthyroid state, six patients (6.1%) became hypothyroid, and 18 patients (18.4%) remained hyperthyroid. The rate of euthyroidism was statistically different between the study group and the control group (75.5 vs. 50%, P=0.03). Of 98 patients with Graves' disease in the study group, 19 patients were additionally treated with ATD during follow-up, and 12 patients achieved euthyroidism. In different age groups or duration of hyperthyroidism groups, the rate of euthyroidism was not statistically different among subgroups of goiter grade 1, grade 2, and grade 3 (P>0.05). Similarly, in different age groups or duration of hyperthyroidism groups, the incidence of hypothyroidism was not statistically different among subgroups of goiter grade 1, grade 2, and grade 3 (P>0.05). However, binary logistic regression analysis showed that thyroid size was associated with overtreatment and undertreatment in our study., Conclusion: Individual doses of radioiodine, adjusted according to the patient's age, thyroid size, and duration of hyperthyroidism, combined with low-dose ATD for some patients, 1 month or more after radioiodine therapy, was an effective method for treating Graves' disease. Our data showed that using tailored individual doses of radioiodine and fine tuning using low-dose ATD may well be a way to keep both high rate of euthyroidism and low incidence of hypothyroidism. The dose of radioiodine should be decreased a little for small goiter and increased a little for large goiter on the basis of our treatment protocol in future study.

Background: Celecoxib, a cyclooxygenase-2 inhibitor, is a commonly ingested drug that is used by some women during pregnancy. Although use of celecoxib is associated with increased cardiovascular risk in adults, its effect on fetal heart development remains unknown., Methods: Zebrafish embryos were exposed to celecoxib or other relevant drugs from tailbud stage (10.3-72 h postfertilization). Heart looping and valve formation were examined at different developmental stages by in vivo confocal imaging. In addition, whole mount in situ hybridization was performed to examine drug-induced changes in the expression of heart valve marker genes., Results: In celecoxib-treated zebrafish embryos, the heart failed to undergo normal looping and the heart valve was absent, causing serious blood regurgitation. Furthermore, celecoxib treatment disturbed the restricted expression of the heart valve markers bone morphogenetic protein 4 and versican-but not the cardiac chamber markers cardiac myosin light chain 2, ventricular myosin heavy chain, and atrial myosin heavy chain. These defects in heart development were markedly relieved by treatment with the cyclooxygenase-2 downstream product prostaglandin E2, and mimicked by the cyclooxygenase-2 inhibitor NS398, implying that celecoxib-induced heart defects were caused by the inhibition of cyclooxygenase-2 activity., Conclusions: These findings provide the first in vivo evidence that celecoxib exposure impairs heart development in zebrafish embryos by inhibiting cyclooxygenase-2 activity.

Background: Severe bleeding after injury requires transfusion of blood products, including fresh frozen plasma (FFP). Many centers are keeping thawed plasma (TP) ready for massively transfused patients. According to the American Association of Blood Banks Standards, TP is approved for transfusion up to 5 days after thawing, when stored at 1°C to 6°C. However, there are no clinical data analyzing the effects of the approved 5-day storage on plasma. We hypothesize that the hemostatic potential (HP) of freshly thawed (FFP-0) was superior to plasma stored for 5 days (FFP-5)., Methods: FFP from 30 single donors were thawed at 37°C and kept at 1°C to 6°C for 5 days. HP was evaluated at day 0 and 5 by measuring kinetics of thrombin generation (TG), kinetics of clot formation by thromboelastography, clotting factors and inhibitors, and cell-derived microparticles (MPs) by flow cytometry., Results: When comparing FFP-5 to FFP-0, FFP-5 exhibited only 40% of the potential of FFP-0 for TG (6.2 nM/min vs. 14.3 nM/min, p<0.0001), a slower clotting response via thromboelastography (reaction time: 4.3 minutes vs. 3.2 minutes, p<0.0001) and a longer delay in reaching maximum thrombus generation (5.7 minutes vs. 4.6 minutes, p<0.01). Diminished HP was accompanied by a significant decline in multiple coagulation proteins, including FV, VII, VIII, von Willebrand factor, and free Protein S, by up to 30%, and a decrease of 50% in MP counts., Conclusion: The HP and clot forming ability of TP significantly declined with storage. Hence, freshly TP may have a greater ability to restore hemostasis and correct coagulopathy compared with FFP-5. The clinical consequences for transfused patients deserve further exploration.

Factor XIII catalyzes the cross-linking of fibrin. Cross-sectional studies have suggested that a common polymorphism site at residue 34 of the A subunit of factor XIII (FXIIIA) with a substitution of Leu for Val (FXIIIA Val34Leu) was associated with reduced coronary heart disease (CHD). This association has not been examined in prospective studies. Healthy subjects (n=15 792) were recruited from 4 US communities into the Atherosclerosis Risk in Communities (ARIC) study from 1987 to 1989. They were followed, and incident CHD events were identified and verified. For the present study, we included 423 patients with CHD as cases and 479 noncases. FXIIIA Val34Leu polymorphism was determined by the single-strand conformational polymorphism method. There were no significant differences in the genotype frequencies between cases and noncases. The genotypes showed little association with known CHD risk factors. A weighted proportional hazards regression analysis adjusting for other risk factors confirmed no association of the genotypes with risk of CHD. This prospective study did not provide evidence of a reduced CHD risk for the FXIIIA 34Leu allele.