Effectiveness and safety of tourniquet utilization for civilian vascular extremity trauma in the pre-hospital settings: a systematic review and meta-analysis.

BACKGROUND: Tourniquets (TQ) have been increasingly adopted in pre-hospital settings recently. This study examined the effectiveness and safety of applying TQ in the pre-hospital settings for civilian patients with traumatic vascular injuries to the extremities. MATERIALS AND METHODS: We systematically searched the Ovid Embase, PubMed, and Cochrane Central Register of Controlled Trials databases from their inception to June 2023. We compared pre-hospital TQ (PH-TQ) use to no PH-TQ, defined as a TQ applied after hospital arrival or no TQ use at all, for civilian vascular extremity trauma patients. The primary outcome was overall mortality rate, and the secondary outcomes were blood product use and hospital stay. We analyzed TQ-related complications as safety outcomes. We tried to include randomized controlled trials (RCTs) and non-randomized studies (including non-RCTs, interrupted time series, controlled before-and-after studies, cohort studies, and case-control studies), if available. Pooled odds ratios (ORs) were calculated and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. RESULTS: Seven studies involving 4,095 patients were included. In the primary outcome, pre-hospital TQ (PH-TQ) use significantly decrease mortality rate in patients with extremity trauma (odds ratio [OR], 0.48, 95% confidence interval [CI] 0.27-0.86, I2 = 47%). Moreover, the use of PH-TQ showed the decreasing trend of utilization of blood products, such as packed red blood cells (mean difference [MD]: -2.1 [unit], 95% CI: -5.0 to 0.8, I2 = 99%) or fresh frozen plasma (MD: -1.0 [unit], 95% CI: -4.0 to 2.0, I2 = 98%); however, both are not statistically significant. No significant differences were observed in the lengths of hospital and intensive care unit stays. For the safety outcomes, PH-TQ use did not significantly increase risk of amputation (OR: 0.85, 95% CI: 0.43 to 1.68, I2 = 60%) or compartment syndrome (OR: 0.94, 95% CI: 0.37 to 2.35, I2 = 0%). The certainty of the evidence was very low across all outcomes. CONCLUSION: The current data suggest that, in the pre-hospital settings, PH-TQ use for civilian patients with vascular traumatic injury of the extremities decreased mortality and tended to decrease blood transfusions. This did not increase the risk of amputation or compartment syndrome significantly.

Diagnostic performance of ultrasound in acute cholecystitis: a systematic review and meta-analysis.

BACKGROUND: An updated overview of ultrasound (US) for diagnosis of acute cholecystitis (AC) remains lacking. This systematic review was conducted to evaluate the diagnostic performance of US for AC. METHODS: A systematic review was conducted following PRISMA guidelines. We meticulously screened articles from MEDLINE, Embase, and the Cochrane Library, spanning from inception to August 2023. We employed the search strategy combining the keywords "bedside US", "emergency US" or "point-of-care US" with "AC". Two reviewers independently screened the titles and abstracts of the retrieved articles to identify suitable studies. The inclusion criteria encompassed articles investigating the diagnostic performance of US for AC. Data regarding diagnostic performance, sonographers, and sonographic findings including the presence of gallstone, gallbladder (GB) wall thickness, peri-GB fluid, or sonographic Murphy sign were extracted, and a meta-analysis was executed. Case reports, editorials, and review articles were excluded, as well as studies focused on acalculous cholecystitis. The study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS: Forty studies with 8,652 patients were included. The majority of studies had a low risk of bias and applicability concerns. US had a pooled sensitivity of 71% (95% CI, 69-72%), a specificity of 85% (95% CI, 84-86%), and an accuracy of 0.83 (95% CI, 0.82-0.83) for the diagnosis of AC. The pooled sensitivity and specificity were 71% (95% CI, 67-74%) and 92% (95% CI, 90-93%) performed by emergency physicians (EPs), 79% (95% CI, 71-85%) and 76% (95% CI, 69-81%) performed by surgeons, and 68% (95% CI 66-71%) and 87% (95% CI, 86-88%) performed by radiologists, respectively. There were no statistically significant differences among the three groups. CONCLUSION: US is a good imaging modality for the diagnosis of AC. EP-performed US has a similar diagnostic performance to radiologist-performed US. Further investigations would be needed to investigate the impact of US on expediting the management process and improving patient-centered outcomes.

Video characteristics for remote recognition of agonal respiration: A pilot study.

Aim: The mobile network quality in ambulances can be variable and limited. This pilot study aimed to identify a suitable network setting for recognizing agonal respiration under limited network conditions. Methods: We recruited five emergency medical technicians, and each participant viewed 30 real-life videos with different resolutions, frame rates, and network scenarios. Thereafter, they reported the respiration pattern of the patient and identified agonal respiration cases. The time at which agonal respiration was identified was also recorded. The answers provided by the five participants were compared with those of two emergency physicians to compare the accuracy and time delay in breathing pattern recognition. Results: The overall accuracy for initial respiratory pattern recognition was 80.7% (121/150). The accuracy for normal breathing was 93.3% (28/30), for not breathing was 96% (48/50), and for agonal breathing was 64.3% (45/70). There was no significant difference in successful recognition between video resolutions. However, the rate of time delay in recognizing agonal respiration less than 10 seconds between 15-fps group and 30-fps group had statistical significance (21% vs 52%, p = 0.041). Conclusion: The frame rate emerges as one of critical factors in agonal respiration recognition through telemedicine, outweighing the significance of video resolution.

Effect of using G-FAST to recognize emergent large vessel occlusion: A city-wide community experience.

BACKGROUND/PURPOSE: A prehospital bypass strategy was suggested for large vessel occlusion. This study aimed to evaluate the effect of a bypass strategy using the gaze-face-arm-speech-time test (G-FAST) implemented in a metropolitan community. METHODS: Pre-notified patients with positive Cincinnati Prehospital Stroke Scale and symptom onset <3 h from July 2016 to December 2017 (pre-intervention period) and those with positive G-FAST and symptom onset <6 h from July 2019 to December 2020 (intervention period) were included. Patients aged <20 years and those with missing in-hospital data were excluded. The primary outcomes were the rates of receiving endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT). The secondary outcomes were total prehospital time, door-to-computed tomography (CT) time, door-to-needle (DTN) time, and door-to-puncture (DTP) time. RESULTS: We included 802 and 695 pre-notified patients from the pre-intervention and intervention periods, respectively. The characteristics of the patients in the two periods were similar. In the primary outcomes, pre-notified patients during the intervention period showed higher rates of receiving EVT (4.49% vs. 15.25%, p < 0.001) and IVT (15.34% vs. 21.58%, p = 0.002). In the secondary outcomes, pre-notified patients during intervention period had longer total prehospital time (mean 23.38 vs 25.23 min, p < 0.001), longer door-to-CT time (median 10 vs 11 min, p < 0.001), longer DTN time (median 53 vs 54.5 min, p < 0.001) but shorter DTP time (median 141 vs 139.5 min, p < 0.001). CONCLUSION: The prehospital bypass strategy with G-FAST showed benefits for stroke patients.

Anti-inflammatory constituents from Phyllostachys makinoi Hayata.

A novel chromone analogue, phyllomakin A (1), and a new flavonolignan, (-)-quiquelignan C (2), along with 18 phenolic and 2 triterpenoids, were isolated from the leaves of Phyllostachys makinoi Hayata. The structures of 1-22 were elucidated by an application of various spectroscopic analyses (1D & 2D NMR and MS) and compared with reported data. A biological evaluation showed that compound 3 had very potent anti-NO production activity (IC50 = 4.80 µM), while compounds 2, 6, 11, and 15 showed moderate inhibitory effects (IC50 = 10.19, 13.26, 13.56, and 10.96 µM, respectively) without affecting cell viability at 20 µM.

Depression and Somatic Symptoms in a Non-Western Physician.

Because of the high prevalence and association of somatic symptoms in depression, a holistic treatment plan that also targets the associated somatic symptoms can be the cornerstone for such patients. In this paper, we present the case of a 53-year-old male physician with depression associated with the somatic symptoms of dysphagia. The initial failure in treating his swallowing defect led to the deterioration in his condition. Moreover, his unique history, complicated by multifactorial life stressors, also raises the attention that there are a variety of presentations of depression.

Design, synthesis and antitumour evaluation of novel anthraquinone derivatives.

We report the design, synthesis, and biological evaluation of 13 new and 1 known anthraquinone derivatives which exerted cytotoxicity against PC3, A549 and NTUB1 cell lines. The results indicate that, among these 14, compounds-1 and 14 showed the highest growth inhibitory effect on NTUB1 and PC3 cells, respectively. Compound-1 at lower doses targets DNA, induces DNA damage and subsequently triggers G2/M arrest and apoptotic cell death at 24 h. Previously we reported that 14 induced PC3 cell autophagy and in treated PC3 cells, cleaved caspase-3 and cleaved PARP, and survivin did not increase and increase, respectively. The autophagic and necrotic cell deaths mediated by 14-triggered ROS generation. Our study is the first to investigate the biological mechanism of 14 action in detail. We find that when 14 was co-administrated with Bafilomycin A1 (BAF) in PC3 cells, rapid necrotic cell death occurred with no cleaved caspase-3 and cleaved PARP activation and increasing the expression of survivin. We further show that necrotic signaling in these cells coincided with production of reactive oxygen species. In the present study, we developed methods to synthesize five new 14 analogues for studing the structure-activity relationships. This study could provide valuable sight to find new antitumor agents for cancer therapy.

Discovering a Racemate Polycyclic Prenylated Acylphloroglucinol with Unprecedented Skeleton by an ESI-LCMS Analytical Approach.

By an ESI-LC/MS analytical method, a racemate 1 consisting of a pair of unprecedented phloroglucinol enantiomers with a 5/6/5/5/6 fused ring system, (-)-garcinielliptone HG [((-)-1a] and (+)-garcinielliptone HH [(+)-1b], was obtained from the isolates of a CH2Cl2 extract of Garcinia subelliptica (heartwood). The gross structure of 1 was elucidated by spectroscopic methods and X-ray single-crystal diffraction data. The absolute configurations of 1a and 1b were unequivocally assigned by analysis on the calculated and experimental circular dichroism spectra and X-ray single-crystal diffraction data.

Medical Applications of Collagen and Hyaluronan in Regenerative Medicine.

In order to develop and commercialize for the regenerative medicinal products, smart biomaterials with biocompatibility must be needed. In this chapter, we introduce collagen and hyaluronic acid (HA) as extracellular matrix as well as deal with the molecular mechanism as microenvironment, mechanistic effects, and gene expression. Application of collagen and HA have been reviewed in the area of orthopedics, orthopedics, ophthalmology, dermatology and plastic surgery. Finally, the ongoing and commercial products of collagen and HA for regenerative medicine have been introduced.

1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate induced autophagic cell death in human PC3 cells.

The autophagy of human prostate cancer cells (PC3 cells) induced by a new anthraquinone derivative, 1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate (PA) was investigated, and the relationship between autophagy and reactive oxygen species (ROS) generation was studied. The results indicated that PA induced PC3 cell death in a time- and dose-dependent manner, could inhibit PC3 cell growth by G1 phase cell cycle arrest and corresponding decrease in the G2/M cell population and induced S-phase arrest accompanied by a significant decrease G2/M and G1 phase numbers after PC3 cells treated with PA for 48 h, and increased the accumulation of autophagolysosomes and microtubule-associated protein LC3-ll, a marker of autophagy. However, these phenomenon were not observed in the group pretreated with the autophagy inhibitor 3-MA or Bafilomycin A1 (BAF), suggesting that PA induced PC3 cell autophagy. In addition, we found that PA triggered ROS generation in cells, while the levels of ROS decreased in the N-acetylcysteine (NAC) co-treatment, indicating that PA-mediated autophagy was partly blocked by NAC. In summary, the autophagic cell death of human PC3 cells mediated by PA-triggered ROS generation.

Triterpenoids and an alkamide from Ganoderma tsugae.

Ganoderma tsugae is a medicinal mushroom. In a continual study on the bioactive constituents of this fungus, a new lanostanoid, 3ß-acetoxy-16α-hydroxy-24ξ-methyl-5α-lanosta-8,25-dien-21-oic acid, named tsugaric acid F (1) and a novel palmitamide, N-(3'α,4'ß-dihydroxy-2'ß-(hydroxymethyl)-1'ß-(cyclobutyl)palmitamide (2) were isolated and characterized from the fruit bodies of G. tsugae, and three novel seco-lanostanoids, 3,4-seco-8α,9α-epoxy-5α-lanosta-21-oic acid 3,4 lactone (5), 3,4-seco-5ß-lanosta-7,9(11),4(29)-trien-3,21-dioic acid-3-methyl ester (6), 3,4-seco-5ß-lanosta-7,9(11),4(29)-trien-3,21-dioic acid (7), and a known compound, 3-oxo-5α-lanosta-8-en-21-oic acid (4) were prepared from 3. The structures of new compounds, 1, 2, 5-7 were determined by spectroscopic methods. Compounds 1 and 4 showed inhibitory effects on xanthine oxidase (XO) with an IC50 values of 313.3 ± 80.0 and 43.9 ± 29.9 µM, respectively when 7 exhibited potent inhibitory effect on superoxide anion generation in rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB) with an IC50 values of 1.3 ± 0.2 µM. Compounds 4-7 showed weak cytotoxic activities against PC3 cells. These results indicated that 4 and 7 may be used as cancer chemopreventive agents.

Basic fibroblast growth factor induces VEGF expression in chondrosarcoma cells and subsequently promotes endothelial progenitor cell-primed angiogenesis.

Chondrosarcoma, a common malignant tumour, develops in bone. Effective adjuvant therapy remains inadequate for treatment, meaning poor prognosis. It is imperative to explore novel remedies. Angiogenesis is a rate-limiting step in progression that explains neovessel formation for blood supply in the tumour microenvironment. Numerous studies indicate that EPCs (endothelial progenitor cells) promote angiogenesis and contribute to tumour growth. bFGF (basic fibroblast growth factor), a secreted cytokine, regulates biological activity, including angiogenesis, and correlates with tumorigenesis. However, the role of bFGF in angiogenesis-related tumour progression by recruiting EPCs in human chondrosarcoma is rarely discussed. In the present study, we found that bFGF induced VEGF (vascular endothelial growth factor) expression via the FGFR1 (fibroblast growth factor receptor 1)/c-Src/p38/NF-κB (nuclear factor κB) signalling pathway in chondrosarcoma cells, thereby triggering angiogenesis of endothelial progenitor cells. Our in vivo data revealed that tumour-secreted bFGF promotes angiogenesis in both mouse plug and chick CAM (chorioallantoic membrane) assays. Xenograft mouse model data, due to bFGF-regulated angiogenesis, showed the bFGF regulates angiogenesis-linked tumour growth. Finally, bFGF was highly expressed in chondrosarcoma patients compared with normal cartilage, positively correlating with VEGF expression and tumour stage. The present study reveals a novel therapeutic target for chondrosarcoma progression.

Chalcone derivatives inhibit human platelet aggregation and inhibit growth in human bladder cancer cells.

In an effort to develop potent cyclooxygenase-1 (COX-1) inhibitors used as anticancer agent, a series of 2',5'-dimethoxychalcones was screened to evaluate their antiplatelet effect on human washed platelets suspension. Compound 2 exhibited potent inhibition of human washed platelet aggregation induced by collagen, significantly inhibited collagen- and arachidonic acid-induced thromboxane B2 release, and revealed inhibitory effect on COX-1 activity. Molecular docking studies showed that 1, 2, and 4 were bound in the active site of COX-1. These indicated that the antiplatelet effect of these compounds were mainly mediated through the suppression of COX-1 activity and reduced the thromboxane formation. To investigate the mechanistic action of COX-1 inhibitor enhanced the cytotoxic effect against human bladder cancer cells, NTUB1, we assessed the cytotoxic effect of 2 against NTUB1. Treatment of NTUB1 cells with various concentrations of 2 led to a concentration-dependent increase of cell death and decrease of reactive oxygen species levels. The flow-cytometric analysis showed that 2 induced a G1 phase cell cycle arrest but did not accompany an appreciable sub-G1 phase in NTUB1 cells. In addition, compound 2 increased p21 and p27 expressions and did not inhibit the expression of COX-1 in NTUB1 cells. Our results suggested that 2 enhanced cell growth inhibition or antiproliferative activity in NTUB1 cells through G1 arrest by COX-1 independent mechanism.

Anti-cancer effects of ursane triterpenoid as a single agent and in combination with cisplatin in bladder cancer.

Ursolic acid and most of its derivatives are cytotoxic to bladder cancer cells. An ursolic acid derivative, isopropyl 3ß-hydroxyurs-12-en-28-oat (UA17), previously reported that it exhibited potent cytotoxicity against bladder cancer cells, NTUB1 cells. In this study, we further investigated the underlying mechanism of UA17 and evaluated its potential clinical use. UA17 may exert the onset of a p53-mediated p38 MAPK activation to up-regulate GADD153. GADD153, in turn, down-regulated Bcl-2 protein to cause mitochondrial membrane potential loss and apoptosis through intracellular ROS generation. In addition, UA17 markedly decreased the levels of cyclins (D1 and E), cyclin-dependent kinases (CDK2 and CDK4), and caused increase of p21 and p27 levels. To assess the suitability of UA17 as a chemotherapeutic agent against NTUB1 cells, its cytotoxic effects have been further evaluated in the combination with cisplatin. The addition of UA17 to cisplatin induces possibly additive cell growth inhibition which correlated to the accumulation of S phase cells and a corresponding decrease in accumulation of G1 phase cells, accompanied an increased accumulation of sub-G1 phase cells. Furthermore, UA17/cisplatin combination exhibited increase of p21, cyclin E, and p-p53 level, and decrease of p27 and cyclin D1 proteins, and slightly diminishing the level of CDK2. P-p38 up-regulation induced by UA17/cisplatin combination through generation of ROS and Bcl-2 down-regulation induced by UA17/cisplatin combination increased cell death. Finally, the antitumorigenic effects of UA17 or UA17/cisplatin combination were further supported by their inhibition on growth of bladder tumor cells in a therapeutic murine MBT-2 bladder tumor model.

Lantabetulic acid derivatives induce G1 arrest and apoptosis in human prostate cancer cells.

Ten new lantabetulic acid (1) derivatives 2-11 were synthesized and their cytotoxicities against human prostate cancer cells were evaluated. PC3 cells treated with 10 µM 8 exhibited the most potent G1 phase arrest. In addition, 10 µM 8 markedly decreased the levels of cyclin E and cdk2 and caused an increase in the p21 and p27 levels, while 20 µM 8 mainly led to cell death through the apoptotic pathway, which correlated with an increase in reactive oxygen species levels, decreased expression levels of Bcl-2 and caspase-8, the induction of mitochondrial changes, and decreased levels of cytochrome c in mitochondria. The dual action of 8 could provide a new approach for the development of chemotherapeutic drugs.

Xanthine oxidase inhibitory lanostanoids from Ganoderma tsugae.

Two new lanostanoids, 3α-acetoxy-22-oxo-5α-lanosta-8,24-dien-21-oic acid, named tsugaric acid D (1) and 16α-hydroxy-3-oxo-5α-lanosta-6,8,24(24(1))-trien-21-oic acid, named tsugaric acid E (2) were isolated from the fruit bodies of Ganoderma tsugae. The structures 1 and 2 were determined by spectroscopic methods. Compound 1 and known compounds 3 and 6 exhibited significant inhibitory effects on xanthine oxidase (XO) activity with an IC50 values of 90.2±24.2, 116.1±3.0, and 181.9±5.8 µM, respectively. Known compound 5 was able to protect human keratinocytes against damage induced by UVB light, which showed 5 could protect keratinocytes from photodamage. The 1 and 5 µM 1 combined with 5 µM cisplatin, respectively, enhanced the cytotoxicity induced by cisplatin. It suggested that 1 and 5 µM 1 combined with low dose of cisplatin may enhance the therapeutic efficacy of cisplatin and reduce side effect and cisplatin resistant.

Cytotoxic and antioxidant constituents from Garcinia subelliptica.

Two new triterpenoids, garcinielliptones Q (1) and S (3), and a new phloroglucinol, garcinielliptone R (2), were isolated from the seed of Garcinia subelliptica. Their structures were established by analysis of their spectroscopic data. Phloroglucinol, garcinielliptone FC (4) from this plant exhibited a significant increase of antiproliferative effect, while 4 combined with cisplatin significantly caused decrease of cell inhibition induced by cisplatin in NTUB1. Exposure of NTUB1 cells to 4 cotreated with cisplatin for significantly decreased the amount of reactive oxygen species (ROS) than that of the total amount generated by 4 and cisplatin. These results suggested that 4 could protect the cisplatin toxicity through reduction of ROS in NTUB1. Phloroglucinols, garcinielliptones, A (5) and F (7), and garsubelline A (6), from this plant, revealed ABTS radical cation scavenging activity and 5 displayed an inhibitory effect on xanthine oxidase. These finding showed that 5-7 may be used as antioxidants.

18ß-Glycyrrhetinic acid derivatives induced mitochondrial-mediated apoptosis through reactive oxygen species-mediated p53 activation in NTUB1 cells.

Twenty six 18ß-glycyrrhetinic acid (GA) (1) derivatives 2-27 including twelve new GA derivatives 10, 11, 13-17, 21-25 were synthesized and evaluated for cytotoxicities against NTUB1 cells (human bladder cancer cell lines). seco-Compounds 9, 25, and 27 are the most potent compounds of this series, inhibiting cell growth of human NTUB1 cells with an IC(50) values of 2.34 ± 0.28, 4.76 ± 1.15, and 3.31 ± 0.61 µM, respectively. Exposure of NTUB1 to 25 for 24h significantly increased the production of reactive oxygen species (ROS). Flow cytometric analysis exhibited that treatment of NTUB1 with 25 did not induce cell cycle arrest but accompanied by an increase of apoptotic cell death in a dose-dependant manner after 24h. Mitochondrial membrane potential (MMP) decreased significantly in a dose-dependant manner when the NTUB1 cells were exposed to 25 for 24h. Marked collapse of the MMP suggested that dysfunction of the mitochondria may be involved in the oxidative burst and apoptosis induced by 25. Western blot analysis shows that NTUB1 cells treated with 25 increased the level of p-p53 in a dose-dependant manner. Further, NAC treatment prevented p53 phosphorylation stimulated by 25. These results suggested that 25 induced a mitochondrial-mediated apoptosis in NTUB1 cells through activation of p53, which are mainly mediated ROS generated by 25.

Antioxidant constituents from the stems and fruits of Momordica charantia.

A new cucurbitane-type triterpene glycoside taiwacin A (1), a new 23,24,25,26,27-pentanorcucurbitane, taiwacin B (2) and a known cucurbitane-type triterpene glycoside (3), and a known steroid glycoside (4), were isolated from the stems and fruits of Momordica charantia, respectively. The structure of new compound was elucidated by spectroscopic methods. These four compounds, 1, 2, 3 and 4 revealed ABTS radical cation scavenging activity with an IC(50) values of 119.1±4.3, 204.5±1.2, 159.7±11.0 and 98.1±2.4µM, respectively. Compounds 1 and 3 displayed an inhibitory effect on xanthine oxidase (XO) activity with IC(50) values of 24.1±3.4 and 158.3±35.6µM, respectively. Compounds 2-4 significantly displayed O(2)(-) scavenging activity with an IC(50) values of 12.5±2.2, 16.5±0.1 and 27.3±1.4µM, respectively and the relative oxygen radical absorbance capacity (ORAC) values of 2 and 3, using ORAC-pyrogallol red (PGR) assay, were determined to be 0.88±0.02 and 0.55±0.09, respectively. These findings showed that 1-4 may be used as antioxidants.