Inhibitory mechanisms of decoy receptor 3 in cecal ligation and puncture-induced sepsis.

Despite its high mortality, specific and effective drugs for sepsis are lacking. Decoy receptor 3 (DcR3) is a potential biomarker for the progression of inflammatory diseases. The recombinant human DcR3-Fc chimera protein (DcR3.Fc) suppresses inflammatory responses in mice with sepsis, which is critical for improving survival. The Fc region can exert detrimental effects on the patient, and endogenous peptides are highly conducive to clinical application. However, the mechanisms underlying the effects of DcR3 on sepsis are unknown. Herein, we aimed to demonstrate that DcR3 may be beneficial in treating sepsis and investigated its mechanism of action. Recombinant DcR3 was obtained in vitro. Postoperative DcR3 treatment was performed in mouse models of lipopolysaccharide- and cecal ligation and puncture (CLP)-induced sepsis, and their underlying molecular mechanisms were explored. DcR3 inhibited sustained excessive inflammation in vitro, increased the survival rate, reduced the proinflammatory cytokine levels, changed the circulating immune cell composition, regulated the gut microbiota, and induced short-chain fatty acid synthesis in vivo. Thus, DcR3 protects against CLP-induced sepsis by inhibiting the inflammatory response and apoptosis. Our study provides valuable insights into the molecular mechanisms associated with the protective effects of DcR3 against sepsis, paving the way for future clinical studies. IMPORTANCE: Sepsis affects millions of hospitalized patients worldwide each year, but there are no sepsis-specific drugs, which makes sepsis therapies urgently needed. Suppression of excessive inflammatory responses is important for improving the survival of patients with sepsis. Our results demonstrate that DcR3 ameliorates sepsis in mice by attenuating systematic inflammation and modulating gut microbiota, and unveil the molecular mechanism underlying its anti-inflammatory effect.

Research progress on alternative kombucha substrate transformation and the resulting active components.

Kombucha is a customary tea-based beverage that is produced through the process of fermenting a mixture of tea and sugar water with symbiotic culture of bacteria and yeast (SCOBY). Traditional kombucha has various beneficial effects and can improve immunity. The significant market share of Kombucha can be attributed to the growing consumer inclination towards healthy foods within the functional beverage industry. The research focus has recently expanded from the probiotics of traditional black tea kombucha to encompass other teas, Chinese herbs, plant materials, and alternative substrates. There is a lack of comprehensive literature reviews focusing on substance transformation, functional, active substances, and efficacy mechanisms of alternative kombucha substrates. This article aimed to bridge this gap by providing an in-depth review of the biological transformation pathways of kombucha metabolites and alternative substrates. The review offers valuable insights into kombucha research, including substance metabolism and transformation, efficacy, pharmacological mechanism, and the purification of active components, offering direction and focus for further studies in this field.

Fucoxanthin Ameliorates Sepsis via Modulating Microbiota by Targeting IRF3 Activation.

To improve patient survival in sepsis, it is necessary to curtail exaggerated inflammatory responses. Fucoxanthin (FX), a carotenoid derived from brown algae, efficiently suppresses pro-inflammatory cytokine expression via IRF3 activation, thereby reducing mortality in a mouse model of sepsis. However, the effects of FX-targeted IRF3 on the bacterial flora (which is disrupted in sepsis) and the mechanisms by which it impacts sepsis development remain unclear. This study aims to elucidate how FX-targeted IRF3 modulates intestinal microbiota compositions, influencing sepsis development. FX significantly reduced the bacterial load in the abdominal cavity of mice with cecal ligation and puncture (CLP)-induced sepsis via IRF3 activation and increased short-chain fatty acids, like acetic and propionic acids, with respect to their intestines. FX also altered the structure of the intestinal flora, notably elevating beneficial Verrucomicrobiota and Akkermansia spp. while reducing harmful Morganella spp. Investigating the inflammation-flora link, we found positive correlations between the abundances of Morganella spp., Proteus spp., Escherichia spp., and Klebsiella spp. and pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α) induced by CLP. These bacteria were negatively correlated with acetic and propionic acid production. FX alters microbial diversity and promotes short-chain fatty acid production in mice with CLP-induced sepsis, reshaping gut homeostasis. These findings support the value of FX for the treatment of sepsis.

Research Progress on Natural Small-Molecule Compounds for the Prevention and Treatment of Sepsis.

Sepsis is a serious disease with high mortality and has been a hot research topic in medical research in recent years. With the continuous reporting of in-depth research on the pathological mechanisms of sepsis, various compounds have been developed to prevent and treat sepsis. Natural small-molecule compounds play vital roles in the prevention and treatment of sepsis; for example, compounds such as resveratrol, emodin, salidroside, ginsenoside, and others can modulate signaling through the NF-κB, STAT3, STAT1, PI3K, and other pathways to relieve the inflammatory response, immunosuppression, and organ failure caused by sepsis. Here, we discuss the functions and mechanisms of natural small-molecule compounds in preventing and treating sepsis. This review will lay the theoretical foundation for discovering new natural small-molecule compounds that can potentially prevent and treat sepsis.

Research Progress of DcR3 in the Diagnosis and Treatment of Sepsis.

Decoy receptor 3 (DcR3), a soluble glycosylated protein in the tumor necrosis factor receptor superfamily, plays a role in tumor and inflammatory diseases. Sepsis is a life-threatening organ dysfunction caused by the dysregulation of the response to infection. Currently, no specific drug that can alleviate or even cure sepsis in a comprehensive and multi-level manner has been found. DcR3 is closely related to sepsis and considerably upregulated in the serum of those patients, and its upregulation is positively correlated with the severity of sepsis and can be a potential biomarker for diagnosis. DcR3 alone or in combination with other markers has shown promising results in the early diagnosis of sepsis. Furthermore, DcR3 is a multipotent immunomodulator that can bind FasL, LIGHT, and TL1A through decoy action, and block downstream apoptosis and inflammatory signaling. It also regulates T-cell and macrophage differentiation and modulates immune status through non-decoy action; therefore, DcR3 could be a potential drug for the treatment of sepsis. The application of DcR3 in the treatment of a mouse model of sepsis also achieved good efficacy. Here, we introduce and discuss the progress in, and suggest novel ideas for, research regarding DcR3 in the diagnosis and treatment of sepsis.

Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial.

Importance: Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection. Objective: To evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection. Design, Setting, and Participants: This was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020). Interventions: EC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years. Results: Among 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, -3.6% [95% CI, -10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, -5.4% [95% CI, -12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, -0.2% to 4.0%]; P = .08). Conclusions and Relevance: Among patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01758614.

Research Progress of Macromolecules in the Prevention and Treatment of Sepsis.

Sepsis is associated with high rates of mortality in the intensive care unit and accompanied by systemic inflammatory reactions, secondary infections, and multiple organ failure. Biological macromolecules are drugs produced using modern biotechnology to prevent or treat diseases. Indeed, antithrombin, antimicrobial peptides, interleukins, antibodies, nucleic acids, and lentinan have been used to prevent and treat sepsis. In vitro, biological macromolecules can significantly ameliorate the inflammatory response, apoptosis, and multiple organ failure caused by sepsis. Several biological macromolecules have entered clinical trials. This review summarizes the sources, efficacy, mechanism of action, and research progress of macromolecular drugs used in the prevention and treatment of sepsis.

Advances in Fucoxanthin Research for the Prevention and Treatment of Inflammation-Related Diseases.

Owing to its unique structure and properties, fucoxanthin (FX), a carotenoid, has attracted significant attention. There have been numerous studies that demonstrate FX's anti-inflammatory, antioxidant, antitumor, and anti-obesity properties against inflammation-related diseases. There is no consensus, however, regarding the molecular mechanisms underlying this phenomenon. In this review, we summarize the potential health benefits of FX in inflammatory-related diseases, from the perspective of animal and cellular experiments, to provide insights for future research on FX. Previous work in our lab has demonstrated that FX remarkably decreased LPS-induced inflammation and improved survival in septic mice. Further investigation of the activity of FX against a wide range of diseases will require new approaches to uncover its molecular mechanism. This review will provide an outline of the current state of knowledge regarding FX application in the clinical setting and suggest future directions to implement FX as a therapeutic ingredient in pharmaceutical sciences in order to develop it into a treatment strategy against inflammation-associated disorders.

A double scrambling-DNA row and column closed loop image encryption algorithm based on chaotic system.

In this paper, a dynamic update algorithm of double scrambling-DNA row and column closed loop based on chaotic system is proposed. The classical scrambling and diffusion structure are used in the whole process. In the scrambling stage, a new pixel reconstruction method is proposed by combining the Hilbert curve with Knuth-Durstenfeld shuffle algorithm to overcome the shortcoming of nearby storage of Hilbert curve. This method reconstructs the pixel matrix of one-dimensional vector according to the Hilbert curve coding method, and achieves good scrambling effect, while reducing its time complexity and space complexity. In the diffusion stage, combining the plaintext row, the ciphertext row and the key row, and taking advantage of the parallel computing power and high storage density of the DNA encoding, the existing block diffusion operation is improved, and the two-round diffusion of the DNA encoding is proposed. When the last line of ciphertext is generated, the first line of ciphertext is updated and the closed-loop dynamic update of the encryption system is realized. Finally, SHA-256 is used to give the secret key and calculate the initial value of the chaotic system. The simulation results show that the "double scrambling-DNA row and column closed loop dynamic" update algorithm proposed in this paper can effectively improve the efficiency of information transmission and have high security.

China Intracranial Aneurysm Project (CIAP): protocol for a prospective cohort study of interventional treatment and craniotomy for unruptured aneurysms.

INTRODUCTION: There are two approaches for the treatment of intracranial aneurysm (IA): interventional therapy and craniotomy, both of which have their advantages and disadvantages in terms of treatment efficacy. To avoid overtreatment of unruptured aneurysms (UIA), to save valuable medical resources and to reduce patient mortality and disability rate, it is vital that neurosurgeons select the most appropriate type of treatment to provide the best levels of care. In this study, we propose a refined, prospective, multicentre study for the Chinese population with strictly defined patient inclusion criteria, along with the selection of representative clinical participating centres. METHODS AND ANALYSIS: This report describes a multicentre, prospective cohort study. As IA is extremely harmful if it ruptures, ethical issues need to be taken into account with regard to this study. Researchers are therefore not able to use randomised controlled trials. The study will be conducted by 12 clinical centres located in different regions of China. The trial recruitment programme begins in 2016 and is scheduled to be completed in 2020. We expect 1500 participants with UIA to be included. Clinical information relating to the participants will be recorded objectively. The primary endpoints are an evaluation of the safety and efficiency of interventional treatment and craniotomy for 6 months after surgery, with each participant completing at least 1 year of follow-up. The secondary endpoint is the evaluation of safety and efficacy of interventional therapy and craniotomy clipping when participants are treated for 12 months. We also address the success of treatment and the incidence of adverse events. ETHICS AND DISSEMINATION: The research protocol and the informed consent form for participants in this study were approved by the Ethics Committee of Zhujiang Hospital of Southern Medical University (2017-SJWK-001). The results of this study are expected to be disseminated in peer-reviewed journals in 2021. TRIAL REGISTRATION NUMBER: NCT03133598.

[The application of rhinoscope in microsurgical treatment of intracranial aneurysms intraoperative clinical research].

This paper analysed the rhinoscope's clinical value in microsurgical treatment of intracranial aneurysms. Application of the rhinoscope in 87 patients, only 2 patients had ruptured during operation. However, 11 cases had ruptured in 94 cases without using rhinoscope, P < 0.05, they had a significant difference. By DSA follow-up review, 82 cases of used rhinoscope only 2 cases had remained the aneurysm neck, but 9 cases had the aneurysm neck in 77 cases which had not used the rhinoscope in the microsurgical treatment, P < 0.05, they also had significant difference. The application of rhinoscope in microsurgical treatment of intracranial aneurysms intraoperative, can reduce the risk of the intraoperative aneurysm rupture. It can achieve better clinical effect.

Intraoperative assessment of anterior circulation aneurysms using the indocyanine green video angiography technique.

We performed a prospective study to evaluate the intraoperative value of indocyanine green (ICG) video angiography in anterior circulation aneurysms. From January 2007 to April 2008, 42 patients with anterior circulation aneurysms who were to undergo aneurysm clipping were enrolled in the study. Intraoperative ICG video angiography was performed using a fluorescence microscope. After the operation, three-dimensional CT angiography (CTA), digital substraction angiography (DSA) and magnetic resonance angiography (MRA) were used to evaluate the use of intraoperative ICG video angiography. Of the 42 patients, on ICG video angiography after initial clip placement, neck remnants of the aneurysm were found in two patients, inadvertent clipping of branching vessels in one patient, and inadvertent clipping of perforating vessels in two patients. ICG video angiography after adjustment of the clip position showed a perfect residual elimination with no abnormal findings. Post-operative DSA, CTA and MRA results corresponded to the intraoperative ICG video angiography findings. Therefore, ICG video angiography is an important tool to monitor residual aneurysm, parent artery stenosis or perforating artery occlusion during intracranial aneurysm clipping.

Significant improvement of visual functions after removal of an intracranial giant optic nerve glioma revealing exophytic growth: case report.

OBJECTIVE AND IMPORTANCE: Intracranial giant optic nerve gliomas, usually presumed as optic chiasmatic gliomas, are much less common. The architectural tumor form of optic nerve glioma without neurofibromatosis type 1 is usually the expansile-intraneural pattern. The exophytic optic nerve gliomas without neurofibromatosis type 1 are relatively uncommon. Surgical decompression for intracranial optic gliomas frequently leads to clinical improvement, but obvious improvement of vision is rare. We report a case that demonstrated significant recovery of visual function after removal of the intracranial giant optic nerve glioma, revealing exophytic growth. CLINICAL PRESENTATION: A 13-year-old boy presented with visual impairment in both eyes. Magnetic resonance images (MRI) disclosed a 6 cm diameter mass in the suprasellar area. On heavily T2-reversed MRIs, it was obvious that the intracranial portion of right optic nerve was enlarged, and optic tracts were shifted to the left by the tumor. The relationship of the tumor to the chiasma could not be affirmed on MRIs. INTERVENTION: A right frontotemporal craniotomy for decompression of the optic apparatus was performed. After the majority of the tumor was resected, it became clear that the tumor originated in the right optic nerve. The tumor exophytically grew and dislocated the optic chiasma and optic tracts. Significant improvement of visual functions began from the first week after surgery and continued gradually thereafter. The histological diagnosis was pilocytic astrocytoma. A follow-up MRI taken 4 years after surgery showed no regrowth of the residual tumor. CONCLUSION: Giant exophytic gliomas without neurofibromatosis type 1 may arise from the intracranial portion of an isolated optic nerve. Direct visualization of optic component by heavily T2-reversed MRI could more precisely delineate the relationship of the intracranial optic nerve glioma to the optic apparatus. Surgery may be indicated in giant exophytic intracranial optic nerve gliomas and preoperative postulated optic chiasmatic gliomas. Microsurgical resection can induce postoperative visual improvement without regrowth of the residual tumor.

Proton magnetic resonance spectroscopy of normal human brain and glioma: a quantitative in vivo study.

BACKGROUND: In vivo proton magnetic resonance spectroscopy (MRS) provides a noninvasive method of examining a wide variety of cerebral metabolites in both healthy subjects and patients with various brain diseases. Absolute metabolite concentrations have been determined using external and internal standards with known concentrations. When an external standard is placed beside the head, variations in signal amplitudes due to B1 field inhomogeneity and static field inhomogeneity may occur. Hence an internal standard is preferable. The purpose of this study was to quantitatively analyze the metabolite concentrations in normal adult brains and gliomas by in vivo proton MRS using the fully relaxed water signal as an internal standard. METHODS: Between January 1998 and October 2001, 28 healthy volunteers and 16 patients with gliomas were examined by in vivo proton MRS. Single-voxel spectra were acquired using the point-resolved spectroscopic pulse sequence with a 1.5 T scanner (TR/TE/Ave = 3000 ms/30 ms/64). RESULTS: The calculated concentrations of N-acetyl-asparatate (NAA), creatine (Cre), choline (Cho), and water (H2O) in the normal hemispheric white matter were (23.59 +/- 2.62) mmol/L, (13.06 +/- 1.8) mmol/L, (4.28 +/- 0.8) mmol/L, and (47,280.96 +/- 5414.85) mmol/L, respectively. The metabolite concentrations were not necessarily uniform in different parts of the brain. The concentrations of NAA and Cre decreased in all gliomas (P < 0.001). The ratios of NAA/Cho and NAA/H2O showed a significant difference between the normal brain and gliomas, and also between the high and low grades (P < 0.001). CONCLUSIONS: Quantitative analysis of in vivo proton MR spectra using the fully relaxed water signal as an internal standard is useful. The concentrations of NAA and the ratios of NAA/H2O and NAA/Cho conduce to discriminating between the glioma and normal brain, and also between the low-grade glioma and high-grade glioma.

In vivo quantification of the metabolites in normal brain and brain tumors by proton MR spectroscopy using water as an internal standard.

Metabolite concentrations in normal adult brains and in gliomas were quantitatively analyzed by in vivo proton magnetic resonance spectroscopy (MRS) using the fully relaxed water signal as an internal standard. Between January 1998 and October 2001, 28 healthy volunteers and 18 patients with gliomas were examined by in vivo proton MRS. Single voxel spectra were acquired using the point-resolved spectroscopic pulse sequence with a 1.5-T scanner (TR/TE/Ave = 3000 ms/30 ms/64). The calculated concentrations of N-acetyl-aspartate (NAA), creatine (Cre), choline (Cho), and water (H2O) in the normal hemispheric white matter were 23.59 +/- 2.62 mM (mean +/- SD), 13.06 +/- 1.8 mM, 4.28 +/- 0.8 mM, and 47280.96 +/- 5414.85 mM, respectively. The metabolite concentrations were not necessarily uniform in different parts of the brain. The concentrations of NAA and Cre decreased in all gliomas (p < 0.001). The NAA/Cho and NAA/H2O ratios can distinguish the normal brain from gliomas, and low-grade astrocytoma from high-grade group (p < 0.001). The concentration of taurine (Tau) in medulloblastomas was 29.64 +/- 5.76 mM. This is the first quantitative analysis of Tau in medulloblastoma in vivo and confirms earlier in vitro findings.

In vivo quantification of the metabolites in normal brain and brain tumors by proton MR spectroscopy using water as an internal standard.

Metabolite concentrations in normal adult brains and in gliomas were quantitatively analyzed by in vivo proton magnetic resonance spectroscopy (MRS) using the fully relaxed water signal as an internal standard. Between January 1998 and October 2001, 28 healthy volunteers and 18 patients with gliomas were examined by in vivo proton MRS. Single-voxel spectra were acquired using the point-resolved spectroscopic (PRESS) pulse sequence with a 1.5 T scanner (TR/TE/Ave = 3000 ms/30 ms/64). The calculated concentrations of N-acetyl-aspartate (NAA), creatine (Cre), choline (Cho), and water(H(2)O) in the normal hemispheric white matter were 23.59 +/- 2.62 mM (mean +/- SD), 13.06 +/- 1.8 mM, 4.28 +/- 0.8 mM, and 47280.96 +/- 5414.85 mM, respectively. The metabolite concentrations were not necessarily uniform in different parts of the brain. The concentrations of NAA and Cre decreased in all gliomas (p < 0.001). The NAA/Cho and NAA/H(2)O ratios can distinguish the normal brain from gliomas and low-grade from high-grade astrocytoma (p < 0.001). The concentration of taurine (Tau) in medulloblastomas was 29.64 +/- 5.76 mM. This is the first quantitative analysis of Tau in medulloblastoma in vivo and confirms earlier in vitro findings.

[Value and economic analysis of emergency endoscopy in the diagnosis and treatment of massive upper gastrointestinal hemorrhage].

OBJECTIVE: To study the application value of emergency endoscopy in the diagnosis and treatment of massive upper gastrointestinal hemorrhage, and to evaluated by the economic analysis whether the emergency endoscopy was safe and effective,or shorten the hospitalization days and reduced the medical costs. METHODS: Ninety-one patients with massive upper gastrointestinal hemorrhage were randomly divided into emergency endoscopy group (group A) and non-emergency endoscopy group (group B). The patients in group A underwent endoscopy as soon as the blood pressures were normal and the patients of group B underwent endoscopy at 24-48 hours after hospitalization. They would be treated depending on the conditions by endoscopy. Then the correct diagnosis rates, rebleeding rates, complication rates, mean hospitalization days, the endoscopy costs, the blood transfusion costs, the drugs costs and the total hospitalization costs of two groups were evaluated and the cost-effect ratio (C/E) was calculated. RESULTS: The correct diagnosis rates and the endoscopy costs of group A were higher than the group B (100.0 percent vs.90.2 percent, P<0.05; (714.78+/-263.54) yuan vs. (383.57+/-251.72) yuan, P<0.01), and the rebleeding rates, the mean hospitalizations days, the blood transfusion costs and the drugs costs and the total hospitalization costs were all lower compared to the group B (6.1 percent vs. 26.8 percent, P<0.05; (5.42+/-1.70) days vs. (8.51+/-2.30) days, P<0.01; (791.80+/-258.35) yuan vs. (1270.29+/-569.21) yuan, P<0.01; (945.22+/-125.82) yuan vs. (1223.81+/-254.44) yuan, P<0.01; (2785.76+/-353.26) yuan vs. (3 527.76+/-555.62)yuan, P<0.01. The C/E of group A was lower than the group B (2785.76 yuan per patient vs. 3527.76 yuan per patient, P<0.01). CONCLUSION: Emergency endoscopy is not only safe and effective but also economical in the diagnosis and treatment of massive upper gastrointestinal hemorrhage.