Complement inhibition alleviates donor brain death-induced liver injury and posttransplant cascade injury by regulating phosphoinositide 3-kinase signaling.

Brain death (BD) donors are the primary source of donor organs for liver transplantation. However, the effects of BD on donor livers and outcomes after liver transplantation remain unclear. Here, we explored the role of complement and the therapeutic effect of complement inhibition in BD-induced liver injury and posttransplantation injury in a mouse BD and liver transplantation model. For complement inhibition, we used complement receptor 2 (CR2)-Crry, a murine inhibitor of C3 activation that specifically targets sites of complement activation. In the mouse model, BD resulted in complement activation and liver injury in donor livers and a cascade liver injury posttransplantation, mediated in part through the C3a-C3aR (C3a receptor) signaling pathway, which was ameliorated by treatment with CR2-Crry. Treatment of BD donors with CR2-Crry improved graft survival, which was further improved when recipients received an additional dose of CR2-Crry posttransplantation. Mechanistically, we determined that complement inhibition alleviated BD-induced donor liver injury and posttransplant cascade injury by regulating phosphoinositide 3-kinase (PI3K) signaling pathways. Together, BD induced donor liver injury and cascade injury post-transplantation, which was mediated by complement activation products acting on PI3K signaling pathways. Our study provides an experimental basis for developing strategies to improve the survival of BD donor grafts in liver transplantation.

Distance and depth modulation of Talbot imaging via specified design of the grating structure.

For positioning Talbot encoder and Talbot lithography, etc., properties manipulation of Talbot imaging is highly expected. In this work, an investigation on the distance and depth modulation of Talbot imaging, which employs a specially designed grating structure, is presented. Compared with the current grating structure, the proposed grating structure is characterized by having the phase layers with uneven thicknesses. Such a specific structural design can cause the offset of Talbot image from its nominal position, which in turn generates the spatial distance modulation of self-imaging and imaging depth expansion. Theoretical analysis is performed to explain its operating principle, and simulations and experiments are carried out to demonstrate its effectiveness.

Multidomain Oriented Particle Chains Based on Spatial Electric Field and Their Optical Application.

The manipulation technology of particles is significant in drug screening, disease detection and treatment, etc. Here, we reported the multidomain oriented particle chains based on a spatial electric field and their optical application. According to the differences in the dielectric behavior of particles, the preparation of multidomain oriented particle chains in the gel was successfully realized by using the dielectrophoretic force and electroosmotic rotation. This provides a new idea for manufacturing multistructure, multilayer, and multifunctional intelligent response materials. In addition, the factors affecting the alignment height of the particles in the gel were discussed, which was the basis for the preparation of bilayer particle chains. As an example of structural hierarchy, particle assembly has broad application prospects in optoelectronic devices and soft robots.

Natural immunoglobulin M initiates an inflammatory response important for both hepatic ischemia reperfusion injury and regeneration in mice.

Complement plays a role in both hepatic ischemia reperfusion (IR) injury (IRI) and liver regeneration, but it is not clear how complement is activated in either process. We investigated the role of self-reactive immunoglobulin M (IgM) antibodies in activating complement after hepatic IR and liver resection. Natural IgM antibodies that recognize danger-associated molecular patterns (neoepitopes) activate complement following both hepatic IR and liver resection. Antibody-deficient Rag1-/- mice were protected from hepatic IRI, but had increased hepatic injury and an impaired regenerative response after 70% partial hepatectomy (PHx). We identified two IgM monoclonal antibodies (mAbs) that specifically reversed the effect of Rag1 deficiency in both models; B4 (recognizes Annexin IV) and C2 (recognizes subset of phospholipids). Focusing on the B4-specific response, we demonstrated sinusoidal colocalization of IgM and C3d in Rag1-/- mice that were reconstituted with B4 mAb, and furthermore that the Annexin IV neoepitope is specifically and similarly expressed after both hepatic IR and PHx in wild-type (WT) mice. A single-chain antibody construct (scFv) derived from B4 mAb blocked IgM binding and reduced injury post-IR in WT mice, although, interestingly, B4scFv did not alter regeneration post-PHx, indicating that anti-Annexin IV antibodies are sufficient, but not necessary, for the regenerative response in the context of an entire natural antibody repertoire. We also demonstrated expression of the B4 neoepitope in postischemic human liver samples obtained posttransplantation and a corollary depletion in IgM recognizing the B4 and C2 neoepitopes in patient sera following liver transplantation. Conclusion: These data indicate an important role for IgM in hepatic IRI and regeneration, with a similar cross-species injury-specific recognition system that has implications for the design of neoepitope targeted therapeutics. (Hepatology 2018;67:721-735).

Donor pretreatment with nebulized complement C3a receptor antagonist mitigates brain-death induced immunological injury post-lung transplant.

Donor brain death (BD) is an inherent part of lung transplantation (LTx) and a key contributor to ischemia-reperfusion injury (IRI). Complement activation occurs as a consequence of BD in other solid organ Tx and exacerbates IRI, but the role of complement in LTx has not been investigated. Here, we investigate the utility of delivering nebulized C3a receptor antagonist (C3aRA) pretransplant to BD donor lungs in order to reduce post-LTx IRI. BD was induced in Balb/c donors, and lungs nebulized with C3aRA or vehicle 30 minutes prior to lung procurement. Lungs were then cold stored for 18 hours before transplantation into C57Bl/6 recipients. Donor lungs from living donors (LD) were removed and similarly stored. At 6 hours and 5 days post-LTx, recipients of BD donor lungs had exacerbated IRI and acute rejection (AR), respectively, compared to recipients receiving LD lungs, as determined by increased histopathological injury, immune cells, and cytokine levels. A single pretransplant nebulized dose of C3aRA to the donor significantly reduced IRI as compared to vehicle-treated BD donors, and returned IRI and AR grades to that seen following LD LTx. These data demonstrate a role for complement inhibition in the amelioration of IRI post-LTx in the context of donor BD.

Overexpression of Yes-associated protein and its association with clinicopathological features of hepatocellular carcinoma: A meta-analysis.

BACKGROUND: Yes-associated protein (YAP) overexpression is reported to be associated with risk of hepatocellular carcinoma (HCC) but current studies have not explored the relationship between YAP expression with HCC clinicopathological features. METHODS: To assess these associations, a meta-analysis was performed which included four eligible studies including 391 HCC cases and 334 controls. There were eight eligible studies to investigate the association between YAP expression in HCC and clinicopathological features of liver cancer patients. Literature was obtained from PubMed, Embase, Wangfang and China National Knowledge Infrastructure. RESULTS: Analysis indicated that YAP expression in HCC was greater than in adjacent non-tumour tissue (odds ratio [OR], 15.80, 95% confidence interval [CI], 10.53-23.70, P<.00001; heterogeneity=.30). YAP overexpression in HCC was significantly associated with vascular invasion (OR, 2.21, 95% CI, 11.64-2.97, P<.00001, heterogeneity=.10), less cellular differentiation (OR, 2.38, 95% CI, 1.61-3.51, P<.00001, heterogeneity=.333), tumours larger than 5 cm (OR, 2.52, 95% CI, 1.75-3.62, P<.00001; heterogeneity=.17) and TNM tumour stage I + II (OR, 0.44, 95% CI, 0.28-0.75, P=.00003, heterogeneity=.12). CONCLUSIONS: Overexpression of YAP contributes to HCC formation, and its overexpression is associated with vascular invasion, low cellular differentiation tumours larger than 5 cm and TNM tumour stage III + IV.

HOXA7 plays a critical role in metastasis of liver cancer associated with activation of Snail.

BACKGROUND: Liver cancer is one of the main causes of cancer-related death in human. HOXA7 has been proved to be related with several cancers. METHOD: The expression levels of HOXA7 were examined by Western blot, qRT-PCR or ICH. MTT was used to detect the proliferative rate of liver cancer cells. The invasive abilities were examined by matrigel and transwell assay. The metastatic abilities of liver cancer cells were revealed in BALB/c nude mice. RESULTS: In this report, we revealed that HOXA7 promoted metastasis of HCC patients. First, increased levels of HOXA7 were examined in liver cancer especially in metastatic liver cancer. Moreover, higher expression level of HOXA7 was associated with poorer prognosis of liver cancer patients. Overexpression of HOXA7 significantly enhanced proliferation, migration, invasion in vitro and tumor growth and metastasis in vivo meanwhile silencing HOXA7 significantly inhibited the aboves abilities of liver cancer cells. In this research, we identified that HOXA7 performed its oncogenic characteristics through activating Snail. CONCLUSION: Collectively, we identify the critical role and possible mechanism of HOXA7 in metastasis of liver cancer which suggest that HOXA7 may be a potential therapeutic target of liver cancer patients.

C-reactive protein to albumin ratio predict responses to programmed cell death-1 inhibitors in hepatocellular carcinoma patients.

BACKGROUND: Over the years, programmed cell death-1 (PD-1) inhibitors have been routinely used for hepatocellular carcinoma (HCC) treatment and yielded improved survival outcomes. Nonetheless, significant heterogeneity surrounds the outcomes of most studies. Therefore, it is critical to search for biomarkers that predict the efficacy of PD-1 inhibitors in patients with HCC. AIM: To investigate the role of the C-reactive protein to albumin ratio (CAR) in evaluating the efficacy of PD-1 inhibitors for HCC. METHODS: The clinical data of 160 patients with HCC treated with PD-1 inhibitors from January 2018 to November 2022 at the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. RESULTS: The optimal cut-off value for CAR based on progression-free survival (PFS) was determined to be 1.20 using x-tile software. Cox proportional risk model was used to determine the factors affecting prognosis. Eastern Cooperative Oncology Group performance status [hazard ratio (HR) = 1.754, 95% confidence interval (95%CI) = 1.045-2.944, P = 0.033], CAR (HR = 2.118, 95%CI = 1.057-4.243, P = 0.034) and tumor number (HR = 2.932, 95%CI = 1.246-6.897, P = 0.014) were independent prognostic factors for overall survival. CAR (HR = 2.730, 95%CI = 1.502-4.961, P = 0.001), tumor number (HR = 1.584, 95%CI = 1.003-2.500, P = 0.048) and neutrophil to lymphocyte ratio (HR = 1.120, 95%CI = 1.022-1.228, P = 0.015) were independent prognostic factors for PFS. Two nomograms were constructed based on independent prognostic factors. The C-index index and calibration plots confirmed that the nomogram is a reliable risk prediction tool. The ROC curve and decision curve analysis confirmed that the nomogram has a good predictive effect as well as a net clinical benefit. CONCLUSION: Overall, we reveal that the CAR is a potential predictor of short- and long-term prognosis in patients with HCC treated with PD-1 inhibitors. If further verified, CAR-based nomogram may increase the number of markers that predict individualized prognosis.

Fei-Yan-Qing-Hua decoction decreases hyperinflammation by inhibiting HMGB1/RAGE signaling and promotes bacterial phagocytosis in the treatment of sepsis.

ETHNOPHARMACOLOGICAL RELEVANCE: Fei-Yan-Qing-Hua decoction (FYQHD), derived from the renowned formula Ma Xing Shi Gan tang documented in Zhang Zhong Jing's "Treatise on Exogenous Febrile Disease" during the Han Dynasty, has demonstrated notable efficacy in the clinical treatment of pneumonia resulting from bacterial infection. However, its molecular mechanisms underlying the therapeutic effects remains elusive. AIM OF THE STUDY: This study aimed to investigate the protective effects of FYQHD against lipopolysaccharide (LPS) and carbapenem-resistant Klebsiella pneumoniae (CRKP)-induced sepsis in mice and to elucidate its specific mechanism of action. MATERIALS AND METHODS: Sepsis models were established in mice through intraperitoneal injection of LPS or CRKP. FYQHD was administered via gavage at low and high doses. Serum cytokines, bacterial load, and pathological damage were assessed using enzyme-linked immunosorbent assay (ELISA), minimal inhibitory concentration (MIC) detection, and hematoxylin and eosin staining (H&E), respectively. In vitro, the immunoregulatory effects of FYQHD on macrophages were investigated through ELISA, MIC, quantitative real-time PCR (Q-PCR), immunofluorescence, Western blot, and a network pharmacological approach. RESULTS: The application of FYQHD in the treatment of LPS or CRKP-induced septic mouse models revealed significant outcomes. FYQHD increased the survival rate of mice exposed to a lethal dose of LPS to 33.3%, prevented hypothermia (with a rise of 3.58 °C), reduced pro-inflammatory variables (including TNF-α, IL-6, and MCP-1), and mitigated tissue damage in LPS or CRKP-induced septic mice. Additionally, FYQHD decreased bacterial load in CRKP-infected mice. In vitro, FYQHD suppressed the expression of inflammatory cytokines in macrophages activated by LPS or HK-CRKP. Mechanistically, FYQHD inhibited the PI3K/AKT/mTOR/4E-BP1 signaling pathway, thereby suppressing the translational level of inflammatory cytokines. Furthermore, it reduced the expression of HMGB1/RAGE, a positive feedback loop in the inflammatory response. Moreover, FYQHD was found to enhance the phagocytic activity of macrophages by upregulating the expression of phagocytic receptors such as CD169 and SR-A1. CONCLUSION: FYQHD provides protection against bacterial sepsis by concurrently inhibiting the inflammatory response and augmenting the phagocytic ability of immune cells.

Dehydrozaluzanin C- derivative protects septic mice by alleviating over-activated inflammatory response and promoting the phagocytosis of macrophages.

Host-directed therapy (HDT) is a new adjuvant strategy that interfere with host cell factors that are required by a pathogen for replication or persistence. In this study, we assessed the effect of dehydrozaluzanin C-derivative (DHZD), a modified compound from dehydrozaluzanin C (DHZC), as a potential HDT agent for severe infection. LPS-induced septic mouse model and Carbapenem resistant Klebsiella pneumoniae (CRKP) infection mouse model was used for testing in vivo. RAW264.7 cells, mouse primary macrophages, and DCs were used for in vitro experiments. Dexamethasone (DXM) was used as a positive control agent. DHZD ameliorated tissue damage (lung, kidney, and liver) and excessive inflammatory response induced by LPS or CRKP infection in mice. Also, DHZD improved the hypothermic symptoms of acute peritonitis induced by CRKP, inhibited heat-killed CRKP (HK-CRKP)-induced inflammatory response in macrophages, and upregulated the proportions of phagocytic cell types in lungs. In vitro data suggested that DHZD decreases LPS-stimulated expression of IL-6, TNF-α and MCP-1 via PI3K/Akt/p70S6K signaling pathway in macrophages. Interestingly, the combined treatment group of DXM and DHZD had a higher survival rate and lower level of IL-6 than those of the DXM-treated group; the combination of DHZD and DXM played a synergistic role in decreasing IL-6 secretion in sera. Moreover, the phagocytic receptor CD36 was increased by DHZD in macrophages, which was accompanied by increased bacterial phagocytosis in a clathrin- and actin-dependent manner. This data suggests that DHZD may be a potential drug candidate for treating bacterial infections.

Layered double hydroxide nanosheets-built porous film-covered Au nanoarrays as enrichment and enhancement chips for efficient SERS detection of trace styrene.

Styrene, a prevalent volatile organic compounds (VOCs), is very harmful to atmosphere and humans. Consequently, the development of efficient detection technologies for styrene is of high importance, which is still in challenge! In this work, we crafted a layered double hydroxide (LDH) porous film-coated gold nanoarray, designed to act as a surface enhanced Raman spectroscopy (SERS) chip for the efficient and portable detection of gaseous styrene. This chip features a covering layer composed of cross-linked LDH nanosheets, notable for their porous structure and high specific surface area. When the covering layer is 100-300 nm in thickness, this composite chip has significant enrichment effect and strong SERS performance to gaseous styrene with a lowest detectable concentration below 1 ppb (4.64 ×10-3 mg/m3), and can response within 10 s, showing the rapid response and high sensitivity. Additionally, the chip has strong anti-interference capabilities and maintains excellent response to styrene, even in mixed benzene-VOCs gases. The exceptional SERS performances of this chip is ascribed to its LDH covering layer-induced styrene-enrichment and structurally-enhanced SERS performances. This study provides a simple route and practical chip for the rapid and ultrasensitive SERS-based detection of gaseous styrene, which is also potentially beneficial for the detection of other gaseous VOCs.

Facile Synthesis of ZnO/WO3 Nanocomposite Porous Films for High-Performance Gas Sensing of Multiple VOCs.

Volatile organic compounds (VOCs) in indoor environments have typical features of multiple components, high concentration, and long duration. The development of gas sensors with high sensitivity to multiple VOCs is of great significance to protect human health. Herein, we proposed a sensitive ZnO/WO3 composite chemi-resistive sensor facilely fabricated via a sacrificial template approach. Based on the transferable properties of self-assembled monolayer colloidal crystal (MCC) templates, two-dimensional honeycomb-like ordered porous ZnO/WO3 sensing matrixes were constructed in situ on commercial ceramic tube substrates with curved and rough surfaces. The nanocomposite thin films are about 250 nm in thickness with large-scale structural consistency and integrity, which facilitates characteristic responses with highly sensitivity and reliability. Furthermore, the nanocomposite sensor shows simultaneous responses to multiple VOCs that commonly exist in daily life with an obvious suppression sensing for traditional flammable gases. Particularly, a detection limit of 0.1 ppm with a second-level response/recovery time can be achieved, which is beneficial for real-time air quality assessments. We proposed a heterojunction-induced sensing enhancement mechanism for the ZnO/WO3 nanocomposite film in which the formation of abundant heterojunctions between ZnO and WO3 NPs significantly increases the thickness of the electron depletion layer in the bulk film and improves the formation of active oxygen species on the surface, which is conducive to enhanced responses for reducing VOC gases. This work not only provides a simple approach for the fabrication of high-performance gas sensors but also opens an achievable avenue for air quality assessment based on VOC concentration detection.

Solid-State Au Nanocone Arrays Substrate for Reliable SERS Profiling of Serum for Disease Diagnosis.

Surface-enhanced Raman scattering (SERS) is a widely used rapid and noninvasive method for detecting biological substances in serum samples and is commonly employed in disease screening and diagnosis. Solid-state nanoarray SERS substrates used in serum detection may cause spectral instability due to imperfections in the detection method. For the purpose of identifying optimal detection conditions, various dilution levels of the serum were tested in this study. The study found that a complete and stable serum SERS spectrum can be obtained when the serum is diluted by a factor of 50. The study reports the successful preparation of an Au nanocone array (Au NCA) plasmonic substrate with a uniform, controllable microstructure and high activity, achieved through a combination of PS colloidal sphere template-assisted reactive ion etching (RIE) process and magnetron sputtering deposition technology. Based on this substrate, a standard detection scheme was developed to obtain highly stable and repeatable serum SERS spectra. The study verified the reliability of the optimized serum detection scheme by comparing the SERS spectra of serum samples from healthy individuals and gastric cancer patients, and confirmed the potential benefits of the scheme for disease screening and diagnosis.

Self-Assembled Bifunctional Copper Hydroxide/Gold-Ordered Nanoarray Composites for Fast, Sensitive, and Recyclable SERS Detection of Hazardous Benzene Vapors.

Volatile organic compounds (VOCs), particularly monoaromatic hydrocarbon compounds (MACHs), pose a potential risk to the atmospheric environment and human health. Therefore, the progressive development of efficient detection methodologies is a pertinent need, which is still a challenge at present. In this study, we present a rapid and sensitive method to detect trace amounts of MACHs using a bifunctional SERS composite substrate. We prepared an Au/SiO2 enhanced layer and a porous Cu(OH)2 adsorption layer via microfluidic-assisted gas-liquid interface self-assembly. The composite substrate effectively monitored changes in benzaldehyde using time-varying SERS spectra, and track-specifically identified various VOCs such as benzene, xylene, styrene, and nitrobenzene. In general, the substrate exhibited a rapid response time of 20 s to gaseous benzaldehyde, with a minimum detection concentration of less than 500 ppt. Further experimental assessments revealed an optimum Cu(OH)2 thickness of the surrounding adsorption layer of 150 nm, which can achieve an efficient SERS response to MACHs. Furthermore, the recoverable and reusable property of the composite substrate highlights its practicality. This study presents a straightforward and efficient approach for detecting trace gaseous VOCs using SERS, with significant implications in the designing of SERS substrates for detecting other VOCs.

Blockade of C5aR1 alleviates liver inflammation and fibrosis in a mouse model of NASH by regulating TLR4 signaling and macrophage polarization.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an advanced form of chronic fatty liver disease, which is a driver of hepatocellular carcinoma. However, the roles of the C5aR1 in the NASH remain poorly understood. Here, we aimed to investigate the functions and mechanisms of the C5aR1 on hepatic inflammation and fibrosis in murine NASH model. METHODS: Mice were fed a normal chow diet with corn oil (ND + Oil), a Western diet with corn oil (WD + Oil) or a Western diet with carbon tetrachloride (WD + CCl4) for 12 weeks. The effects of the C5a-C5aR1 axis on the progression of NASH were analyzed and the underlying mechanisms were explored. RESULTS: Complement factor C5a was elevated in NASH mice. C5 deficiency reduced hepatic lipid droplet accumulation in the NASH mice. The hepatic expression levels of TNFα, IL-1ß and F4/80 were decreased in C5-deficient mice. C5 loss alleviated hepatic fibrosis and downregulated the expression levels of α-SMA and TGFß1. C5aR1 deletion reduced inflammation and fibrosis in NASH mice. Transcriptional profiling of liver tissues and KEGG pathway analysis revealed that several pathways such as Toll-like receptor signaling, NFκB signaling, TNF signaling, and NOD-like receptor signaling pathway were enriched between C5aR1 deficiency and wild-type mice. Mechanistically, C5aR1 deletion decreased the expression of TLR4 and NLRP3, subsequently regulating macrophage polarization. Moreover, C5aR1 antagonist PMX-53 treatment mitigated the progression of NASH in mice. CONCLUSIONS: Blockade of the C5a-C5aR1 axis reduces hepatic steatosis, inflammation, and fibrosis in NASH mice. Our data suggest that C5aR1 may be a potential target for drug development and therapeutic intervention of NASH.

The prognostic value of fibrinogen to albumin ratio in malignant tumor patients: A meta-analysis.

Background: Recent studies have shown that the fibrinogen to albumin ratio (FAR) is closely related to the prognosis of various cancers. The aim of this systematic review and meta-analysis was to investigate the prognostic value of FAR in malignancies based on the available evidence. Method: To systematically search the Cochrane Library, Embase, PubMed, Google Scholar, Baidu scholars, CNKI and VIP databases for relevant studies published before April 1, 2022, and to evaluate the fibrinogen-to-albumin ratio (FAR) and survival of patients with malignant tumors through a meta-analysis relationship between the results. Results. This meta-analysis included 19 eligible studies involving 5926 cancer patients. We found that high FAR was associated with poor overall survival (HR=2.25, 95%CI 1.86-2.74, p<0.001), recurrence-free survival (HR=2.29, 95%CI 1.91-2.76, P<0.001), progression-free survival (HR: 2.10, 95%CI 1.58-2.79, p<0.001), disease-free survival (HR=1.52, 95%CI 1.17-1.96, p=0.001), and time to recurrence (HR: 1.555, 95%CI 1.031-2.346, P=0.035) was significantly correlated. Conclusions: High FAR is significantly associated with poor clinical outcomes in cancer, suggesting that it may be an important predictor of prognosis in patients with malignancies.

Da Vinci robot-assisted pancreato-duodenectomy in a patient with situs inversus totalis: A case report and review of literature.

BACKGROUND: Situs inversus totalis (SIT) is an extremely rare congenital malformation characterized by mirror displacement of the thoracoabdominal organs such as the heart, liver, spleen, and stomach. Herein, we describe a patient with SIT complicated with cholangiocarcinoma who underwent successful pancreaticoduodenectomy with the assistance of a da Vinci robot. CASE SUMMARY: A 58-year-old female presented to the hospital with paroxysmal pain in her left upper abdomen, accompanied by jaundice and staining of the sclera as chief complaints. Imaging examination detected a mass at the distal end of the common bile duct, with inverted thoracic and abdominal organs. Endoscopic retrograde cholangiopancreatography forceps biopsy revealed the presence of a well-differentiated adenocarcinoma. The patient successfully underwent robotic-assisted pancreaticoduodenectomy; the operation lasted 300 min, the intraoperative blood loss was 500 mL, and there were no intraoperative and postoperative complications. CONCLUSION: SIT is not directly related to the formation of cholangiocarcinoma. Detailed preoperative imaging examination is conducive to disease diagnosis and also convenient for determining the feasibility of tumor resection. Robot-assisted pancreaticoduodenectomy for SIT complicated with cholangiocarcinoma provides a safe, feasible, minimally invasive, and complication-free alternative with adequate preoperative planning combined with meticulous intraoperative procedures.

Investigating the effects of Liushen Capsules on the metabolome of seasonal influenza: A randomized clinical trial.

Background: Traditional Chinese Medicines (TCMs) are effective strategies for preventing influenza infection. Liushen Capsules can inhibit influenza virus proliferation, significantly mitigate virus-induced inflammation and improve acute lung injury in vitro or in vivo. However, the efficacy and safety of LS in clinical trials, and the role of LS in regulating metabolites in patients are not well known. Materials and methods: A randomized, double-blind, placebo-controlled clinical trial was designed in this study. All participants were enrolled between December 2019 and November 2020. The efficacy and safety were assessed by primary efficacy endpoint ((area under the curve (AUC) analysis)) and secondary endpoint (individual scores for each symptom, remission of symptoms, and rates of inflammatory factors). The serum samples were collected from patients to detect the levels of inflammatory factors using RT-PCR and to identify metabolites using a non-targeted metabolomics ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS). Results: 81 participants from The Second Affiliated Hospital of Guangzhou University of Chinese Medicine and the First Affiliated Hospital of Guangzhou Medical University were completed the full study. After 14 days of intervention, the area under the curve (AUC) of the total symptom scores in LS group was significantly smaller than that in Placebo group (p < 0.001). Alleviation of sore throat, cough and nasal congestion in the LS group was significantly better than that in the Placebo group. The time and number to alleviation of symptoms or complete alleviation of symptoms in LS group was significantly better than that in Placebo group. The adverse effects of clinical therapy were slightly higher in LS group than in Placebo group, but there was no statistical difference. After 14 days of LS intervention, the levels of IL-1ra, Eotaxin, IFN-γ, IL-6, IL-10, IL-13, SCF and TRAIL in serum of participants with influenza infection were significantly decreased compared with Placebo group. It was observed that there were significant differences in the serum metabolic profiles between start- and end- LS groups. Further correlation analysis showed a potential regulatory crosstalk between glycerophospholipids, sphingolipids fatty acyls and excessive inflammation and clinical symptoms. Importantly, it may be closely related to phospholipid, fatty acid, arachidonic acid and amyl-tRNA synthesis pathway metabolic pathways. Conclusion: The study showed there were no clinically significant adverse effects on LS, and a significant improvement in influenza-like symptomatology and inflammatory response in patients treated with LS. Further analysis showed that LS could significantly correct the metabolic disorders in the serum metabolite profile of the patients. This provided new insights into the potential mechanism of LS for the treatment of influenza.

Corrigendum: Investigating the effects of Liushen Capsules (LS) on the metabolome of seasonal influenza: A randomized clinical trial.

[This corrects the article DOI: 10.3389/fphar.2022.968182.].