Ultrasonographic and cytological characterization of ultrasound-guided fine-needle aspiration cytology of cervical lymph nodes for false-negative and false-positive diagnosis.

OBJECTIVES: The primary goal of this study was to examine the ultrasound and cytological characteristics of inconsistent cases (false negatives and false positives)of ultrasound-guided fine-needle aspiration cytology (US-FNAC) of cervical lymph nodes, to investigate factors influencing the diagnostic accuracy of fine-needle aspiration, and to improve diagnostic efficiency. METHODS: The results of US and FNAC of cervical lymph nodes in 562 cases treated at our institution from February 2019 to June 2021 were retrospectively analyzed. FNAC cytology results were compared with the final diagnostic results (242 surgical resections/core-needle biopsy, 320 cases followed up for more than 1 year), and the final diagnostic results were taken as the gold standard, and the ultrasound features and clinicopathology-related features were systematically retrospectively analyzed in cases of inconsistency. RESULTS: The overall diagnostic accuracy of US-FNAC for cervical lymph nodes was 94.9%, with a false-negative rate of 6.7% and a false-positive rate of 3.8%. Analyzing the cases, sampling error due to factors associated with ultrasound features, such as larger, more numerous nodes, non-solid, hypoechoic, inhomogeneous, and increased vascularity are the main causes of false-negative diagnosis, while smaller nodules, overlapping cytologic patterns, and overinterpretation by pathologists are associated with false-positive FNAC results. CONCLUSIONS: Proper interpretation of cytomorphologic and ultrasound features can improve diagnostic accuracy, and diagnostic misdiagnosis should be carefully observed, the identification of both features should be enhanced to reduce interpretation errors and sampling errors and to reduce the rate of misdiagnosis and missed diagnoses in fine needle aspiration of lymph nodes.

Comparison Between Wedge Resection and Lobectomy/Segmentectomy for Early-Stage Non-small Cell Lung Cancer: A Bayesian Meta-analysis and Systematic Review.

BACKGROUND: Surgery has become an accepted method for the treatment of early-stage non-small cell lung cancer (NSCLC). The purpose of this Bayesian meta-analysis was to compare the overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) between wedge resection and lobectomy/segmentectomy for treatment of early-stage NSCLC. METHODS: Eligible studies were retrieved from Web of Science, PubMed, MEDLINE, Cochrane Library, EMBASE, CNKI, and WanFang up to July 2021 and screened based on established selection criteria. The Bayesian meta-analysis was performed with the combination of the reported survival outcomes of the individual studies using a random-effect model. The OS, DFS, and RFS of the wedge resection group was compared with the lobectomy/segmentectomy group. The hazard ratio (HR) and standard error were extracted or calculated for each study using the Kaplan-Meier method. RESULTS: This study was registered with PROSPERO (INPLASY202080090).The pooled OS hazard ratio between segmentectomy and lobectomy was 1.1 [95% confidence interval (CI) 0.92-1.4], the pooled HR between lobectomy and wedge resection was 0.71 [95% CI 0.52-0.96], and the pooled HR between segmentectomy and wedge was 0.80 [95% CI 0.56-1.10]. The pooled HR of DFS or RFS was not statistically significant among the three surgical approaches. CONCLUSIONS: Patients with early-stage NSCLC received lobectomy had the lowest hazard ratio of OS than patients received wedge resection, indicating that the overall survival of patients received lobectomy was higher than patients received wedge resection. However, regarding DFS and RFS, the three surgical approaches showed no significant difference.

Advanced Glycation End Products Induced Mitochondrial Dysfunction of Chondrocytes through Repression of AMPKα-SIRT1-PGC-1α Pathway.

INTRODUCTION: Our previous studies have demonstrated advanced glycation end products (AGEs) was an important mediator in osteoarthritis (OA) which may induce mitochondrial dysfunction. AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and its downstream target peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) are the critical sensors that regulate mitochondrial biogenesis and have been recognized as therapeutic targets in OA. This study was designed to test whether AGEs caused mitochondrial dysfunction through modulation of AMPKα/SIRT1/PGC-1α. METHODS: We knocked down or overexpressed AMPKα, SIRT1, and PGC-1α by small interfering RNA or plasmid DNA transfection, respectively. Mitochondrial membrane potential (△Ψ) was detected by tetraethylbenzimidazolyl carbocyanine iodide (JC-1) fluorescence probe. RESULTS: The results showed that AGEs impaired △Ψ, intracellular ATP level, and mitochondrial DNA content, linked to decreased AMPKα, SIRT1, and PGC-1α expression in chondrocyte. AMPKα pharmacologic activation or overexpression of AMPKα, SIRT1, and PGC-1α reversed impairments of mitochondrial biogenesis, oxidative stress, and inflammation in AGEs-induced chondrocytes. However, AMPKα activation using AICAR had decreased capacity to increase each of those same effect readouts in AGEs-treated SIRT1-siRNA or PGC-1α-siRNA chondrocyte. CONCLUSION: Taken together, AGEs reduced the AMPKα/SIRT1/PGC-1α signaling in chondrocytes, leading to mitochondrial dysfunction as a result of increased oxidative stress, inflammation, and apoptosis. These results indicated that target AMPK may be as a novel therapeutic strategy for AGEs-related OA prevention.

TBA loop mapping with 3'-inverted-deoxythymidine for fine-tuning of the binding affinity for α-thrombin.

TBA is a 15-mer DNA aptamer for human α-thrombin, and its three T-rich loops are involved in the binding interactions with thrombin differently. In order to clarify their specific spatial locations in the binding interactions and search for more favourable positions, here a systematic investigation of all the loop residues was conducted with 3'-inverted thymidine (iT), by which both unnatural 3'-3'- and 5'-5'-linkages for each incorporation were introduced in the tertiary structure. The changes in Tm values and CD spectra revealed that motifs T3T12 and T4T13 are structurally distinct. Longer anti-clotting time was obtained for the T3 and T12 modifications, respectively, while T4 and T13 were completely intolerant with such changes, in terms of stability and binding to thrombin. In particular, the increased affinity bindings and longer anti-clotting time were obtained with the replacement on the central loop T7G8T9, which were closely related to the existence of a monovalent ion, K+ or Na+, consistently with the supposed binding site of these ions in TBA. It is worthwhile to note that both the subtle variations of the loop residues induced by iT and the monovalent ions determined the interacting residues of TBA and the binding strength rather than the thermal stability of the TBA structure.

Novel hypolipidemic conjugates of fatty acid and bile acid with lysine for linkage.

Novel fatty acid-bile acid conjugates (1a-1k) were designed and synthesized by coupling of the fatty acids to the 3-OH of bile acids using lysine for linkage. In the conjugates, the 24-COOH of the bile acids was kept intact to preserve liver-specific recognition. The ability of the newly synthesized conjugates (at 100 mg/kg dosage) to reduce total cholesterol (TC) and triglyceride (TG) levels in mice fed with high-fat diet (HFD) was evaluated. Conjugates of stearic acid with cholic acid and palmitic acid with ursodeoxycholic acid (at dosages of 50, 100, and 200 mg/kg) were further evaluated to determine their ability to reduce aspartate aminotransferase (AST), alanine aminotransferase (ALT), TC, and TG levels in mice fed with HFD. All conjugates showed potent hypolipidemic activity. Further investigation revealed that compounds 1c and 1 g not only dose-dependently reduced serum levels of TC and TG, but also inhibited the elevation of serum AST and ALT levels in mice fed with HFD. Thus, compounds 1c and 1 g are promising hypolipidemic agents with hepatocyte protective effects against HFD-induced liver damage.

Alteration of Intestinal Flora Stimulates Pulmonary microRNAs to Interfere with Host Antiviral Immunity in Influenza.

The intestinal flora may be an important and modifiable factor that contributes to the immune response in influenza. To investigate the effect of intestinal flora alteration induced by antibiotic interference on microRNA (miRNA) communication in antiviral immunity, BALB/c mice received two weeks of antibiotic treatment before infection with the influenza A virus. The changes in intestinal flora and pulmonary flora were detected and analyzed by 16S ribosomal RNA (rRNA) gene sequencing. The amplification of the influenza virus in the lungs was measured by RT-PCR. The involvement of pulmonary miRNA was explored using miRNA microarray analysis. The results showed that the antibiotics destroyed the symbiotic relationship of the intestinal flora, resulting in a reduction in bacterial diversity, but they did not affect the pulmonary flora. The alteration of intestinal flora affected the expression of pulmonary miRNAs and resulted in an enhancement of pulmonary influenza virus amplification. The conclusion is that alteration of intestinal flora induced by antibiotic interference affected the expression of pulmonary miRNAs to interfere with host antiviral immunity, of which miR-146b and miR-29c might be good resources of resistance to influenza under antibiotic abuse.

Characterization, Stability and Antioxidant Activity of Vanilla Nano-Emulsion and Its Complex Essential Oil.

As a natural flavoring agent, vanilla essential oil has a special aroma and flavor, but its volatility and instability limit its value. Therefore, in this study, vanilla essential oil was compounded with cinnamon essential oil to prepare nano-emulsions (composite nano-emulsions called C/VT and C/VM), and the stability of the composite essential oil emulsions was investigated. Transmission electron microscopy (TEM) images showed that the nano-emulsions were spherical in shape and some flocs were observed in C/VM and C/VT. The results showed that the average droplet sizes of C/VM and C/VT increased only by 14.99% and 15.01% after heating at 100 °C for 20 min, and the average droplet sizes were less than 120 nm after 24 days of storage at 25 °C. Possibly due to the presence of reticulated flocs, which have a hindering effect on the movement of individual droplets, the instability indices of C/VM and C/VT were reduced by 34.9% and 39.08%, respectively, in comparison to the instability indices of C/VM and C/VT. In addition, the results of antioxidant experimental studies showed that the presence of composite essential oil flocs had no significant effect on the antioxidant capacity. These results indicate that the improved stability of the composite essential oil nano-emulsions is conducive to broadening the application of vanilla essential oil emulsions.

Are Published Cancer Care Trial Protocols With Traditional Chinese Medicine Interventions Concordant With SPIRIT-TCM Extension 2018? A Scoping Review on Published Trial Protocols Between 2019 and 2022.

BACKGROUND: The SPIRIT-TCM Extension 2018 was created to guide the design and reporting of Traditional Chinese Medicine (TCM) clinical trial protocols. This study aims to investigate the extent of concordance with this guideline in the relevant field of cancer care research. METHODS: A scoping review of TCM cancer trial protocols published in English and Chinese since January 2019 was conducted. Five major academic databases (MEDLINE, EMBASE, CINAHL, CENTRAL, and China National Knowledge Infrastructure) were searched. Concordance with the SPIRIT-TCM Extension 2018 was assessed by descriptive analysis. RESULTS: Fifty-three TCM cancer care trial protocols were identified, comprising 23 acupuncture, 26 Chinese herbal medicine (CHM), and 4 Tai Chi/Qigong (TCQ) interventions. The majority of the checklist items had a low rate of concordance, especially in the reporting of quality control and safety, dosage, TCM diagnostic patterns, possible interactions between Western Medicine and TCM interventions, and TCM-related outcome assessments. CONCLUSIONS: Although the SPIRIT-TCM Extension 2018 guideline was established through extensive Delphi consultation, there are low rates of concordance between published TCM cancer care clinical trial protocols with the guideline. Further research is necessary to understand the low rate of concordance and how scientific rigors of reporting can be improved in TCM cancer care research.

Adsorption of Per- and Polyfluoroalkyl Substances (PFAS) and Microcystins by Virgin and Weathered Microplastics in Freshwater Matrices.

Microplastics and per- and polyfluoroalkyl substances (PFAS) both represent persistent groups of environmental contaminants that have been associated with human health risks. Microcystin toxins are produced and stored in the cells of cyanobacteria and may be released into sources of drinking water. Recent concerns have emerged regarding the ability of microplastics to adsorb a range of organic contaminants, including PFAS and microcystins. This study examined the adsorption of two long-chain and two short-chain PFAS, as well as two common microcystins, by both virgin and weathered microplastics in freshwater. Natural weathering of microplastic surfaces may decrease adsorption by introducing hydrophilic oxygen-containing functional groups. Up to 50% adsorption of perfluorooctanesulfonic acid (PFOS) was observed for virgin PVC compared to 38% for weathered PVC. In contrast, adsorption capacities for microcystins by virgin LDPE were approximately 5.0 µg/g whereas no adsorption was observed following weathering. These results suggest that adsorption is driven by specific polymer types and dominated by hydrophobic interactions. This is the first known study to quantify PFAS and microcystins adsorption when considering environmentally relevant concentrations as well as weathered microplastics.

Proanthocyanidins attenuates ferroptosis against influenza-induced acute lung injury in mice by reducing IFN-γ.

BACKGROUND: Acute lung injury (ALI) is associated with high morbidity and mortality and is partly driven promoted by ferroptosis. Proanthocyanidins (PAs) is a natural bioactive flavonoid with anti-inflammatory and antioxidant activities. PAs can also significantly protect against acute lung inflammation and ferroptosis in alveolar epithelial cells. However, it is unclear whether PAs can alleviate ALI by reducing ferroptosis. This study aimed to evaluate the protective effects of PAs and the potential mechanisms against Influenza A virus (IAV)-induced ALI. METHODS: Mice were inoculated nasally with IAV to induce ALI. IAV-induced pulmonary inflammation and ferroptosis was tested by measuring the levels of malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and acyl-CoA synthetase long-chain family member (ACSL4) in lung tissue. The potential targets that PAs protect against IAV-induced ALI were determined via a systemic pharmacological analysis. The molecular mechanism of PAs in ALI treatment was investigated by assessing the level of inflammation and ferroptosis markers using Western Blot and quantitative real-time PCR. RESULTS: Systemic pharmacological analysis suggested that PAs protect against IAV-induced pneumonia thorough TGF-ß1 and its relative signaling pathway. PAs effectively alleviated histopathological lung injury, reduced inflammatory cytokines and chemokines secretion, which were increased in IAV-infected mice. Meanwhile, PAs further prevented mouse airway inflammation in ALI, concomitant with the decreased expression TGF-ß1, smad2/3, p-Smad2, p-Smad3 and ferroptosis mediator IFN-γ. Furthermore，IFN-γ promotes cell lipid peroxidation and ferroptosis，PAs significantly reduced MDA and ACSL4 levels and upregulated GSH, GPX4, and SLC7A11. CONCLUSION: Overall, PAs can attenuate ferroptosis against IAV-induced ALI via the TGF-ß1/Smad2/3 pathway and is a promising novel therapeutic candidate for ALI.

1,8-cineole ameliorates colon injury by downregulating macrophage M1 polarization via inhibiting the HSP90-NLRP3-SGT1 complex.

Ulcerative colitis (UC) is characterized by chronic relapsing intestinal inflammation. Currently, there is no effective treatment for the disease. According to our preliminary data, 1,8-cineole, which is the main active compound of Amomum compactum Sol. ex Maton volatile oil and an effective drug for the treatment of pneumonia, showed remarkable anti-inflammatory effects on colitis pathogenesis. However, its mechanism of action and direct targets remain unclear. This study investigated the direct targets and mechanism through which 1,8-cineole exerts its anti-inflammatory effects using a dextran sulfate sodium salt-induced colitis mouse model. The effects of 1,8-cineole on macrophage polarization were investigated using activated bone marrow-derived macrophages and RAW264.7 cells. In addition, 1,8-cineole targets were revealed by drug affinity responsive target stability, thermal shift assay, cellular thermal shift assay, and heat shock protein 90 (HSP90) adenosine triphosphatases (ATPase) activity assays. The results showed that 1,8-cineole exhibited powerful anti-inflammatory properties in vitro and in vivo by inhibiting the macrophage M1 polarization and protecting intestinal barrier function. Mechanistically, 1,8-cineole directly interacted with HSP90 and decreased its ATPase activity, also inhibited nucleotide-binding and oligomerization domain-, leucine rich repeat-, and pyrin domain-containing 3 (NLRP3) binding to HSP90 and suppressor of G-two allele of SKP1 (SGT1) and suppressed NLRP3 inflammasome activation in macrophages. These results demonstrated that 1,8-cineole is a potential drug candidate for UC treatment.

Network pharmacology and in vivo experiments reveal the pharmacological effects and molecular mechanisms of Simiao Powder in prevention and treatment for gout.

BACKGROUND: Gout is a common disease with high incidence due to unhealthy diet and living habits. Simiao Powder, as a classic formula consisted of four common herbs, has been widely used in clinical practice since ancient times to prevent and treat gout. However, the pharmacological mechanism of Simiao Powder is still unclear. METHODS: Based on network pharmacology, Simiao Powder active compounds were identified in TCMSP, ETCM and BATMAN database, used to establish a network of interaction between potential targets of Simiao Powder and known therapeutic targets of gout. Subsequently, the key potential targets are being used for protein-protein interaction, GO enrichment analysis and KEGG pathway enrichment analysis through several authoritative open databases. Molecular docking through AutoDockTools software can verify interaction between molecules. Finally, to validate the predicted results, in vivo experiments based on hyperuricemic-gout mice model were designed and treated with Simiao powder and allopurinol. Serum levels of uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN) and xanthine oxidase (XOD) were determined using a customized assay kit while the expression of PPAR-γ, PTGS1, IL-6 and Bcl2 mRNA were analyzed through qRT-PCR. RESULTS: Disease-target-compound network was visualized basing on the 20 bioactive compounds and the 19 potential targets using Cytoscape software. The results of PPI analysis, GO enrichment and KEGG pathway enrichment analysis indicate that the potential mechanism of Simiao Powder in treating gout may be achieved by regulating immune and inflammatory reactions, improving metabolism and endocrine. The results of molecular docking show that most of the targets and components have good binding activity. In vivo experiments revealed that Simiao powder can decreased serum UA and XOD levels in hyperuricemic-gout mice, and improved renal function. Furthermore, Simiao powder certainly regulates the expression of PPAR-γ, PTGS1, IL-6 and Bcl2 mRNA in ankle tissue in hyperuricemic-gout mice. CONCLUSION: Collectively, this research predicted a multiple compounds, targets, and pathways model mechanism of Simiao Powder in the prevention and treatment of gout, providing new ideas and methods for in-depth research, via vivo experiments.

Adlay (Coix lacryma-jobi L.) Polyphenol Improves Hepatic Glucose and Lipid Homeostasis through Regulating Intestinal Flora via AMPK Pathway.

SCOPE: Non-alcoholic fatty liver disease (NAFLD) is a type of metabolic syndrome characterized of abnormal lipid deposition in the liver. Adlay polyphenol (AP), an effective component extracted from Coix lacryma-jobi L., has been reported that it can be used as a dietary supplement to prevent NAFLD. In this study, the mechanism and action of AP on lipid metabolism and regulation of intestinal flora are investigated. METHODS AND RESULTS: AP significantly decreases the lipid accumulation in free fatty acid-treated HepG2 cells. Western blot results indicate that AP improves lipid metabolism via activating the p-AMPK/p-ACC pathway. In vivo experiments show AP treatment significantly decreases the body weight, liver weight, hepatic triglyceride, and total cholesterol contents, as well as the serum glucose levels in high fat diet-fed mice, which may affect lipid accumulation by activating AMPK pathway and changing intestinal bacterial communities and intestinal microbiome metabolism. CONCLUSION: AP can be used as a food supplement for improving lipid metabolic dysfunction and reducing the incidence of metabolic diseases.

Identification of Potential Biomarkers of Depression and Network Pharmacology Approach to Investigate the Mechanism of Key Genes and Therapeutic Traditional Chinese Medicine in the Treatment of Depression.

BACKGROUND: To explore the potential target of depression and the mechanism of related traditional Chinese medicine in the treatment of depression. METHOD: Differential gene expression in depression patients and controls was analyzed in the GEO database. Key genes for depression were obtained by searching the disease databases. The COREMINE Medical database was used to search for Chinese medicines corresponding to the key genes in the treatment of depression, and the network pharmacological analysis was performed on these Chinese medicines. Then, protein-protein interaction analysis was conducted. Prediction of gene phenotypes was based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment scores. RESULTS: The total number of differentially expressed genes in the GEO database was 147. Combined with the GEO dataset and disease database, a total of 3533 depression-related genes were analyzed. After screening in COREMINE Medical, it was found that the top 4 traditional Chinese medicines with the highest frequency for depression were Paeonia lactiflora Pall., Crocus sativus L., Bupleurum chinense DC., and Cannabis sativa L. The compound target network consisted of 24 compounds and 138 corresponding targets, and the key targets involved PRKACA, NCOA2, PPARA, and so on. GO and KEGG analysis revealed that the most commonly used Chinese medicine could regulate multiple aspects of depression through these targets, related to metabolism, neuroendocrine function, and neuroimmunity. Prediction and analysis of protein-protein interactions resulted in the selection of nine hub genes (ESR1, HSP90AA1, JUN, MAPK1, MAPK14, MAPK8, RB1, RELA, and TP53). In addition, a total of four ingredients (petunidin, isorhamnetin, quercetin, and luteolin) from this Chinese medicine could act on these hub genes. CONCLUSIONS: Our research revealed the complicated antidepressant mechanism of the most commonly used Chinese medicines and also provided a rational strategy for revealing the complex composition and function of Chinese herbal formulas.

GeGen QinLian decoction alleviate influenza virus infectious pneumonia through intestinal flora.

Influenza in humans is often accompanied by gastroenteritis-like symptoms. GeGen QinLian decoction (GQD), a Chinese herb formula, has been widely used to treat infectious diarrhea for centuries and has the effect of restoring intestinal flora. Studies have also reported that GQD were used to treat patients with influenza. However, whether regulating the intestinal flora is one of the ways GQD treats influenza has not been confirmed. In present research, we conducted a systemic pharmacological study, and the results showed that GQD may acts through multiple targets and pathways. In influenza-infected mice, GQD treatment reduced mortality and lung inflammation. Most importantly, the mortality and lung inflammation were also reduced in influenza-infected mice that have undergone fecal microbiota transplantation (FMT) from GQD (FMT-GQD) treated mice. GQD treatment or FMT-GQD treatment restores the intestinal flora, resulting in an increase in Akkermansia_muciniphila, Desulfovibrio_C21_c20 and Lactobacillus_salivarius, and a decrease in Escherichia_coli. FMT-GQD treatment inhibited the NOD/RIP2/NF-κB signaling pathway in the intestine and affected the expression of downstream related inflammatory cytokines in mesenteric lymph nodes (mLNs) and serum. In addition, FMT-GQD treatment showed systemic protection by restraining the inflammatory differentiation of CD4+ T cells. In conclusion, our study shows that GQD can affect systemic immunity, at least in part, through the intestinal flora, thereby protect the mice against influenza virus infectious pneumonia.

Carvacrol inhibits the excessive immune response induced by influenza virus A via suppressing viral replication and TLR/RLR pattern recognition.

ETHNOPHARMACOLOGICAL RELEVANCE: Carvacrol, a monoterpene phenol from Mosla chinensis Maxim, which is a commonly Chinese herbal medicine. The most important pharmacology of it is dispelling exogenous evils by increasing perspiration. And it is the gentleman medicine in the Chinese herbal compound prescription of Xin-Jia-Xiang-Ru-Yin, mainly for the treatment of summer colds with dampness including influenza virus A infection. AIM OF THE STUDY: Our preliminary study verified that the Xin-Jia-Xiang-Ru-Yin could inhibit acute lung injury of mice with influenza virus A infection. And there have been some reports implicating the high antimicrobial activity of carvacrol for a wide range of product preservation, but little research including the effects of it on viral infection. The aim of this study was to reveal the antiviral effects of carvacrol, the main constituent in Mosla chinensis Maxim. MATERIALS AND METHODS: Initially, C57BL/6 mice were grouped and intranasally administered FM1 virus to construct viral infection models. After treatment with ribavirin and carvacrol for 5 days, all mice were euthanized, and specimens were immediately obtained. Histology, flow cytometry and Meso Scale Discovery (MSD) analysis were used to analyze pathological changes in lung tissue, the expression levels of cytokines and the differentiation and proportion of CD4+ T cells subsets, while Western blot and qRT-PCR were used to detect the expression of related proteins and mRNA. RESULTS: Carvacrol attenuated lung tissue damage, the proportions of Th1, Th2, Th17 and Treg in CD4+ T cells and the relative proportions of Th1/Th2 and Th17/Treg cells. Carvacrol inhibited the expression of inflammation-associated cytokines including IFN-γ, IL-2, IL-4, IL-5, IL-12 and TNF-ɑ, IL-1, IL-10, IL-6. Decreased levels of TLR7, MyD88, IRAK4, TRAK6, NF-κB, RIG-I, IPS-I and IRF mRNA in carvacrol-treated mice were observed comparing to the mice in VC group. Further, the total expression of RIG-I, MyD88 and NF-κB proteins had increased significantly in the VC group but reduced obviously in the group treated with ribavirin or carvacrol. CONCLUSIONS: These results indicate that carvacrol is a potential alternative treatment for the excessive immune response induced by influenza virus A infection, the cold-fighting effect of Mosla chinensis Maxim may depend on the anti-virus of carvacrol.

Efficacy comparison of different acupuncture methods for herpes zoster: A Bayesian analysis protocol.

BACKGROUND: Acupuncture methods (include moxibustion) are used frequently in the treatment of herpes zoster. However, the choice is usually made only based on personal experience among different acupuncture methods. This study aims to compare the efficacy of different acupuncture methods for herpes zoster. METHODS: All randomized controlled trials of acupuncture methods for herpes zoster will be searched in 7 databases including Cochrane Library, Embase, PubMed, Web of Science, Wan-fang database, China National Knowledge Infrastructure database, and VIP Chinese Science and Technique Journals database database. After screening process, effectiveness rate will be extracted from all the included randomized controlled trials as primary outcomes. The Bayesian network meta-analysis will be conducted by generate mixed treatment comparisons 0.14.3, Stata13.0, and Review Man 5.3. RESULTS: The results of this study will be submitted to a peer-reviewed journal for publication. CONCLUSIONS: Our review will compare the efficacy of different acupuncture treatments for herpes zoster and find a better selection guideline for clinicians and patients. PROSPERO REGISTRATION NUMBER: CRD42020175189.

Potential Molecular Mechanisms of Plantain in the Treatment of Gout and Hyperuricemia Based on Network Pharmacology.

BACKGROUND: The incidence of gout and hyperuricemia is increasing year by year in the world. Plantain is a traditional natural medicine commonly used in the treatment of gout and hyperuricemia, but the molecular mechanism of its active compounds is still unclear. Based on network pharmacology, this article predicts the targets and pathways of effective components of plantain for gout and hyperuricemia and provides effective reference for clinical medication. METHOD: Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SymMap databases were used to screen out the active compounds and their targets in plantain. GeneCards, Therapeutic Target Database (TTD), and Online Mendelian Inheritance in Man (OMIM) databases were used to find the targets corresponding to gout and hyperuricemia. Venn diagram was used to obtain the intersection targets of plantain and diseases. The interaction network of the plantain active compounds-targets-pathways-diseases was constructed by using Cytoscape 3.7.2 software. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out. RESULT: Seven active compounds were identified by network pharmacological analysis, including dinatin, baicalein, baicalin, sitosterol, 6-OH-luteolin, stigmasterol, and luteolin. Plantain plays a role in gout and hyperuricemia diseases by regulating various biological processes, cellular components, and molecular functions. The core targets of plantain for treating gout are MAPK1, RELA, TNF, NFKBIA, and IFNG, and the key pathways are pathways in cancer, hypoxia-inducible factor-1 (HIF-1) signaling pathway, interleukin (IL)-17 signaling pathway, Chagas disease (American trypanosomiasis), and relaxin signaling pathway. The core targets of plantain for hyperuricemia are RELA, MAPK1, NFKBIA, CASP3, CASP8, and TNF, and the main pathways are pathways in cancer, apoptosis, hepatitis B, IL-17 signaling pathway, and toxoplasmosis. CONCLUSION: This study explored the related targets and mechanisms of plantain for the treatment of gout and hyperuricemia from the perspective of network pharmacological analysis, reflecting the characteristics of multiple components, multiple targets, and multiple pathways, and it provides a good theoretical basis for the clinical application of plantain.

Prolonged exposure to high humidity and high temperature environment can aggravate influenza virus infection through intestinal flora and Nod/RIP2/NF-κB signaling pathway.

Seasonal influenza is an acute viral infection caused by influenza virus, which is often prevalent in the summer and winter. The influenza virus can infect pigs and poultry. Some literature reports that the influenza virus has an outbreak in summer. The summer climate is characterized by a high humidity and high temperature environment, which is the same as many animal feeding and growing environments. We established a flu animal model under a high temperature and humidity environment during the day to observe the impact of high humidity and high temperature environment on the mice after contracting the influenza virus. Our results indicate that the intestinal flora of 16 s rDNA cultured in High humidity and high temperature environment changes, the intestinal mucosal permeability increases, the expression of pIgR, sIgA, and IgA in the intestinal mucosal immune system decreases, and the NLR immune recognition signaling pathway NOD1 is activated. The expression of related genes such as NOD2, NF-κB, and pIgR increases, which leads to the increase of related inflammatory factors in the vicinity of the intestines, aggravating local inflammation. High humidity and high temperature environment can cause the expression of inflammatory cytokines in the body to rise, causing Th17/Treg immune imbalance, inhibiting Treg maturation and differentiation, and increasing the expression of IL-2, IL-6, and other cytokines, while the expression of IFN-γ and IL-17A decreases. This condition worsens after infection with the influenza virus. Overall, our study found that High humidity and high temperature environment affect the intestinal flora and the body's immune status, thereby aggravating the status of influenza virus infection.

Gegen Qinlian Decoction Downregulates the TLR7 Signalling Pathway to Control Influenza A Virus Infection.

ETHNOPHARMACOLOGICAL RELEVANCE: In recent years, Gegen Qinlian decoction (GQD) has been applied to treat influenza virus infection, and its clinical effectiveness has been shown. However, the potential mechanism by which GQD acts on influenza A virus (IAV) has not been fully elucidated. Traditional Chinese medicine (TCM) formulas are well known to have multiple targets and effects. Our previous experiments examined the mechanism by which TCM can be used to treat influenza from the perspective of the influenza immune mechanism. AIM OF THE STUDY: To explore the possible mechanism by which GQD affects mice infected with the FM1 strain of influenza virus. MATERIALS AND METHODS: Forty-eight C57BL/6 mice were divided randomly into four groups: a normal control (NG) group, an IAV infection (VG) group, an IAV + oseltamivir (30.44 mg/kg) treatment (VO) group, and an IAV + GQD (9.74 g/kg) treatment (VQ) group. We also grouped forty-eight Toll-like receptor 7 knockout (TLR7-/-) mice in the same manner. The pulmonary mRNA expression of TLR7, myeloid differentiation factor 88 (MyD88), and nuclear factor (NF)-κB p65 was measured by RT-qPCR, and the pulmonary protein expression of TLR7, MyD88, and NF-κB p65 was measured by western blot. The proportions of T helper (Th) 1, Th2, Th17 and regulatory T (Treg) cells were measured by flow cytometry. RESULTS: IAV infection led to low body weights and high viral load. Compared with those in the NG group, the mRNA expression levels of TLR7, MyD88, and NF-κB p65 in the VG group were upregulated (P < 0.05). However, the mRNA and protein expression levels of TLR7, MyD88, and NF-κB p65 were lower in the VO and VQ groups than in the VG group (P < 0.05). IAV infection led to increased proportions of Th1/Th2 and Th17/Treg cells in the VG group. In the VO and VQ groups, both Th2 and Th1 cell numbers were increased, resulting in a lower Th1/Th2 proportion than that in the VG group. CONCLUSIONS: GQD downregulated the expression of some key TLR signalling pathway factors. GQD also affected the differentiation of CD4+ T cells, thereby exerting a protective systemic effect on influenza virus infection. In conclusion, GQD activated a balanced inflammatory response in the host to limit immune pathological injury and improve clinical and survival outcomes.