Perceptions and factors influencing exercise interventions in elderly patients with debilitating spinal surgery and healthcare professionals: A qualitative study.

BACKGROUND: Older spine surgery patients have a high incidence of debilitation, which can be managed with certain exercises. AIM: To investigate the current status and influencing factors related to the knowledge of exercise intervention among patients and professionals. METHODS: Descriptive research methods were used to classify and summarize patients and professionals' perceptions and factors affecting exercise interventions. Data were analysed using the Colaizzi seven-step analysis method to distill and refine themes. RESULTS: A total of 7 themes were identified: (1) The current status of patients' exercise is unsatisfactory; (2) patients' health literacy is low, coupled with a lack of social and family support; (3) there are numerous challenges with systematic exercise interventions; (4) healthcare professionals acknowledge the importance and need for exercise interventions; (5) there's a pronounced willingness among patients to participate in exercise intervention programs; (6) healthcare professionals believe that exercise interventions are beneficial; and (7) participants offered invaluable insights and suggestions on perioperative exercise during spinal surgery. CONCLUSION: To investigate the current status and influencing factors related to the knowledge of exercise intervention among patients and the related healthcare professionals to provide a reference for the construction of exercise management programs for these patients.

Mammalian orthoreovirus capsid protein σ3 antagonizes RLR-mediated antiviral responses by degrading MAVS.

Mammalian orthoreovirus (MRV) outer capsid protein σ3 is a multifunctional protein containing a double-stranded RNA-binding domain, which facilitates viral entry and assembly. We reasoned that σ3 has an innate immune evasion function. Here, we show that σ3 protein localizes in the mitochondria and interacts with mitochondrial antiviral signaling protein (MAVS) to activate the intrinsic mitochondria-mediated apoptotic pathway. Consequently, σ3 protein promotes the degradation of MAVS through the intrinsic caspase-9/caspase-3 apoptotic pathway. Moreover, σ3 protein can also inhibit the expression of the components of the RNA-sensing retinoic acid-inducible gene (RIG)-like receptor (RLR) signaling pathway to block antiviral type I interferon responses. Mechanistically, σ3 inhibits RIG-I and melanoma differentiation-associated gene 5 expression is independent of its inhibitory effect on MAVS. Overall, we demonstrate that the MRV σ3 protein plays a vital role in negatively regulating the RLR signaling pathway to inhibit antiviral responses. This enables MRV to evade host defenses to facilitate its own replication providing a target for the development of effective antiviral drugs against MRV. IMPORTANCE: Mammalian orthoreovirus (MRV) is an important zoonotic pathogen, but the regulatory role of its viral proteins in retinoic acid-inducible gene-like receptor (RLR)-mediated antiviral responses is still poorly understood. Herein, we show that MRV σ3 protein co-localizes with mitochondrial antiviral signaling protein (MAVS) in the mitochondria and promotes the mitochondria-mediated intrinsic apoptotic pathway to cleave and consequently degrade MAVS. Furthermore, tryptophan at position 133 of σ3 protein plays a key role in the degradation of MAVS. Importantly, we show that MRV outer capsid protein σ3 is a key factor in antagonizing RLR-mediated antiviral responses, providing evidence to better unravel the infection and transmission mechanisms of MRV.

Associations between per and polyfluoroalkyl ether sulfonic acids and vitamin D biomarker levels in Chinese newborns.

Skeleton develops extremely fast during fetal and neonatal stages; thus, fetuses and newborns exhibit unique vulnerabilities to vitamin D metabolism dysregulation, giving vitamin D's principal role in calcium homeostasis. Previous studies linked legacy per and polyfluoroalkyl ether sulfonic acids (PFAS) with vitamin D biomarker status in adults and children; however, how PFAS, especially emerging CI-PFESAs, influence vitamin D among newborns is unknown. This study focused on the epidemiological linkages between PFAS and vitamin D biomarkers. Eleven PFAS, including legacy PFAS and emerging CI-PFESAs, as well as two vitamin D metabolites [25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3)], were determined in cord sera of 992 newborns from a birth cohort in Wuhan, China. The cord serum levels of 25(OH)D2 and 25(OH)D3 were summed as total 25(OH)D, which is a reliable biomarker of vitamin D status. The associations of separated PFAS with vitamin D biomarker levels were analyzed via multiple linear models, whereas the mixture effect was estimated by utilizing the weighted quantile sum (WQS) regression. We observed that per doubling changes in perfluorotridecanoate (PFTrDA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) were associated with a 6.04 to 9.05 % change in total 25(OH)D levels. PFHxS contributed over half of the PFAS mixture effect on total 25(OH)D. Stratified analysis indicated that the associations of certain PFAS with vitamin D biomarkers were more pronounced among boys. The emerging CI-PFESAs were not robustly related to vitamin D biomarker levels. The results suggested that exposure to legacy PFAS might disturb vitamin D status in newborns. Future epidemiological studies are required to confirm the association and to determine healthy implications at a later age.

Genomic Profiling and Response to Immune Checkpoint Inhibition plus Tyrosine Kinase Inhibition in FH-Deficient Renal Cell Carcinoma.

BACKGROUND: FH-deficient renal cell carcinoma (RCC) is a rare and exceptionally aggressive RCC subtype. There is currently limited understanding of the molecular alterations, pathogenesis, survival outcomes, and systemic therapy efficacy for this cancer. OBJECTIVE: To perform a retrospective multicenter analysis of molecular profiling and clinical outcomes for patients with FH-deficient RCC, with an emphasis on treatment response to first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI/TKI) versus bevacizumab plus erlotinib (Bev/Erlo) combination therapy in patients with advanced disease. DESIGN, SETTING, AND PARTICIPANTS: The study included 77 cases of FH-deficient RCC from 15 centers across China. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinical characteristics, molecular correlates, 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging, and treatment outcomes were analyzed. RESULTS AND LIMITATIONS: A total of 77 patients were identified, including 70 cases with a germline FH alteration (hereditary leiomyomatosis RCC syndrome [HLRCC]-associated RCC) and seven patients with somatic FH loss. Recurrent pathogenic alterations were found in NF2 (six/57, 11%), CDH1 (six/57, 11%), PIK3CA (six/57, 11%), and TP53 (five/57, 8.8%). Sixty-seven patients were evaluable for response to first-line systemic therapy with Bev/Erlo (n = 12), TKI monotherapy (n = 29), or ICI/TKI (n = 26). ICI/TKI combination therapy was associated with more favorable overall survival on systemic treatment (hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.04-0.90) and progression-free survival on first-line therapy (HR 0.22, 95% CI 0.07-0.71) compared to Bev/Erlo combination therapy. The main limitation is the retrospective study design. CONCLUSIONS: We described the genomic characteristics of FH-deficient RCC in an Asian population and observed a favorable response to ICI/TKI combinational therapy among patients with advanced disease. PATIENT SUMMARY: This real-world study provides evidence supporting the antitumour activity of combining molecular targeted therapy plus immunotherapy for kidney cancer deficient in fumarate hydratase. Further studies are needed to investigate the efficacy of this combination strategy in this rare cancer.

Outer membrane protein Amuc_1100 of Akkermansia muciniphila alleviates antibiotic-induced anxiety and depression-like behavior in mice.

Akkermansia muciniphila is present in the mucus layer of its host gut, and its outer membrane protein Amuc_1100 has a significant ameliorative effect on metabolic disorders and emotional memory aspects of enteritis, obesity, depression, and anxiety in the host. Antibiotics affect gut microbial composition, leading to imbalance and behavioral changes in the gut-brain axis, while probiotics have a protective effect against behavioral changes caused by gut flora disorders. In the present study, a depressed mouse model using a broad-spectrum cocktail mixture resulted in increased anxiety and depression-like behavior, decreased serum and hippocampal levels of 5-hydroxytryptamine (5-HT), and increased serum corticosterone (cort) levels. After application of A. muciniphila and Amuc_1100, anxiety and depression-like behavior in antibiotic-treated mice were significantly alleviated. In addition, the brain derived neurotrophic factor / Tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway was altered, glial fibrillary acidic protein (GFAP) expression increased, and c-Fos protein expression decreased in the hippocampus of antibiotic-treated mice. After treatment with A. muciniphila and Amuc_1100, BDNF and TrkB levels were restored in the hippocampus and cortex. These results suggest that A. muciniphila and Amuc_1100 may alleviate antibiotic-induced anxiety and depression by affecting the BDNF/TrkB signaling pathway.

The modified outer membrane protein Amuc_1100 of Akkermansia muciniphila improves chronic stress-induced anxiety and depression-like behavior in mice.

Akkermansia muciniphila is a next-generation probiotic. The interaction between outer membrane protein Amuc_1100 of A. muciniphila and toll-like receptor 2 (TLR2) in intestinal epithelial cells influences the level of intestinal 5-hydroxytryptamine (5-HT). Amuc_1100Δ80 is a truncated form of Amuc_1100 lacking the first 80 N-terminal amino acids and has a higher affinity for TLR2 than the wild-type protein. Here, we report that Amuc_1100Δ80 could significantly reduce anxiety and depression-like behavior of mice when they were exposed to chronic unpredictable mild stress (CUMS). The experimental results of the rat insulinoma cell line RIN-14B showed that Amuc_1100Δ80 also induced a significantly higher upregulation of tryptophan hydroxylase 1 (Tph1), a rate-limiting enzyme of intestinal 5-HT synthesis. The imbalance of the gut microflora could be diminished when CUMS mice were fed with Amuc_1100Δ80. These results reveal that Amuc_1100Δ80 could affect the 5-HT level and the downstream 5-HTR1A-CREB-BDNF signal pathway via interacting with TLR2 and by altering the gut microbial composition. In parallel, the downregulation exerted by Amuc_1100Δ80 on the inflammation and hyperactivated HPA axis was closely related to the improvement of depression-like symptoms in CUMS mice. This study not only provides new insights into the antidepressant effect of A. muciniphila and its outer membrane protein Amuc_1100 but also identifies new potential targets and pathways in the gut for future research and the development of antidepressant drugs.

Oncogenic ß-catenin stimulation of AKT2-CAD-mediated pyrimidine synthesis is targetable vulnerability in liver cancer.

CTNNB1, encoding ß-catenin protein, is the most frequently altered proto-oncogene in hepatic neoplasms. In this study, we studied the significance and pathological mechanism of CTNNB1 gain-of-function mutations in hepatocarcinogenesis. Activated ß-catenin not only triggered hepatic tumorigenesis but also exacerbated Tp53 deletion or hepatitis B virus infection-mediated liver cancer development in mouse models. Using untargeted metabolomic profiling, we identified boosted de novo pyrimidine synthesis as the major metabolic aberration in ß-catenin mutant cell lines and livers. Oncogenic ß-catenin transcriptionally stimulated AKT2, which then phosphorylated the rate-limiting de novo pyrimidine synthesis enzyme CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase) on S1406 and S1859 to potentiate nucleotide synthesis. Moreover, inhibition of ß-catenin/AKT2-stimulated pyrimidine synthesis axis preferentially repressed ß-catenin mutant cell proliferation and tumor formation. Therefore, ß-catenin active mutations are oncogenic in various preclinical liver cancer models. Stimulation of ß-catenin/AKT2/CAD signaling cascade on pyrimidine synthesis is an essential and druggable vulnerability for ß-catenin mutant liver cancer.

Development and application of an indirect ELISA to detect antibodies to Neospora caninum in cattle based on a chimeric protein rSRS2-SAG1-GRA7.

Neospora caninum is an important apicomplexan parasite causing neosporosis in cattle. The disease is recognized as one of the most important cause of reproductive problems and abortion in cattle worldwide. In this context, we developed an indirect enzyme-linked immunosorbent assays (ELISA) with chimeric protein rSRS2-SAG1-GRA7 to diagnose antibodies to Neospora-infection. This indirect ELISA was compared to indirect fluorescent antibody test (IFAT) and western blotting (WB), and the sensitivity and specificity results of ELISA were calculated to be 86.7 and 96.1%, respectively. The overall coincidence rate was 92.6% using IFAT and WB. Additionally, 329 aborting dairy cattle serum samples were tested using this ELISA to evaluate the prevalence of N. caninum in Ningxia, China. The positive rate of N. caninum in these farms was from 19.05 to 57.89%, and the mean rate was 41.64% (±11.01%), indicating that infection with N. caninum may be one of the important causes of cattle abortion in this region. This established rSRS2-SAG1-GRA7 indirect ELISA is capable for detecting the antibodies against N. caninum, and it could be a useful screening tool for monitoring the epidemiology of neosporosis in cattle.

Rapid Profiling of Chemical Constituents in Qingfei Paidu Granules Using High Performance Liquid Chromatography Coupled with Q Exactive Mass Spectrometry.

Qingfei Paidu (QFPD) granules have played a critical role during the Coronavirus Disease 2019 (COVID-19) in China. However, worldwide acceptance has been a problem because of the complex ingredients and unique theory of treatment. In this study, high-performance liquid chromatography (HPLC)-Q Exactive Orbitrap-mass spectrometry (MS) and the Orbitrap traditional Chinese medicine library (OTCML) were used to investigate the chemical constituents of QFPD granules. By comparing retention times, masses, isotope ion patterns, and MS2 profiles, 108 compounds were putatively identified using the OTCML combined with manual verification, including 12 alkaloids, 49 flavonoids, 13 terpenoids, 14 phenylpropanoids, 4 phenolic acids, 5 phenols, and 11 other phytochemicals. Of these compounds, 17 were confirmed using reference standards. In addition, representative compounds of these different chemical types were used as examples to analyze the fragmentation pathways and characteristic product ions. Moreover, 20 herbs within the QFPD granules were also identified to establish the sources of these chemical components. This is the first rapid profiling of the chemical constituents of QFPD granules using HPLC-Q Exactive Orbitrap-MS and yields valuable information for further quality control and mechanistic studies of QFPD granules. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10337-021-04085-0.

The outer membrane protein Amuc_1100 of Akkermansia muciniphila alleviates the depression-like behavior of depressed mice induced by chronic stress.

Akkermansia muciniphila is a symbiotic intestinal bacterium with a high medicinal value. Amuc_1100 is the outer membrane protein of A. muciniphila and plays an important role in the interaction between A. muciniphila and its host. The objective of this study was to evaluate the antidepressant activity of Amuc_1100 in a chronic unpredictable mild stress (CUMS) model. Amuc_1100 intervention ameliorated CUMS-induced depression-like behavior and CUMS-induced down-regulation of serotonin (5-hydroxytryptamine, or simply, 5-HT) in the serum and colon of mice. Microbial analysis of mouse feces showed that Amuc_1100 could improve the gut microbiota dysregulation induced by CUMS. In addition, Amuc_1100 intervention could also improve the down-regulation of brain-derived neurotrophic factor (BDNF) and inflammation in the hippocampus induced by CUMS. These results suggest that Amuc_1100 has a good antidepressant effect, and the mechanism may be related to the improvement of gut microbiota, the up-regulation of the BDNF level, and the inhibition of the neuroinflammatory response.

The outer membrane protein Amuc_1100 of Akkermansia muciniphila promotes intestinal 5-HT biosynthesis and extracellular availability through TLR2 signalling.

Akkermansia muciniphila is a probiotic inhabiting host intestinal mucus layers and displays evident easing or therapeutic effects on host enteritis and metabolic disorders such as obesity and diabetes. The outer membrane protein Amuc_1100 of A. muciniphila is likely to play a crucial role during the interaction with the host. 5-HT is a neurotransmitter and a key signal molecule regulating the gastrointestinal tract functions and other organs, which is involved in diverse physiological and pathological processes. This study demonstrated that Amuc_1100 could promote the expression of the 5-HT synthesis rate-limiting enzyme Tph1 in RIN-14B cells and reduce the expression of the serotonin reuptake transporter (SERT) in Caco-2 cells through direct interaction with TLR2, thereby improving 5-HT biosynthesis and extracellular availability. Using antibiotic-treated mice as animal models, we found that after gavage with A. muciniphila or Amuc_1100, Tph1 expression increased and SERT expression decreased in colon tissues. The 5-HT concentrations in colon tissues and blood were markedly elevated simultaneously. We also found that A. muciniphila or Amuc_1100 improved the gastrointestinal motility function and restored gut microbiota abundance and species diversity in antibiotic-treated mice. These results suggest that A. muciniphila can regulate the host intestinal 5-HT system via its outer membrane protein Amuc_1100 and TLR2. This mechanism represented an important approach through which A. muciniphila interacts with the host and further influences 5-HT-related physiological functions. These results advance the understanding of interplay mechanisms between the gut microbiota and the host, which could be the basis for new intervention strategies for related diseases.

Qualitative analysis of chemical components in Lianhua Qingwen capsule by HPLC-Q Exactive-Orbitrap-MS coupled with GC-MS.

The Lianhua Qingwen (LHQW) capsule is a popular traditional Chinese medicine for the treatment of viral respiratory diseases. In particular, it has been recently prescribed to treat infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, due to its complex composition, little attention has been directed toward the analysis of chemical constituents present in the LHQW capsule. This study presents a reliable and comprehensive approach to characterizing the chemical constituents present in LHQW by high-performance liquid chromatography-Q Exactive-Orbitrap mass spectrometry (HPLC-Q Exactive-Orbitrap-MS) coupled with gas chromatography-mass spectrometry (GC-MS). An automated library alignment method with a high mass accuracy (within 5 ppm) was used for the rapid identification of compounds. A total of 104 compounds, consisting of alkaloids, flavonoids, phenols, phenolic acids, phenylpropanoids, quinones, terpenoids, and other phytochemicals, were successfully characterized. In addition, the fragmentation pathways and characteristic fragments of some representative compounds were elucidated. GC-MS analysis was conducted to characterize the volatile compounds present in LHQW. In total, 17 compounds were putatively characterized by comparing the acquired data with that from the NIST library. The major constituent was menthol, and all the other compounds were terpenoids. This is the first comprehensive report on the identification of the major chemical constituents present in the LHQW capsule by HPLC-Q Exactive-Orbitrap-MS, coupled with GC-MS, and the results of this study can be used for the quality control and standardization of LHQW capsules.

Sweroside ameliorates NAFLD in high-fat diet induced obese mice through the regulation of lipid metabolism and inflammatory response.

ETHNOPHARMACOLOGICAL RELEVANCE: Sweroside, an iridoid derived from Traditional Chinese Medicine, is an active component in Swertia pseudochinensis Hara. Swertia pseudochinensis Hara is first recorded in "Inner Mongolia Chinese Herb Medicine"and is considered as a folk medicine for treating hepatitis in northern China. AIM OF THE STUDY: This study sought to elucidate the role of sweroside in high fat diet induced obesity and fatty liver by using mouse model and investigated the primary molecular mechanism via transcriptomics analysis. MATERIALS AND METHODS: C57BL/6 mice were fed high-fat diet (HFD) for 14 weeks to induce obesity, hyperglycemia, and fatty liver. These mice were subsequently treated with HFD alone or mixed with sweroside (at a daily dosage of 60 mg per kg of BW, 120 mg per kg of BW and 240 mg per kg of BW) for 6 weeks. BW and food intake was monitored weekly. Biochemical and pathological analysis were conducted to investigate the effect of sweroside on NAFLD. RNA-sequence and RT-qPCR analysis were performed to analyze the potential mechanism. RESULTS: The mice treated with sweroside were resistant to HFD-induced body weight gain, insulin resistance and hepatic steatosis. Ingenuity pathway analysis (IPA) demonstrated that hepatic gene networks related to lipid metabolism and inflammatory response were down-regulated in the HFD + sweroside group. PPAR-ɑ was located in the center of the hepatic gene network, and the significantly altered genes were CD36 and FGF21, which are related to hepatic inflammation and lipid metabolism. Consistently, upstream-regulators analysis revealed that the main enriched upstream-regulator was PPAR-ɑ. CONCLUSION: Our results indicate that sweroside may ameliorate obesity with fatty liver via the regulation of lipid metabolism and inflammatory responses. The beneficial effects of sweroside might be closely associated with the regulation of PPAR-α.

Targeting PDGFRα-activated glioblastoma through specific inhibition of SHP-2-mediated signaling.

BACKGROUND: Glioblastoma (GBM) is the most malignant primary brain tumor, with dismal median survival. Treatment of GBM is particularly challenging given the intrinsic resistance to chemotherapy and difficulty of drugs to reach the tumor beds due to the blood-brain barrier. Here, we examined the efficacy of SHP099, a potent, selective, and oral SHP-2 inhibitor for treating GBM with activated platelet derived growth factor receptor alpha (PDGFRα) signaling. METHODS: The effects of SHP099 on cell survival of neural progenitor cells (NPCs), GBM cell lines, and patient-derived glioma stem-like cells (GSCs) were evaluated. Brain and plasma pharmacokinetics of SHP099 and its ability to inhibit SHP-2 signaling were assessed. SHP099 efficacy as a single agent or in combination with temozolomide (TMZ) was assessed using transformed mouse astrocyte and GSC orthotopic xenograft models. RESULTS: Activated PDGFRα signaling in established GBM cells, GSCs, and transformed mouse astrocytes was significantly inhibited by SHP099 compared with NPCs in vitro and in vivo through targeting SHP-2-stimulated activation of extracellular signal-regulated protein kinases 1 and 2 in GBM. SHP099 treatment specifically inhibited expression of JUN, a downstream effector of PDGFR signaling, thereby attenuating cell cycle progression in GBM cells with activated PDGFRα. Moreover, SHP099 accumulated at efficacious concentrations in the brain and effectively inhibited orthotopic GBM tumor xenograft growth. SHP099 exhibited antitumor activity either as a single agent or in combination with TMZ and provided significant survival benefits for GBM tumor xenograft-bearing animals. CONCLUSIONS: Our data demonstrate the utility and feasibility of SHP099 as a potential therapeutic option for improving the clinical treatment of GBM in combination with TMZ.

A new ionone derivative from the leaves of Picrasma quassioides.

Nigakialcohol A (1), as unusual cyclization ionone derivative, together with eight known ones (2-9), were isolated from the leaves of Picrasma quassioides (D. Don) Benn (Simaroubaceae). Their structures were elucidated by extensive spectroscopic analyses and comparison with literature data. Compound 2 showed a weak inhibitory effect on NO production at non-cytotoxic concentration (100 µM) with inhibitory rate of 59%, and thus it should be regarded as potential anti-inflammatory agents.

[Systematical analysis of multiple components in drainage bear bile powder from different sources].

Bear Bile Powder contains bile acids, protein, amino acids, bilirubin and microelements and other compounds. Among them, the bile acids are the most active components. Currently, there are many studies on bile acids, but few reports on other components. Therefore, the purpose of this study is to carry out a systematical analysis of multiple components in drainage Bear Bile Powder from different sources. Bilirubin and protein were quantified by microplate spectrophotometer. The contents of bile acids and amino acids were determined by liquid chromatography coupled with mass spectrometry (LC-MS). The contents of microelements were determined by inductively coupled plasma mass spectrometry (ICP-MS) The result indicated that among 20 batches of bear bile powder from different sources there is high similarity (0.922-0.977). Tauroursodeoxycholic acid (TUDCA) and taurochenodeoxycholic acid (TCDCA) were the two most abundant components. The total contents of them were 41%-59% and met the current standard for quality control of bear bile powder. However, significant differences were found in their contents among samples from different sources. Besides, bilirubin, protein, amino acids and microelements also contributed to the differentiation of samples from different sources. The main components of bear bile powder from the different sources were with satisfactory similarity. But bile acids, bilirubin, protein, amino acids and microelements all contributed to the different among samples. Our present study provided a systematical approach for the better quality control and evaluation of bear bile powder.

Comparison of the Efficacy of Different Analgesia Treatments for Total Knee Arthroplasty: A Network Meta-Analysis.

BACKGROUND AND AIM: The severe pain after total knee arthroplasty (TKA) brings many patients more suffering, longer hospital stay, and higher expenses. This study was designed to assess the relative efficacy of several clinical treatments for postoperative analgesia of TKA through network meta-analysis based on multiple published randomized controlled trials. METHODS: Embase and PubMed were utilized to conduct this network meta-analysis from inception until 2016. Pain score, morphine consumption (milligrams), and length of hospitalization (day) were selected as the endpoints. RESULTS: A total of 58 studies with 3501 patients were included in this network meta-analysis. Except for patient-controlled epidural analgesia+femoral nerve block (FNB) and sciatic nerve block, all treatments were significantly superior to placebo in pain score 6 to 8 hours. In terms of pain score 24 hours, only continuous femoral nerve block (cFNB), periarticular infiltration, periarticular infiltration+FNB, single-dose FNB, and sciatic nerve block+FNB exhibited better performance than control group. For pain score 48 hours after surgery, only cFNB and intra-articular infiltration yielded better results than control group [standard mean difference=-0.68, 95% credible intervals (CrIs)=-1.03 to -0.33; standard mean difference=-0.53, 95% CrIs=-1.07 to -0.01, respectively]. Only cFNB exhibited better results with respect to morphine consumption day 2 after surgery (mean difference=-12.95, 95% CrIs=-19.70 to -6.53). CONCLUSIONS: Considering both pain score and morphine consumption, cFNB was potentially the most efficacious postoperative treatment for patients undergoing TKA.

Anti-oral common pathogenic bacterial active acetylenic acids from Thesium chinense Turcz.

Discovery of agents for oral infectious diseases is always encouraged in natural products chemistry. A bioassay-guided isolation led to the isolation of two new acetylenic acids (1, 2) along with seven known ones (3-9) from the ethanol extract of Thesium chinense Turcz, a commonly used oral anti-bacterial and anti-inflammatory herb. Their structures were elucidated on the basis of spectroscopic and chemical evidence. Exocarpic acid (3) demonstrated the most promising activity against three tested oral pathogenic bacterial strains, Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mutans, with minimum inhibitory concentration values of 0.86, 3.43, and 13.70 µg/mL, respectively. Compounds 1, 2, 4, 5 and 7 also showed potential activities against periodontal bacteria (P. gingivalis, F. nucleatum).

Antifungal Amide Alkaloids from the Aerial Parts of Piper flaviflorum and Piper sarmentosum.

Sixty-three amide alkaloids, including three new, piperflaviflorine A (1), piperflaviflorine B (2), and sarmentamide D (4), and two previously synthesized ones, (1E,3S)-1-cinnamoyl-3- hydroxypyrrolidine (3) and N-[7'-(4'-methoxyphenyl)ethyl]-2-methoxybenzamide (5), were isolated from the aerial parts of Piper flaviflorum and Piper sarmentosum. Their structures were elucidated by detailed spectroscopic analysis and, in case of 3, by single-crystal X-ray diffraction. Most of the isolates were tested for their antifungal and antibacterial activities. Ten amides (6-15) showed antifungal activity against Cryptococcus neoformans ATCC 90 113 with IC50 values in the range between 4.7 and 20.0 µg/mL.

Two New Oleanane-type Triterpenoids from Methanolyzed Saponins of Momordica cochinchinensis.

Two new oleanane-type triterpenoid saponins (1 and 2) were isolated from the methanolyzed total saponins of the seeds of Momordica cochinchinensis (Lour.) Spreng, together with 16 known compounds (3-18). Their structures were elucidated on the basis of detailed spectroscopic, including 1D and 2D NMR, mass spectrometric, methanolysis and LC-MS analysis. All the isolates were tested for their cytotoxic activities against five human cancer cell lines (HL-60, SMMC-7721, PANC-1, A-549, and SW-480) and the glucose uptake activity. The known compound 6 exhibited toxic effects against HL-60 with an IC50 value of 18.1 µM, while 10 showed cytotoxicity against SMMC-7721 and A-549 cell lines, with IC50 values of 34.4 and 32.8 µM, respectively. In addition, the new compound 2 showed glucose uptake activity with a glucose consumption value of 0.29 µM at 10 µM concentration.