Surgical advantage of modified labial salivary gland biopsy using chalazion forceps: a prospective randomized controlled study.

Labial salivary gland biopsy (LSGB) is one of the specific diagnostic criteria for primary Sjögren's syndrome (pSS). In traditional LSGB, there is no lower lip fixation device, the field of view is unclear due to intraoperative bleeding, and the incision is large, which is unfavourable for healing. The use of auxiliary devices to improve the shortcomings of traditional LSGB technique would be meaningful. Therefore, this case-control study aimed to assess the value of modified LSGB using chalazion forceps as compared with traditional LSGB. After obtaining written informed consent from all participating parents and patients, we randomly assigned 217 eligible participants to undergo LSGB using chalazion forceps (n = 125) or traditional LSGB (n = 92). The outcome variables were surgical time, incision length, intraoperative bleeding, pain score at 24 h after surgery, incision healing status at 7 days after surgery, gland collection, and pathological results. The final diagnostic results of the two surgical methods were compared, and the match rates between the pathological results and the final clinical diagnoses were compared between the two groups. The data were analysed using parametric and nonparametric tests. Compared with the traditional group, the modified group had a smaller incision, shorter operative time, less blood loss, lower 24 h pain score, and better Grade A incision healing at 7 days after surgery (p < 0.01). There was no statistically significant difference between the patients in the two surgical-method groups in terms of the positive biopsy results and the final diagnosis based on expert opinions (p > 0.05). By multivariable regression analysis, only a focus score (FS) of ≥ 1 (p < 0.01), dry eye disease (p < 0.05) and anti-nuclear antibodies (ANA) titre ≥ 1:320 (p < 0.05) were correlated with the diagnosis of pSS. The positive biopsy results of patients in the different surgical-method groups had a biopsy accuracy of > 80.0% for the diagnosis of pSS. The positive biopsy results in the different surgical-method groups were consistent with the expert opinions and the 2016 ACR-EULAR primary SS classification criteria. The modified LSGB using an auxiliary chalazion forceps offers a good safety with a small incision, shorter operative time, less bleeding, reduced pain and a low incidence of postoperative complications.The match rate of LSGB pathological results of the proposed surgical procedure with the final diagnosis of pSS is high.

T cell exhaustion and senescence for ovarian cancer immunotherapy.

Ovarian cancer is a common gynecological malignancy, and its treatment remains challenging. Although ovarian cancer may respond to immunotherapy because of endogenous immunity at the molecular or T cell level, immunotherapy has so far not had the desired effect. The functional status of preexisting T cells is an indispensable determinant of powerful antitumor immunity and immunotherapy. T cell exhaustion and senescence are two crucial states of T cell dysfunction, which share some overlapping phenotypic and functional features, but each status possesses unique molecular and developmental signatures. It has been widely accepted that exhaustion and senescence of T cells are important strategies for cancer cells to evade immunosurveillance and maintain the immunosuppressive microenvironment. Herein, this review summarizes the phenotypic and functional features of exhaust and senescent T cells, and describes the key drivers of the two T cell dysfunctional states in the tumor microenvironment and their functional roles in ovarian cancer. Furthermore, we present a summary of the molecular machinery and signaling pathways governing T cell exhaustion and senescence. Possible strategies that can prevent and/or reverse T cell dysfunction are also explored. An in-depth understanding of exhausted and senescent T cells will provide novel strategies to enhance immunotherapy of ovarian cancer through redirecting tumor-specific T cells away from a dysfunctional developmental trajectory.

Design and Experimental Study of an Improved Pressure Core Sampler for Marine Gas Hydrates.

A pressure core sampler (PCS) is considered an effective tool to retrieve marine gas hydrate cores from hydrate-bearing sediments. However, according to the sampling application statistics, the success rate of pressure coring changed from 30% to 85% in different drilling wells. Such severe fluctuation will cause huge uncertainty in the practical application of technology and economic benefits. Herein, we present a new PCS designed to improve pressure-retaining reliability. The work principle, design and calculations, and structure composition were described. Through the laboratory tests and drilling experiments, the maximum holding pressure in the pressure chamber was 32.1 MPa, and the pressure loss rates of holding pressure after 2 h changed from 1.96% to 2.46%. The maximum temperature-rising value in the pressure chamber was 0.96 °C under a temperature of 23.5 °C in 2 h. Furthermore, the success rate of the pressure core reached 87.5% and the core recovery was not less than 80%, which were verified by 8 pressure core runs in three different offshore wells. Therefore, we conclude that this new and improved PCS has great application value in gas hydrate exploration that seeks to recover more accurate cores in situ, especially in the silt and sand layers.

[Research on mechanism of hypolipidemic effect of Massa Medicata Fermentata based on metabolomics].

This paper aims to study the therapeutic effect of Massa Medicata Fermentata on hyperlipidemia model rats and investigate its mechanism of hypolipidemic effect with the help of non-targeted metabolomics. The mixed hyperlipidemia model rats were constructed by giving high-fat chow. After successful modeling, the rats were divided into the model group, pravastatin sodium group(4.4 mg·kg~(-1)), lipotropic group(0.1 g·kg~(-1)), high-dose group(2.4 g·kg~(-1)), medium-dose group(1.2 g·kg~(-1)), and low-dose group(0.6 g·kg~(-1)) of Massa Medicata Fermentata, and they were administered for four weeks once daily. An equal volume of ultrapure water was given to the blank group and model group. Serum lipid level and liver hematoxylin-eosin(HE) staining were used as indicators to estimate the intervention effect of Massa Medicata Fermentata on mixed hyperlipidemia, and the changes in metabolites in plasma of mixed hyperlipidemia model rats were analyzed by non-targeted metabolomics. The mechanism of the hypolipidemic effect of Massa Medicata Fermentata was analyzed through metabolite pathway enrichment. The results showed that compared with the model group, the Massa Medicata Fermentata administration group, especially the high-dose group, could significantly reduce the content of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c)(P<0.05 or P<0.01), and liver HE staining revealed that the number of adipocytes in the high-dose group was reduced to some extent. The potential biomarkers obtained by non-targeted metabolomics screening included glycerol 3-phosphate, sphingomyelin, sphingosine 1-phosphate, and deoxyuridine, which were mainly involved in the sphingolipid metabolism process, glycerophospholipid metabolism process, glycerol ester metabolism pathway, and pyrimidine metabolism pathway, totaling four possible metabolic pathways related to lipid metabolism. This study provides a reference for an in-depth investigation of the hypolipidemic mechanism of Massa Medicata Fermentata, which is of great significance for further promoting the clinical application of Massa Medicata Fermentata and increasing the indications.

Widely targeted metabolomics reveals differences in metabolites of Paeonia lactiflora cultivars.

INTRODUCTION: Paeonia lactiflora contains diverse active constituents and exhibits various pharmacological activities. However, only partial identification of biologically active substances from P. lactiflora has been achieved using low-throughput techniques. Here, the roots of P. lactiflora, namely, Fenyunu (CK), Dafugui (DFG), and Red Charm (HSML), were studied. The primary and secondary metabolites were investigated using ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESIMS/MS). METHODS: The chemical compounds and categories were detected using broadly targeted UPLC-MS/MS. Principal component analysis (PCA), orthogonal partial least-squares discriminant analysis (OPLS-DA), and hierarchical clustering analysis (HCA) were carried out for metabolites of different varieties of P. lactiflora. RESULTS: A total of 1237 compounds were detected and classified into 11 categories. HCA, PCA, and OPLS-DA of these metabolites indicated that each variety of P. lactiflora was clearly separated from the other groups. Differential accumulated metabolite analysis revealed that the three P. lactiflora varieties contained 116 differentially activated metabolites (DAMs) involved in flavonoid, flavone, and flavonol metabolism. KEGG pathway analysis revealed that, in 65 pathways, 336 differentially abundant metabolites (DMs) were enriched in the CK and DFG groups; moreover, the type and content of terpenoids were greater in the CK group than in the DFG group. The CK and HSML groups contained 457 DMs enriched in 61 pathways; the type and amount of flavonoids, terpenoids, and tannins were greater in the CK group than in the HSML group. The DFG and HSML groups contained 497 DMs enriched in 65 pathways; terpenoids and alkaloids were more abundant in the HSML variety than in the DFG variety. CONCLUSIONS: A total of 1237 compounds were detected, and the results revealed significant differences among the three P. lactiflora varieties. Among the three P. lactiflora varieties, phenolic acids and flavonoids composed the largest and most diverse category of metabolites, and their contents varied greatly. Therefore, CK is suitable for medicinal plant varieties, and DFG and HSML are suitable for ornamental plant varieties. Twelve proanthocyanidin metabolites likely determined the differences in color among the three varieties.

Decorating Pd-Au Nanodots Around Porous In2O3 Nanocubes for Tolerant H2 Sensing Against Switching Response and H2S Poisoning.

With the recently-booming hydrogen (H2) economy by green H2 as the energy carriers and the newly-emerged exhaled diagnosis by human organ-metabolized H2 as a biomarker, H2 sensing is simultaneously required with fast response, low detection limit, and tolerant stability against humidity, switching, and poisoning. Here, reliable H2 sensing has been developed by utilizing indium oxide nanocubes decorated with palladium and gold nanodots (Pd-Au NDs/In2O3 NCBs), which have been synthesized by combined hydrothermal reaction, annealing, and chemical bath deposition. As-prepared Pd-Au NDs/In2O3 NCBs are observed with surface-enriched NDs and nanopores. Beneficially, Pd-Au NDs/In2O3 NCBs show 300 ppb-low detection limit, 5 s-fast response to 500 ppm H2, 75%RH-high humidity tolerance, and 56 days-long stability at 280 °C. Further, Pd-Au NDs/In2O3 NCBs show excellent stability against switching sensing response, and are tolerant to H2S poisoning even being exposed to 10 ppm H2S at 280 °C. Such excellent H2 sensing may be attributed to the synergistic effect of the boosted Pd-Au NDs' spillover effect and interfacial electron transfer, increased adsorption sites over the porous NCBs' surface, and utilized Pd NDs' affinity with H2 and H2S. Practically, Pd-Au NDs/In2O3 NCBs are integrated into the H2 sensing device, which can reliably communicate with a smartphone.

Novel peptides from sea cucumber intestines hydrolyzed by neutral protease alleviate exercise-induced fatigue via upregulating the glutaminemediated Ca2+ /Calcineurin signaling pathway in mice.

Sea cucumber intestines are considered a valuable resource in the sea cucumber processing industry due to their balanced amino acid composition. Studies have reported that peptides rich in glutamate and branched-chain amino acids have anti-fatigue properties. However, the function of the sea cucumber intestine in reducing exercise-induced fatigue remains unclear. In this study, we enzymatically hydrolyzed low molecular weight peptides from sea cucumber intestines (SCIP) and administered SCIP orally to mice to examine its effects on exercise-induced fatigue using swimming and pole-climbing exhaustion experiments. The results revealed that supplementation with SCIP significantly prolonged the exhaustion time of swimming in mice, decreased blood lactate and urea nitrogen levels, and increased liver and muscle glycogen levels following a weight-loaded swimming test. Immunofluorescence analysis indicated a notable increase the proportion of slow-twitch muscle fiber and a significant decrease the proportion of fast-twitch muscle fiber following SCIP supplementation. Furthermore, SCIP upregulated mRNA expression levels of Ca2+ /Calcineurin upstream and downstream regulators, thereby contributing to the promotion of skeletal muscle fiber type conversion. This study presents the initial evidence establishing SCIP as a potential enhancer of skeletal muscle fatigue resistance, consequently providing a theoretical foundation for the valuable utilization of sea cucumber intestines.

Interfering with the AKT/mTOR/STAT3/ID1 signaling axis with usenamine A restrains the proliferative and invasive potential of human hepatocellular carcinoma cells.

BACKGROUND: Usenamine A, a novel natural compound initially isolated from the lichen Usnea longissima, has exhibited promising efficacy against hepatoma in prior investigation. Nevertheless, the underlying mechanisms responsible for its antihepatoma effects remain unclear. Furthermore, the role of the AKT/mechanistic target of the rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3)/inhibitor of differentiation/DNA binding 1 (ID1) signaling axis in hepatocellular carcinoma (HCC), and the potential anti-HCC effects of drugs targeting this pathway are not well understood. METHODS: CCK-8 assay was used to investigate the effects of usenamine A on the proliferation of human HCC cells. Moreover, the effects of usenamine A on the invasion ability of human HCC cells were evaluated by transwell assay. In addition, expression profiling analysis, quantitative real-time PCR, immunoblotting, immunohistochemistry (IHC) analysis, RNAi, immunoprecipitation, and chromatin immunoprecipitation (ChIP) assay were used to explore the effects of usenamine A on the newly identified AKT/mTOR/STAT3/ID1 signaling axis in human HCC cells. RESULTS: Usenamine A inhibited the proliferation and invasion of human HCC cell lines (HepG2 and SK-HEP-1). Through the analysis of gene expression profiling, we identified that usenamine A suppressed the expression of ID1 in human HCC cells. Furthermore, immunoprecipitation experiments revealed that usenamine A facilitated the degradation of the ID1 protein via the ubiquitin-proteasome pathway. Moreover, usenamine A inhibited the activity of STAT3 in human HCC cells. ChIP analysis demonstrated that STAT3 positively regulated ID1 expression at the transcriptional level in human HCC cells. The STAT3/ID1 axis played a role in mediating the anti-proliferative and anti-invasive impacts of usenamine A on human HCC cells. Additionally, usenamine A suppressed the STAT3/ID1 axis through AKT/mTOR signaling in human HCC cells. CONCLUSION: Usenamine A displayed robust anti-HCC potential, partly attributed to its capacity to downregulate the AKT/mTOR/STAT3/ID1 signaling pathway and promote ubiquitin-proteasome-mediated ID1 degradation. Usenamine A has the potential to be developed as a therapeutic agent for HCC cases characterized by abnormal AKT/mTOR/STAT3/ID1 signaling, and targeting the AKT/mTOR/STAT3 signaling pathway may be a viable option for treating patients with HCC exhibiting elevated ID1 expression.