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1.
Hepatol Int ; 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35028922

RESUMO

BACKGROUND AND AIMS: Gamma-delta (γδ) T cells are involved in the development of diverse liver and autoimmune diseases, whereas the role of γδ T cells in primary biliary cholangitis (PBC) remains unclear. METHODS: We analyzed the number, phenotypes, and functional molecules of both circulating and hepatic γδ T cells in PBC patients and healthy controls (HCs) by flow cytometric analysis and immunohistochemistry. RESULTS: We identified two distinct functional subsets of circulating γδ T cells according to the CD3/TCRγδ complex: the TCRγδhigh and TCRγδlow subsets. Approximately, three-quarters of cells in the TCRγδhigh subset were Vδ1 T cells, while Vδ2 T cells were enriched in the TCRγδlow subset in HCs. The frequency and absolute number of circulating TCRγδlow cells were significantly decreased in PBC patients compared with HCs (p < 0.001). Furthermore, the frequency of TCRγδlow cells was correlated with disease severity and ursodeoxycholic acid (UDCA) response. TCRγδlow cells exhibited a similar apoptotic and proliferative phenotype, but enhanced liver-homing chemokine receptor (CXCR6) expression in PBC patients compared with HCs. In addition, circulating TCRγδlow cells were more activated and produced higher granzyme B (GZMB) in PBC patients compared with HCs. Finally, compared with heathy liver controls, hepatic γδ T cells were increased and infiltrated in the inflamed portal tracts in PBC liver. Furthermore, the number of hepatic γδ T cells was correlated with cholestatic markers and UDCA response. CONCLUSION: The circulating TCRγδlow subset may migrate to the liver via the CXCR6-CXCL16 axis and be involved in the pathogenesis of PBC by increasing GZMB production.

2.
Br J Pharmacol ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34997582

RESUMO

BACKGROUND AND PURPOSE: As the only ionotropic receptor in 5-HT receptor family, 5-HT3 receptor (5-HT3R) involves in psychiatric disorders and its modulators have potential therapeutic effects for cognitive impairment in these disorders. However, it remains unclear how 5-HT3Rs shape synaptic plasticity for memory function. EXPERIMENTAL APPROACH: Extracellular as well as whole-cell recordings were used to monitor hippocampal long-term potentiation (LTP) and synaptic transmission in hippocampal slices from 5-HT3AR knock-out or 5-HT3AR-GFP mice. Immunocytochemistry, qRT-PCR and Western blot were used to measure receptor expression. We also assessed hippocampal dependent cognition and memory using the Morris water maze (MWM) and novel object recognition. KEY RESULTS: We found that 5-HT3R dysfunction impaired hippocampal LTP in Schaffer collateral (SC)-CA1 pathway in hippocampal slices by facilitating GABAergic inputs in pyramidal cells. This effect was dependent on 5-HT3Rs on axon-terminals. It resulted from reduced expression and function of cannabinoid receptor 1 (CB1R) co-localized with 5-HT3Rs on axon terminals, which led to diminishment of tonic inhibition of GABA release by CB1Rs. Inhibition of CB1Rs mimicked the facilitation of GABAergic transmission by 5-HT3R disruption. Consequently, mice with hippocampal 5-HT3R disruption exhibited impaired spatial memory in Morris water maze tasks. CONCLUSION AND IMPLICATIONS: These results suggest that 5-HT3Rs are crucial in enabling hippocampal synaptic plasticity via a novel CB1R-GABAA -dependent pathway to regulate spatial memory.

3.
Asian J Surg ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35031180

RESUMO

BACKGROUND: Enhanced Recovery After Surgery (ERAS) has been used to improve surgical outcomes in recent years. However, its safety and efficacy in elderly patients with gastric cancer remain unclear. The aim of this study was to reveal the safety and efficacy of the ERAS protocol in elderly patients with gastric cancer. METHODS: Elderly gastric cancer patients (age≥70 years) who underwent gastrectomy were divided into the ERAS group and the conventional group. Postoperative complications, postoperative hospital stay, hospitalization expenses, and readmission rates were compared between the two groups. RESULTS: From December 2019 to January 2021, 100 eligible patients were enrolled in our study. All baseline data were balanced between the ERAS group and the conventional group. There was no significant difference in terms of complications (18% vs. 16%, P = 0.14) between the two groups. The most common complication was pneumonia. Four patients were observed in the conventional group and three patients in the ERAS group. The postoperative hospital stay was shorter in the ERAS group (8.2 vs. 10.4, P = 0.001). CONCLUSIONS: The ERAS protocol could be safely used in elderly gastric cancer patients undergoing gastrectomy and shorten postoperative hospital stay.

4.
Mol Ther Nucleic Acids ; 27: 122-132, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-34976432

RESUMO

Effective treatments for prostate cancer (PCa) require further development, and previous studies have reported that PTEN and its downstream target CDKN1B are significantly downregulated in PCa cells compared with normal cells. Therefore, modulation of PTEN and CDKN1B expression might be a promising therapeutic approach for PCa treatment. Expression of PTEN and CDKN1B was verified in specimens from PCa patients and transgenic adenocarcinoma mouse prostate (TRAMP) mice. The effect of PTEN on PCa cell migration, apoptosis, and the cell cycle was analyzed in vitro using a wound-healing assay and flow cytometry. We assessed the ability of intraprostatic and intratumoral injections of recombinant adeno-associated virus (rAAV) 9 expressing Pten or Cdkn1b into TRAMP mice and a subcutaneous tumor xenograft mouse model, respectively, to inhibit PCa progression. PTEN and CDKN1B were significantly downregulated in human and mouse PCa samples, and CDKN1B expression correlated positively with PTEN expression. PTEN overexpression significantly inhibited cell migration and cell-cycle progression and promoted apoptosis in PCa cells by decreasing Ccnd1 expression and increasing that of Cdkn1b. Importantly, treatment with the rAAV9.Pten or rAAV9.Cdkn1b extended the lifespan of TRAMP mice and inhibited the growth rate of tumor xenografts by regulating downstream gene expression. Moreover, neoplasia in treated prostates was significantly diminished compared with that in control prostates, and apoptosis was markedly observed in xenografts treated with Pten or Cdkn1b. These data indicate that rAAV-based PTEN/CDKN1B delivery is promising for the development of novel therapeutics for PCa.

5.
Arch Microbiol ; 204(1): 112, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982208

RESUMO

In this study, a bacteriocin PA996 isolated from Pseudomonas azotoformans (P. azotoformans) was purified to homogeneity by ammonium sulphate precipitation and SP-Sepharose column chromatography. P. azotoformans began to grow at 6 h, reached exponential phase at 12-18 h. Bacteriocin PA996 was produced at 18 h and reached a maximum level of 2400 AU/mL. The molecular mass of purified bacteriocin PA996 was estimated by SDS-PAGE and its molecular mass was approximately 50 kDa. By screening in vitro, the bacteriocin PA996 showed an antimicrobial activity against Pasteurella multocida (P. multocida). The bacteriocin PA996 showed antibacterial activity in the range of pH2-10 and it was heat labile. The inhibitory activities were diminished after treatment with proteinase K, trypsin and papain, respectively, while catalase treatment was ineffective. The minimal inhibitory concentration (MIC) and bactericidal kinetics curves showed that the bacteriocin PA996 had a good inhibitory ability against P. multocida. Our data indicate that bacteriocin PA996 could inhibit the growth of P. maltocida and it may have the potential to apply as an alternative therapeutic drug.


Assuntos
Antibacterianos , Bacteriocinas , Pasteurella multocida/efeitos dos fármacos , Pseudomonas , Antibacterianos/farmacologia , Bacteriocinas/farmacologia , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana
6.
Cytokine ; 149: 155729, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34673333

RESUMO

OBJECT: Goal of this research was to investigate values of serum cytokines in childhood HLH with different triggers, with the expectation to find secretion spectrum of 5 main types of underlying diseases. METHOD: 118 newly diagnosed HLH were included, and serum concentrations of 6 cytokines were tested before treatment began. Absolute cytokine levels and ratios between them were then studied in the HLH groups collectively and separately RESULTS: In general, IFN-γ, IL-10 and IL-6 showed differences among 5 HLH groups. Specifically, relative levels of these three cytokines to each other were meaningful in distinguishing 4 types of HLH. Level of IL-6 was higher than those of IFN-γ or IL-10 in HLH driven by Systemic auto-inflammatory disorders (SAIDs) or Langerhans Cell Histiocytosis (LCH), while primary HLH and EBV-HLH shared elevated ratio of IL-10 to IL-6. Although more than one distinctive ratios were found in 3 HLH groups, combination of these parameters didn't offer optimal balance between sensitivity and specificity. CONCLUSION: As a group of easily gained laboratory findings, cytokine levels were reliable in the procedure of roughly classifying HLH cases with the help of patients' clinical phenotype. However, adequate data is still needed to explore the significance of these indicators in identifying one particular underlying disease accurately.

7.
J Colloid Interface Sci ; 607(Pt 2): 933-941, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34571314

RESUMO

A subtle flower-like MIL-125-NH2@BiOI was fabricated by a facile solvothermal method for simultaneously eliminating Cr(VI)/tetracycline mixed pollutants under visible light. The strong interaction between amino in MIL-125-NH2 and Bi3+ of BiOI promotes the formation of this unique inlaid structure and enables the favorable contact between MIL-125-NH2 and BiOI, thus accelerating the transfer of charge carriers. Remarkably, MIL-125-NH2@BiOI displays a superior activity compared with that of two monomers for the photocatalytic reduction of Cr(VI) and degradation of tetracycline. More significantly, the photocatalytic efficiency can be further boosted in the coexistence of Cr(VI) and tetracycline, which is 1.8 and 1.6 times that of single Cr(VI) and tetracycline, respectively. The synergistic effect between Cr(VI) reduction and tetracycline oxidative degradation can further facilitate the separation of photo-induced electrons and holes, resulting in the improved efficiencies in the Cr(VI)/tetracycline coexistent environment. This work sheds light on that MOF-based photocatalysts possess huge potential for practical environmental remediation.


Assuntos
Estruturas Metalorgânicas , Titânio , Catálise , Cromo , Tetraciclina
8.
Oncol Lett ; 23(1): 7, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34820006

RESUMO

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by breakpoint cluster region-abelson leukemia virus (BCR/ABL) kinase. Targeting BCR/ABL kinase with tyrosine kinase inhibitors combined with chemotherapy is the standard first-line therapy for Ph+ ALL. Imatinib and dasatinib are the preferred agents for the treatment of Ph+ ALL. Dasatinib treatment can induce a faster and deeper remission than imatinib treatment; however, the side effects of dasatinib, especially the cardiovascular side effects, are markedly greater than those of imatinib. Patients will benefit from treatments that improve the efficacy of imatinib without increasing its side effects. The present study revealed that tanshinone IIA markedly potentiated the cytotoxic and apoptotic induction effects of imatinib by regulating the AKT-MDM2-P53 signaling pathway and inhibiting the anti-apoptotic proteins BCL2 and MCL1 apoptosis regulator, BCL2 family member in Ph+ ALL cell lines. In vitro studies, MTT assay, flow cytometry, western blotting and reverse transcription-quantitative PCR were performed in the present study to detect cell viability, cell apoptosis, protein expression and gene expression, respectively. In a Ph+ ALL mouse model, imatinib combined with tanshinone IIA also exhibited a synergistic effect on the reduction in leukemia burden without increasing the toxic side effects of imatinib. These results demonstrated that imatinib combined with tanshinone IIA might be a promising treatment strategy for patients with Ph+ ALL.

9.
Cell Biol Int ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34854517

RESUMO

The key to successful in vitro embryo production (IVEP) is to mimic the natural in vivo oviductal microenvironment. Although the chemically defined media in extensive use for the in vitro culture of mammalian embryos is based on the composition of oviductal fluid, the IVEP systems in current use must still bypass the oviduct to produce embryos in vitro. Extracellular vesicles (EVs) in the oviduct are versatile intercellular delivery vehicles for maternal-embryo communication, and a lack of them can be associated with failed early embryonic development under in vitro culture conditions. Herein, we isolated EVs from porcine oviduct fluid and confirmed that oviductal EV supplementation improves the embryonic development of parthenogenetically activated (PA) embryos in terms of blastocyst formation rates and total cell numbers. Our experiments also revealed that a beneficial effect of oviductal EVs on PA embryos was achievable, at least in part, by relieving endoplasmic reticulum stress. These results suggest that the maternal-embryo communication mediated by oviductal EVs benefits early embryonic development. Given the contribution of oviductal EVs to early embryonic development, these findings offer novel insights for the optimization of current IVEP systems.

10.
World J Diabetes ; 12(11): 1894-1907, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34888014

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with a heightened level of oxidative stress, which is characterized by the overproduction of reactive oxygen species (ROS) from mitochondria. Previous studies showed that mitochondrial dysfunction is regulated by dynamin-related protein 1 (Drp1) and p66Shc in GDM. AIM: The aim was to investigate the expression of Drp1 and p66Shc and their possible mechanisms in the pathogenesis of GDM. METHODS: A total of 30 pregnant women, 15 with GDM and 15 without GDM, were enrolled. Peripheral blood mononuclear cells and placental tissue were collected. The human JEG3 trophoblast cell line was cultivated in 5.5 mmol/L or 30 mmol/L glucose and transfected with wild-type (wt)-p66Shc and p66Shc siRNA. P66Shc and Drp1 mRNA levels were detected by quantitative real-time polymerase chain reaction. The expression of p66Shc and Drp1 was assayed by immunohistochemistry and western blotting. ROS was assayed by dihydroethidium staining. RESULTS: The p66Shc mRNA level was increased in the serum (P < 0.01) and placentas (P < 0.01) of women with GDM, and the expression of Drp1 mRNA and protein were also increased in placentas (P < 0.05). In JEG3 cells treated with 30 mmol/L glucose, the mRNA and protein expression of p66Shc and Drp1 were increased at 24 h (both P < 0.05), 48 h (both P < 0.01) and 72 h (both P < 0.001). ROS expression was also increased. High levels of Drp1 and ROS expression were detected in JEG3 cells transfected with wt-p66Shc (P < 0.01), and low levels were detected in JEG3 cells transfected with p66Shc siRNA (P < 0.05). CONCLUSION: The upregulated expression of Drp1 and p66shc may contribute to the occurrence and development of GDM. Regulation of the mitochondrial fusion-fission balance could be a novel strategy for GDM treatment.

11.
J Healthc Eng ; 2021: 4377156, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868519

RESUMO

Sports violence is a critical issue that has hindered China's sports development. Dual logic is currently the mainstream rule of law and industrial autonomy, although it has not produced satisfactory results. In this paper, we used expert interviews, text analysis, and case analysis to investigate the flaws in the current governance process and found that the dual logic of sports violence governance has problems of varying degrees. The low degree of legislative specialization, the hazy limit of judicial intervention, and disparate law enforcement are examples of the rule of law. The clash of rights and interests between the association and the state, the association's ineffectual control over the junior leagues, and the limited scope of governance are all examples of industry autonomy. Based on the issues mentioned above, this paper proposes dual logic strengthening measures and the notion of integrated governance. In particular, we should improve the rule of law thinking and construct a legal system for sports violence in China from legislation, justice and law enforcement, and law-abidingness to compensate for the current lack of law in sports violence. Second, we define the scope of the association's "postdecoupling era" powers and obligations, resolve conflicts through state involvement based on the rule of law, and remove governance hurdles. Finally, we thoroughly investigate three aspects of integrated governance between the rule of law and industry autonomy: respecting industry autonomy and providing specific implementation space for industry norms, not excluding the rule of law's intervention, and establishing an industry autonomy supervision mechanism. The rule of law and industry autonomy permeate each other and realize integration.

12.
J Healthc Eng ; 2021: 2887639, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858562

RESUMO

Objective: To study the qualitative value of multislice spiral CT (MSCT) dynamic enhancement scanning for solitary nodules (SPN) of the chest. Methods: In this paper, 40 cases of chest nodules (including 25 cases of malignant nodules, 8 cases of inflammatory nodules, and 7 cases of benign nodules) were first scanned to determine the scope of nodules. At the two rates of 5 ml/s and 3 ml/s, CT dynamic enhancement scans were performed at the center of the nodule, and the CT values, peak enhancement (PH) and peak time (PT) before and after SPN enhancement, were recorded. It is mainly strengthened, with 80% (20/25) of net added value between 20 and 60 Hu, and 20% (5/25) >60 Hu or <20 Hu. The enhancement peak and peak time are (31.31 ± 10.62) Hu and 45 s, respectively. The time-density curve (T-DC) showed a slowly rising type; the inflammatory nodules were mainly severely strengthened, with a net increase of >40 Hu. The enhancement peak value is (49.25 ± 12.44) Hu, and the peak time is 80 s and 140 s. There is a characteristic of rising and falling and then rising in the curve. Conclusion: Multislice spiral CT dynamic enhancement scan reflects the dynamic characteristics of chest nodular blood flow, which can be used to noninvasively evaluate and diagnose SPN.

13.
Metabolism ; 128: 154958, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34958817

RESUMO

BACKGROUND: With metabolic dysfunction-associated fatty liver disease (MAFLD) incidence and prevalence increasing, it is necessary to identify patients with advanced fibrosis (F3-F4 stages). We evaluated the performance of new biomarkers and algorithms for diagnosing advanced fibrosis in an Asian population. METHODS: Data from two Asian cohorts (including 851 biopsy-proven MAFLD [578 from Wenzhou, 273 from Hong Kong]) were studied. The association between N-terminal propeptide of type 3 collagen (PRO-C3) and the histologic stage of liver fibrosis was analyzed by multivariable linear regression. The area under the receiver operating characteristic curve (AUROC) was used to test the diagnostic performance of serum PRO-C3 and the ADAPT score for advanced fibrosis and compared them to other established non-invasive tests. RESULTS: Serum PRO-C3 levels increased progressively across liver fibrosis stages and correlated with advanced fibrosis (P < 0.001). The ADAPT score had an AUROC of 0.865 (95% confidence interval 0.829-0.901) for advanced fibrosis; the accuracy, sensitivity and negative predictive values were 81.4%, 82.2% and 96.1%, respectively. This result was better compared to that of PRO-C3 alone or other non-invasive fibrosis biomarkers (aspartate aminotransferase-to-platelet ratio index, Fibrosis-4, BARD, and NAFLD fibrosis score). In subgroup analyses (including sex, age, diabetes, NAFLD activity score, body mass index or serum alanine aminotransferase levels), the ADAPT score had good diagnostic performance. CONCLUSION: PRO-C3 and the ADAPT score reliably exclude advanced fibrosis in MAFLD patients and reduce the need for liver biopsy.

16.
Chin J Nat Med ; 19(11): 856-867, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34844724

RESUMO

Chansu has demonstrated adverse reactions in clinical settings, which is associated with its toxicity and limits its clinical applications. But there are methodological limitations for drug safety evaluation. In the current study, ultra-high performance liquid chromatography, lipidomic profiling, and molecular docking were used to systemically assess Chansu-induced acute inflammatory irritation and further identify the underlying drug targets. Compared with the EtOAc extract, Chansu water fraction containing indolealkylamines caused acute inflammatory irritation in rats, including acute pain (spontaneous raising foot reaction), and inflammation (paw edema). At the molecular level, lipids analysis revealed significantly higher levels of pro-inflammatory mediators of the COX and LOX pathways. However, anti-inflammatory mediators from the CYP 450, ALA, and DHA pathways markedly decreased after exposure to Chansu water fraction. Moreover, four indolealkylamines from Chansu showed a high theoretical affinity to a known irritation target, 5-HT2AR. These results suggest that Chansu-induced inflammatory irritation is related to the distinct dysregulation of inflammatory lipids, and peripheral 5-HT2AR is a potential target for irritation therapy. The strategy used in this study can be a crucial approach in the safety evaluation of natural medicinal substances.

17.
Nanomaterials (Basel) ; 11(11)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34835788

RESUMO

The manipulations of nanoscale multi-channel vector beams (VBs) by metasurfaces hold potential applications in various important fields. In this paper, the metasurface with two sets of nanoslits arranged on elliptic curves was proposed to generate the dual-channel focused vector beams (FVBs). Each set of nanoslits was composed of the in-phase and the out-of-phase groups of nanoslits to introduce the constructive interference and destructive interference of the output light field of the nanoslits, focusing the converted spin component and eliminating the incident spin component at the focal point. The two sets of nanoslits for the channels at the two focal points were interleaved on the same ellipses, and by setting their parameters independently, the FVBs in the two channels are generated under illumination of linearly polarized light, while their orders and polarization states of FVBs were controlled independently. The generation of the FVBs with the designed metasurfaces was demonstrated by the finite-difference time domain (FDTD) simulations and by the experimental verifications. The work in this paper is of great significance for the generation of miniaturized multi-channel VBs and for broadening the applications of metasurfaces.

18.
Clin Mol Hepatol ; 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34839623

RESUMO

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD. Methods: We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392 and vitamin D and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed. Results: Carriage of the rs495392 A allele had a protective effect on steatosis severity (OR = 0.61, 95% CI: 0.42 - 0.89, P = 0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR = 0.66, 95% CI: 0.45 - 0.98, P = 0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis. Conclusions: The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.

19.
Microbiol Spectr ; : e0080221, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787462

RESUMO

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although dysbiosis of the lung and gut microbiota have been associated with NSCLC, their relative contributions are unclear; in addition, their roles in distant metastasis (DM) are still illusive. We recruited in total 121 participants, including 87 newly diagnosed treatment-naive NSCLC patients of various stages and 34 healthy volunteers, and surveyed their fecal and sputum microbiota. We compared the microbial profiles between groups, identified microbial biomarkers, and generated machine learning models for distinguishing healthy individuals from patients with NSCLC and patients of various stages. We found significant perturbations of gut and sputum microbiota in patients with NSCLC and DM. A machine learning model combining both microbiota (combined model) performed better than an individual data set in patient stratification, with the highest area under the curve (AUC) value of 0.896. Sputum and gut microbiota both contributed to the combined model; in most cases, sputum-only models performed similar to the combined models. Several microbial biomarkers were shared by both microbiotas, indicating their similar roles at distinct body sites. Microbial biomarkers of distinct disease stages were mostly shared, suggesting biomarkers for DM could be acquired early. Furthermore, Pseudomonas aeruginosa, a species previously associated with wound infections, was significantly more abundant in brain metastasis, indicating that distinct types of DMs could have different microbes. Our results indicate that alterations of the sputum microbiota have stronger relationships with NSCLC and DM than the gut and strongly support the feasibility of metagenome-based noninvasive disease diagnosis and risk evaluation. (This study has been registered at ClinicalTrials.gov under registration no. NCT03454685). IMPORTANCE Our survey on gut and sputum microbiota revealed that both were significantly disturbed in non-small cell lung cancer (NSCLC) and associated with distant metastasis (DM) while only the sputum microbiota was associated with non-DM NSCLC. The lung microbiota could therefore have a stronger association with (and thus may contribute more to) disease development than the gut microbiota. Mathematic models using both microbiotas performed better in patient stratification than using individual microbiota. Sputum models, however, performed similar to the combined models, suggesting a convenient, noninvasive diagnostic for NSCLC. Microbial biomarkers of distinct disease stages were mostly shared, suggesting that the same set of microbes were underlying disease progression, and the signals for distant metastasis could be acquired at early stages of the disease. Our results strongly support the feasibility of noninvasive diagnosis of NSCLC, including distant metastasis, are of clinical importance, and should warrant further research on the underlying molecular mechanisms.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34816608

RESUMO

AIM: The present study aimed to investigate the prevalence rate of objective and subjective psychosis-like experiences (PLEs) in non-help-seeking college students and to explore their differential contributions to suicidal ideation. METHODS: First-year college students were recruited and surveyed with the Chinese version of the 16-item Prodromal Questionnaire (CPQ-16), Childhood Trauma Questionnaire (CTQ-SF), Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7) and Beck Scale for Suicide Ideation (BSI). The Structured Interview of Psychosis-Risk Syndromes (SIPS) was conducted in individuals with a CPQ-16 score of 9 or higher. RESULTS: Data were available for 8367 students. Three hundred and seventy of them scored 9 or higher on the CPQ-16, suggesting potential PLEs (4.42%). Among them, 194 agreed to the SIPS screening. The PLEs were confirmed in 103 individuals who scored 1-5 on any positive symptom scales of the SIPS (objective PLEs, oPLEs). For the remaining 91 individuals, their PLEs were not confirmed by the SIPS and thus were categorized as individuals with subjective PLEs (sPLEs). In univariate logistic regression, oPLEs was associated with a two times risk of suicidal ideation compared to sPLEs (OR = 1.971, p = .029). In multivariate logistic regression when non-PLE status was set as a reference, oPLEs significantly predicted suicidal ideation (OR = 3.441, p = .011), while the sPLEs (OR = 2.277, p = .091) was no longer a significant predictor after controlling for PHQ-9, GAD-7 and CPQ-SF scores. CONCLUSIONS: OPLEs and sPLEs have differential contributions to suicidal ideation. OPLEs seems to be associated with a higher risk of suicidal ideation and is independent of other psychopathology.

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