Human Wharton's jelly-derived mesenchymal stem cells prevent pregnancy loss in a rat by JAK/STAT-mediated immunomodulation.

AIM: Spontaneous abortion (SA) is a multiple-original syndrome with immune imbalance as one of its major risk factors. As Wharton's jelly-mesenchymal stem cells (WJ-MSCs) are considered to be able to prevent abortion, this study aims to explore the currently poorly understood underlining molecular signaling pathways and regulatory mechanisms of WJ-MSCs in pregnancy maintenance. METHODS: Abortion mode is established by subcutaneous injection of bromocriptine in rat on day 9 and abortion prevention is achieved by WJ-MSCs injection via tail vein. WJ-MSCs were cultured with/without the inhibitors of JAK/STAT or NF-κB. The uterus was collected on the 14th day of gestation and the rate of embryo absorption was calculated. The expression of Th1/Th2/Th3 cytokines in decidual, placental tissue, and peripheral blood was analyzed. RESULTS: WJ-MSCs treatment significantly reduced the abortion rate in bromocriptine-treated pregnancy such that it was not significantly different from a normal pregnancy. JAK/STAT inhibition abolished pregnancy preserving effects of WJ-MSCs but NF-κB inhibition did not. The levels of Th1-related cytokines and mRNA levels in the bromocriptine abortion model were significantly higher than the normal pregnancy group and ethanol control group, while levels of the Th2-related cytokines and mRNA levels significantly decreased. WJ-MSCs transfusion into the abortion model restored cytokine profiles such that they were not significantly different from the normal pregnancy group and ethanol control group. JAK/STAT inhibition of WJ-MSCs prevented their effect on cytokine and mRNA levels, but NF-κB inhibition did not. CONCLUSIONS: WJ-MSCs significantly lower the rate of embryo resorption of spontaneous abortion by reducing Th1-related cytokines while increasing Th2 and Th3-related cytokines in JAK/STAT-dependent manner.

Cellulomonas triticagri sp. nov., isolated from the rhizosphere soil of wheat (Triticum aestivum L.).

A Gram-positive, motile, rod-shaped and lignin-degrading novel actinomycete, designated strain NEAU-YY56T, was isolated from the rhizosphere soil of wheat (Triticum aestivum L.) collected from Zhumadian, Henan Province, Central China and characterized using a polyphasic approach. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain NEAU-YY56T belonged to the genus Cellulomonas and exhibited 16S rRNA gene sequence similarities of 98.7, 98.2 and 98.1% to Cellulomonas pakistanensis JCM 18755T, Cellulomonas denverensis JCM 14733T and Cellulomonas hominis JCM 12133T, respectively. The whole-cell sugars were glucose, rhamnose and ribose. The peptidoglycan of strain NEAU-YY56T contained ornithine and glutamic acid. The phospholipid profile was found to contain diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannoside and two unknown glycolipids. The major menaquinone was MK-9(H4). The major fatty acids (> 5.0%) were identified as anteiso-C15:0, C16:0, C14:0 and anteiso-C17:0. Meanwhile, DNA G+C content was 74.7%. The morphological and chemotaxonomic properties of strain NEAU-YY56T were also confirmed the affiliation of the isolate to the genus Cellulomonas. However, physiological and biochemical characteristics indicated that strain NEAU-YY56T can be clearly differentiated from its closest relatives. In addition, the ANI values and dDDH levels between strain NEAU-YY56T and related Cellulomonas species were lower than the accepted threshold value. Therefore, it is concluded that strain NEAU-YY56T represents a novel species of the genus Cellulomonas, for which the name Cellulomonas triticagri sp. nov. is proposed. The type strain is NEAU-YY56T (= DSM 106717T = JCM 32550T).

Interaction of influenza A virus NS1 and cytoskeleton scaffolding protein α-actinin 4.

NS1 (Non-structural protein 1) is a non-structural protein that can highly express when the avian influenza virus infects the host cells. NS1 can interact with various proteins to alter the intracellular distribution of host proteins and regulate the virulence and pathogenicity of the avian influenza virus. To further study the role of NS1 protein in replication and pathogenesis of avian influenza virus, Glutathione S-transferase (GST) Pull-down was used for screening more proteins interacting with NS1 in human lung adenocarcinoma cell line A549. By mass spectrometry, a potential interacted protein is identified as α-actinin 4 and its interaction with NS1 has not been reported yet. The interaction between NS1 and α-actinin 4 in vitro was confirmed by enzyme-linked immunosorbent assay experiments, and the results showed that the absorbance value of OD450nm in the experimental group was positively correlated with the concentration of NS1-GST protein compared to the negative control group. The co-immunoprecipitation and immunofluorescence results further confirmed the interaction between NS1 and α-actinin 4 at the cellular level. The interaction between NS1 and α-actinin 4 provided a new target for pathogenic mechanism studying and drug screening.

Performance of Xpert MTB/RIF for Diagnosis of Tuberculosis in HIV-Infected People in China: A Retrospective, Single-Center Study.

BACKGROUND There are few studies of GeneXpert MTB/RIF (hereafter referred to as Xpert) detection technology in HIV-infected people in China. Therefore, this study aimed to evaluate the value of Xpert in HIV/TB co-infected patients and to provide reference and guidance for the diagnosis of TB in HIV-infected populations. MATERIAL AND METHODS This study reviewed medical records of human immunodeficiency virus (HIV) patients hospitalized at the Infection Center of Beijing Ditan Hospital affiliated to Capital Medical University from January 2018 to May 2020, and patients diagnosed with pulmonary and extrapulmonary tuberculosis were screened as study subjects. Sensitivity and specificity of Xpert were analyzed using ROC curves. RESULTS Of the 413 HIV patients, 177 patients met the entry criteria, of which the diagnosis was active pulmonary tuberculosis (PTB): 145 and extrapulmonary tuberculosis (EPTB): 32. The sensitivity of Xpert for PTB and EPTB was 82.0% and 100%, higher than that of acid-fast bacilli (AFB) (61.0% and 58.3%), and slightly lower than that of T-SPOT.TB (91.0% and 100%); the specificity was 83.7% and 93.5%, higher than that of AFB (72.6%, 87.1%) and T-SPOT.TB (16.6%, 21.2%). The sensitivity of Xpert was 100% in bronchoalveolar lavage fluid (BALF) and 80.0% in sputum; in patients with CD4⁺ <200 cells/mm³, the sensitivity of Xpert was 90.0% and specificity was 84.8%, higher than that of AFB (60.0%, 75.5%) and T-SPOT.TB (90.0%, 21.5%). CONCLUSIONS Xpert has a high accuracy in HIV/TB co-infected patients, and Xpert still shows a high sensitivity and specificity even in HIV patients with CD4⁺ <200 cells/mm³. Xpert is recommended for the diagnosis of tuberculosis in HIV-infected patients.

Nanoenabled Intracellular Calcium Bursting for Safe and Efficient Reversal of Drug Resistance in Tumor Cells.

Multidrug resistance (MDR) of a tumor is the main cause of failure of clinical chemotherapy. Herein, we report a simple, yet versatile, tumor-targeting "calcium ion nanogenerator" (TCaNG) to reverse drug resistance by inducing intracellular Ca2+ bursting. Consequently, the TCaNG could induce Ca2+ bursting in acidic lysosomes of tumor cells and then reverse drug resistance according to the following mechanisms: (i) Ca2+ specifically accumulates in mitochondria, suppressing cellular respiration and relieving tumor hypoxia, thus inhibiting P-glycoprotein biosynthesis by downregulating HIF-1α expression. (ii) Ca2+-bursting-induced respiratory depression blocks intracellular ATP production, which further leads to the P-gp incompetence. As a result, the TCaNG could decrease the IC50 of DOX to MCF-7/ADR cells by approximately 30 times and reduce the proliferation of drug-resistant tumors by approximately 13 times without obvious side effects. This simple, safe, and effective "Ca2+ bursting" strategy holds the potential for clinical application in tumor treatment.

Comparative Analysis of Calcium-Dependent Protein Kinase in Cucurbitaceae and Expression Studies in Watermelon.

Both the calcium-dependent protein kinases (CDPKs) and CDPK-related kinases (CRKs) play numerous roles in plant growth, development, and stress response. Despite genome-wide identification of both families in Cucumis, comparative evolutionary and functional analysis of both CDPKs and CRKs in Cucurbitaceae remain unclear. In this study, we identified 128 CDPK and 56 CRK genes in total in six Cucurbitaceae species (C. lanatus, C. sativus, C. moschata, C. maxima, C. pepo, and L. siceraria). Dot plot analysis indicated that self-duplication of conserved domains contributed to the structural variations of two CDPKs (CpCDPK19 and CpCDPK27) in C. pepo. Using watermelon genome as reference, an integrated map containing 25 loci (16 CDPK and nine CRK loci) was obtained, 16 of which (12 CDPK and four CRK) were shared by all seven Cucurbitaceae species. Combined with exon-intron organizations, topological analyses indicated an ancient origination of groups CDPK IV and CRK. Moreover, the evolutionary scenario of seven modern Cucurbitaceae species could also be reflected on the phylogenetic trees. Expression patterns of ClCDPKs and ClCRKs were studied under different abiotic stresses. Some valuable genes were uncovered for future gene function exploration. For instance, both ClCDPK6 and its ortholog CsCDPK14 in cucumber could be induced by salinity, while ClCDPK6 and ClCDPK16, as well as their orthologs in Cucumis, maintained high expression levels in male flowers. Collectively, these results provide insights into the evolutionary history of two gene families in Cucurbitaceae, and indicate a subset of candidate genes for functional characterizations in the future.

Low-Temperature Oxygen Storage of CrIV-CrV Mixed-Valence YCr1-xPxO4-δ Driven by Local Condensation around Oxygen-Deficient Orthochromite.

The oxygen storage capability and related defect structure of tetrahedral orthochromite(V) compound YCr1-xPxO4 (x = 0, 0.3, 0.5, and 0.7) were investigated by employing thermal gravimetry and in situ X-ray spectroscopy for reversible oxygen store/release driven by heating-cooling cycles in the temperature range from 50 to 600 °C. YCr1-xPxO4 started releasing oxygen as heated from 50 °C under ambient atmosphere, with reduction of CrV to CrIV, while the reduced YCr1-xPxO4-δ phase was significantly reoxidized via absorbing oxygen by cooling to 50 °C under ambient atmosphere, recovering the original stoichiometric phase. Operando X-ray adsorption spectroscopy and first-principles calculations demonstrate that nonstoichiometric YCr1-xPxO4-δ phases were stabilized by forming linking polyhedral CrIV2O76- via corner sharing between oxygen-deficient CrIVO32- and adjacent CrIVO44-. YCr1-xPxO4 was found to have an extremely low reduction enthalpy of about 20 kJ mol-1 probably due to the relatively high reduction potential of high-valence-state Cr(V)/Cr(IV) redox pairs, thereby resulting in reversible oxygen storage in such a low-temperature region.

Combined effects of age and polymorphisms in Notch3 in the pathogenesis of cerebral infarction disease.

Cerebral infarction disease is a severe hypoxic ischemic tissue necrosis in the brain, often leading to long-term functional disability and residual impairments. The Notch signaling pathway plays key roles in proliferation and survival of the stem/progenitor cells of the central and peripheral nervous systems. Notch3 is an important member of the pathway, but the relationships between the genetic abnormalities and cerebral infarction disease still remain unclear. The aim of this work was to evaluate variations in Notch3 gene for their possible associations with the cerebral infarction disease. We sequenced the Notch3 gene for 260 patients with cerebral infarction disease, 300 normal controls with old ages and 300 normal controls with younger ages, and identified the variations. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE. Six variations, including rs1044116, rs1044009, rs1044006, rs10408676, rs1043996 and rs16980398 within or near the Notch3 gene, were found. The genetic heterozygosity of rs1044116, rs1044009, rs1044006, and rs1043996 was very high, whereas that of rs10408676 and rs16980398 was very low. Statistical analyses showed that rs1044009 and rs1044006 were associated with the risk of cerebral infarction disease in the Chinese Han agedness population. The SNPs rs1044009 and rs1044006 in the Notch3 gene were associated with the risk of cerebral infarction diseases in the Chinese Han agedness population.

Identification of NS1 domains of avian H5N1 influenza virus which influence the interaction with the NOLC1 protein.

Non-structural protein 1 (NS1) is an important virulence factor encoded by influenza A virus. NS1 can interact with a variety of host cell proteins to interfere with the host innate immune response and to promote effective viral replication. Our previous work has shown that only the effector domain of NS1 (amino acid residues 74-230/237) is sufficient to interact with nucleolar and coiled-body phosphoprotein 1 (NOLC1). To investigate the exact region of NS1 that interacts with NOLC1, we used only the effector domain of NS1 and constructed various mutants having different deletions, and then tested their ability to interact with NOLC1 via pull-down assay. Only the mutant containing amino acid residues 104-200 showed positive interaction with NOLC1. To further determine the key amino acids of the NS1 effector domain which are crucial for interaction with NOLC1, several mutants containing a single amino acid substitution were made and their interaction with NOLC1 was tested. Only the mutant D120A or R195A showed reduced binding with NOLC1, suggesting that D120 and R195 were crucial to the binding of NS1 to NOLC1. This study lays the foundation for further research aiming at furthering our understanding of the interaction between NS1 and host cells.

Identification of two novel critical mutations in PCNT gene resulting in microcephalic osteodysplastic primordial dwarfism type II associated with multiple intracranial aneurysms.

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a highly detrimental human autosomal inherited recessive disorder. The hallmark characteristics of this disease are intrauterine and postnatal growth restrictions, with some patients also having cerebrovascular problems such as cerebral aneurysms. The genomic basis behind most clinical features of MOPD II remains largely unclear. The aim of this work was to identify the genetic defects in a Chinese family with MOPD II associated with multiple intracranial aneurysms. The patient had typical MOPD II syndrome, with subarachnoid hemorrhage and multiple intracranial aneurysms. We identified three novel mutations in the PCNT gene, including one single base alteration (9842A>C in exon 45) and two deletions (Del-C in exon 30 and Del-16 in exon 41). The deletions were co-segregated with the affected individual in the family and were not present in the control population. Computer modeling demonstrated that the deletions may cause drastic changes on the secondary and tertiary structures, affecting the hydrophilicity and hydrophobicity of the mutant proteins. In conclusion, we identified two novel mutations in the PCNT gene associated with MOPD II and intracranial aneurysms, and the mutations were expected to alter the stability and functioning of the protein by computer modeling.

Unveiling the Origin of Fast Hydride Ion Diffusion at Grain Boundaries in Nanocrystalline TiN Membranes.

Nanocrystalline titanium nitride (TiN) has been determined to be a promising alternative to noble metal palladium (Pd) for fabricating base membranes for the energy-efficient production of pure hydrogen. However, the mechanism of transport of hydrogen through a TiN membrane remains unclear. In this study, we established an atomistic model of the transport of grain boundary hydride ions through such a membrane. High-resolution transmission electron microscopy and X-ray reflectivity confirmed that a nanocrystalline TiN1.0 membrane with a (100) preferred growth orientation retained about 4 Å-wide interfacial spaces along its grain boundaries. First-principles calculations based on the density functional theory showed that these grain boundaries allowed the diffusion of interfacial hydride ion defects with very small activation barriers (<12 kJ mol-1). This was substantiated by the experiment. In addition, the narrow boundary produced a sieving effect, resulting in a selective H permeation. Both the experimental and theoretical results confirmed that the granular microstructures with the 4 Å-wide interlayer enabled the transition metal nitride to exhibit pronounced hydrogen permeability.

VIRMA promotes the progression of head and neck squamous cell carcinoma by regulating UBR5 mRNA and m6A levels.

Head and neck squamous cell carcinoma (HNSCC) is a globally prevalent and lethal cancer form, whose precise mechanisms remain incompletely understood. Increasing evidence suggests that N6-methyladenosine (m6A) plays a crucial role in cancer progression. This study aimed to explore the biological function of m6A modification and vir-like m6A methyltransferase associated (VIRMA) in HNSCC. We conducted an analysis of VIRMA expression in HNSCC cells using The Cancer Genome Atlas (TCGA) database and employed reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting to assess its expression levels in HNSCC cell lines. Additionally, m6A levels in HNSCC cells were quantified, and the correlation between VIRMA expression levels and the clinical and pathological features of other genes was analyzed. Upon knocking down VIRMA levels, we assessed HNSCC cell proliferation, migration, and invasion and validated downstream genes using RT-qPCR and western blot. Our findings suggested that VIRMA, as an m6A-related regulator, may significantly influence HNSCC progression by regulating ubiquitin protein ligase E3 component N-recognin 5 (UBR5) through m6A modification. Therefore, VIRMA may serve as a prognostic biomarker.

Myricetin, a natural inhibitor of CD147, increases sensitivity of cisplatin in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is the most lethal gynecological tumor, but it currently lacks effective therapeutic targets. CD147, which is overexpressed in OC, plays a crucial role in promoting malignant progression and is associated with poor prognosis in patients. Therefore, CD147 has been identified as a potential therapeutic target. However, there is a limited amount of research on the development of CD147 inhibitors. METHODS: Surface plasmon resonance (SPR) assay and virtual molecular docking analysis were performed to identify potential natural compounds targeting CD147. The anti­tumor effects of myricetin were evaluated using various assays, including CCK8, Alkaline comet, immunofluorescence and xenograft mouse models. The underlying mechanism was investigated through western blot analysis and lentivirus short hairpin RNA (LV-shRNA) transfection. RESULTS: Myricetin, a flavonoid commonly found in plants, was discovered to be a potent inhibitor of CD147. Our findings demonstrated that myricetin exhibited a strong affinity for CD147 and down-regulated the protein level of CD147 by facilitating its proteasome-dependent degradation. Additionally, we observed synergistic antitumor effects of myricetin and cisplatin both in vivo and in vitro. Mechanistically, myricetin suppressed the expression of FOXM1 and its downstream DNA damage response (DDR) genes E×O1and BRIP1, thereby enhancing the DDR induced by cisplatin. CONCLUSION: Our data demonstrate that myricetin, a natural inhibitor of CD147, may have clinical utility in the treatment of OC due to its ability to increase genomic toxicity when combined with cisplatin.

Inositol hexaphosphate enhances chemotherapy by reversing senescence induced by persistently activated PERK and diphthamide modification of eEF2.

Oxaliplatin is an important initial chemotherapy benefiting advanced-stage colorectal cancer patients. Frustratingly, acquired oxaliplatin resistance always occurs after sequential chemotherapy with diverse antineoplastic drugs. Therefore, an exploration of the mechanism of oxaliplatin resistance formation in-depth is urgently needed. We generated oxaliplatin-resistant colorectal cancer models by four representative compounds, and RNA-seq revealed that oxaliplatin resistance was mainly the result of cells' response to stimulus. Moreover, we proved persistent stimulus-induced endoplasmic reticulum stress (ERs) and associated cellular senescence were the core causes of oxaliplatin resistance. In addition, we screened diverse phytochemicals for ER inhibitors in silico, identifying inositol hexaphosphate (IP6), whose strong binding was confirmed by surface plasmon resonance. Finally, we confirmed the ability of IP6 to reverse colorectal cancer chemoresistance and investigated the mechanism of IP6 in the inhibition of diphthamide modification of eukaryotic elongation factor 2 (eEF2) and PERK activation. Our study demonstrated that oxaliplatin resistance contributed to cell senescence induced by persistently activated PERK and diphthamide modification of eEF2 levels, which were specifically reversed by combination therapy with IP6.

Deciphering decidual deficiencies in recurrent spontaneous abortion and the therapeutic potential of mesenchymal stem cells at single-cell resolution.

BACKGROUND: Recurrent spontaneous abortion (RSA) is a challenging condition that affects the health of women both physically and mentally, but its pathogenesis and treatment have yet to be studied in detail. In recent years, Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have been shown to be effective in treating various diseases. Current understanding of RSA treatment using WJ-MSCs is limited, and the exact mechanisms of WJ-MSCs action in RSA remains largely unclear. In this study, we explored the decidual deficiencies in RSA and the therapeutic potential of WJ-MSCs at single-cell resolution. METHODS: Three mouse models were established: a normal pregnancy group, an RSA group, and a WJ-MSC treatment group. Decidual tissue samples were collected for single-cell RNA sequencing (scRNA-seq) and functional verification, including single-cell resolution in situ hybridization on tissues (SCRINSHOT) and immunofluorescence. RESULTS: We generated a single-cell atlas of decidual tissues from normal pregnant, RSA, and WJ-MSC-treated mice and identified 14 cell clusters in the decidua on day 14. Among these cell populations, stromal cells were the most abundant cell clusters in the decidua, and we further identified three novel subclusters (Str_0, Str_1, and Str_2). We also demonstrated that the IL17 and TNF signaling pathways were enriched for upregulated DEGs of stromal cells in RSA mice. Intriguingly, cell-cell communication analysis revealed that Str_1 cell-related gene expression was greatly reduced in the RSA group and rescued in the WJ-MSC treatment group. Notably, the interaction between NK cells and other cells in the RSA group was attenuated, and the expression of Spp1 (identified as an endometrial toleration-related marker) was significantly reduced in the NK cells of the RSA group but could be restored by WJ-MSC treatment. CONCLUSION: Herein, we implemented scRNA-seq to systematically evaluate the cellular heterogeneity and transcriptional regulatory networks associated with RSA and its treatment with WJ-MSCs. These data revealed potential therapeutic targets of WJ-MSCs to remodel the decidual subpopulations in RSA and provided new insights into decidua-derived developmental defects at the maternal-foetal interface.

Machine-Learning-Assisted Development of Gel Polymer Electrolytes for Protecting Zn Metal Anodes from the Corrosion of Water Molecules.

Rechargeable aqueous zinc-ion batteries (RAZIBs) offer low cost, high energy density, and safety but struggle with anode corrosion and dendrite formation. Gel polymer electrolytes (GPEs) with both high mechanical properties and excellent electrochemical properties are a powerful tool to aid the practical application of RAZIBs. In this work, guided by a machine learning (ML) model constructed based on experimental data, polyacrylamide (PAM) with a highly entangled structure was chosen to prepare GPEs for obtaining high-performance RAZIBs. By controlling the swelling degree of the PAM, the obtained GPEs effectively suppressed the growth of Zn dendrites and alleviated the corrosion of Zn metal caused by water molecules, thus improving the cycling lifespan of the Zn anode. These results indicate that using ML models based on experimental data can effectively help screen battery materials, while highly entangled PAMs are excellent GPEs capable of balancing mechanical and electrochemical properties.

Interaction of avian influenza virus NS1 protein and nucleolar and coiled-body phosphoprotein 1.

Nonstructural protein 1 (NS1) is a non-structural protein of avian influenza virus. It can interact with a variety of proteins of the host cells, enhancing the expression of viral proteins and changing the growth and metabolism of the host cells, thereby enhancing the virus' pathogenicity and virulence. To investigate whether there are more host proteins that can interact with NS1 during viral infection, T7-phage display system was used to screen human lung cell cDNA library for proteins that could interact with NS1. One positive and specific clone was obtained and identified as nucleolar and coiled-body phosphoprotein 1(NOLC1). The interaction between these two proteins was further demonstrated by His-pull-down and co-immunoprecipitation experiments. Co-expression of both proteins in HeLa cell showed that NS1 and NOLC1 were co-localized in the cell's nucleus. Gene truncation experiments revealed that the effector domain of NS1 was sufficient to interact with NOLC1. The results demonstrated a positive interaction between a viral NS1 and NOLC1 of the host cells, and provided a new target for drug screening.

Ice crystal sublimation for easily producing MnO2 cathodes with hierarchically porous structure and enhanced cyclic reversibility.

The charge/discharge performance of rechargeable aqueous zinc ion batteries (RAZIBs) at high currents is often unsatisfactory due to the cathode preparation process and the use of hydrophobic binders. By adding freeze-drying treatment to the preparation process of the cathodes, MnO2 cathodes with hierarchically porous structures are obtained, which provide additional channels for ion transfer, thus greatly enhancing the charge/discharge performance in aqueous Zn-MnO2 batteries.

A nomogram for predicting invasiveness of lung adenocarcinoma manifesting as pure ground-glass nodules: incorporating subjective CT signs and histogram parameters based on artificial intelligence.

PURPOSE: To construct a nomogram based on subjective CT signs and artificial intelligence (AI) histogram parameters to identify invasiveness of lung adenocarcinoma presenting as pure ground-glass nodules (pGGNs) and to evaluate its diagnostic performance. METHODS: 187 patients with 228 pGGNs confirmed by postoperative pathology were collected retrospectively and divided into pre-invasive group [atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS)] and invasive group [minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC)]. All pGGNs were randomly assigned to training cohort (n = 160) and validation cohort (n = 68). Nomogram was developed using subjective CT signs and AI-based histogram parameters by logistic regression analysis. The diagnostic performance was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) curve. RESULTS: The nomogram was constructed with nodule shape, 3D mean diameter, maximum CT value, and skewness. It showed better discriminative power in differentiating invasive lesions from pre-invasive lesions with area under curve (AUC) of 0.849 (95% CI 0.790-0.909) in the training cohort and 0.831 (95% CI 0.729-0.934) in the validation cohort, which performed better than nodule shape (AUC 0.675, 95% CI 0.609-0.741), 3D mean diameter (AUC 0.762, 95% CI 0.688-0.835), maximum CT value (AUC 0.794, 95% CI 0.727-0.862), or skewness (AUC 0.594, 95% CI 0.506-0.682) alone in training cohort (for all, P < 0.05). CONCLUSION: For pulmonary pGGNs, the nomogram based on subjective CT signs and AI histogram parameters had a good predictive ability to discriminate invasive lung adenocarcinoma from pre-invasive lung adenocarcinoma, and it has the potential to improve diagnostic efficiency and to help the patient management.

Pharmacokinetics of Efavirenz 600mg in Combination with Rifampicin in Chinese HIV/TB Co-Infection Patients.

Background: Rifampicin is a known inducer of the cytochrome P450 (CYP2B6) enzyme, which can lead to a decrease in the concentration of efavirenz. Therefore, we conducted a study to evaluate the effect of daily rifampicin intake on efavirenz 600mg pharmacokinetics and HIV-1 virological suppression. Methods: Patients receiving antiretroviral therapy containing efavirenz (600mg daily), and we collected efavirenz concentration at four visit points: ART day 14 (PK1), ART day 42 (PK2), ART day 140 (PK3), and ART day 336 (PK4), and performed pharmacokinetics analysis. Results: From February 2017 to November 2020, 29 HIV/TB co-infection patients were included. Ninety percent of patients had a concentration of ≥1000ng/mL of efavirenz during the study. All patients had efavirenz Cmax ≥1000ng/mL, 86% patients showed good virology response. Conclusion: Our study shows that the use of rifampicin in HIV/TB co-infection patients does not affect efavirenz drug concentrations, that virological suppression is good and that no efavirenz dose adjustment is required.