Bioactive Nanotherapeutic Ultrasound Contrast Agent for Concurrent Breast Cancer Ultrasound Imaging and Treatment.

Contrast-enhanced ultrasound (CEUS) plays a crucial role in cancer diagnosis. The use of ultrasound contrast agents (UCAs) is inevitable in CEUS. However, current applications of UCAs primarily focus on enhancing imaging quality of ultrasound contrast rather than serving as integrated platforms for both diagnosis and treatment in clinical settings. In this study, we innovatively prepared a novel UCA, termed NPs-DPPA(C3F8), using a combination of nanoprecipitation and ultrasound vibration methods. The DPPA lipid possesses inherent anti-angiogenic and anti-tumor activities, and when combined with C3F8, it functions as a theranostic agent. Notably, the preparation of NPs-DPPA(C3F8) is straightforward, requiring only one hour from raw materials to the final product due to the use of a single material, DPPA. NPs-DPPA(C3F8) exhibits inherent anti-angiogenic and biotherapeutic activities, effectively inhibiting triple-negative breast cancer (TNBC) angiogenesis and reducing VEGFA expression both in vitro and in vivo. Clinically, NPs-DPPA(C3F8) enables simultaneous real-time imaging, tumor assessment, and anti-tumor activity. Additionally, through ultrasound cavitation, NPs-DPPA(C3F8) can overcome the dense vascular walls to increase accumulation at the tumor site and facilitate internalization by tumor cells. The successful preparation of NPs-DPPA(C3F8) offers a novel approach for integrating clinical diagnosis and treatment of TNBC. This article is protected by copyright. All rights reserved.

Deep learning models for thyroid nodules diagnosis of fine-needle aspiration biopsy: a retrospective, prospective, multicentre study in China.

BACKGROUND: Accurately distinguishing between malignant and benign thyroid nodules through fine-needle aspiration cytopathology is crucial for appropriate therapeutic intervention. However, cytopathologic diagnosis is time consuming and hindered by the shortage of experienced cytopathologists. Reliable assistive tools could improve cytopathologic diagnosis efficiency and accuracy. We aimed to develop and test an artificial intelligence (AI)-assistive system for thyroid cytopathologic diagnosis according to the Thyroid Bethesda Reporting System. METHODS: 11 254 whole-slide images (WSIs) from 4037 patients were used to train deep learning models. Among the selected WSIs, cell level was manually annotated by cytopathologists according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) guidelines of the second edition (2017 version). A retrospective dataset of 5638 WSIs of 2914 patients from four medical centres was used for validation. 469 patients were recruited for the prospective study of the performance of AI models and their 537 thyroid nodule samples were used. Cohorts for training and validation were enrolled between Jan 1, 2016, and Aug 1, 2022, and the prospective dataset was recruited between Aug 1, 2022, and Jan 1, 2023. The performance of our AI models was estimated as the area under the receiver operating characteristic (AUROC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. The primary outcomes were the prediction sensitivity and specificity of the model to assist cyto-diagnosis of thyroid nodules. FINDINGS: The AUROC of TBSRTC III+ (which distinguishes benign from TBSRTC classes III, IV, V, and VI) was 0·930 (95% CI 0·921-0·939) for Sun Yat-sen Memorial Hospital of Sun Yat-sen University (SYSMH) internal validation and 0·944 (0·929 - 0·959), 0·939 (0·924-0·955), 0·971 (0·938-1·000) for The First People's Hospital of Foshan (FPHF), Sichuan Cancer Hospital & Institute (SCHI), and The Third Affiliated Hospital of Guangzhou Medical University (TAHGMU) medical centres, respectively. The AUROC of TBSRTC V+ (which distinguishes benign from TBSRTC classes V and VI) was 0·990 (95% CI 0·986-0·995) for SYSMH internal validation and 0·988 (0·980-0·995), 0·965 (0·953-0·977), and 0·991 (0·972-1·000) for FPHF, SCHI, and TAHGMU medical centres, respectively. For the prospective study at SYSMH, the AUROC of TBSRTC III+ and TBSRTC V+ was 0·977 and 0·981, respectively. With the assistance of AI, the specificity of junior cytopathologists was boosted from 0·887 (95% CI 0·8440-0·922) to 0·993 (0·974-0·999) and the accuracy was improved from 0·877 (0·846-0·904) to 0·948 (0·926-0·965). 186 atypia of undetermined significance samples from 186 patients with BRAF mutation information were collected; 43 of them harbour the BRAFV600E mutation. 91% (39/43) of BRAFV600E-positive atypia of undetermined significance samples were identified as malignant by the AI models. INTERPRETATION: In this study, we developed an AI-assisted model named the Thyroid Patch-Oriented WSI Ensemble Recognition (ThyroPower) system, which facilitates rapid and robust cyto-diagnosis of thyroid nodules, potentially enhancing the diagnostic capabilities of cytopathologists. Moreover, it serves as a potential solution to mitigate the scarcity of cytopathologists. FUNDING: Guangdong Science and Technology Department. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Artificial intelligence enables precision diagnosis of cervical cytology grades and cervical cancer.

Cervical cancer is a significant global health issue, its prevalence and prognosis highlighting the importance of early screening for effective prevention. This research aimed to create and validate an artificial intelligence cervical cancer screening (AICCS) system for grading cervical cytology. The AICCS system was trained and validated using various datasets, including retrospective, prospective, and randomized observational trial data, involving a total of 16,056 participants. It utilized two artificial intelligence (AI) models: one for detecting cells at the patch-level and another for classifying whole-slide image (WSIs). The AICCS consistently showed high accuracy in predicting cytology grades across different datasets. In the prospective assessment, it achieved an area under curve (AUC) of 0.947, a sensitivity of 0.946, a specificity of 0.890, and an accuracy of 0.892. Remarkably, the randomized observational trial revealed that the AICCS-assisted cytopathologists had a significantly higher AUC, specificity, and accuracy than cytopathologists alone, with a notable 13.3% enhancement in sensitivity. Thus, AICCS holds promise as an additional tool for accurate and efficient cervical cancer screening.

Epidermal growth factor receptor (EGFR) is a target of the tumor-suppressor E3 ligase FBXW7.

FBXW7 is an E3 ubiquitin ligase that targets proteins for proteasome-mediated degradation and is mutated in various cancer types. Here, we use CRISPR base editors to introduce different FBXW7 hotspot mutations in human colon organoids. Functionally, FBXW7 mutation reduces EGF dependency of organoid growth by ~10,000-fold. Combined transcriptomic and proteomic analyses revealed increased EGFR protein stability in FBXW7 mutants. Two distinct phosphodegron motifs reside in the cytoplasmic tail of EGFR. Mutations in these phosphodegron motifs occur in human cancer. CRISPR-mediated disruption of the phosphodegron motif at T693 reduced EGFR degradation and EGF growth factor dependency. FBXW7 mutant organoids showed reduced sensitivity to EGFR-MAPK inhibitors. These observations were further strengthened in CRC-derived organoid lines and validated in a cohort of patients treated with panitumumab. Our data imply that FBXW7 mutations reduce EGF dependency by disabling EGFR turnover.

SMYD4 monomethylates PRMT5 and forms a positive feedback loop to promote hepatocellular carcinoma progression.

Both lysine and arginine methyltransferases are thought to be promising therapeutic targets for malignant tumors, yet how these methyltransferases function in malignant tumors, especially hepatocellular carcinoma (HCC), has not been fully elucidated. Here, we reported that SMYD4, a lysine methyltransferase, acts as an oncogene in HCC. SMYD4 was highly upregulated in HCC and promoted HCC cell proliferation and metastasis. Mechanistically, PRMT5, a well-known arginine methyltransferase, was identified as a SMYD4-binding protein. SMYD4 monomethylated PRMT5 and enhanced the interaction between PRMT5 and MEP50, thereby promoting the symmetrical dimethylation of H3R2 and H4R3 on the PRMT5 target gene promoter and subsequently activating DVL3 expression and inhibiting expression of E-cadherin, RBL2, and miR-29b-1-5p. Moreover, miR-29b-1-5p was found to inversely regulate SMYD4 expression in HCC cells, thus forming a positive feedback loop. Furthermore, we found that the oncogenic effect of SMYD4 could be effectively suppressed by PRMT5 inhibitor in vitro and in vivo. Clinically, high coexpression of SMYD4 and PRMT5 was associated with poor prognosis of HCC patients. In summary, our study provides a model of crosstalk between lysine and arginine methyltransferases in HCC and highlights the SMYD4-PRMT5 axis as a potential therapeutic target for the treatment of HCC.

Autocrine phosphatase PDP2 inhibits ferroptosis by dephosphorylating ACSL4 in the Luminal A Breast Cancer.

Phosphatases can dephosphorylate phosphorylated kinases, leading to their inactivation, and ferroptosis is a type of cell death. Therefore, our aim is to identify phosphatases associated with ferroptosis by analyzing the differentially expressed genes (DEGs) of the Luminal A Breast Cancer (LumABC) cohort from the Cancer Genome Atlas (TCGA). An analysis of 260 phosphatase genes from the GeneCard database revealed that out of the 28 DEGs with high expression, only the expression of pyruvate dehydrogenase phosphatase 2 (PDP2) had a significant correlation with patient survival. In addition, an analysis of DEGs using gene ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis revealed a significant variation in the expression of ferroptosis-related genes. To further investigate this, we analyzed 34 ferroptosis-related genes from the TCGA-LumABC cohort. The expression of long-chain acyl-CoA synthetase 4 (ACSL4) was found to have the highest correlation with the expression of PDP2, and its expression was also inversely proportional to the survival rate of patients. Western blot experiments using the MCF-7 cell line showed that the phosphorylation level of ACSL4 was significantly lower in cells transfected with the HA-PDP2 plasmid, and ferroptosis was correspondingly reduced (p < 0.001), as indicated by data from flow cytometry detection of membrane-permeability cell death stained with 7-aminoactinomycin, lipid peroxidation, and Fe2+. Immunoprecipitation experiments further revealed that the phosphorylation level of ACSL4 was only significantly reduced in cells where PDP2 and ACSL4 co-precipitated. These findings suggest that PDP2 may act as a phosphatase to dephosphorylate and inhibit the activity of ACSL4, which had been phosphorylated and activated in LumABC cells. Further experiments are needed to confirm the molecular mechanism of PDP2 inhibiting ferroptosis.

Application of noninvasive sampling technique in mitochondrial genome intraspecific phylogeny of the endangered butterfly, Teinopalpus aureus (Lepidoptera: Papilionidae).

The butterfly genus of Teinopalpus, endemic to Asia, embodies a distinct species of mountain-dwelling butterflies with specific habitat requirements. These species are rare in the wild and hold high conservation and research value. Similar to other protected species, the genetic analysis of the rare Teinopalpus aureus poses challenges due to the complexity of sampling. In this study, we successfully extracted DNA and amplified mitochondrial genomic DNA from various noninvasive sources such as larval feces, larval exuviae, larval head capsules, pupal exuviaes, and filamentous gland secretions, all integral parts of butterfly metamorphosis. This was conducted as part of a research initiative focused on the artificial conservation of T. aureus population in Jinggang Shan Nature Reserve. Our findings illustrated the successful extraction of DNA from multiple noninvasive sources, achieved through modified DNA extraction methodologies. Although the DNA concentration obtained from noninvasive samples was lower than that from muscle tissues of newly dead larvae during rearing, all samples met the requirements for PCR amplification and sequencing, yielding complete circular sequences. These sequences are pivotal for both interspecific and intraspecific genetic relationship analysis. Our methods can be extended to other insects, especially scarce species.

Gankyrin inhibits ferroptosis through the p53/SLC7A11/GPX4 axis in triple-negative breast cancer cells.

Gankyrin is found in high levels in triple-negative breast cancer (TNBC) and has been established to form a complex with the E3 ubiquitin ligase MDM2 and p53, resulting in the degradation of p53 in hepatocarcinoma cells. Therefore, this study sought to determine whether gankyrin could inhibit ferroptosis through this mechanism in TNBC cells. The expression of gankyrin was investigated in relation to the prognosis of TNBC using bioinformatics. Co-immunoprecipitation and GST pull-down assays were then conducted to determine the presence of a gankyrin and MDM2 complex. RT-qPCR and immunoblotting were used to examine molecules related to ferroptosis, such as gankyrin, p53, MDM2, SLC7A11, and GPX4. Additionally, cell death was evaluated using flow cytometry detection of 7-AAD and a lactate dehydrogenase release assay, as well as lipid peroxide C11-BODIPY. Results showed that the expression of gankyrin is significantly higher in TNBC tissues and cell lines, and is associated with a poor prognosis for patients. Subsequent studies revealed that inhibiting gankyrin activity triggered ferroptosis in TNBC cells. Additionally, silencing gankyrin caused an increase in the expression of the p53 protein, without altering its mRNA expression. Co-immunoprecipitation and GST pull-down experiments indicated that gankyrin and MDM2 form a complex. In mouse embryonic fibroblasts lacking both MDM2 and p53, this gankyrin/MDM2 complex was observed to ubiquitinate p53, thus raising the expression of molecules inhibited by ferroptosis, such as SLC7A11 and GPX4. Furthermore, silencing gankyrin in TNBC cells disrupted the formation of the gankyrin/MDM2 complex, hindered the degradation of p53, increased SLC7A11 expression, impeded cysteine uptake, and decreased GPX4 production. Our findings suggest that TNBC cells are able to prevent cell ferroptosis through the gankyrin/p53/SLC7A11/GPX4 signaling pathway, indicating that gankyrin may be a useful biomarker for predicting TNBC prognosis or a potential therapeutic target.

Advances in the Applications of Extracellular Vesicle for the Treatment of Skin Photoaging: A Comprehensive Review.

Skin photoaging is a complex biological process characterized by the accumulation of oxidative damage and structural changes in the skin, resulting from chronic exposure to ultraviolet (UV) radiation. Despite the growing demand for effective treatments, current therapeutic options for skin photoaging remain limited. However, emerging research has highlighted the potential of extracellular vesicles (EVs), including exosomes, micro-vesicles, apoptotic bodies and liposomes, as promising therapeutic agents in skin rejuvenation. EVs are involved in intercellular communication and can deliver bioactive molecules, including proteins, nucleic acids, and lipids, to recipient cells, thereby influencing various cellular processes. This comprehensive review aims to summarize the current research progress in the application of EVs for the treatment of skin photoaging, including their isolation and characterization methods, roles in skin homeostasis, therapeutic potential and clinical applications for skin photoaging. Additionally, challenges and future directions in EVs-based therapies for skin rejuvenation are discussed.

Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer.

BACKGROUND: The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. METHODS: We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. RESULTS: We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors. CONCLUSIONS: Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC.

Intravenous lidocaine improves postoperative cognition in patients undergoing laparoscopic colorectal surgery: a randomized, double-blind, controlled study.

BACKGROUND: The risk of postoperative cognitive dysfunction(POCD) in laparoscopic surgery should not be overlooked. Intravenous lidocaine can reduce perioperative inflammatory response in patients undergoing laparoscopic surgery, while the effect of intraoperative intravenous lidocaine on postoperative cognitive function in patients undergoing laparoscopic colorectal cancer surgery has not been well studied. We investigated whether intraoperative lidocaine improves postoperative cognitive function after laparoscopic radical resection for colorectal cancer. METHODS: We conducted a prospective, randomized double blinded controlled trial to investigate the effect of intravenous lidocaine on rapid postoperative recovery in patients undergoing laparoscopic radical resection of colorectal cancer. The patients were randomly assigned to receive either intravenous lidocaine or saline. The primary outcome was cognitive dysfunction defined by a decrease from pre- to postoperative ≥ 2 of the Mini-Mental State Examination (MMSE) score, at the 3rd and the 7th postoperative days. Secondary outcomes were the MMSE raw score and parameters of the patients' postoperative recovery such as agitation and length of stay in the post-anaesthesia care unit (PACU), length of hospital stay, markers of inflammation (white blood cell count and CRP), and incidence of complications. RESULTS: Seventy-three patients in the lidocaine group and 77 patients in the control group completed the trial. The rate of cognitive dysfunction was lower in the lidocaine group than that in the control group, both at the 3rd (18.57% vs. 63.64% for each group respectively; RR = 0.26, 95%CI = 0.19-0.32; p < 0.0001) and at the 7th postoperative day (12.33% vs. 53.25% for each group respectively; RR = 0.28, 95%CI = 0.22-0.35; P < 0.001). The postoperative MMSE scores were also higher in the lidocaine group than in the control group both at the 3rd (median 25 vs. 24 respectively) and at the 7th postoperative day (26 vs. 24 respectively). Also, patients in the lidocaine group displayed a lower white blood cell count than the control group at the 1st postoperative day (8.5 ± 2.7 vs. 10.4 ± 3.3; p < 0. 001). No differences were evidenced for the other secondary outcomes. CONCLUSIONS: Intraoperative intravenous lidocaine can significantly improve postoperative cognitive function in patients undergoing laparoscopic radical resection of colorectal cancer. TRIAL REGISTRATION: Chinese Clinical Trial Registry (16/1/2022, registration number: ChiCTR2200055683).

[Factors Influencing and Adverse Reactions of Voriconazole Clearance in Patients with Hematological Diseases].

OBJECTIVE: To monitor the changes of voriconazole minimum concentration(Cmin) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole. METHODS: 136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole Cmin were analyzed, and the changes of voriconazole Cmin after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole. RESULTS: Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole Cmin and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole Cmin was negatively correlated with albumin level (r=-2.673). Voriconazole Cmin in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole Cmin showed that compared with voriconazole Cmin 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole Cmin> 5.0 mg/L group was increased (χ2=4.318, P=0.038). CONCLUSION: The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole Cmin, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole Cmin of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.

Comparisons of the effects of topical anti-scar drugs on post-surgical facial scar formation: a clinical investigation.

OBJECTIVES: Scarring is a common but intricate problem, and topical anti-scarring drugs are the most widely used treatment. However, the wide range of drugs available makes it difficult for doctors and patients to choose from because of the lack of clinical comparisons. Therefore, we conducted an observational study to compare the clinical efficacy of different topical anti-scarring drugs. METHODS: Patients with post-suturing facial scars were enrolled in this study. The questionnaire was designed to record the basic characteristics of the patients. The Vancouver Scar Scale, SCAR scale, and measurements of scar width and thickness were used to evaluate scar quality. Patients who met the inclusion criteria were divided into four groups for comparison: the silicone preparation (SP), onion extract (OE), asiaticoside (AC) groups, and the untreated blank control (BC) group. The overall data were analyzed before they were confined to the zygomatic region. RESULTS: A total of 127 eligible patients were enrolled in this study. The results of the total and zygomatic scars demonstrated that SP, OE, and AC groups resulted in narrower scars and lower scar scale scores. The SP group depicted higher melanin efficacy than the other two groups. The OE group had the best pliability, whereas the AC group had the thinnest scar. CONCLUSIONS: In this study, we acquired expertise with different topical anti-scar agents: SP significantly reduced melanin levels, OE mainly benefited scar pliability, and AC was better at reducing scar thickness. These differences may be more instructive for clinical applications.

Proteasomal inhibitors induce myeloma cell pyroptosis via the BAX/GSDME pathway.

Proteasomes are overexpressed in multiple myeloma (MM) and proteasomal inhibitors (PIs) have been widely used for the treatment of MM. PIs are reported to induce MM cell apoptosis but impair necroptosis. In the present study, we found that PIs MG132 and bortezomib induce MM cell pyroptosis, a novel type of cell death, in a GSDME-dependent manner. Lack of GSDME totally blocks PI-induced pyroptosis. Interestingly, we found that Caspase-3/6/7/9 are all involved in pyroptosis triggered by PIs because the specific inhibitor of each caspase ablates GSDME activation. PIs markedly reduce mitochondrial membrane potential. Moreover, PIs disrupt the interaction of Bcl-2 and BAX, induce cytochrome c release from mitochondria to cytosol and activate GSDME. Furthermore, we found that overexpression of an N-terminal portion of GSDME suffices to release cytochrome c from mitochondria and to activate Caspase-3/9, suggesting N-GSDME might penetrate the mitochondrial membrane. Consistent with Bcl-2 inhibition, BAX can induce MM cell pyroptosis in a GSDME-dependent manner. In accordance with these findings, inhibition of Bcl-2 synergizes with PIs to induce MM cell pyroptosis. Therefore, the present study indicates that PIs trigger MM cell pyroptosis via the mitochondrial BAX/GSDME pathway and provides a rationale for combined treatment of MM with Bcl-2 and proteasome inhibitors to increase therapeutic efficiency via induction of pyroptosis.

Estimation of gastric cancer burden attributable to Helicobacter pylori infection in Asia.

BACKGROUND: Helicobacter pylori causes large burden of gastric cancer (GC) in Asia. We aimed to comprehensively quantify the burden of GC attributable to H. pylori infection in Asia. METHODS: We searched related articles from January 1998 to December 2020 to obtain the prevalence and relative risks (or odds ratio) of GC associated with H. pylori in Asia. The burden of GC attributable to H. pylori infection was quantified by Population Attributable Fraction (PAF) and Disability-adjusted life-years (DALYs). RESULTS: We quantified the burden of GC attributable to H. pylori infection with 415.6 thousand DALYs and 38.03% PAF through the five included Asian countries in 2019. The study found that the burden had obvious regional differences. The DALYs ranged from 298.9 thousand in China to 1.9 thousand in Malaysia, and the PAFs were between 58.00% in Japan and 30.89% in China. The average prevalence of H. pylori in the included general population was estimated to be 56.29%. CONCLUSIONS: Helicobacter pylori poses a huge disease burden of GC to the population, and its eradication should receive attention, especially in the countries with high incidence of and mortality due to GC.

Bacterial Vaginosis Decreases the Risk of Cervical Cytological Abnormalities.

Genital tract infections, including vulvovaginal candidiasis and bacterial vaginosis, have emerged as potential modulators of persistent human papillomavirus (HPV) infections causing cervical cytologic abnormalities and cervical cancer. This study aimed to investigate whether vulvovaginal candidiasis or bacterial vaginosis had an additional effect on HPV infection and thus caused such abnormalities. ThinPrep cytologic tests were used to detect cytologic abnormalities, vulvovaginal candidiasis, and bacterial vaginosis in 14,679 women. Cytologic abnormalities included atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, atypical squamous cells-cannot exclude HSIL, and squamous cell carcinoma. Logistic regression Model 1 (univariate regression) and Model 2 (multivariate logistic regression analysis adjusted for age combined with HPV infection) were used to analyze the association between bacterial vaginosis and cytologic abnormalities, or vulvovaginal candidiasis and cytologic abnormalities, alone or in the presence of HPV infection. Bacterial vaginosis infection rates were found to be significantly higher in the cytology-negative group among all participants and those with HPV infection (P = 0.003, P < 0.001, respectively). Analyses using Model 1 and Model 2 both pointed to bacterial vaginosis as a protective factor against cytologic abnormalities for all participants (OR = 0.36, 0.17, respectively, P < 0.05) and for HPV-infected participants (OR = 0.17, 0.16, respectively, P < 0.05). Neither vulvovaginal candidiasis nor vulvovaginal candidiasis + HPV was significantly associated with the incidence of cytologic abnormalities based on Model 1 (OR = 0.94, 0.71, respectively, P > 0.05) and Model 2 (OR = 0.91, 0.74, respectively, P > 0.05). Furthermore, neither vulvovaginal candidiasis nor bacterial vaginosis increased the incidence of cytologic abnormalities regardless of HPV infection status, while bacterial vaginosis might possibly prevent cytologic abnormalities in women coinfected by HPV. PREVENTION RELEVANCE: Neither vulvovaginal candidiasis nor bacterial vaginosis was found to increase the incidence of cervical cytologic abnormalities with or without the presence of HPV. On the contrary, bacterial vaginosis may play a role in preventing cytologic abnormalities in women with HPV coinfection.

Factors Influencing and Adverse Reactions of Voriconazole Clearance in Patients with Hematological Diseases / 中国实验血液学杂志

OBJECTIVE@#To monitor the changes of voriconazole minimum concentration(Cmin) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole.@*METHODS@#136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole Cmin were analyzed, and the changes of voriconazole Cmin after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole.@*RESULTS@#Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole Cmin and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole Cmin was negatively correlated with albumin level (r=-2.673). Voriconazole Cmin in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole Cmin showed that compared with voriconazole Cmin 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole Cmin> 5.0 mg/L group was increased (χ2=4.318, P=0.038).@*CONCLUSION@#The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole Cmin, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole Cmin of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.