The long-term effects of coronavirus disease 2019 (COVID-19) were increasingly drawing public attention and posed a significant challenge to global healthcare systems. This study developed a deep learning system that integrated CT scans and optional clinical information from the acute phase to predict residual lung lesion (RLL) status in COVID-19 survivors at short-(1 month), medium-(3 months), and long-term (6 months) of follow-ups. A retrospective CT database of 3524 scans from 881 confirmed COVID-19 patients, followed at 1-, 3-, and 6month intervals across five medical centers, was analyzed. Patients were categorized based on the presence (RLL) or absence (NRLL) of residual lung lesions on follow-up CT scans. A cascaded multi-head framework with cross-period fusion pathway was introduced, enabling deeper supervision and ensuring consistency across time-period predictions. The proposed model outperformed other comparative methods across all follow-up periods, achieving average AUC of 0.832. Additionally, integrating embedded image features with clinical characteristics using SVM classifiers enhanced predictive performance even more. These findings provided valuable insights for optimizing follow-up and management strategies for COVID-19 survivors.
The effect of a high-fat diet (HFD) on mood is a widely debated topic, with the underlying mechanisms being poorly understood. This study explores the anxiolytic effects of a four-week HFD in C57BL/6 mice. Five-week-old mice were exposed to either an HFD (60% calories from fat) or standard chow diet (CD) for four weeks, followed by cannula implantation, virus infusion, behavioral tests, and biochemical assays. Results revealed that four weeks of an HFD induced anxiolytic-like behaviors and increased the protein levels of mature brain-derived neurotrophic factor (mBDNF) and phosphorylated tyrosine kinase receptor B (p-TrkB) in the medial prefrontal cortex (mPFC). Administration of a BDNF-neutralizing antibody to the mPFC reversed HFD-induced anxiolytic-like behaviors. Elevated BDNF levels were observed in both neurons and astrocytes in the mPFC of HFD mice. Additionally, these mice exhibited a higher number of dendritic spines in the mPFC, as well as upregulation of postsynaptic density protein 95 (PSD95). Furthermore, mRNA levels of the N6-methyladenosine (m6A) demethylase, fat mass and obesity-associated protein (FTO), and the hydrolase matrix metalloproteinase-9 (MMP9), also increased in the mPFC. These findings suggest that an HFD may induce FTO and MMP9, which could potentially regulate BDNF processing, contributing to anxiolytic-like behaviors. This study proposes potential molecular mechanisms that may underlie HFD-induced anxiolytic behaviors.
The advancement of molecular pathology techniques has led to the discovery of rare EGFR mutations for targeted therapy in lung cancer. Additionally, a substantial body of evidence indicates a connection between the development of lung cancer and genetic variations in the EGFR gene. Here, we present a case report of a patient with multifocal lung adenocarcinoma who possessed a rare germline mutation, EGFR R776H. An investigation into the family history of the patient exposed the notable incidence of lung adenocarcinoma, indicating a plausible genetic vulnerability to the ailment. To be specific, the patient's older brother and sister both suffered from lung cancer, which underlines the hereditary predisposition. Furthermore, it should be noted that the patient's daughter has inherited the germline mutation and also presented with multiple lung ground-glass nodules, emphasizing the clinical importance of this genetic variation. Following the lobectomy, the patient received treatment with almonertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), and at the latest follow-up, the patient has achieved partial remission. This case highlights the significance of taking into account germline possibilities when multiple lesions carry the same mutation. It stresses the importance of acquiring a comprehensive family history and performing genetic testing on leukocytes. Moreover, for the infrequent EGFR R776H mutation, third generation EGFR-TKIs may be a viable option.
BACKGROUND:Due to the size and location of the tumor, incomplete radiofrequency ablation (iRFA) of the target tumor inhibits tumor immunity. In this study, a murine herpes simplex virus (oHSV2-mGM) armed with granulocyte-macrophage colony-stimulating factor (GM-CSF) was constructed to explore its effect on innate and adaptive immunity during iRFA, and the inhibitory effect of programmed cell death-1 (PD1) on tumor. METHODS:We verified the polarization and activation of RAW264.7 cells mediated by oHSV2-mGM in vitro. Subsequently, we evaluated the efficacy of oHSV2-mGM alone and in combination with αPD1 in the treatment of residual tumors after iRFA in two mouse models. RNA-seq was used to characterize the changes of tumor microenvironment. RESULTS:oHSV2-mGM lysate effectively stimulated RAW264.7 cells to polarize into M1 cells and activated M1 phenotypic function. In the macrophage clearance experiment, oHSV2-mGM activated the immune response of tumor in mice. The results in vivo showed that oHSV2-mGM showed better anti-tumor effect in several mouse tumor models. Finally, oHSV2-mGM combined with PD1 antibody can further enhance the anti-tumor effect of oHSV2-mGM and improve the complete remission rate of tumor in mice. CONCLUSION:The application of oHSV2-mGM leads to the profound remodeling of the immune microenvironment of residual tumors. oHSV2-mGM also works in synergy with PD1 antibody to achieve complete remission of tumors that do not respond well to monotherapy at immune checkpoints. Our results support the feasibility of recombinant oncolytic virus in the treatment of residual tumors after iRFA, and propose a new strategy for oncolytic virus treatment of tumors.
Radiofrequency ablation (RFA) is one of the most common minimally invasive techniques for the treatment of solid tumors, but residual malignant tissues or small satellite lesions after insufficient RFA (iRFA) are difficult to remove, often leading to metastasis and recurrence. Here, Fe-TPZ nanoparticles are designed by metal ion and (TPZ) ligand complexation for synergistic enhancement of RFA residual tumor therapy. Fe-TPZ nanoparticles are cleaved in the acidic microenvironment of the tumor to generate Fe2+ and TPZ. TPZ, an anoxia-dependent drug, is activated in residual tumors and generates free radicals to cause tumor cell death. Elevated Fe2+ undergoes a redox reaction with glutathione (GSH), inducing a strong Fenton effect and promoting the production of the highly toxic hydroxyl radical (center dot OH). In addition, the ROS/GSH imbalance induced by this treatment promotes immunogenic cell death (ICD), which triggers the release of damage-associated molecular patterns, macrophage polarization, and lymphocyte infiltration, thus triggering a systemic antitumor immune response and noteworthy prevention of tumor metastasis. Overall, this integrated treatment program driven by multiple microenvironment-dependent pathways overcomes the limitations of the RFA monotherapy approach and thus improves tumor prognosis. Furthermore, these findings aim to provide new research ideas for regulating the tumor immune microenvironment. This study prepares Fe-TPZ nanoparticles by a one-step complexation method for synergistic enhancement of RFA tumor immunotherapy. Fe-TPZ not only exhibits improved physical and chemical properties, but also disrupts the balance of intracellular redox system through Fenton reaction, promotes activation through hypoxic microenvironment, and activates anti-tumor immune response to treat residual tumors and reduce metastasis. image
Purpose: The purpose of this study was to assess the impact of oversizing in thoracic endovascular aortic repair (TEVAR) on early and long-term survival and major adverse events in patients with uncomplicated type B aortic dissection (TBAD). Methods: Between January 2010 and December 2018, 226 patients who were diagnosed with uncomplicated TBAD and received TEVAR were analyzed retrospectively. The patients were divided into ≤5% oversizing (n=153) and >5% oversizing (n=73) groups. Primary end points were all-cause and aortic-related mortalities. Secondary end points were procedure-related complications, including retrograde type A aortic dissection (RTAD), endoleak, distal stent-induced new entry (SINE), and late reintervention. All-cause and aortic-related mortalities were assessed using the Kaplan-Meier survival method, while procedure-related complications were evaluated using a competing risk model with all-cause death as a competing risk. Results: Mean oversizing was 2.1%±1.5% in the ≤5% oversizing group and 9.6%±4.1% in the >5% oversizing group. Differences in the 30-day mortality and adverse events between the 2 groups were statistically insignificant. The freedom from all-cause mortality was comparable between the ≤5% oversizing group and the >5% oversizing group (≤5%: 93.3% at 5 years, >5%: 92.3% at 5 years, p=0.957). No significant difference was observed between both groups in the freedom from aortic-related mortality (≤5%: 95.0% at 5 years, >5%: 96.7% at 5 years, p=0.928). However, the competing risk analyses revealed that the cumulative incidence of RTAD was statistically significantly greater in the >5% oversizing group than in the ≤5% oversizing group (≤5%: 1(0.7%) at 5 years, >5%: 6(6.9%) at 5 years, p=0.007). All RTADs occurred within a year of TEVAR. The differences in the cumulative incidences of type I endoleak, distal SINE, and late reintervention were not significant between the 2 groups. Conclusion: The differences in the 5-year all-cause mortality and aortic-related mortality between patients with uncomplicated TBAD who received TEVAR with ≤5% oversizing and those who got TEVAR with >5% oversizing were insignificant. However, oversizing >5% was considerably associated with an increased risk of RTAD within a year of TEVAR, suggesting that oversizing ≤5% may be the appropriate size for TEVAR in patients with uncomplicated TBAD. Clinical Impact For patients with uncomplicated TBAD, choosing oversizing ≤5% in endovascular treatment is beneficial to reduce the risk of postoperative retrograde type A aortic dissection. This finding provides a basis for stent size selection in endovascular repair. In addition, one year after TEVAR is the main time period for postoperative retrograde type A aortic dissection, and attention should be paid to the management and follow-up of this period.
Hepatocellular carcinoma (HCC) is a highly refractory cancer and the fourth leading cause of cancer-related mortality worldwide. Despite the development of a detailed treatment strategy for HCC, the survival rate remains unsatisfactory. Oncolytic virus has been extensively researched as a new cancer therapeutic agent in the treatment of HCC. Researchers have designed a variety of recombinant viruses based on natural oncolytic diseases, which can increase the targeting of oncolytic viruses to HCC and their survival in tumors, as well as kill tumor cells and inhibit the growth of HCC through a variety of mechanisms. The overall efficacy of oncolytic virus therapy is known to be influenced by anti-tumor immunity, toxic killing effect and inhibition of tumor angiogenesis, etc. Therefore, a comprehensive review of the multiple oncolytic mechanisms of oncolytic viruses in HCC has been conducted. So far, a large number of relevant clinical trials are under way or have been completed, and some encouraging results have been obtained. Studies have shown that oncolytic virus combined with other HCC therapies may be a feasible method, including local therapy, chemotherapy, molecular targeted therapy and immunotherapy. In addition, different delivery routes for oncolytic viruses have been studied so far. These studies make oncolytic virus a new and attractive drug for the treatment of HCC.
Transarterial chemoembolization (TACE) has been widely used for hepatocellular carcinoma. Reducing hypoxia in the tumor microenvironment after TACE remains a challenge as tumor progression is common in post-TACE patients due to the hypoxic tumor microenvironment. In this study, melatonin loaded on p(N-isopropyl-acrylamide-co-butyl methylacrylate) (PIB-M) was used for tumor embolism. Two types of human hepatoma cell lines were used to explore the mechanism by which melatonin prevents the growth and metastasis of cancer cells in vitro. A VX2 rabbit tumor model was used to evaluate the efficacy, mechanism, and safety of PIB-M in vivo. We found that under hypoxic condition, melatonin could inhibit tumor cell proliferation and migration by targeting hypoxia inducible factor-1 & alpha; (HIF-1 & alpha;) and vascular endothelial growth factor A (VEGF-A) in vitro. In vivo, PIB-M inhibited tumor growth and metastasis in rabbit VX2 tumors by promoting apoptosis of tumor cells and targeting related angiogenic proteins and vascular permeability proteins. A high concentration of melatonin in the PIB-M group could be maintained in tumor tissue for 72 h after embolization. The liver and kidney functions were most damaged on the first day but recovered to normal on the seventh day after embolization in the PIB-M group. This novel method may open avenues for reduction of tumor growth and metastasis after TACE and is efficacy and safety, which may be used for treatment for other solid tumors and clinical translation.
3D digital subtraction angiography (DSA) reconstruction from rotational 2D projection X-ray angiography is an important basis for diagnosis and treatment of intracranial aneurysms (IAs). The gold standard requires approximately 133 different projection views for 3D reconstruction. A method to significantly reduce the radiation dosage while ensuring the reconstruction quality is yet to be developed. We propose a self-supervised learning method to realize 3D-DSA reconstruction using ultra-sparse 2D projections. 202 cases (100 from one hospital for training and testing, 102 from two other hospitals for external validation) suspected to be suffering from IAs were conducted to analyze the reconstructed images. Two radiologists scored the reconstructed images from internal and external datasets using eight projections and identified all 82 lesions with high diagnostic confidence. The radiation dosages are approximately 1/16.7 compared with the gold standard method. Our proposed method can help develop a revolutionary 3D-DSA reconstruction method for use in clinic.
Abstract The number of gray levels in medical images significantly exceeds the range of human eye recognition. In this paper, we propose a series of definitions for real-time pseudo-color enhancement based on the hue, saturation, and value (HSV) color space. First, the definitions of gray window and color window are given as follows: in the HSV color space, the gray window means mapping pixel values to value, and saturation is set to zero. Thereafter, the color window was defined by mapping pixel values to hue, with the maximum saturation and value. Moreover, pixel values greater than the upper bound of the gray window were converted to hues in the double window. The images in the double window display the details shown in the lung window, mediastinal window, and bone window for chest computed tomography and showed more details than the grayscale image in brain magnetic resonance imaging. The proposed method enhances the display effect in some cases; for example, when the image histogram has more than one peak, the information displayed white in a regular grayscale image is displayed in color.
Background:This study aimed to explore the coordinated and independent actions of lung lobes during respiration using quantitative computed tomography (CT) in order to increase our in vivo understanding of pulmonary anatomy. Methods:Cases for whom test results showed normal pulmonary function tests (PFTs) results, and normal paired inspiratory-expiratory chest CT findings, as assessed by 2 radiologists, were retrospectively included in this study. From the chest CT results, we measured quantitative indices of lung volume (LV) and mean lung density (MLD) for the total lung (TL), left lung (LL), right lung (RL), and 5 lobes in inspiratory and expiratory phases. The differences of these measures between bilateral lungs and among the lobes were evaluated to study whether they were consistent or different during respiration. Results:A total of 70 cases were included {median age of 49.5 [interquartile range (IQR), 38.0 to 60.3] years; 32 males; 38 females}. Overall, the inspiratory and expiratory volumes of the LL were smaller than those of the RL (both P<0.001). For the ventilation workload (λ, which indicates the ratio of lobar volume to total LV), the end-expiratory volume ratio (λex ) of the LL was 0.44 (IQR, 0.43 to 0.46), while the end-inspiratory volume ratio (λin ) had risen to 0.46 (IQR, 0.45 to 0.47) (P<0.001). Comparing the 5 lobes, not all lobes shared the same LV. However, the left lower lobe (LLL) and right lower lobe (RLL) showed some similarities. The λin-LLL and λin-RLL was higher than λex-LLL and λex-RLL , respectively (both P<0.001), while the ratios of the other lobes reduced. The pairwise mean absolute difference (PMAD) on λin and λex of the bilateral lower lobes was low in inspiration (0.0288) and expiration (0.0346). The MLD of bilateral lower lobes showed consistency in inspiration or in expiration (inspiration: P>0.999; expiration: P=0.975). In addition, the PMADs between the right middle lobe (RML) and other lobes were significantly larger than the PMAD between other pairs of lobes in both inspiration and expiration. Beyond that, the expiratory MLD of RML [-789.6 (IQR, -814 to -762.05) HU] was the lowest among the 5 lobes. Conclusions:We found that the LL assumes a higher workload during ventilation than it does during respiration. The 5 normal lobes were non-synchronous during respiration and contributed differently to ventilation. The bilateral lower lobes showed similarities and had a high-ventilation function, while and the LV and MLD of the RML showed the least changes within a respiration cycle.
Optical‐resolution photoacoustic microscopy (OR‐PAM) technique is a noninvasive imaging technique that can be used to obtain high‐resolution images. This technique does not require the use of exogenous contrast agents. The technique can be effectively used to realize endogenous and exogenous imaging of microvasculature. However, the depth of focus (DOF) realized using OR‐PAM is low and inadequate to cover the entire 3D data for microvasculature imaging. A varying extent of signal‐to‐noise ratio (SNR) is recorded when varying depths of the 3D sample are studied. This significantly hindered the processes of image recognition, segmentation, and analysis. Herein, a deep learning‐based OR‐PAM technique to image and analyze 3D datasets is proposed. Endogenous and exogenous multi‐organ imaging data are sequentially imaged and segmented, and excellent generalization ability is observed. Wide‐field and ultradense exogenous 3D imaging of mouse brain vasculature located at different depths is obtained and segmented by OR‐PAM for the first time. The results reveal that the proposed method can be used for effectively imaging the entire microvasculature. The method can be potentially used for imaging the microcirculation system in clinics.
Abstract Purpose To explore whether there are particular genital microbiota compositions in the reproductive tract in ovarian cancer patients and analyze their potential impact on the preventive, precisive, and personalized treatment. Methods The samples of cotton swabs from the cervical, uterine cavity, fallopian tubes, and ovaries were collected in the operation of the malignant/benign lesion patients, and subjected to metagenomic shotgun sequencing analysis. The distribution characteristics of the microbiota in the reproductive tract of different patients was analyzed with the consideration of associated clinical data. Results Bacteria accounted for the highest proportion in each sample, with a median of 99%. The microbiota of the upper female reproductive tract are mainly from the cervical, charactering in low bacterial biomass and high bacterial diversity. Ovarian cancer had a distinct microbiota signature. The tubal ligation affects its microbial distribution. There were no different species on the surface of ovarian tissue between platinum-sensitive and platinum-resistant patients. Conclusion The identification of the distinct microbiota may benefit in the prediction as well as prevention of different types of ovarian cancer. Moreover, it may dedicate to strengthen the therapeutic effect of adjuvant treatment of cancer. These findings may provide new strategies for prevention, diagnosis, and therapeutic effects to enhance health outcomes for women with ovary cancer.
OBJECTIVE:We investigated the risk factors for distal stent graft-induced new entry (dSINE) after thoracic endovascular aortic repair for patients with uncomplicated type B aortic dissection (TBAD) and reported the outcomes of using a tapered stent graft and dSINE reintervention. METHODS:A total of 226 patients with uncomplicated TBAD who had undergone thoracic endovascular aortic repair between January 2010 and December 2018 were analyzed retrospectively. The global features of the thoracic aorta and the local features of the proximal and distal landing zones were evaluated and compared between the dSINE and non-dSINE groups. A multivariate Cox model was used to identify the independent risk factors for dSINE. The cumulative incidence of reintervention was estimated using competing risk models. RESULTS:After a median follow-up of 4.6 years, 16 patients (7.1%) had developed dSINE. Multivariable Cox regression analysis demonstrated that a type III aortic arch, decreased angle, increased distal oversizing, and increased distal mismatch ratio were significant risk factors for dSINE. Of the patients with tapered stent grafts, five with a ≤4-mm taper had developed dSINE. However, no dSINE was seen in the >4-mm taper group (P = .024). Reintervention was performed for 7 of the 16 patients with dSINE (43.8%). The mean time from the initial detection of dSINE to reintervention was 6.43 ± 4.62 months. The competing risk analyses showed that the cumulative incidence of reintervention in the dSINE group at 1, 3, and 5 years was 25.0%, 37.5%, and 43.5%, respectively. CONCLUSIONS:A type III aortic arch, excessive distal oversizing and mismatch ratio, and severe angulation were associated with dSINE in patients with uncomplicated TBAD. The use of a tapered stent graft with a >4-mm taper could help prevent dSINE in patients with a high taper ratio. Aggressive reintervention was associated with favorable long-term outcomes for patients with progressive dSINE.
We investigated whether ovarian cancer could alter the genital microbiota in a specific way with clinical values. Furthermore, we proposed how such changes could be envisioned in a paradigm of predictive, preventive, and personalized medicine (PPPM). The samples were collected using cotton swabs from the cervical, uterine cavity, fallopian tubes, and ovaries of patients subjected to the surgical procedures for the malignant/benign lesions. All samples were then analyzed by metagenomic shotgun sequencing. The distribution patterns and characteristics of the microbiota in the reproductive tract of subjects were analyzed and were interpreted in relation to the clinical outcomes of the subjects. While the ovarian cancer was able to alter the genital microbiota, the bacteria were the dominant microorganisms in all samples across all cohorts in the study (median 99%). The microbiota of the upper female reproductive tract were mainly from the cervical, identified by low bacterial biomass and high bacterial diversity. Ovarian cancer had a distinct microbiota signature. The tubal ligation affects its microbial distribution. There were no different species on the surface of platinum-sensitive ovarian tissues compared to samples from platinum-resistant patients. The ovarian cancer–induced changes in microbiota magnify the potential of microbiota as a biotherapeutic modality in the treatment of ovarian cancer in this study and very likely for several malignancies and other conditions. Our findings demonstrated, for the first time, that microbiota could be dissected and applied in more specific fashion based on a predictive, preventive, and personalized medicine (PPPM) model in the treatment of ovarian cancer. Utilizing microbiota portfolio in a PPPM system in ovarian cancer would provide a unique opportunity to a clinically intelligent and novel approach in the treatment of ovarian cancer as well as several other conditions and malignancies.
Background: The aim of this study was to explore the predictive values of quantitative CT indices of the total lung and lung lobe tissue at discharge for the pulmonary diffusion function of coronavirus disease 2019 (COVID-19) patients at 5 months after symptom onset. Methods: A total of 90 patients with moderate and severe COVID-19 underwent CT scans at discharge, and pulmonary function tests (PFTs) were performed 5 months after symptom onset. The differences in quantitative CT and PFT results between Group 1 (patients with abnormal diffusion function) and Group 2 (patients with normal diffusion function) were compared by the chi-square test, Fisher’s exact test or Mann–Whitney U test. Univariate analysis, stepwise linear regression and logistic regression were used to determine the predictors of diffusion function in convalescent patients. Results: A total of 37.80% (34/90) of patients presented diffusion dysfunction at 5 months after symptom onset. The mean lung density (MLD) of the total lung tissue in Group 1 was higher than that in Group 2, and the percentage of the well-aerated lung (WAL) tissue volume (WAL%) of Group 1 was lower than that of Group 2 (all p < 0.05). Multiple stepwise linear regression identified only WAL and WAL% of the left upper lobe (LUL) as parameters that positively correlated with the percent of the predicted value of diffusion capacity of the lungs for carbon monoxide (WAL: p = 0.002; WAL%: p = 0.004), and multiple stepwise logistic regression identified MLD and MLDLUL as independent predictors of diffusion dysfunction (MLD: OR (95%CI): 1.011 (1.001, 1.02), p = 0.035; MLDLUL: OR (95%CI): 1.016 (1.004, 1.027), p = 0.008). Conclusion: At five months after symptom onset, more than one-third of moderate and severe COVID-19 patients presented with diffusion dysfunction. The well-aerated lung and mean lung density quantified by CT at discharge could be predictors of diffusion function in convalesce.
Ovarian cancer (OC) remains a clinical challenge for its difficulty in early diagnosis and insensitivity to treatments. Gut microbiota modulate multiple carcinoma progression through immunoregulation. The relationship between OC and gut microbiota has not been fully characterized. We find that the feces of patients with OC demonstrate different characteristics from benign controls. After fecal microbiota transplantation (FMT) from patients with OC into OC-bearing mice, the tumor development accelerates. Further, an Akkermansia supplementation with FMT significantly suppresses OC progression in mice. RNA sequencing of tumors shows that T cell activation pathways are upregulated after Akkermansia supplementation with FMT. Moreover, acetate accumulation accompanies Akkermansia abundance elevation, which is associated with enhanced interferon g (IFNg) secretion of CD8+ T cells and also its tumor-killing property. This work highlights the importance of protective gut microbiome in immune surveillance of OC, which connects accumulation of acetate and the cytotoxic function of CD8+ T cells by increasing IFNg secretion.
The vaginal microbiota is closely related to HPV infection and cervical cancer (CC), but its relationship with platinum-based chemotherapy responsiveness is unknown. The study aimed to investigate the vaginal microbiota diversity of women with locally advanced cervical cancer (LACC) and compare the differences between responders and nonresponders. We characterized the 16S rRNA gene sequencing of vaginal microbiome of 66 vaginal samples, including 26 LACC patients before neoadjuvant chemotherapy and 40 healthy controls. Compared with the healthy controls, alpha diversity was significantly increased in CC patients (p <0.05) with more unconventionality bacterial colonization. Beta diversity also significantly differed between cervical cancer patients and controls (p <0.01). Within the CC patients, alpha diversity in vaginal samples was significantly higher in the nonresponders versus the responders (p <0.01), and the Ace index and Chao index were negatively correlated with mass reduction (p <0.001). Moreover, the Bacteroides genus enriched in the nonresponders had a ROC-plot AUC value reaching 0.84. The study suggests the vaginal microbiota in LACC patients is associated with platinum-based chemotherapy responsiveness. Alpha diversity and Bacteroides abundance have the potential of identifying platinum-resistant patients at an early time. These findings provide a basis for further research on the relationship between vaginal microbiome and chemotherapy effect in LACC.
The characteristics of COVID-19 patients with persistent SARS-CoV-2 infection are not yet well described. Here, we compare the clinical and molecular features of patients with long duration of viral shedding (LDs) with those from patients with short duration patients (SDs), and healthy donors (HDs). We find that several cytokines and chemokines, such as interleukin (IL)-2, tumor necrosis factor (TNF) and lymphotoxin α (LT-α) are present at lower levels in LDs than SDs. Single-cell RNA sequencing shows that natural killer (NK) cells and CD14+ monocytes are reduced, while regulatory T cells are increased in LDs; moreover, T and NK cells in LDs are less activated than in SDs. Importantly, most cells in LDs show reduced expression of ribosomal protein (RP) genes and related pathways, with this inversed correlation between RP levels and infection duration further validated in 103 independent patients. Our results thus indicate that immunosuppression and low RP expression may be related to the persistence of the viral infection in COVID-19 patients.