Identification critical host factors for Japanese encephalitis virus replication via CRISPR screening of human sgRNA library.

Japanese encephalitis virus (JEV) is a pathogen with a substantial impact on both livestock and human health. However, the critical host factors in the virus life cycle remain poorly understood. Using a library comprising 123411 small guide RNAs (sgRNAs) targeting 19050 human genes, we conducted a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based screen to identify essential genes for JEV replication. By employing knockout or knockdown techniques on genes, we identified eleven human genes crucial for JEV replication, such as prolactin releasing hormone receptor (PRLHR), activating signal cointegrator 1 complex subunit 3 (ASCC3), acyl-CoA synthetase long chain family member 3 (ACSL3), and others. Notably, we found that PRLHR knockdown blocked the autophagic flux, thereby inhibiting JEV infection. Taken together, these findings provide effective data for studying important host factors of JEV replication and scientific data for selecting antiviral drug targets.

Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway.

OBJECTIVE: To explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it's down-stream mediators in colorectal cancer (CRC) cells. METHODS: Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues. RESULTS: PZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05). CONCLUSION: The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

Expression and Clinical Significance of MAGE-A Proteins and mRNA in Lung Cancer Patients: A Retrospective Study.

Objective: This study investigated the expression and clinical significance of Melanoma Associated Antigen (MAGE)-A proteins and mRNA in patients with non-small cell lung cancer (NSCLC). Methods: A retrospective study was conducted, and we selected a cohort of 88 NSCLC patients treated at our hospital from January 2015 to January 2020. Adjacent tissues were chosen as controls. The expression of MAGE-A proteins in lung cancer and adjacent tissues was assessed via Western blot, while MAGE-As mRNA expression was measured using RT-PCR. Results: The relative expression levels of MAGE-A proteins and mRNA in NSCLC tissues were significantly higher than those in adjacent tissues (P < .05), with values of (0.343 ± 0.101) and (0.728 ± 0.112), respectively. Furthermore, MAGE-As protein expression was significantly higher in stage III - IV lung cancer compared to stage I - II (P < .05). No significant differences were observed in MAGE-A protein expression concerning gender, age, tumor diameter, pathological type, and differentiation degree (P > .05). The relative expression of MAGE-As mRNA was significantly higher in clinical stage III - IV and moderately differentiated lung cancer tissues compared to stage I - II and well-differentiated tissues (P < .05). No significant differences were found in MAGE-As mRNA expression concerning gender, age, tumor diameter, and pathological type (P > .05). Patients with high MAGE-As mRNA expression had a significantly shorter median overall survival of 33 months (95% CI: 31.64-34.36) compared to those with low MAGE-As mRNA expression (P < .05). However, no significant difference was observed in median overall survival between patients with high and low MAGE-As protein expression (P > .05). Conclusions: In NSCLC, the up-regulation of MAGE-A proteins and mRNA is associated with clinical stage and differentiation degree, warranting further investigation.

Catalyst-Oriented Design Based on Elementary Reactions (CODER) for Triarylamine Synthesis.

Recently, the application of computational tools to the rational design of catalysts has received considerable attention, but progress has been limited by the reliance on databases and because mechanistic data have been almost neglected. Herein, we report a new strategy for catalyst design, designated catalyst-oriented design based on elementary reactions (CODER), which fully utilizes mechanistic data, combines the strengths of computational tools and researcher experience. CODER enabled the development of extremely efficient Pd catalysts for C-N coupling, which markedly improved the efficiency of the synthesis of widely used triarylamine optoelectronic materials by enhancing the turnover numbers (up to 340000) to 1-3 orders of magnitude towards literature values.

Oxidative Three-Component Selenofunctionalization of Alkenes: Convenient Access to Vicinally Functionalized Selenides.

Three-component selenofunctionalization processes of olefins, diselenides and sulfonamides, water, alcohols, or acids utilizing 1-fluoropyridinium triflate (FP-OTf) as a reaction promoter are reported. Under the optimal conditions, a broad range of vicinally functionalized selenide derivatives was accessible with high yields and excellent functional group compatibilities. Mechanistic studies revealed that the FP-OTf played a key role in this selenofunctionalization process.

Photocatalytic Aerobic Cyclization of N-Propargylamides Enabled by Selenium-π-Acid Catalysis.

A dual catalytic approach combining photocatalyst and selenium-π-acid synergy has been used to cyclized of N-propargylamides. This method offers readily access to oxazole aldehydes under chemical oxidant-free conditions with low catalyst loadings, where air acts as a terminal and gratuitous oxidant. The reaction is demonstrated with a range of substrates, including aryl and alkyl propargyl amides, and in the late-stage functionalization of several amide-containing drug molecules. Mechanistic studies suggest that the acridinium catalyst is able to oxidize diselenide and generate singlet oxygen (1 O2 ), which is responsible for this transformation.

Effect of Capsaicin Atomization on Cough and Swallowing Function in Patients With Hemorrhagic Stroke: A Randomized Controlled Trial.

BACKGROUND: Patients with hemorrhagic stroke have high mortality and disability rates. Nevertheless, early rehabilitation interventions can improve their outcomes. We aimed to apply capsaicin atomization as early intervention to patients with hemorrhagic stroke and explore improvements in cough and swallowing functions. METHOD: Patients with hemorrhagic stroke were randomly divided into the control group, which received routine care, and the intervention group, which underwent the capsaicin solution nebulization scheme in addition to routine care. Differences in the presence/absence of cough reflex and number of coughs in response to capsaicin, the presence/absence of swallowing reflex in response to water, the presence/absence of postswallow residue, substance P (SP) concentration, and pulmonary inflammation between the two groups were determined before and after the intervention. RESULTS: A total of 53 patients with hemorrhagic stroke were included. Results showed no statistically significant difference in cough reflex in both groups after the intervention (p > .05). The degree of cough in the intervention group was stronger than that in the control group (p = .046). No statistically significant difference was observed in the number of patients with swallowing reflex in response to water between the groups (p > .05). The presence/absence of postswallow residue of the intervention group was stronger than that of the control group (p = .032). No statistically significant difference was observed between the Glasgow Coma Scale scores of the groups after the intervention (p > .05). SP in the intervention group was significantly increased (p = .031). The Clinical Pulmonary Infection Score was significantly lower in the control group, and the difference was statistically significant (p = .028). CONCLUSIONS: Capsaicin nebulization can help enhance the number of coughs in response to capsaicin, reduce postswallow residue, and increase the level of SP in patients with hemorrhagic stroke and has a positive effect on pulmonary inflammation. This study provides intervention points for cough and swallowing rehabilitation after a hemorrhagic stroke. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21956903.

Analysis of the feasibility and prognostic value of circulating tumor DNA monitoring in detecting gene mutations in patients with diffuse large B-cell lymphoma receiving chimeric antigen receptor T-cell therapy / 中华血液学杂志

Objective: To explore the prognostic value of circulating tumor DNA (ctDNA) testing in patients with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) undergoing chimeric antigen receptor T-cell (CAR-T) therapy, and to guide the prevention and subsequent treatment of CAR-T-cell therapy failure. Methods: In this study, 48 patients with R/R DLBCL who received CAR-T-cell therapy at the First Affiliated Hospital of Zhejiang University School of Medicine between December 2017 and March 2022 were included. Furthermore, ctDNA testing of 187 lymphoma-related gene sets was performed on peripheral blood samples obtained before treatment. The patients were divided into complete remission and noncomplete remission groups. The chi-square test and t-test were used to compare group differences, and the Log-rank test was used to compare the differences in survival. Results: Among the patients who did not achieve complete remission after CAR-T-cell therapy for R/R DLBCL, the top ten genes with the highest mutation frequencies were TP53 (41%), TTN (36%), BCR (27%), KMT2D (27%), IGLL5 (23%), KMT2C (23%), MYD88 (23%), BTG2 (18%), MUC16 (18%), and SGK1 (18%). Kaplan-Meier survival analysis revealed that patients with ctDNA mutation genes >10 had poorer overall survival (OS) rate (1-year OS rate: 0 vs 73.8%, P<0.001) and progression-free survival (PFS) rate (1-year PFS rate: 0 vs 51.8%, P=0.011) compared with patients with ctDNA mutation genes ≤10. Moreover, patients with MUC16 mutation positivity before treatment had better OS (2-year OS rate: 56.8% vs 26.7%, P=0.046), whereas patients with BTG2 mutation positivity had poorer OS (1-year OS rate: 0 vs 72.5%, P=0.005) . Conclusion: ctDNA detection can serve as a tool for evaluating the efficacy of CAR-T-cell therapy in patients with R/R DLBCL. The pretreatment gene mutation burden, mutations in MUC16 and BTG2 have potential prognostic value.

N-Fluorobenzenesulfonimide-Mediated Intermolecular Carboselenenylation of Olefins with Aromatics and Diselenides.

Intermolecular carboselenenylation of easily accessible alkenes by utilizing diselenides and N-fluorobenzenesulfonimide (NFSI) under metal-free and mild conditions is reported. Preliminary mechanistic studies indicate that the oxidation of diselenide by NFSI through a single-electron-transfer process produces an active selenenyl cationic radical species that initiates the intermolecular carboselenenylation of olefins, forming key Se-C and C-C bonds. Under optimized conditions, a broad spectrum of functionally and structurally diverse selenoether derivatives with promising yields is accessed with a very high functional group tolerance.

Combining stereotactic body radiotherapy with camrelizumab for unresectable hepatocellular carcinoma: a single-arm trial.

PURPOSE: Stereotactic body radiotherapy (SBRT) may have significant immunomodulatory effects that enhance tumor response to immune checkpoint inhibitors. This phase 2 clinical trial was conducted to evaluate the safety and efficacy of combining palliative SBRT with camrelizumab (an anti-PD1 monoclonal antibody) in patients with unresectable hepatocellular carcinoma (uHCC). METHODS: Patients with uHCC, Child-Pugh A/B liver function, and at least one measurable lesion were enrolled between April 2020 and August 2022. Patients were administered 200 mg camrelizumab intravenously from the first day of palliative SBRT and then every 3 weeks. Palliative SBRT was delivered daily over five fractions per week, with a dose range of 30-50 Gy. The primary endpoints were objective response rate (ORR) and safety. This trial was registered at ClinicalTrials.gov (NCT04193696). RESULTS: Twenty-one patients were enrolled; the median radiation dose was 40 Gy, and the median number of cycles of camrelizumab was five. The ORR was 52.4%. After a median follow-up of 19.7 months, the median progression-free and overall survival were 5.8 and 14.2 months, respectively. The overall survival probability was 85.7% at 6 months, 76.2% at 9 months, and 59.9% at 12 months. All grade 3 treatment-related adverse events (TRAEs) occurred in five patients (23.8%) and were manageable. No grade 4/5 TRAEs were observed. CONCLUSION: Palliative SBRT plus camrelizumab showed promising antitumor activity against uHCC. Toxicities were manageable with no unexpected safety issues. This study provides evidence of a new therapeutic method for the treatment of uHCC.

Iodine pentoxide-mediated oxidative selenation and seleno/thiocyanation of electron-rich arenes.

A simple and efficient method for the regioselective selenation of electron-rich arenes by employing non-metal inorganic iodine pentoxide (I2O5) as a reaction promoter under ambient conditions has been developed. The present protocol showed broad functional group tolerance and easy-to-operate and time-economical features. Additionally, this protocol also allows access to 3-seleno and 3-thiocyanoindoles by the use of readily available selenocyanate and thiocyanate salts. A mechanistic study indicated that the transformation operated through selenenyl iodide-induced electrophilic substitution processes.

Small lesion depiction and quantification accuracy of oncological 18F-FDG PET/CT with small voxel and Bayesian penalized likelihood reconstruction.

BACKGROUND: To investigate the influence of small voxel Bayesian penalized likelihood (SVB) reconstruction on small lesion detection compared to ordered subset expectation maximization (OSEM) reconstruction using a clinical trials network (CTN) chest phantom and the patients with 18F-FDG-avid small lung tumors, and determine the optimal penalty factor for the lesion depiction and quantification. METHODS: The CTN phantom was filled with 18F solution with a sphere-to-background ratio of 3.81:1. Twenty-four patients with 18F-FDG-avid lung lesions (diameter < 2 cm) were enrolled. Six groups of PET images were reconstructed: routine voxel OSEM (RVOSEM), small voxel OSEM (SVOSEM), and SVB reconstructions with four penalty factors: 0.6, 0.8, 0.9, and 1.0 (SVB0.6, SVB0.8, SVB0.9, and SVB1.0). The routine and small voxel sizes are 4 × 4 × 4 and 2 × 2 × 2 mm3. The recovery coefficient (RC) was calculated by dividing the measured activity by the injected activity of the hot spheres in the phantom study. The SUVmax, target-to-liver ratio (TLR), contrast-to-noise ratio (CNR), the volume of the lesions, and the image noise of the liver were measured and calculated in the patient study. Visual image quality of the patient image was scored by two radiologists using a 5-point scale. RESULTS: In the phantom study, SVB0.6, SVB0.8, and SVB0.9 achieved higher RCs than SVOSEM. The RC was higher in SVOSEM than RVOSEM and SVB1.0. In the patient study, the SUVmax, TLR, and visual image quality scores of SVB0.6 to SVB0.9 were higher than those of RVOSEM, while the image noise of SVB0.8 to SVB1.0 was equivalent to or lower than that of RVOSEM. All SVB groups had higher CNRs than RVOSEM, but there was no difference between RVOSEM and SVOSEM. The lesion volumes derived from SVB0.6 to SVB0.9 were accurate, but over-estimated by RVOSEM, SVOSEM, and SVB1.0, using the CT measurement as the standard reference. CONCLUSIONS: The SVB reconstruction improved lesion contrast, TLR, CNR, and volumetric quantification accuracy for small lesions compared to RVOSEM reconstruction without image noise degradation or the need of longer emission time. A penalty factor of 0.8-0.9 was optimal for SVB reconstruction for the small tumor detection with 18F-FDG PET/CT.

Clinical value of laboratory indicators for predicting disease progression and death in patients with COVID-19: a retrospective cohort study.

OBJECTIVES: As early prediction of severe illness and death for patients with coronavirus disease 2019 (COVID-19) is important, we aim to explore the clinical value of laboratory indicators in evaluating the progression and prognosis of patients with COVID-19. DESIGN: Retrospective cohort study. SETTING: Hospital-based study in China. PARTICIPANTS: Adult patients with COVID-19 from December 15, 2019 to March 15, 2020. END POINT: Disease severity and mortality. METHODS: Clinical data of 638 patients with COVID-19 were collected and compared between severe and non-severe groups. The predictive ability of laboratory indicators in disease progression and prognosis of COVID-19 was analysed using the receiver operating characteristic curve. The survival differences of COVID-19 patients with different levels of laboratory indicators were analysed utilising Kaplan-Meier analysis. RESULTS: 29.8% (190/638) of patients with COVID-19 progressed to severe. Compared with patients with no adverse events, C reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and D-dimer were significantly higher in severe patients with adverse events, such as acute myocardial injury, respiratory failure, acute kidney injury, mechanical ventilation, intensive care unit admission, multiple organ dysfunction syndromes and death (all p<0.05). The multivariate logistic analysis suggested that CRP, NLR and D-dimer were independent risk factors for the disease progression of COVID-19 (all p<0.05). The model combining all of them owned the highest area under the receiver operating characteristic curve (AUC) predicting disease progression and death of COVID-19, with AUC of 0.894 (95% CI 0.857 to 0.931) and 0.918 (95% CI 0.873 to 0.962), respectively. Survival analysis suggested that the patients with a high level of CRP, NLR or D-dimer performed shorter overall survival time (all p<0.05). CONCLUSIONS: The combination of CRP, NLR and D-dimer could be an effective predictor for the aggravation and death in patients with COVID-19. The abnormal expression of these indicators might suggest a strong inflammatory response and multiple adverse events in patients with severe COVID-19.

Association between apolipoprotein gene polymorphisms and hyperlipidemia: a meta-analysis.

BACKGROUND: Hyperlipidemia plays an important role in the etiology of cardio-cerebrovascular disease. Over recent years, a number of studies have explored the impact of apolipoprotein genetic polymorphisms in hyperlipidemia, but considerable differences and uncertainty have been found in their association with different populations from different regions. RESULTS: A total of 59 articles were included, containing in total 13,843 hyperlipidemia patients in the case group and 15,398 healthy controls in the control group. Meta-analysis of the data indicated that APOA5-1131 T > C, APOA1 -75 bp, APOB XbaI, and APOE gene polymorphisms were significantly associated with hyperlipidemia, with OR values of 1.996, 1.228, 1.444, and 1.710, respectively. All P-values were less than 0.05. CONCLUSIONS: Meta-analysis of the data indicated that the C allele of APOA5 1131 T > C, the A allele at APOA1-75 bp, the APOB XbaI T allele, and the ε2 and ε4 allele of APOE were each a risk factor for susceptibility for hyperlipidemia.

A bibliometric analysis of infectious diseases in patients with liver transplantation in the last decade.

BACKGROUND: A bibliometric analysis was performed to reveal the current status of investigations in infectious diseases in patients with liver transplantation (LT) and to prioritize future research needs. METHODS: The present study comprehensively retrieved publications relevant to infectious diseases in LT recipients published between 2010 and 2020. The search was conducted on the Web of Science (WoS) database. A bibliometric analysis was conducted through machine learning and visualization tools, including VOSviewer, Bibliographic Item Co-Occurrence Matrix Builder, and Graphical Clustering Toolkit. Research hotspots and trends in the field were assessed, while the contributions and collaborations of countries, institutions, and authors were documented. RESULTS: A total of 691 publications were analyzed. Research output sharply increased in 2015, with a fast drop afterward. "Liver transplantation" was the most frequent keyword, with strong links to "hepatitis C virus" and "infection". Study areas included risk factors of infectious diseases in LT recipients, pathogens causing post-transplantation infections, antibacterial therapy and prophylaxis for peritransplant infection complications, living donor LT, and pediatric LT. The efficacy and safety of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection among liver transplant recipients has attracted recent research interest. Didier Samuel was the most productive author, while Xavier Forns was the top-cited author. Shanghai Jiao Tong University was the most productive contributor, and Gilead Sciences was the most cited organization. Moreover, the USA was the greatest contributor. Gastroenterology was the most cited journal, while Liver Transplantation was the most prolific journal. CONCLUSIONS: This bibliometric analysis will better understand the research status of infectious complications in LT recipients and forecast future research trends. Priority should be given to identifying risk factors for peritransplantation infections and effective treatments against infectious complications in the coming years.

A narrative review of research progress on FoxM1 in breast cancer carcinogenesis and therapeutics.

OBJECTIVE: The purpose of this review is to clarify the potential roles of forkhead box transcription factor M1 (FoxM1) in the occurrence and progression of breast cancer, as well as the predictive value of FoxM1 as a prognostic biomarker and potential therapeutic target for breast cancer. BACKGROUND: Breast cancer, well-known as a molecularly heterogeneous cancer, is still one of the most frequently diagnosed malignant tumors among females worldwide. Tumor recurrence and metastasis are the central causes of high mortality in breast cancer patients. Many factors contribute to the occurrence and progression of breast cancer, including FoxM1. FoxM1, widely regarded as a classic proliferation-related transcription factor, plays pivotal roles in the occurrence, proliferation, invasion, migration, drug resistance, and epithelial-mesenchymal transition (EMT) processes of multiple human tumors including breast cancer. METHODS: The PubMed database was searched for articles published in English from February 2008 to May 2021 using related keywords such as "forkhead box transcription factor M1", "human breast cancer", "FoxM1", and "human tumor". About 90 research papers and reports written in English were identified, most of which were published after 2015. These papers mainly concentrated on the functions of FoxM1 in the occurrence, development, drug resistance, and treatment of human breast cancer. CONCLUSIONS: Considering that the abnormal expression of FoxM1 plays a significant role in the proliferation, invasion, metastasis, and chemotherapy drug resistance of breast cancer, and its overexpression is closely correlated with the unfavorable clinicopathological characteristics of breast tumor patients, it is considerably important to comprehend the regulatory mechanism of FoxM1 in breast cancer. This will provide strong evidence for FoxM1 as a potential biomarker for the targeted treatment and prognostic evaluation of breast cancer patients.

Effect of Babao Dan on angiogenesis of gastric cancer in vitro by regulating VEGFA/VEGFR2 signaling pathway.

BACKGROUND: To further elucidate the anti-angiogenesis effect of Babao Dan (BBD) in vitro, gastric cancer (GC) cells and human umbilical vein endothelial cells (HUVECs) were used to evaluate the regulation role of BBD by vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway. METHODS: After induced by VEGFA, GC cells (AGS, MGC80-3 and BGC823) were treated by different concentrations of BBD and then were detected cell viability, migration and VEGFA level. And the anti-angiogenesis effect of BBD was evaluated with HUVECs. To furtherly mimic the tumor microenvironment of angiogenesis, VEGFA as an inducer (10 ng/mL) was used to trigger a cascade of angiogenesis of HUVECs in vitro. RESULTS: The viability and migration of GC cells with VEGFA-induced or non-induced and VEGFA levels in GC cells were significantly inhibited by BBD with concentration-dependent manner (P<0.01). BBD significantly inhibited the HUVECs viability with concentration-dependent manner (P<0.01), which was consistent with the inhibitory action on augmentation of cell viability induced by VEGFA (P<0.01). BBD exhibited the similar inhibitory trend on cyto behavioral variability such as wound repairing (P<0.05), migration (P<0.01) and tube formation (P<0.01) and activation effect on cell apoptosis rate (P<0.01) with VEGFA-induced or non-induced. Moreover, BBD notably regulated the levels of VEGFA, VEGFR2, matrix metalloprotein 2 (MMP2) and matrix metalloprotein 9 (MMP9) of HUVECs on present or absent of VEGFA with dose-dependent manner. CONCLUSIONS: BBD inhibited GC growth against VEGFA-induced angiogenesis of HUVECs by VEGFA/VEGFR2 signaling pathway in vitro.

Clinical, radiological, and laboratory characteristics and risk factors for severity and mortality of 289 hospitalized COVID-19 patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a global pandemic, with 10%-20% of severe cases and over 508 000 deaths worldwide. OBJECTIVE: This study aims to address the risk factors associated with the severity of COVID-19 patients and the mortality of severe patients. METHODS: 289 hospitalized laboratory-confirmed COVID-19 patients were included in this study. Electronic medical records, including patient demographics, clinical manifestation, comorbidities, laboratory tests results, and radiological materials, were collected and analyzed. According to the severity and outcomes of the patients, they were divided into three groups: nonsurvived (n = 49), survived severe (n = 78), and nonsevere (n = 162) groups. Clinical, laboratory, and radiological data were compared among these groups. Principal component analysis (PCA) was applied to reduce the dimensionality and visualize the patients on a low-dimensional space. Correlations between clinical, radiological, and laboratory parameters were investigated. Univariate and multivariate logistic regression methods were used to determine the risk factors associated with mortality in severe patients. Longitudinal changes of laboratory findings of survived severe cases and nonsurvived cases during hospital stay were also collected. RESULTS: Of the 289 patients, the median age was 57 years (range, 22-88) and 155 (53.4%) patients were male. As of the final follow-up date of this study, 240 (83.0%) patients were discharged from the hospital and 49 (17.0%) patients died. Elder age, underlying comorbidities, and increased laboratory variables, such as leukocyte count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) on admission, were found in survived severe cases compared to nonsevere cases. According to the multivariate logistic regression analysis, elder age, a higher number of affected lobes, elevated CRP levels on admission, increased prevalence of chest tightness/dyspnea, and smoking history were independent risk factors for death of severe patients. A trajectory in PCA was observed from "nonsevere" toward "nonsurvived" via "severe and survived" patients. Strong correlations between the age of patients, the affected lobe numbers, and laboratory variables were identified. Dynamic changes of laboratory findings of survived severe cases and nonsurvived cases during hospital stay showed that continuing increase of leukocytes and neutrophil count, sustained lymphopenia and eosinopenia, progressing decrease in platelet count, as well as high levels of NLR, CRP, PCT, AST, BUN, and serum creatinine were associated with in-hospital death. CONCLUSIONS: Survived severe and nonsurvived COVID-19 patients had distinct clinical and laboratory characteristics, which were separated by principle component analysis. Elder age, increased number of affected lobes, higher levels of serum CRP, chest tightness/dyspnea, and smoking history were risk factors for mortality of severe COVID-19 patients. Longitudinal changes of laboratory findings may be helpful in predicting disease progression and clinical outcome of severe patients.

Long-Term Survival Analysis of Transarterial Chemoembolization Plus Radiotherapy vs. Radiotherapy for Hepatocellular Carcinoma With Macroscopic Vascular Invasion.

Background: Macroscopic vascular invasion (MVI) is a terminal manifestation of hepatocellular carcinoma (HCC) and carries an extremely poor prognosis. In Chinese and Korean HCC guidelines, transarterial chemoembolization (TACE), or/and radiotherapy (RT) is adopted for treatment of MVI. In the current study, we aimed to compare the long-term outcome of TACE + RT to that of RT alone in patients with local advanced HCC with MVI. Methods: In this retrospective study, 148 treatment-naive patients of HCC with MVI were enrolled. Of the patients enrolled, 49 received TACE + RT treatment, whereas 99 patients received RT alone as a monotherapy. Overall survival (OS), progression-free survival (PFS), and intrahepatic control were evaluated using univariable and propensity score-matched analyses. Results: During follow-up, 126 patients (85.1%) died. The median follow-up time was 55.0 months in the RT group and 57.0 months in the TACE + RT group. The TACE + RT group showed better OS and PFS than the RT group, but intrahepatic control was comparable in these two groups. Of 41 cases well-pairs after propensity score matching, the associations between TACE + RT and better OS and PFS remained (15.0 vs. 8.0 months, and 8.0 vs. 4.0 months, all P < 0.05). The 1-, 2-, 3-, and 5-years OS rates in the TACE + RT group were 56.1, 28.6, 20.8, and 15.7 vs. 31.5%, 13.1%, 9.8%, and 6.7% in the RT group, respectively (P = 0.017). The 6-, 12-, and 24-months rates in the TACE + RT group were 51.2, 39.0, and 23.1% vs. 36.6%, 13.9%, and 11.1% in the RT group, respectively (P = 0.04). Two patients (4.1%) experienced radiation-induced liver disease (RILD), and one (2.0%) experienced RT-related gastrointestinal (GI) bleed in the TACE + RT groups. Nine patients (9.1%) experienced RILD, and two (2.0%) experienced RT-related GI bleed in the RT groups. Conclusion: Transarterial chemoembolization + RT had well-complementarity with no more complications than RT alone, providing a better PFS and OS compared with RT-alone treatment for HCC with MVI.

An isolated vaginal metastasis from intestinal signet ring cell carcinoma: a case report and literature review.

BACKGROUND: Isolated vaginal metastases from intestinal signet ring cell carcinoma are extremely rare. There are no reported cases in the domestic or foreign literature. The characteristics of such cases of metastasis remain relatively unknown. As a life-threatening malignant tumor, it is very important to carry out a systemic tumor examination and transvaginal biopsy, even though clinical symptoms are not typical and there is no systemic tumor history. CASE PRESENTATION: We present a case of an isolated vaginal metastasis from intestinal cancer in a 45-year-old female patient. The patient experienced a small amount of irregular vaginal bleeding and difficulty urinating. She had no history of systemic cancer. An early physical examination and transvaginal ultrasound (TVS) showed marked thickening of the entire vaginal wall. Pelvic nuclear magnetic resonance imaging (MRI) and a colposcopic biopsy were used to diagnose her with chronic vaginitis. An analysis of the vaginal wall biopsy showed signet ring cell carcinoma. Colorectal colonoscopy revealed advanced interstitial signet ring cell carcinoma as the primary source of vaginal wall infiltration. We review previous case reports of vaginal metastases from colorectal cancer and discuss the symptoms, pathological type, and outcomes. CONCLUSIONS: We hypothesize that vaginal wall thickening and stiffness accompanied by chronic inflammatory-like changes may be clinical features of a vaginal metastasis of signet ring cell carcinoma of the intestine. We also emphasize that it is very important to perform a systemic tumor examination in a timely manner when a patient has the abovementioned symptoms.