Integrated Metabolomics and Transcriptomics Reveal the Key Role of Flavonoids in the Cold Tolerance of Chrysanthemum.

Chrysanthemum (Chrysanthemum morifolium, ground-cover Chrysanthemums), one of the important garden flowers, has a high ornamental and economic value. However, its ornamental value is significantly diminished by the low temperature experienced in northeastern China. Here, metabolomics and transcriptomics were performed on three Chrysanthemum cultivars before and after a low temperature to investigate the dynamic metabolite changes and the molecular regulatory mechanisms. The results showed that 1324 annotated metabolites were detected, among which 327 were identified as flavonoids derived from Chrysanthemum. The accumulation of metabolites and gene expression related to the flavonoid biosynthesis pathway significantly increased in the three cultivars under the low temperature, indicating flavonoid metabolism actively participates in the Chrysanthemum cold response. Specifically, the content of cyanidin and pelargonidin derivatives and the expression of anthocyanin biosynthesis genes significantly increases in XHBF, providing a reasonable explanation for the change in petal color from white to purple under the low temperature. Six candidate UDP-glycosyltransferase genes involved in the glycosylation of flavonoids were identified through correlation networks and phylogenetic analysis. CmNAC1, CmbZIP3, and other transcription factors potentially regulating flavonoid metabolism and responding to low temperatures were discovered by correlation analysis and weighted gene co-expression network analysis (WGCNA). In conclusion, this study elucidated the specific response of flavonoids to low temperatures in Chrysanthemums, providing valuable insights and metabolic data for investigating cold tolerance.

Cox model risk score to predict survival of intrahepatic cholangiocarcinoma after ultrasound-guided ablation.

PURPOSE: To explore factors associated with overall survival (OS) and progression-free survival (PFS) of intrahepatic cholangiocarcinoma (iCCA) after ultrasound-guided ablation and establish a model for survival risk evaluation. METHODS: Data from 54 patients with 86 iCCAs between August 2008 and October 2022 were retrospectively analyzed. Cox regression were used to analyze the effects of clinical features on OS and PFS. Based on the variables screened by multivariable analysis, a model was established to predict the survival of the patients. Time-dependent receiver operating characteristic (timeROC) curve was constructed to evaluate the performance of this model. The model was further verified by bootstrap validation. The clinical usefulness of the model was evaluated by the decision curve analysis (DCA). RESULTS: During follow up, 39 patients died and 49 patients developed recurrence. Pre-ablation CA199 level > 140 U/ml was the only independent predictor of poor PFS. Age > 70 years, early recurrence, maximal diameter of tumor size > 1.5 cm and pre-ablation CA199 level > 140 U/ml were significantly associated with poor OS. Then a model was established based on the above four variables. The areas under the timeROC curve (AUC) for 1-year, 2-year, 3-year, 5-year were 0.767, 0.854, 0.791 and 0.848, respectively. After bootstrapping for 1000 repetitions, the AUCs were similar to the initial model. DCA also demonstrated that the model had good positive net benefits. CONCLUSION: The established model in this study could predict the survival outcomes of the patients with iCCA after thermal ablation, but further research was needed to validate the results.

Three-dimensional ultrasound fusion imaging in precise needle placement for thermal ablation of hepatocellular carcinoma.

PURPOSE: To investigate the value of three-dimensional ultrasound fusion imaging (3DUS FI) technique for guiding needle placement in hepatocellular carcinoma (HCC) thermal ablation. METHODS: A total of 57 patients with 60 HCCs with 3DUS FI-guided thermal ablation were retrospectively included in the study. 3DUS volume data of liver were acquired preoperatively by freehand scanning with the tumor and predetermined 5 mm ablative margin automatically segmented. Plan of needle placement was made through a predetermined simulated ablation zone to ensure a 5 mm ablative margin with the coverage rate toward tumor and ablative margin. With real-time ultrasound and 3DUS fusion imaging, ablation needles were placed according to the plan. After ablation, the ablative margin was immediately evaluated by contrast-enhanced ultrasound and 3DUS fusion imaging. The rate of adequate ablative margin, complete response (CR), local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) was evaluated. RESULTS: According to postoperative contrast-enhanced CT or MR imaging, the complete response rate was 100% (60/60), and 83% of tumors (30/36) achieved adequate ablative margin (>5 mm) three-dimensionally. During the follow-up period of 6.0-42.6 months, LTP occurred in 5 lesions, with 1- and 2-year LTP rates being 7.0% and 9.4%. The 1- and 2-year DFS rates were 76.1% and 65.6%, and 1- and 2-year OS rates were 98.1% and 94.0%. No major complications or ablation-related deaths were observed in any patients. CONCLUSIONS: Three-dimensional ultrasound fusion imaging technique may improve the needle placement of thermal ablation for HCC and reduce the rate of LTP.

Quantitative Parameters of Contrast-Enhanced Ultrasound Predicting the Response to Combined Immune Checkpoint Inhibitor and Anti-angiogenesis Therapies for Unresectable Hepatocellular Carcinoma.

OBJECTIVE: The aim of the work described here was to explore the value of contrast-enhanced ultrasound (CEUS) quantitative parameters in predicting the response of combined immune checkpoint inhibitor (ICI) and anti-angiogenesis therapies for unresectable hepatocellular carcinoma (HCC). METHODS: Sixty-six HCC patients who underwent combined ICI and anti-angiogenesis therapies were prospectively enrolled. A CEUS examination was performed at baseline, and tumor perfusion parameters were obtained with perfusion quantification software. The differences in CEUS quantitative parameters between the responder and non-responder groups were compared, and the correlations between CEUS parameters and progression-free survival (PFS) was evaluated. RESULTS: The objective response rate (ORR) was 21.2%. The values of rising time (RT) ratio, time to peak ratio, fall time ratio, peak enhancement ratio, wash-in rate ratio, wash-in perfusion index ratio and wash-out rate ratio differed significantly differed between the responder and non-responder groups (all p values < 0.05). Multivariable logistic regression analysis revealed that the RT ratio was the only independent factor associated with the ORR (odds ratio = 0.007, 95% confidence interval: 0.000-0.307, p = 0.010). The median RT ratios of the responder and non-responder groups were 36.9 and 58.9, respectively (p = 0.006). The appropriate cutoff point of the RT ratio was 80.1, determined with the X-tile program. Survival analysis indicated high PFS for the patients with a lower RT ratio (high RT ratio vs. low RT ratio = 4.4 mo vs. not reached, p = 0.001). CONCLUSION: CEUS quantitative parameters may predict the efficacy of ICI and anti-angiogenesis combined therapies for HCC.

Development and Assessment of Nomogram Based on AFP Response for Patients with Unresectable Hepatocellular Carcinoma Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been increasingly used to treat hepatocellular carcinoma (HCC). Prognostic biomarkers are an unmet need. We aimed to develop a prognostic nomogram for patients with unresectable HCC receiving ICIs therapy. METHODS: A total of 120 patients with unresectable HCC receiving ICIs treatment were enrolled in this study. Patients were randomly divided into a training set (n = 84) and a validation set (n = 36) in a 7:3 ratio. Clinical characteristics were retrospectively analyzed. Serum α-fetoprotein protein (AFP) response was defined as a decline of ≥20% in AFP levels within the initial eight weeks of treatment. Univariable and multivariable Cox analyses were used to select relevant variables and construct the nomogram. The areas under the receiver operating characteristic curves (AUCs) were used to determine the performance of the model. Kaplan-Meier analysis with the log-rank test was used to compare different risk groups. RESULTS: The median progression-free survival (PFS) was 7.7 months. In the multivariate Cox analysis, the presence of extrahepatic metastasis (hazard ratio [HR] = 2.08, 95% confidence interval [CI]: 1.02-4.27, p < 0.05), white blood cell count (HR = 3.48, 95% CI: 1.02-11.88, p < 0.05) and AFP response (HR = 0.41, 95% CI: 0.18-0.95, p < 0.05) independently predicted PFS. A nomogram for PFS was established with AUCs of 0.79 and 0.70 in the training and validation sets, respectively. The median PFS of the high- and low-risk subgroups was 3.5 and 11.7 months, respectively (p < 0.05). CONCLUSION: The nomogram could predict PFS in patients with unresectable HCC receiving ICIs treatment and further help decision making in daily clinical practice.

Stiffness on shear wave elastography as a potential microenvironment biomarker for predicting tumor recurrence in HBV-related hepatocellular carcinoma.

BACKGROUND: To explore the pathologic basis and prognostic value of tumor and liver stiffness measured pre-operatively by two-dimensional shear wave elastography (2D-SWE) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who undergo hepatic resection. METHODS: A total of 191 HBV-infected patients with solitary resectable HCC were prospectively enrolled. The stiffness of intratumoral tissue, peritumoral tissue, adjacent liver tissue, and distant liver tissue was evaluated by 2D-SWE. The correlations between stiffness and pathological characteristics were analyzed in 114 patients. The predictive value of stiffness for recurrence-free survival (RFS) was evaluated, and Cutoff Finder was used for determining optimal cut-off stiffness values. Cox proportional hazards analysis was used to identify independent predictors of RFS. RESULTS: Pathologically, intratumoral stiffness was associated with stroma proportion and microvascular invasion (MVI) while peritumoral stiffness was associated with tumor size, capsule, and MVI. Adjacent liver stiffness was correlated with capsule and liver fibrosis stage while distant liver stiffness was correlated with liver fibrosis stage. Peritumoral stiffness, adjacent liver stiffness, and distant liver stiffness were all correlated to RFS (all p < 0.05). Higher peritumoral stiffness (> 49.4 kPa) (HR = 1.822, p = 0.023) and higher adjacent liver stiffness (> 24.1 kPa) (HR = 1.792, p = 0.048) were significant independent predictors of worse RFS, along with tumor size and MVI. The nomogram based on these variables showed a C-index of 0.77 for RFS prediction. CONCLUSIONS: Stiffness measured by 2D-SWE could be a tumor microenvironment and tumor invasiveness biomarker. Peritumoral stiffness and adjacent liver stiffness showed important values in predicting tumor recurrence after curative resection in HBV-related HCC. CLINICAL RELEVANCE STATEMENT: Tumor and liver stiffness measured by two-dimensional shear wave elastography serve as imaging biomarkers for predicting hepatocellular carcinoma recurrence, reflecting biological behavior and tumor microenvironment. KEY POINTS: • Stiffness measured by two-dimensional shear wave elastography is a useful biomarker of tumor microenvironment and invasiveness. • Higher stiffness indicated more aggressive behavior of hepatocellular carcinoma. • The study showed the prognostic value of peritumoral stiffness and adjacent liver stiffness for recurrence-free survival. • The nomogram integrating peritumoral stiffness, adjacent liver stiffness, tumor size, and microvascular invasion showed a C-index of 0.77.

Comparison of non-radiomics imaging features and radiomics models based on contrast-enhanced ultrasound and Gd-EOB-DTPA-enhanced MRI for predicting microvascular invasion in hepatocellular carcinoma within 5 cm.

OBJECTIVES: The purpose of this study is to establish microvascular invasion (MVI) prediction models based on preoperative contrast-enhanced ultrasound (CEUS) and ethoxybenzyl-enhanced magnetic resonance imaging (EOB-MRI) in patients with a single hepatocellular carcinoma (HCC) ≤ 5 cm. METHODS: Patients with a single HCC ≤ 5 cm and accepting CEUS and EOB-MRI before surgery were enrolled in this study. Totally, 85 patients were randomly divided into the training and validation cohorts in a ratio of 7:3. Non-radiomics imaging features, the CEUS and EOB-MRI radiomics scores were extracted from the arterial phase, portal phase and delayed phase images of CEUS and the hepatobiliary phase images of EOB-MRI. Different MVI predicting models based on CEUS and EOB-MRI were constructed and their predictive values were evaluated. RESULTS: Since univariate analysis revealed that arterial peritumoral enhancement on the CEUS image, CEUS radiomics score, and EOB-MRI radiomics score were significantly associated with MVI, three prediction models, namely the CEUS model, the EOB-MRI model, and the CEUS-EOB model, were developed. In the validation cohort, the areas under the receiver operating characteristic curve of the CEUS model, the EOB-MRI model, and the CEUS-EOB model were 0.73, 0.79, and 0.86, respectively. CONCLUSIONS: Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm. CLINICAL RELEVANCE STATEMENT: Radiomics models based on CEUS and EOB-MRI are effective for MVI predicting and conducive to pretreatment decision-making in patients with a single HCC within 5 cm. KEY POINTS: • Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. • There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm.

Characteristics of Virulent ST5-SCCmec II Methicillin-Resistant Staphylococcus aureus Prevalent in a Surgery Ward.

Objective: To investigate the transmission pathway of a MRSA prevalence in a pancreatic surgery ward in a Chinese teaching hospital. Methods: Molecular epidemiology investigations were carried out combined PFGE, MLST, SCCmec typing and whole-genome sequencing for 20 successive MRSA isolates (2 isolates from the ward environment). Resistance and virulence genes were detected using specific PCR. Bacterial identification and AST were performed using the Vitek 2 Compact System. Clinical data of enrolled cases were retrieved from electronic case records. Results: From January 2020 to May 2020, successive isolated 20 MRSA strains were clarified to 2 PFGE patterns (A = 19, B = 1) in the ward. Both isolates from environment and patients belonged to sequence type ST5-SCCmec II-spa type t311. MRSA-related resistance genes mecA, blaZ, ermA, ant(4')-Ia and norA were found in each clone. All 20 isolates carried tst, hlg, hla, eta, eap, fnbA and seo virulence genes, other virulence genes such as sea, sec, seb, seg, sei, sem, sen, ebpS and fnbB were also found in partial stains. All patients had fever symptom, 27.8% were accompanied by diarrhea, 88.9% had undergone surgery or invasive procedures within 30 days. Finally, 94.4% of these patients recovered. Conclusion: This study confirmed a prevalence of ST5-MRSA-II-t311 clone in a surgery ward, indicated MRSA is a risk factor for post-surgery nosocomial infection and hand hygiene and environmental surveillance should not be ignored.

Influence factors on registration of three-dimensional contrast-enhanced ultrasound fusion imaging in evaluating the ablative margin - A phantom study.

BACKGROUND: Registration of three-dimensional contrast-enhanced ultrasound fusion imaging (3DCEUS-FI) is time-consuming to obtain high success rate. OBJECTIVE: To investigate the influence factors on registration success rate of 3DCEUS-FI. METHODS: Water tank phantoms were made to obtain mimicked pre- and post- radiofrequency ablation three-dimensional contrast-enhanced ultrasound (3DCEUS) and CT images. Orthogonal trials were designed according to factors including size, depth, enhancement level of mimicked tumor, diameter and number of mimicked adjacent vessels. Mimicked pre- and post-RFA 3DCEUS images of 72 trials were fused to assess ablative margin (AM) by two radiologists. With CT images as standard, 3DCEUS-FI accuracy was considered as the consistency of AM evaluation. The inter-observer agreement and the influence factors on registration success rates were analyzed. RESULTS: The intraclass correlation coefficient (ICC) for the consistency of AM evaluation between CT and 3DCEUS-FI in x-axis, y-axis or z-axis was 0.840∼0.948 (P < 0.001). The ICC for inter-observer agreement was 0.840∼0.948 (P < 0.001). The success rates of registration within mimicked vessels with diameter of 2 mm were significantly lower than those with diameter of 3 mm and 4 mm. CONCLUSIONS: The mimicked AM measured by 3DCEUS-FI had high accuracy and inter-observer agreement. Diameter of the mimicked adjacent vessels was significantly related to success rate of registration.

The "stiff rim" sign of hepatocellular carcinoma on shear wave elastography: correlation with pathological features and potential prognostic value.

PURPOSE: To explore the pathologic basis, the influencing factors and potential prognostic value of the stiff rim sign in two-dimensional shear wave elastography (2D-SWE) of hepatocellular carcinoma (HCC). METHODS: HCC patients who underwent tumor 2D-SWE examination before resection were prospectively enrolled. The stiff rim sign was defined as increased stiffness in the peritumoral region. Interobserver and intraobserver variability of the stiff rim sign was assessed. The correlation between the stiff rim sign and pathological characteristics was analyzed. Multivariate analysis was performed to examine clinical and radiological factors influencing the appearance of stiff rim sign. The Kaplan-Meier method was used to analyze the relationship between recurrence-free survival (RFS) and the stiff rim sign. RESULTS: The stiff rim sign on 2D-SWE was present in 44.7% of HCC lesions. Interobserver agreement and intraobserver agreement for the stiff rim sign were substantial (κ = 0.772) and almost perfect (κ = 0.895), respectively. Pathologically, the stiff rim sign was associated with capsule status, capsule integrity, capsule thickness, proportion of peritumoral fibrous tissue, and peritumoral fibrous arrangement. Multivariate analysis showed that tumor size was an independent clinical predictor for the appearance of stiff rim sign (OR 1.201, p = 0.008). Kaplan-Meier analysis showed RFS was significantly poorer in the stiff rim sign (+) group than the stiff rim sign (-) group in solitary tumors smaller than 5 cm (p = 0.007) and solitary tumors with intratumoral stiffness less than 33.7 kPa (p = 0.007). CONCLUSION: The stiff rim sign on 2D-SWE was mainly correlated with peritumoral fibrous tissue status and was a poor prognostic indicator for HCC.

Radiomics models for preoperative prediction of microvascular invasion in hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE: To assess the methodological quality and to evaluate the predictive performance of radiomics studies for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: Publications between 2017 and 2021 on radiomic MVI prediction in HCC based on CT, MR, ultrasound, and PET/CT were included. The risk of bias was assessed using the prediction model risk of bias assessment tool (PROBAST). Methodological quality was assessed through the radiomics quality score (RQS). Fourteen studies classified as TRIPOD Type 2a or above were used for meta-analysis using random-effects model. Further analyses were performed to investigate the technical factors influencing the predictive performance of radiomics models. RESULTS: Twenty-three studies including 4947 patients were included. The risk of bias was mainly related to analysis domain. The RQS reached an average of (37.7 ± 11.4)% with main methodological insufficiencies of scientific study design, external validation, and open science. The pooled areas under the receiver operating curve (AUC) were 0.85 (95% CI 0.82-0.89), 0.87 (95% CI 0.83-0.92), and 0.74 (95% CI 0.67-0.80), respectively, for CT, MR, and ultrasound radiomics models. The pooled AUC of ultrasound radiomics model was significantly lower than that of CT (p = 0.002) and MR (p < 0.001). Portal venous phase for CT and hepatobiliary phase for MR were superior to other imaging sequences for radiomic MVI prediction. Segmentation of both tumor and peritumor regions showed better performance than tumor region. CONCLUSION: Radiomics models show promising prediction performance for predicting MVI in HCC. However, improvements in standardization of methodology are required for feasibility confirmation and clinical translation.

Characterization of Carbapenem-Resistant Klebsiella pneumoniae ST15 Clone Coproducing KPC-2, CTX-M-15 and SHV-28 Spread in an Intensive Care Unit of a Tertiary Hospital.

OBJECTIVE: Nosocomial infection caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great threat to severely ill patients. Here we report an outbreak of K. pneumoniae ST15 isolates co-producing KPC-2, CTX-M-15, and SHV-28 in the cardiac surgery intensive care unit (CSICU) of a tertiary hospital. MATERIALS AND METHODS: From November 2019 to August 2020, all non-duplicated CRKP isolates were collected from the CSICU. The VITEK-2 compact system was used for bacterial identification and antimicrobial susceptibility testing. Clinical data were retrieved from electronic case records. All strains were also subjected to antibiotic resistance genes detection. Clonal relationships were analyzed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). RESULTS: A total of 28 non-duplicated CRKP isolates were collected, including 23 strains belonging to ST15 and 5 strains belonging to ST11. All ST15 isolates were susceptible to amikacin, tigecycline, polymyxin B and ceftazidime/avibactam, but resistant to carbapenems, cephalosporins, quinolones, tobramycin and gentamicin. The detection of resistant determinants showed that 21 strains of ST15 CRKP co-harboured blaKPC-2, blaCTX-M-15, blaSHV-28, blaTEM-1, blaOXA-1 and aac(6')-Ib-cr. All the 28 CRKP isolates were classified into five PFGE patterns (A, B, C, D and E), of which type A and B belonged to ST15 and type C, D and E belonged to ST11. PFGE type A was the predominant clonotype of this nosocomial infection and belonged to ST15. CONCLUSION: K. pneumoniae ST15 co-producing KPC-2, CTX-M-15, SHV-28, TEM-1, OXA-1 and aac(6')-Ib-cr is the predominant clone spread in the CSICU. Surveillance and comprehensive infection control measures should be strengthened in clinical practice.

Clinical Characteristics of Refractory Coronavirus Disease 2019 in Wuhan, China.

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe adult respiratory syndrome coronavirus 2, occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. METHODS: In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 1 January to 5 February. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy of treatment after hospitalization, and the differences between groups were compared. RESULTS: Compared with patients with general COVID-19 (45.2%), those with refractory disease were older, were more likely to be male, and had more underlying comorbid conditions, a lower incidence of fever, higher maximum temperatures among patients with fever, higher incidences of shortness of breath and anorexia, more severe disease assessment at admission, higher neutrophil, aspartate aminotransferase, lactate dehydrogenase, and C-reactive protein levels, lower platelet counts and albumin levels, and higher incidences of bilateral pneumonia and pleural effusion (P < .05). Patients with refractory COVID-19 were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment, including corticosteroids, antiviral drugs, and immune enhancers (P < .05). Considering the factors of disease severity at admission, mechanical ventilation, and intensive care unit transfer, patients with refractory COVID-19 were also more likely to be male, have manifestations of anorexia on admission, and receive oxygen, expectorant, and adjunctive agents (P < .05). CONCLUSION: In nearly 50% of patients with COVID-19 obvious clinical and radiological remission was not achieved within 10 days after hospitalization. Male, anorexia, and no fever at admission was predictive of poor treatment efficacy.

Clinical Characteristics of 33 Asymptomatic COVID-19 Infections in Wuhan, China.

Clinical characteristics of 33 asymptomatic COVID-19 infections were analyzed in this study. The data showed most of asymptomatic patients had small body mass index, good prognosis and low infectivity. This study suggests that screening from high-risk populations to find and isolate asymptomatic patients is an important disease prevention and control strategy for COVID-19.

A Risk Prediction Model for Evaluating the Disease Progression of COVID-19 Pneumonia.

Background and Objective: The epidemic of coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has expanded from China throughout the world. This study aims to estimate the risk of disease progression of patients who have been confirmed with COVID-19. Methods: Meta-analysis was performed in existing literatures to identify risk factors associated with COVID-19 pneumonia progression. Patients with COVID-19 pneumonia were admitted to hospitals in Wuhan or Hangzhou were retrospectively enrolled. The risk prediction model and nomogram were developed from Wuhan cohort through logistic regression algorithm, and then validated in Hangzhou and Yinchuan cohorts. Results: A total of 270 patients admitted to hospital between Dec 30, 2019, and Mar 30, 2020, were retrospectively enrolled (Table 1). The development cohort (Wuhan cohort) included 87 (43%) men and 115 (57%) women, and the median age was 53 years old. Hangzhou validation cohort included 20 (48%) men and 22 (52%) women, and the median age was 59 years old. Yinchuan validation cohort included 12 (46%) men and 14 (54%) women, and the median age was 44 years old. The meta-analysis along with univariate logistic analysis in development cohort have shown that age, fever, diabetes, hypertension, CREA, BUN, CK, LDH, and neutrophil count were significantly associated with disease progression of COVID-19 pneumonia. The model and nomogram derived from development cohort show good performance in both development and validation cohorts. Conclusion: The severe COVID-19 pneumonia is associated with various types of risk factors including age, fever, comorbidities, and some laboratory examination indexes. The model integrated with these factors can help to evaluate the disease progression of COVID-19 pneumonia.

Prognostic significance of spontaneous shockable rhythm conversion in adult out-of-hospital cardiac arrest patients with initial non-shockable heart rhythms: A systematic review and meta-analysis.

BACKGROUND: There remains controversy over the prognostic significance of spontaneous shockable rhythm conversion in out-of-hospital cardiac arrest (OHCA) patients with initial non-shockable heart rhythms (pulseless electrical activity [PEA] or asystole). The aim of this study was to examine the association of shockable rhythm conversion with multiple OHCA outcomes, and to explore effect modifiers. METHODS: A dual-reviewer search was conducted in PubMed and EMBASE databases in March 2017. Data on study design, patient characteristics, outcomes, adjusting and stratifying variables were extracted. Estimates were combined using random-effects models. RESULTS: Twelve studies involving 1,108,281 OHCA patients with initial non-shockable heart rhythms were identified using pre-specified eligibility criteria. Combined adjusted estimates showed that shockable rhythm conversion was associated with higher odds of pre-hospital return of spontaneous circulation (ROSC) (odds ratio [OR]=1.47, 95% confidence interval [CI] 1.40-1.55). Although shockable rhythm conversion was not associated with survival to hospital discharge (OR=1.36, 95% CI 0.77-2.38), it was associated with higher odds of one-month survival (OR=1.96, 95% CI 1.66-2.31), and one-month favourable neurological outcome (OR=2.69, 95% CI 2.00-3.62). Subgroup analyses found that shockable rhythm conversion from asystole, but not PEA, was associated with pre-hospital ROSC and survival to hospital discharge, and that earlier shockable rhythm conversions, compared to those occurring later during cardiopulmonary resuscitation, were associated with higher odds of one-month favourable neurological outcome. CONCLUSION: Shockable rhythm conversion from initial non-shockable heart rhythms was associated with better OHCA outcomes, depending on the type of initial heart rhythm, and time of rhythm conversion.

Conversion to shockable rhythms is associated with better outcomes in out-of-hospital cardiac arrest patients with initial asystole but not in those with pulseless electrical activity.

BACKGROUND: The prognostic implication of conversion from initially non-shockable to shockable rhythms in patients with out-of-hospital cardiac arrest (OHCA) remains unclear. Our objective is to determine whether the conversion to shockable rhythms is a reliable predictor of short- and long-term outcomes both in patients who initially presented with pulseless electrical activity (PEA) and in those with asystole. METHODS: A secondary analysis was performed on non-traumatic OHCA cases ≥18 years old with PEA or asystole as initial rhythms, who were treated in the field and enrolled in the Resuscitation Outcomes Consortium (ROC) PRIMED study (clinicaltrials.gov/ct2/show/NCT00394706). We reported the characteristics and outcomes for those patients with or without shocks delivered in the field. Logistic regression analysis assessed the association of shock delivery with pre-hospital return of spontaneous circulation (ROSC), survival to hospital discharge and favorable neurological outcome as well. RESULTS: Of the 9902 included cases, 3415 (34.5%) were initially in PEA and 6487 (65.5%) were in asystole. 744 (21.8%) PEA and 1134 (17.5%) asystolic patients underwent rhythm conversions and received subsequent shocks. For asystolic patients, the adjusted odds ratios (ORs) of shock delivery for pre-hospital ROSC, survival to discharge and favorable neurological outcome were 1.862 (95%CI 1.590-2.180), 3.778 (95%CI 2.374-6.014) and 4.154 (95%CI 2.192-7.871) respectively, while for PEA patients they were 0.951 (95%CI 0.796-1.137), 1.115 (95%CI 0.720-1.726) and 1.373 (95%CI 0.790-2.385) respectively. CONCLUSIONS: Conversion to shockable rhythms was associated with better outcomes in initially asystolic OHCA patients, whereas such associations were not observed in patients initially in PEA.

Palmitic acid induces autophagy in hepatocytes via JNK2 activation.

AIM: Free fatty acid-induced lipotoxicity plays a crucial role in the progression of nonalcoholic fatty liver disease (NAFLD). In the present study we investigated the effects of a high-fat diet and free fatty acids on the autophagic process in hepatocytes in vivo and in vitro and the underlying mechanisms. METHODS: LC3-II expression, a hallmark of autophagic flux, was detected in liver specimens from patients with non-alcoholic steatohepatitis (NASH) as well as in the livers of C57BL/6 mice fed a high-fat diet (HFD) up to 16 weeks. LC3-II expression was also analyzed in human SMMC-7721 and HepG2 hepatoma cells exposed to palmitic acid (PA), a saturated fatty acid. PA-induced apoptosis was detected by Annexin V staining and specific cleavage of PARP in the presence and absence of different agents. RESULTS: LC3-II expression was markedly increased in human NASH and in liver tissues of HFD-fed mice. Treatment of SMMC-7721 cells with PA increased LC3-II expression in time- and dose-dependent manners, whereas the unsaturated fatty acid oleic acid had no effect. Inhibition of autophagy with 3MA sensitized SMMC-7721 cells to PA-induced apoptosis, whereas activation of autophagy by rapamycin attenuated PA-induced PARP cleavage. The autophagy-associated proteins Beclin1 and Atg5 were essential for PA-induced autophagy in SMMC-7721 cells. Moreover, pretreatment with SP600125, an inhibitor of JNK, effectively abrogated PA-mediated autophagy and apoptosis. Specific knockdown of JNK2, but not JNK1, in SMMC-7721 cells significantly suppressed PA-induced autophagy and enhanced its pro-apoptotic activity; whereas specific knockdown of JNK1 had the converse effect. Similar results were obtained when HepG2 cells were tested. CONCLUSION: JNK1 promotes PA-induced lipoapoptosis, whereas JNK2 activates pro-survival autophagy and inhibits PA lipotoxicity. Our results suggest that modulation of autophagy may have therapeutic benefits in the treatment of lipid-related metabolic diseases.

Associations between MTHFR Ala222Val polymorphism and risks of hepatitis and hepatitis-related liver cancer: a meta-analysis.

Chronic infection of viral hepatitis is the main cause of liver cancer. There were many studies assessing the associations of methylenetetrahydrofolate reductase (MTHFR) Ala222Val polymorphism with risks of hepatitis and hepatitis-related liver cancer, but no consistent results were reported. To investigate the associations of MTHFR Ala222Val polymorphism with risks of hepatitis and hepatitis-related liver cancer, we performed a meta-analysis of published case-control studies. Eligible studies were searched from PubMed and Chinese National Knowledge Infrastructure (CNKI) databases. The odds ratio (OR) and corresponding 95 % confidence interval (95 %CI) were used to assess the associations. Twenty-one individual studies with a total of 8,187 subjects were included. Overall, MTHFR Ala222Val polymorphism was not significantly associated with risks of liver cancer, hepatitis-related liver cancer, and non-hepatitis-related liver cancer. However, MTHFR Ala222Val polymorphism was significantly associated with risk of hepatitis infection (Val vs. Ala: OR = 1.15, 95 %CI 1.01-1.32, P = 0.03; ValVal/AlaVal vs. AlaAla: OR = 1.37, 95 %CI 1.11-1.68, P = 0.003). Therefore, MTHFR Ala222Val polymorphism is significantly associated with risk of hepatitis infection but not liver cancer. More studies are needed to further assess the association between MTHFR Ala222Val polymorphism and hepatitis-related liver cancer.

Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases.

BACKGROUND: The liver is frequently subject to insult because of viral infection, alcohol abuse, or toxic chemical exposure. Extensive research has been conducted to identify blood markers that can better discern liver damage, but little progress has been achieved in clinical practice. Recently, circulating microRNAs (miRNAs) have been reported as potential biomarkers for the noninvasive diagnosis of cancer. In this study, we investigated whether plasma miRNAs have diagnostic utility in identifying liver disease. METHODS: The study was divided into 2 phases: marker selection by real-time quantitative PCR analysis of a small set of plasma samples, and marker validation with a large set of plasma samples from 83 patients with chronic hepatitis B viral infections, 15 patients with skeletal muscle disease, and 40 healthy controls. Two mouse model systems, d-galactosamine- and alcohol-induced liver injury, were also developed to evaluate whether differences in miRNA concentration were associated with various liver diseases. RESULTS: Among the miRNA candidates identified, miR-122 presented a disease severity-dependent change in plasma concentration in the patients and animal models. Compared with an increase in aminotransferase activity in the blood, the change in miR-122 concentration appeared earlier. Furthermore, this change was more specific for liver injury than for other organ damage and was more reliable, because the change was correlated with liver histologic stage. CONCLUSIONS: Our findings suggest that circulating miR-122 has potential as a novel, predictive, and reliable blood marker for viral-, alcohol-, and chemical-induced liver injury.