GALAD score as a prognostic model for recurrence of hepatocellular carcinoma after local ablation.

BACKGROUND: Currently, the high recurrence rate still forms severe challenges in hepatocellular carcinoma (HCC) treatment. The GALAD score, including age, gender, alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) was developed as a diagnostic model. However, evidence is still lacking to confirm the capability of the GALAD score to predict the recurrence of HCC. METHODS: This study included 390 HCC patients after local ablation at Beijing You'an Hospital from January 1, 2018, to December 31, 2022. Firstly, the area under the receiver operating characteristic (ROC) curve (AUC) was calculated to assess the predictive capability of the GALAD score. Then, the Kaplan-Meier (KM) curve and log-rank test were used to compare the prognosis between two groups classified by GALAD score. Finally, a nomogram for high-risk patients was established by Lasso-Cox regression. It was assessed by ROC curves, calibration curves, and decision curve analysis (DCA). RESULTS: The ROC curve (AUC: 0.749) and KM curve showed the GALAD score had good predictive ability and could clearly stratify patients into two groups through the risk of recurrence. Prognostic factors selected by Lasso-Cox regression contained tumor number, tumor size, and globulin. The nomogram for high-risk patients showed reliable discrimination, calibration, and clinical utility. CONCLUSION: This research displayed that the GALAD score is an effective model for predicting the recurrence of HCC. Meanwhile, we found the poor prognosis of the high-risk group and created a nomogram for these patients.

Ultrasensitive single-step CRISPR detection of monkeypox virus in minutes with a vest-pocket diagnostic device.

The emerging monkeypox virus (MPXV) has raised global health concern, thereby highlighting the need for rapid, sensitive, and easy-to-use diagnostics. Here, we develop a single-step CRISPR-based diagnostic platform, termed SCOPE (Streamlined CRISPR On Pod Evaluation platform), for field-deployable ultrasensitive detection of MPXV in resource-limited settings. The viral nucleic acids are rapidly released from the rash fluid swab, oral swab, saliva, and urine samples in 2 min via a streamlined viral lysis protocol, followed by a 10-min single-step recombinase polymerase amplification (RPA)-CRISPR/Cas13a reaction. A pod-shaped vest-pocket analysis device achieves the whole process for reaction execution, signal acquisition, and result interpretation. SCOPE can detect as low as 0.5 copies/µL (2.5 copies/reaction) of MPXV within 15 min from the sample input to the answer. We validate the developed assay on 102 clinical samples from male patients / volunteers, and the testing results are 100% concordant with the real-time PCR. SCOPE achieves a single-molecular level sensitivity in minutes with a simplified procedure performed on a miniaturized wireless device, which is expected to spur substantial progress to enable the practice application of CRISPR-based diagnostics techniques in a point-of-care setting.

Construction and validation of a machine learning-based nomogram to predict the prognosis of HBV associated hepatocellular carcinoma patients with high levels of hepatitis B surface antigen in primary local treatment: a multicenter study.

Background: Hepatitis B surface antigen (HBsAg) clearance is associated with improved long-term outcomes and reduced risk of complications. The aim of our study was to identify the effects of levels of HBsAg in HCC patients undergoing TACE and sequential ablation. In addition, we created a nomogram to predict the prognosis of HCC patients with high levels of HBsAg (≥1000U/L) after local treatment. Method: This study retrospectively evaluated 1008 HBV-HCC patients who underwent TACE combined with ablation at Beijing Youan Hospital and Beijing Ditan Hospital from January 2014 to December 2021, including 334 patients with low HBsAg levels and 674 patients with high HBsAg levels. The high HBsAg group was divided into the training cohort (N=385), internal validation cohort (N=168), and external validation cohort (N=121). The clinical and pathological features of patients were collected, and independent risk factors were identified using Lasso-Cox regression analysis for developing a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves in the training and validation cohorts. Patients were classified into high-risk and low-risk groups based on the risk scores of the nomogram. Result: After PSM, mRFS was 28.4 months (22.1-34.7 months) and 21.9 months (18.5-25.4 months) in the low HBsAg level and high HBsAg level groups (P<0.001). The content of the nomogram includes age, BCLC stage, tumor size, globulin, GGT, and bile acids. The C-index (0.682, 0.666, and 0.740) and 1-, 3-, and 5-year AUCs of the training, internal validation, and external validation cohorts proved good discrimination of the nomogram. Calibration curves and DCA curves suggested accuracy and net clinical benefit rates. The nomogram enabled to classification of patients with high HBsAg levels into low-risk and high-risk groups according to the risk of recurrence. There was a statistically significant difference in RFS between the two groups in the training, internal validation, and external validation cohorts (P<0.001). Conclusion: High levels of HBsAg were associated with tumor progression. The nomogram developed and validated in the study had good predictive ability for patients with high HBsAg levels.

Antigenicity assessment of SARS-CoV-2 saltation variant BA.2.87.1.

The recent emergence of a SARS-CoV-2 saltation variant, BA.2.87.1, which features 65 spike mutations relative to BA.2, has attracted worldwide attention. In this study, we elucidate the antigenic characteristics and immune evasion capability of BA.2.87.1. Our findings reveal that BA.2.87.1 is more susceptible to XBB-induced humoral immunity compared to JN.1. Notably, BA.2.87.1 lacks critical escaping mutations in the receptor binding domain (RBD) thus allowing various classes of neutralizing antibodies (NAbs) that were escaped by XBB or BA.2.86 subvariants to neutralize BA.2.87.1, although the deletions in the N-terminal domain (NTD), specifically 15-23del and 136-146del, compensate for the resistance to humoral immunity. Interestingly, several neutralizing antibody drugs have been found to restore their efficacy against BA.2.87.1, including SA58, REGN-10933 and COV2-2196. Hence, our results suggest that BA.2.87.1 may not become widespread until it acquires multiple RBD mutations to achieve sufficient immune evasion comparable to that of JN.1.

Machine Learning-Based Nomogram for Predicting Overall Survival in Elderly Patients with Cirrhotic Hepatocellular Carcinoma Undergoing Ablation Therapy.

Purpose: The aim of the study is to identify and evaluate multifaceted factors impacting the survival of elderly cirrhotic HCC patients following ablation therapy, with the goal of constructing a nomogram to predict their 3-, 5-, and 8-year overall survival (OS). Patients and Methods: A retrospective analysis was conducted on 736 elderly cirrhotic HCC patients who underwent ablation therapy between 2014 and 2022. LASSO regression, random survival forest (RSF), and multivariate Cox analyses were employed to identify independent prognostic factors for OS, followed by the development and validation of a predictive nomogram. Harrell's concordance index (C-index), calibration plot and decision curve analysis (DCA) were used to assess the performance of the nomogram. The nomogram was finally utilized to stratify patients into low-, intermediate-, and high-risk groups, aiming to assess its efficacy in precisely discerning individuals with diverse overall survival outcomes. Results: Alcohol drinking, tumor number, globulin (Glob) and prealbumin (Palb) were identified and integrated to establish a novel prognostic nomogram. The nomogram exhibited strong discriminative ability with C-indices of 0.723 (training cohort) and 0.693 (validation cohort), along with significant Area Under the Curve (AUC) values for 3-year, 5-year, and 8-year OS in both cohorts (0.758, 0.770, and 0.811 for training cohort; 0.744, 0.699 and 0.737 for validation cohort). Calibration plots substantiated its consistency, while DCA curves corroborated its clinical utility. The nomogram further demonstrated exceptional effectiveness in discerning distinct risk populations, highlighting its robust applicability for prognostic stratification. Conclusion: Our study successfully developed and validated a robust nomogram model based on four key clinical parameters for predicting 3-, 5- and 8-year OS among elderly cirrhotic HCC patients following ablation therapy. The nomogram exhibited a remarkable capability in identifying high-risk patients, furnishing clinicians with invaluable insights for postoperative surveillance and tailored therapeutic interventions.

A nomogram prognostic model for early hepatocellular carcinoma with diabetes mellitus after primary liver resection based on the admission characteristics.

Background: Patients diagnosed with early-stage hepatocellular carcinoma (HCC) and diabetes mellitus (DM) are at a higher risk of experiencing complications and facing increased mortality rates. Hence, it is crucial to develop personalized clinical strategies for this particular subgroup upon their admission. The objective of this study is to determine the key prognostic factors in early HCC patients who received liver resection combined with DM and develop a practical personalized model for precise prediction of overall survival in these individuals. Method: A total of 1496 patients diagnosed hepatitis B virus (HBV) - related liver cancer from Beijing You'an Hospital were retrospectively enrolled, spanning from 1 January 2014, to 31 December 2019, and ultimately, 622 eligible patients of hepatocellular carcinoma (HCC) patients with diabetes were included in this present investigation. A multivariate COX regression analysis was conducted to identify prognostic factors that are independent of each other and develop a nomogram. The performance of the nomogram was evaluated using various statistical measures such as the C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) in both the training and validation groups. Survival rates were estimated using the Kaplan-Meier method. Results: The study included a total of 622 early HCC patients who underwent liver resection combined with DM. Random Forrest model and Multivariate Cox regression analysis revealed that drinking, tumor number, monocyte-to-lymphocyte ratio, white blood cell count and international normalized ratio at admission were identified as independent prognostic factors for early HCC patients who underwent liver resection combined with DM. The nomogram demonstrated good predictive performance in the training and validation cohorts based on the C-index values of 0 .756 and 0 .739 respectively, as well as the area under the curve values for 3-, 5-, and 8-year overall survival (0.797, 0.807, 0.840, and 0.725, 0.791, 0.855). Calibration curves and decision curve analysis indicated high accuracy and net clinical benefit rates. Furthermore, the nomogram successfully stratified enrolled patients into low-risk and high-risk groups based on their risk of overall survival. The difference in overall survival between these two groups was statistically significant in both the training and validation cohorts (p < 0.0001 and p = 0.0064). Conclusion: Our results indicate that the admission characteristics demonstrate a highly effective ability to predict the overall survival of early HCC patients who have undergone liver resection in combination with DM. The developed model has the potential to support healthcare professionals in making more informed initial clinical judgments for this particular subgroup of patients.

Development and Validation of a Prognostic Nomogram for Patients with AFP and DCP Double-Negative Hepatocellular Carcinoma After Local Ablation.

Purpose: Although alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) have a certain predictive ability for the prognosis of hepatocellular carcinoma (HCC), there are still some cases of aggressive recurrence among patients with AFP and DCP double-negative HCC (DNHC) after local ablation. However, prediction models to forecast the prognosis of DNHC patients are still lacking. Thus, this retrospective study aims to explore the prognostic factors in DNHC patients and develop a nomogram to predict recurrence. Patients and methods: 493 DNHC patients who underwent the local ablation at Beijing You'an Hospital between January 1, 2014, and December 31, 2022, were enrolled. A part that was admitted from January 1, 2014, to December 31, 2018, was designated to the training cohort (n = 307); others from January 1, 2019, to December 31, 2022, were allocated to the validation cohort (n = 186). Lasso regression and Cox regression were employed with the aim of screening risk factors and developing the nomogram. The nomogram outcome was assessed by discrimination, calibration, and decision curve analysis (DCA). Results: Independent prognostic factors selected by Lasso-Cox analysis included age, tumor size, tumor number, and gamma-glutamyl transferase. The area under the receiver operating characteristic (ROC) curves (AUCs) of the training and validation groups (0.738, 0.742, 0.836, and 0.758, 0.821) exhibited the excellent predicted outcome of the nomogram. Calibration plots and DCA plots suggest desirable calibration performance and clinical utility. Patients were stratified into three risk groups by means of the nomogram: low-risk, intermediate-risk, and high-risk, respectively. There exists an obvious distinction in recurrence-free survival (RFS) among three groups (p<0.0001). Conclusion: In conclusion, we established and validated a nomogram for DNHC patients who received local ablation. The nomogram showed excellent predictive power for the recurrence of HCC and could contribute to guiding clinical decisions.

The Current State and Progress of Mpox Vaccine Research.

On July 23, 2022, the World Health Organization (WHO) declared the monkeypox (mpox) outbreak a "Public Health Emergency of International Concern." Since 2022, outbreaks of mpox in many countries around the world have primarily resulted in fatalities among immunocompromised individuals, such as untreated HIV/AIDS patients. Since the eradication of smallpox was declared by the WHO in 1980, the global vaccination against smallpox has been gradually discontinued. China also stopped routine smallpox vaccination in 1981. The protective effect of the smallpox vaccine has decreased over time due to aging and declining immunity in those who were vaccinated. For individuals, timely vaccination against smallpox is an effective means of protection against mpox. However, due to safety concerns with the smallpox vaccine and the limitations of current mpox vaccines, there is no vaccine that is safe, effective, and has low side effects applied in clinical settings. This article provides a comprehensive review of the development of mpox virus (MPXV) vaccines, their application in special populations, and the current state of vaccine research, considering the etiology, transmission, and prevention of the MPXV. Vaccination, as an effective method of epidemic prevention, can provide long-term immune protection and effectively reduce the severity of infection. However, as there is no licensed specific MPXV vaccine available globally, the vaccines currently used for mpox prevention are mostly smallpox vaccines. These smallpox vaccines can offer some degree of protection against mpox by activating cross-protection in the body.

A novel nomogram to predict the overall survival of early-stage hepatocellular carcinoma patients following ablation therapy.

Introduction: This study aimed to assess factors affecting the prognosis of early-stage hepatocellular carcinoma (HCC) patients undergoing ablation therapy and create a nomogram for predicting their 3-, 5-, and 8-year overall survival (OS). Methods: The research included 881 early-stage HCC patients treated at Beijing You'an Hospital, affiliated with Capital Medical University, from 2014 to 2022. A nomogram was developed using independent prognostic factors identified by Lasso and multivariate Cox regression analyses. Its predictive performance was evaluated with concordance index (C-index), receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). Results: The study identified age, tumor number, tumor size, gamma-glutamyl transpeptidase (GGT), international normalized ratio (INR), and prealbumin (Palb) as independent prognostic risk factors. The nomogram achieved C-indices of 0.683 (primary cohort) and 0.652 (validation cohort), with Area Under the Curve (AUC) values of 0.776, 0.779, and 0.822 (3-year, 5-year, and 8-year OS, primary cohort) and 0.658, 0.724, and 0.792 (validation cohort), indicating that the nomogram possessed strong discriminative ability. Calibration and DCA curves further confirmed the nomogram's predictive accuracy and clinical utility. The nomogram can effectively stratify patients into low-, intermediate-, and high-risk groups, particularly identifying high-risk patients. Conclusions: The established nomogram in our study can provide precise prognostic information for HCC patients following ablation treatment and enable physicians to accurately identify high-risk individuals and facilitate timely intervention.

A field diagnostic method for rapid and sensitive detection of mpox virus.

The mpox outbreak has subdued with fewer reported cases at the present in high-income countries. It is known that mpox virus (MPXV) infection has been epidemic for more than 50 years in African countries. The ancestral MPXV strain has changed into multiple clades, indicating the ongoing evolution of MPXV, which reflects the historical neglect of mpox in Africa, especially after smallpox eradication, and bestows the danger of more severe mpox epidemics in the future. It is thus imperative to continue the development of mpox diagnostics and treatments so we can be prepared in the event of a new mpox epidemic. In this study, we have developed an MPXV detection tool that leverages the recombinase-aid amplification assay by integrating lateral flow strips (RAA-LF) and one-step sample DNA preparation, with visible readout, no need of laboratory instrument, and ready for field deployment. The detection limit reaches 10 copies per reaction. The performance of our RAA-FL assay in diagnosing mpox clinical samples is on par with that of the quantitative polymerase chain reaction (PCR) assay. Taken together, we have developed a point-of-care RAA-LF method of high accuracy and sensitivity, readily deployable for field detection of MPXV. This diagnostic tool is expected to improve and accelerate field- and self-diagnosis, allow timely isolation and treatment, reduce the spread of MPXV, thus effectively mitigate MPXV outbreak in the future.

Development and Validation of a Nomogram to Predict the Recurrence of HCC Patients Undergoing CECT After Ablation.

Purpose: We first aimed to compare the prognostic difference between the application of Contrast-enhanced computed tomography (CECT) and Non-enhanced computed tomography (NECT) in hepatocellular carcinoma(HCC) patients with early-stage immediately after ablation. We secondly propose to explore the risk factors for recurrence in patients undergoing CECT, and then develop a nomogram. Patients and Methods: Clinical data were collected from 711 patients who received TACE combined with ablation from January 1, 2015, to December 31, 2022, at Beijing Youan Hospital. According to the imaging methods applied after ablation, patients were categorized into the CECT group and the NECT group and then were compared by Kaplan-Meier (KM) curves. Lasso regression is used to screen risk factors for recurrence and the nomogram was plotted. Finally, discrimination, calibration plot, and decision curve analysis (DCA) were used to measure the performance of the nomogram. Results: The KM curve indicates that recurrence-free survival (RFS) was longer in the CECT group than in the NECT group (HR =0.759, 95% CI 0.606-0.951, P=0.016). Six variables were selected to construct the nomogram. 1-, 3-, and 5-year area under the curves (AUCs) (0.867, 0.731, 0.773 and 0.896, 0.784, 0.773) of the training and validation cohorts proved the good predictive performance of the nomogram. Calibration curves and DCA curves suggested accuracy and net clinical benefit rates. The nomogram enabled to classify of patients into three groups according to the risk of recurrence: low risk, intermediate risk, and high risk. There was a statistically significant difference in RFS between the two groups in the training and validation cohorts (P<0.001). Conclusion: We demonstrated that HCC patients who underwent CECT evaluation after ablation had a better prognosis, making this evaluation method highly recommended for guiding clinical management.

Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting.

The continuing emergence of SARS-CoV-2 variants highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by vaccination based on the ancestral (hereafter referred to as WT) strain would compromise the antibody response to Omicron-based boosters1-5. Vaccination strategies to counter immune imprinting are critically needed. Here we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. In mice, the efficacy of single Omicron boosting is heavily limited when using variants that are antigenically distinct from WT-such as the XBB variant-and this concerning situation could be mitigated by a second Omicron booster. Similarly, in humans, repeated Omicron infections could alleviate WT vaccination-induced immune imprinting and generate broad neutralization responses in both plasma and nasal mucosa. Notably, deep mutational scanning-based epitope characterization of 781 receptor-binding domain (RBD)-targeting monoclonal antibodies isolated from repeated Omicron infection revealed that double Omicron exposure could induce a large proportion of matured Omicron-specific antibodies that have distinct RBD epitopes to WT-induced antibodies. Consequently, immune imprinting was largely mitigated, and the bias towards non-neutralizing epitopes observed in single Omicron exposures was restored. On the basis of the deep mutational scanning profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated that these mutations could further boost the immune-evasion capability of XBB.1.5 while maintaining high ACE2-binding affinity. Our findings suggest that the WT component should be abandoned when updating COVID-19 vaccines, and individuals without prior Omicron exposure should receive two updated vaccine boosters.

Total flavonoids of Litchi chinensis Sonn. seed inhibit prostate cancer growth in bone by regulating the bone microenvironment via inactivation of the HGFR/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Litchi chinensis Sonn. (Litchi) seed, a traditional Chinese medicine, is habitually used in the clinical treatment of prostate cancer (PCa)-induced bone pain. In our previous study, flavonoids have been identified as the active ingredient of litchi seed against PCa. However, its anti-tumor activities in bone and associated molecular mechanisms are still unclear. AIM OF THE STUDY: To investigate the effects and underlying mechanisms of total flavonoids of litchi seed (TFLS) on the growth of PCa in bone. MATERIALS AND METHODS: The effect of TFLS on the growth of PCa in bone was observed using a mouse model constructed with tibial injection of luciferase-expressing RM1-luc cells. Conditioned medium (CM) from bone marrow stromal cells OP9 and CM treated with TFLS (T-CM) was used to investigate the effect on the proliferation, colony formation, and apoptosis of PCa cells (LNCaP, PC3, RM1). An antibody microarray was performed to detect cytokine expression in the supernatant fraction of OP9 cell cultures treated with TFLS or left untreated. Western blot assay was employed to determine the expression and activity of HGFR and its key downstream proteins, Akt, mTOR, NF-κB, and Erk, in PCa cells. The potential target was further verified using immunofluorescence and immunohistochemistry assays. RESULTS: Treatment with TFLS (80 mg/kg, 24 days) significantly suppressed the growth of RM1 cells in bone. CM from bone marrow stromal cells OP9 stimulated the proliferation and colony formation of the PCa cells as well as inhibited the apoptosis of PC3 cells, while T-CM reversed the effects mediated by OP9 cells in vitro. In an antibody array assay, TFLS regulated the majority of cytokines in OP9 cell culture supernatant, among which HGF, HGFR, IGF-1R, and PDGF-AA showed the greatest fold changes. Mechanistically, CM upregulated HGFR and promoted phosphorylation of NF-κB while T-CM induced reduction of HGFR and dephosphorylation of NF-κB in PC3 cells. Moreover, T-CM inhibited NF-κB entry into PC3 cell nuclei. Data from in vivo experiments further confirmed the inhibitory effects of TFLS on NF-κB. CONCLUSION: TFLS suppresses the growth of PCa in bone through regulating bone microenvironment and the underlying mechanism potentially involves attenuation of the HGFR/NF-κB signaling axis.

Nasal spray of an IgM-like ACE2 fusion protein HH-120 prevents SARS-CoV-2 infection: Two investigator-initiated postexposure prophylaxis trials.

HH-120, an IgM-like angiotensin converting enzyme 2 (ACE2) fusion protein, has been developed as a nasal spray against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently undergoing human trials. HH-120 nasal spray was assessed for postexposure prophylaxis (PEP) in two investigator-initiated (NS01 and NS02) trials with different risk levels of SARS-CoV-2 exposure. NS01 enrolled family caregiver participants who had continuous contacts with laboratory-confirmed index cases; NS02 enrolled participants who had general contacts (Part 1) or close contacts (Part 2) with index cases. The primary endpoints were safety and laboratory-confirmed and/or symptomatic SARS-CoV-2 infection. In NS01 trial (14 participants), the SARS-CoV-2 infection rates were 25% in the HH-120 group and 83.3% in the external control group (relative risk reduction [RRR]: 70.0%). In NS02-Part 1 (193 participants), the infection rates were 4% (HH-120) versus 11.3% (placebo), symptomatic infection rates were 0.8% versus 3.5%, hence with a RRR of 64.6% and 77.1%, respectively. In Part 2 (76 participants), the infection rates were 17.1% (HH-120) versus 30.4% (placebo), symptomatic infection rates were 7.5% versus 27.3%, with a RRR of 43.8% and 72.5%, respectively. No HH-120-related serious adverse effects were observed. The HH-120 nasal spray used as PEP was safe and effective in preventing laboratory-confirmed and symptomatic SARS-CoV-2 infection.

Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455-456 synergistically enhances antibody evasion and ACE2 binding.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of XBB lineages on the receptor-binding domain (RBD) L455F and F456L is observed, resulting in variants with substantial growth advantages, such as EG.5, FL.1.5.1, XBB.1.5.70, and HK.3. Here, we show that neutralizing antibody (NAb) evasion drives the convergent evolution of F456L, while the epistatic shift caused by F456L enables the subsequent convergence of L455F through ACE2 binding enhancement and further immune evasion. L455F and F456L evade RBD-targeting Class 1 public NAbs, reducing the neutralization efficacy of XBB breakthrough infection (BTI) and reinfection convalescent plasma. Importantly, L455F single substitution significantly dampens receptor binding; however, the combination of L455F and F456L forms an adjacent residue flipping, which leads to enhanced NAbs resistance and ACE2 binding affinity. The perturbed receptor-binding mode leads to the exceptional ACE2 binding and NAb evasion, as revealed by structural analyses. Our results indicate the evolution flexibility contributed by epistasis cannot be underestimated, and the evolution potential of SARS-CoV-2 RBD remains high.

Risk Factors for Predicting Mortality and Amputation of Patients with Necrotizing Soft-Tissue Infections: Retrospective Analysis of 111 Cases from a Single Medical Center.

Objective: Necrotizing soft-tissue infections (NSTIs) are rare clinical infections with surgical emergencies having a high mortality rate. This study aimed to investigate risk factors for mortality and amputation of patients with NSTI. Methods: We retrospectively analyzed critical factors for outcomes of 111 patients with NSTI hospitalized in our department from 1 January 1999 to 31 December 2018. NSTI diagnosis was based on the patient's clinical characteristics, laboratory risk indicator for necrotizing fasciitis (LRINEC) score, laboratory test data, and microbiological findings in blood and wound culture. The risk factors for mortality and amputation of NSTI were determined using univariate or multivariate logistic regression analysis, receiver operating characteristics (ROC), and the area under the ROC curve (AUC) at 90 days after admission. Results: Diagnosis of 111 patients with NSTI was confirmed according to clinical features, LRINEC score, image data, laboratory findings, and microorganism culture in blood and wounds. The mortality rate was 9.91% (11/111) at day 90 follow-up. High white blood cell (WBC), low hematocrit (HCT), and multiple surgeries were identified to be critical risk factors for NSTI mortality in univariate and multivariate logistic analyses. AUCs, 95% confidence intervals (CI), and P values of risk factors were 0.699, 0.54-0.95, and P = 0.0117 for high WBC; 0.788, 0.63-0.97, and P = 0.0006 for low HCT; and 0.745, 0.59-0.90, and P = 0.0018 for multiple surgeries, respectively. These patients also had high LRINEC scores. Amputation occurred in 34.23% (38/111) of patients. Risk factors for amputation were higher age, low hemoglobin (Hb), and multiple wounds. AUCs, 95% confidence intervals (CI), and P values were 0.713, 0.11-0.32, and P < 0.0001 for higher age; 0.798, 0.08-0.29, and P=0.0007 for low Hb; and 0.757, 0.17-0.34, and P < 0.0001 for multiple lesion sites, respectively. Conclusions: High LRINEC scores, high WBC, low HCT, and multiple surgeries were relevant to increased mortality. Higher age, low Hb, and multiple wounds were associated with amputation risk. These clinical features must be paid attention to when patients are diagnosed with NSTI.

Assessing airborne transmission risks in COVID-19 hospitals by systematically monitoring SARS-CoV-2 in the air.

IMPORTANCE: Risk management and control of airborne transmission in hospitals is crucial in response to a respiratory virus pandemic. However, the formulation of these infection control measures is often based on epidemiological investigations, which are an indirect way of analyzing the transmission route of viruses. This can lead to careless omissions in infection prevention and control or excessively restrictive measures that increase the burden on healthcare workers. The study provides a starting point for standardizing transmission risk management in designated hospitals by systemically monitoring viruses in the air of typical spaces in COVID-19 hospitals. The negative results of 359 air samples in the clean and emergency zones demonstrated the existing measures to interrupt airborne transmission in a designated COVID-19 hospital. Some positive cases in the corridor of the contaminant zone during rounds and meal delivery highlighted the importance of monitoring airborne viruses for interrupting nosocomial infection.

Reduced neutralization and Fc effector function to Omicron subvariants in sera from SARS-CoV-1 survivors after two doses of CoronaVac plus one dose subunit vaccine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron harbors more than 30 mutations of the spike protein and exhibits substantial immune evasion. Although previous study indicated that BNT162b2 messenger RNA vaccine induces potent cross-clade pan-sarbecovirus neutralizing antibodies in survivors of the infection by SARS-CoV-1, the neutralization activity and Fc-mediated effector functions of these cross-reactive antibodies elicited in SARS-CoV-1 survivors to Omicron subvariants still remain largely unknown. In this study, the neutralization activity and Fc-mediated effector functions of antibodies boosted by a third dose vaccination were characterized in SARS-CoV-1 convalescents and healthy individuals. Potent cross-clade broadly neutralizing antibodies were observed in SARS-CoV-1 survivors who received a three-dose vaccination regimen consisting of two priming doses of CoronaVac followed by one booster dose of the protein subunit vaccine ZF2001. However, the induced antibodies exhibited both reduced neutralization and impaired Fc effector functions targeting multiple Omicron subvariants. Importantly, the data also support the notion that immune imprints resulted from SARS-CoV-1 infection may exacerbate the impairment of neutralization activity and Fc-mediated effector functions to Omicron subvariants and provided invaluable information to vaccination strategy in future.