Retinol-binding protein 4 as a promising serum biomarker for the diagnosis and prognosis of hepatocellular Carcinoma.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is universally poor. Early diagnosis plays a pivotal role in determining the outcome of HCC. METHODS: We employed a comparative proteomics approach to identify potential biomarkers and validated the application of retinol-binding protein 4 (RBP4) as a biomarker for HCC. RBP4 protein expression was examined in liver tissues from 80 HCC patients through immunohistochemical analysis. Serum RBP4 concentrations were measured by ELISA in a cohort comprising 290 HCC patients, matched 202 chronic hepatitis B patients and 269 healthy controls. Survival data were collected from HCC patients. The diagnostic and prognostic values of RBP4 were evaluated using receiver operating curve (ROC) analysis. RESULTS: The validation results demonstrated a significant reduction in RBP4 levels in both liver tissues and serum samples from HCC patients. ROC analysis of the diagnostic value of RBP4 revealed an AUC of 0.879 (95 % CI: 0.854∼0.903) for HCC. When combined with AFP, the AUC increased to 0.919, with a sensitivity of 87.9 % and specificity of 80 %. Survival analysis revealed significantly reduced overall survival time in individuals with low-expression of RBP4 compared to those with high-expression. The joint prognostic model exhibited an AUC of 0.926 (95 % CI: 0.888∼0.964), which was significantly higher than that of AFP alone (AUC=0.809; P <0.0001). CONCLUSIONS: RBP4 shows a great potential as a biomarker with appreciable diagnostic value, complementing the AFP in HCC diagnosis. Additionally, it holds promise as a prognostic biomarker that, when integrated into a combined prognostic model, could greatly improve HCC prognosis efficiency.

Automatic extraction of facial median sagittal plane for patients with asymmetry based on the EDMA alignment algorithm.

BACKGROUND: We aimed to establish a novel method for automatically constructing three-dimensional (3D) median sagittal plane (MSP) for mandibular deviation patients, which can increase the efficiency of aesthetic evaluating treatment progress. We developed a Euclidean weighted Procrustes analysis (EWPA) algorithm for extracting 3D facial MSP based on the Euclidean distance matrix analysis, automatically assigning weight to facial anatomical landmarks. METHODS: Forty patients with mandibular deviation were recruited, and the Procrustes analysis (PA) algorithm based on the original mirror alignment and EWPA algorithm developed in this study were used to construct the MSP of each facial model of the patient as experimental groups 1 and 2, respectively. The expert-defined regional iterative closest point algorithm was used to construct the MSP as the reference group. The angle errors of the two experimental groups were compared to those of the reference group to evaluate their clinical suitability. RESULTS: The angle errors of the MSP constructed by the two EWPA and PA algorithms for the 40 patients were 1.39 ± 0.85°, 1.39 ± 0.78°, and 1.91 ± 0.80°, respectively. The two EWPA algorithms performed best in patients with moderate facial asymmetry, and in patients with severe facial asymmetry, the angle error was below 2°, which was a significant improvement over the PA algorithm. CONCLUSIONS: The clinical application of the EWPA algorithm based on 3D facial morphological analysis for constructing a 3D facial MSP for patients with mandibular deviated facial asymmetry deformity showed a significant improvement over the conventional PA algorithm and achieved the effect of a dental clinical expert-level diagnostic strategy.

Automatic three-dimensional facial symmetry reference plane construction based on facial planar reflective symmetry net.

OBJECTIVES: Three-dimensional (3D) facial symmetry analysis is based on the 3D symmetry reference plane (SRP). Artificial intelligence is widely used in the dental and oral sciences. This study developed a novel deep learning model called the facial planar reflective symmetry net (FPRS-Net) to automatically construct an SRP and established a method for defining a 3D point-cloud region of interest (ROI) and high-dimensional feature computations suitable for this network model. METHODS: Overall, 240 patients were enrolled. The deep learning model was trained and predicted using 200 samples, and its clinical suitability was evaluated with 40 samples. Four FPRS-Net models were prepared, each using supervised and unsupervised learning approaches based on full facial and ROI data (FPRS-NetS, FPRS-NetSR, FPRS-NetU, and FPRS-NetUR). These models were trained on 160 3D facial datasets, validated on 20 cases, and tested on another 20 cases. The model predictions were evaluated using an additional 40 clinical 3D facial datasets by comparing the mean square error of the SRP between the parameters predicted by the four FPRS-Net models and the truth plane. The clinical suitability of FPRS-Net models was evaluated by measuring the angle error between the predicted and ground-truth planes; experts evaluated the predicted SRP of the four FPRS-Net models using the visual analogue scales (VAS) method. RESULTS: The FPRS-NetSR and FPRS-NetU models achieved an average angle error of 0.84° and 0.99° in predicting 3D facial SRP, respectively, with a VAS value of >8. Using the four FPRS-Net models to create an SRP in 40 cases of 3D facial data required <4 s. CONCLUSIONS: Our study demonstrated a new solution for automatically constructing oral clinical 3D facial SRPs. CLINICAL SIGNIFICANCE: This study proposes an innovative deep learning algorithm (FPRS-Net) to construct a symmetry reference plane that can reduce workload, shorten the time required for digital design, reduce dependence on expert experience, and improve therapeutic efficiency and effectiveness in dental clinics.

Chairside digital design and manufacturing method for children's band and loop space maintainers.

OBJECTIVES: This study proposes a chairside digital design and manufacturing method for band and loop space maintainers and preliminarily validates its clinical feasibility. METHODS: Clinical cases of 10 children requiring space maintenance caused by premature loss of primary teeth were collected. Intraoral scan data of the affected children were also collected to establish digital models of the missing teeth. Using a pediatric band and loop space maintainer design software developed by our research team, a rapid personalized design of band and loop structures was achieved, and a digital model of an integrated band and loop space maintainer was ultimately generated. A chairside space maintainer was manufactured through metal computer numerical control machining for the experimental group, whereas metal 3D printing in the dental laboratory was used for the control group. A model fitting assessment was conducted for the space maintainers of both groups, and senior pediatric dental experts were invited to evaluate the clinical feasibility of the space maintainers with regard to fit and stability using the visual analogue scale scoring system. Statistical analysis was also performed. RESULTS: The time spent in designing and manufacturing the 10 space maintainers of the experimental group was all less than 1 h. Statistical analysis of expert ratings showed that the experimental group outperformed the control group with regard to fit and stability. Both types of space maintainers met clinical requirements. CONCLUSIONS: The chairside digital design and manufacturing method for pediatric band and loop space maintainers proposed in this study can achieve same-day fitting of space maintainers at the first appointment, demonstrating good clinical feasibility and significant potential for clinical application.

Spatial Trueness Evaluation of 3D-Printed Dental Model Made of Photopolymer Resin: Use of Special Structurized Dental Model.

(1) Background: Various 3D printers are available for dental practice; however, a comprehensive accuracy evaluation method to effectively guide practitioners is lacking. This in vitro study aimed to propose an optimized method to evaluate the spatial trueness of a 3D-printed dental model made of photopolymer resin based on a special structurized dental model, and provide the preliminary evaluation results of six 3D printers. (2) Methods: A structurized dental model comprising several geometrical configurations was designed based on dental crown and arch measurement data reported in previous studies. Ninety-six feature sizes can be directly measured on this original model with minimized manual measurement errors. Six types of photo-curing 3D printers, including Objet30 Pro using the Polyjet technique, Projet 3510 HD Plus using the Multijet technique, Perfactory DDP and DLP 800d using the DLP technique, Form2 and Form3 using the SLA technique, and each printer's respective 3D-printable dental model materials, were used to fabricate one set of physical models each. Regarding the feature sizes of the simulated dental crowns and dental arches, linear measurements were recorded. The scanned digital models were compared with the design data, and 3D form errors (including overall 3D deviation; flatness, parallelism, and perpendicularity errors) were measured. (3) Results: The lowest overall 3D deviation, flatness, parallelism, and perpendicularity errors were noted for the models printed using the Objet30 Pro (overall value: 45 µm), Form3 (0.061 ± 0.019 mm), Objet30 Pro (0.138 ± 0.068°), and Projet 3510 HD Plus (0.095 ± 0.070°), respectively. In color difference maps, different deformation patterns were observed in the printed models. The feature size proved most accurate for the Objet30 Pro fabricated models (occlusal plane error: 0.02 ± 0.36%, occlusogingival direction error: -0.06 ± 0.09%). (4) Conclusions: The authors investigated a novel evaluation approach for the spatial trueness of a 3D-printed dental model made of photopolymer resin based on a structurized dental model. This method can objectively and comprehensively evaluate the spatial trueness of 3D-printed dental models and has a good repeatability and generalizability.

Three-Dimensional Virtual Reconstruction of External Nasal Defects Based on Facial Mesh Generation Network.

(1) Background: In digital-technology-assisted nasal defect reconstruction methods, a crucial step involves utilizing computer-aided design to virtually reconstruct the nasal defect's complete morphology. However, current digital methods for virtual nasal defect reconstruction have yet to achieve efficient, precise, and personalized outcomes. In this research paper, we propose a novel approach for reconstructing external nasal defects based on the Facial Mesh Generation Network (FMGen-Net), aiming to enhance the levels of automation and personalization in virtual reconstruction. (2) Methods: We collected data from 400 3D scans of faces with normal morphology and combined the structured 3D face template and the Meshmonk non-rigid registration algorithm to construct a structured 3D facial dataset for training FMGen-Net. Guided by defective facial data, the trained FMGen-Net automatically generated an intact 3D face that was similar to the defective face, and maintained a consistent spatial position. This intact 3D face served as the 3D target reference face (3D-TRF) for nasal defect reconstruction. The reconstructed nasal data were extracted from the 3D-TRF based on the defective area using reverse engineering software. The '3D surface deviation' between the reconstructed nose and the original nose was calculated to evaluate the effect of 3D morphological restoration of the nasal defects. (3) Results: In the simulation experiment of 20 cases involving full nasal defect reconstruction, the '3D surface deviation' between the reconstructed nasal data and the original nasal data was 1.45 ± 0.24 mm. The reconstructed nasal data, constructed from the personalized 3D-TRF, accurately reconstructed the anatomical morphology of nasal defects. (4) Conclusions: This paper proposes a novel method for the virtual reconstruction of external nasal defects based on the FMGen-Net model, achieving the automated and personalized construction of the 3D-TRF and preliminarily demonstrating promising clinical application potential.

Predictive role of ctDNA in esophageal squamous cell carcinoma receiving definitive chemoradiotherapy combined with toripalimab.

The combination of toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) demonstrated encouraging efficacy against locally advanced esophageal squamous cell carcinoma (ESCC) in the EC-CRT-001 phase II trial (NCT04005170). The primary endpoint of this trial was the clinical complete response rate (cCR), and the secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and quality of life. The exploratory analyses of EC-CRT-001 include exploring the role of circulating tumor DNA (ctDNA) and blood-based tumor mutational burden (bTMB) in predicting the response and survival. In total, 118 blood and 35 tissue samples from 42 enrolled patients were included in the analyses. We found that ctDNA-negative patients achieved a higher cCR compared to those with detectable ctDNA during CRT (83%, 19/23 vs. 39%, 7/18; p = 0.008) or post-CRT (78%, 21/27 vs. 30%, 3/10; p = 0.017). Patients with detectable ctDNA during CRT had shorter PFS (p = 0.014). Similarly, patients with post-CRT detectable ctDNA had a significantly shorter PFS (p = 0.012) and worse OS (p = 0.004). Moreover, patients with high bTMB levels during CRT had prolonged OS (p = 0.027). In conclusion, ctDNA and bTMB have the potential to predict treatment efficacy and survival in ESCC treated with CRT and immunotherapy.

Definitive concurrent chemoradiotherapy with docetaxel plus cisplatin versus 5-fluorouracil plus cisplatin in patients with esophageal squamous cell carcinoma: long-term follow-up results of a phase II randomized controlled trial.

BACKGROUND: Definitive radiotherapy plus concurrent chemotherapy has been a standard treatment for esophagus patients who are unfit to undergo surgery. However, there are a variety of concurrent chemotherapy regimens with varying efficacy. In this phase II prospective study, we compared the efficacy and toxicity of DP (docetaxel and cisplatin) and PF (cisplatin and 5-fluorouracil) regimens with concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC) and analyzed the 5-year overall survival (OS) and progression free survival (PFS). We also summarized the salvage treatments and late toxicities. METHODS: We enrolled 86 patients with clinical stage II-IVA from the Sun Yat-sen University Cancer Center. The patients were divided into two groups: PF group (41) and DP group (45). Statistics were analyzed using SPSS version 19.0. RESULTS: The 5-year OS rates were 62.9% ± 7.6% in PF group, and 52.7% ± 7.5% in DP group (P = 0.131), respectively. The 5-year PFS rates were 43.9% ± 7.8% for PF group, and 40.0% ± 7.3% for DP group (P = 0.398), respectively. Sixteen patients in the DP group and thirteen in the PF group received salvage treatment. For those patients with local residual or local recurrent disease, the median survival time after salvage treatment was 13.5 months and the 1, 2, and 3-year survival rates were 79.0%, 50.3%, and 43.1%, respectively. For all patients, thirteen (15.1%) had Grade 2 late cardiac toxicities. One patient had Grade 2 pleural effusion and required diuretic. Most patients with pneumonia are mild, and only one patient in PF group had Grade 2 pneumonia. One patient in the DP group developed tracheoesophageal fistula. CONCLUSIONS: The 5-year follow-up confirmed that definitive CCRT with the DP regimen did not improve the treatment response, OS, or PFS in patients with ESCC compared to the PF regimen. The PF regimen remains the standard regimen for definitive CCRT for patients with locally advanced ESCC. Long-term follow-up also suggested that appropriate and active salvage treatment has a survival benefit for some patients, and late cardiopulmonary toxicities should be noticed during follow-up. TRIAL REGISTRATION: The trial was registered at https://clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT02969473, October 2010).

A phase II clinical trial of toripalimab combined with neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma (NEOCRTEC1901).

Background: To evaluate the efficacy and safety of toripalimab combined with neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: In this single arm, phase II trial, 44 ESCC patients were enrolled from December 2019 to July 2021 at Sun Yat-sen University Cancer Center (Guangzhou, China). All patients received concurrent radiotherapy (44 Gy in 20 fractions), chemotherapy (paclitaxel 50 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, and 22), and toripalimab (240 mg on days 1 and 22). Within 6-8 weeks of neoadjuvant treatment, patients underwent surgery. The results of the study patients were compared with those of 86 matched patients between July 2015 and March 2022. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoints were treatment-related adverse events and R0 rates. This trail was registered with ClinicalTrails.gov, NCT04006041. Findings: All patients received neoadjuvant treatment, and 42 completed esophagectomy. Of the 42 patients, 21 (50%; 95% CI 35-65) achieved pCR and 2 (5%) patients were ypT0N+. The R0 resection rate was 98% (41/42). Nine (20%) of 44 patients had grade 3/4 adverse events. Among the perioperative complications (n = 42), anastomotic leakage occurred in five cases (12%), tracheal fistula in three cases (7%), and postoperative death in one case (2%) due to tracheal fistula. Compared with the control cohort, the pCR rate of the study group was higher but without significant difference (50% vs. 36%, P = 0.19). Interpretation: Toripalimab combined with NCRT failed to show significantly better pCR rate than historical data. Nevertheless, considering the signs of efficacy and acceptable safety of this regimen, further evaluation in phase III randomized trials might be warranted. Funding: National Natural Science Foundation of China.

Design, synthesis, and biological evaluation of a series of new anthraquinone derivatives as anti-ZIKV agents.

The major severe complications linked to Zika virus (ZIKV) cause the global public health problems, including microcephaly and other congenital abnormalities in newborns, and Guillain-Barré syndrome, meningoencephalitis, multi-organ failure in adults. However, neither approved vaccines nor drugs are available for ZIKV. In this study, we describe the design, synthesis and the anti-ZIKV activities of a series of anthraquinone analogs. Most of the newly synthesized compounds demonstrated moderate to excellent potency against ZIKV. Among all, compound 22, showed the most potent anti-ZIKV activity (EC50 value from 1.33 µM to 5.72 µM) with low cytotoxicity (CC50＞50 µM) in multiple cellular model. Importantly, 22 significantly improved the survival of ZIKV-infected mice (Ifnar1-/-), alleviated ZIKV-associated pathological damages and suppressed the excessive inflammatory response and pyroptosis induced by ZIKV in vivo and in vitro. Furthermore, the molecular docking simulation analysis and the surface plasmon resonance results demonstrated the direct binding between 22 and ZIKV RdRp, and the mechanistic study revealed that 22 suppressed viral RNA synthesis by ZIKV NS5 in cells. Taken together, this study highlights that 22 may be a novel anti-ZIKV drug candidate and provides treatment options for ZIKV-associated diseases.

Subjective evaluation of facial asymmetry with three-dimensional simulated images among the orthodontists and laypersons: a cross-sectional study.

OBJECTIVES: We used three-dimensional (3D) virtual images to undertake a subjective evaluation of how different factors affect the perception of facial asymmetry among orthodontists and laypersons with the aim of providing a quantitative reference for clinics. MATERIALS AND METHODS: A 3D virtual symmetrical facial image was acquired using FaceGen Modeller software. The left chin, mandible, lip and cheek of the virtual face were simulated in the horizontal (interior/exterior), vertical (up/down), or sagittal (forward or backward) direction in 3, 5, and 7 mm respectively with Maya software to increase asymmetry for the further subjective evaluation. A pilot study was performed among ten volunteers and 30 subjects of each group were expected to be included based on 80% sensitivity in this study. The sample size was increased by 60% to exclude incomplete and unqualified questionnaires. Eventually, a total of 48 orthodontists and 40 laypersons evaluated these images with a 10-point visual analog scale (VAS). The images were presented in random order. Each image would stop for 30 s for observers with a two-second interval between images. Asymmetry ratings and recognition accuracy for asymmetric virtual faces were analyzed to explore how different factors affect the subjective evaluation of facial asymmetry. Multivariate linear regression and multivariate logistic regression models were used for statistical data analysis. RESULTS: Orthodontists were found to be more critical of asymmetry than laypersons. Our results showed that observers progressively decreased ratings by 1.219 on the VAS scale and increased recognition rates by 2.301-fold as the degree of asymmetry increased by 2 mm; asymmetry in the sagittal direction was the least noticeable compared with the horizontal and vertical directions; and chin asymmetry turned out to be the most sensitive part among the four parts we simulated. Mandible asymmetry was easily confused with cheek asymmetry in the horizontal direction. CONCLUSIONS: The degree, types and parts of asymmetry can affect ratings for facial deformity as well as the accuracy rate of identifying the asymmetrical part. Although orthodontists have higher accuracy in diagnosing asymmetrical faces than laypersons, they fail to correctly distinguish some specific asymmetrical areas.

The pretherapeutic systemic inflammation score is a prognostic predictor for elderly patients with oesophageal cancer: a case control study.

BACKGROUND: The systemic inflammation score (SIS), based on serum albumin (Alb) and lymphocyte-to-monocyte ratio (LMR), is a novel prognostic tool for some tumours. Studies indicate that the SIS can be used as a postoperative prognostic marker. However, its predictive value in elderly oesophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy is unclear. METHODS: In total, 166 elderly ESCC patients who received radiotherapy with or without chemotherapy were included. Based on different combinations of Alb and LMR levels, the SIS was divided into 3 groups, SIS = 0 (n = 79), SIS = 1 (n = 71) and SIS = 2 (n = 16). The Kaplan-Meier method was used for survival analysis. Univariate and multivariate analyses were performed to assess prognosis. Time-dependent receiver operating characteristic (t-ROC) curves were used to compare the prognostic accuracy of the SIS with that of Alb, LMR, neutrophil-to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII). RESULTS: Decreased Alb and LMR were both associated with shorter OS, whereas a lower SIS was significantly associated with better outcomes. The OS of SIS = 0, SIS = 1 and SIS = 2 was 28.0 ± 2.9, 16.0 ± 2.8 and 10.0 ± 7.0 months, respectively (p = 0.000). Similar results were also observed for PFS. Multivariate analysis of the model with SIS revealed that the SIS was a significant independent biomarker for predicting OS and PFS. The nomogram showed that the C-index was improved to 0.677 when the SIS factor was incorporated. Furthermore, the 3-year OS rates for patients in the SIS-high group (SIS = 1 and SIS = 2) undergoing concurrent radiotherapy with a single agent (CCRT-1) and concurrent radiotherapy with two agents (CCRT-2) were 42% and 15%, respectively (p = 0.039). The t-ROC curve showed that the SIS was more sensitive than other prognostic factors for predicting overall survival. CONCLUSION: The SIS may be a useful prognostic marker in elderly patients with ESCC receiving radiotherapy alone or chemoradiotherapy. The SIS showed a better predictive ability for OS than the continuous variable Alb and could stratify patient prognosis in different therapeutic regimens. CCRT-1 may be the best treatment for SIS-high patients.

Phase I study of cisplatin and nanoparticle albumin-bound-paclitaxel combined with concurrent radiotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: This phase I study aimed to assess the safety, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and preliminary effect of nanoparticle albumin-bound (nab)-paclitaxel in combination with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients with locally advanced ESCC who were ineligible or refused surgery were enrolled. Nab-paclitaxel (60 mg/m2 , 75 mg/m2 , and 90 mg/m2 ) and cisplatin (25 mg/m2 ) were administered intravenously weekly on days 1, 8, 15, 22, and 29 on the basis of the 3 + 3 dose escalation method. The total dose of radiation was 50-64 Gy. The primary endpoint was the safety of chemotherapy. RESULTS: The study enrolled 12 patients across three dose levels. No treatment-related deaths occurred. One patient in the 60 mg/m2 dose level occurred dose-limiting Grade 3 febrile neutropenia. No DLT was found in the 90 mg/m2 dose level thus the MTD was not reached. The phase II study's recommended dose was 75 mg/m2 based on the available preclinical and clinical data including pharmacokinetics, pharmacodynamics, efficacy, and toxicity. The frequent hematologic toxicities were leukocytopenia (Grade 1-2 of 66.7% and Grade 3-4 of 33.3%), neutropenia (Grade 1-2 of 91.7% and Grade 3-4 of 8.3%). Nonhematologic toxicities were mild and manageable. Overall response rate (ORR) of all patients achieved 100%. CONCLUSIONS: Weekly schedule of cisplatin and nab-paclitaxel in combination with concurrent radiotherapy showed manageable toxicities and promising antitumor activity in patients with locally advanced ESCC. The recommended dose of nab-paclitaxel for further studies is 75 mg/m2 .

Efficacy and cost-effectiveness analysis of pretreatment percutaneous endoscopic gastrostomy in unresectable locally advanced esophageal cancer patients treated with concurrent chemoradiotherapy (GASTO 1059).

BACKGROUND: We launched a single-arm phase II study to determine the efficacy and cost-effectiveness of percutaneous endoscopic gastrostomy (PEG) before concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Eligible patients received pretreatment PEG and enteral nutrition during CCRT. The primary outcome was the change of weight during CCRT. The secondary outcome included nutrition status, loco-regional objective response rate (ORR), loco-regional progression-free survival (LRFS), overall survival (OS), and toxicities. A 3-state Markov model was applied for cost-effectiveness analysis. Eligible patients were matched and compared with those who had nasogastric tube feeding (NTF) or oral nutritional supplements (ONS). RESULTS: Sixty-three eligible patients received pretreatment PEG-based CCRT. The mean change of weight during CCRT was -1.4% (standard deviation, 4.4%), and after CCRT, 28.6% of patients gained weight and 98.4% had normal albumin levels. The loco-regional ORR and 1-year LRFS were 98.4% and 88.3%. The incidence of grade ≥3 esophagitis was 14.3%. After matching, another 63 patients were included in the NTF group and 63 in the ONS group. More patients gained weight after CCRT in the PEG group (p = 0.001). The PEG group showed higher loco-regional ORR (p = 0.036) and longer 1-year LRFS (p = 0.030). In cost analysis, the PEG group showed an incremental cost-effectiveness ratio of $3457.65 per quality-adjusted life-years (QALY) compared with the ONS group with a probability of cost-effectiveness of 77.7% at the $10,000 per QALY willingness-to-pay threshold. CONCLUSION: Pretreatment PEG is associated with better nutritional status and treatment outcome in ESCC patients treated with CCRT compared with ONS and NTF. Pretreatment of PEG can be cost-effective because of its significant clinical benefits.

Fungal community remediate quartz tailings soil under plant combined with urban sludge treatments.

Introduction: Tailings can cause extensive damage to soil structure and microbial community. Phytoremediation is an effective strategy for remedied tailings soil due to its environmentally friendly and low-cost advantage. Fungi play a crucial role in nutrient cycling, stress resistance, stabilizing soil structure, and promoting plant growth. However, the fungal community variation in phytoremediation remains largely unexplored. Methods: We analyzed soil fungal community based on high-throughput sequencing during three plant species combined with urban sludge to remediate quartz tailings soil. Results: The results indicated that the fungal diversity was significantly increased with plant diversity, and the highest fungal diversity was in the three plant species combination treatments. Moreover, the fungal diversity was significantly decreased with the addition of urban sludge compared with plant treatments, while the abundance of potential beneficial fungi such as Cutaneotrichosporon, Apiotrichum, and Alternaria were increased. Notably, the fungal community composition in different plant species combination treatments were significant difference at the genus level. The addition of urban sludge increased pH, available phosphorus (AP), and available nitrogen (AN) content that were the main drivers for fungal community composition. Furthermore, the fungal networks of the plant treatments had more nodes and edges, higher connectedness, and lower modularity than plant combined with urban sludge treatments. Conclusion: Our results showed that three plant species combined with urban sludge treatments improved fungal community and soil properties. Our results provide insights for quartz tailings soil remediation using plant-fungi- urban sludge.

Repurposing of Doramectin as a New Anti-Zika Virus Agent.

Zika virus (ZIKV), belonging to the Flavivirus family and mainly transmitted by mosquitoes, causes a variety of adverse outcomes, including Guillain-Barré syndrome, microcephaly, and meningoencephalitis. However, there are no approved vaccines or drugs available for ZIKV. The discovery and research on drugs for ZIKV are still essential. In this study, we identified doramectin, an approved veterinary antiparasitic drug, as a novel anti-ZIKV agent (EC50 value from 0.85 µM to 3.00 µM) with low cytotoxicity (CC50 > 50 µM) in multiple cellular models. The expression of ZIKV proteins also decreased significantly under the treatment of doramectin. Further study showed that doramectin directly interacted with the key enzyme for ZIKV genome replication, RNA-dependent RNA polymerase (RdRp), with a stronger affinity (Kd = 16.9 µM), which may be related to the effect on ZIKV replication. These results suggested that doramectin might serve as a promising drug candidate for anti-ZIKV.

A Surrogate Endpoint for Overall Survival in Locally Advanced and Resectable Esophageal Squamous Cell Carcinoma: A Reanalysis of Data From the NEOCRTEC5010 Trial.

PURPOSE: This study aimed to investigate disease-free survival (DFS) as a surrogate endpoint for overall survival (OS) in patients with locally advanced and resectable esophageal squamous cell carcinoma. METHODS AND MATERIALS: We re-analyzed patient data from the NEOCRTEC5010 randomized controlled trial (N = 451 patients) to compare their OS with that of an age- and sex-matched cohort from the general population of China. We used expected survival and the standardized mortality ratio, respectively, in our analysis of data collected from a neoadjuvant chemoradiation therapy (NCRT) plus surgery group and a surgery-only group. Published data from 6 randomized controlled trials and 20 retrospective studies were used to examine the correlation between DFS and OS at the trial level. RESULTS: The annual hazard rate of disease progression decreased to 4.9% and 8.1% within 3 years in the NCRT and surgery groups, respectively. Patients who were disease-free at 36 months had a 5-year OS of 93.9% (95% CI, 89.7%-98.4%) in the NCRT group with a standardized mortality ratio of 1.1 (95% CI, 0.7-1.8; P = .5639). In contrast, the 5-year OS was only 12.9% (95% CI, 7.3%-22.6%) for patients in the NCRT group who exhibited disease progression within 36 months. At the trial level, DFS and OS were correlated with treatment effect (R2 = 0.605). CONCLUSIONS: Disease-free status at 36 months is a valid surrogate endpoint for 5-year OS in patients with locally advanced and resectable esophageal squamous cell carcinoma. Patients who were disease-free at 36 months showed a favorable OS, which was indistinguishable from that of the age- and sex-matched comparison group from the general population; otherwise, their 5-year OS was extremely poor.

Host factor DUSP5 potently inhibits dengue virus infection by modulating cytoskeleton rearrangement.

Cytoskeleton has been reported to play an essential role in facilitating the viral life cycle. However, whether the host can exert its antiviral effects by modulating the cytoskeleton is not fully understood. In this study, we identified that host factor DUSP5 was upregulated after dengue virus (DENV) infection. In addition, we demonstrated that overexpression of DUSP5 remarkably inhibited DENV replication. Conversely, the depletion of DUSP5 led to an increase in viral replication. Moreover, DUSP5 was found to restrain viral entry into host cells by suppressing F-actin rearrangement via negatively regulating the ERK-MLCK-Myosin IIB signaling axis. Depletion of dephosphorylase activity of DUSP5 abolished its above inhibitory effects. Furthermore, we also revealed that DUSP5 exhibited broad-spectrum antiviral effects against DENV and Zika virus. Taken together, our studies identified DUSP5 as a key host defense factor against viral infection and uncovered an intriguing mechanism by which the host exerts its antiviral effects through targeting cytoskeleton rearrangement.

Comparison of stereotactic body radiation therapy versus surgery for multiple primary lung cancers after prior radical resection: A multicenter retrospective study.

Background: Patients who previously underwent surgical resection of initial primary lung cancer are at a high risk of developing multiple primary lung cancers (MPLCs). The purpose of this study was to compare the efficacy and safety between stereotactic body radiation therapy (SBRT) and surgery for MPLCs patients after prior radical resection for the first lung cancers. Methods: In this multicenter retrospective study, eligible MPLC patients with tumor diameter of 5.0 cm or less at N0M0 who underwent SBRT or reoperation between January 2013 and August 2020 were enrolled. The primary endpoint was the 3-year locoregional recurrence and treatment-related toxicity. Kaplan-Meier method was used to calculate survival rates. The χ2 test was adapted to assess the difference of categorical variables between the two subgroup patients. Results: A total of 203 (73 in the SBRT group and 130 in the surgery group) patients from three academic cancer centers were evaluated with a median follow-up of 38.3 months. The cumulative 1-, 2-, and 3-year incidences of locoregional recurrence were 5.6 %, 7.0 % and 13.1 % in the SBRT group versus 3.2 %, 4.8 % and 7.4 % in the surgery group, respectively [hazard ratio (HR), 1.97; 95 % confidence interval (CI), 0.74-5.24; P = 0.14]. The cancer-specific survival rates were 95.9 %, 94.5 % and 88.1 % versus 96.9 %, 94.6 % and 93.8 % in the SBRT and surgery groups respectively (HR, 1.72; 95 % CI, 0.67-4.44; P = 0.23). In the SBRT group, two patients (2.7 %) suffered from grade 3 radiation pneumonitis, while in the surgery group, grade 3 complications occurred in four (3.1 %) patients, and four cases were expired due to pneumonia or pulmonary heart disease within 90 days after surgery. Conclusions: SBRT is an effective therapeutic option with limited toxicity compared to surgery for patients with MPLCs after prior radical surgical resection, and it could be considered as an alternative treatment for those patients.

Comparison Study of Extraction Accuracy of 3D Facial Anatomical Landmarks Based on Non-Rigid Registration of Face Template.

(1) Background: Three-dimensional (3D) facial anatomical landmarks are the premise and foundation of facial morphology analysis. At present, there is no ideal automatic determination method for 3D facial anatomical landmarks. This research aims to realize the automatic determination of 3D facial anatomical landmarks based on the non-rigid registration algorithm developed by our research team and to evaluate its landmark localization accuracy. (2) Methods: A 3D facial scanner, Face Scan, was used to collect 3D facial data of 20 adult males without significant facial deformities. Using the radial basis function optimized non-rigid registration algorithm, TH-OCR, developed by our research team (experimental group: TH group) and the non-rigid registration algorithm, MeshMonk (control group: MM group), a 3D face template constructed in our previous research was deformed and registered to each participant's data. The automatic determination of 3D facial anatomical landmarks was realized according to the index of 32 facial anatomical landmarks determined on the 3D face template. Considering these 32 facial anatomical landmarks manually selected by experts on the 3D facial data as the gold standard, the distance between the automatically determined and the corresponding manually selected facial anatomical landmarks was calculated as the "landmark localization error" to evaluate the effect and feasibility of the automatic determination method (template method). (3) Results: The mean landmark localization error of all facial anatomical landmarks in the TH and MM groups was 2.34 ± 1.76 mm and 2.16 ± 1.97 mm, respectively. The automatic determination of the anatomical landmarks in the middle face was better than that in the upper and lower face in both groups. Further, the automatic determination of anatomical landmarks in the center of the face was better than in the marginal part. (4) Conclusions: In this study, the automatic determination of 3D facial anatomical landmarks was realized based on non-rigid registration algorithms. There is no significant difference in the automatic landmark localization accuracy between the TH-OCR algorithm and the MeshMonk algorithm, and both can meet the needs of oral clinical applications to a certain extent.