RBM10 regulates the tumorigenic potential of human cancer cells by modulating PPM1B and YBX1 activities.

RNA binding protein RBM10 participates in various RNA metabolism, and its decreased expression or loss of function by mutation has been identified in many human cancers. However, how its dysregulation contributes to human cancer pathogenesis remains to be determined. Here, we found that RBM10 expression was decreased in breast tumors, and breast cancer patients with low RBM10 expression presented poorer survival rates. RBM10 depletion in breast cancer cells significantly promotes the cellular proliferation and migration. We further demonstrated that RBM10 forms a triple complex with YBX1 and phosphatase 1B (PPM1B), in which PPM1B serves as the phosphatase of YBX1. RBM10 knock-down markedly attenuated association between YBX1 and PPM1B, leading to elevated levels of YBX1 phosphorylation and its nuclear translocation. Furthermore, cancer cells with RBM10 depletion had a significantly accelerated tumor growth in nude mice. Importantly, these enhanced tumorigenic phenotypes can be reversed by overexpression of PPM1B. Our findings provide the mechanistic bases for functional loss of RBM10 in promoting tumorigenicity, and are potentially useful in the development of combined therapeutic strategies for cancer patients with defective RBM10.

Learning CT-free attenuation-corrected total-body PET images through deep learning.

OBJECTIVES: Total-body PET/CT scanners with long axial fields of view have enabled unprecedented image quality and quantitative accuracy. However, the ionizing radiation from CT is a major issue in PET imaging, which is more evident with reduced radiopharmaceutical doses in total-body PET/CT. Therefore, we attempted to generate CT-free attenuation-corrected (CTF-AC) total-body PET images through deep learning. METHODS: Based on total-body PET data from 122 subjects (29 females and 93 males), a well-established cycle-consistent generative adversarial network (Cycle-GAN) was employed to generate CTF-AC total-body PET images directly while introducing site structures as prior information. Statistical analyses, including Pearson correlation coefficient (PCC) and t-tests, were utilized for the correlation measurements. RESULTS: The generated CTF-AC total-body PET images closely resembled real AC PET images, showing reduced noise and good contrast in different tissue structures. The obtained peak signal-to-noise ratio and structural similarity index measure values were 36.92 ± 5.49 dB (p < 0.01) and 0.980 ± 0.041 (p < 0.01), respectively. Furthermore, the standardized uptake value (SUV) distribution was consistent with that of real AC PET images. CONCLUSION: Our approach could directly generate CTF-AC total-body PET images, greatly reducing the radiation risk to patients from redundant anatomical examinations. Moreover, the model was validated based on a multidose-level NAC-AC PET dataset, demonstrating the potential of our method for low-dose PET attenuation correction. In future work, we will attempt to validate the proposed method with total-body PET/CT systems in more clinical practices. CLINICAL RELEVANCE STATEMENT: The ionizing radiation from CT is a major issue in PET imaging, which is more evident with reduced radiopharmaceutical doses in total-body PET/CT. Our CT-free PET attenuation correction method would be beneficial for a wide range of patient populations, especially for pediatric examinations and patients who need multiple scans or who require long-term follow-up. KEY POINTS: • CT is the main source of radiation in PET/CT imaging, especially for total-body PET/CT devices, and reduced radiopharmaceutical doses make the radiation burden from CT more obvious. • The CT-free PET attenuation correction method would be beneficial for patients who need multiple scans or long-term follow-up by reducing additional radiation from redundant anatomical examinations. • The proposed method could directly generate CT-free attenuation-corrected (CTF-AC) total-body PET images, which is beneficial for PET/MRI or PET-only devices lacking CT image poses.

DNMT3a-mediated methylation of TCF21/hnRNPA1 aggravates hepatic fibrosis by regulating the NF-κB signaling pathway.

Hepatic fibrosis is caused by liver damage as a consequence of wound healing response. Recent studies have shown that hepatic fibrosis could be effectively reversed, partly through regression of activated hepatic stellate cells (HSCs). Transcription factor 21 (TCF21), a member of the basic helix-loop-helix (bHLH) transcription factor, is involved in epithelial-mesenchymal transformation in various diseases. However, the mechanism by which TCF21 regulates epithelial-mesenchymal transformation in hepatic fibrosis has not been elucidated. In this research, we found that hnRNPA1, the downstream binding protein of TCF21, accelerates hepatic fibrosis reversal by inhibiting the NF-κB signaling pathway. Furthermore, the combination of DNMT3a with TCF21 promoter results in TCF21 hypermethylation. Our results suggest that DNMT3a regulation of TCF21 is a significant event in reversing hepatic fibrosis. In conclusion, this research identifies a novel signaling axis, DNMT3a-TCF21-hnRNPA1, that regulates HSCs activation and hepatic fibrosis reversal, providing a novel treatment strategy for hepatic fibrosis. The clinical trial was registered in the Research Registry (researchregistry9079).

Tissue-resident immune cells in the pathogenesis of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) in which genetic and environmental factors contribute to disease progression. Both innate and adaptive immune cells, including T cells, B cells, activated macrophages and microglia, have been identified to be involved in the pathogenesis of MS, leading to the CNS inflammation, neurodegeneration and demyelination. In recent years, there has been considerable progress in understanding the contribution of tissue-resident immune cells in the pathogenesis of MS. METHODS: We performed a keyword-based search in PubMed database. We combined "multiple sclerosis" with keywords, such as tissue-resident memory T cells, microglia to search for relevant literatures in PubMed. RESULTS AND CONCLUSION: In this review, we comprehensively describe the characteristics of tissue-resident memory T cells and microglia, summarize their role in the pathogenesis of MS, and discuss their interaction with other immune cells in the CNS.

Successful Reconstruction of Complex Sacrococcygeal Defects Using Chimeric Perforator Propeller Flap.

BACKGROUND: Complex soft tissue defects, which result from the surgical resection of sacral tumors, manifest as a combination of skin defects, dead space, infection, and prosthesis exposure. Because the traditional musculocutaneous flap lacks flexibility because of the close connection between the skin flap and the muscle component, the musculocutaneous flap is not suitable for reconstructing complex soft tissue defects where the dead space and skin defects are located at different sites. Furthermore, the perforator flap is also not appropriate for reconstructing complex defects because it lacks the muscular component. We considered the possibility of using the chimeric perforator propeller flap for reconstructing complex sacrococcygeal defects. METHODS: This study included 7 patients who underwent, between July 2007 and July 2021, the reconstruction of complex soft tissue defects of the sacrococcygeal region using a chimeric perforator propeller flap. RESULTS: Among the included cases, the etiologies were chordoma (n = 3), sacral tumor (n = 3), and squamous cell carcinoma (n = 1). In all the cases, vacuum-assisted closure therapy was used to treat wound infections before surgery. The average sizes of the skin and muscle flaps were 195.8 cm 2 (range, 100-350 cm 2 ) and 83.6 cm 2 (range, 60-140 cm 2 ), respectively. The superior gluteal artery was the source artery for the chimeric perforator propeller flap. The donor sites were primarily closed in all cases. One patient had delayed wound healing, and the secondary wound healed using conservative dressing changes. The other 6 flaps had no complications. The average follow-up time was 5.3 months (range, 1-9 months). Muscle weakness and compromised ambulation in the affected lower extremities were not observed in any of the patients. Furthermore, all 7 patients had no tumor recurrence, prosthesis exposure, and infection events in the sacrococcygeal region. CONCLUSIONS: The chimeric perforator propeller flap may be an option for reconstructing complex soft tissue defects in the sacrococcygeal region.

Extensive Defect Reconstruction With Pre-expanded Anterolateral Thigh Flap: Tissue Expansion of the "Outskirts".

BACKGROUND: Previously reported pre-expansion techniques of the anterolateral thigh flap are mainly perforator-based. The expansion will interfere with the flap harvest if the requisite perforator is found unsuitable as a pedicle. Expansion of the peripheral territories of the flap donor site can minimize the interference from the expansion. METHODS: Forty-eight peripheral pre-expansions of the anterolateral thigh flap were retrospectively reviewed in 38 patients from 2012 to 2021. The reconstructive outcomes, including flap success, increase in flap size, donor-site closure, and complications, were assessed. In addition, subgroup analysis was performed based on the expanded territories. RESULTS: Rate of successful flap elevation of 100% and flap survival rate of 97.9% were achieved. One patient had total flap necrosis, which was salvaged with skin grafting. Peripheral expansion attained a mean 55.5% ± 19.6% increase in flap width. Primary donor-site closure was accomplished in 95.8% of flaps and fascial restoration in 97.9% of the donor sites. Three patients developed major expansion-related complications, which required surgical intervention. One patient had wound dehiscence in the donor site, which healed by secondary intention. Compared with other subgroups, the lateral-and-medial-side expansion provided a larger flap for reconstruction (P = 0.001). CONCLUSIONS: If time is not of the essence, peripheral pre-expansion permits direct donor-site closure with size augment of the anterolateral thigh flap. In addition, it preserves the reliability and versatility of the anterolateral thigh flap.

Oncological prognosis and morbidity of hepatectomy in elderly patients with hepatocellular carcinoma: a propensity score matching and multicentre study.

PURPOSE: With increasing life expectancy, the number of elderly patients (≥ 65 years) with hepatocellular carcinoma (HCC) has steadily increased. Hepatectomy remains the first-line treatment for HCC patients. However, the prognosis of hepatectomy for elderly patients with HCC remains unclear. METHODS: Clinical and follow-up data from 1331 HCC patients who underwent surgery between 2008 and 2020 were retrospectively retrieved from a multicentre database. Patients were divided into elderly (≥ 65 years) and non-elderly (< 65 years) groups, and PSM was used to balance differences in the baseline characteristics. The postoperative major morbidity and cancer-specific survival (CSS) of the two groups were compared and the independent factors that were associated with the two study endpoints were identified by multivariable regression analysis. RESULTS: Of the 1331 HCC patients enrolled in this study, 363 (27.27%) were elderly, while 968 (72.73%) were not. After PSM, 334 matched samples were obtained. In the propensity score matching (PSM) cohort, a higher rate of major morbidity was found in elderly patients (P = 0.040) but the CSS was similar in the two groups (P = 0.087). Multivariate analysis revealed that elderly age was not an independent risk factor associated with high rates of major morbidity (P = 0.117) or poor CSS (P = 0.873). The 1-, 3- and 5-year CSS rates in the elderly and non-elderly groups were 91.0% versus 86.2%, 71.3% versus 68.8% and 55.9% versus 58.0%, respectively. Preoperative alpha fetoprotein (AFP) level, Child‒Pugh grade, intraoperative blood transfusion, extended hemi hepatectomy, and tumour diameter could affect the postoperative major morbidity and preoperative AFP level, cirrhosis, Child‒Pugh grade, macrovascular invasion, microvascular invasion (MVI), satellite nodules, and tumor diameter were independently and significantly associated with CSS. CONCLUSION: Age itself had no significant effect on the prognosis of elderly patients with HCC after hepatectomy. Hepatectomy can be safely performed in elderly patients after cautious perioperative management.

Transfer Patterns and Clinical Applications of the Forehead Flaps Based on the Supratrochlear Artery and Supraorbital Artery.

This study aimed to describe the application of transferring preexpanded forehead flaps based on the supratrochlear and supraorbital arteries in 3 patterns for facial reconstruction: Pattern I, interpolated flap; Pattern II, island flap; and Pattern III, propeller flap, which was subdivided into direct propeller flap (Pattern IIIa) and indirect propeller flap (Pattern IIIb). During the first stage, a tissue expander was inserted underneath the forehead. After sufficient inflation of the expander, a forehead flap based on the supratrochlear or supraorbital artery was elevated and transferred to reconstruct the facial defects. Three weeks after the surgery, pedicle division was performed, in which Pattern I and Pattern IIIb flaps were used. Twenty-four patients underwent facial reconstruction. Twenty-three flaps survived without any perfusion-related complications. Venous congestion developed in an island flap. All patients were followed up after surgery, ranging from 2 to 156 (mean, 19) months. The color and texture of the flap matched those of the adjacent skin. The patients and their families were satisfied with the final functional and esthetic outcomes. The forehead flap based on the supratrochlear and supraorbital arteries provides reliable coverage of facial defects. The conventional interpolated flap continues to be the most dependable. Single-stage reconstruction using the island flap and direct propeller flap is applicable to patients who decline the pedicle division procedure. The novel technique of using the indirect propeller flap is safe for cheek reconstruction with minimal donor-site morbidity and esthetically pleasing results.

Utility of Indocyanine Green Angiography for Preventing Pre-expanded Extended Lower Trapezius Myocutaneous Flap Necrosis: How to Make the Correct Decision for Hypoperfused Areas.

BACKGROUND: Designing a skin flap that perfectly covers the anatomical and dynamic territories is challenging. Tissues capturing territories beyond may be insufficiently perfused, and these hypoperfused areas can lead to partial flap necrosis. Indocyanine green angiography (ICGA) is an effective tool for identifying hypoperfused areas. This retrospective study proposes a standardized strategy for managing the hypoperfused areas identified by ICGA in pre-expanded extended lower trapezius myocutaneous (e-LTMC) flaps. METHODS: Patients who underwent pre-expanded e-LTMC flap surgery with perfusion assessment using ICGA between June 2016 and January 2022 were identified. A standardized protocol was applied, and patients were divided into four groups according to different management options for hypoperfused areas detected by ICGA. Preoperative and operative variables of interest and postoperative outcomes, including flap necrosis and flap survival length, were collected and analyzed. RESULTS: Sixty-nine flaps were included in the study. No total flap necrosis was observed. Partial necrosis occurred in 10 flaps. Significant differences were observed in the incidence of full-thickness necrosis between the management groups. The incidence of flap necrosis in cases where management relied on ICGA findings was significantly lower than that of cases where management did not rely on ICGA findings. There were no differences in the relative survival length of the flap between cases with and without intervention for the hypoperfused areas. CONCLUSION: The proposed standard strategy effectively reduced the necrosis rate of the pre-expanded e-LTMC flap, thus it is sensible to act on the ICGA findings. Prophylactic resection of the hypoperfused area should be recommended. Where resection may lead to poor reconstructive outcomes, flap trimming or a second flap should be the preferred option.

Association of Preoperative Body Mass Index with Surgical Textbook Outcomes Following Hepatectomy for Hepatocellular Carcinoma: A Multicenter Study of 1206 Patients.

BACKGROUND: Assessment of quality in the perioperative period is critical to ensure good patient care. Textbook outcomes (TO) have been proposed to combine several parameters into a single defined quality metric. The association of preoperative body mass index (BMI) with incidences of achieving or not achieving TO (non-TO) among patients undergoing hepatectomy for hepatocellular carcinoma (HCC) was characterized. METHODS: Patients who underwent curative-intent hepatectomy for HCC between 2015 and 2018 were identified from a multicenter database. These patients were divided into three groups based on preoperative BMI: low-BMI (≤ 18.4 kg/m2), normal-BMI (18.5-24.9 kg/m2), and high-BMI (≥ 25.0 kg/m2). The incidences of non-TO among these three groups were compared. Multivariate analyses were performed to identify whether there was any independent association between preoperative BMI and non-TO. RESULTS: Among 1206 patients, 100 (8.3%), 660 (54.7%), and 446 (37.0%) were in the low-BMI, normal-BMI, and high-BMI groups, respectively. The incidence of non-TO was 65.6% in the whole cohort. The incidence of non-TO was significantly higher among patients in the low- and high-BMI cohorts versus the normal-BMI cohort (75.0% and 74.7% versus 58.0%, both P < 0.01). After adjustment of other confounding factors on multivariate analysis, low-BMI and high-BMI were independently associated with higher incidences of non-TO compared with normal-BMI (OR: 1.98 and 2.27, both P < 0.05). CONCLUSIONS: Two out of three patients did not achieve TO after hepatectomy for HCC. Both preoperative low-BMI and high-BMI were independently associated with lower odds to achieve optimal TO following HCC resection.

Lower Trapezius Myocutaneous Propeller Flap Based on Dorsal Scapular Artery.

BACKGROUND: The pedicled lower trapezius myocutaneous flap is generally transferred to the recipient site through a subcutaneous tunnel, and a portion of the flap buried in the tunnel needs to be de-epithelialized. Thus, considerable amount of normal skin is sacrificed, and the redundant tissue buried in the tunnel can cause bulging deformity. We believe that transferring the lower trapezius myocutaneous flap in a propeller fashion can avoid the aforementioned issues. METHODS: A retrospective review was performed on all lower trapezius myocutaneous propeller flap reconstructions by a single surgeon from July 2013 to March 2021. Data on patient demographics, diagnosis, features of the defect, characteristics of the flap, and the outcome were collected and analyzed. RESULTS: Thirty-three lower trapezius myocutaneous propeller flaps were used to reconstruct soft tissue defects in the head, neck, and back. The etiologies were malignancy, trauma, postburn scar contracture, and congenital melanocytic nevus. The mean skin paddle dimensions were 29.0 cm in length (range, 13-45 cm) and 10.9 cm in width (range, 6-15 cm). The donor sites were closed primarily in 30 patients, closed using a skin graft in 1 patient, and covered with the second flap in 2 patients. Venous congestion occurred in the distal portion of 4 flaps and partial necrosis in the distal 6 cm of 1 flap. The average follow-up time was 17.5 months (range, 1-56 months). The normal contour of the back was preserved without bulging deformity. No patient developed a winged scapula or a decrease in shoulder elevation. CONCLUSIONS: The lower trapezius myocutaneous propeller flap may be an option for reconstruction of soft tissue defects of the head, neck, and back with less waste of normal tissue and bulging deformity.

Comparison of Conduits Fabricated by Fresh and Predegenerated Skeletal Muscles for Peripheral Nerve Repairing.

ABSTRACT: Reconstruction of peripheral nerve injury remains a challenge for clinical medicine. Previous reports have confirmed that external oblique muscle-fabricated nerve conduit (EMC) could effectively be used to promote peripheral nerve regeneration. In this study, we compared between conduits fabricated from fresh muscle and conduits fabricated from predegenerated muscle for the repair of peripheral nerve defects in a mouse sciatic nerve transection model. We found that the number, diameter, and myelin sheath thickness of the myelinated nerve fibers of the regenerative nerve in the EMC group were larger than those of the predegenerated-EMC (P-EMC) group eight weeks after surgery. The sciatic function index and gastrocnemius wet-weight mass ratio in the EMC group were higher than those in the P-EMC group. The Bcl-2/Bax ratio and the number of Schwann cell nucleus in the proximal nerve stumps in the EMC group were greater than those in the P-EMC group. In conclusion, our results confirmed that the use of fresh skeletal muscle nerve conduit increased the Bcl-2/Bax ratio and promoted the survival of Schwann cells of the proximal nerve stump compared with that of predegenerated skeletal muscle nerve conduits, thus achieving better functional recovery after sciatic nerve defect.

Phenotype Analysis and Genetic Study of Chinese Patients With Treacher Collins Syndrome.

OBJECTIVE: The aim of this study was to confirm the pathogenic variants, explore the genotype-phenotype correlation and characteristics of Chinese patients with Treacher Collins syndrome (TCS). DESIGN: Clinical details of 3 TCS family cases and 2 sporadic cases were collected and analyzed. Whole-exome sequencing and Sanger sequencing were conducted to detect causative variants. SETTING: Tertiary clinical care. PATIENTS: This study included 8 patients clinically diagnosed with TCS who were from 3 familial cases and 2 sporadic cases. MAIN OUTCOME MEASURES: When filtering the database, variants were saved as rare variants if their frequency were less than 0.005 in the 1000 Genomes Project Database, the Exome Aggregation Consortium (ExAC) browser, and the Novogene database, or they would be removed as common ones. The pathogenic variants identified were verified by polymerase chain reaction. The sequencing results were analyzed by Chromas 2.1 software. RESULTS: Two novel pathogenic variants (NM_000356.3: c.537del and NM_000356.3: c.1965_1966dupGG) and 2 known pathogenic variants (NM_000356.3: c.1535del, NM_000356.3: c.4131_4135del) were identified within TCOF1 which are predicted to lead to premature termination codons resulting in a truncated protein. There was a known missense SNP (NM_015972.3: c.139G>A) within POLR1D. No phenotype-genotype correlation was observed. Instead, these 8 patients demonstrated the high genotypic and phenotypic heterogeneity of TCS. CONCLUSIONS: This study expands on the pathogenic gene pool of Chinese patients with TCS. Besides the great variation among patients which is similar to international reports, Chinese patients have their own characteristics in clinical phenotype and pathogenesis mutations.

The Role of Verteporfin in Prevention of Periprosthetic Capsular Fibrosis: An Experimental Study.

BACKGROUND: Capsular contracture (CC) characterized by excessive fibrosis is one of the most common complications after silicone implant surgery. Verteporfin (VP), an inhibitor of Yes-associated protein 1 (YAP1), has recently been found to reduce the fibrotic process. OBJECTIVES: The aim of this study was to use an in vivo rabbit model to evaluate the efficacy of VP for the prevention of CC. METHODS: Twenty-four New Zealand rabbits received 10-cc smooth saline silicone implants inserted in the dorsal skin and were randomly divided into 2 groups to receive 2 mL VP (1.5 mg/mL) or 2 mL phosphate-buffered saline solution instillation in the implant pocket. When the animals were killed on Day 60, capsule formation was observed both macroscopically and microscopically. Histologic evaluation included capsule thickness, fibrosis degree, and myofibroblast (α smooth muscle actin positive) content. In addition, the YAP1 expression level was examined by immunofluorescence staining. Transforming growth factor ß1, collagen I, and connective tissue growth factor expression were measured by real-time quantitative polymerase chain reaction. RESULTS: The VP-treated group exhibited thinner, more transparent capsules and less fibrosis than the control group at 60 days postsurgery (P < 0.05). Moreover, the VP treatment significantly reduced α smooth muscle actin, YAP1, transforming growth factor ß1, collagen I, and connective tissue growth factor expression levels in the capsular tissues (P < 0.05). CONCLUSIONS: VP reduced capsule formation after silicone implantation by inhibiting YAP1-mediated mechanical signaling, thereby attenuating excessive collagen deposition in the rabbit model. This preclinical study may provide a feasible strategy to prevent periprosthetic capsular fibrosis in clinical application.

Polydatin protects Schwann cells from methylglyoxal induced cytotoxicity and promotes crushed sciatic nerves regeneration of diabetic rats.

Oxidative stress plays the main role in the pathogenesis of diabetes mellitus and peripheral neuropathy. Polydatin (PD) has been shown to exhibit strong antioxidative and antiinflammatory effects. At present, no research has focused on the possible effects of PD on Schwann cells and impaired peripheral nerves in diabetic models. Here, we used an in vitro Schwann cell damage model induced by methylglyoxal and an in vivo diabetic sciatic nerve crush model to study problems in such an area. In our experiment, we demonstrated that PD potently alleviated the decrease of cellular viability, prevented reactive oxygen species generation, and suppressed mitochondrial depolarization as well as cellular apoptosis in damaged Schwann cells. Moreover, we found that PD could upregulate Nrf2 and Glyoxalase 1 (GLO1) expression and inhibit Keap1 and receptor of AGEs (RAGE) expression of damaged Schwann cells. Finally, our in vivo experiment showed that PD could promote sciatic nerves repair of diabetic rats. Our results revealed that PD exhibited prominent neuroprotective effects on Schwann cells and sciatic nerves in diabetic models. The molecular mechanisms were associated with activating Nfr2 and GLO1 and inhibiting Keap1 and RAGE.

Outcomes of surgery for giant hepatic hemangioma.

BACKGROUND: The surgical indications for liver hemangioma remain unclear. METHODS: Data from 152 patients with hepatic hemangioma who underwent hepatectomy between 2004 and 2019 were retrospectively reviewed. We analyzed characteristics including tumor size, surgical parameters, and variables associated with Kasabach-Merritt syndrome and compared the outcomes of laparoscopic and open hepatectomy. Here, we describe surgical techniques for giant hepatic hemangioma and report on two meaningful cases. RESULTS: Most (63.8%) patients with hepatic hemangioma were asymptomatic. Most (86.4%) tumors from patients with Kasabach-Merritt syndrome were larger than 15 cm. Enucleation (30.9%), sectionectomy (28.9%), hemihepatectomy (25.7%), and the removal of more than half of the liver (14.5%) were performed through open (87.5%) and laparoscopic (12.5%) approaches. Laparoscopic hepatectomy is associated with an operative time, estimated blood loss, and major morbidity and mortality rate similar to those of open hepatectomy, but a shorter length of stay. 3D image reconstruction is an alternative for diagnosis and surgical planning for partial hepatectomy. CONCLUSION: The main indication for surgery is giant (> 10 cm) liver hemangioma, with or without symptoms. Laparoscopic hepatectomy was an effective option for hepatic hemangioma treatment. For extremely giant hemangiomas, 3D image reconstruction was indispensable. Hepatectomy should be performed by experienced hepatic surgeons.

An iterative reconstruction method for sparse-projection data for low-dose CT.

Reducing X-ray radiation is beneficial for reducing the risk of cancer in patients. There are two main approaches for achieving this goal namely, one is to reduce the X-ray current, and another is to apply sparse-view protocols to do image scanning and projections. However, these techniques usually lead to degradation of the reconstructed image quality, resulting in excessive noise and severe edge artifacts, which seriously affect the diagnosis result. In order to overcome such limitation, this study proposes and tests an algorithm based on guided kernel filtering. The algorithm combines the characteristics of anisotropic edges between adjacent image voxels, expresses the relevant weights with an exponential function, and adjusts the weights adaptively through local gray gradients to better preserve the image structure while suppressing noise information. Experiments show that the proposed method can effectively suppress noise and preserve the image structure. Comparing with similar algorithms, the proposed algorithm greatly improves the peak signal-to-noise ratio (PSNR), structural similarity (SSIM), and root mean square error (RMSE) of the reconstructed image. The proposed algorithm has the best effect in quantitative analysis, which verifies the effectiveness of the proposed method and good image reconstruction performance. Overall, this study demonstrates that the proposed method can reduce the number of projections required for repeated CT scans and has potential for medical applications in reducing radiation doses.

Two novel online nomograms for predicting the survival of individual patients undergoing partial hepatectomy for huge hepatocellular carcinoma.

BACKGROUND: A method for predicting prognosis of patients who undergo partial hepatectomy for huge hepatocellular carcinoma (HHCC, diameter ≥10 cm) is currently lacking. This study aimed to establish two online nomograms to predict the overall survival (OS) and disease-free survival (DFS) for patients undergoing resection for HHCC. METHODS: The clinicopathologic characteristics and follow-up information of patients who underwent partial hepatectomy for HHCC at two medical centers were reviewed. Using a training cohort, a Cox model was used to identify the predictors of survival. Two dynamic nomograms for OS and DFS were developed and validated based on the data. RESULTS: Eight and nine independent factors derived from the multivariate analysis of the training cohort were screened and incorporated into the nomograms for OS and DFS, respectively. In the training cohort, the nomogram achieved concordance indices (C-indices) of 0.745 and 0.738 in predicting the OS and DFS, respectively. These results were supported by external validation (C-indices: 0.822 for OS and 0.827 for DFS). Further, the calibration curves of the endpoints showed a favorable agreement between the nomograms' assessments and actual observations. CONCLUSIONS: The two web-based nomograms demonstrated optimal predictive performance for patients undergoing partial hepatectomy for HHCC. This provides a practical method for a personalized prognosis based on an individual's underlying risk factors.

The establishment of reference sequence for SARS-CoV-2 and variation analysis.

Starting around December 2019, an epidemic of pneumonia, which was named COVID-19 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full-length genomic sequences of SARAS-CoV-2 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS-CoV-2 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%-100%) at the nucleotide level and 99.99% (99.79%-100%) at the amino acid level. Although overall variation in open-reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS-COV-2, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS-CoV-2 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS-CoV-2 infection in the future.

Assessing SARS-CoV-2 RNA levels and lymphocyte/T cell counts in COVID-19 patients revealed initial immune status as a major determinant of disease severity.

The magnitude of SARS-CoV-2 infection, the dynamic changes of immune parameters in patients with the novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. The clinical and laboratory results from 154 confirmed COVID-19 patients were collected. The SARS-CoV-2 RNA levels in patients were estimated using the Ct values of specific RT-PCR tests. The lymphocyte subsets and cytokine profiles in the peripheral blood were analyzed by flow cytometry and specific immunoassays. 154 confirmed COVID-19 patients were clinically examined up to 4 weeks after admission. The initial SARS-CoV-2 RNA Ct values at admission varied, but were comparable in the patient groups classified according to the age, gender, underlying diseases, and disease severity. Three days after admission, significant higher Ct values were found in severe cases. Significantly reduced counts of T cells and T cell subsets were found in patients with old age and underlying diseases at admission and were characteristic for the development of severe COVID-19. Severe COVID-19 developed preferentially in patients with underlying compromised immunity and was not associated with initial virus levels. Higher SARS-CoV-2 RNA levels in severe cases were apparently a result of impaired immune control associated with dysregulation of inflammation.