Assessing the genomic feature of Chinese patients with ampullary adenocarcinoma: potential therapeutic targets.

BACKGROUNDS: Ampullary adenocarcinoma (AMPAC) is a rare malignancy, treated as pancreatic or intestinal cancer based on its histologic subtype. Little is known about the genomic features of Chinese patients with AMPAC. MATERIALS AND METHODS: We enrolled 145 Chinese AMPAC patients in our local cohort and performed a compressive somatic and germline genetic testing using a 156 gene panel. Expression of PD-L1 (clone 28 - 8) was also assessed in tumor specimens from 64 patients. RESULTS: The frequency of genetic alterations (GAs) in Chinese patients with AMPAC was found to be distinctive, with TP53, KRAS, SMAD4, APC, CTNNB1, ARID1A, and CDKN2A emerged as the most frequently mutated genes. Comparing with Western patients, significant differences were observed in the prevalence of PIK3CA and ARID2. Furthermore, the incidence of MSI-H was lower in the Chinese cohort, with only two patients identified as MSI-H. Conversely, 11 patients (8.27%) had pathogenic/likely pathogenic germline alterations, all of which were in the DNA damage response (DDR) pathway. In our cohort, 34.48% (22/64) of patients exhibited positive PD-L1 expression in tumor cells, and this expression was associated with GAs in CTNNB1 and BLM. Importantly, over three-fourths of Chinese AMPAC patients in our study had at least one actionable GA, with more than one-fifth of them having actionable GAs classified as Level 3. These actionable GAs were primarily involved in the DDR and PI3K pathways. Notably, GAs in the DDR pathway were detected in both Chinese and Western patients, and regardless of their functional impact, these alterations demonstrated enhanced overall survival rates and higher tumor mutational burden (TMB) levels. CONCLUSION: These findings underscore the distinct genomic landscape of Chinese AMPAC patients and highlight the potential for targeted therapies based on the identified GAs.

Multiphase MRI-Based Radiomics for Predicting Histological Grade of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer. Accurate preoperative prediction of histological grade holds potential for improving clinical management and disease prognostication. PURPOSE: To evaluate the performance of a radiomics signature based on multiphase MRI in assessing histological grade in solitary HCC. STUDY TYPE: Retrospective. SUBJECTS: A total of 405 patients with histopathologically confirmed solitary HCC and with liver gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI within 1 month of surgery. FIELD STRENGTH/SEQUENCE: Contrast-enhanced T1-weighted spoiled gradient echo sequence (LAVA) at 1.5 or 3.0 T. ASSESSMENT: Tumors were graded (low/high) according to results of histopathology. Basic clinical characteristics (including age, gender, serum alpha-fetoprotein (AFP) level, history of hepatitis B, and cirrhosis) were collected and tumor size measured. Radiomics features were extracted from Gd-EOB-DTPA-enhanced MRI data. Three feature selection strategies were employed sequentially to identify the optimal features: SelectFromModel (SFM), SelectPercentile (SP), and recursive feature elimination with cross-validation (RFECV). Probabilities of five single-phase radiomics-based models were averaged to generate a radiomics signature. A combined model was built by combining the radiomics signature and clinical predictors. STATISTICAL TESTS: Pearson χ2 test/Fisher exact test, Wilcoxon rank sum test, interclass correlation coefficient (ICC), univariable/multivariable logistic regression analysis, area under the receiver operating characteristic (ROC) curve (AUC), DeLong test, calibration curve, Brier score, decision curve, Kaplan-Meier curve, and log-rank test. A P-value <0.05 was considered statistically significant. RESULTS: High-grade HCCs were present in 33.8% of cases. AFP levels (odds ratio [OR] 1.89) and tumor size (>5 cm; OR 2.33) were significantly associated with HCC grade. The combined model had excellent performance in assessing HCC grade in the test dataset (AUC: 0.801), and demonstrated satisfactory calibration and clinical utility. DATA CONCLUSION: A model that combined a radiomics signature derived from preoperative multiphase Gd-EOB-DTPA-enhanced MRI and clinical predictors showed good performance in assessing HCC grade. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 5.

Synthesis and Antiviral and Antitumor Activities of Novel 18ß-Glycyrrhetinic Acid Derivatives.

A series of novel derivatives of 18ß-glycyrrhetinic acid (GA) were synthesized by introducing aromatic or heterocyclic structures to extend the side chain, thereby enhancing their interaction with amino acid residues in the active pocket of the target protein. These compounds were structurally characterized using 1H NMR, 13C NMR, and HRMS. The compounds were subsequently evaluated for their inhibitory effects on HIV-1 protease and cell viability in the human cancer cell lines K562 and HeLa and the mouse cancer cell line CT26. Towards HIV-1 protease, compounds 28 and 32, which featured the introduction of heterocyclic moieties at the C3 position of GA, exhibited the highest inhibition, with inhibition rates of 76% and 70.5%, respectively, at 1 mg/mL concentration. Further molecular docking suggests that a 3-substituted polar moiety would be likely to enhance the inhibitory activity against HIV-1 protease. As for the anti-proliferative activities of the GA derivatives, incorporation of a thiazole heterocycle at the C3- position in compound 29 significantly enhanced the effect against K562 cells with an IC50 value of 8.86 ± 0.93 µM. The introduction of electron-withdrawing substituents on the C3-substituted phenyl ring augmented the anti-proliferative activity against Hela and CT26 cells. Compound 13 exhibited the highest inhibitory activity against Hela cells with an IC50 value of 9.89 ± 0.86 µM, whereas compound 7 exerted the strongest inhibition against CT26 cells with an IC50 value of 4.54 ± 0.37 µM. These findings suggest that further modification of GA is a promising path for developing potent novel anti-HIV and anticancer therapeutics.

Synthesis and Activity Evaluation of Vinpocetine-Derived Indole Alkaloids.

This study focuses on the synthesis of novel vinpocetine derivatives (2-25) and their biological evaluation. The chemical structures of the synthesized compounds were fully characterized using techniques such as 1H NMR, 13C NMR, and HRMS. The inhibitory activity of the synthesized compounds on PDE1A was evaluated, and the results revealed that compounds 3, 4, 5, 12, 14, 21, and 25 exhibited superior inhibitory activity compared to vinpocetine. Compound 4, with a para-methylphenyl substitution, showed a 5-fold improvement in inhibitory activity with an IC50 value of 3.53 ± 0.25 µM. Additionally, compound 25, with 3-chlorothiazole substitution, displayed an 8-fold increase in inhibitory activity compared to vinpocetine (IC50 = 2.08 ± 0.16 µM). Molecular docking studies were conducted to understand the binding models of compounds 4 and 25 within the active site of PDE1A. The molecular docking study revealed additional binding interactions, such as π-π stacking and hydrogen bonding, contributing to the enhanced inhibitory activity and stability of the ligand-protein complexes. Overall, the synthesized vinpocetine derivatives demonstrated promising inhibitory activity on PDE1A, and the molecular docking studies provided insights into their binding modes, supporting further development of these compounds as potential candidates for drug research and development.

Correlation of CT-derived pectoralis muscle status and COVID-19 induced lung injury in elderly patients.

OBJECTIVES: To explore the association between CT-derived pectoralis muscle index (PMI) and COVID-19 induced lung injury. METHODS: We enrolled 116 elderly COVID-19 patients linked to the COVID-19 outbreak in Nanjing Lukou international airport. We extracted three sessions of their CT data, including one upon admission (T1), one during the first 2 weeks when lung injury peaked (T2) and one on day 14 ± 2 (T3). Lung injury was assessed by CT severity score (CTSS) and pulmonary opacity score (POS). Pneumonia evolution was evaluated by changes of CT scores at T2 from T1(Δ). RESULTS: The maximum CT scores in low PMI patients were higher than those of normal PMI patients, including CTSS1 (7, IQR 6-10 vs. 5, IQR 3-6, p < 0.001), CTSS2 (8, IQR 7-11 vs. 5, IQR 4-7, p < 0.001) and POS (2, IQR 1-2.5 vs. 1, IQR 1-2, p < 0.001). Comorbidity (OR = 6.15, p = 0.023) and the presence of low PMI (OR = 5.43, p = 0.001) were predictors of lung injury aggravation with ΔCTSS1 > 4. The presence of low PMI (OR = 5.98, p < 0.001) was the predictor of lung injury aggravation with ΔCTSS2 > 4. Meanwhile, presence of low PMI (OR = 2.82, p = 0.042) and incrementally increasing D-dimer (OR = 0.088, p = 0.024) were predictors of lung injury aggravation with ΔPOS = 2. CONCLUSIONS: PMI can be easily assessed on chest CT images and can potentially be used as one of the markers to predict the severity of lung injury in elderly COVID-19 patients.

Bone Sclerostin and Dickkopf-related protein-1 are positively correlated with bone mineral density, bone microarchitecture, and bone strength in postmenopausal osteoporosis.

BACKGROUND: Wnt-catenin signaling antagonists sclerostin and dickkopf-related protein-1 (Dkk-1) inhibit bone formation and are involved in the pathogenesis of postmenopausal osteoporosis (PO). However, the association between sclerostin and Dkk-1 and bone mineral density (BMD) in women with PO remains unclear. OBJECTIVE: This study aimed to determine the association between sclerostin and Dkk-1 and BMD, bone microarchitecture, and bone strength in PO. METHODS: Trabecular bone specimens were obtained from the femoral heads of 76 Chinese women with PO who underwent hip arthroplasty for femoral neck fractures. Micro-computed tomography (Micro-CT) was used to assess the BMD and bone microarchitecture of the trabecular bone. Subsequently, a mechanical test was performed. Finally, sclerostin and Dkk-1 in the bone were measured by enzyme-linked immunosorbent (Elisa) assay. Serum ionized serum ionised calcium, propeptide of type 1 collagen, C-terminal ß-telopeptide of type-1 collagen, sclerostin, and Dkk-1 were also detected. RESULTS: Bone sclerostin was positively correlated with serum ionised calcium, serum sclerostin, BMD, bone volume/tissue volume (BV/TV), trabecular number (Tb.N), maximum compressive force, and yield strength (r = 0.32, 0.906, 0.355, 0.401, 0.329, 0.355, and 0.293, respectively, P < 0.05) and negatively correlated with age and trabecular separation (Tb.Sp) (r = - 0.755 and - 0.503, respectively, P < 0.05). Bone Dkk-1 was positively correlated with serum ionised calcium, serum Dkk-1, BMD, BV/TV, trabecular thickness, Tb.N, maximum compressive force, yield strength, and Young's modulus (r = 0.38, 0.809, 0.293, 0.293, 0.228, 0.318, 0.352, 0.315, and 0.266, respectively, P < 0.05) and negatively correlated with age and Tb.Sp (r = - 0.56 and - 0.38, respectively, P < 0.05). Serum levels of sclerostin and Dkk-1 reflected the levels of sclerostin and Dkk-1 in the bone. CONCLUSION: Bone sclerostin and Dkk-1 were positively correlated with BMD in women with PO, and higher levels of bone sclerostin and Dkk-1 might predict better BMD, bone microarchitecture, and bone strength. The potential molecular mechanisms still require further study.

Identification and Physicochemical Properties of the Novel Hemolysin(s) From Oral Secretions of Helicoverpa armigera (Lepidoptera: Noctuidae).

Hemolysins cause the lysis of invading organisms, representing major humoral immunity used by invertebrates. Hemolysins have been discovered in hemolymph of Helicoverpa armigera larvae as immune factors. As oral immunity is great important to clear general pathogens, we presumed that hemolysins may be present in oral secretions (OS). To confirm this hypothesis, we conducted four testing methods to identify hemolysin(s) in larval OS of H. armigera, and analyzed physicochemical properties of the hemolysin in comparison with hemolytic melittin of Apis mellifera (L.) (Hymenoptera: Apidae) venom. We found hemolysin(s) from OS of H. armigera for the first time, and further identified in other lepidopteran herbivores. It could be precipitated by ammonium sulfate, which demonstrates that the hemolytic factor is proteinaceous. Labial gland showed significantly higher hemolytic activity than gut tissues, suggesting that hemolysin of OS is mainly derived from saliva secreted by labial glands. Physicochemical properties of hemolysin in caterpillar's OS were different from bee venom. It was noteworthy that hemolytic activity of OS was only partially inhibited even at 100°C. Hemolytic activity of OS was not inhibited by nine tested carbohydrates contrary to bee venom melittin. Moreover, effects of metal ions on hemolytic activity were different between OS and bee venom. We conclude that there is at least a novel hemolysin in OS of herbivorous insects with proposed antibacterial function, and its hemolytic mechanism may be different from melittin. Our study enriches understanding of the potential role of hemolysins in insect immunity and provides useful data to the field of herbivorous insect-pathogen research.

Prospective comparison between DCE-MRR and 99m Tc-DTPA-based SPECT for determination of allograft renal function.

BACKGROUND: Glomerular filtration rate (GFR) is a preferred indicator of allograft renal function, but direct measurement of GFR remains complicated. PURPOSE: To prospectively compare dynamic contrast-enhanced MR renography (DCE-MRR) with 99m Tc-DTPA-based single-photon emission computed tomography (SPECT) for determination of allograft renal function. STUDY TYPE: Prospective. POPULATION: Seventy kidney-transplant recipients FIELD STRENGTH: A low-dose DCE-MRR with a 3.0T scanner and a 99m Tc-DTPA-based SPECT after renal transplantation were performed. ASSESSMENT: A Baumann-Rudin (BR) and a modified two-compartment model (JZ2C) were used for DCE-MRR analysis. Standard Gate's method was used for SPECT analysis. An endogenous creatinine clearance rate (CCr) constituted the reference standard. STATISTICAL TESTS: Pearson correlation test and Bland-Altman agreement analysis. RESULTS: The reference CCr-GFR was 59.58 ± 23.72 mL/min/1.73 m2 . GFR determined by eGFR, BR, JZ2C, and SPECT was 90.22 ± 34.38, 36.78 ± 14.46, 48.99 ± 23.88, and 67.32 ± 18.44 mL/min/1.73 m2 , respectively. DCE-MRR using JZ2C had the best overall performance, with a Pearson correlation coefficient of 0.81, a bias of -10.58 mL/min/1.73 m2 , and a precision of 14.61 mL/min/1.73 m2 , as well as high accuracy (30-50% intervals: 74.3-90.0%). Although SPECT had a small bias (7.74 mL/min/1.73 m2 ), it had a poor correlation coefficient (0.38), poor precision (23.93 mL/min/1.73 m2 ), and low accuracy (64.3-72.3%) as compared with DCE-MRR using JZ2C. DATA CONCLUSION: DCE-MRR using JZ2C is superior to 99m Tc-DTPA-based SPECT to determine allograft renal function. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:262-269.

Effects of depression on healing and inflammatory responses of acute wounds in rats.

This study aimed to elucidate the effect of depression on the healing of acute wounds in rats. We hypothesized that depression would have negative effects on inflammation and wound healing and that antidepressant therapy would reverse these effects. This study included 100 rats randomly allocated into five groups: control group (CG), depression group (DG), pre-depression group (PDG), antidepressant group (AG), and pre-antidepressant group (PAG). Acute wounds were created on the rats' backs. The groups were subjected to no interventions (CG), aversive stimuli before (PDG) and after (DG) wound creation, and antidepressant treatment before (PAG) and after (AG) wound creation. On the day of wound creation and on days 3, 6, 9, and 12 after wound creation, observations of the wound area and degree of depression (evaluated using the sucrose preference test, open-field test, and weight change) were recorded. On days 6 and 12 after wound creation, venous serum and wound tissues were collected. Tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-6, and IL-10 levels were measured using the enzyme-linked immunosorbent assay. Results showed an initial increase followed by a decrease in the degree of depression in all groups except DG (continuous decline). The wound-healing rate was significantly lower in PDG and DG than in CG; it was higher in AG and PAG than in CG. DG and PDG had higher concentrations of inflammatory cytokines than CG, and AG and PAG had lower concentrations than CG. This indicates that the onset of depression delays the healing of acute wounds and aggravates the inflammatory response in rats. Antidepressant treatment counteracts both of these negative effects.

A Comparative Study of Biological Characteristics and Transcriptome Profiles of Mesenchymal Stem Cells from Different Canine Tissues.

Mesenchymal stem cells (MSCs) are the most promising seed cells for cell therapy. Comparing the biological and transcriptome gene characteristics of MSCs from different sources provides an important basis for the screening of clinically used cells. The main purpose of this experiment was to establish methods for the isolation and culture of MSCs from five different canine sources, including adipose tissue, bone marrow, umbilical cord, amniotic membrane, and placenta, and compare biological and transcriptome characteristics of MSCs, in order to provide a basis for the clinical application of canine MSCs. MSCs were isolated from Chinese pastoral dogs, and the following experiments were performed: (1) the third, sixth, and ninth generations of cells were counted, respectively, and a growth curve was plotted to calculate the MSC population doubling time; (2) the expression of CD34 and CD44 surface markers was studied by immunofluorescence; (3) the third generation of cells were used for osteogenetic and adipogenic differentiation experiments; and (4) MSC transcriptome profiles were performed using RNA sequencing. All of the five types of MSCs showed fibroblast-like adherent growth. The cell surface expressed CD44 instead of CD34; the third-generation MSCs had the highest proliferative activity. The average population doubling time of adipose mesenchymal stem cells (AD-MSCs), placenta mesenchymal stem cells (P-MSCs), bone marrow mesenchymal stem cells (BM-MSCs), umbilical cord mesenchymal stem cells (UC-MSCs), and amniotic mesenchymal stem cells (AM-MSCs) were 15.8 h, 21.2 h, 26.2 h, 35 h, and 41.9 h, respectively. All five types of MSCs could be induced to differentiate into adipocytes and osteoblasts in vitro, with lipid droplets appearing after 8 days and bone formation occurring 5 days after AD-MSC induction. However, the multilineage differentiation for the remaining of MSCs was longer compared to that of the AD-MSCs. The MSC transcriptome profiles showed that AD-MSC and BM-MSCs had the highest homology, while P-MSCs were significantly different compared to the other four types of MSCs. All the isolated MSCs had the main biological characteristics of MSCs. AD-MSCs had the shortest time for proliferation, adipogenesis, and osteogenic differentiation.

Synthesis, crystal structure, and biological activities of two chiral mononuclear Mn((III)) complexes.

Two new chiral mononuclear Mn((III)) complexes, [MnL((R)) Cl (C2 H5 OH)]•C2 H5 OH () and [MnL((S)) (CH3 OH)2 ]Cl•CH3 OH (), {H2 L = (R,R)-or (S,S)-N,N'-bis-(2-hydroxy-1-naphthalidehydene)-cyclohexanediamine} were synthesized and characterized by various physicochemical techniques. Bond valence sum (BVS) calculations and the Jahn-Teller effect indicate that the Mn centers are in a +3 oxidation state. The statuses of the two complexes in the solution were confirmed as a pair of enantiomers by electrospray ionization, mass spectrometry (ESI-MS) spectrum. The binding ability of the complexes with calf thymus CT-DNA was investigated by spectroscopic and viscosity measurements. Both of the complexes could interact with CT-DNA via an intercalative mode with the order of (R-enantiomer) > (S-enantiomer). Under the physiological conditions, the two compounds exhibit efficient DNA cleavage activities without any external agent, which also follows the order of R-enantiomer > S-enantiomer. Interestingly, the concentration-dependent DNA cleavage experiments indicate an optimal concentration of 17.5 µM. In addition, the interaction of the compounds with bovine serum albumin (BSA) was also investigated, which indicated that the complexes could quench the intrinsic fluorescence of BSA by a static quenching mechanism.

Dose requirements of remifentanil for intubation in nonparalyzed Chinese children.

BACKGROUND: The objective of this study was to determine ED50 and ED95 of remifentanil for intubation combined with propofol in nonparalyzed Chinese children. METHODS: Forty-seven American Society of Anesthesiologists Class I children aged 4-11 years weighing 14-33.5 kg underwent general anesthesia with 2.5 mg·kg(-1) of intravenous propofol followed by remifentanil in Wenzhou, China. The initial dose of remifentanil was 2.5 µg·kg(-1) injected over 60 s. Intubation was attempted 30 s after the completion of remifentanil injection. Level of difficulty to intubate was graded on a scoring system. If the initial intubation condition was deemed satisfactory, subsequent remifentanil doses were decreased by 0.25 µg·kg(-1). If the intubating condition was deemed unsatisfactory, subsequent remifentanil doses were increased by 0.25 µg·kg(-1). Mean arterial pressure, heart rate, and pulse oximetry were documented before and after induction, immediately after intubation, and 1 min after intubation. RESULTS: The ED50 of remifentanil used to render a satisfactory intubating condition used in combination with 2.5 mg·kg(-1) of propofol in nonparalyzed Chinese children was 2.30 µg·kg(-1) (95% confidence interval: 2.28-2.31 µg·kg(-1)), and the ED95 is 2.75 µg·kg(-1) (95% confidence interval: 2.59-3.35 µg·kg(-1)). These doses were lower than previously reported. CONCLUSION: When used in combination with 2.5 mg·kg(-1) of intravenous propofol, ED50 and ED95 of remifentanil for adequate intubation in nonparalyzed children were lower than previously reported, at 2.30 and 2.75 µg·kg(-1), respectively.

A simple and effective machine learning model for predicting the stability of intracranial aneurysms using CT angiography.

Background: It is vital to accurately and promptly distinguish unstable from stable intracranial aneurysms (IAs) to facilitate treatment optimization and avoid unnecessary treatment. The aim of this study is to develop a simple and effective predictive model for the clinical evaluation of the stability of IAs. Methods: In total, 1,053 patients with 1,239 IAs were randomly divided the dataset into training (70%) and internal validation (30%) datasets. One hundred and ninety seven patients with 229 IAs from another hospital were evaluated as an external validation dataset. The prediction models were developed using machine learning based on clinical information, manual parameters, and radiomic features. In addition, a simple model for predicting the stability of IAs was developed, and a nomogram was drawn for clinical use. Results: Fourteen machine learning models exhibited excellent classification performance. Logistic regression Model E (clinical information, manual parameters, and radiomic shape features) had the highest AUC of 0.963 (95% CI 0.943-0.980). Compared to manual parameters, radiomic features did not significantly improve the identification of unstable IAs. In the external validation dataset, the simplified model demonstrated excellent performance (AUC = 0.950) using only five manual parameters. Conclusion: Machine learning models have excellent potential in the classification of unstable IAs. The manual parameters from CTA images are sufficient for developing a simple and effective model for identifying unstable IAs.

Synthesis and pharmacological activity of vinpocetine derivatives.

Vinpocetine and its derivatives were extensively employed in the treatment of ischemic stroke, serving as effective cerebrovascular vasodilators. They could also be utilized for neuroprotection, anti-inflammatory purposes, anti-aging interventions, insomnia treatment, and antidepressant effects. However, due to issues such as hepatic first-pass effect, low bioavailability, and poor patient compliance with multiple dosing, the secondary development of Vinpocetine to address these limitations became a prominent area of research. Five primary methodologies were employed for the synthesis of Vinpocetine derivatives. These included substitution on the A ring to modify the 14-ester group, alteration of the 16-ethyl group, simplification of the D and E rings, and modification of the conformation of Vinpocetine. This paper summarized the current synthesis and activity studies of Vinpocetine and its derivatives, with the aim of providing a reference for the discovery of more potent derivatives of Vinpocetine.

Radiomic Analysis Based on Gd-EOB-DTPA Enhanced MRI for the Preoperative Prediction of Ki-67 Expression in Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: To develop and validate a random forest model based on radiomic features in Gd-EOB-DTPA enhanced MRI for predicting the Ki-67 expression in solitary HCC. MATERIALS AND METHODS: This retrospective study analyzed 258 patients with solitary HCC. Significant clinicoradiological factors were identified through univariate and multivariate analyses for distinguishing HCC with high (>20%) and low (≤20%) Ki-67 expression. Radiomic features were extracted at Gd-EOB-DTPA enhanced MRI. The recursive feature elimination (RFE) strategy was employed to screen robust radiomic features, and the Random Forest (RF) algorithm was utilized to rank radiomic features and construct prediction models. The AUC, accuracy, precision, recall, and f1-score were used to evaluate the performance of RF models. RESULTS: Multivariate analysis identified serum AFP level, tumor size, growth type, and peritumoral enhancement as independent predictors for HCC with high Ki-67 expression. The clinicoradiological-radiomic model that incorporated the clinicoradiological predictors and the top ten radiomic features outperformed the clinicoradiological model in the training set (AUCs 0.876 vs. 0.780; p < 0.001), though the test set did not have a statistical significance (AUCs 0.809 vs. 0.723; p = 0.123). The addition of clinicoradiological predictors did not yield a significant improvement in the performance of radiomic features in both sets (training, p = 0.692; test, p = 0.229). Decision curve analysis further confirmed the clinical utility of the RF models. CONCLUSION: The RF models based on radiomic features of Gd-EOB-DTPA enhanced MRI achieved satisfactory performance in preoperatively predicting Ki-67 expression in HCC.

Recombinant Human Collagen Type III Improves Hypertrophic Scarring by Regulating the Ratio of Type I/III Collagen.

Hypertrophic scar development is a complication associated with wound healing, impacting local appearance and function. The type I/III collagen ratio affects the extent of hypertrophic scarring; a reduced ratio can ameliorate this. In this study, recombinant human collagen type III was developed. Liquid chromatography-tandem mass spectrometry was used to determine its amino acid sequence and confirm its high level of homology with natural human type III collagen. Recombinant human collagen type III displayed no cytotoxicity and did not confer skin irritation and sensitization. Immunofluorescence and western blot analyses of histidine following incubation with fibroblasts suggested cell entry of recombinant human collagen type III. Furthermore, recombinant human collagen type III promoted the synthesis of the natural type III collagen in fibroblasts, resulting in a more obvious increase of type III collagen content in fibroblasts than that of type I collagen, and then decreased the ratio of type I/III collagen. The results of 5-ethynyl-2'-deoxyuridine staining assay suggested enhanced fibroblast proliferation. Following local injection of recombinant human collagen type III, rabbit ear scarring was significantly reduced after 60 days. Vancouver Scar Scale evaluation showed that all index scores were significantly reduced. Western blotting and Picro-Sirius red staining showed that the natural type III collagen increase in scar tissue was greater than that of type I collagen, decreasing the type I/III ratio. In summary, recombinant human collagen type III can be taken up by fibroblasts and promote natural collagen synthesis-especially that of type III-thereby reducing the type I/III ratio and improving hypertrophic scarring.

A modified percutaneous transforaminal endoscopic surgery for central calcified thoracic disc herniation at the T11/T12 level using foraminoplasty and decompression: A case report.

Background: Thoracic disc herniation (TDH) is uncommon. Central calcified TDH (CCTDH) is even rare. Traditional open surgery was considered a gold standard to treat CCTDH, but it was accompanied by a high risk of complications. Recently, a technique called percutaneous transforaminal endoscopic decompression (PTED) was adopted to treat TDH. Gu et al. designed a simplified PTED technique and named it percutaneous transforaminal endoscopic surgery (PTES) to treat various types of lumbar disc herniation; it offered the advantages of simple orientation, easy puncture, reduced steps, and little x-ray exposure. However, PTES to treat CCTDH has not been reported in the literature. Methods: Here, we describe the case of a patient with CCTDH treated with a modified PTES through the unilateral posterolateral approach under local anesthesia and conscious sedation by using a flexible power diamond drill. First, we report that the patient was treated with PTES with later-stage endoscopic foraminoplasty, with an inside-out technique employed at the initial endoscopic decompression stage. Results: A 50-year-old male with progressive gait disturbance and bilateral leg rigidity with paresis and numbness was diagnosed with CCTDH at the T11/T12 level on MRI and CT examinations. A modified PTES was performed on November 22, 2019. The total mJOA (modified Japanese Orthopedic Association) score preoperatively was 12. The method of the determination of incision and the soft tissue trajectory establishment process were the same as those in the original PTES technique. The foraminoplasty process was divided into initial fluoroscopic and final endoscopic stages. At the fluoroscopic stage, the hand trephine's saw teeth were just rotated into the lateral portion of the ventral bone from the superior articular process (SAP) to seize the SAP firmly, while at the endoscopic stage, in order to remove the ventral bone from the SAP safely under direct endoscopic visualization, adequate foramen enlargement was achieved without causing any risk of damage to the neural structures in the spinal canal. During the endoscopic decompression process, the soft disc fragments ventral to the calcified shell were undermined to form a cavity using an inside-out technique. Then, a flexible endoscopic diamond burr was introduced to degrade the calcified shell, and a curved dissector or a flexible radiofrequency probe was used to dissect the thin bony shell from the dural sac. Eventually, the shell was fractured within the cavity piece by piece to remove the whole CCTDH and achieve adequate dural sac decompression, resulting in minimal blood loss and no complications. The symptoms were gradually alleviated and the patient almost completely recovered at the 3-month follow-up, with no symptom recurrence found at the 2-year follow-up. The mJOA score improved to 17 at the 3-month follow-up and to 18 at the 2-year follow-up compared with 12 points preoperatively. Conclusions: A modified PTES may be an alternative minimally invasive technique for the treatment of CCTDH and provide similar or better outcomes over traditional open surgery. However, this procedure requires good endoscopic experience on the part of the surgeon and is beset with technical challenges and therefore should be performed with utmost care.

Complete lumbarization with calcified disc herniations at L5S1 and S1-2 levels treated with percutaneous endoscopic interlaminar discectomy: a case report and technique note.

Objective: This study aims to report a case of a patient with complete lumbarization (Castellvi-IB) who developed symptomatic calcified disc herniations at L5S1 and lumbarized S1-2 levels and achieved excellent neurological recovery following percutaneous endoscopic interlaminar discectomy (PEID). Summary of Background Data: In 1984, Castellvi et al. classified lumbosacral transitional vertebra (LSTV) into four types. They incorrectly classified I LSTV anomalies as only type I sacralization, not realizing type I lumbarization also belonged to type I LSTV, with the latter exhibiting a well-developed S1-2 disc (lumbosacral transitional disc, LSTD). Patients with type I lumbarization rarely develop calcified disc herniations concomitantly at L5S1 and LSTD levels. PEID has been developed to perform discectomy for neurological decompression at the lumbar region, especially at the lowest level where the higher iliac crest and/or widened transverse process exists. Methods: A 47-year-old male presented to our hospital complaining of an intractable left leg radiating pain for 3 weeks after suffering from chronic radiating pain for 4 years. His physical examination found hyperalgesia at the lateral side of the left calf, decreased dorsal flexion strength of the ankle (grade 4/5), and a positive sign of straight leg raising test at the left side (30°). The preoperational Lumbar JOA (Japanese Orthopaedic Association) score was 12. Image examinations including whole spinal radiograph, MRI, and CT confirmed complete lumbarization (Castellvi-IB) with calcified disc herniations at L5S1 and LSTD levels at the left side. PEID was carried out at two index levels to accomplish decompression via the left approach. Results: The patient's neurological function recovered quickly. One day postoperatively, he began to walk without discomfort. After 3 months, his muscle strength recovered to normal, and after 6 months, the residual dysesthesia at his posterolateral calf disappeared. The follow-up Lumbar JOA score was 26. Conclusion: Calcified lumbar disc herniation could develop at two distal levels concomitantly in the case of type I complete lumbarization. This anomaly might be misinterpreted as a normal lumbar sequence by only lumbar MRI. PEID may be an effective procedure to treat such calcified disc herniations in a single visit.

Percutaneous Transforaminal Endoscopic Diskectomy for Lumbar Disk Herniation: Young (Age <60 years) versus Older (Age ≥60 years) Patients.

BACKGROUND: We compare the differences in the efficacy of percutaneous transforaminal endoscopic diskectomy (PTED) between the younger (age <60 years) and older (age ≥60 years) patients with lumbar disk herniation (LDH). METHODS: From December 2016 to December 2017, 128 patients with symptomatic LDH underwent PTED and were followed up. Forty-four 60 years old and above, including 19 males and 25 females with an average age of 68.7 (61-82) years, were classified as the elderly age group. Eighty-four patients younger than 60 years were classified as the young age group, which included 48 males and 36 females with an average age of 44.7 (16-58) years. The visual analog scale (VAS) scores, Japanese Orthopaedic Association (JOA) scores, and satisfaction rates of the two groups before and after surgery were compared. RESULTS: The operation was completed successfully in both groups. The average follow-up times of the elderly and young age groups were 18.47 ± 2.62 (12-23) and 17.90 ± 3.27 (12-23) months, respectively. One patient in the young age group had recurrence 7 months after surgery, and the symptoms were relieved after PTED was performed again. Two patients with nerve root injury after surgery in the young age group completely recovered after 2 months of conservative treatment. There were no significant surgical complications in the elderly age group. There was no significant difference in postoperative VAS, JOA, and MacNab scores between the two groups. The MacNab scores in the elderly age group were excellent for 28 patients, good for 10 patients, and fair for 6 patients; the satisfaction rate was 86.3%. In the young age group, scores were excellent for 63 patients, good for 14 patients, fair for 5 patients, and poor for 2 patients; the satisfaction rate was 91.7%. CONCLUSION: The clinical effectiveness of PTED for treatment of LDH in both elderly and young patients is satisfactory. Age is not a predictor of poor outcomes of PTED.

Endophytic Colletotrichum (Sordariomycetes, Glomerellaceae) species associated with Citrusgrandis cv. "Tomentosa" in China.

Colletotrichum species are well-known plant pathogens, saprobes, endophytes, human pathogens and entomopathogens. However, little is known about Colletotrichum as endophytes of plants and cultivars including Citrusgrandis cv. "Tomentosa". In the present study, 12 endophytic Colletotrichum isolates were obtained from this host in Huazhou, Guangdong Province (China) in 2019. Based on morphology and combined multigene phylogeny [nuclear ribosomal internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (gapdh), chitin synthase 1 (chs-1), histone H3 (his3) actin (act), beta-tubulin (ß-tubulin) and glutamine synthetase (gs)], six Colletotrichum species were identified, including two new species, namely Colletotrichumguangdongense and C.tomentosae. Colletotrichumasianum, C.plurivorum, C.siamense and C.tainanense are identified as being the first reports on C.grandis cv. "Tomentosa" worldwide. This study is the first comprehensive study on endophytic Colletotrichum species on C.grandis cv. "Tomentosa" in China.