A preliminary study on the normal values of the thoracic Haller index in children.

OBJECTIVES: The Haller index (HI) is widely utilized as a quantitative indicator to assess the extent of the pectus excavatum (PE) deformity, which is the most common chest wall abnormality in children. Both preoperative correction planning and postoperative follow-up need to be based on the standard of normal thoracic growth and development. However, there is currently no established reference range for the HI in children. Consequently, the goal of this study was to conduct a preliminary investigation of normal HI values among children to understand thoracic developmental characteristics. METHODS: Chest computed tomography images obtained from January 2012 to March 2022 were randomly selected from the imaging system of the Children's Hospital of Chongqing Medical University. We divided the images of children into a total of 19 groups: aged 0-3 months (1 group), 4-12 months (1 group) and 1 year to 17 years (17 groups), with 50 males and 50 females, totaling 100 children in each group. HI was measured in the plane where the lowest point of the anterior thoracic wall was located and statistically analysed using SPSS 26.0 software. RESULTS: A total of 1900 patients were included in the study. Our results showed that HI, transverse diameter and anterior-posterior diameter were positively correlated with age (P < 0.05). Using age as the independent variable and HI as the dependent variable, the best-fit regression equations were HI-male = 2.047 * Age0.054(R2 = 0.276, P<0.0001) and HI-female = 2.045 * Age0.067(R2 = 0.398, P<0.0001). Males had significantly larger thoracic diameters than females, and there was little difference in the HI between the 2 sexes. CONCLUSIONS: The HI rapidly increases during the neonatal period, slowly increases during infancy and stops increasing during puberty, with no significant differences between the sexes.

Preoperative computed tomography-guided transscapular sens-cure needle localization for pulmonary nodule located behind the scapula.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is an approach that is commonly used to resect pulmonary nodules (PNs). However, when these PNs are located behind the scapula, a transscapular access approach is generally required. In this study, the safety, efficacy, and feasibility of preoperative computed tomography (CT)-guided Sens-cure needle (SCN) localization was assessed for PNs located behind the scapula. METHODS: From January 2020 - June 2022, a total of 122 PN patients in our hospital underwent preoperative CT-guided SCN localization and subsequent VATS resection, of whom 12 (9.8%) exhibited PNs behind the scapula necessitating a transscapular approach for this localization procedure. RESULTS: This study included 12 patients, each of whom had one PN located behind the scapula. The CT-guided transscapular SCN localization approach was successful in all patients, and no complications near the operative site were observed. The median localization time was 12 min, and 2 (16.7%) and 1 (8.3%) patients respectively developed pneumothorax and pulmonary hemorrhage after the localization procedure was complete. Wedge resection procedures for these PNs achieved technical success in all cases. Four patients were diagnosed with invasive adenocarcinomas and subsequently accepted lobectomy and systematic lymph node dissection. The median VATS duration and the median blood loss was 80 min and 10 mL, respectively. In total, 3, 5, and 4 PNs were respectively diagnosed as benign, mini-invasive adenocarcinomas, and invasive adenocarcinomas. CONCLUSION: Preoperative CT-guided transscapular SCN localization represents a safe, straightforward, and effective means of localizing PNs present behind the scapula.

Clinical Analysis of Primary Tracheobronchial Tumors in Children and Evaluation of the Predicting Models for Mucoepidermoid Carcinoma.

OBJECTIVE: To determine the clinical characteristics and prognosis of primary tracheobronchial tumors (PTTs) in children, and to explore the most common tumor identification methods. METHODS: The medical records of children with PTTs who were hospitalized at the Children's Hospital of Chongqing Medical University from January 1995 to January 2020 were reviewed retrospectively. The clinical features, imaging, treatments, and outcomes of these patients were statistically analyzed. Machine learning techniques such as Gaussian naïve Bayes, support vector machine (SVM) and decision tree models were used to identify mucoepidermoid carcinoma (ME). RESULTS: A total of 16 children were hospitalized with PTTs during the study period. This included 5 (31.3%) children with ME, 3 (18.8%) children with inflammatory myofibroblastic tumors (IMT), 2 children (12.5%) with sarcomas, 2 (12.5%) children with papillomatosis and 1 child (6.3%) each with carcinoid carcinoma, adenoid cystic carcinoma (ACC), hemangioma, and schwannoma, respectively. ME was the most common tumor type and amongst the 3 ME recognition methods, the SVM model showed the best performance. The main clinical symptoms of PPTs were cough (81.3%), breathlessness (50%), wheezing (43.8%), progressive dyspnea (37.5%), hemoptysis (37.5%), and fever (25%). Of the 16 patients, 7 were treated with surgery, 8 underwent bronchoscopic tumor resection, and 1 child died. Of the 11 other children, 3 experienced recurrence, and the last 8 remained disease-free. No deaths were observed during the follow-up period. CONCLUSION: PTT are very rare in children and the highest percentage of cases is due to ME. The SVM model was highly accurate in identifying ME. Chest CT and bronchoscopy can effectively diagnose PTTs. Surgery and bronchoscopic intervention can both achieve good clinical results and the prognosis of the 11 children that were followed up was good.

A correlative study of iron metabolism based on q-Dixon MRI in benign prostatic hyperplasia and prostate cancer.

Clinical staging, Gleason score, and prostate-specific antigen (PSA) have been accepted as factors for evaluating the prognosis of prostate cancer (PCa). With the in-depth study of iron metabolism and the development of multiparametric magnetic resonance imaging technology, we used q-Dixon magnetic resonance imaging (MRI) to measure the iron content of the PCa patients' lesions, and used enzyme-linked immunosorbent assay (ELISA) to measure the iron metabolism indicators in the patients' serum samples, combined with the patients' postoperative clinical data for analysis. We found that the serum indexes were correlated with the T2 star values, International Society of Urological Pathology (ISUP) grade, and pathological classification in PCa patients (all P < 0.001) but not in benign prostatic hyperplasia (BPH) patients (all P > 0.05). The utilization of q-Dixon-based MRI and serum indexes allows the noninvasive measurement of iron content in prostate lesions and the assessment of differential iron metabolism between PCa and BPH, which may be helpful for evaluating the prognosis of PCa.

Assessment of peripheral neuropathy in type 2 diabetes by diffusion tensor imaging.

BACKGROUND: To evaluate the diagnostic accuracy of diffusion tensor imaging (DTI) in diabetic peripheral neuropathy (DPN) for patients with type 2 diabetes and detect the correlations with electrophysiology. METHODS: A total of 27 patients with type 2 diabetes with DPN, 24 patients with type 2 diabetes without peripheral neuropathy (NDPN), as well as 32 healthy controls (HC) were enrolled in this study. Clinical examinations and neurophysiologic tests were used to determine the presence of DPN. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of peripheral nerves, including the tibial nerve (TN) and common peroneal nerve (CPN), were calculated. Receiver operating characteristic (ROC) analysis was performed for FA and ADC values. Pearson's correlation coefficient was used to assess the correlation between DTI and electrophysiology parameters in the patient group. RESULTS: The tibial and common peroneal nerve FAs were lowest (P=0.003, 0.001, respectively) and ADC was highest (P=0.004, 0.005, respectively) in the DPN group. The FA value of the axonal injury group was lower than that in the demyelination group (P=0.035, 0.01, respectively), while the ADC value was higher (P=0.02, 0.01, respectively). In the DPN group, FA value was positively correlated with motor conduction velocity (MCV) (tibial nerve: r=0.420, P=0.007; common peroneal nerve: r=0.581, P<0.001) and motor amplitude (MA) (tibial nerve: r=0.623, P<0.001; common peroneal nerve: r=0.513; P=0.001), while ADC values was negatively correlated with MCV (tibial nerve: r=-0.320, P=0.044; common peroneal nerve: r=-0.569; P<0.001), and MA (tibial nerve: r=-0.491, P=0.001; common peroneal nerve: r=-0.524; P=0.001). CONCLUSIONS: With a lower FA value and higher ADC value, DTI accurately discriminated DPN. The DTI multi-parameter quantitative analysis of peripheral nerves differentiated DPN axonal injury from the demyelinating lesion, and hence, could be applied in the diagnosis of DPN.

Iliac ecchymosis, a valuable sign for hollow viscus injuries in blunt pelvic trauma patients.

PURPOSE: Pelvic fractures are characterized by high energy injuries and often accompanied with abdominal and pelvic organ injury. CT has been applied for several decades to evaluate blunt pelvic trauma patients. However, it has a certain rate of inaccurate diagnosis of abdominal hollow viscus injury (HVI), especially in the early stage after injury. The delayed diagnosis of HVI could result in a high morbidity and mortality. The bowel injury prediction score (BIPS) applied 3 clinical variables to determine whether an early surgical intervention for blunt HVI was necessary. We recently found another clinical variable (iliac ecchymosis, IE) which appeared at the early stage of injury, could be predicted for HVI. The main objective of this study was to explore the novel combination of IE and BIPS to enhance the early diagnosis rate of HVI, and thus reduce complications and mortalities. METHODS: We conducted a retrospective analysis from January 2008 to December 2018 and recorded blunt pelvic trauma patients in our hospital. The inclusion criteria were patients who were verified with pelvic fractures using abdomen and pelvis CT scan in the emergency department before any surgical intervention. The exclusion criteria were abdominal CT insufficiency before operation, abdominal surgery before CT scan, and CT mesenteric injury grade being 5. The MBIPS was defined as BIPS plus IE, which was calculated according to 4 variables: white blood cell counts of 17.0 or greater, abdominal tenderness, CT scan grade for mesenteric injury of 4 or higher, and the location of IE. Each clinical variable counted 1 score, totally 4 scores. The location and severity of IE was also noted. RESULTS: In total, 635 cases were hospitalized and 62 patients were enrolled in this study. Of these included patients, 77.4% (40 males and 8 females) were operated by exploratory laparotomy and 22.6% (8 males and 6 females) were treated conservatively. In the 48 patients underwent surgical intervention, 46 were confirmed with HVI (45 with IE and 1 without IE). In 46 patients confirmed without HVI, only 3 patients had IE and the rest had no IE. The sensitivity and specificity of IE in predicting HVI was calculated as 97.8% (45/46) and 81.3% (13/16), respectively. The median MBIPS score for surgery group was 2, while 0 for the conservative treatment group. The incidence of HVI in patients with MBIPS score ≥ 2 was significantly higher than that in patients with MBIPS score less than ≤ 2 (OR = 17.3, p < 0.001). CONCLUSION: IE can be recognized as an indirect sign of HVI because of the high sensitivity and specificity, which is a valuable sign for HVI in blunt pelvic trauma patients. MBIPS can be used to predict HVI in blunt pelvic trauma patients. When the MBIPS score is ≥ 2, HVI is strongly suggested.

Host protein CD63 promotes viral RNA replication by interacting with human astrovirus non-structural protein nsP1a/4.

Human astrovirus non-structural protein nsP1a/4, located at the C-terminal end of nsP1a, is thought to be involved in regulating RNA replication. Here, we show that host protein CD63 interacts with the nsP1a protein. Further research showed that the large loop (LEL) domain of CD63 also interacts with nsP1a/4. Confocal microscopy showed that nsP1a/4 protein and CD63 co-localized in the cytoplasm of co-transfected cells. Co-localization of nsP1a/4 and CD63 was also observed in HAstV-1-infected cells. Overexpression of CD63 promoted replication of HAstV-1, whereas knockdown of CD63 reduced production of HAstV-1 viral progeny. These results suggest that CD63 plays a critical role in HAstV-1 replication, and provide an avenue to further understanding the interactions between host and virus proteins during replication and pathogenesis of HAstV.

In vitro effect of Porphyromonas gingivalis combined with influenza A virus on respiratory epithelial cells.

OBJECTIVE: Respiratory epithelial cells are the first natural barrier against bacteria and viruses; hence, the interactions among epithelial cells, bacteria, and viruses are associated with disease occurrence and development. The effect of co-infection by P. gingivalis and influenza A virus (IAV) on respiratory epithelial cells remains unknown. The aim of this study was to analyze in vitro cell viability and apoptosis rates in respiratory epithelial A549 cells infected with P. gingivalis or IAV alone, or a combination of both pathogens. DESIGN: A549 cells were first divided into a control group, a P. gingivalis group, an IAV group, and a P. gingivalis + IAV group, to examine cell viability and apoptosis rates, the levels of microtubule associated protein 1 light chain 3 B (LC3-II), microtubule associated protein 1 light chain 3A (LC3-I), and sequestosome 1 (P62), and the formation of autophagosomes. The autophagy inhibitor, 3-methyladenine (3MA), was used to assess autophagy and apoptosis in A549 cells infected with P. gingivalis or IAV. RESULTS: An MTT assay revealed that cell viability was significantly lower in the IAV group than in the P. gingivalis + IAV group (P < 0.05). Flow cytometry indicated that the apoptosis rate was significantly higher in the IAV group than in the P. gingivalis + IAV group (P < 0.05). The fluorescence levels of GFP-LC3 increased significantly, the LC3-II/LC3-I ratio was significantly higher, and the P62 protein levels were statistically lower in the P. gingivalis + IAV group compared with the IAV group (all P < 0.05). Western blotting revealed that the LC3- II/LC3-I ratio was significantly lower, and caspase-3 levels were significantly higher in the 3MA + P. gingivalis + IAV group compared to the P. gingivalis + IAV group (all P < 0.05). CONCLUSION: In vitro studies showed that infection by P. gingivalis combined with IAV temporarily inhibited apoptosis in respiratory epithelial cells, and this may be related to the initiation of autophagy.

Effect of Period 2 on the proliferation, apoptosis and migration of osteosarcoma cells, and the corresponding mechanisms.

Period 2 (per2) is a core circadian clock gene. Dysregulation of the per2 gene has been identified in a number of types of human cancer and may be associated with a poor prognosis. To confirm the influence of per2 gene on MNNG/HOS human osteosarcoma cells, small interfering (si)RNA against per2 or plasmids containing per2 were transfected into MNNG/HOS cells, and the proliferation, apoptosis and migration were observed. The present study demonstrated that per2 knockdown significantly enhanced MNNG/HOS cell proliferation and migration and protected MNNG/HOS cells from apoptosis. Per2 overexpression inhibited MNNG/HOS cell proliferation and migration and promoted apoptosis. Furthermore, the protein expression of phosphorylated (p)-protein kinase B (Akt) and Bcl-2 were inhibited in per2-overexpressing cells, while the expression of p27, p21 and cleaved caspase-3 was promoted. In contrast, the expression of p-Akt and Bcl-2 was promoted in per2-knockdown cells, and p27, p21 and cleaved caspase-3 were decreased. This initial study may provide an alternative therapeutic strategy for the treatment of osteosarcoma.

Quercetin Stimulates Bone Marrow Mesenchymal Stem Cell Differentiation through an Estrogen Receptor-Mediated Pathway.

OBJECTIVES: The present study aimed to investigate the overall effect of quercetin on mouse bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation in vitro. MATERIALS AND METHODS: BMSCs were treated with different concentrations of quercetin for 6 days. The effects of quercetin on cell proliferation were assessed at predetermined times using Cell Counting Kit-8 (CCK-8) assay. The cells were then treated with quercetin, estrogen, or an estrogen receptor (ER) antagonist (which was also administered in the presence of quercetin or estrogen) for 7 or 21 days. The effects of quercetin on BMSC osteogenic differentiation were analyzed by an alkaline phosphatase (ALP) assay kit, Alizarin Red S staining (ARS), quantitative real-time PCR (qPCR), and western blotting. RESULTS: The CCK-8 and ALP assays and ARS staining showed that quercetin significantly enhanced BMSC proliferation, ALP activity, and extracellular matrix production and mineralization, respectively. The qPCR results indicated that quercetin promoted osterix (OSX), runt-related transcription factor 2 (RUNX2), and osteopontin (OPN) transcription in the presence of osteoinduction medium, and the western blotting results indicated that quercetin enhanced bone morphogenetic protein 2 (BMP2), Smad1, Smad4, RUNX2, OSX, and OPN expression and Smad1 phosphorylation. Treatment with the ER inhibitor ICI182780 blocked the effects of quercetin. CONCLUSIONS: Our data demonstrated that quercetin promotes BMSC proliferation and osteogenic differentiation. Quercetin enhances BMP signaling pathway activation and upregulates the expression of downstream genes, such as OSX, RUNX2, and OPN, via the ER.

Nano-beam and nano-target effects in ion radiation.

Full three dimensional (3D) simulations of ion implantation are necessary in a wide range of nanoscience and nanotechnology applications to capture the increasing effect of ion leakage out of surfaces. Using a recently developed 3D Monte Carlo simulation code IM3D, we first quantify the relative error of the 1D approach in three applications of nano-scale ion implantation: (1) nano-beam for nitrogen-vacancy (NV) center creation, (2) implantation of nanowires to fabricate p-n junctions, and (3) irradiation of nano-pillars for small-scale mechanical testing of irradiated materials. Because the 1D approach fails to consider the exchange and leakage of ions from boundaries, its relative error increases dramatically as the beam/target size shrinks. Lastly, the "Bragg peak" phenomenon, where the maximum radiation dose occurs at a finite depth away from the surface, relies on the assumption of broad beams. We discovered a topological transition of the point-defect or defect-cluster distribution isosurface when one varies the beam width, in agreement with a previous focused helium ion beam irradiation experiment. We conclude that full 3D simulations are necessary if either the beam or the target size is comparable or below the SRIM longitudinal ion range.

Laboratory nutritional parameters predict one-year mortality in elderly patients with intertrochanteric fracture.

BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate the contributing value of nutrition related blood parameters to one-year mortality following intertrochanteric fracture surgery in a Chinese population over the age of 65. METHODS AND STUDY DESIGN: Nutritional status was evaluated by using admission serum albumin and total lymphocyte count (TLC). One hundred and seventy-four intertrochanteric fracture patients were entered into this study for nutritional status assessment. Gender differences were evaluated by univariate analysis. The predictive value of the variables for one-year mortality was assessed by multiple logistic regression analysis. RESULTS: The mean albumin was 31.0 g/L with 73% of patients less than 35 g/L and the mean TLC was 1.19×10(9) cells/L with 81% less than 1.50×10(9) cells/L. There were no significant differences in albumin (p=0.674) or TLC (p=0.804) between men and women. Survival information was obtained in 149 patients who received surgical treatment. The general one-year mortality was 31% with 35% in men and 29% in women, respectively. The surviving patients were younger and had higher albumin, TLC and calcium than those who died. However, multivariate analysis identified only serum albumin and TLC as independent and significant risk factors associated with one-year mortality; the optimal cut-off points were 29.5 g/L and 0.93×10(9) cells/L, respectively, based on the receiver operating characteristic (ROC) curve. CONCLUSIONS: Malnutrition is a common phenomenon in an aged Chinese population suffering from intertrochanteric fractures. A lower serum albumin level and total lymphocyte count at admission are significant risk factors to predict the one-year mortality.

Study of the Clinical Outcome between Traumatic and Degenerative (non-traumatic) Meniscal Tears after Arthroscopic Surgery: A 4-Years Follow-up Study.

INTRODUCTION: The meniscus is a biconcave fibrocartilage in the knee joint interpose between the femoral condyles and tibial plateau; the meniscus has functions in load bearing, load transmission, shock absorption joint stability, joint lubrication, and joint congruity. AIM: The aim of this study is to provide orthopeadic surgeon a base of reference in the choice of the optimal course of management for meniscal tears. MATERIALS AND METHODS: One hundred and seventeen patients met the criteria of inclusion for the present study. Patients were divided in two groups T and NT according to the presence of distinct previous traumatic events to the knees. Two subgroups were formed in each groups T and NT respectively at a mean follow up of 1 and 4 years. Postoperative clinical outcome were assessed using Lysholm scores and Rand SF-36 survey. RESULTS: One hundred and seventeen patients were included in the present study with 60(51.28%) patients in the traumatic group and 57(48.71%) in the degenerative group. 95(81.19%) patients in total were satisfied with their health status at end of follow up. The mean value of Lysholm scores at 1 year were respectively 85.25±8.78 for traumatic group and 86.38±12.14 for non-traumatic group and at 4 years were respectively 92.63±7.31 for traumatic group and 72.90±20.77 for non-traumatic group. According to Rand SF-36 health, traumatic group showed better improvements compare to non-traumatic group between 1 and 4 years after arthroscopic meniscus surgery. CONCLUSION: A total of 95(81.19%) patients in total were satisfied with their health status at follow up, however, we found that arthroscopy as a treatment for meniscal tear have a relatively better mid-term clinical outcome for traumatic meniscal tears compare to non-traumatic/degenerative meniscal tears.

IM3D: A parallel Monte Carlo code for efficient simulations of primary radiation displacements and damage in 3D geometry.

SRIM-like codes have limitations in describing general 3D geometries, for modeling radiation displacements and damage in nanostructured materials. A universal, computationally efficient and massively parallel 3D Monte Carlo code, IM3D, has been developed with excellent parallel scaling performance. IM3D is based on fast indexing of scattering integrals and the SRIM stopping power database, and allows the user a choice of Constructive Solid Geometry (CSG) or Finite Element Triangle Mesh (FETM) method for constructing 3D shapes and microstructures. For 2D films and multilayers, IM3D perfectly reproduces SRIM results, and can be ∼10(2) times faster in serial execution and > 10(4) times faster using parallel computation. For 3D problems, it provides a fast approach for analyzing the spatial distributions of primary displacements and defect generation under ion irradiation. Herein we also provide a detailed discussion of our open-source collision cascade physics engine, revealing the true meaning and limitations of the "Quick Kinchin-Pease" and "Full Cascades" options. The issues of femtosecond to picosecond timescales in defining displacement versus damage, the limitation of the displacements per atom (DPA) unit in quantifying radiation damage (such as inadequacy in quantifying degree of chemical mixing), are discussed.

Paeonia lactiflora Pall. protects against ANIT-induced cholestasis by activating Nrf2 via PI3K/Akt signaling pathway.

BACKGROUND: Paeonia lactiflora Pall. (PLP), a traditional Chinese herbal medicine, has been used for hepatic disease treatment over thousands of years. In our previous study, PLP was shown to demonstrate therapeutic effect on hepatitis with severe cholestasis. The aim of this study was to evaluate the antioxidative effect of PLP on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis by activating NF-E2-related factor 2 (Nrf2) via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. MATERIALS AND METHODS: Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the main compounds present in PLP. The mechanism of action of PLP and its therapeutic effect on cholestasis, induced by ANIT, were further investigated. Serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), and total bile acid (TBA) were measured, and histopathology of liver was also performed to determine the efficacy of treatment with PLP. Moreover, in order to illustrate the underlying signaling pathway, liver glutathione (GSH) content and mRNA or protein levels of glutamate-cysteine ligase catalytic subunit (GCLc), glutamate-cysteine ligase modulatory subunit (GCLm), Akt, heme oxygenase-1 (HO-1), NAD(P)H/quinone oxidoreductase 1 (Nqo1), and Nrf2 were further analyzed. In addition, validation of PLP putative target network was also performed in silico. RESULTS: Four major compounds including paeoniflorin, albiflorin, oxypaeoniflorin, and benzoylpaeoniflorin were identified by LC-MS analysis in water extract of PLP. Moreover, PLP could remarkably downregulate serum levels of TBIL, DBIL, AST, ALT, ALP, γ-GT, and TBA, and alleviate the histological damage of liver tissue caused by ANIT. It enhanced antioxidative system by activating PI3K/Akt/Nrf2 pathway through increasing Akt, Nrf2, HO-1, Nqo1, GCLc, and GCLm expression. The putative targets network validation also confirmed the important role of PLP in activating Akt expression. CONCLUSION: The potential mechanism of PLP in alleviating ANIT-induced cholestasis could to be related to the induction of GSH synthesis by activating Nrf2 through PI3K/Akt-dependent pathway. This indicates that PLP might be a potential therapeutic agent for cholestasis.

Causes, Features, and Outcomes of Drug-Induced Liver Injury in 69 Children from China.

BACKGROUND/AIMS: Drug-induced liver injury (DILI) is a frequent cause of pediatric liver disease; however, the data on DILI are remarkably limited. METHODS: All 69 children hospitalized with DILI between January 2009 and December 2011 were retrospectively studied. RESULTS: A total of 37.7% of the children had medical histories of respiratory infection. The clinical injury patterns were as follows hepatocellular 89.9%, cholestatic 2.9%, and mixed 7.2%. Liver biopsies from 55 children most frequently demonstrated chronic (47.3%) and acute (27.3%) hepatitis. Hypersensitivity features, namely, fever (31.9%), rash (21.7%), and eosinophilia (1.4%), were found. Twenty-four children (34.8%) developed chronic DILI. Antibiotics (26.1%) were the most common Western medicines (WMs) causing DILI, and the major implicated herbs were Ephedra sinica and Polygonum multiflorum. Compared with WM, the children whose injuries were caused by Chinese herbal medicine (CHM) showed a higher level of total bilirubin (1.4 mg/dL vs. 16.6 mg/dL, p=0.004) and a longer prothrombin time (11.8 seconds vs. 17.3 seconds, p=0.012), but they exhibited less chronic DILI (2/15 vs. 18/39, p=0.031). CONCLUSIONS: Most cases of DILI in children are caused by antibiotics or CHM used to treat respiratory infection and present with hepatocellular injury. Compared with WM, CHM is more likely to cause severe liver injury, but liver injury caused by CHM is curable.

[Clinical Analysis of Drug-induced Liver Injury Caused by Polygonum multiflorum and its Preparations].

OBJECTIVE: To analyze hepatotoxicity of Polygonum multiflorum and clinical character- istics of drug-induced liver injury (DILI) caused by Polygonum multiflorum and its preparations. METHODS: A retrospective study was performed in 158 patients treated at 302 Military Hospital between January 2009 and January 2014. All of them had used Polygonum multiflorum and its preparations before the onset of DILI, and their clinical characteristics and prognoses were analyzed. RESULTS: Of the 158 DILI patients who used Polygonum multiflorum or its preparations, 92 (58.2%) combined with Western medicine or Chinese herbal preparations without Polygonum multiflorum; 66 patients (41.8%) used Polygonum mult florum and its preparations alone. In 66 DILI patients induced by Polygonum multiflorum or its preparations alone, 51 cases (77.3%) were induced by Polygonum multiflorum compounds and 22.7% by single Po- lygonum multiflorum; 4 cases (6.1%) were caused by crude Polygonum multiflorum and 62 (93.9%) by processed Polygonum multiflorum and its preparations. Clinical injury patterns were hepatocellular 92.4% (61 cases), cholestatic 1.5% (1 case), and mixed 6.1% (4 cases). Pathological examination was per- formed by liver biopsy in 32 cases (48.15%), manifested as hepatocellular degeneration and necrosis, fibroplasia, Kupffer cells with pigment granule, and a large number of eosinophil infiltration, were ob- served. Four patients were developed into liver failure, 4 into cirrhosis, and 1 died. CONCLUSION: Polygo- num multiflorum and its preparations could induce DILI, but clinical diagnosis of Polygonum multiflorum induced hepatotoxicity should be cautious.

Reversion effects of curcumin on multidrug resistance of MNNG/HOS human osteosarcoma cells in vitro and in vivo through regulation of P-glycoprotein.

BACKGROUND: P-glycoprotein (P-gp) encoded by ATP-binding cassette sub-family B member 1 (ABCB1) gene is a kind of ATP-dependent drug transporter, which plays important roles in multidrug resistance (MDR) of human cancers, such as osteosarcoma. Curcumin is a natural phenolic coloring compound originating from the rhizomes of Curcuma longa, which is proved to possess antitumor biological activities including reversion of MDR. However, the effect and molecular mechanisms of curcumin to osteosarcoma MDR remain unclear. METHODS: We established a human osteosarcoma drug-resistant cell line MNNG/HOS/MTX by pulse exposure to methotrexate (MTX) and verified that the new cell lines were cross-resistant to other anticancer agents. Then, according to the cytotoxicity assay, we reversed MDR of MNNG/HOS/MTX by 30 µmol/L curcumin, and detected the mechanisms of curcumin reversing MDR through Real-time PCR, Western blotting assay, and Rhodamine123 (Rh123) transport test. Finally, we evaluated the effect of curcumin reversing MDR in vivo by MNNG/HOS/MTX cells xenograft-nude mice model. RESULTS: MNNG/HOS/MTX was proved to be a human osteosarcoma MDR cell line. MTT tumor chemosensitivity test indicates that 30 µmol/L curcumin attenuates the half maximal inhibitory concentration (IC50) and resistance index (RI) to MTX, diamminedichloroplatinum (DDP), adriamycin (ADM), ifosfamide (IFO), and epirubicin (EPI) in MNNG/HOS/MTX cells (P < 0.05). Real-time PCR and Western blotting assays demonstrated that curcumin down-regulated P-gp expression of MNNG/HOS/MTX cells. Rh123 transport test showed that curcumin inhibited the transport function of P-gp in vitro. In vivo studies showed that curcumin displayed the features of sensitizing antitumor drugs and inhibiting the proliferation, invasion, and metastasis of osteosarcoma MDR cells. CONCLUSION: Down-regulation of P-gp and inhibition of the function of P-gp efflux pump may contribute to MDR reversion induced by curcumin in vitro and in vivo.

Poly (I:C), an agonist of toll-like receptor-3, inhibits replication of the Chikungunya virus in BEAS-2B cells.

BACKGROUND: Double-stranded RNA (dsRNA) and its mimic, polyinosinic acid: polycytidylic acid [Poly (I:C)], are recognized by toll-like receptor 3 (TLR3) and induce interferon (IFN)-ß in many cell types. Poly (I:C) is the most potent IFN inducer. In in vivo mouse studies, intraperitoneal injection of Poly (I:C) elicited IFN-α/ß production and natural killer (NK) cells activation. The TLR3 pathway is suggested to contribute to innate immune responses against many viruses, including influenza virus, respiratory syncytial virus, herpes simplex virus 2, and murine cytomegalovirus. In Chikungunya virus (CHIKV) infection, the viruses are cleared within 7-10 days postinfection before adaptive immune responses emerge. The innate immune response is important for CHIKV clearance. RESULTS: The effects of Poly (I:C) on the replication of CHIKV in human bronchial epithelial cells, BEAS-2B, were studied. Poly (I:C) suppressed cytopathic effects (CPE) induced by CHIKV infection in BEAS-2B cells in the presence of Poly (I:C) and inhibited the replication of CHIKV in the cells. The virus titers of Poly (I:C)-treated cells were much lower compared with those of untreated cells. CHIKV infection and Poly (I:C) treatment of BEAS-2B cells induced the production of IFN-ß and increased the expression of anti-viral genes, including IFN-α, IFN-ß, MxA, and OAS. Both Poly (I:C) and CHIKV infection upregulate the expression of TLR3 in BEAS-2B cells. CONCLUSIONS: CHIKV is sensitive to innate immune response induced by Poly (I:C). The inhibition of CHIKV replication by Poly (I:C) may be through the induction of TLR3, which triggers the production of IFNs and other anti-viral genes. The innate immune response is important to clear CHIKV in infected cells.