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Marginal zone lymphoma (MZL) is an uncommon subtype of non-Hodgkin lymphoma (NHL). Combination of rituximab and cladribine (R-2CdA) is a potential option for indolent NHL (iNHL) and mantle cell lymphoma (MCL) patients. The goal of this multicenter retrospective study was to assess the efficacy and safety of R-2CdA in MZL to support consensus-reaching in first-line therapy in advanced-stage patients. We searched electronic medical records databases of eight centers in China. Between November 2014 and December 2019, 183 symptomatic advanced MZL patients (42 treated with R-2CdA and 141 with rituximab plus cyclophosphamide, adriamycin, vincristine, and prednisone [R-CHOP]) were identified. After propensity score matching (PSM) (1:1) to adjust for clinical characteristics, 39 patients from each treatment arm were selected. The overall response rate (ORR) (84.6% vs. 94.9%, P = 0.263) and complete response rate (59.0% vs. 66.7%, P = 0.487) were comparable between two protocols. Neither progression-free survival (PFS), including the 5-year PFS (67.7% vs. 56.1%, P = 0.352), nor overall survival was improved by R-2CdA versus R-CHOP. However, R-2CdA was more tolerable than R-CHOP in MZL patients regarding grade 3/4 hematological adverse events (odds ratio [OR] 0.565, 95% confidence interval [CI] neutropenic fever (OR 0.795, 95% CI 0.678-0.932), and infections (OR 0.800, 95% CI 0.640-1.000). Overall, our study demonstrated that R-2CdA is potentially as effective as but safer than R-CHOP in advanced MZL.

Summary Background Seborrhoeic dermatitis (SD) is a common chronic inflammatory dermatosis. Current theories on the pathogenesis of SD highlight the role of microbes on the skin surface. Ketoconazole is commonly used for the treatment of SD; however, there are limited data focusing on the effects of ketoconazole in shaping the skin microbiome in patients with SD. Aim In this prospective cohort study, we used a high-throughput DNA sequencing method to characterize the cutaneous microbial communities of patients with SD before and after topical ketoconazole treatment. Methods In total, 30 patients with facial SD and 15 age- and sex-matched healthy controls (HCs) were enrolled in this study. Skin swabs were collected from SD lesional sites of the cheek at baseline, after ketoconazole treatment and 2 weeks post-treatment. DNA was extracted from skin samples. The bacterial 16S V3V4 rRNA and fungal internal transcribed spacer 1–5F regions were sequenced, and the microbial community compositions were analysed. Results Significantly lower bacterial and fungal diversities were detected at the lesional sites of facial SD compared with HCs. A decreased relative abundance of Cutibacterium and increased abundances of Malassezia and Staphylococcus were found in facial SD. Disease diversity was positively correlated with the relative abundances of Malassezia, Staphylococcus and Corynebacterium, while transepidermal water loss was negatively associated with the relative abundance of Cutibacterium. After ketoconazole treatment, fungal Shannon diversity and the relative abundances of Candida and Aspergillus were significantly increased at the lesional sites, and the relative abundance of Malassezia showed a decreasing trend. These changing trends were maintained until 2 weeks post-treatment. Conclusion Facial SD showed lower fungal diversity accompanied by increased relative abundances of Malassezia and Staphylococcus and decreased relative abundance of Cutibacterium. Ketoconazole treatment reduced Malassezia and increased fungal diversity to restore skin microbial communities.

To explore the associations between serum phenylacetylglutamine (PAGln) and chronic heart failure (HF).Totally 956 subjects were enrolled consecutively from the Department of Cardiovascular Medicine, Ruijin Hospital. Baseline data were obtained from all participants, and 471 stable chronic HF subjects were followed up. Serum PAGln was analysed by liquid chromatography-tandem mass spectrometry. The association between PAGln and basic renal indicators was assessed by simple correlation analysis. Logistic regression analysis was conducted to measure the association between PAGln and HF risk. Event-free survival was determined by Kaplan-Meier curves, and differences in survival were assessed using log-rank tests. Cox proportional hazards analysis was used to assess the prognostic value of PAGln in HF. Serum PAGln levels were increased in patients with chronic HF (3.322 ± 8.220 μM vs. 1.249 ± 1.168 μM, P 0.001) and were associated with HF after full adjustment [odds ratio (OR), 1.507; 95% confidence interval (CI): 1.213-1.873; P 0.001]. PAGln levels were correlated with the levels of basic renal indicators. High PAGln levels indicated a high risk of renal dysfunction in HF (OR: 1.853; 95% CI: 1.344-2.556; P 0.001), and elevated PAGln levels were associated with a high risk of cardiovascular death in patients with chronic HF (HR: 2.049; 95% CI: 1.042-4.029; P = 0.038).Elevated PAGln levels are an independent risk factor for HF and are associated with a higher risk of cardiovascular death. High PAGln levels could indicate renal dysfunction in HF patients. PAGln can be a valuable indicator of HF.

This study aimed to explore bone remodeling after condylar fracture fragments have been removed from patients with intracapsular condylar fractures. it also evaluated whether condyle fracture removal can be used alternatively when the authors treat patients with comminuted or small pieces of fracture or in extremely difficult operations.Records of patients who sustained intracapsular condylar fractures and treated by removal of fragments for the period of February 2013 to September 2019 were retrieved. Data about age, gender, date of injury, dates of admission and discharge, mechanism of trauma, location and pattern of fracture, other mandibular fracture, treatment methods and time of review were recorded and analyzed. Image dates of pre- and post-treatment (including the time of review) were also recorded.The data of a total of 103 patients ranging from 5 to 84 years old were retrieved during this study. A total of 135 sides of condylar fragments were removed. Almost all of the patients with comminuted condyle head fracture or type A fracture presented apparent shortening of the ramus height, and none of them showed osteogenesis (or new bone formation) during their follow-up. Present study only observed osteogenesis in few patients who sustained type B/C intracapsular condylar fractures during their follow-up. The younger the patient was, the longer the follow-up time was, and the higher the possibility of new bone formation was. No correlation was found between the amount of osteogenesis and follow-up time, the amount of osteogenesis was generally small, and no patient could form a new condyle head similar to the normal (or original) condyle head. Condylar hypertrophy only occurred in children. Four patients developed temporomandibular joint ankylosis.Removal of fracture fragments is an alternative treatment option for patients who sustained comminuted or small pieces of fracture or in extremely difficult operations.

Early-stage natural killer/T-cell lymphoma (NK/TCL) patients usually receive a combination of chemotherapy and radiotherapy, but the optimal treatment approach has not yet been established. This study aimed to investigate the efficacy and safety profile of a novel chemotherapy regimen and sandwiched radiotherapy in early-stage NK/TCL. Patients with newly diagnosed stage IE/IIE disease were eligible. Patients were initially treated with two courses of the GELAD regimen (gemcitabine 1·0 g/m2 day 1, etoposide 60 mg/m2 days 1-3, pegaspargase 2000 units/m2 day 4, and dexamethasone 40 mg days 1-4), followed by intensity-modulated radiotherapy (IMRT; 50-56 Gy in 25-28 fractions) and two additional courses of GELAD chemotherapy. A total of 52 patients were enrolled. The overall response rate and complete response rate per Lugano 2014 criteria were 94·2% and 92·3% respectively. With a median follow-up of 32 months, the estimated four-year overall survival rate and progression-free survival rate were 94·2% [95% confidence interval (CI), 83·2% to 93·1%] and 90·4% (95% CI, 78·4% to 95·9%) respectively. The most common adverse events were related to pegaspargase. Haematological toxicities were mild, with grade 3/4 neutropenia in 15·4% of patients. Our study provides a new approach with high activity and improved safety for the treatment of early-stage NK/TCL patients. This study was registered at www.clinicaltrials.gov as NCT02733458.

This study (ORIENT-4) aimed to assess the efficacy and safety of sintilimab, a humanized anti-PD-1 antibody, in patients with relapsed/refractory extranodal NK/T cell lymphoma (r/r ENKTL). ORIENT-4 is a multicenter, single-arm, phase 2 clinical trial (NCT03228836). Patients with r/r ENKTL who failed to at least one asparaginase-based regimen were enrolled to receive sintilimab 200 mg intravenously every 3 weeks for up to 24 months. The primary endpoint was the objective response rate (ORR) based on Lugano 2014 criteria. Twenty-eight patients with r/r ENKTL were enrolled from August 31, 2017 to February 7, 2018. Twenty-one patients (75.0%, 95% CI: 55.1–89.3%) achieved an objective response. With a median follow-up of 30.4 months, the median overall survival (OS) was not reached. The 24-month OS rate was 78.6% (95% CI, 58.4–89.8%). Most treatment-related adverse events (TRAEs) were grade 1–2 (71.4%), and the most common TRAE was decreased lymphocyte count (42.9%). Serious adverse events (SAEs) occurred in 7 (25.0%) patients, and no patient died of adverse events. Sintilimab is effective and well tolerated in patients with r/r ENKTL and could be a novel therapeutic approach for the control of ENKTL in patients.

This study aimed to explore and impart understanding of bone remodelling in children with intracapsular fractures treated conservatively. Records of children (less than 12 years), who sustained intracapsular fractures and treated conservatively, were retrieved consecutively for the period of March 2011 to February 2016. Data about age, gender, date of injury, dates of admission and discharge, mechanism of trauma, location and pattern of fracture, other mandibular fractures, treatment methods and time of review were recorded and analysed. Image dates of pre- and post-treatments, including date of review, were also recorded. A total of 22 patients complete their follow-up and show bone remodelling process. During their follow-up, all the displaced condylar fragments fused with the ramus stump at the displaced position. Regardless of the type of conservative procedure, both treatments cannot promote the spontaneous fracture reduction in patients with intracapsular condylar fractures. During follow-up, the absorption of the lateral process of the condyle after the closed treatment becomes close to the ‘horizontal absorption’, until the height (or articular surface) of the lateral condylar process dropped and aligned to the articular surface of the medial process. In children with intracapsular condylar fractures, the fracture fragment of the condyle determines the ramus height of the mandible. Closed treatment cannot restore the fracture fragment. If the height of the fracture fragments dropped remarkably, then open reduction and rigid internal fixation become more suitable.

Seborrheic dermatitis (SD) and dandruff (DF) are common chronic inflammatory skin diseases characterized by recurrent greasy scales, sometimes with erythema and itchiness. Although the exact pathophysiology of the disease is still unclear, current theories highlight the role of microbes on the skin surface in the pathogenesis of SD. Here, we conducted a systematic review to investigate the skin microbiome alterations in patients with SD/DF. We searched Medline/PubMed, Embase and Web of Science for research studies published in English between 1 January 2000 and 31 December 2020. A total of 12 studies with 706 SD/DF samples and 379 healthy samples were included in this study. The scalp and face were predominated by the fungi of Ascomycota and Basidiomycota and the bacteria of Actinobacteria and Firmicutes. In general, the included studies demonstrated an increased Malassezia restricta/Malassezia globosa ratio and a reduction in the Cutibaterium/Staphylococcus ratio in the setting of SD/DF. Staphylococcus was associated with epidermal barrier damage, including elevated levels of trans-epidermal water loss and pH, while Cutibacterium had a positive correlation with water content. Malassezia was also found to be related to an increased itching score and disease severity. Further studies focusing on the interactions between various microbes and the host and microbes can help us to better understand the pathogenesis of SD/DF.

Eleven new seco-iridoids, valeridoids G-Q (1-6 and 8-12), along with four known products, 9-epi-valtral C (7), desacylbaldrinal (13), 11-methoxyviburtinal (14) and baldrinal (15), were obtained from Valeriana jatamansi. Among them, the new compounds were identified by their NMR, HR-ESI-MS spectroscopic data and ECD calculation. Moreover, valeridoid N and O were a pair of C

Tinea capitis is an infection of the scalp and hair shaft caused by dermatophytes that predominantly occurs in children. Skin fungal infections have been found to be associated with alterations in the overall bacterial and fungal communities. However, the scalp microbiome in tinea capitis have not been fully investigated.To investigate and compare the scalp bacterial and fungal microbiomes between children with tinea capitis and healthy children and between children and adults.Skin samples were collected from the scalp. Bacterial and fungal community compositions were analysed by amplification sequencing of the V3-V4 of 16S rDNA and ITS1-5F, respectively.The predominant fungi detected using amplicon sequencing were consistent with the culture- or real-time PCR-positive pathogens in most samples. Children with tinea capitis had lower fungal and higher bacterial Shannon diversity than healthy children. A higher relative abundance of pathogenic fungi and significant alterations in the bacterial community in the lesional sites of tinea capitis than healthy scalps. Compared with adults, healthy children were characterised by higher Shannon diversities with significantly lower relative abundances of Malassezia and Cutibacterium and higher relative abundances of Candida and Streptococcus.We demonstrated that tinea capitis was characterised by significant alterations in both fungal and bacterial communities and amplicon sequencing could be a complementary method for pathogen identification.

OBJECTIVE This study aimed to assess whether ramus height is restored in children with extracapsular condylar fractures treated by conservative or surgery procedures. METHODS The sample consisted of 35 children (collected consecutively) less than 12 years old who presented with extracapsular condylar fractures and treated within an 8-year period (June 2011 to April 2019). Data on the age, gender, date of injury, mechanism of trauma, location and pattern of mandibular condylar fracture, associated injuries and treatment methods were recorded and analyzed. Ramus height restoration is the main evaluation indicator during the follow-up period. RESULTS Within the 8-year record retrieval, the 35 children sustained 41 extracapsular condylar fractures. For the sample size, 10 (24.4%) and 31 (75.6%) had condylar neck and base fractures, respectively. Deviation and green-stick fracture were the predominant types in condylar neck and base fractures, accounting for more than 3 quarters (31, 75.6%). The majority (33, 80.5%) of patients were treated with nonsurgical treatment, and 8 (19.5%) were treated by open reduction and internal fixation (ORIF). During the follow-up period (1-1419 days, average time of 110.6 days), only 1 patient (with bilateral extracapsular condylar fractures) had their ramus height restored (follow-up period, 256 days). Most members of the ORIF group (5 of 8, 62.5%) postoperatively showed bended ramus (deviated angularly/fragment angulation). CONCLUSION Conservative treatment could hardly restore the ramus height of children with extracapsular condylar fractures. Anatomically or totally restoring the ramus height is difficult even with the surgical treatment of ORIF; however, surgical treatment of ORIF can substantially restore the ramus height for dislocated fractures or seriously displaced fractures.

Objective This study aims to reveal the reconstruction process in pediatric patients with extracapsular condylar fractures after conservative treatment. We clarify that the "upright" position (or "recontouring" or favorable prognosis) of condyles is not a result of the anatomical reduction of the deviated condylar processes but originates from the remodeling of the skeleton. We also explore the related mechanism. Methods The sample consisted of 27 pediatric patients aged less than 12 years who presented with extracapsular condylar fractures and were treated conservatively within an 8-year period (June 2011-April 2019). Data on the age, gender, date of injury, mechanism of trauma, location and pattern of mandibular condylar fracture and associated injuries and treatment methods of the patients were obtained. The process of bone remodeling in condyles was also recorded and analyzed. Results The 27 children in this study sustained 33 extracapsular condylar fractures over the 8-year period of record retrieval. Amongst these fractures, 8 (24.2%) and 25 (75.8%) were condylar neck and condylar base fractures, respectively. Deviation and green-stick fractures were the predominant types and accounted for over 3 quarters of the condylar neck and base fractures (28, 84.8%), followed by dislocation fracture (3, 9.1%), displacement fracture (1, 3.0%), and non-displaced fracture (1, 3.0%). The period of follow-up ranged from 2 days to 257 days (average, 58.78 days). Only 1 patient with bilateral extracapsular condylar fractures showed vertically reconstructed condyles, which indicates an upright position of the condylar processes. One patient showed less angulation after treatment than before treatment, 1 patient revealed greater angulation after treatment than before treatment and all other patients (20 patients) showed the same angulation pre- and post-treatment. Both patients with only extracapsular condylar fractures showed no obvious deviations in dentition and facial asymmetry after their injury and treatment. The shortest and longest times observed for bone remodeling were 33 and 256 days, respectively. Children whose condylar head remained completely or at least partly inside the glenoid fossa showed satisfactory remodeling results during follow-up. Computed tomography scan during follow-up generally showed bone regeneration in the lateral condyle articular surface and the medial portion of the ascending ramus and bone resorption in the displaced direction (ie, the medial condyle head became sharp). Condylar heads displaced completely outside of the glenoid fossa showed serious shortening of the ascending ramus, and no obvious bone remodeling was observed. Only 1 patient with bilateral extracapsular condylar fractures showed a normal contour (ie, a vertically reconstructed condyle reflecting the upright position of the condylar processes) after 8 months. Conclusion Stress stimulation originating from the glenoid fossa and ascending ramus of the mandible is a prerequisite for good condylar reconstruction. Conservative treatment could be carried out if the condylar head remains completely or at least partly inside the glenoid fossa. When the condylar head is dislocated completely outside the glenoid fossa, the glenoid-condylar relationship ceases to exist, joint function is lost and the height of the ascending ramus is significantly reduced. In this case, open reduction may be suitable.

The influenza pandemic continues to threaten public health due to its high morbidity and mortality rates, despite some successes in antiviral research. Natural drugs are important alternative therapies in the treatment of and recovery from influenza and have been the subjects of intense investigation during the last few decades. Many reports have shown that the development of novel bioactive chemicals extracted from natural drugs has significant advantages. Oseltamivir is a successful case of an anti-influenza drug synthesized using two natural products, quinic acid, and shikimic acid, as starting materials. In China, traditional Chinese medicine (TCM) plays an important role in the treatment of influenza. TCM herbal extracts and prescriptions or their isolated bioactive constituents have shown significant therapeutic and preventive effects against influenza. For example, the roots of Isatis indigotica (Banlangen) fight viral infection by targeting both the virus and the host and have significantly different effects than those of synthetic chemicals. Lianhuaqingwen capsule exerts its anti-influenza activity by regulating the immune response to interfere with both viral and host reactions and might well be an alternative therapeutic option to treat influenza virus infection. This paper reviews the chemical ingredients, crude extracts, and TCM prescriptions with anti-influenza activity reported during the period of 2010-September 2019. We hope that this comprehensive review will not only fuel research on anti-influenza active natural products and TCM research but also provide a promising alternative candidate for further anti-influenza drug development.

Hepatocellular carcinoma (HCC) poses a serious threat to people’s health worldwide. Artesunate (ART), one of the classical antimalarial drugs, has recently been shown to exert significant cytotoxicity in various cancers, but its bioavailability is low. Cyclometalated iridium(iii) complexes have emerged as a promising class of anticancer therapeutic agents. Herein, through conjugation of two of them, three novel Ir(iii)–ART conjugates, [Ir(C–N)2(bpy-ART)](PF6) (bpy = 2,2′-bipyridine, C–N = 2-phenylpyridine (ppy, Ir-ART-1), 2-(2-thienyl)pyridine (thpy, Ir-ART-2), and 2-(2,4-difluorophenyl)pyridine (dfppy, Ir-ART-3)) have been synthesized, and their potential as anti-HCC agents was evaluated. We demonstrate that Ir-ART-1–3 display higher cytotoxicity against HCC cell lines than normal liver cells, and they can especially locate to mitochondria of HepG2 cells and induce a series of mitochondria-mediated apoptosis events. Moreover, Ir-ART-1–3 can regulate the cell cycle and inhibit metastasis of HepG2 cells. Finally, in vivo antitumor evaluation also demonstrates the inhibitory activity of Ir-ART-1 on tumor growth. Taken together, these Ir(iii)–ART conjugates have the potential to become drug candidates for future anti-HCC treatments.

Ubiquitin-specific protease 3 (USP3), a kind of cysteine protease, is a crucial family member of deubiquitinating enzymes. USP3 is aberrantly expressed in several tumors, which may contribute to cancer progression. However, the role of USP3 in gallbladder cancer (GBC) is still unknown. In the current study, we detected the expression of USP3 in GBC tissues, measured its contribution to the cell proliferation in GBC progression, and further studied the underlying mechanism of USP3 in GBC through pyruvate kinase L/R (PKLR; a kind of glycolytic enzyme). We found that the expression of USP3 in GBC tissues were higher than that of adjacent tissues, and the protein levels of USP3 and PKLR were positively correlated. Additionally, overexpressed USP3 significantly promoted cell proliferation in vitro and tumor growth in vivo, while the silencing of USP3 inhibited proliferation and tumor growth. Glycolysis in GBC cells ws promoted by the USP3 overexpression and inhibited bye USP3 downregulation. Moreover, the loss of USP3 promoted the ubiquitination and weakened the stability of PKLR. Results of the rescue assay confirmed that PKLR knockdown suppressed USP3-induced oncogenic activity in USP3 overexpressed GBC cells. These findings imply that USP3 is an essential positive regulator in GBC progression, and USP3-PKLR plays a vital role in the progression and metabolism of GBC.

In this paper, we propose an end-to-end deep learning architecture, referred as MCG-Net, integrating convolutional neural network (CNN) with transformer-based global context block for fine-grained delineation and diagnostic classification of four cardiac events from magnetocardiogram (MCG) data, namely Q-, R-, S- and T-waves. MCG-Net} takes advantage of a multi-resolution CNN backbone as well as the state-of-the-art (SOTA) transformer encoders that facilitate global temporal feature aggregation. Besides the novel network architecture, we introduce a multi-task learning scheme to achieve simultaneous delineation and classification. Specifically, the problem of MCG delineation is formulated as multi-class heatmap regression. Meanwhile, a binary diagnostic classification label as well as a duration are jointly estimated for each cardiac event using features that are temporally aligned by event heatmaps. The framework is evaluated on a clinical MCG dataset, containing data collected from 270 subjects with cardiac anomalies and 108 control subjects. We designed and conducted a two-fold cross-validation study to validate the proposed method and to compare its performance with the SOTA methods. Experimental results demonstrated that our method outperformed counterparts on both event delineation and diagnostic classification tasks, achieving respectively an average ECG-F1 of 0.987 and an average Event-F1 of 0.975 for MCG delineation, and an average accuracy of 0.870, an average sensitivity of 0.732, an average specificity of 0.914 and an average AUC of 0.903 for diagnostic classification. Comprehensive ablation experiments are additionally performed to investigate effectiveness of different network components.

Background Qingwenjiere Mixture (QJM) is a traditional Chinese medicine (TCM) that has been shown to have remarkable clinical efficacy against COVID-19. However, little is known about the antiviral and anti-inflammatory activities of QJM against a wider range of HCoV strains. Purpose The study aims to investigate the antiviral and anti-inflammatory activities of QJM, as well as the underlying mechanisms against human coronavirus (HCoV) infections. Methods The chemical compositions from QJM were analyzed by LC-MS. The inhibitory effect of QJM on infections of HCoV-OC43, HCoV-229E, HCoV-NL63, and SARS-CoV-2 was evaluated in HRT-18 cells, Huh7 cells, LLC-MK2 cells, and Vero-E6 cells, respectively, by using cytopathic effect (CPE) inhibition assay or RT-qPCR detection of viral n, s, or RdRp/Hel genes. The expression of pro-inflammatory cytokines induced by HCoV-OC43, HCoV-229E, and SARS-CoV-2, as well as the host ace2 gene was also determined by RT-qPCR assay. Furthermore, the expression of key molecules in the NF-κB/MAPKs signaling pathways was determined by western blot. Results In alcohol-extraction groups of QJM and reference decoction pieces, 53 similar ion peaks were identified, the majority of which were phenylpropanoids, iridoids, and flavonoids. In addition, QJM reduced CPE caused by HCoVs and the expression of viral n genes or N protein. Pretreatment with QJM also exerted inhibitory effect on viral n gene expression. QJM also inhibited the expression of RdRp/Hel and s genes of SARS-CoV-2, as well as the host ace2 gene. Besides, QJM markedly reduced virus-induced mRNA expression of a panel of pro-inflammatory cytokines, such as IL-6, CXCL-8/IL-8, CXCL-10/IP-10, CCL-5/RANTES, TNF-α, IFN-α, CCL-2/MCP-1, CXCL-9/MIG, and IL1-α. We further showed that QJM inhibited the phosphorylation of NF-κB p65, and JNK, ERK 1/2, and p38 MAPKs in HCoV-OC43-infected HRT-18 cells. Conclusions QJM has broad antiviral and anti-inflammatory activity against both common and newly emerged HCoVs possibly by inhibiting the activation of key components in NF-κB/MAPKs signaling pathway. QJM also has a prevention effect against HCoV infections and inhibits the host receptor required for virus entry. These results indicate that QJM may have the therapeutic potential in the treatment of diseases caused by a broad range of HCoVs., Graphical abstract Image, graphical abstract

Scoliosis is a common medical condition, which occurs most often during the growth spurt just before puberty. Untreated Scoliosis may cause long-term sequelae. Therefore, accurate automated quantitative estimation of spinal curvature is an important task for the clinical evaluation and treatment planning of Scoliosis. A couple of attempts have been made for automated Cobb angle estimation on single-view x-rays. It is very challenging to achieve a highly accurate automated estimation of Cobb angles because it is difficult to utilize x-rays efficiently. With the idea of developing methods for accurate automated spinal curvature estimation, AASCE2019 challenge provides spinal anterior-posterior x-ray images with manual labels for training and testing the participating methods. We review eight top-ranked methods from 12 teams. Experimental results show that overall the best performing method achieved a symmetric mean absolute percentage (SMAPE) of 21.71%. Limitations and possible future directions are also described in the paper. We hope the dataset in AASCE2019 and this paper could provide insights into quantitative measurement of the spine.

Background Achalasia is a rare primary esophageal motility disorder disease. It is reported that the long-term effect of fully coated anti-reflux metal stent (FCARMS) implantation is satisfactory. Operated by a skilled and experienced endoscopist, the effect of per-oral endoscopic myotomy (POEM) treatment is equivalent to that of surgical myotomy. So far, there is still few evidence to prove FCARMS implantation or POEM which is better for achalasia. The choice of treatment for achalasia is still controversial. The aim of this study is to find a more suitable therapy for achalasia by comparing the efficacy of FCARMS implantation and POEM. Methods A propensity score (PS) matching (1:2) was used in this retrospective cohort study. Data collected from consecutive patients of Achalasia, receiving FCARMS implantation or POEM therapy at the department of gastroenterology, the Seventh Medical Center of the Chinese People’s Liberation Army General Hospital from May 2007 to May 2018. According to their previous treatment, they are divided into two groups, FCARMS group and POEM group. Clinical efficacy and complications were compared between the two groups. Results A total of 166 cases were collected, including 113 cases of FCARMS and 53 cases of POEM. By PS matching, 150 patients were enrolled (100 cases of FCARMS and 50 cases of POEM). By comparison, the FCARMS group has shorter operation time, shorter fasting time and lower hospitalization costs than the POEM group (p p = 0.00 p = 0.39), and the 2-year remission rates were 61% and 90%, respectively (p = 0.00). Conclusions Stent placement is a cost-effective and safe treatment option for achalasia. The short-term effect (less than 6 months) of FCARMS is similar to that of POEM, the long-term effect (more than 2 years), POEM is better than FCARMS. HRMIIis most suitable for POEM treatment. It indicate that Patients can choose treatment methods according to their own conditions.

Inflammatory factors have specific value in acute myocardial infarction (AMI). Our previous studies have identified the prognostic value of interleukin (IL)-34 during chronic heart failure. However, the potential impact of IL-34 on AMI remains unknown.Serum IL-34 was measured in 287 AMI patients, and they were followed up for the composite endpoint, including cardiovascular death, heart failure hospitalization, recurrent nonfatal myocardial infarction (MI), and nonfatal stroke.IL-34 levels were significantly associated with the presence of heart failure at baseline and its aggravation after a year. During the five-year follow-up, there was a significant increase in the risk of the composite endpoint (hazard ratio [HR] 1.38 [95% confidence intervals (CI) 1.12-1.70], P < 0.01) and cardiovascular death (HR 1.48 [95%CI 1.03-2.27], P = 0.03) after full adjustment as IL-34 levels increased.Higher IL-34 levels in the acute phase were associated with an increased risk of heart failure after MI and poor prognosis.

Background: Condylomata acuminata (CA) are a common sexually transmitted disease. The recurrence rate of condyloma acuminatum using traditional treatments is higher than that of applying ph...

Metal-organic frameworks (MOFs) have drawn great interest in recent decades due to their fascinating structures, unusual physical properties, versatile modification strategies, and biological compatibilities. In this review, we describe recent progress in the application of MOFs to matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Owing to their high porosities, specific affinities, and photon absorption capacities, MOFs can be used as solid adsorbents to selectively capture peptides (including endogenous peptides, phosphopeptides, and glycopeptides) and as matrices in MALDI MS. Current developments in and future prospects for this field of research are also discussed.

Extranodal natural killer/T‐cell lymphoma (ENKL), nasal‐type is a rare but highly aggressive disease with poor prognosis. Optimal treatment strategies for newly diagnosed localized ENKL have not been fully defined. Here we retrospectively analyzed 72 patients with newly diagnosed stage IE/IIE ENKL treated with gemcitabine, dexamethasone, and cisplatin (GDP) regimen chemotherapy with sandwiched radiotherapy in our department between May 2012 and September 2014. After 2 cycles of GDP induction chemotherapy, the complete response rate (CRR) and overall response rate (ORR) were 30.6% (22/72) and 91.7% (66/72). After whole treatment completion, the CRR and ORR were 81.9% (59/72) and 91.7% (66/72), respectively. With a median follow‐up of 57.8 months (Interquartile Range 54.0‐64.5 months), the 5‐year progression‐free survival rate was 70.9% (95% CI, 60.1% to 81.7%), and the 5‐year overall survival rate was 72.0% (95% CI, 61.6% to 82.4%), respectively. Patients with CRR after treatment had better prognosis than their counterparts. The major adverse events were myelosuppression, liver dysfunction, gemcitabine‐related skin rash, and digestive tract toxicities. Grade 3 to 4 neutropenia and thrombocytopenia were 18.0% (13/72) and 15.3% (11/72), respectively. No treatment related deaths were observed. It is concluded that the GDP regimen with sandwiched radiotherapy was an effective and well‐tolerated treatment for newly diagnosed stage IE/IIE ENKL, nasal‐type.

This study aimed to evaluate and compare the demographic characteristics of mandibular condylar fractures between children and adolescents.The sample was composed of all children (less than 12 years) and adolescents (between 13 and 18 years old) who presented with mandibular condylar fractures within a 5-year period (January 2011 to April 2016). The age, gender, time of injury, mechanism of trauma, location and pattern of fracture, associated injuries and treatment methods were recorded and analysed. Data analysis included chi-square test and Fisher exact test. Differences at p less than 0.05 were considered significant.A total of 111 children and 39 adolescent patients with condylar fractures were registered and compared. More children than adolescents were involved in falls from a height (p = 0.007), but nearly no relationship was observed between the trauma aetiology and type of condylar fracture in the two patient groups. Condylar head fractures occurred most frequently in the children and adolescents, especially in the children (p 0.05). Condylar neck fractures were more frequently observed in the adolescent patients (p 0.001) than in the children. Green-stick fractures occurred only in the child patients (p = 0.005). The patients who fractured other sites of the mandible tended to show a decreased frequency of dislocation (condylar head was out of the glenoid fossa) (p = 0.024). Symphysis/para-symphysis fractures were highly common in the children who sustained unilateral condylar fractures, compared to adolescents (p 0.05). The patients with bilateral condylar fractures were more frequently associated with other mandibular fractures (children, p = 0.001; adolescents, p = 0.011), especially the fracture of the mandibular body or symphysis. The children who sustained extracapsular fractures were more prone to fractures of other mandibular sites (p = 0.009), especially fracture of the symphysis/para-symphysis (p = 0.014). Intracapsular fractures in children were treated non-surgically more frequently than surgically (p 0.001). The extracapsular fractures (mild and serious fractures) in children were also treated non-surgically more frequently (p 0.05).The trauma mechanisms, incidence, pattern and treatment of condylar fractures in children substantially differ from those in adolescents. This study was conducted to enable the understanding of the differences in condylar fractures between children and adolescents. Accordingly, preventive measures and treatment plans in children or adolescents should be applied differently.

Multi-drug resistance (MDR) is one of the dominant reasons for the failure of cancer chemotherapy. P-glycoprotein (P-gp) over-expression in the plasma membrane of drug-resistant tumor cells promotes the efflux of chemotherapeutic agents and plays a significant role in MDR. Several investigations have suggested that dihydro-β-agarofuran sesquiterpenes are the potential modulators of MDR. However, their cellular mechanism in regulating P-gp has not been fully explored. Seven dihydro-β-agarofuran sesquiterpenes (1–7) from Tripterygium hypoglaucum was evaluated for the chemoreversal activity of HepG2/Adr cells. 1, 2, 4, 5, and 7 were active with reversal fold ranging from 47.68 to 456.90. The image-based high-screening indicated that all of the active compounds were capable of decreasing the efflux of doxorubicin (Dox). The most potent 4 did not affect the expression or subcellular distribution of P-gp. P-gp ATPase activity was stimulated by 4 in a dose-depend manner, suggesting that 4 may be the substrate of P-gp. The docking data implied that 4 took PHE 979, PHE 332, and GLN 986 to bind with P-gp. Taken together, the results demonstrated that dihydro-β-agarofuran sesquiterpenes from T. Hypoglaucum were the substrate of P-gp and potential modulators of MDR.

Six artesunate (ART) conjugated ruthenium(II) complexes (Ru(II)-ART conjugates) with the formula [Ru(N^N)2bpy(4-CH3-4′-CH2OART)](PF6)2 (Ru-ART-1-3) and [Ru(N^N)2bpy(4-CH2OART-4′-CH2OART)](PF6)2 (Ru-ART-4–6) (N^N = 2,2′-bipyridine (bpy, in Ru-ART-1 and Ru-ART-4), 1,10-phenanthroline (phen, in Ru-ART-2 and Ru-ART-5) and 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru-ART-3 and Ru-ART-6)), were synthesized and characterized. Among them, Ru-ART-1-3 and Ru-ART-4-6 carry one and two ART moieties, respectively. Ru-ART-3 and Ru-ART-6 exhibit better cytotoxicity among six Ru(II)-ART conjugates. These two complexes can be effectively taken up by human cervical carcinoma (HeLa) cells. In addition, they selectively kill cancer cell lines while mildly affect normal cells. Mechanism studies have shown that HeLa cells treated with Ru-ART-3 and Ru-ART-6 show typical apoptotic characteristics (morphology changes, mitochondrial dysfunction, caspase cascade, etc.). On the other hand, the up regulation of Beclin-1 and conversion of LC3-I to LC3-II note the appearance of autophagy. As a result, Ru-ART-3 and Ru-ART-6 induce autophagy-dependent cell apoptosis via mitochondrial dysfunction and reactive oxygen species (ROS) accumulation.

Vernoramyosides A-F (1-6), six new Δ7,9(11) stigmastane-type steroid saponins, along with four known analogues (7-10) were isolated from the leaves of Vernonia amygdalina Delile (Compositae). Their structures were determined by the combination of NMR, ECD and HR-ESI-MS data. These compounds all possessed highly oxidized side chain and a γ-lactam or α,β-unsaturated five-membered lactone ring. All isolates were screened for their activities in reversing resistance in MCF/DOX cells.

Forty-three quinolizidine alkaloids (1–43), including twelve new matrine-type ones, sophalodes A–L (1–7, 17, 19 and 28–30), were isolated from the seeds of Sophora alopecuroides. Structurally, compounds 1–4 were the first examples of C-11 oxidized matrine-type alkaloids from Sophora plants. The structures and absolute configurations of new compounds were elucidated by extensive spectroscopic techniques, X-ray diffraction analysis, and quantum chemical calculation. In addition, the NMR data and absolute configuration of compound 18 was reported for the first time. All the isolates were evaluated for their inhibition on nitric oxide production induced by lipopolysaccharide in RAW 264.7 macrophages, among them, compounds 29, 38 and 42 exhibited the most significant activity with IC50 values of 29.19, 25.86 and 33.30 μM, respectively. Further research about new compound 29 showed that it also suppressed the protein levels of iNOS and COX-2, which revealed its anti-inflammatory potential. Moreover, additional research showed that compound 16 exhibited marginal cytotoxicity against HeLa cell lines, with an IC50 value of 24.27 μM.

The present study was conducted to (a) identify the clients and therapists' perceptual directional discrepancy and temporal congruence in different aspects of working alliance (i.e., goals/tasks and bond), (b) examine the moderating effect of therapists' client-specific self-efficacy on the directional discrepancy and congruence, (c) clarify the relationship between specific working alliance aspects congruence and the next-session symptom, and (d) test the relationship between the congruence of goals/tasks or bond and the psychotherapy outcome under different levels of therapists' self-efficacy. Clients (n = 87, 80.9% female, average age = 21.78 [1.90]) and therapists (n = 43, 65% female) in a Chinese university mental health center evaluated the working alliance session by session. Clients self-reported session-level symptom severity were assessed at the beginning of every session and therapists' self-efficacy for a specific client were assessed at the end of the first session. The truth-and-bias approach was used to analyze the perceptual directional discrepancy and temporal congruence in goals/tasks and bond, and examine the moderating effect of therapists' self-efficacy. Multilevel polynomial regression and response surface analysis were used to clear the relationship between congruence/incongruence and client symptom level in the next session. (a) Clients and therapists temporally agreed on both the goals/tasks and bond dimensions of the working alliance. Averagely, therapists tended to rate goals/tasks agreement lower than clients but did not rate more or less intense bond than clients. (b) Therapists with low or medium self-efficacy for specific client underrated goals/tasks and bond more than therapists with high client-specific efficacy, and among the therapist-client dyads, the higher therapists' client-specific self-efficacy, the higher temporal congruence in bond rather than goals/tasks. (c) For both goals/tasks and bond, when clients and therapists were in agreement, client symptoms decreased as the congruent combinations of therapists' and clients' goals/tasks increased. Clients' symptom level increased more sharply as the degree of discrepancy increases for goals/tasks, not affected by the direction. (d) However, for therapists with high client-specific self-efficacy, their underestimations were more associated with the less severe next-session symptoms of their clients than their overestimations. This association was not found among clients whose therapists' self-efficacies for them were low. The findings provide a deeper insight into the congruence of the working alliance. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Seventeen quinolizidine alkaloids, including a new matrine-type one, sophcence A (

Ionizing radiation (IR) confers a survival advantage in tongue squamous cell carcinoma (TSCC), however, IR resistance limits its efficacy. Although Yin Yang 1 (YY1) has been reported to play a role in genotoxic drug resistance by accelerating DNA repair, its role in TSCC radioresistance remains unclear. In this study, we examined YY1 mRNA and protein expression in human tongue cancer samples using qRT-PCR and western blotting, respectively. DNA array data identified YY1 mRNA expression in IR sensitivity or resistance cell lines and tissues. Tongue carcinoma primary cells and CAL27 cells with YY1 stably overexpressed or knocked-down were exposed to IR and evaluated for cell proliferation and apoptosis by CCK8-assay and caspase-3 assay, respectively. We also examined DNA damage- or repair-related indicators, such as YY1, p-H2AX, nuclear PTEN, p-PTEN, and Rad51 through Western blot analysis. Additionally, we explored the mechanism of IR-induced PTEN nuclear translocation by introducing a series of PTEN phosphorylation site mutations and co-IP assay. We observed that YY1 mRNA and protein are highly expressed in TSCC tissues, which was correlated with worse overall survival. Moreover, higher expression of YY1 and Rad51 was observed in radioresistant cells and tissues, overexpression of YY1 led to IR resistance in TSCC cells, whereas YY1 knockdown sensitized TSCC cells to IR. The underlying mechanism showed that the overexpression of YY1 upregulated nuclear PTEN and Rad51 expression, which is essential for DNA repair. IR upregulated YY1, nuclear PTEN, and Rad51; thus, knockdown of YY1 completely blocked IR-induced upregulation of nuclear PTEN/Rad51. IR upregulated PTEN phosphorylation, and mutation of the phosphorylation site of Ser380 nearly completely blocked IR-induced PTEN nuclear translocation. Furthermore, the phosphatase PP2A negatively regulated pS380-PTEN, and knockdown of YY1 completely blocked IR-induced pS380-PTEN through PP2A. In conclusion, knockdown of YY1 enhanced TSCC radiosensitivity through PP2A-mediated dephosphorylation of PTEN Ser380; thus, antagonizing the IR-induced nuclear PTEN/Rad51 axis and targeting YY1 may reverse IR resistance in TSCC.

The anti-inflammatory effects of shikonofuran E from Onosma paniculatum on RAW 264.7 murine macrophage cells induced by lipopolysaccharide (LPS) were first time examined. A series of non-cytotoxic concentrations of shikonofuran E (

Acute kidney injury (AKI) incidence among hospitalized patients is increasing steadily. Despite progress in prevention strategies and support measures, AKI remains correlated with high mortality, particularly among ICU patients, and no effective AKI therapy exists. Here, we investigated the function in kidney ischaemia‐reperfusion injury (IRI) of C1orf54, a newly identified protein encoded by an open reading frame on chromosome 1. C1orf54 expression was high in kidney and low in heart, liver, spleen, lung and skeletal muscle in healthy mice, and in the kidney, C1orf54 was expressed in tubular epithelial cells (TECs), but not in glomeruli. C1orf54 expression was markedly decreased on Day 1 after kidney IRI and then gradually recovered to baseline levels by Day 7. Notably, relative to wild‐type mice, C1orf54‐knockout mice exhibited impaired TEC proliferation and delayed recovery after kidney IRI, which led to deteriorated renal function and increased mortality. Conversely, adenovirus‐mediated C1orf54 overexpression promoted TEC proliferation and ameliorated kidney pathology, which resulted in accelerated renal repair and improved renal function. Mechanistically, C1orf54 was found to promote TEC proliferation through PI3K/AKT signalling. Thus, C1orf54 holds considerable potential as a therapeutic target in kidney IRI.

The standard treatment in elderly patients with diffuse large B cell lymphoma (DLBCL) has not yet been finely established. We investigated the efficacy and safety of rituximab with a reduced-dose of EPOCH chemotherapy in elderly patients who had advanced DLBCL with high IPI scores. The dose of 70% EPOCH was given to patients aged 75 to 79 years, and dose of 50% to patients aged over 80 years. Thirty-one patients with a median age of 79 years (range 75–86 years) were enrolled. Patients received a median of 6 cycle’s chemotherapy. The complete response rate was 71.0%. The 3-year overall survival (OS) and progression-free survival rates were 62.8 and 60.3%, respectively. The most frequent grade 3/4 adverse effects were neutropenia (3 patients, 7 events), febrile neutropenia (3 patients, 5 events), and pulmonary infection (3 patients, 3 events). Our study showed that ECOG score 3–4, bulky disease, β2-MG > 5.0 mg/L, and loss of any IADL are prognostic factors for OS in univariate analysis. In summary, reduced-dose EPOCH-R chemotherapy for very elderly patients is very effective with acceptable toxicities. Our preliminary study may provide an alternative approach to manage very elderly fit patients with advanced and poor risk DLBCL by first-line treatment with reduced-dose EPOCH-R.

This study aims to identify and distinguish various factors that may influence the clinical symptoms (limited mouth opening and malocclusion) in patients with maxillofacial fractures. From January 2000 to December 2009, 963 patients with maxillofacial fractures were enrolled in this statistical study to aid in evaluating the association between various risk factors and clinical symptoms. Patients with fractured posterior mandibles tended to experience serious limitation in mouth opening. Patients who sustained coronoid fractures have the highest risk of serious limitation in mouth opening (OR = 9.849), followed by arch fractures, maxilla fractures, condylar fractures, zygomatic complex fractures and symphysis fractures. Meanwhile, the combined fracture of zygomatic arch and condylar process results in normal or mild mouth opening. High risks of sustaining malocclusion are preceded by the fracture of nasal bone (OR = 3.067), mandible, condylar neck/base, combined fracture of zygomatic arch and condylar process, mandibular body, bilateral condylar, dental trauma, mandibular ramus, symphysis, mandibular angle and mid-facial. Patients who experienced serious limitation in mouth opening are treated with surgery more frequently (OR = 2.118). No relationship exists between the treatment options and the patients with malocclusion.

Objective The cholinergic deficit is thought to underlie progressed cognitive decline in Alzheimer Disease. The lineage reprogramming of somatic cells into cholinergic neurons may provide strategies toward cell-based therapy of neurodegenerative diseases. Methods and results Here, we found that a combination of neuronal transcription factors, including Ascl1, Myt1l, Brn2, Tlx3, and miR124 (5Fs) were capable of directly converting human brain vascular pericytes (HBVPs) into cholinergic neuronal cells. Intriguingly, the inducible effect screening of reprogramming factors showed that a single reprogramming factor, Myt1l, induced cells to exhibit similarly positive staining for Tuj1, MAP2, ChAT, and VAChT upon lentivirus infection with the 5Fs after 30 days. HBVP-converted neurons were rarely labeled even after long-term incubation with BrdU staining, suggesting that induced neurons were directly converted from HBVPs rather than passing through a proliferative state. In addition, the overexpression of Myt1l induced the elevation of Ascl1, Brn2, and Ngn2 levels that contributed to reprogramming. Conclusions Our findings provided proof of the principle that cholinergic neurons could be produced from HBVPs by reprogramming factor-mediated fate instruction. Myt1l was a critical mediator of induced neuron cell reprogramming. HBVPs represent another excellent alternative cell resource for cell-based therapy to treat neurodegenerative disease.

Background Gansui-Banxia Decoction (GSBXD) is a classic formula of traditional Chinese medical (TCM) sage Zhang Zhongjing to treat stagnation of evil heat and obstruction of qi. At present GSBXD is wildly used to treat cancerous ascites, pleural effusion, peritoneal effusion, pericardial effusion, cranial cavity effusion and several types of cancers, such as hepatocellular carcinoma (HCC) and esophageal cancer. Myeloid-derived suppressor cells (MDSCs) are a kind of immature and heterogeneous cells which can suppress lymphocytes activation by forming a suppressive environment. MDSCs accumulation in peripheral blood and tumors are closely related to the cancer stage and low survival rate of clinical patients. The antitumor immune effect of GSBXD has not received widespread attention. Purpose To investigate the effects of GSBXD on MDSCs accumulation and the mediators including AKT/STAT3/ERK signaling pathways. Methods The chemical components of GSBXD were analyzed by UHPLC-MS, and the putative pathways of GSBXD based on Network pharmacology were predicted. Mice were vaccinated with Hepatoma 22 (H22) to establish tumor growth model, which were then administrated with GSBXD ethanol extraction (0.49 mg/kg/day, 1.75 mg/kg/day), sorafenib (60 mg/kg) or saline for 14 days. The cell morphology was evaluated by hematoxylin and eosin (H&E) staining, and immunity cells were determined through flowcytometry analysis. The levels of cytokines production in blood were evaluated by using ELISA kits. STAT3, ERK and AKT/mTOR signaling transduction associated proteins were determined by Western blot. Results GSBXD could inhibit tumor growth and splenomegaly in H22 tumor model mice. Importantly, GSBXD reduced MDSCs accumulation and differentiation, and inhibited proliferation of F4/80+ CD11b+ macrophages and apoptosis of T cells and B cells, and increased the percentage of CD 3− NK1.1+ NK cells. To better understand the active component of GSBXD, the ethanol-extraction powdered GSBXD was prepared and analyzed by UHPLC-MS. Combined with these main chemical compounds, we predicted that the anti-tumor effect of GSBXD mainly mediated PI3K-AKT and RAS-MAPK signal pathways based on Network Pharmacology. Western blot analysis of tumor tissues and MDSCs cells demonstrated that phosphorylation of AKT, ERK and STAT3 were significantly reduced, specially the activation of ERK. The levels of IL-1β and IFN-γ were significantly decreased by ELISA analysis. Conclusion GSBXD exhibited antitumor immune activity by reducing the accumulation of MDSCs in vivo, which is possible via down-regulation of AKT/STAT3/ERK signaling pathway and suppression of IL-1β and IFN-γ.

A phytochemical investigation on the flowers of Sophora davidii resulted in the isolation of three unusual matrine–adenine hybrids, sophovicines A–C, together with biogenetically related analogue sophocarpine. Their structures and absolute configurations were determined by NMR analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) data. Since sophovicines represent the first example of matrine-adenine hybrids, a putative biosynthetic pathway toward sophovicines A–C was proposed. In addition, computational molecular modeling suggested that compounds sophovicines B and C may have potent activities against human cytomegalovirus (HCMV). So, the inhibit effects of isolates on HCMV were evaluated. The results show that sophovicines B and C can inhibit HCMV replication effectively with IC50 values of 7.12 and 7.32 μM, respectively.

Cell death is essential for cancer, which can be induced through multiple mechanisms. Ferroptosis, a newly emerging form of non-apoptotic cell death, involves the generation of iron-dependent reactive oxygen species (ROS). In this study, we designed and synthesized two artesunate (ART) conjugated phosphorescent rhenium(I) complexes (Re(I)-ART conjugates), [Re(N^N)(CO)3(PyCH2OART)](PF6) (Re-ART-1 and Re-ART-2) (Py = pyridine, N^N = 1,10-phenanthroline (phen, in Re-ART-1) and 4,7-diphenyl-1,10-phenanthroline (DIP, in Re-ART-2)) that can specifically locate in the mitochondria of human cervical carcinoma (HeLa). Mechanism studies show that Re-ART-1 and Re-ART-2 exhibit high cytotoxicity against cancer cells lines and can induce both apoptosis and ferroptosis in HeLa cells through mitochondrial damage, caspase cascade, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4) inactivation and lipid peroxidation accumulation. As a result, this work presents the rational design of Re(I)-ART conjugates as a promising strategy to induce both apoptosis and ferroptosis and improve therapeutic efficiency of cancer treatment.

Background Biomarkers of early plaque progression are still elusive. Myeloid DAP12-associating lectin-1 (MDL-1), also called CLEC5A, is a C-type lectin receptor implicated in the progression of multiple acute and chronic inflammatory diseases. However, the relationship between its level and atherosclerosis is unknown. In this study, we aimed to investigate the correlation between macrophage MDL-1 expression and early atherosclerosis progression. Methods Immunofluorescence staining, real-time PCR and western blot were performed to analyze MDL-1 expression in aorta or mice macrophages. The role of MDL-1 in macrophage survival was further investigated by adenovirus infection and TUNEL assay. Results Significant MDL-1 expression was found in advanced human and apoE−/− mice atherosclerotic plaques, especially in lesional macrophages. In the model of atherosclerosis regression, we found MDL-1 expression was highly downregulated in lesional macrophages from ldlr−/− mouse regressive plaques, coincident with a reduction in lesional macrophage content and marker of M1 proinflammatory macrophages. Furthermore, we found MDL-1 was significantly expressed in inflammatory M1 subtype polarized bone marrow-derived macrophages. In vitro experiments, the level of MDL-1 was remarkably elevated in macrophages treated with pathophysiological drivers of plaque progression, such as oxidized low-density lipoprotein (ox-LDL) and hypoxia. Mechanistically, we demonstrated that MDL-1 overexpression notably promoted macrophage survival and decreased cleaved caspase-3 expression under ox-LDL stimulation, which suggested that it could maintain lesional macrophage survival and cause its accumulation. Conclusions This study firstly demonstrated that MDL-1 is mainly expressed in atherosclerotic lesional macrophages and increased macrophage MDL-1 expression is associated with early plaque progression and promotes macrophage survival. Electronic supplementary material The online version of this article (10.1186/s12967-017-1336-z) contains supplementary material, which is available to authorized users.

Grb2-associated-binding protein 1 (Gab1) is a docking/scaffolding molecule known to play an important role in cell growth and survival. Here, we report that Gab1 is decreased in cholinergic neurons in Alzheimer’s disease (AD) patients and in a mouse model of AD. In mice, selective ablation of Gab1 in cholinergic neurons in the medial septum impaired learning and memory and hippocampal long-term potentiation. Gab1 ablation also inhibited SK channels, leading to an increase in firing in septal cholinergic neurons. Gab1 overexpression, on the other hand, improved cognitive function and restored hippocampal CaMKII autorphosphorylation in AD mice. These results suggest that Gab1 plays an important role in the pathophysiology of AD and may represent a novel therapeutic target for diseases involving cholinergic dysfunction.

Curcumin possesses strong anti-inflammatory, anti-rheumatoid and anti-oxidative activities, and has the potential to inhibit nuclear factor‑κB (NF‑κB) signaling. Cartilage damage in osteoarthritis (OA) is largely mediated by interleukin-1β (IL-1β) via activation of various transcription factors, including NF‑κB and activator protein‑1. The aim of the present study was to determine whether IL‑1β induces matrix metalloproteinase-13 (MMP-13) expression and inhibits type II collagen expression, as well as to examine whether cell proliferation may be inhibited by curcumin through the inhibition of NF‑κB signaling. The effects of curcumin were investigated in rat articular chondrocyte cell cultures treated with IL‑1β in the presence or absence of curcumin or the NF‑κB inhibitor pyrrolidine dithiocarbamate. Western blotting and reverse transcription‑quantitative polymerase chain reaction were conducted to evaluate protein and mRNA expression levels of type II collagen, MMP‑13, NF‑κB inhibitor α (IκBα), phosphorylated‑IκBα and NF‑κB subunit p65/RelA. Western blotting and immunofluorescence were performed to examine the effects of curcumin on the expression, phosphorylation and nuclear translocation of NF‑κB‑associated proteins. The effects of curcumin on cell proliferation were evaluated by Cell Counting Kit‑8 (CCK‑8). Curcumin was demonstrated to inhibit the IL‑1β‑induced activation of NF‑κB by suppressing IκBα phosphorylation and p65/RelA nuclear translocation. These events were associated with the downregulation of MMP‑13 expression and the upregulation of type II collagen expression, both of which are considered to be NF‑κB targets. CCK‑8 assays revealed that co‑treatment with curcumin resulted in increased proliferation in IL‑1β‑treated chondrocytes. These findings implicated curcumin as a naturally occurring anti‑inflammatory agent for the treatment of OA via inhibition of NF‑κB signaling.

This study aims to investigate the molecular mechanisms underlying the pathogenesis of severe acute pancreatitis (SAP) and SAP-associated liver injury, we performed an association analysis of the functions of tissue factor (TF) and blood coagulation system in both SAP patients and mouse SAP model. Our results showed that serum TF and tissue factor-microparticle (TF-MP) levels were highly up-regulated in both SAP patients and SAP mouse model, which was accompanied by the dysfunction of blood coagulation system. Besides, TF expression was also highly up-regulated in the Kupffer cells (KCs) of SAP mouse model. After inhibiting KCs in SAP mouse model, the amelioration of blood coagulation system functions was associated with the decrease in serum TF and TF-MPs levels, and the reduction of SAP-associated liver injury was associated with the decrease of TF expression in KCs. In conclusion, the dis-regulated TF expression and associated dysfunction of blood coagulation system are critical factors for the pathogenesis of SAP and SAP-associated liver injury. TF may serve as a potential and effective target for treating SAP and SAP-associated liver injury.

OBJECTIVE: To investigate the effect of placement of peripherally inserted central catheter (PICC) via the upper versus lower extremity veins in neonates through a Meta analysis. METHODS: CNKI, Wanfang Data, VIP Data, CBMdisc, PubMed, Web of Knowledge, Embase, Medline, Cochrane Library and Google Scholar were searched for control studies on the effect of PICC placement via the upper versus lower extremity veins in neonates. RevMan 5.3 was used to perform a Meta analysis of the studies which met the inclusion criteria. RESULTS: A total of 18 studies were included, among which there were 8 randomized controlled trials and 10 cohort studies, with 4 890 subjects in total. Compared with those undergoing PICC placement via the upper extremity veins, the neonates undergoing PICC placement via the lower extremity veins had significantly lower incidence rates of complications (RR=0.83, 95%CI:0.75-0.92, P < 0.05), catheter-related infections (RR=0.77, 95%CI:0.60-0.99, P < 0.05), catheter malposition (RR=0.28, 95%CI:0.18-0.42, P < 0.05), extravasation of the infusate (RR=0.52, 95%CI:0.40-0.70, P < 0.05), and unplanned extubation (RR=0.82, 95%CI:0.69-0.98, P < 0.05). They also had a significantly higher first-attempt success rate of puncture (RR=1.17, 95%CI:1.05-1.30, P < 0.05) and a significantly shorter PICC indwelling time (MD=-0.93, 95%CI:-1.26-0.60, P < 0.05). CONCLUSIONS: The above evidence shows that PICC placement via the lower extremity veins has a better effect than PICC placement via the upper extremity veins in neonates.

Fifteen diterpenoids (1-15), including three undescribed ones with ent-atisane skeleton, eupnerias G-I (1-3), were obtained from Euphorbia neriifolia. Compounds 1-3 were established through comprehensive spectroscopic analysis. Compounds 4 and 5 exhibited obvious anti-HIV-1 effect, and their EC50 were 6.6±3.2 and 6.4±2.5 μg mL-1 , respectively. Compound 6 exhibited moderate cytotoxicity on HepG2 and HepG2/Adr cells with IC50 at 13.70 and 15.57 μm, respectively. In addition, compound 15 exhibited significant cytotoxicity on HepG2 cell lines (IC50 =0.01 μm), while it did not show any cytotoxicity against HepG2/Adr cell lines.

Five new cucurbitane-typetriterpenoid glycosides, named Xuedanoside F&ndash, J (1&ndash, 5), were obtained from the rhizomes of Hemsleya penxianensis (Xue dan), which belongs to the family of Cucurbitaceae. These new compounds were elucidated byspectroscopic analysis, including 1D, 2D NMR, and HR-ESI-MS spectra. Additionally, all the isolates were evaluated for cytotoxicity against three human cancer cell lines (Hela, MCF-7, and A-549) with the IC50 ranging from 2.25 to 49.44 &micro, M in vitro with treatment 48 h and showed low cytotoxicity in human normal liver L-02 cells (IC50 &gt, 50 &micro, M). Compound 5 showed the most significant cytotoxic activity with the IC50 value of 2.25, 4.72, and 5.33 &micro, M in 48 h, respectively.

Objective This study aimed to explore and make an understanding of absorption existed in children with intracapsular fractures. Methods The sample was composed of all children (less than 12 years) who presented with intracapsular fractures within a 5-year period (January 2011 to April 2016). Data about age, gender, date of injury, dates of admission and discharge, transfer and/or referral by other clinics or local facilities, mechanism of trauma, location and pattern of fracture, associated injuries, centimeter of mouth opening, treatment methods, image date of pre- and post-treatment (including time of review), position of condylar head in pre-treatment or post-treatment, and absorption of condylar head in pre-treatment or post-treatment were recorded and analyzed. Data analysis included the Chi-Square test, the Fisher exact test, and the t-test. Logistic regression analysis was utilized to control the confounding variables. Probabilities of p less than 0.05 were considered statistically significantly different. Results In the 5 years records retrieved during this study, 93 children patients sustained a total of 140 condylar head fractures. Statistical analysis revealed that abduction of condylar process in post-treatment was highly related to the condylar absorption. Patients associated with other mandibular fractures were highly related to abduction of condylar process. Patients with condylar head fractures, the closer to the medial of the condylar process, the higher the risk of abduction of the condyle. No matter what kind of treatment method is used, it is very difficult to reverse the abduction of condylar process in children patients with intracapsular fractures efficaciously. Conclusion Abduction of condylar process in post-treatment was highly related to the condylar absorption. Patients associated with other mandibular fractures were highly related to abduction of condylar process. Children patients who presented with condylar head fractures, the closer to the medial of the condylar process the higher the risk of abduction of the condyle. Neither surgery nor conservative treatment can recover the abduction of condylar process efficaciously.

Six new compounds, including three terpenoids (