[Single-center study of different treatment for advanced or unresectable angiosarcoma patients].

Objective: To evaluate the efficacy and safety of different medical treatment in advanced or unresectable angiosarcoma. Methods: This study was a single-center retrospective clinical study. Fifty-five advanced or unresectable angiosarcoma patients treated in Sun-Yat Sen University Cancer Center from January 2005 to August 2020 were enrolled. There were 34 patients who received first-line doxorubicin-based chemotherapy (doxorubicin group), 12 patients received first-line doxorubicin or liposome doxorubicin plus paclitaxel or albumin bound paclitaxel chemotherapy (combination therapy group), and 4 patients received first-line paclitaxel-based treatment (paclitaxel group). There were 6 patients who received anti-angiogenesis targeted therapy, another 2 patients received anti-PD-1 antibody plus anti-angiogenesis targeted therapy. Targeted therapy and immunotherapy plus targeted therapy included 5 cases of first-line therapy and 3 cases of second-line therapy. The therapeutic effect was evaluated by RECIST 1.1 standard. The adverse reactions were evaluated by CTCAE4.0 standard. Kaplan-Meier survival analysis was evaluated with Log rank test. Cox proportional hazard model was used to analyze the influencing factors. Results: There were 18 patients achieved partial response (PR) in 34 patients in the doxorubicin group, median progression-free survival (mPFS) was 4.5 months, and median overall survival (mOS) was 15 months. Four patients achieved PR in 12 patients in the combination therapy group, mPFS and mOS were 4 months and 19 months. Two patients achieved PR in 4 patients in the paclitaxel group, mPFS and mOS were 3 months and 9 months. However, only 1 in 6 patients achieved PR for anti-angiogenesis targeted therapy, mPFS and mOS were 3 months and 16 months. Two patients who received anti-PD-1 immunotherapy combined with anti-angiogenesis targeted therapy acquired PR for 17 months and more than 16 months. Median PFS (7.5 months) were longer in those with primary liver, lung and spleen angiosarcoma than in those with other primary site (3.0 months, P=0.028). The mOS (20 months) was longer in females than that in males (12 months, P=0.045). Primary tumor site, sex, age and treatment were not independent prognostic factors for angiosarcoma patients (P>0.05). Grade 3-4 cardiac toxicity was found in 2 patients in the combination therapy group. Conclusions: Doxorubicin-based and paclitaxel-based chemotherapy are the most important treatment for advanced angiosarcoma. Potential efficacy for targeted therapy combined with anti-PD-1 immunotherapy are showed in some patients with long duration of response and moderate adverse event.

[Application of multi-state Markov model in studying transition of number of chronic complications and influencing factors in type 2 diabetes mellitus patients].

Objective: To establish a multi-state Markov model of type 2 diabetes mellitus (T2DM) patients and explore the transition rule between the cumulative number of different chronic complications, estimate the transition probability and intensity between status, and explore the possible factors affecting the transition between status. Methods: A retrospective cohort study of 33 575 patients with T2DM was conducted. According to the baseline and the cumulative number of chronic complications during the follow-up period, the patients were classified based on five status: T2DM, one complication, two complications, three complications, four and above complication, indicated by S0, S1, S2, S3 and S4, respectively. A time-continuous and state-discrete multi-state irreversible Markov model was used for statistical analysis. Results: The study included 33 575 T2DM patients, and their average age was 60 years old, the median of follow-up length was 8 years. In these patients, 32 653 had no baseline complications. At the end of follow-up, the transition probabilities of S0→S1, S1→S2, S2→S3 and S3→S4 were 16.4%, 32.4%, 45.6% and 25.9%, respectively. The results of multivariate analysis showed that being female (HR=0.919), less than 60 years old (HR=0.929), higher fasting plasma glucose (HR=1.601), lower high-density lipoprotein (HR=1.087), higher total cholesterol (HR=1.090),weekly exercise (HR=0.897), vegetarian diet (HR=0.852) and heavy diet (HR=1.887) were the risk factors for S0 to S1. And being female (HR=0.768), less than 60 years old (HR=0.859) and lower high-density lipoprotein (HR=1.160) were the risk factors for S1 to S2. Conclusions: The probability of multiple complications in T2DM patients increased over time, the transition intensity of S2→S3 was largest, followed by S1→S2. Therefore, we need to conduct both early and long-term indicators monitoring and disease prevention, strengthen the health education to improve patients' daily living habits at early stage of the illness, encourage patients to have moderate exercise and balanced diet, strengthen the monitoring of fasting blood- glucose, cholesterol and high-density lipoprotein levels to prevent the deterioration of the illness.

Epidemiological characteristics of COVID-19 patients in convalescence period.

This study aimed to investigate the clinical characteristics and to analyse the epidemiological features of coronavirus disease 2019 (COVID-19) patients during convalescence. In this study, we enrolled 71 confirmed cases of COVID-19 who were discharged from hospital and transferred to isolation wards from 6 February to 26 March 2020. They were all employees of Zhongnan Hospital of Wuhan University or their family members of which three cases were <18 years of age. Clinical data were collected and analysed statistically. Forty-one cases (41/71, 57.7%) comprised medical faculty, young and middle-aged patients (aged ⩽60 years) accounted for 81.7% (58/71). The average isolation time period for all adult patients was 13.8 ± 6.1 days. During convalescence, RNA detection results of 35.2% patients (25/71) turned from negative to positive. The longest RNA reversed phase time was 7 days. In all, 52.9% of adult patients (36/68) had no obvious clinical symptoms, and the remaining ones had mild and non-specific clinical symptoms (e.g. cough, sputum, sore throat, disorders of the gastrointestinal tract etc.). Chest CT signs in 89.7% of adult patients (61/68) gradually improved, and in the others, the lesions were eventually absorbed and improved after short-term repeated progression. The main chest CT manifestations of adult patients were normal, GGO or fibre streak shadow, and six patients (8.8%) had extrapulmonary manifestations, but there was no significant correlation with RNA detection results (r = -0.008, P > 0.05). The drug treatment was mainly symptomatic support therapy, and antibiotics and antiviral drugs were ineffective. It is necessary to re-evaluate the isolation time and standard to terminate isolation for discharged COVID-19 patients.

Spatial distribution of perfluoroalkyl acids (PFAAs) and their precursors and conversion of precursors in seawater deeply affected by a city in China.

Conversion of perfluoroalkyl acid (PFAA) precursors in the environment has been a hotspot research in recent years. This study firstly determined the spatial distribution of PFAAs and their precursors including 8:2 fluorotelomer unsaturated acid (8:2 FTUCA), perfluorooctane sulfoneamide (FOSA), and diperfluorooctane sulfonamido ethanol-based phosphate (di-SAmPAP), then investigated the conversion of the potential precursors in the seawater and sewage treatment plants (STPs) effluents. The results indicated that the target pollutants showed a typical concentration gradient from nearshore to offshore. And the obviously increased concentration of perfluorinated carboxylic acids (△[PFCAs]) after oxidation treatment can verify the existence of PFAA precursors in the seawater and STP effluents. The concentrations of PFCAs with carbon atom numbers 4-9 (PFCAC4-C9) revealed the most increase. Moreover, the levels of △[PFCAs] and the ratios of △[PFCAs] to their concentration before oxidation (△[PFCA]/[PFCA]before oxidation) indicated obvious spatial variations in the seawater and STP effluents. The higher levels of △[PFCAC4-C12] and the lower ratios of ∑△[PFCAC4-C12]/∑[PFAA]before oxidation were observed in the STP effluents, which implied that precursors might be decomposed during the sewage treatment process. These results suggested the STP effluents might have an important effect on the PFAAs levels of seawater.

Promising High-Confinement Regime for Steady-State Fusion.

A reproducible stationary high-confinement regime with small "edge-localized modes" (ELMs) has been achieved recently in the Experimental Advanced Superconducting Tokamak, which has a metal wall and low plasma rotation as projected for a fusion reactor. We have uncovered that this small ELM regime is enabled by a wide edge transport barrier (pedestal) with a low density gradient and a high density ratio between the pedestal foot and top. Nonlinear simulations reveal, for the first time, that the underlying mechanism for the observed small ELM crashes is the upper movement of the peeling boundary induced by an initial radially localized collapse in the pedestal, which stops the growth of instabilities and further collapse of the pedestal, thus providing a physics basis for mitigating ELMs in future steady-state fusion reactors.

Brain regions preferentially responding to transient and iso-intense painful or tactile stimuli.

How pain emerges from cortical activities remains an unresolved question in pain neuroscience. A first step toward addressing this question consists in identifying brain activities that occur preferentially in response to painful stimuli in comparison to non-painful stimuli. A key confound that has affected this important comparison in many previous studies is the intensity of the stimuli generating painful and non-painful sensations. Here, we compared the brain activity during iso-intense painful and tactile sensations sampled by functional MRI in 51 healthy participants. Specifically, the perceived intensity was recorded for every stimulus and only the stimuli with rigorously matched perceived intensity were selected and compared between painful and tactile conditions. We found that all brain areas activated by painful stimuli were also activated by tactile stimuli, and vice versa. Neural responses in these areas were correlated with the perceived stimulus intensity, regardless of stimulus modality. More importantly, among these activated areas, we further identified a number of brain regions showing stronger responses to painful stimuli than to tactile stimuli when perceived intensity was carefully matched, including the bilateral opercular cortex, the left supplementary motor area and the right frontal middle and inferior areas. Among these areas, the right frontal middle area still responded more strongly to painful stimuli even when painful stimuli were perceived less intense than tactile stimuli, whereas in this condition other regions showed stronger responses to tactile stimuli. In contrast, the left postcentral gyrus, the visual cortex, the right parietal inferior gyrus, the left parietal superior gyrus and the right cerebellum had stronger responses to tactile stimuli than to painful stimuli when perceived intensity was matched. When tactile stimuli were perceived less intense than painful stimuli, the left postcentral gyrus and the right parietal inferior gyrus still responded more strongly to tactile stimuli while other regions now showed similar responses to painful and tactile stimuli. These results suggest that different brain areas may be engaged differentially when processing painful and tactile information, although their neural activities are not exclusively dedicated to encoding information of only one modality but are strongly determined by perceived stimulus intensity regardless of stimulus modality.

Comparison of the strength of two multi-strand tendon repair configurations in a chicken model.

We sought to investigate the strength of two multi-strand tendon repair configurations in a chicken model. Fifty-six chicken flexor tendons were repaired with one to two different four-strand configurations: 1) a four-strand repair consisting of a two-strand core modified Kessler suture with a circle loop repair and 2) a four-strand core Kessler suture repair with three separate peripheral suture points. The strength of the repaired tendons were measured 2, 3 and 4 weeks after the surgical repair and were analyzed statistically. The strength of the two repair methods was not statistically different 2 weeks after surgery. The tendons repaired with the four-strand core Kessler suture repair and three separate peripheral suture points were significantly stronger than those repaired with a two-strand core modified Kessler suture and a circle loop repair at 3 weeks (P = 0.033) and 4 weeks (P = 0.039). The four-strand repair with three separate peripheral suture points had greater strength than a two-strand repair with one circle loop suture based on an in vivo chicken flexor tendon model.

[Prevalence of attention deficit and hyperactivity disorder in children in China: a systematic review and Meta-analysis].

Objective: To understand the prevalence of attention deficit and hyperactivity disorder (ADHD) in children in China and provide scientific basis for early prevention and treatment of ADHD in children. Methods: A systematic literature retrieval was conducted by using CNKI, Wanfang data, CBM and VIP databases for the information about the prevalence of ADHD in children in China published from 1979 to 2017. Pubmed database was used to retrieve the literatures about ADHD prevalence in children in China published from 1946 to 2017. The quality of literature was evaluated based on the cross-sectional study criteria according to STROBE statement. Stata 12.0 was used for combined prevalence and subgroup analyses, including gender, regions, publication year, diagnostic criteria, sampling methods, and so on. Egger testing and the evaluation of funnel graph were used to evaluate the publication bias of these literatures, and sensitivity analysis was done by using different models and eliminating the influence of any one of these articles on combined effect value. Results: Twenty articles were included. The total sample size was 88 755, including 46 216 boys and 42 539 girls. The prevalence of ADHD in children in China was 5.6% (95%CI: 5.0%-6.3%). The prevalence was 7.7% (95%CI: 6.7%-8.8%) in boys and 3.4% (95%CI: 3.0%-3.8%) in girls, the difference was statistically significant (P<0.05). No statistically significance difference in the ADHD prevalence was observed between different regions publication years, diagnostic criteria and sampling methods. Conclusions: The prevalence of ADHD in children in China was high, and boys tended to have a higher prevalence compared with girls. Appropriate screening methods for early detection and intervention conduction of ADHD should be taken among children in China.

[HSP90 inhibitor 17-AAG plays an important role in JAK3/STAT5 signaling pathways in HTLV-1 infection cell line HUT-102].

Objective: To analyze whether heat-shock protein 90 (HSP90) be involved in a permanently abnormal activated JAK/STAT signaling in ATL cells in vitro. Methods: The effect of 17-AAG on proliferation of ATL cell lines HUT-102 was assessed using CCK8 at different time points. Cell apoptosis was measured by flow cytometry. The specific proteins HSP90, STAT5, p-STAT5 and JAK3 were detected by Western blotting. Results: Overexpression of HSP90 in HUT-102 cell lines was disclosed (P<0.05) , and constitutive activation of JAK3/STAT5 signaling was observed in HTLV-1-infected T-cell lines but not in normal PBMCs; Treatment of ATL cell lines with 17-AAG led to reduced cell proliferation, but there was no significant change in terms of cell proliferation when the concentration of 17-AAG between 2 000-8 000 nmol/L (P>0.05) . 17-AAG induced cell apoptosis in different time-points and concentrations. 17-AAG don't affect the expression of JAK3 gene. Conclusion: This study indicated that JAK3 as HSP90 client protein was aberrantly activated in HTLV-1-infected T-cell lines, leading to constitutive activation of p-STAT5 in JAK/STAT signal pathway, which demonstrated that HSP90-inhibitors 17-AAG inhibited the growth of HTLV-1-infected T-cell lines by reducing cell proliferation and inducing cell apoptosis.

Modulation of digital flexor tendon healing by vascular endothelial growth factor gene transfection in a chicken model.

A major challenge in tendon injury is the weak intrinsic healing capacity of tendon that may cause rupture of the repair after surgery. Growth factors are believed to be critical during tendon healing. This study aimed to investigate the effects of vascular endothelial growth factor (VEGF) genes delivered by adeno-associated virus (AAV) vectors on tendon healing and molecular events involved in a chicken model. A total of 128 deep flexor tendons in the long toes of chickens were completely transected and injected with 2 × 109 particles of AAV2-VEGF or saline before surgically repaired. At postoperative 4, 6 and 8 weeks, the gliding excursions of tendon were recorded and adhesions around the repair site scored. At 2, 4, 6 and 8 weeks, the ultimate strengths of the healing tendons were tested. Terminal deoxynucleotide transferase dUTP nick end labeling assay were performed to detect cellular apoptosis and immunofluorescence staining to detect type III collagen and matrix metalloprotease-2 (MMP2) expression in tendon tissues. The gliding excursion and adhesion score were similar between AAV2-VEGF-treated tendons and the control tendons. Delivery of AAV2-VEGF significantly increased ultimate strength of the healing tendons at postoperative 4, 6 and 8 weeks (P<0.05). Apoptotic reaction was inhibited from postoperative 2 to 8 weeks in tendon core area or surface area. Type III collagen expression was enhanced at 2, 4, 6 and 8 weeks and MMP2 expression enhanced at 2 and 4 weeks after AAV2-VEGF transfection. The current study confirms the therapeutic efficacy of AAV2-VEGF in improving healing strength of tendon without aggravating adhesion formation after tendon injury, shedding light on the application of molecular therapy in modulating tendon healing.

[Application of ultrasound guidance for fascia iliaca compartment block in pediatric femoral surgery].

Objective: To evaluate the efficacy of ultrasound guidance for fascia iliaca compartment block in pediatric femoral surgery. Methods: This study was a prospective study, thirty children who were American Society of Anesthesiologists (ASA) statusⅠ with 5-10 years old scheduled for femoral surgery were selected in orthopedics department in Second Affiliated Hospital of Wenzhou Medical University from May to December in 2014. After induction of general anesthesia, all the children were inserted the laryngeal mask. Then they were received fascia iliaca compartment block using ultrasound guidance under sevoflurane inhalation anesthesia. The indicators including heart rate(HR), mean arterial pressure(MAP), oxygen saturation(SpO(2)) and exhaled sevoflurane concentration were recorded before skin incision(T(1)), at 1, 5, 10 min after incision(T(2)-T(4))and at the end of the surgery(T(5)). Postoperative pain were assessed using the pain behavior assessment scale at awake time, 2 h and 4 h after surgery. The efficacy of postoperative analgesia and the satisfaction of parents at 2 h and 4 h after surgery were recorded. Results: The differences between HR、MAP and SpO(2) in children at T(1)-T(5) were no statistical significance (all P>0.05). Exhaled sevoflurane concentration at T(1)-T(5) were(2.50±0.51)%, (2.51±0.42)%, (2.50±0.41)%, (2.54±0.31)% and(0.61±0.20)%, respectively, the differences were statistically significant(F=13.503, P<0.05), among them that at T(5) was significantly lower than at T(1)-T(4)(all P<0.05). The pain score at awake time, 2 h and 4 h after surgery were (1.6±0.7), (3.3±1.4) and (3.9±1.3) scores, respectively. The parents satisfaction were 87% and 73% at 2 h and 4 h afer surgery respectively. Conclusion: The way of ultrasound guidance for fascia iliaca compartment block combined with general anesthesia can be safely and effectively used in pediatric femoral surgery. Using the technique of ultrasonic imaging, the fascia iliaca compartment can be directly observed and then the local anesthetics is injected, therefore the efficacy of block is improved.

Active site-targeted carbon dots for the inhibition of human insulin fibrillation.

Carbon nano-dots (C-Dots) possess great benign properties, making them ideal for use in biomedical fields, especially due to their high aqueous solubility, outstanding photoluminescence (PL), favorable biocompatibility, low toxicity, chemical inertness, and easy functionalization properties. Herein, the C-Dots with sizes of about 2.4 ± 0.9 nm and containing the groups -OH, C[double bond, length as m-dash]C and C[double bond, length as m-dash]O, were shown to prolong the lag phase of human insulin (HI) fibrillation following a dose-dependent manner in an in vitro study. The spontaneous growth of fibrils after a lag phase was accompanied by exothermic heat, determined by isothermal titration calorimetry (ITC), demonstrating the inhibitory effect of C-Dots. Moreover, as the dose of C-Dots was increased to 4 mg mL-1, the fibrillation process could be totally deterred for more than half a month. However, the deterrent effect of the C-Dots on HI fibrillation disappeared when just a few fibril seeds were added. This is because the association constant of HI monomers interacting with fibril seeds (K2: 1.56 × 105 M-1) is much larger than that with C-Dots (K2: 8.28 × 103 M-1), as determined by analyzing the ITC results. An ''active-site targeted'' inhibitory mechanism has also been proposed. The "active site" is mainly on the B-chain of HI, and the ITC results show that the binding between the C-Dots and HI monomers is mainly driven by the electrostatic force. This is the first time that the anti-fibrillation mechanism in the presence of C-Dots has been analyzed by ITC. These results indicate that ITC is a promising approach for comprehensively clarifying the mechanisms of protein fibrillation inhibition.

[Effect of ligustrazine peritoneal dialysate on CD40 expression of rat peritoneal mesothellial cells].

OBJECTIVE: To explore the effect of Ligustrazine (LGZ) affecting the expression of CD40 on mesothelial cells (MC). METHODS: Rat's peritoneal MC isolated from peritoneal cavity were cultured and maintained under the defined conditions in vitro. They were cultured with 4.25% peritoneal dialysis solution (PDS), 4.25% PDS added LGZ (40 mg/L), 4.25% PDS added IFN-gamma (100 u/ml) and 4.25% PDS added IFN-gamma and LGZ for 30 min, the DMEM/F12 cultural medium was taken as control. The expression of CD40 on MC was detected by reverse transcript polymerase chain reaction (RT-PCR) and flow cytometry analysis. RESULTS: MC cultured in vitro expressed CD40 markedly, the expression of CD40 mRNA and its protein was markedly up-regulated following stimulation with 4.25% PDS or IFN-gamma and 4.25% PDS. LGZ (40 mg/L) could reduce the expression of CD40 mRNA and its protein significantly as it was added in 4.25% PDS and 4.25% PDS with IFN-gamma. CONCLUSION: The PDS stimulates the expression of CD40 on MC. LGZ has the function of down-regulating the expression of CD40 on MC. During long-term continuous ambulatory peritoneal dialysis, it might be helpful to alleviate chronic inflammatory reaction by adding LGZ into standard PDS, therefore prevent or retard the occurence and development of peritoneal fibrosis.

CD40 ligand expression on macrophages during peritonitis in continuous ambulatory peritoneal dialysis patients.

CD40-CD40 ligand (CD40L) interaction plays an important role in macrophage/monocyte-mediated inflammatory processes by up-regulating cytokine production by macrophages/monocytes and by preventing macrophage apoptosis at the inflammation sites. The present study investigated the possible regulation of CD40L expression in peritonitis during continuous ambulatory peritoneal dialysis (CAPD). We used fluorescence-activated cell sorter (FACS) analysis to detect CD40L expression on macrophages obtained from peritoneal dialysate. Our results showed that CD40L expression on macrophages was significantly increased in a peritonitis group (4.62 +/- 6.54) as compared to a control group (0.76 +/- 0.30, p < 0.01). The CD40L-positive cells were also significantly increased during peritonitis (97.86% +/- 1.67% in the peritonitis group as compared to 73.10% +/- 26.94% in the control group, p < 0.05). After successful treatment, the expression of CD40L was significantly reduced (3.66 +/- 1.12 vs 1.05 +/- 0.02, p < 0.05). We conclude that functionally expressed CD40L on macrophages may take part in acute inflammatory response during peritonitis in CAPD and may play an important role in the local defense against infection in the peritoneal cavity.

Antagonistic effects of dihydropyridines and verapamil on CaCl2 and 5-HT-evoked contraction in porcine coronary artery.

In porcine coronary arterial strips, the antagonistic effects of nifedipine (Nif), nimodipine (Nim), nicardipine (Nic), felodipine (Fel), and verapamil (Ver) to CaCl2-evoked contraction in Ca(2+)-free, K(+)-depolarized solution were greater than that to 5-HT. The order of potency (pD2') was Nif (9.1) greater than Fel (8.4) greater than Nim (7.9) greater than Nic (7.8) greater than Ver (7.2) to CaCl2 and Nif (8.3) greater than Nim (7.5) greater than Fel (6.8) greater than Ver (5.6) greater than Nic (5.3) to 5-HT. Ver inhibited 2 components of 5-HT-evoked contraction in Ca(2+)-free solution, but Fel inhibited only extracellular Ca(2+)-dependent contraction, suggesting that their action modes are different.