[Analysis of disease burden of lung cancer attributable to chromium in Chinese population from 1990 to 2019].

Objective: To analyze the disease burden and change trend of lung cancer attributable to chromium in Chinese population from 1990 to 2019, and to provide reference for the formulation of health policies and strategies of disease prevention and control. Methods: In October 2022, using the data and findings of the burden of disease, injury and risk factor published in the Global Burden of Disease Study 2019 (GBD 2019), the burden of lung cancer and its changes caused by occupational hexavalent chromium exposure in Chinese population from 1990 to 2019 were analyzed according to year and gender. The average age structure of the world population was used as the standard population to calculate standardized indicators, and then compared with the global population. Results: The incidence number, death number, disability adjusted life years (DALY) of lung cancer attributable to chromium in Chinese population of 2019 were 833 cases, 790 cases and 22118 person years, respectively. Compared with 1990 (257 cases, 277 cases, 8631 person years), the increase was 224.1%, 185.2%, 156.3%, higher than the global level (101.0%, 134.2%, 117.2%). The standardized morbidity, mortality and DALY rates of lung cancer attributable to chromium in Chinese population of 2019 were 0.059/100000, 0.056/100000 and 1.555/100000, which respectively increased by 169.7%, 137.4%, 113.3% in comparison with that of 1990 (0.022/100000, 0.023/100000 and 0.729/100000). The average annual percent changes were 18.8%, 15.1% and 13.5%, which were higher than the global level (5.7%, 8.4% and 7.0%). In 2019, the DALY caused by chromium-related lung cancer in the Chinese population accounted for 0.0058% (22118/382205568) of the all-cause disease burden in the Chinese population, and 51.8% (22118/42718) of the global population. In 2019, the disease burden of lung cancer attributable to chromium was higher in males than in females, the number of incidence, death and DALY were 576 cases (69.1%), 525 cases (66.5%) and 14717 person years (66.5%), respectively. Conclusion: In 2019, the proportion of disease burden caused by lung cancer attributable to chromium in the Chinese population is low, but it accounts for a high proportion of the global population burden of lung cancer attributable to chromium, and the standardized incidence, mortality and DALY rates show an increasing trend year by year from 1990 to 2019.

People living with HIV have low trabecular bone mineral density, high bone marrow adiposity, and poor trabecular bone microarchitecture at the proximal femur.

People living with HIV (PLWH) have increased risk of osteoporosis and fractures. We assessed the proximal femur of PLWH and age-matched seronegative controls using quantitative computed tomography and magnetic resonance imaging. Results suggest that the trabecular compartment is compromised at fracture-prone regions in the proximal femur of PLWH. INTRODUCTION: People living with HIV (PLWH) have increased risk of osteoporosis and fractures. However, studies assessing the main determinants of bone strength in the proximal femur exclude this vulnerable population. We assessed the proximal femur of 40 PLWH and 26 age-matched seronegative controls using quantitative computed tomography and magnetic resonance imaging. METHODS: We examined cortical volumetric bone mineral density (Ct.vBMD), trabecular vBMD (Tb.vBMD), cortical thickness (Ct.Th), bone marrow adiposity (BMA), and trabecular number, separation, and bone volume fraction. Parametric comparisons between the two groups were made for the femoral head, femoral neck, trochanter, and total hip using linear regression adjusting for several covariates, including metrics of body composition. In addition, we investigated the associations of BMA with Tb.vBMD and trabecular microarchitecture with Spearman's rank partial correlations. RESULTS: PLWH had lower Tb.vBMD and deteriorated trabecular microarchitecture in the femoral neck, trochanter and total hip, and elevated BMA in the femoral head, femoral neck, and total hip. Ct.vBMD and Ct.Th were not significantly different between the two groups. BMA was significantly associated with lower Tb.vBMD and deteriorated trabecular microarchitecture in both groups albeit at different femoral regions. CONCLUSIONS: Our findings suggest that the trabecular, and not the cortical, compartment is compromised in the proximal femur of PLWH. The observed impairments in fracture-prone regions in PLWH indicate lower femoral strength and suggest higher fracture risk. The inverse associations of BMA with trabecular bone density and microarchitecture quality agree with findings at other anatomic sites and in other populations, suggesting that excess BMA possibly due to a switch from the osteoblast to the adipocyte lineage may be implicated in the pathogenesis of bone fragility at the femur in PLWH.

[Efficacy of omalizumab in the treatment of eosinophilic granulomatous polyangiitis with asthma as the first symptom].

Objective: To investigate the efficacy, and safety of omalizumab in the treatment of eosinophilic granulomatous with polyangiitis (EGPA) with asthma as the first symptom. Method: The clinical characteristics of 22 EGPA patients with asthma as the first symptom treated with omalizumab in the First Affiliated Hospital of Guangzhou Medical University from March 2018 to December 2020 were retrospectively analyzed. The asthma control test (ACT) score, the frequency of asthma exacerbation (AE), the Birmingham Vasculitis Activity Score (BVAS), the variation rate of peak expiratory flow (PEF), the percentage of PEF to predicted value of PEF (PEFpred%), the percentage of forced expiratory volume in first second (FEV1) to predicted value of FEV1 (FEV1pred%), the dosage of oral corticosteroid (OCS) and other clinical data [M(Q1, Q3)] were collected before and after treatment, to observe the efficacy and adverse reactions of omalizumab. Results: There were 22 subjects recruited in this study. The median age was 42 (22-70) years. Eleven of the patients were males. After treated with omalizumab for 4 months, there were 68.2%(15/21) of patients who responded to the treatment. In the response group (n=15), the patients' ACT score increased from 19.0 (16.5, 21.0) to 23.0 (21.5, 24.0) (P=0.001). The frequency of AE decreased from 0.7 (0.3, 1.0) to 0 (0, 0.7) per four mouths (P<0.001). The BVAS decreased from 4.0 (2.0, 6.0) to 2.0 (2.0, 4.0) (P=0.007). The variation rate of PEF decreased from 18.8% (14.0%, 27.7%) to 9.2% (6.8%, 11.9%) (P=0.007). The PEFpred% increased from 80.8% (73.5%, 90.7%) to 100.5% (79.4%, 114.0%) (P=0.005). The maintenance dosage of OCS reduced from 15.0 (10.0, 20.0) mg/d to 8.8 (5.0, 10.0) mg/d (P=0.005). The level of baseline eosinophil in peripheral blood of patients in non-response group was higher than that in response group [11.4% (9.2%, 22.6%) vs 3.4% (1.1%, 6.5%), P<0.05]. A total of 190 injections were performed in 22 patients, and only 4 patients (2.1%) had adverse reactions after a single injection of omalizumab, such as dizziness, swelling of injection site and pruritus. The adverse reactions were tolerable. Conclusions: Omalizumab has certain curative effect on EGPA, can reduce asthmatic symptoms and OCS maintenance dosage, and has a good safety profile. The rate of response to the treatment is higher in patients with mild eosinophilic inflammation.

[Correlation between serum IgM antibody and viral load with clinical symptoms in neonates infected with cytomegalovirus].

To investigate the correlation between serum cytomegalovirus (CMV) IgM antibody/viral load and infection-related clinical symptoms in neonates infected with CMV, and provide basis for clinical assessment and monitoring of neonatal CMV infection. A total of 70 neonates with CMV infection admitted to neonatology in Women's Hospital, School of Medicine Zhejiang University, from January 2014 to December 2020 were included in this study. Using real-time quantitative PCR as the diagnostic criteria, congenital cytomegalovirus-infected neonates (n=29) was diagnosed within the first 3 weeks of life, otherwise, it was postnatally acquired cytomegalovirus infection (n=41). The differences in general information and clinical indicators between IgM antibody positive and negative patients were analyzed, combined with the PCR result, the correlation between the IgM/viral load and the occurrence of symptoms were analyzed. T-test and non-parametric test were used to compare the differences of indicators between groups, logistic regression was used for multivariate analysis, and ROC curve was used to evaluate the auxiliary diagnostic value of relevant indicators. In the congenital CMV infection group and the postnatally acquired CMV infection group, viral load and the proportion of symptomatic patients in IgM positive group were significantly higher than IgM negative group (Z=-2.616, P=0.008; 80% vs. 21%, P=0.005) (Z=-2.405, P=0.016; 56% vs. 19%, P=0.025). Logistic regression analysis of the included population showed the risk factors of CMV infection-related symptoms were IgM positive (OR 4.562, 95%CI:1.461-14.246,P=0.009) and viral load (OR 1.728, 95%CI:1.068-2.798,P=0.026). Regressive analysis for single symptom with correction showed IgM antibody positive was associated with hearing dysfunction(OR 3.954, 95%CI:1.066-14.677,P=0.040),the CMV viral load was associated with thrombocytopenia (OR 2.228, 95%CI:1.124-4.413,P=0.022), and brain imaging abnormalities (OR 3.956, 95%CI:1.421-11.011, P=0.008). Receiver operating characteristic (ROC) analysis showed the area under ROC curve of CMV viral load for brain imaging abnormalities was 0.883 (P<0.001), with a sensitivity of 75.0% and specificity of 90.3%. For neonates infected with CMV, the risk of infection-related clinical symptoms and hearing dysfunction may be increased when IgM antibody was positive. Meanwhile, the higher the CMV viral load at diagnosis, the higher the risk of thrombocytopenia and abnormal brain imaging.

Cross-modality and in-vivo validation of 4D flow MRI evaluation of uterine artery blood flow in human pregnancy.

OBJECTIVES: Clinical assessment of uterine artery (UtA) hemodynamics is currently limited to Doppler ultrasound (US) velocimetry. We have demonstrated previously the feasibility of applying four-dimensional (4D) flow magnetic resonance imaging (MRI) to evaluate UtA hemodynamics during pregnancy, allowing flow quantification of the entire course of the vessel. In this study, we sought to further validate the physiological relevance of 4D flow MRI measurement of UtA blood flow by exploring its association with pregnancy outcome relative to US-based metrics. METHODS: Recruited into this prospective, cross-sectional study were 87 women with a singleton pregnancy who underwent 4D flow MRI between May 2016 and April 2019 to measure the UtA pulsatility index (MRI-PI) and blood flow rate (MRI-flow, in mL/min). UtA-PI was also measured using US (US-PI). The primary outcome was a composite (COMP) of pre-eclampsia (PE) and/or small-for-gestational-age (SGA) neonate, and secondary outcomes were PE and SGA neonate individually. We assessed the ability of MRI-flow, MRI-PI and US-PI to distinguish between outcomes, and evaluated whether MRI-flow changed as gestation progressed. RESULTS: Following 4D flow postprocessing and exclusions from the analysis, 74 women had 4D flow MRI data analyzed for both UtAs. Of these, 18 developed a COMP outcome: three developed PE only, 11 had a SGA neonate only and four had both. A comparison of the COMP group vs the no-COMP group found no differences in maternal age, body mass index, nulliparity, gravidity or race. For 66 of the 74 subjects, US data were also available. In these subjects, both median MRI-PI (0.95 vs 0.70; P < 0.01) and median US-PI (0.95 vs 0.73; P < 0.01) were significantly increased in subjects in the COMP group compared with those in the no-COMP group. The UtA blood-flow rate, as measured by MRI, did not increase significantly from the second to the third trimester (median flow (interquartile range (IQR)), 543 (419-698) vs 575 (440-746) mL/min; P = 0.77), but it was significantly lower overall in the COMP compared with the no-COMP group (median flow (IQR), 486 (366-598) vs 624 (457-749) mL/min; P = 0.04). The areas under the receiver-operating-characteristics curves for MRI-flow, MRI-PI and US-PI in predicting COMP were not significantly different (0.694, 0.737 and 0.731, respectively; P = 0.87). CONCLUSIONS: 4D flow MRI can yield physiological measures of UtA blood-flow rate and PI that are associated with adverse pregnancy outcome. This may open up new avenues in the future to expand the potential of this technique as a robust tool with which to evaluate UtA hemodynamics in pregnancy. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

[Preliminary clinical observation of omalizumab therapy for moderate to severe asthma].

Objective: To observe the effectiveness, safety and management of omalizumab therapy for moderate to severe asthma in real-world clinical practice in China. Methods: This retrospective analysis involved 79 patients with moderate to severe asthma who received omalizumab therapy for at least 4 months in the First Affiliated Hospital of Guangzhou Medical University from March 2018 to April 2020. All participants were between 14 to 76 years old(median 50 years),including 30 males and 49 females. Data regarding the patients' clinical manifestations, eosinophil count, fractional exhaled nitric oxide (FeNO), lung function, oral corticosteroid dosage, and adverse reactions were collected before and after treatment. Paired t-test or non-parametric paired Wilcoxon analysis was used for pairwise comparison, Mann Whitney analysis for inter-group comparison, and Chi square test or Fisher test for inter-group comparison of count data. Results: The following changes were noted after 4 months of omalizumab thearpy. The patients' Asthma Control Test (ACT) scores increased from 17.0 (13.0-19.0) to 20.0 (18.0-24.0) points (P<0.001). The frequency of acute exacerbations(AE) decreased from 1.0 (0-1.0) to 0 (0-1.0) episodes every 4 months (P<0.001). The variation rate of the peak expiratory flow (PEF) decreased from 16.5 (13.8-27.3)% to 10.4 (6.0-16.2)% (P<0.001). The percent predicted value of PEF (PEFpred%) increased from 71.7 (51.4-91.6)% to 87.5 (65.2-105.5)% (P<0.001). The percent predicted value of the forced expiratory volume in 1 second(FEV1%pred) increased from 73.6 (53.9-90.8)% to 80.6 (68.7-91.8)% (P=0.007). The maintenance dose of oral corticosteroids (OCS) decreased from 12.0 (10.0-20.0) to 5.0 (0-17.5) mg/day (P=0.001). After 4 months of treatment, the response rate of the 79 patients with asthma was 74.7%. The response rate of patients with allergic asthma (77.3%) was higher than that of patients with non-allergic asthma (25.0%) (P=0.019). Among 5 patients who completed 1 year of treatment, the ACT score, frequency of AE, PEFpred%, variation rate of PEF and OCS maintenance dose were still improved after 1 year of treatment. Adverse reactions occurred in 3 patients (3.8%), for a total of 3 (0.6%) times. Stratified analysis showed that after 4 months of treatment, the improvement in the ACT score and the decrease in the PEF variation rate among patients who reached the recommended treatment dose (full dose) [3.0 (1.0-8.0) points, 6.5 (3.5-15.8) %] were significantly higher than those among patients who did not reach the recommended treatment dose (insufficient dose) [1.0 (-0.3-3.0) points, 2.9 (1.5-5.0) %] (P<0.05). Additionally, the treatment response rate in patients with a sufficient dose (80.0%) was higher than that in patients with an insufficient dose (50.0%) (P=0.019).The main factors associated with stopping treatment within 1 year despite a response to omalizumab was economic burden (70.3%), followed by satisfactory improvement by self-evaluation (21.9%) and less improvement in symptoms than expected (7.8%). Conclusion: Omalizumab was an effective treatment for moderate to severe allergic asthma with few adverse effects. The response rate was higher when the recommended injection dose was achieved. Financial difficulty was the main reason for stopping treatment within 1 year despite a good therapeutic response.

Absence of Evidence of Electrical Switching of the Antiferromagnetic Néel Vector.

Much theoretical and experimental attention has been focused on the electrical switching of the antiferromagnetic (AFM) Néel vector via spin-orbit torque. Measurements employing multiterminal patterned structures of Pt/AFM show recurring signals of the supposedly planar Hall effect and magnetoresistance, implying AFM switching. We show in this Letter that similar signals have been observed in structures with and without the AFM layer, and of an even larger magnitude using different metals and substrates. These may not be the conclusive evidence of spin-orbit torque switching of AFM, but the thermal artifacts of patterned metal structure on substrate. Large current densities in the metallic devices, beyond the Ohmic regime, can generate unintended anisotropic thermal gradients and voltages. AFM switching requires unequivocal detection of the AFM Néel vector before and after SOT switching.

[Clinical characteristics analysis of children with reversible posterior leukoen-cephalopathy syndrome during the treatment of hematological tumor].

OBJECTIVE: To analyze the clinical characteristics of patients with hematological tumor or disease before and after reversible posterior leukoen-cephalopathy syndrome (RPLS). METHODS: Five patients were both from Peking University First Hospital Pediatric Hematology-oncology Department in the period from March 2012 to March 2017. The gender, age, BMI, underlying diseases, with or without renal damage, hypertension family history, clinical manifestations of convulsions, hemoglobin, and blood pressure, serum sodium levels before and after convulsion, and other data of the children with RPLS were retrospectively analyzed. In the meantime, we followed up the five patients for 6 months to 66 months, kept a watchful eye on their original condition and the recovery of symptoms and signs of the nervous system. The relevant literature was reviewed. RESULTS: All of the subjects were females in school-age or pre-school age. The underlying diseases were malignant tumor associated with renal involvement or on one side of nephrectomy in 4 of these subjects, while the other one was refractory autoimmune hemolytic anemia. All of the subjects suffered from mild or moderate anemia. The day before RPLS occurred they received chemotherapy made up with cyclophosphamide, vincristine, and actinomycin-D, or the therapy with cyclosporin A and glucocorticoid. The clinical manifestations were afebrile convulsion after getting up in the mooring or in the afternoon. We observed elevation of blood pressure and cutting down of serum sodium compared with themselves. All of the cases recovered soon after management with diazepam, furosemide and amlodipine besylate. Four of them had a good outcomes and did not remain any sequela, while only one girl became childish in emotion and behavior, and then returned gradually to normal two years later. However, by long-term follow-up, the elevation of blood pressure was mainly reviewed in literature. CONCLUSION: The patients attacked by RPLS, with hematology or oncology cases, could have the underlying disease of renal damage and anemia. Blood pressure elevation and serum sodium falling down at the same time may play an important role during the occurrence of RPLS. Remaining stable of blood pressure and electrolyte level together will possibly reduce or mitigate RPLS.

[Pathological insights of radiotherapy-related damage to surgical margin after preoperative radiotherapy in patients with rectal cancer].

Objective: To investigate the effect of irradiation to anastomosis from preoperative radiotherapy for patients with rectal cancer by studying the pathological changes. Methods: In this retrospective study, patients enrolled in the FOWARC study from January 2011 to July 2014 in the Sixth Affiliated Hospital of Sun Yat-Sen University were included. In the FOWARC study, enrolled patients with local advanced rectal cancer were randomly assigned to receive either neoadjuvant chemo-radiotherapy or chemotherapy. Among these patients, 23 patients were selected as radiation proctitis (RP)group, who fulfilled these conditions: (1) received neoadjuvant chemo-radiotherapy followed by sphincter-preserving surgery; (2) developed radiation proctitis as confirmed by preoperative imaging diagnosis; (3) had intact clinical samples of surgical margins. Twenty-three patients who had received neoadjuvant chemo-radiotherapy but without development of radiation proctitis were selected as non-radiation proctitis (nRP) group. Meanwhile, 23 patients received neoadjuvant chemotherapy only were selected as neoadjuvant chemotherapy (CT) group. Both nRP and CT cases were selected by ensuring the basic characteristics such as sex, age, tumor site, lengths of proximal margin and distal margin all maximally matched to the RP group. Both proximal and distal margins were collected for further analysis for all selected cases. Microscopy slices were prepared for hematoxylin & eosin staining and Masson staining to show general pathological changes, and also for immunohistochemistry with anti-CD-34 as primary antibody to reveal the microvessel. Microvessel counting in submucosal layer and proportion of macrovessel with stenosis were used to evaluate the blood supply of the proximal and distal end of anastomosis. A modified semi-quantitative grading approach was used to evaluate the severity of radiation-induced injury. Either ANOVA analysis, Kruskal-Wallis rank-sum test or χ(2) test was used for comparison among three groups, and Mann-Whitney U test was used for comparison between two groups. Results: Compared to group of neoadjuvant chemotherapy only, patients receiving neoadjuvant chemo-radiotherapy had lower microvessel count in both proximal and distal margins (M(Q(R)): proximal, 25.5 (19.6) vs. 50.0 (25.0), Z=3.915, P=0.000; distal, 20.5 (17.5) vs. 49.0 (28.0), Z=3.558, P=0.000), higher proportions of macrovessel with stenosis (proximal, 9.5% (23.8%) vs. 0, Z=3.993, P=0.000; distal, 11.5%(37.3%) vs. 0 (2.0%), Z=2.893, P=0.004), higher histopathologic score (proximal, 4.0 (2.0) vs. 1.0 (2.0), Z=6.123, P=0.000; distal, 5.0 (3.0) vs. 2.0 (1.0), Z=4.849, P=0.000). In patients receiving neoadjuvant chemo-radiotherapy, compared to nRP group, RP group had lower microvessel count in both proximal and distal margins (proximal, 19.0 (23.0) vs. 30.4 (38.0), Z=2.845, P=0.004; distal, 19.0 (13.0) vs. 30.0(29.1), Z=2.022, P=0.043), higher proportions of macrovessel with stenosis (proximal, 23.0% (40.0%) vs. 0(11.0%), Z=3.248, P=0.001; distal, 27.0% (45.0%) vs. 3.0% (19.0%), Z=2.164, P=0.030). Rate of anastomotic leakage for CT, nRP and RP group were 8.7% (2/23), 30.4% (7/23), and 52.2% (12/23), and the differences among three groups were statistically significant (χ(2)=10.268, P=0.007). Conclusion: Radiation-induced injury existed on both margins of the resected rectal site after preoperative radiotherapy, and those diagnosed as radiation proctitis had more severe microvascular injury.

[Non-invasive fibrosis indexes in predicting acute liver function deterioration after transcatheter arterial chemoembolization].

OBJECTIVE: To investigate the ability of two non-invasive fibrosis indexes-APRI, i. e. aspartate transaminase (AST) to platelet (PLT) ratio index, and fibrosis index based on the 4 factors (FIB-4)score in predicting ALFD in patients with unresectable primary HCC and underwent TACE. METHODS: Clinical data of those patients treated with TACE in Department of Interventional Radiology of the Center from Jan 2010 to Aug 2014 were investigated retrospectively. A total of 366 cases were enrolled after randomized selection, 62 (18.5%) of which developed ALFD after TACE. Child-Pugh score, APRI and FIB-4 score in every case were calculated, receiver operating characteristic (ROC) curve of each model were performed and the predictive abilities of them were assessed by area under the curve (AUC), positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity. RESULTS: The AUC of Child-Pugh score, APRI and FIB-4 score were 0.783, 0.752 and 0.758 respectively, while the difference had no significance in statistics, indicating that predictive accuracies of them were similar. APRI≤1.15 and FIB-4≤3.08 had better NPV (90.6% and 93.6%) and sensitivity (65.6% and 80.0%) than Child-Pugh score>6 (NPV=85.8%, sensitivity=27.4%), PPV and specificity of them are 35.7%, 32.9%, 89.5% and 73.7%, 64.2%, 99.3% respectively. CONCLUSION: Comparing to Child-Pugh score, APRI and FIB-4 score have similar accuracy but better NPV and sensitivity in predicting post-TACE ALFD. Thereafter they are good for selection of low-risk patients for TACE treatment. Candidates with an APRI≤1.15 or a FIB-4≤3.08 or in Child-Pugh a stage are unlikely to develop ALFD thus could receive TACE safely.

[Radiofrequency ablation combined with systemic chemotherapy in the management of nasopharyngeal carcinoma with liver metastasis].

Objective: To determine the treatment efficacy of systemic chemotherapy combined with sequential CT-guided radiofrequency ablation (chemo-RFA) in the management of nasopharyngeal carcinoma (NPC) with liver metastasis. Methods: A total of 427 NPC patients diagnosed with liver metastasis at Sun Yat-sen University Cancer Center between January 2000 and December 2013 were enrolled. Of the patients, 340 cases were male, 87 cases were female, the median age was 45 years (range 18-80 years), all patients received systemic chemotherapy and part of them also received RFA treatment. Patients were evaluated for response every two cycles during systemic chemotherapy and then every three months until death. One-to-one matched pairs between chemo-RFA group with chemo-only group were generated using propensity score matching; survival analysis was further conducted. Results: Of all the enrolled patients, 56 patients (13.1%) received combined treatment, 371 patients (86.9%)received chemotherapy alone. After propensity score matching, 56 pairs of well-matched liver metastatic NPC patients were selected from different treatment groups. The 1-, 3-, 5- year overall survival (OS) rates for chemo-RFA group were 89.2%, 45.5% and 32.5% and chemo-only group were 77.1%, 27.5% and 4.8% respectively; the 1-, 3-, 5- year progression-free survival (PFS) rates for chemo-RFA group were 64.0%, 25.4% and 10.7% and chemo-only group were 44.1%, 5.5% and 5.5% respectively.The adjusted hazard ratio in OS and PFS of the choice for chemo-RFA approach to chemo-only was HR 0.43, 95% CI 0.25-0.73 and HR 0.44, 95% CI 0.28-0.71 respectively. Conclusion: CT-guided RFA combined with chemotherapy approach could improve the survival rate for NPC patients with liver metastasis.

Safety and efficacy of transarterial chemoembolization plus sorafenib for hepatocellular carcinoma with portal venous tumour thrombus.

AIM: To evaluate the safety and efficacy of combined therapy with transarterial chemoembolization (TACE) and sorafenib for hepatocellular carcinoma (HCC) with portal venous tumour thrombus (PVTT). MATERIALS AND METHODS: This study was approved by the institutional review board. From May 2009 to May 2012, 170 consecutive patients were newly diagnosed with advanced-stage HCC and treated with TACE plus sorafenib. Among them, 41 patients with PVTT were retrospectively enrolled in the study. The adverse events (AEs), overall survival (OS), time to progression (TTP), and prognostic factors were analysed. Statistical analysis was performed with the Kaplan-Meier method using the log-rank test and Cox regression models. RESULTS: The most common AEs were hand-foot skin reaction related to sorafenib and fever related to TACE. Procedure-related mortality and grade 4 AEs were not observed. Grade 3 AEs were observed in five patients. During the median follow-up period of 13.5 months (range 1.4-45 months), the 6-month and 1-year survival rates were 87.7% and 53.6%, respectively. The median OS was 13 months (range 1.4-44.8 months), and the median TTP was 7 months (range 1-18.6 months). The Child-Pugh class (p = 0.022), extrahepatic metastasis (p = 0.009), and gross morphological type (nodular type versus diffuse type; p = 0.008) were prognostic factors related to OS in the multivariate analysis. CONCLUSION: TACE plus sorafenib in an interrupted therapeutic scheme was well tolerated and might improve OS for HCC patients with PVTT, especially in those with Child-Pugh class A, no extrahepatic metastasis, or nodular-type HCC.

Tacrolimus abrogates TGF-ß1-induced type I collagen production in normal human fibroblasts through suppressing p38MAPK signalling pathway: implications on treatment of chronic atopic dermatitis lesions.

BACKGROUND: Atopic dermatitis (AD) is a commonly encountered inflammatory skin disease. Although acute lesions of acute AD are characterized by intense inflammation, the hallmarks of chronic AD lesions include lichenified fibrosis and thickening of the upper dermis. The increased expression of transforming growth factor beta 1 (TGF-ß1), a well-known fibrogenic cytokine, is observed in chronic AD lesions. Tacrolimus (FK506) ointment has been reported to be effective for treating AD as well as some TGF-ß1-induced fibrotic diseases. OBJECTIVES: To evaluate the effect of tacrolimus on TGF-ß1-stimulated cultured normal human dermal fibroblasts and explore the potential signalling pathways involved. METHODS: Fibroblasts cultured from healthy adult human foreskins were treated with TGF-ß1 with or without tacrolimus. The impact on cell viability and proliferation were assessed by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and BrdU incorporation assay respectively. Reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA) and western blotting were performed to evaluate the relevant expressions of mRNA or proteins in fibroblasts. RESULTS: Our results revealed that the increased expressions of transforming growth factor-ß receptor I (TGF-ßRI) and TGF-ßRII in TGF-ß1-treated fibroblasts were suppressed by tacrolimus treatment. In addition, tacrolimus significantly inhibited fibroblast proliferation enhanced by TGF-ß1. TGF-ß1 increased type I collagen production, and this enhancing effect was suppressed by tacrolimus. The down-regulation of MMP-1 and up-regulation of TIMP-1 induced by TGF-ß1 were reversed by tacrolimus. The increase in phosphorylated p38 mitogen-activated protein kinase (p38MAPK) expression stimulated by TGF-ß1 was down-regulated by tacrolimus. Moreover, the fibroblasts treated with p38MAPK inhibitor significantly reduced type I collagen expression induced by TGF-ß1. CONCLUSIONS: The present results demonstrated that tacrolimus significantly inhibited physiological functions of fibroblasts enhanced by TGF-ß1 in vitro. Clinically, we propose that topical tacrolimus may not only reduce AD recurrence but also ameliorate dermal fibrosis often seen in chronic AD lesions.

[Clinical analysis of 11 cases multisystem inflammatory syndrome associated with SARS-CoV-2 Omicron variant infection in children].

Objective: To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection. Methods: A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study. Results: The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months. Conclusions: MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Epithelial-mesenchymal transition biomarkers and support vector machine guided model in preoperatively predicting regional lymph node metastasis for rectal cancer.

BACKGROUND: Current imaging modalities are inadequate in preoperatively predicting regional lymph node metastasis (RLNM) status in rectal cancer (RC). Here, we designed support vector machine (SVM) model to address this issue by integrating epithelial-mesenchymal-transition (EMT)-related biomarkers along with clinicopathological variables. METHODS: Using tissue microarrays and immunohistochemistry, the EMT-related biomarkers expression was measured in 193 RC patients. Of which, 74 patients were assigned to the training set to select the robust variables for designing SVM model. The SVM model predictive value was validated in the testing set (119 patients). RESULTS: In training set, eight variables, including six EMT-related biomarkers and two clinicopathological variables, were selected to devise SVM model. In testing set, we identified 63 patients with high risk to RLNM and 56 patients with low risk. The sensitivity, specificity and overall accuracy of SVM in predicting RLNM were 68.3%, 81.1% and 72.3%, respectively. Importantly, multivariate logistic regression analysis showed that SVM model was indeed an independent predictor of RLNM status (odds ratio, 11.536; 95% confidence interval, 4.113-32.361; P<0.0001). CONCLUSION: Our SVM-based model displayed moderately strong predictive power in defining the RLNM status in RC patients, providing an important approach to select RLNM high-risk subgroup for neoadjuvant chemoradiotherapy.

Low-loss terahertz metamaterial from superconducting niobium nitride films.

This paper reports a type of low Ohmic loss terahertz (THz) metamaterials made from low-temperature superconducting niobium nitride (NbN) films. Its resonance properties are studied by THz time domain spectroscopy. Our experiments show that its unloaded quality factor reaches as high as 178 at 8 K with the resonance frequency at around 0.58 THz, which is about 24 times that of gold metamaterial at the same temperature. The unloaded quality factor keeps at a high level, above 90, even when the resonance frequency increases to 1.02 THz, which is close to the gap frequency of NbN film. All these experimental observations fit well into the framework of Bardeen-Copper-Schrieffer theory and equivalent circuit model. These new metamaterials offer an efficient way to the design and implementation of high performance THz electronic devices.

FK506 inhibits the enhancing effects of transforming growth factor (TGF)-ß1 on collagen expression and TGF-ß/Smad signalling in keloid fibroblasts: implication for new therapeutic approach.

BACKGROUND: Keloid is a unique proliferative disorder of fibroblasts resulting from derailment of the typical wound healing process. Due to lack of animal models for therapeutic testing, treatment of keloids remains a clinical challenge. Transforming growth factor (TGF)-ß1-related signalling plays a key role in keloid formation. As tacrolimus (FK506) has been reported to inhibit the effects of TGF-ß1 on cultured fibroblasts, we hypothesized that FK506 may be useful in treating keloids. OBJECTIVES: To explore the effects of FK506 on TGF-ß1-stimulated keloid fibroblasts (KFs) in terms of proliferation, migration and collagen production and to investigate the regulatory pathways involved. METHODS: Fibroblasts derived from keloids were treated with TGF-ß1 with or without FK506. Relevant assays including 5-bromo-2'-deoxyuridine incorporation assay, in vitro scratch assay, reverse transcription-polymerase chain reaction (PCR), quantitative PCR and Western blotting were performed. RESULTS: The proliferation and migration of KFs were significantly higher than those of normal fibroblasts. FK506 markedly inhibited KF proliferation, migration and collagen production enhanced by TGF-ß1. The increase in TGF-ß receptor I and II expression in TGF-ß1-treated KFs was suppressed by FK506 treatment. TGF-ß1 increased the phosphorylation of Smad2/3 and Smad4 in KFs, and this enhancing effect was abrogated by FK506. In addition, FK506 significantly increased the expression of Smad7 which was suppressed by TGF-ß1 treatment. CONCLUSIONS: Our results demonstrate that FK506 effectively blocks the TGF-ß/Smad signalling pathway in KFs by downregulation of TGF-ß receptors and suggest that FK506 may be included in the armamentarium for treating keloids.

NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients.

Aims: End-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine. Methods and results: The AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths. Conclusions: Our findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.