Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial chemoembolization for massive unresectable hepatocellular carcinoma:a prospective non.randomized study

Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on large(> 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy(HAIC)might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX(mFOLFOX) regimen and those ofTACE in patients with massive unresectable HCC.Methods: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen(oxaliplatin, 85 mg/m^2 intra-arterial infusion; leucovorin,400 mg/m^2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m^2 continuous infusion)every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression(TTP), and safety were assessed.Results: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group(52.6% vs. 9.8%, P < 0.001;83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months(hazard radio[HR] = 2.35,95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection(10 vs. 3,P = 0.033). The proportions of grade 3-4 adverse events(AE) and serious adverse events(SAE) were lower in the HAIC group than in the TACE group(grade 3-4 AEs: 13 vs. 27, P = 0.007;SAEs: 6 vs. 15,p = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent(10 vs. 2,P = 0.026).Conclusions: HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC.

Potential application of neogalactosylalbumin in positron emission tomography evaluation of liver function

AIM To investigate the evaluation of neogalactosylalbumin(NGA) for liver function assessment based on positron emission tomography technology.METHODS Female Kunming mice were assigned randomly to two groups: fibrosis group and normal control group. A murine hepatic fibrosis model was generated by intraperitoneal injection of 10% carbon tetrachloride(CCl_4) at 0.4 m L every 48 h for 42 d. ^(18)F-labeled NGA([^(18)F]FNGA) was synthesized and administered at a dosage of 3.7 MBq/mouse to both fibrosis mice and normal control mice. Distribution of [^(18)F]FNGA amongst organs was examined, and dynamic scanning was performed. Parameters were set up to compare the uptake of tracers by fibrotic liver and healthy liver. Serologic tests for liver function were also performed.RESULTS The liver function of the fibrosis model mice was significantly impaired by the use of CCl_4. In the fibrosis model mice, hepatic fibrosis was verified by naked eye assessment and pathological analysis. [^(18)F]FNGA was found to predominantly accumulate in liver and kidneys in both control group(n = 21) and fibrosis group(n = 23). The liver uptake ability(LUA), peak time(T_p), and uptake rate(LUR) of [^(18)F]FNGA between healthy liver(n = 8) and fibrosis liver(n = 10) were significantly different(P < 0.05, < 0.01, and < 0.05, respectively). LUA was significantly correlated with total serum protein level(TP)(P < 0.05). T_p was significantly correlated with both TP and glucose(Glu) concentration(P < 0.05 both), and LUR was significantly correlated with both total bile acid and Glu concentration(P < 0.01 and < 0.05, respectively).CONCLUSION[^(18)F]FNGA mainly accumulated in liver and remained for sufficient time. Functionally-impaired liver showed a significant different uptake pattern of [^(18)F]FNGA compared to the controls.

使用mFOLFOX进行肝动脉灌注化疗与肝动脉化疗栓塞术治疗不可切除的巨块型肝细胞癌:一项前瞻性非随机研究

背景与目的肝动脉化疗栓塞术(transarterial chemoembolization,TACE)被推荐为巴塞罗那临床肝癌(Barcelona Clinic Liver Cancer,BCLC)A–B期的不可切除肝细胞癌(hepatocellular carcinoma,HCC)的标准治疗方法。然而,TACE对巨大(≥10 cm)A–B期HCC的疗效远不能令人满意,肝动脉灌注化疗(hepatic artery infusion chemotherapy,HAIC)被认为可能是该疾病更好的一线治疗方法。因此,我们比较了使用改良的FOLFOX方案(modified FOLFOX,mFOLFOX)进行HAIC与TACE治疗不可切除的巨块型HCC的安全性和有效性。方法一项前瞻性非随机II期研究在患有不可切除的巨块型HCC患者中开展。治疗方法为使用mFOLFOX方案每3周进行一次HAIC(奥沙利铂,85 mg/m^2动脉灌注;甲酰四氢叶酸,400 mg/m^2动脉灌注;氟尿嘧啶,400 mg/m^2静脉推注和2400 mg/m^2持续静脉滴注),使用50 mg表柔比星、50 mg洛铂、6 mg丝裂霉素和碘油聚乙烯醇颗粒进行TACE。评估了肿瘤反应、肿瘤进展时间(time-to-progression,TTP)和安全性。结果本研究共招募了79例患者:HAIC组38例,TACE组41例。HAIC组的部分缓解率和疾病控制率均高于TACE组(52.6%vs.9.8%,P<0.001;83.8%vs.52.5%,P=0.004)。HAIC和TACE组的中位TTP分别为5.87和3.6个月[风险比(hazard ratio,HR)=2.35,95%置信区间(confidence interval,CI)=1.16–4.76,P=0.015)]。HAIC组比TACE组有更多的患者接受了手术切除(10 vs.3,P=0.033)。HAIC组中3–4级不良事件(adverse events,AE)和严重不良事件(serious adverse events,SAE)发生数均低于TACE组(3–4级AE:13 vs.27,P=0.007;SAE:6 vs.15,P=0.044)。因无法耐受的治疗相关不良事件或撤回知情同意书而导致治疗提前终止的患者在TACE组中多于HAIC组(10 vs.2,P=0.026)。结论与TACE相比,使用mFOLFOX进行HAIC表现出显著优势的治疗反应性和更低的毒性。对于不可切除的巨块型HCC,HAIC可能是一种可行且有前景的一线治疗方法。

Prognostic value of the neutrophil-to-lymphocyte ratio for hepatocellular carcinoma patients with portal/hepatic vein tumor thrombosis

AIM To investigate whether the preoperative neutrophil-tolymphocyte ratio(NLR) could predict the prognosis of hepatocellular carcinoma(HCC) patients with portal/hepatic vein tumor thrombosis(PVTT/HVTT) after hepatectomy.METHODS The study population included 81 HCC patients who underwent hepatectomy and were diagnosed with PVTT/HVTT based on pathological examination. The demographics, laboratory analyses, and histopathology data were analyzed.RESULTS Overall survival(OS) and disease-free survival(DFS) were determined in the patients with a high(> 2.9) and low(≤ 2.9) NLR. The median OS and DFS duration in the high NLR group were significantly shorter than those in the low NLR group(OS: 6.2 mo vs 15.7 mo, respectively, P = 0.007; DFS: 2.2 mo vs 3.7 mo, respectively, P = 0.039). An NLR > 2.9 was identified as an independent predictor of a poor prognosis of OS(P = 0.034, HR = 1.866; 95%CI: 1.048-3.322) in uni-and multivariate analyses. Moreover, there was a significantly positive correlation between the NLR and the Child-Pugh score(r = 0.276, P = 0.015) and the maximum diameter of the tumor(r = 0.435, P < 0.001). Additionally, the NLR could enhance the prognostic predictive power of the CLIP score for DFS in these patients. CONCLUSION The preoperative NLR is a prognostic predictor after hepatectomy for HCC patients with PVTT/HVTT. NLR > 2.9 indicates poorer OS and DFS.

Study of a ceramic burner for shaftless stoves

A multi-burner-port annular flameless ceramic burner （MAFCB） of the shaftless stove for blast furnaces was designed. The characteristics of pressure drop, homogeneousness of the flows at burner ports, and distribution of the flows in the chambers and joint were studied by cold model experiments. This type of ceramic burner was successfully applied in 6# blast furnace at Liuzhou Iron ＆ Steel Co. Ltd. （LISC） and this practice proved that it could be used in the hot blast stove and other stoves with a higher efficiency and a higher steadiness of hot blast temperature at 1200℃. With the combustion of blast furnace gas alone, the thermal efficiency was up to 78.95%, saving energy remarkably.

Outcome Assessment of Z-shaped Osteotomy in the Management of Humeral Shaft Nonunion Secondary to Failed Plate Osteosynthesis

Restoration of fracture alignment by osteotomy is crucial for the management of humeral nonunion. In the present study, we introduced a new way of osteotomy (Z-shaped) in treating humeral shaft nonunion secondary to failed plate osteosynthesis. Clinical data of 24 patients with humeral shaft nonunion following implant failure (from 2010 to 2014) were retrospectively evaluated. These patients underwent Z-shaped osteotomy in revision surgery after the initial surgery, plate osteosynthesis, was failed. Outcomes were evaluated using visual analogue scale (VAS) and Constant and Murley score. Repeated analysis of variance (ANOVA) was used for statistical analysis. Patients were followed up for a minimum of 24 months (26.83±4.33 months). The operative time was 102.33±10.16 min, and hospital stay averaged 9.75±2.13 days. All patients achieved clinical union at the latest follow-up. Complications included radial palsy (n=1) and superficial wound infection (n=1). The postoperative VAS scores decreased significantly compared to preoperative score (F=257.99, P<0.01). Constant and Murley score increased and reached 81.33±0.95 at 24 months' follow-up 0=247.35, P<0.01). Among all the cases, 15 cases were graded as "excellent", and 9 as "good". In conclusion, Z-shaped osteotomy was easy to perform, and it provided additional medial support with more bone contact areas. Revision surgery using locking plate and Z-shaped osteotomy achieved high union rate and improved functional outcome. It was a reasonable and safe option for treating humeral nonunion following implant failure.

New insights into the heat responses of grape leaves via combined phosphoproteomic and acetylproteomic analyses

Heat stress is a serious and widespread threat to the quality and yield of many crop species,including grape(Vitis vinifera L.),which is cultivated worldwide.Here,we conducted phosphoproteomic and acetylproteomic analyses of leaves of grape plants cultivated under four distinct temperature regimes.The phosphorylation or acetylation of a total of 1011 phosphoproteins with 1828 phosphosites and 96 acetyl proteins with 148 acetyl sites changed when plants were grown at 35℃,40℃,and 45℃in comparison with the proteome profiles of plants grown at 25℃.The greatest number of changes was observed at the relatively high temperatures.Functional classification and enrichment analysis indicated that phosphorylation,rather than acetylation,of serine/arginine-rich splicing factors was involved in the response to high temperatures.This finding is congruent with previous observations by which alternative splicing events occurred more frequently in grapevine under high temperature.Changes in acetylation patterns were more common than changes in phosphorylation patterns in photosynthesis-related proteins at high temperatures,while heat-shock proteins were associated more with modifications involving phosphorylation than with those involving acetylation.Nineteen proteins were identified with changes associated with both phosphorylation and acetylation,which is consistent with crosstalk between these posttranslational modification types.

Role of miR-132/methyl-CpG-binding protein 2 in the regulation of neural stem cell differentiation

Methyl-CpG-binding protein 2(MeCP2)is a well-known transcription repressor,and mutations in MECP2 cause serious neurological disorders.Many studies have suggested that Me CP2 is involved in neural maturation only,and have not reported its role in neural stem cell differentiation.In the present study,we investigated this possible role of Me CP2 in neural stem cells.We used two different differentiation methods to explore how Me CP2 influences neural stem cell differentiation.When we transfected Me CP2-overexpressing lentivirus into neural stem cells,astrocytic differentiation was impaired.This impaired astrocytic differentiation occurred even in conditions of 20%fetal bovine serum,which favored astrocytic differentiation.In addition,mi R-132 had the largest expression change after differentiation among several central nervous system related mi RNAs.A luciferase assay confirmed that mi R-132 directly targeted Me CP2,and that mi R-132 was able to reduce Me CP2 expression at both the RNA and protein levels.The upregulation of mi R-132 by mi RNA mimics promoted astrocytic differentiation,which was fully recovered by Me CP2 overexpression.These results indicate that mi R-132 regulates cell lineage differentiation by reducing Me CP2.The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital of Tong Ji University,China(approval No.SHDSYY-2018-4748)on March 10,2018.

Inflammation and cutaneous nervous system involvement in hypertrophic scarring

This study aimed to use a mouse model of hypertrophic scarring by mechanical loading on the dorsum of mice to determine whether the nervous system of the skin and inflammation participates in hypertrophic scarring. Results of hematoxylin-eosin and immunohistochemical staining demonstrated that inflammation contributed to the formation of a hypertrophic scar and increased the nerve density in scar tissue.Western blot assay verified that interleukin-13 expression was increased in scar tissue. These findings suggest that inflammation and the cutaneous nervous system play a role in hypertrophic scar formation.

单发肝细胞癌合并微血管侵犯患者根治性切除术后辅助经导管动脉化疗栓塞治疗的疗效和安全性:一项随机临床试验

背景与目的单发肝细胞癌(hepatocellular carcinoma,HCC)合并微血管侵犯(microvascular invasion,MVI)患者根治性切除术后的最佳辅助治疗方案一直存有争议。本试验旨在评估肝切除术后辅助经导管动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)与单纯肝切除术对直径≥5 cm单发HCC合并MVI患者的疗效和安全性。方法在本随机、开放性、III期试验中,将直径≥5 cm单发HCC合并MVI患者随机分为2组(1∶1):在肝切除术后接受1–2个周期的辅助TACE治疗(肝切除–TACE组)或单纯接受肝切除(单纯肝切除组)。主要终点是无病生存期(disease-free survival,DFS),次要终点包括总生存期(overall survival,OS)和不良事件。结果在2009年6月1日至2012年12月31日期间,共纳入250例患者,随机分为肝切除–TACE组(n=125)或单纯肝切除组(n=125)。两组患者的临床病理特征相似。从随机开始的中位随访时间为37.5个月(四分位距为18.3–48.2个月)。肝切除–TACE组的中位DFS显著长于单纯肝切除组[17.45个月(95%置信区间,confidence interval,CI:11.99–29.14)vs. 9.27个月(95%CI:6.05–13.70),风险比(hazard ratio,HR)=0.70(95%CI:0.52–0.95),P=0.020]。肝切除–TACE组中位OS也显著长于单纯肝切除组[44.29个月(95%CI:25.99–62.58)vs. 22.37个月(95%CI:10.84–33.91),HR=0.68(95%CI:0.48–0.97),P=0.029]。治疗相关不良事件在肝切除–TACE组中更为多见,虽然这些不良事件一般都是轻度和可控的。两组中最常见的3级或4级不良事件为中性粒细胞减少和肝功能异常。结论对于直径≥5 cm单发HCC合并MVI患者,根治术后进行辅助TACE治疗是一种合适的选择,且毒性是可接受的。

Experimental Study on Double Resonance Optical Pumping Spectroscopy in a Ladder-Type System of ^(87)Rb Atoms

Double resonance optical pumping spectroscopy has an outstanding advantage of high signal-to-noise ratio, thus having potential applications in precision measurement. With the counter propagated 780nm and 776nm laser beams acting on a rubidium vapor cell, the high resolution spectrum of 5S1/2 - 5P3/2 - 5D5/2 ladder-type transition of ST Rb atoms is obtained by monitoring the population of the 5S1/2 ground state. The dependence of the spectroscopy lineshape on the probe and coupling fields are comprehensively studied in theory and experiment. This research is helpful for measurement of fundamental physical constants by high resolution spectroscopy.

A Study on the Relationship Among Nurses' Practice Environment, Safety Attitude, and Occupational Wellbeing

Objective:To investigate the status quo of nursing practice environment,nurses'safety attitude,and occupational well-being,as well as to explore the relationship among the three,so as to provide reference for formulating and implementing corresponding measures.Methods:A cross-sectional survey was conducted from October 2021 to December 2021.A total of 1,939 nurses from five tertiary hospitals in a city were surveyed using the Nurses5 Practice Environment Assessment Scale,Safety Attitudes Questionnaire,and Medical WorkersJ Occupational Wellbeing Scale.The data were analyzed using SPSS 22.0.Results:The total score of nurses5 practice environment was 68.81±27.79 points,which is at a relatively general level;the total score of nurses'safety attitude was 111.28±14.38 points,which is at a moderate level;and the total score of occupational well-being was 62.43±28.17 points,which is relatively high.There was a significant positive correlation between nurses'practice environment and their safety attitudes and occupational well-being(p<0.05).Conclusion:Nurses are the main human resources in hospitals,and their practice environment is closely related to patient safety and their work enthusiasm.An unhealthy practice environment not only affects the quality of care,which leads to patient safety issues,but also their job satisfaction.Nurse managers are encouraged to implement targeted interventions in advance to improve nurses,practice environment,strengthen safety attitudes,and enhance the professional wellbeing of nurses.

Adjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety

Background:The optimal strategy for adjuvant therapy after curative resection for hepatocellular carcinoma(HCC)patients with solitary tumor and microvascular invasion(MVI)is controversial.This trial evaluated the efficacy and safety of adjuvant transcatheter arterial chemoembolization(TACE)after hepatectomy versus hepatectomy alone in HCC patients with a solitary tumor≥5 cm and MVI.Methods:In this randomized,open-labeled,phase III trial,HCC patients with a solitary tumor≥5 cm and MVI were randomly assigned(1:1)to receive either 1-2 cycles of adjuvant TACE after hepatectomy(Hepatectomy-TACE)or hepatectomy alone(Hepatectomy Alone).The primary endpoint was disease-free survival(DFS);the secondary end-points included overall survival(OS)and adverse events.Results:Between June 1,2009,and December 31,2012,250 patients were enrolled and randomly assigned to the Hepatectomy-TACE group(n=125)or the Hepatectomy Alone group(n=125).Clinicopathological characteristics were balanced between the two groups.The median follow-up time from randomization was 37.5 months[interquartile range 18.3-48.2 months].The median DFS was significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group[17.45 months(95%confidence interval[CI]11.99-29.14)vs.9.27 months(95%CI 6.05-13.70),hazard ratio[HR]=0.70(95%CI 0.52-0.95),P=0.020],respectively.The median OS was also significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group[44.29 months(95%CI 25.99-62.58)vs.22.37 months(95%CI 10.84-33.91),HR=0.68(95%CI 0.48-0.97),P=0.029].Treatment-related adverse events were more frequently observed in the Hepatectomy-TACE group,although these were generally mild and manageable.The most common grade 3 or 4 adverse events in both groups were neutropenia and liver dysfunction.Conclusion:Hepatectomy followed by adjuvant TACE is an appropriate option after radical resection in HCC patients with solitary tumor≥5 cm and MVI,with acceptable toxicity.

Analytical solutions to ground settlement induced by ground loss and construction loadings during curved shield tunneling

This paper focuses on the ground settlement induced by the construction of a curved shield tunnel.Ground loss and construction loadings are the two factors causing ground settlement,and two corresponding analytical models were developed.First,the ground settlement due to ground loss was analyzed based on 3D image theory.The"integrative gap at shield tail"(IGST)and overcutting gap of a curved tunnel were considered.Second,the ground settlement due to construction loadings was analyzed by modifying Mindlin's solutions.The additional thrust,frictional force,and grouting pressure were considered.Subsequently,a case study and a parameter analysis were conducted.Finally,the obtained solutions were compared with a classical analytical solution,numerical simulations,and monitored results.The proposed model could effectively predict the ground settlement in-duced during curved shield tunneling.

The Scheme to Determine the Convergence Term of the Galerkin Method for Dynamic Analysis of Sandwich Plates on Nonlinear Foundations

The vibration of a plate resting on elastic foundations under a moving load is of great significance in the design of many engineering fields,such as the vehicle-pavement system and the aircraft-runway system.Pavements or runways are always laminated structures.The Galerkin truncation method is widely used in the research of vibration.The number of truncation terms directly affects the convergence and accuracy of the response results.However,the selection of the number of truncation terms has not been clearly stated.A nonlinear viscoelastic foundation model under a moving load is established.Based on the natural frequency of linear undisturbed derivative systems,the truncation terms are used to determine the convergence of vibration response.The criterion for the convergence of the Galerkin truncation term is presented.The scheme is related to the natural frequency with high efficiency and practicability.Through the dynamic response of the sandwich beam under a moving load,the feasibility of the scheme is verified.The effects of different system parameters on the scheme and the truncation convergence of dynamic response are presented.The research in this paper can be used as a reference for the study of the vibration of elastic foundation plates.Especially,the model established and the truncation analysis method proposed are helpful for studying the vibration of vehicle-pavement system and related systems.

High-Sensitivity Detection of Fruit Tree Viruses UsingBacterial Magnetic Particles

Prunus necrotic ring spot virus （PNRSV） and grapevine fanleaf virus （GFLV） were detected by fluoroimmunoassay using bacterial magnetic particles （BMPs）, and a double antibody sandwich enzyme linked immunosorbent assay （DAS-ELISA）. For the fluoroimmunoassay, fluorescein isothiocyanate labeled anti-PNRSV antibody or anti-GFLV antibody was conjugated onto BMPs of Magnetospirillum gryphiswaldense MSR-1. With this method, a very low minimum antigen concentration （1×10^6 dilution of the original sample concentration） could be detected. Using DAS-ELISA, the minimum antigen detection concentration was the original sample concentration. Thus, comparing these two methods, a BMP-based method could increase the sensitivity up to six orders of magnitude （10^6） higher than an ELISA-based method of detection PNRSV and GFLV.

Research status and prospect of direct strip casting manufactured lowcarbon microalloyed steel

Direct strip casting(DSC)is one of the cutting-edge technologies for the steel industry in the twenty-first century.Under the background of carbon peak and carbon neutrality,DSC technology has a bright future of applications as it requires less production time and space with reduced energy consumption.Owing to its sub-rapid cooling rate during solidification and low reduction during hot rolling,DSC process exhibits a series of unique physical metallurgy characteristics.The process characteristics of DSC process and the microstructural evolution during the thermomechanical processing of low-carbon microalloyed steel are reviewed.The effects of hot rolling,cooling,coiling temperatures and microalloying elements on the microstructure and mechanical properties are then discussed.Finally,the future development orientations of DSC technology are suggested to fully utilize its unique features for the enhancement of its competitiveness and for the promotion of carbon neutrality of the steel industry.