Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma:A network meta-analysis

BACKGROUND With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concentrations.However,there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study.The outcomes of interest comprised overall survival(OS),progression-free survival(PFS),tumor response and adverse events.Hazard ratios(HR)and odds ratios(OR)with a 95% confidence interval(CI)were calculated and agents were ranked based on their ranking probability.RESULTS HAIC outperformed Sorafenib(HR=0.55,95%CI:0.42-0.72;HR=0.51,95%CI:0.33-0.78;OR=2.86,95%CI:1.37-5.98;OR=5.45,95%CI:3.57-8.30;OR=7.15,95%CI:4.06-12.58;OR=2.89,95%CI:1.99-4.19;OR=0.48,95%CI:0.25-0.92,respectively)and transarterial chemoembolization(TACE)(HR=0.50,95%CI:0.33-0.75;HR=0.62,95%CI:0.39-0.98;OR=3.08,95%CI:1.36-6.98;OR=2.07,95%CI:1.54-2.80;OR=3.16,95%CI:1.71-5.85;OR=2.67,95%CI:1.59-4.50;OR=0.16,95%CI:0.05-0.54,respectively)in terms of efficacy and safety.HAIC+lenvatinib+ablation,HAIC+ablation,HAIC+anti-programmed cell death 1(PD-1),and HAIC+radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone.HAIC+TACE+S-1,HAIC+lenvatinib,HAIC+PD-1,HAIC+TACE,and HAIC+sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC.HAIC+PD-1,HAIC+TACE+S-1 and HAIC+TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.CONCLUSION HAIC proved more effective and safer than sorafenib and TACE.Furthermore,combined with other interventions,HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

Relapsed primary extraskeletal osteosarcoma of liver:A case report and review of literature

BACKGROUND Extraskeletal osteosarcoma(ESOS)is a highly malignant osteosarcoma that occurs in extraskeletal tissues.It often affects the soft tissues of the limbs.ESOS is classified as primary or secondary.Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient,which is very rare.CASE SUMMARY Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient.The patient had a giant cystic-solid mass in the right hepatic lobe that was evident on ultrasound and computed tomography.Postoperative pathology and immunohistochemistry of the mass,which was surgically removed,suggested fibroblastic osteosarcoma.Hepatic osteosarcoma reoccurred 48 d after surgery,resulting in significant compression and narrowing of the hepatic segment of the inferior vena cava.Consequently,the patient underwent stent implantation in the inferior vena cava and transcatheter arterial chemoembolization.Unfortunately,the patient died of multiple organ failure postoperatively.CONCLUSION ESOS is a rare mesenchymal tumor with a short course and a high likelihood of metastasis and recurrence.The combination of surgical resection and chemotherapy may be the best treatment.

Laboratory scoring system to predict hepatic indocyanine green clearance ability during fluorescence imaging-guided laparoscopic hepatectomy

BACKGROUND Indocyanine green(ICG)fluorescence played an important role in tumor localization and margin delineation in hepatobiliary surgery.However,the preoperative regimen of ICG administration was still controversial.Factors associated with tumor fluorescence staining effect were unclear.AIM To investigate the preoperative laboratory indexes corelated with ICG fluorescence staining effect and establish a novel laboratory scoring system to screen specifical patients who need ICG dose adjustment.METHODS To investigate the predictive indicators of ICG fluorescence characteristics in patients undergoing laparoscopic hepatectomy from January 2018 to January 2021 were included.Blood laboratory tests were completed within 1 wk before surgery.All patients received 5 mg ICG injection 24 h before surgery for preliminary tumor imaging.ImageJ software was used to measure the fluorescence intensity values of regions of interest.Correlation analysis was used to identify risk factors.A laboratory risk model was established to identify individuals at high risk for high liver background fluorescence.RESULTS There were 110 patients who were enrolled in this study from January 2019 to January 2021.The mean values of fluorescence intensity of liver background(FI-LB),fluorescence intensity of gallbladder,and fluorescence intensity of target area were 18.87±17.06,54.84±33.29,and 68.56±36.11,respectively.The receiver operating characteristic(ROC)curve showed that FI-LB was a good indicator for liver clearance ability[area under the ROC curve(AUC)=0.984].Correlation analysis found pre-operative aspartate aminotransferase,alanine aminotransferase,gammaglutamyl transpeptidase,adenosine deaminase,and lactate dehydrogenase were positively associated with FI-LB and red blood cell,cholinesterase,and were negatively associated with FI-LB.Total laboratory risk score(TLRS)was calculated according to ROC curve(AUC=0.848,sensitivity=0.773,specificity=0.885).When TLRS was greater than 6.5,the liver clearance ability of ICG was considered as poor.CONCLUSION Preoperative laboratory blood indicators can predict hepatic ICG clearance ability.Surgeons can adjust the dose and timing of ICG preoperatively to achieve better liver fluorescent staining.

Turner综合征垂体MRI特征及与激素、染色体的关系

目的分析Turner综合征患儿的垂体磁共振成像(MRI)表现特征及与相关激素、染色体的关系,探讨垂体改变的原因。方法选取2010年6月-2018年6月于青岛大学附属医院神经内分泌儿科诊治的43例Turner综合征患儿,回顾性分析垂体MRI大小与相关激素、染色体的相关性。结果患儿垂体MRI多见垂体正常(22例,51.2%)和垂体增大(18例,41.9%);垂体正常组促卵泡激素、黄体生成素低于垂体增大组(P <0.05),雌二醇高于垂体增大组(P <0.05)。结论部分Turner综合征患儿垂体形态异常,主要表现为垂体增大,可能与靶腺(卵巢)功能低下引起负反馈抑制作用减弱,导致垂体代偿性增生有关。

Detecting the spectrum of multigene mutations in non-small cell lung cancer by Snapshot assay

As molecular targets continue to be identified and more targeted inhibitors are developed for personalized treatment of non-small cell lung cancer(NSCLC), multigene mutation determination will be needed for routine oncology practice and for clinical trials. In this study, we evaluated the sensitivity and specificity of multigene mutation testing by using the Snapshot assay in NSCLC. We retrospectively reviewed a cohort of 110 consecutive NSCLC specimens for which epidermal growth factor receptor(EGFR) mutation testing was performed between November 2011 and December 2011 using Sanger sequencing. Using the Snapshot assay, mutation statuses were detected for EGFR, Kirsten rate sarcoma viral oncogene homolog(KRAS), phosphoinositide-3-kinase catalytic alpha polypeptide(PIK3CA), v-Raf murine sarcoma viral oncogene homolog B1(BRAF), v-ras neuroblastoma viral oncogene homolog(NRAS), dual specificity mitogen activated protein kinase kinase 1(MEK1), phosphatase and tensin homolog(PTEN), and human epidermal growth factor receptor 2(HER2) in patient specimens and cell line DNA. Snapshot data were compared to Sanger sequencing data. Of the 110 samples, 51(46.4%) harbored at least one mutation. The mutation frequency in adenocarcinoma specimens was 55.6%, and the frequencies of EGFR, KRAS, PIK3 CA, PTEN, and MEK1 mutations were 35.5%, 9.1%, 3.6%, 0.9%, and 0.9%, respectively. No mutation was found in the HER2, NRAS, or BRAF genes. Three of the 51 mutant samples harbored double mutations: two PIK3 CA mutations coexisted with KRAS or EGFR mutations, and another KRAS mutation coexisted with a PTEN mutation. Among the 110 samples, 47 were surgical specimens, 60 were biopsy specimens, and 3 were cytological specimens; the corresponding mutation frequencies were 51.1%, 41.7%, and 66.7%, respectively(P = 0.532). Compared to Sanger sequencing, Snapshot specificity was 98.4% and sensitivity was 100%(positive predictive value, 97.9%; negative predictive value, 100%). The Snapshot assay is a sensitive and easily customized assay for multigene mutation testing in clinical practice.

Inflammatory pseudotumor-like follicular dendritic cell sarcoma: A brief report of two cases

BACKGROUND Follicular dendritic cell(FDC)sarcoma/tumor is a rare malignant tumor of follicular dendritic cells,which is considered a low-grade sarcoma that can involve lymph nodes or extranodal sites.Conventional FDC sarcomas are negative for Epstein-Barr virus(EBV),whereas the inflammatory pseudotumorlike variant consistently shows EBV in the neoplastic cells.CASE SUMMARY We report two cases of inflammatory pseudotumor-like FDC sarcoma in the liver that received 3D laparoscopic right hepatectomy and open right hepatectomy separately.CONCLUSION EBV probe-based in situ hybridization and detection of immunohistochemical markers of FDC play an important role in the diagnosis and differential diagnosis of inflammatory pseudotumor-like FDC sarcoma.Complete surgical excision combined with regional lymphadenectomy may be effective in reducing the postoperative recurrence and metastasis and improving long-term survival rates.

Imaging findings of inflammatory pseudotumor-like follicular dendritic cell tumors of the liver:Two case reports and literature review

BACKGROUND Inflammatory pseudotumor-like follicular dendritic cell(IPT-like FDC)tumors of the liver is an uncommon tumor with extremely low incidence.To date,the radiologic findings of this tumor in multiphase computed tomography(CT)and magnetic resonance imaging(MRI)imaging have not been described.CASE SUMMARY Patient 1 is a 31-year-old Chinese female,whose complaining incidentally coincided with the finding of multiple liver masses.In the local hospital,an abdominal enhanced CT found two hypo-dense solid lesions,with heterogeneous sustained hypoenhancement,in the upper segment of the liver’s right posterior lobe.In our hospital,enhanced magnetic resonance imaging(MRI)with hepatocyte-specific contrast agents showed a similar enhanced pattern of lesions with patchy hyperintensity in the hepatobiliary phase(HBP).The patient underwent surgery and recovered well.The final pathology confirmed an IPTlike FDC tumor.No recurrence was found on the regular re-examination.Patient 2 is a 48-year-old Chinese male admitted to our hospital for a huge unexpected hepatic lesion.A dynamic enhanced abdominal CT revealed a huge heterogeneous enhanced solid tumor in the right lobe of the liver with a size of 100 mm×80 mm,which showed a heterogeneous sustained hypoenhancement.In addition,enlarged lymph nodes were found in the hilum of the liver.This patient underwent a hepatic lobectomy and lymph node dissection.The final pathology confirmed an IPT-like FDC tumor.No recurrence was found upon regular re-examination.CONCLUSION When a hepatic tumor shows heterogeneous sustained hypoenhancement with a patchy enhancement during HBP,an IPT-like FDC tumor should be considered in the differential diagnosis.

高强度聚焦超声联合竹红菌素软膏对外阴上皮非瘤样病变组织中P16、CD34的影响

目的探讨聚焦超声联合竹红菌素软膏治疗对外阴上皮非瘤样病变组织P16、CD34的影响。方法选取2010年12月-2015年12月在衡水市人民医院进行治疗的80例外阴上皮非瘤样病变(NNED)患者为研究对象。其中,2013年12月以前入院的40例患者作为对照组,选择与其状况相似的2013年12月以后入院的40例患者作为观察组。对照组患者接受聚焦超声治疗,观察组患者接受聚焦超声联合竹红菌素治疗。比较两组患者治疗效果和治疗前后病变组织P16、CD34水平。结果治疗后两组患者外阴瘙痒评分、皮肤弹性评分和外阴白色病变面积均变小(P<0.05),观察组患者外阴瘙痒评分、皮肤弹性评分和外阴白色病变面积小于对照组(均P<0.05)。治疗后两组患者外阴组织P16蛋白水平均上升(P<0.05),但观察组患者治疗后P16水平较对照组更高(P <0.05),CD34蛋白水平下降(P <0.05),但观察组患者治疗后CD34蛋白水平更低(P <0.05)。结论聚焦超声联合竹红菌素软膏治疗NNED疗效好,能增加病变组织中P16蛋白含量,降低CD34蛋白含量,提示NNED的发生发展可能与细胞周期失调和微循环障碍有关。

Analysis of the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal epilepsy

Objective:To detect the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal lobe epilepsy(NFLE).Methods:Blood samples were collected from 215 Southern Han Chinese patients with NFLE and 200 healthy Southern Han Chinese control subjects.Genomic DNA was extracted,and CHRNA7 whole genome exons were amplified by the polymerase chain reaction and subjected to Sanger sequencing.Results:No CHRNA7 gene mutation was detected in all of the NFLE patients.However,five single nucleotide polymorphisms(SNPs)in sporadic cases were found,located in exons 5,6.and 7 of the CHRNA7 gene.Among them,c.690G>A and c.698A>G are known SNPs,while c.370G>A,c.654C>T,and c.497-498delTG were newly discovered SNPs.These SNPs were also found in some of the healthy controls.Conclusions:No CHRNA7 gene mutation was identified in Southern Han Chinese patients with NFLE.The CHRNA7 gene is probably not responsible for NFLE in this population.

Gonadal dysgenesis in Turner syndrome with Y-chromosome mosaicism:Two case reports

BACKGROUND Turner syndrome(TS)has a variety of different karyotypes,with a wide range of phenotypic features,but the specific karyotype may not always predict the phenotype.TS with Y chromosome mosaicism may have mixed gonadal dysgenesis,and the mosaicism is related to the potential for gonadoblastoma.CASE SUMMARY In this case report,we report two cases of TS with different karyotypes and gonadal dysgenesis.Patient 1 had obvious virilization,and was positive for the SRY gene,but her karyotype in peripheral blood lymphocytes was 45X.Patient 2 had a mosaic karyotype,45X/46X,dic(Y:Y)(p11.3:p11.2),and the proportion of Y-bearing cells was 50%in peripheral blood lymphocytes,but the patient had normal female external genitalia and streaky gonads,with no genital virilism.Different tissues in the same TS individual may exhibit different ratios of mosaicism.The gonadal determination and differentiation of mosaic TS are primarily dependent on the predominant cell line in the gonads.CONCLUSION In TS patients with virilization,it is necessary to test at least two to three tissues to search for cryptic Y material.

Monocyte chemotactic protein-inducing protein 1 negatively regulating asthmatic airway inflammation and mucus hypersecretion involvingγ-aminobutyric acid type A receptor signaling pathway in vivo and in vitro

Background:Mounting evidence,consistent with our previous study,showed thatγ-aminobutyric acid type A receptor(GABAAR)played an indispensable role in airway inflammation and mucus hypersecretion in asthma.Monocyte chemotactic protein-inducing protein 1(MCPIP1)was a key negative regulator of inflammation.Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases.However,the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied.This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells,and its potential mechanism.Methods:In vivo,mice were sensitized and challenged by ovalbumin(OVA)to induce asthma.Airway inflammation and mucus secretion were analyzed.In vitro,BEAS-2B cells were chosen.Interleukin(IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells.MCPIP1 Lentiviral vector(LA-MCPIP1)and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells,respectively.MCP-1,thymic stromal lymphopoietin(TSLP),mucin 5AC(MUC5AC),MCPIP1,and GABAARβ2 expressions were measured in both lung and BEAS-2B cells.Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells.Results:MCPIP1 was up-regulated by LA-MCPIP1(P<0.001)and plasmid-MCPIP1(P<0.001)in lung and cells,respectively.OVA-induced airway inflammation and mucus hypersecretion,OVA-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice(all P<0.001).IL-13-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells(all P<0.001).Conclusion:The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells,involving GABAAR signaling pathway.

Establishment of a Novel Method for Screening Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance Mutations in Lung Cancer

Background： Drug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKl-resistant lung cancer using Agena iPLEX chemistry and niatrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform. Methods： A review of the literature revealed 60 mutation hotspots in seven target genes （EGFR, KRAS, PIK3CA, BRAF, ERBB2, NRAS, and BIM） that are closely related to EGFR TKI resistance to lung cancer. A total of 183 primers comprised 61 paired forward and reverse amplification primers, and 61 matched extension primers were designed using Assay Design Software. The detection method was established by analyzing nine cell lines, and by comparison with LungCartaTM kit in ten lung cancer specimens. EGFR, KRAS. and BIM genes in all cell lines and clinical samples were subjected to Sanger sequencing for confirming reproducibility. Results： Our data showed that designed panel was a high-throughput and robust tool, allowing genotyping for sixty hotspots in the same run. Moreover, it made efficient use of patient diagnostic samples for a more accurate EGFR TKIs resistance analysis. The proposed method could accurately detect mutations in lung cancer cell lines and clinical specimens, consistent with those obtained by the LungCartaTM kit and Sanger sequencing. We also established a method for detection of large-fragment deletions based on single-base extension technology of MassARRAY platform. Conclusions： We established an effective method for high-throughput detection of genetic mutations related to EGFR TKI resistance based on the MassARRAY platform, which could provide more accurate information for overcoming cancers with de novo or acquired resistance to EGFR-targeted therapies.

Modification of Ti_(3)C_(2) MXene nanosheets with tunable properties using a post-processing method

MXenes are a family of two-dimensional(2D)transition metal carbides and nitrides with many intriguing properties and applications,many of which require surface modification.Herein,as-synthesized Ti_(3)C_(2) was modified using different treatments(acid and base treatments)and then characterized by a complementary combination of X-ray powder diffraction(XRD),scanning electron microscopy(SEM),Fourier-transform infrared spectroscopy(FTIR),nitrogen adsorption-desorption isotherms,and pore size distribution analysis.The results indicated that the structure and surface properties of the obtained Ti_(3)C_(2) could be tuned using various treatments.The modification methods developed in this study may offer a new direction for tuning the structure and surface properties of MXenes for a wide range of applications.

Integrative Analyses of Lung Squamous Cell Carcinoma in Ten Chinese Patients with Transcriptome Sequencing

Few effective therapies have been developed for the treatment of lung squamous cell carcinoma （SQCC）, in part due to a lack of un- derstanding regarding the mechanisms underlying the initiation and development of this disease. Whole transcriptome sequencing not only provides insight into the expression of all transcribed genes, but offers an efficient approach for identifying genetic variations, including gene fusions, mutations and alternative splicing. In this study, we performed whole transcriptome sequencing of 10 patients with stage IIIA lung SQCC, and discovered a large number of single nucleotide variants （SNVs： mean of 12.2 SNVs/Mb）, with C〉T/G〉A and A〉G/T〉C transitions being the most frequently observed. Additionally, a total of 132 gene fusions were identified based upon TopHat alignments, 70.5% （93/132） of which occurred as a result of intra-chromosomal rearrangements. Based on the number of supporting reads for each fusion, we further validated 20 of the 26 top gene fusions by RT-PCR and Sanger sequencing. Taken together, these data provide an in-depth view of transcriptional alterations in lung SQCC patients, and may be useful for identification of new therapeutic targets.

The spatiotemporal evolution of EGFR C797S mutation in EGFR-mutant non-small cell lung cancer:opportunities for third-generation EGFR inhibitors re-challenge

Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated impressive activity in EGFR T790M-positive non-small cell lung cancer (NSCLC) progressed from prior EGFR-TKIs (1,2)However, resistance inevitably occurred after approximately 10 months of treatment.

Primary pulmonary lymphoepithelioma-like carcinoma combined with situs inversus totalis

To the Editor:According to World Health Organization (WHO) histologic classification of lung tumors, primary pulmonary lymphoepithelioma-like carcinoma (LELC), belonging to the other and unclassified carcinoma, is considered as a rare subtype of variants of lung cancer.