Biochemical overview of the recent findings on the correlation between viral hepatitis and its related hepatocellular carcinoma

As one of the most common primary liver cancers, hepatocellular carcinoma(HCC) usually occurs in the presence of inflammation. Compared to other risk factors such as alcohol abuse, aflatoxin, and obesity, virus-induced hepatitis can be effectively prevented by vaccines. For the past several decades, HCC has been believed to be closely related to viral infections although no comprehensive mechanism was established regarding the contribution of viral hepatitis toward HCC. Recent studies have shown that viral infection plays multiple roles in the process of carcinogenesis by causing an increase in genomic instability, cancer-promoting genetic mutations, signal pathway interruption, and tumor suppressor gene inhibition. Sorafenib has become a novel option for HCC patients, especially those who are in advanced disease stage for which conventional treatment methods are not recommended. Future studies should focus more on novel targeted drugs which can be adopted as alternatives to sorafenib or as second-line drugs after the failure of

The impact of individualized care after artificial knee replacement surgery for patients with valgus deformity of the knee

Objective:To evaluate the perioperative nursing of total knee arthroplasty for patients with valgus deformity of the knee.Methods:Seventy-six patients who underwent surgical treatment were enrolled in the study from March 2014 to March 2018.The patients in the control group were treated with routine nursing.The experimental group was treated not only with routine nursing but also with health education,psychological care,family social support,and other nursing intervention.Hospital for special surgery and Pittsburgh sleep quality index were used to evaluate the effect of nursing intervention on patients after operation.Results:All the index scores of the experimental group were lower than those of the control group(P<0.05),indicating that the function of the diseased limb and the patient's sleep status improved significantly after the intervention.Conclusions:Individualized nursing can improve the recovery of limb function and improve the patients'quality of life.It is very effective for nurses to implement individualized nursing measures for patients after surgery.

Autophagy and cancer treatment: four functional forms of autophagy and their therapeutic applications

Cancer is the leading cause of death worldwide. Drugs play a pivotal role in cancer treatment, but the complex biological processes of cancer cells seriously limit the efficacy of various anticancer drugs. Autophagy, a self-degradative system that maintains cellular homeostasis, universally operates under normal and stress conditions in cancer cells. The roles of autophagy in cancer treatment are still controversial because both stimulation and inhibition of autophagy have been reported to enhance the effects of anticancer drugs. Thus, the important question arises as to whether we should try to strengthen or suppress autophagy during cancer therapy. Currently, autophagy can be divided into four main forms according to its different functions during cancer treatment: cytoprotective(cell survival), cytotoxic(cell death), cytostatic(growth arrest), and nonprotective(no contribution to cell death or survival). In addition, various cell death modes, such as apoptosis, necrosis, ferroptosis, senescence, and mitotic catastrophe, all contribute to the anticancer effects of drugs. The interaction between autophagy and these cell death modes is complex and can lead to anticancer drugs having different or even completely opposite effects on treatment. Therefore, it is important to understand the underlying contexts in which autophagy inhibition or activation will be beneficial or detrimental.That is, appropriate therapeutic strategies should be adopted in light of the different functions of autophagy. This review provides an overview of recent insights into the evolving relationship between autophagy and cancer treatment.

Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non-small-cell lung cancer characterizes the features of response to PD-1 blockade plus chemotherapy

Background:Although programmed cell death 1(PD-1)blockade plus chemotherapy can significantly prolong the progression-free survival(PFS)and overall survival(OS)in first-line settings in patients with driver-negative advanced non-small-cell lung cancer(NSCLC),the predictive biomarkers remain undetermined.Here,we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy.Methods:Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone.Tumor immune microenvironmental markers,including PD-1 ligand(PDL1),CD8,CD68,CD4 and forkhead box P3,were assessed using multiplex immunofluorescence(mIF)assays.Kaplan-Meier curveswere used to determine treatment outcome differences according to their expression status.Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations.Results:Responders had significantly higher CD8/PD-L1(P=0.015)or CD68/PD-L1 co-expression levels(P=0.021)than non-responders in the camrelizumab plus chemotherapy group,while no difference was observed in the chemotherapy group.Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS(P=0.002,P=0.024;respectively)and OS(P=0.006,P=0.026;respectively)than those with low co-expression in camrelizumab plus chemotherapy group.When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification,significantly better PFS(P=0.003)and OS(P=0.032)were observed in high co-expression subgroups.The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features.Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression,the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups(both 13.0%vs.0.0%,P=0.023).Notably,enriched PI3K(P=0.012)and cell cycle pathway(P=0.021)were found in the CD8/PD-L1 co-expression group.Conclusion:Tumor immune microenvironmental marker expression,especially CD8/PD-L1 or CD68/PD-L1 co-expression,was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC.

Comprehensive genomic analysis of early and late-onset hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the major histologic type of primary liver cancer,accounting for approximately 75%of liver cancer cases.'Despite many advancements in its treatment,the prognosis and drug response of HCC patients are dismal.Therefore,there is an unmet clinical need to explore genomic aberrations underlying early-and lateonset HcC,which might facilitate drug discovery and provide personalized biomarker-driven treatment options for these patients.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma(CHANCE001)

There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.

Photosensitive hydrogels: from structure, mechanisms, design to bioapplications

Hydrogel is a smart material with a three-dimensional network structure and has been widely used in various fields due to its good biodegradability, biocompatibility, and modification. Photosensitive hydrogel is a smart hydrogel, and its amenability to remote, precise control, and flexible and convenient regulation of stimulating factors make it an ideal candidate for use in fields such as biological materials, drug carriers, and sensors. In this review, we discuss the structure, mechanisms, design principles,and bioapplications of photosensitive hydrogels as developed in recent years. Finally, their potential for development and potential future challenges are outlined.

用于结直肠癌预后评估和精准免疫治疗的肿瘤免疫微环境转录组学分型

背景:基于免疫环境的生物学标志物或许可以指导预后评估。T细胞失活、T细胞排斥以及T细胞功能障碍均会损害肿瘤微环境进而影响免疫治疗的效果及预后。然而,截至目前尚未见利用免疫相关生物标记物来对结直肠癌患者进行分类的报道。因此,本研究旨在根据肿瘤微环境中的T细胞失活、T细胞排斥和T细胞功能障碍的程度来对结直肠癌患者进行分类。方法:通过肿瘤免疫功能障碍和排斥(TIDE)算法,对TCGA数据库中的618例结直肠癌患者的RNAseq数据和GEO数据库中的316例结直肠癌患者的基因芯片数据进行分析。采用无监督聚类法对患者进行分类。结果:基于骨髓来源抑制细胞、癌相关成纤维细胞、M2型肿瘤相关巨噬细胞、细胞毒性T细胞和PD-L1的表达,将患者聚类分为4型:1型为高度免疫功能障碍,2型为低度免疫激活,3型为强烈免疫排斥,4型为高度免疫激活、中度免疫功能障碍及中度免疫排斥。多因素Cox分析结果显示,与1型相比,2、3、4型患者总体生存的风险比(95%可信区间)分别为0.63(0.35-1.13)、0.55(0.29-1.03)和0.30(0.14-0.64)。利用GSE39582队列进行验证,也得到了相似的聚类分型和预后模式。亚组分析中,在I/II期、微卫星稳定和未接受辅助治疗的患者中,免疫聚类分型与总体生存显著相关。结论:本研究结果表明,免疫分型可作为结直肠癌患者一项可靠的预后指标,且有助于个体化免疫治疗的病例选择。

Robust Carbonated Structural Color Barcodes with Ultralow Ontology Fluorescence as Biomimic Culture Platform

Photonic crystal(PC)barcodes are a new type of spectrum-encoding microcarriers used in multiplex high-throughput bioassays,such as broad analysis of biomarkers for clinical diagnosis,gene expression,and cell culture.Unfortunately,most of these existing PC barcodes suffered from undesired features,including difficult spectrum-signal acquisition,weak mechanical strength,and high ontology fluorescence,which limited their development to real applications.To address these limitations,we report a new type of structural color-encoded PC barcodes.The barcodes are fabricated by the assembly of monodisperse polydopamine-(PDA-)coated silica(PDA@SiO_(2))nanoparticles using a droplet-based microfluidic technique and followed by pyrolysis of PDA@SiO_(2)(C@SiO_(2))barcodes.Because of the templated carbonization of adhesive PDA,the prepared C@SiO_(2)PC beads were endowed with simultaneous easy-to-identify structural color,high mechanical strength,and ultralow ontology fluorescence.We demonstrated that the structural colored C@SiO_(2)barcodes not only maintained a high structural stability and good biocompatibility during the coculturing with fibroblasts and tumor cells capture but also achieved an enhanced fluorescentreading signal-to-noise ratio in the fluorescence-reading detection.These features make the C@SiO_(2)PC barcodes versatile for expansive application in fluorescence-reading-based multibioassays.