5-Aminolevulinic acid-mediated photodynamic activity in patient-derived cholangiocarcinoma organoids

BackgroundAccurate diagnosis of the disease extension of cholangiocarcinoma (CCA) is often difficult in clinical practice. The diagnostic yield of conventional pre-operative imaging or endoscopic procedures is sometimes insufficient for the evaluation of longitudinal spreading of CCA. Here we investigated the usefulness of 5-aminolevulinic acid (5-ALA) for the pre- or intra-operative diagnosis of CCA, using patient-derived organoids.MethodsFour CCA- and two adjacent tissue-derived organoids were established. After 5-ALA treatment, we assessed their photodynamic activity using fluorescence microscopy.ResultsCCA organoids established from different patients showed diverse morphology in contrast to monolayer structures of non-tumor organoids, and had the ability to form subcutaneous tumors in immunodeficient mice. CCA organoids demonstrated remarkably high photodynamic activity based on higher accumulation of protoporphyrin IX as a metabolite of 5-ALA compared to non-tumor organoids (40–71% vs. < 4%, respectively). Importantly, cancer cell-specific high photodynamic activity distinguished the organoids originated from biliary stenotic lesions from those of non-stenotic lesions in a CCA patient. The high photodynamic activity did not depend on the expression profile of heme biosynthesis genes.ConclusionsDistinct 5-ALA-based photodynamic activity could have diagnostic potential for the discrimination of CCA from non-tumor tissues.     

Inhibition of PI3K/Akt/NF-κB signaling by Aloin for ameliorating the progression of osteoarthritis: In vitro and in vivo studies

Osteoarthritis (OA) is a progressive and degenerative joint disease. Aloin is a bitter and yellow-brown-coloured compound from the Aloe plant and is allowed for use in foods as a “natural flavour”. In our study, we examined the protective effects of Aloin on the inhibition of OA development as well as its underlying mechanism in both in vitro and vivo experiments. In in-vitro experiments, the protective effect of aloin on the anabolism and catabolism of the extracellular matrix (ECM) induced by IL-1 β in chondrocytes by inhibiting the expression of pro-inflammatory factors, including TNF-α (p = 0.016), IL-6 (p = 0.006), iNOS (p = 0.001) and COX-2 (p = 0.006). Mechanistically, Aloin suppressed the IL-1β-induced activation of the PI3K/Akt/NF-κB signalling pathway cascades. Moreover, molecular docking studies demonstrated that Aloin bound strongly to PI3K. In vivo, Aloin ameliorated the OA process in the destabilization of the medial meniscus (DMM) model.In summary, our findings demonstrate that Aloin ameliorates the progression of OA via the PI3K/Akt/NF-κB signalling pathways, which supports Aloin as a promising therapeutic agent for the treatment of OA.     

PELP1 signaling contributes to medulloblastoma progression by regulating the NF-κB pathway

Medulloblastoma (MB) is the most common and deadliest brain tumor in children. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein and its oncogenic signaling is implicated in the progression of several cancers. However, the role of PELP1 in the progression of MB remains unknown. The objective of this study is to examine the role of PELP1 in the progression of MB. Immunohistochemical analysis of MB tissue microarrays revealed that PELP1 is overexpressed in the MB specimens compared to normal brain. Knockdown of PELP1 reduced cell proliferation, cell survival, and cell invasion of MB cell lines. The RNA-sequencing analysis revealed that PELP1 knockdown significantly downregulated the pathways related to inflammation and extracellular matrix. Gene set enrichment analysis confirmed that the PELP1-regulated genes were negatively correlated with nuclear factor-κB (NF-κB), extracellular matrix, and angiogenesis gene sets. Interestingly, PELP1 knockdown reduced the expression of NF-κB target genes, NF-κB reporter activity, and inhibited the nuclear translocation of p65. Importantly, the knockdown of PELP1 significantly reduced in vivo MB progression in orthotopic models and improved the overall mice survival. Collectively, these results suggest that PELP1 could be a novel target for therapeutic intervention in MB.     

B cell and B cell-related pathways for novel cancer treatments

B cells are recognized as the main effector cells of humoral immunity which suppress tumor progression by secreting immunoglobulins, promoting T cell response, and killing cancer cells directly. Given these properties, their anti-tumor immune response in the tumor micro-environment (TME) is of great interest. Although T cell-related immune responses have become a therapeutic target with the introduction of immune checkpoint inhibitors, not all patients benefit from these treatments. B cell and B cell-related pathways (CCL19, −21/CCR7 axis and CXCL13/CXCR5 axis) play key roles in activating immune response through humoral immunity and local immune activation via tertiary lymphoid structure (TLS) formation. However they have some protumorigenic works in the TME. Thus, a better understanding of B cell and B cell-related pathways is necessary to develop effective cancer control. In this review, we summarize recent evidences regarding the roles of B cell and B cell-related pathways in the TME and immune response and discuss their potential roles for novel cancer treatment strategies.     

E-Cadherin in Colorectal Cancer: Relation to Chemosensitivity

Background

The conventional chemotherapy of colorectal cancer with irinotecan, 5-fluorouracil, and oxaliplatin remains one of the front-line treatments worldwide. However, its efficacy is quite low. Recently studies of the epithelial–mesenchymal transition (EMT) have become the focus of investigations into the cause of chemoresistance in several types of cancer, including colorectal cancer. The data about the role of EMT in chemosensitivity are controversial.

维生素B12和叶酸干预对绝经后骨质疏松症妇女的骨代谢及同型半胱氨酸水平的影响

目的观察叶酸和维生素B12对绝经后骨质疏松症妇女的骨代谢及同型半胱氨酸水平的影响。方法 80例绝经后骨质疏松症妇女参加研究。所有参与者随机接受叶酸和维生素B12(n=40)或安慰剂(n=40)治疗。在干预前的基线及干预后3个月和6个月,测量两组患者血清同型半胱氨酸、维生素B12和骨代谢标志物的水平。结果治疗前,两组患者血清同型半胱氨酸、维生素B12和骨代谢标志物水平比较差异无统计学意义(P0.05)。治疗后,两组患者同型半胱氨酸均下降,但比较差异无统计学意义(P0.05)。6个月后各组间血清维生素B12、骨钙素、CTX的变化均有显著改变且差异有统计学意义(P0.05)。结论绝经后骨质疏松症妇女补充叶酸和维生素B12可以一定程度改善同型半胱氨酸及骨代谢指标水平。     

Hepatitis B virus infection and the risk of cancer among the Chinese population

The relationship between hepatitis B virus (HBV) and nonhepatocellular cancers remains inconclusive. This large case-control study aimed to assess the associations between HBV infection status and multiple cancers. Cases (n = 50 392) and controls (n = 11 361) were consecutively recruited from 2008 to 2016 at the First Affiliated Hospital of Nanjing Medical University. Multivariable adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression by adjusting age and gender. A meta-analysis based on published studies was also performed to verify the associations. Of these, 12.1% of cases and 5.5% of controls were hepatitis B surface antigen (HBsAg) seropositive. We observed significant associations between HBsAg seropositivity and esophagus cancer (aOR [95% CI] = 1.32 [1.13-1.54]), stomach cancer (1.46 [1.30-1.65]), hepatocellular carcinoma (HCC; 39.11 [35.08-43.59]), intrahepatic and extrahepatic bile duct carcinoma (ICC and ECC; 3.83 [2.58-5.67] and 1.72 [1.28-2.31]), pancreatic cancer (PaC; 1.37 [1.13-1.65]), non-Hodgkin lymphoma (NHL; 1.88 [1.61-2.20]) and leukemia (11.48 [4.05-32.56]). Additionally, compared to participants with HBsAg−/anti-HBs−/anti-HBc−, participants with HBsAg−/anti-HBs−/anti-HBc+, indicating past HBV-infected, had an increased risk of esophagus cancer (aOR [95% CI] = 1.46 [1.24-1.73]), stomach cancer (1.20 [1.04-1.39]), HCC (4.80 [3.95-5.84]) and leukemia (15.62 [2.05-119.17]). Then the overall meta-analysis also verified that HBsAg seropositivity was significantly associated with stomach cancer (OR [95% CI] = 1.23 [1.14-1.33]), ICC (4.05 [2.78-5.90]), ECC (1.73 [1.30-2.30]), PaC (1.26 [1.09-1.46]), NHL (1.95 [1.55-2.44]) and leukemia (1.54 [1.26-1.88]). In conclusion, both our case-control study and meta-analysis confirmed the significant association of HBsAg seropositivity with stomach cancer, ICC, ECC, PaC, NHL and leukemia. Of note, our findings also suggested that the risk of stomach cancer elevated for people whoever exposed to HBV.     

滋阴清嗓汤对咳嗽变异性哮喘发作期患儿IgE、IL-4、IL-5水平的影响及安全性分析

目的:探究滋阴清嗓汤对咳嗽变异性哮喘(CVA)发作期患儿免疫球蛋白E(IgE)、白细胞介素-4(IL-4)、白细胞介素-5(IL-5)的影响及安全性。方法:选取2018年1月—2019年6月在河南省儿童医院东三街院区呼吸科一病区住院治疗的170例CVA患儿,随机分为中医联合组(85例)和西医常规组(85例)。所有患儿均给予西医常规治疗,中医联合组加用滋阴清嗓汤。两组均连续治疗14 d后,观察并比较两组的疗效、症状改善时间、临床主要症状积分、外周血单个核细胞(PBMC)内IL-4、IL-5、血清IgE水平、呼出气一氧化氮(FeNO)及肺功能指标水平。结果:中医联合组患儿痊愈率为80.00%(68/85),显著高于西医常规组痊愈率61.18%(52/85)(P<0.05)。中医联合组患儿症状改善时间(咳嗽减轻、咳嗽消退、夜咳停止的时间)均显著短于西医常规组(P<0.05)。治疗后,两组患儿咳嗽、咽痛、喉痒评分均显著下降,且中医联合组显著低于西医常规组(P<0.05)。治疗后,两组患儿PBMC内IL-4、IL-5及血清IgE水平均显著下降,且中医联合组均显著低于西医常规组(P<0.05)。治疗后,两组患者FeNO和1 s用力呼气容积(FEV1)均显著下降(P<0.05),呼气峰流速(PEF)均显著升高(P<0.05),组间比较,中医联合组均显著优于西医常规组(P<0.05)。两组患者在治疗期间均未发生明显不良反应和不良事件。结论:滋阴清嗓汤对CVA发作期患儿具有良好的疗效,可发挥较好的滋阴清热、止咳平喘、改善慢性炎症作用,有效改善其临床症状,安全性高,值得推广。     

Cranio-caudal approach to hepatic veins in laparoscopic central bisectionectomy (with Video)

BackgroundLaparoscopic central bisectionectomy (Couinaud's segment IV, V, and VIII) needs exposure of the RHV and MHV on the surface of the remnant and the resecting side, respectively. Avoiding venous injury is mandatory and laparoscopy-specific cranio-caudal approach to hepatic veins might be helpful [1]. We present this procedure in performing laparoscopic central bisectionectomy.PatientA 45-year-old female was admitted to our hospital with a 6 cm HCC in the segment VIII and IV. Her comorbid disease was non-cirrhotic HBV hepatitis (Child-Pugh grade A) and diabetes (untreated).MethodAfter cholecystectomy, G₄ branches were dissected and cut by extra- or intra-hepatic approach. Hilar plate was dissected and the G_ant was encircled and occluded by a vascular clip. Afterwards, exposure of the MHV was started at its root on IVC [2,3] and extended in cranio-caudal direction [1]. After sufficient space was obtained around the G_ant, the G_ant and the MHV were cut. Parenchymal transection between right anterior and right posterior sections was also started form the root of the RHV to its cranio-caudal direction. Liver resection was finished with full exposure of the RHV.ResultsThe operating time was 380 minutes, and the blood loss volume was 30 ml. Postoperative CT image showed exposure of the RHV and umbilical portion of Glissonean branch, and no fluid retention.ConclusionLaparoscopy-specific cranio-caudal approach to hepatic veins may be useful to avoid split injury of venous branches [4], especially if the hepatectomy requires complete exposure of hepatic vein, such as central bisectionectomy.