A study on the relationship between changes in serum hs-CRP levels and Chinese ischemic stroke subclassification

Objective: To study the relationship between changes in serum high sensitivity C-reactive protein (hs-CRP) levels and Chinese ischemic stroke subclassification (CISS), and explore the action mechanism of hs-CRP in the pathogenetic process of ischemic stroke. Methods: The serum hs-CRP level was measured in all subjects (including the healthy). As to 177 ischemic stroke patients, they were subclassified based on causes and pathogenesis to explore the relationship between the serum hs-CRP level and CISS. Results: The serum hs-CRP level in the ischemic stroke group was significantly higher than that in the control group (p < .05). The difference of the serum hs-CRP levels in different Chinese ischemic stroke subtypes was of statistical significance (p < .05). Conclusions: The level of serum hs-CRP is closely associated with the incidence of the ischemic stroke, and the difference of the serum hs-CRP levels in different Chinese ischemic stroke subtypes is of statistical significance.

Evolution and current status of the subclassification of intermediate hepatocellular carcinoma

The staging and treatment of intermediate hepatocellular carcinoma(HCC)remains controversial.According to the recommendations of Barcelona Clinic Liver Cancer staging system,patients with intermediate HCC are candidates for transcatheter arterial chemoembolization.However,not all patients with intermediate HCC benefit from transcatheter arterial chemoembolization.Therefore,it is meaningful to propose a novel staging system of intermediate HCC in order to allocate different treatments for different subgroups.Bolondi et al proposed the first subclassification system of intermediate HCC.Subsequently,investigators performed studies to validate the feasibility of Bolondi’s criteria and proposed several novel staging systems.The present study reviewed the literatures and provided a general overview of the evolution and current status of the subclassification of intermediate HCC.We propose to expand the indication of liver resection and add radical treatments as the first option of the treatment for patients with intermediate HCC.

A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct

Intraductal papillary neoplasm of the bile duct(IPNB)is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas.These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010.In 2018,Japanese and Korean pathologists reached a consensus,classifying IPNBs into type l and type 2 IPNBs.IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis.From a molecular genetic perspective,IPNBs exhibit early genetic variations,and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs.The histological subtypes of IPNBs include gastric,intestinal,pancreaticobiliary,or oncocytic subtypes,but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin.Due to the rarity of these lesions and the absence of specific clinical and laboratory features,imaging is crucial for the preoperative diagnosis of IPNB,with local bile duct dilation and growth along the bile ducts being the main imaging features.Surgical resection remains the optimal treatment for IPNBs,but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

Survival rates according to barcelona clinic liver cancer sub-staging system after transarterial embolization for intermediate hepatocellular carcinoma

AIM: To investigate the survival rates after transarterial embolization(TAE).METHODS: One hundred third six hepatocellular carcinoma(HCC) patients [90 barcelona clinic liver cancer(BCLC) B] were submitted to TAE between August 2008 and December 2013 in a single center were retrospectively studied. TAE was performed via superselective catheterization followed by embolization with polyvinyl alcohol or microspheres. The date of the first embolization until death or the last follow-up date was used for the assessment of survival. The survival rates were calculated using the Kaplan-Meier method, and the groups were compared using the log-rank test.RESULTS: The overall mean survival was 35.8 mo(95%CI: 25.1-52.0). The survival rates of the BCLC A patients(33.7%) were 98.9%, 79.0% and 58.0% at 12, 24 and 36 mo, respectively, and the mean survival was 38.1 mo(95%CI: 27.5-52.0). The survival rates of the BCLC B patients(66.2%) were 89.0%, 69.0% and 49.5% at 12, 24 and 36 mo, respectively, and the mean survival was 29.0 mo(95%CI: 17.2-34). The survival rates according to the BCLC B sub-staging showed significant differences between the groups, with mean survival rates in the B1, B2, B3 and B4 groups of 33.5 mo(95%CI: 32.8-34.3), 28.6 mo(95%CI: 27.5-29.8), 19.0 mo(95%CI: 17.2-20.9) and 13 mo, respectively(P = 0.013).CONCLUSION : The BCLC sub-stagingsystem could add additional prognosis information for postembolization survival rates in HCC patients.

Comparative Analysis of General Characteristics of Ischemic Stroke of BAD and non-BAD CISS Subtypes

Summary： Based on the recently proposed Chinese ischemic stroke subclassification （CISS） system, intracranial branch atheromatous disease （BAD） is divided into large artery atherosclerosis （LAA） and penetrating artery disease （PAD）. In the current retrospective analysis, we compared the general charac- teristics of BAD-LAA with BAD-PAD, BAD-LAA with non-BAD-LAA and BAD-PAD with non-BAD-PAD. The study included a total of 80 cases, including 45 cases of BAD and 35 cases of non-BAD. Subjects were classified using CISS system： BAD-LAA, BAD-PAD, non-BAD-LAA and non-BAD-PAD. In addition to analysis of general characteristics, the correlation between the factors and the two subtypes of BAD was evaluated. The number of cases included in the analysis was： 32 cases of BAD-LAA, 13 cases of BAD-PAD, 21 cases of non-BAD-LAA, and 14 cases of non-BAD-PAD. Dia- betes mellitus affected more non-BAD-LAA patients than BAD-LAA patients （P=0.035）. In comparison with non-BAD-PAD, patients with BAD-PAD were younger （P=-0.040）, had higher initial NIHSS score （P〈0.001） and morbidity of ischemic heart disease （P=0.033）. Within patients with BAD, the PAD sub- type was associated with smoking （OR=0.043; P=0.011）, higher low-density lipoprotein （OR=5.339; P=0.029）, ischemic heart disease （OR=9.383; P=0.047） and diabetes mellitus （OR=12.59;P=-0.020）. It was concluded that large artery atherosclerosis was the primary mechanism of BAD. The general char- acteristics showed no significant differences between the CISS subtypes of LAA and PAD within BAD, as well as between the BAD and non-BAD within LAA subtype. Several differences between PAD sub- types of BAD and non-BAD were revealed.

Construction and analysis of tree models for chromosomal classification of diffuse large B-cell lymphomas

AIM: To construct tree models for classification of diffuse large B-cell lymphomas (DLBCL) by chromosome copy numbers, to compare them with cDNA microarray classification, and to explore models of multi-gene, multi-step and multi-pathway processes of DLBCL tumorigenesis. METHODS: Maximum-weight branching and distancebased models were constructed based on the comparative genomic hybridization (CGH) data of 123 DLBCL samples using the established methods and software of Desper et al . A maximum likelihood tree model was also used to analyze the data. By comparing with the results reported in literature, values of tree models in the classification of DLBCL were elucidated. RESULTS: Both the branching and the distance-based trees classified DLBCL into three groups. We combined the classification methods of the two models and classified DLBCL into three categories according to their characteristics. The first group was marked by +Xq, +Xp, -17p and +13q; the second group by +3q, +18q and +18p; and the third group was marked by -6q and +6p. This chromosomal classification was consistent with cDNA classification. It indicated that -6q and +3q were two main events in the tumorigenesis of lymphoma. CONCLUSION: Tree models of lymphoma established from CGH data can be used in the classification of DLBCL. These models can suggest multi-gene, multistep and multi-pathway processes of tumorigenesis. Two pathways, -6q preceding +6q and +3q preceding+18q, may be important in understanding tumorigenesis of DLBCL. The pathway, -6q preceding +6q, may have a close relationship with the tumorigenesis of non-GCB DLBCL.

Oral product input to the GI tract： GIS an oral product performance technology

The patient receives a pharmaceutical product, not a drug. The pharmaceutical products are formulated with a drug, an active ingredient to produce the maximum therapeutic effect after oral absorption. Therefore, it is the product we must optimize for the patients. In order to assure the safety and efficacy of pharmaceutical products, we need an in vivo predictive tool for oral product performance in patients. Currently, we are a surprisingly long way from accomplishing that objective. If the 20th century was the ＇age of the drug＇, i.e., the ＇magic bullet＇, the 21st century must become the ＇age of the guided missile＇, i.e., the delivery system, including the form of the active pharmaceutical ingredient （API） （＇drug＇）. The physical form of the drug and the delivery system must be optimized to maximize the therapeutic benefits of pharmaceutical products for humans. Oral immediate release （IR） dosage forms cannot be optimal for all drugs or likely even any drugs （APIs）. Still, the formulation of pharmaceutical products has to be optimized for patients. But how do we optimize oral delivery of drugs？ It is usually through ＇trial and error＇, in humans! We need a better way to optimize the oral dosage forms. We have suggested to select different dissolution methodologies for this optimization based on BCS Subclasses. In this article, we present the predicted in vivo drug dissolution profile of ketoconazole as a model drug from our laboratory utilizing a gastrointestinal simulator （GIS）, which is an adaptation of the ASD system. GIS consists of three chambers representing stomach, duodenum, and jejunum, to create the human gastrointestinal tract-like environment and enable the control the gastric emptying rate. This dissolution system allows the monitoring of the drug dissolution phenomena and the observation of the super- saturation and the precipitation of pharmaceutical pro- ducts, which is useful information to predict in vivo dissolution of pharmaceutical products. This system canprovide the actual input needed to accurately predict the input into the systemic circulation required by many of the absorption prediction packages available today.

Identification of a TSPY co-expression network associated with DNA hypomethylation and tumor gene expression in somatic cancers

Testis specific protein Y-encoded（TSPY） is a Y-located proto-oncogene predominantly expressed in normal male germ cells and various types of germ cell tumor. Significantly, TSPY is frequently expressed in somatic cancers including liver cancer but not in adjacent normal tissues, suggesting that ectopic TSPY expression could be associated with oncogenesis in non-germ cell cancers. Various studies demonstrated that TSPY expression promotes growth and proliferation in cancer cells; however, its relationship to other oncogenic events in TSPY-positive cancers remains unknown. The present study seeks to correlate TSPY expression with other molecular features in clinical cancer samples, by analyses of RNA-seq transcriptome and DNA methylation data in the Cancer Genome Atlas（TCGA） database. A total of 53 genes,including oncogenic lineage protein 28 homolog B（LIN28B） gene and RNA-binding motif protein Y-linked（RBMY） gene, are identified to be consistently co-expressed with TSPY, and have been collectively designated as the TSPY co-expression network（TCN）. TCN genes were simultaneously activated in subsets of liver hepatocellular carcinoma（30%） and lung adenocarcinoma（10%） regardless of pathological stage, but only minimally in other cancer types. Further analysis revealed that the DNA methylation level was globally lower in the TCN-active than TCN-silent cancers. The specific expression and methylation patterns of TCN genes suggest that they could be useful as biomarkers for the diagnosis,prognosis and clinical management of cancers, especially those for liver and lung cancers, associated with TSPY co-expression network genes.