Transcatheter arterial chemoembolization combined with PD-1 inhibitors and Lenvatinib for hepatocellular carcinoma with portal vein tumor thrombus.

BACKGROUND: Hepatocellular carcinoma (HCC) patients complicated with portal vein tumor thrombus (PVTT) exhibit poor prognoses and treatment responses. AIM: To investigate efficacies and safety of the combination of PD-1 inhibitor, transcatheter arterial chemoembolization (TACE) and Lenvatinib in HCC subjects comorbid with PVTT. METHODS: From January 2019 to December 2020, HCC patients with PVTT types I-IV were retrospectively enrolled at Beijing Ditan Hospital. They were distributed to either the PTL or TACE/Lenvatinib (TL) group. The median progression-free survival (mPFS) was set as the primary endpoint, while parameters like median overall survival, objective response rate, disease control rate (DCR), and toxicity level served as secondary endpoints. RESULTS: Forty-one eligible patients were finally recruited for this study and divided into the PTL (n = 18) and TL (n = 23) groups. For a median follow-up of 21.8 months, the DCRs were 88.9% and 60.9% in the PTL and TL groups (P = 0.046), res-pectively. Moreover, mPFS indicated significant improvement (HR = 0.25; P < 0.001) in PTL-treated patients (5.4 months) compared to TL-treated (2.7 months) patients. There were no treatment-related deaths or differences in adverse events in either group. CONCLUSION: A triplet regimen of PTL was safe and well-tolerated as well as exhibited favorable efficacy over the TL regimen for advanced-stage HCC patients with PVTT types I-IV.

Subunit vaccine based on glycoprotein B protects pattern animal guinea pigs from tissue damage caused by infectious bovine rhinotracheitis virus.

Infectious bovine rhinotracheitis (IBR) is caused by Bovine herpesvirus type 1 (BoHV-1), which seriously threatens the global cattle industry. Only vaccination to improve immunity is the most direct and effective means to prevent IBR. Attempts are being made to use subunit vaccines, deleted or recombinant viral vaccines to reduce or eradicate IBR. For investigating the immunological characteristics of glycoprotein B subunit vaccine in pattern animal guinea pigs, the partial glycoprotein B (gB) of BoHV-1 with dominant antigenic characteristic was selected. A recombinant prokaryotic expression vector pET-32a-gB with the truncated gB gene was constructed, expressed, identified and the purified proteins were used to immunize guinea pigs. The immune effect of the subunit vaccine was assessed by monitoring clinical symptoms, viral load, antibody secretion, and histopathological changes. The results indicated that guinea pigs immunized with the gB subunit vaccine produced high levels of anti-gB antibodies and virus-neutralizing antibodies. The gB subunit vaccine significantly reduced viral shedding and lung tissue damage after IBRV challenge. The animals inoculated the gB subunit vaccine also had less virus reactivation. Its protective effect on viral shedding and tissue damage was similar to that of inactivated BoHV-1 vaccine. This work is a proof-of-concept study of subunit vaccine-induced protection against BoHV-1. And it is expected to be a candidate vaccine for the prevention of IBR.

Downregulation of VMP1 confers aggressive properties to colorectal cancer.

Vacuole membrane protein 1 (VMP1) was recently found to be involved in the process of tumor metastasis and is also considered to play a vital role in balancing apoptosis and autophagy. In the present study, the expression of VMP1 in colorectal cancer and matched adjacent non­cancerous tissues was evaluated by immunohistochemistry (IHC) for studying the role of VMP1 in the process of colorectal cancer. Kaplan­Meier analysis and the log-rank test were used to calculate the correlation of classic clinicopathological characteristics related to survival and the expression of VMP1. In vitro, a VMP1 stable gene silencing cell model was constructed using a lentiviral vector. The invasive ability and proliferation of colorectal cancer cells were evaluated by Transwell and MTT assays, respectively, and the underlying signaling pathway was explored by western blotting. Additionally, drug susceptibility to cisplatin, oxaliplatin and 5-FU was tested before and after VMP1 knockout. Finally, an animal model was constructed to explore the role of VMP1 in the physiopathologic process of colorectal cancer. Our results indicated that VMP1 showed increased expression in the adjacent non-cancer tissues compared with that in the colorectal cancer tissues. For different stages of colorectal cancer, expression of VMP1 had a negative correlation with the malignancy of the cancer. In clinical research, we also found that the median survival of patients with low VMP1 expression was much shorter than the survival of patients with high expression. In vitro, after infection with the lentivirus, cells with VMP1 knockout gained significant aggressive properties in regards to invasion and proliferation, and the mechanisms may be related to the activation of the PI3K/Akt/ZO-1/E-cadherin pathway. We also found that shVMP1 cells were more sensitive to 5-FU, but not cisplatin and oxaliplatin. Finally, we found a higher number of formed nodules in nude mice after intraperitoneal injection with shVMP1 cells in the in vivo study.

Effects of dihydrotestosterone on adhesion and proliferation via PI3-K/Akt signaling in endothelial progenitor cells.

The protective effects of male hormones on the cardiovascular system are still in dispute. There is now ample evidence that testosterone level is negatively correlated to the incidence and mortality of cardiovascular disease in men. Endothelial progenitor cells (EPCs) play a vital role in endothelial healing and vascular integrity, which are useful for promoting cardiovascular health. In this study, we investigated the effects of dihydrotestosterone (DHT), a non-aromatizable androgen, on human EPC function and the activation of the phosphatidylinositol-3-kinase (PI3-K)/Akt pathway in vitro. EPCs were incubated with a series of concentrations (1, 10, or 100 nmol/L in DMSO) of DHT for 24 h or with 10 nmol/L DHT for different time (6, 12, 24, 48 h). EPC adhesion and proliferation and the activation of Akt were assayed by cell counting, 5-ethynyl-2'-deoxyuridine incorporation assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and Western blot analysis. Our data demonstrated that DHT significantly increased the proliferative activity and adhesive ability of EPCs in a dose- and time-dependent manner, maximum at 10 nmol/L, 24 h (p < 0.05). Western blot analysis revealed that DHT promoted the phosphorylation of Akt, and the effects of different concentrations of DHT on Akt phosphorylation were consistent with those on EPC proliferation and adhesion (p < 0.05). However, the enhancing effects of DHT on EPCs decreased with administration of the pharmacological PI3-K blocker LY294002 (p < 0.05). In conclusion, DHT can modulate EPC proliferation and adhesion and the PI3-K/Akt pathway plays an important role in this process.

PKA-induced dimerization of the RhoGAP DLC1 promotes its inhibition of tumorigenesis and metastasis.

Deleted in Liver Cancer 1 (DLC1) is a tumour suppressor that encodes a RhoGTPase-activating protein (RhoGAP) and is frequently inactivated in many human cancers. The RhoGAP activity of DLC1 against Rho signalling is well documented and is strongly associated with the tumour suppressor functions of DLC1. However, the mechanism by which the RhoGAP activity of DLC1 is regulated remains obscure. Here, we report that phosphorylation of DLC1 at Ser549 by cyclic AMP-dependent protein kinase A contributes to enhanced RhoGAP activity and promotes the activation of DLC1, which suppresses hepatoma cell growth, motility and metastasis in both in vitro and in vivo models. Intriguingly, we found that Ser549 phosphorylation induces the dimerization of DLC1 and that inducible dimerization of DLC1 can rescue the tumour suppressive and RhoGAP activities of DLC1 containing a Ser549 deletion. Our study establishes a novel regulatory mechanism for DLC1 RhoGAP activity via dimerization induced by protein kinase A signalling.

Effect of sex on biomechanical properties of the proper hepatic artery in pigs and humans for liver xenotransplant.

OBJECTIVES: This study investigated the relation between biomechanical properties of the proper hepatic artery and sex in pigs and humans to provide the theoretical basis for selecting suitable donor in pig-to-human liver xenotransplant. MATERIALS AND METHODS: The proper hepatic arteries of 32 Chinese Hubei white pigs (8 males, 8 females, 8 castrated males, and 8 ovariectomized females) and 10 deceased donors (5 human men, 5 human women) were obtained. The pressure-diameter relations of the proper hepatic arteries were measured on biomechanical test equipment to calculate the incremental elastic modulus (Einc), pressure-strain elastic modulus (Ep), volume elastic modulus (Ev), and compliance. Each sample was sliced into 5-µm frozen sections and stained with hematoxylin-eosin. RESULTS: There were significant differences in Einc (F=10.24; P = .001), Ep (F=3.75; P = .001), and Ev (F=3.41; P = .002) of the proper hepatic arteries of female, male, and gonadectomized pigs; females had the lowest elastic modulus and the gonadectomized group had the highest (P < .01). There was a significant difference in compliance of the porcine proper hepatic arteries between the sexes, highest in the female group and lowest in the gonadectomized group (P < .01). No difference in the elastic modulus and compliance of the proper hepatic artery between the male pig and the human man. There was no difference between the female pig and the human woman. CONCLUSIONS: There were differences in the biomechanical properties of the proper hepatic arteries of the female, male, and gonadectomized pigs. The biomechanical properties of the human men/women proper hepatic artery match those of the porcine male/female hepatic artery. The correlation between sex and biomechanical properties of the proper hepatic artery in pigs could imply that a pig of the same sex should be chosen for pig-to-human liver xenotransplant.

Morphological and biomechanical remodeling of the hepatic portal vein in a swine model of portal hypertension.

OBJECTIVES: To obtain the morphological and biomechanical remodeling of portal veins in swine with portal hypertension (PHT), so as to provide some mechanical references and theoretical basis for clinical practice about PHT. METHODS: Twenty white pigs were used in this study, 14 of them were subjected to both carbon tetrachloride- and pentobarbital-containing diet to induce experimental liver cirrhosis and PHT, and the remaining animals served as the normal controls. The morphological remodeling of portal veins was observed. Endothelial nitric oxide synthase expression profile in the vessel wall was assessed at both mRNA and protein level. The biomechanical changes of the hepatic portal veins were evaluated through assessing the following indicators: the incremental elastic modulus, pressure-strain elastic modulus, volume elastic modulus, and the incremental compliance. RESULTS: The swine PHT model was successfully established. The percentages for the microstructural components and the histological data significantly changed in the experimental group. Endothelial nitric oxide synthase expression was significantly downregulated in the portal veins of the experimental group. Three incremental elastic moduli (the incremental elastic modulus, pressure-strain elastic modulus, and volume elastic modulus) of the portal veins from PHT animals were significantly larger than those of the controls (P < 0.05), whereas the incremental compliance of hepatic portal vein decreased. CONCLUSIONS: Our study suggests that the morphological and biomechanical properties of swine hepatic portal veins change significantly during the PHT process, which may play a critical role in the development of PHT and serve as potential therapeutic targets during clinical practice.

Morphological and biomechanical remodelling of the hepatic artery in a swine model of portal hypertension.

OBJECTIVES: To obtain the biomechanical and morphological remodelling of hepatic arteries in swine with portal hypertension. METHODS: A number of 20 white pigs was used, of which 14 were subjected to liver cirrhosis and portal hypertension (PHT) induced by carbon tetrachloride and pentobarbital; the rest were used as the control group. The biomechanical remodelling of the hepatic arteries was measured, namely, the incremental elastic modulus (E inc), pressure-strain elastic modulus (E p), volume elastic modulus (E v), the incremental compliance (C), the opening angle and the stained microstructural components of the vessels. RESULTS: The percentages for the microstructural components and the histologic data significantly changed in the experimental group, three incremental elastic moduli (E inc, E p, and E v) of the experimental group were significantly larger than those of the control group (P < 0.05); the compliance of hepatic arteries decreased greatly (P < 0.05) too. The opening angle (OA) was considerably larger than that of control group (P < 0.05). CONCLUSIONS: The study suggests that the morphological and biomechanical properties of swine hepatic arteries have changed significantly during the process of portal hypertension and that from biomechanical aspects, the hepatic arteries have also suffered from extensive remodelling, which in turn deteriorates the existing portal hypertension.

[The prognostic value of a modified WPSS based on routine laboratory parameters in patients with myelodysplastic syndromes: a preliminary result].

OBJECTIVE: To investigate the prognostic value of a modified WPSS based on routine laboratory parameters in Chinese patients with myelodysplastic syndromes (MDS). METHODS: One hundred and sixty four adult MDS patients were retrospectively analyzed. RESULTS: The median follow-up time was 19 (1-138) months and the median survival (MS) was 36 months. 2-year prospective survival (PS) was 60% and 5-year PS was 42%. In patients with very low-risk, low-risk, intermediate-risk, high-risk and very high-risk stratified by WPSS, 2-year PS was 100%, 96%, 81%, 38% and 14%, and 5-year PS was 100%, 83%, 54%, 20% and 0, respectively (P<0.01). Among parameters of laboratory routine examination, elevated mean cell volume (MCV), mean cell hemoglobin (MCH), neutrophil alkaline phosphatase (N-ALP) index and nucleated RBC PAS negative were good prognostic factors, while reduced Hb, BPC and bone marrow elevated blasts, dysplasia more than 1 lineage, and lymphocyte-like micromegakaryocyte (MEGly) as well as elevated serum LDH were poor prognostic factors in uni-variable analysis. Among them, MCV, MEGly and blast had independent prognostic significance in multi-variable analysis (P = 0.011, 0.013 and 0.016, respectively). WPSS was modified by omitting chromosomal karyotype and transfusion dependence and adding MCV and MEGly. In patients with low-risk, intermediate-risk and high-risk stratified by modified WPSS, 2-year PS was 94%, 68% and 49%, respectively; and 5-year PS was 86%, 53% and 14%, respectively (P<0.01). CONCLUSION: The modified WPSS worked well for prognostic prediction in Chinese patients with MDS.

[Study on karyotypic abnormalities and its prognostic significance in Chinese patients with primary myelodysplastic syndromes].

OBJECTIVE: To investigate the features and prognostic significance of chromosomal karyotype in patients with primary myelodysplastic syndromes (MDS). METHODS: Results of chromosomal karyotypes of 351 adult patients with primary MDS were retrospectively analyzed. RESULTS: Two hundred and thirty-seven cases (67.5%) had karyotypic abnormalities. Of them, 99 (41.7%) were numerical, 70 (29.5%) were structural, and 68 (28.8%) were complex abnormalities. In addition, among the 237 patients with chromosomal abnormalities, 130 (54.8%) showed single abnormality, 54 (22.8%) double abnormalities and 53 (22.4%) complex abnormalities (> or = 3 two independent aberrations). Four cases (1.7%) were multiploid. Aneuploidy or of chromosomal arm anomaly were detected all of the 46 chromosomes and the aberrations in frequent order were +8, -20/20q-, -7/7q-, -5/5q-, -18, -11/11q-/, +21, -Y, -21, -10, -16, -22, +9, del(12)(p12). The incidence of -5/5q- (5.1%) was lower in our series than in western countries (8.7% -23.4%) and 5q- syndrome was even less (0.3%). The incidences of +8 (19.1%) and -20/20q- (9.4%) were higher in our series than in western countries (1.2% -7.0%, 2.0% -3.5%, respectively). Chromosome translocations were detected in 31 cases (13.1%), including 12 novel translocations that have not been reported in MDS patients before. In addition, i(17)(q10) was detected in 9 cases (3.8%) of which 6 were simplex abnormality. Chromosomal duplication presented in 7 cases (3.0%) with 4 cases involved chromosome 1. According to IPSS chromosomal prognostic classification, the incidence of poor-risk karyotypes was increased in the advanced WHO subtypes (P < 0.001). The follow-up data were available in 177 patients with a median follow-up duration of 14.5 (1-131) months. The median OS was 36 [95% confident interval (CI) 25-46] months. According to IPSS chromosomal prognostic classification, the median OS of patients with good, intermediate and poor-risk cytogenetic subgroup were 51 (95% CI 25-77), 35 (95% CI 5-65) and 13 (95% CI 9-17) months, respectively (P = 0.004) and for NN-AN-AA karyotype classification, the median OS of NN, AN and AA were 51 (95% CI 24-78), 36 (95% CI 0.3-71) and 23 (95% CI 10-35) months, respectively (P = 0.039). CONCLUSION: The features of chromosomal abnormalities in Chinese patients with primary MDS shows some difference from that in western countries. Karyotype analysis is of great importance to predict prognosis and to tailor individualized therapy for MDS.

[Re-evaluation of classification of myelodysplastic syndromes with low percentage bone marrow blasts].

OBJECTIVE: To apply the WHO criteria and the minimal diagnostic criteria to the classification of myelodysplastic syndromes (MDS) with low percentage (< 0.050) bone marrow (BM) blasts. METHODS: Two hundred and ten MDS patients with less than 0.050 BM blasts diagnosed between 1988 and 2005 according to FAB criteria were retrospectively reclassified with WHO criteria (2001) and minimal diagnostic criteria. RESULTS: According to the WHO criteria, 5 patients were diagnosed as refractory anemia (RA), 7 as refractory anemia with ringed sideroblasts (RARS), 76 as refractory cytopenia with multilineage dysplasia (RCMD), 9 as RCMD-RS, 35 as MDS-unclassified (MDS-U), 3 as 5q - syndromes, and the rest 75 patients could not be classified suitably. Among the latter 75 patients 16 BM smears showed dysplasia in more than 2 cell lineage but only unilineage cytopenia in peripheral blood (PB). Nine of them were reclassified as RCMD after followed up for more than half a year. Forty-four BM smears showed erythroid dysplasia only, but bicytopenia or pancytopenia in PB. Twenty-seven of them were classified as RCMD after follow-up. Fifteen BM smears not showed dysplasia in any myeloid lineage were reclassified as MDS (5 patients), HS-MDS (5 patients) and idiopathic cytopenia of uncertain significance (ICUS) (5 patients) according to the MDS minimal diagnostic criteria. CONCLUSION: According to WHO criteria (2001), RA is the least diagnosis in MDS. The minimal diagnostic criteria for MDS classification of patients not fulfilled the standard criteria of MDS.

Unique cytogenetic features of primary myelodysplastic syndromes in Chinese patients.

Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms. Chromosomal abnormalities have been detected in 40-70% patients with primary MDS and are heterogeneous among patients of different races and from different backgrounds. In the current study, 351 Chinese adult patients with primary MDS were retrospectively analyzed for their chromosomal abnormalities by karyotyping. Among the 237 cases (67.5%) of chromosomal abnormalities, 99 were copy number changes alone (41.7%), 70 were structural abnormalities alone (29.5%), and 68 displayed both of these changes (28.8%). Overall, the frequency of -5/5q-/del(5)(q13-33) was 5.1% in these Chinese MDS patients, which was lower than that in the MDS patients of western countries (8.7-23.4%), and the incidence of 5q- syndrome was only 0.3% in Chinese MDS patients. On the other hand, the frequencies of trisomy 8 (19.1%) and -20/20q-/del(20)(q11-13) (9.4%) were higher than those in western countries (1.2-7.0% and 2.0-3.5%, respectively). Chromosomal translocations were also detected in 31 cases (13.1%) including 12 rare translocations that have not been reported in MDS patients before. In addition, i(17)(q10) was detected in nine cases (3.8%), of which six cases only had this single abnormality. According to the IPSS chromosomal prognostic classification, the incidence of poor-risk karyotypes increased in the advanced WHO subtypes (p < 0.001). Together, we detected the unique cytogenetic features of chromosomal abnormalities and some rare translocations of MDS among Chinese patients.

[Studying of clinical and laboratory features of chronic eosinophilic leukemias /hypereosinophilic syndrome].

OBJECTIVE: To investigate the clinical and laboratory features of chronic eosinophilic leukemias (CEL) and hypereosinophilic syndrome (HES). METHODS: The clinical manifestations, laboratory parameters were retrospectively analyzed in 20 patients with HES/CEL. Detection of the FIP1L1-PDGFRA fusion gene was performed by nested RT-PCR. JAK2 V617F mutation screening was processed through allele-specific PCR combined with sequence analysis. PCR-RFLP was used to discriminate homozygous from heterozygous mutation patterns. TCR gamma rearrangement was detected by PCR. RESULTS: Of the 20 patients, 19 were males and one female, with a median age of 33 (20 to 57) years. The FIP1L1-PDGFRA fusion gene positivity in bone marrow mononuclear cells in 12 cases was identified. All the breakpoints were identified by direct sequencing of cloned RT-PCR products in FIP1L1 intron 10 - 12 and in PDGFRA exon 12. In CEL the most common involved organs were lungs, heart and nervous system. Splenomegaly was significantly more frequent in CEL than in HES (92.5% vs 42.5%, P = 0.031). Anemia and myelofibrosis were common in CEL. There was no significant difference in circulating absolute eosinophil, leukocyte, platelet counts, hemoglobin level and percentages of eosinophil and blast cell in bone marrow between CEL and HES. The morphological abnormalities of eosinophils on bone marrow smear were easily found in CEL, including hypogranularity, and cytoplasmic vacuolization, increased basophilic granule. One patient with HES was found to have heterozygous JAK2 V617F mutation. Six patients had TCR gamma rearrangement, including 4 CEL and 2 HES. CONCLUSIONS: (1) There is a male predominance in HES/CEL, and the median age was in the thirties. (2) The most common involved organs in CEL were lung, heart and nervous system. Bone marrow morphology might be of a little help in diagnosis of CEL. (3) JAK2 V617F may be involved in the pathogenesis of HES. (4) Patients with CEL carried the FIP1L1-PDGFRA fusion gene and TCR gamma rearrangement concurrently, their relationship warrants further study.

[Polymorphisms of RAD51(G135C) and XRCC3(C241T) genes and correlations thereof with prognosis and clinical outcomes of acute myeloid leukemia].

OBJECTIVE: To investigate the impacts of RAD51G(135C) and XRCC3(C241T) genotypes on the response, adverse effects, and prognosis of acute myelocytic leukemia (AML). METHODS: RAD51(G135C), XRCC3(C241T), GSTT1, and GSTM1 genotypes were analyzed in 372 patients with AML, 226 males and 146 females, by PCR-RFLP or PCR. The Complete remission (CR) rate, adverse effects, overall survival (OS), and relapse-free survival (RFS) were compared among the groups with different genotypes. RESULTS: (1) During the induction chemotherapy, XRCC3(C241T) polymorphic allele was significantly associated with the shorter survival of the AML patients with t (15; 17)/PML-RARalpha (OR = 8.750, P = 0.046). Among the non-M3 patients, the complete remission (CR) rate of those with double RAD51(G135C) and GSTT1 wild genotypes was 71.6%, significantly higher than that of those not with double RAD51(G135C) and GSTT1 wild genotypes (54.4%, P = 0.028). (2) The OS of the non-M3 AML patients with double RAD51(G135C) and GSTT1 wild genotypes was (39.1 +/- 7.1) months, significantly longer than those with double variant types [(22.4 +/- 3.2) months, P = 0.042]. The relapse-free survival (RFS) of the M4EO and M2 patients with double XRCC3(C241T) and GSTT1 wild type genotype were 48.3 months and 56.5 months, both significantly longer than those of the patients with double variant genotypes (28.8 months and 10.0 months respectively, both P < 0.05). The OS of the M2 patients with triple RAD51(G135C), GSTT1, and GSTM1 variant genotypes was (22.4 +/- 3.2) months, significantly shorter than those with triple RAD51(G135C), GSTT1, and GSTM1 wild genotypes [(39.1 +/- 7.1) months, P = 0.042]. The RFS of the M2 patients with triple RAD51(G135C), GSTT1, and GSTM1 variant genotypes was 10.0 months, significantly shorter than that of the patients with triple RAD51(G135C), GSTT1, and GSTM1 wild genotypes (64.2 months, P = 0.015). (3) The risk levels of neutropenia, nausea and vomiting, and alopecia of the patients with variant XRCC3(C241T) genotype were all significantly higher than those of the wild type genotype (all P < 0.05). The risk of hematuria of the patients with variant genotype was significantly higher than that of the patients with wild genotype (P = 0.017). CONCLUSION: The polymorphisms of XRCC3(C241T) and RAD51(G135C) genes are significantly related to response to therapy, adverse effects, and prognosis of AML. Detection of the XRCC3(C241T) and RAD51(G135C) genotypes may be useful in selecting individual chemotherapy regimens for patients with AML.

[Preliminary study of diagnosis of patients with myelodysplastic syndromes by routine laboratory parameters].

OBJECTIVE: To explore the value of routine laboratory parameters in diagnosis of myelodysplastic syndromes (MDS) and differential diagnosis of patients with hypoplastic MDS from chronic aplastic anemia (CAA) for providing reference standard for primary hospitals. METHODS: The laboratory parameters at diagnosis of 152 MDS patients with less than 0.05 bone marrow blasts and 86 CAA patients were retrospectively analyzed. RESULTS: There were significant differences between MDS and CAA in Hb, red cell distribution width-coefficient variation (RDW-CV), immature reticulocyte fraction (IRF), BPC, the ratio of G1 (the sum percentage of myeloblast and promyelocyte) to G2 (the sum percentage of neutrophilic myelocyte and metamyelocyte) (Ratio G), the ratio of El (the sum percentage of proerythroblast and early erythroblast) to E2 (the sum percentage of intermediate erythroblast and late erythroblast) (Ratio E), megakaryocyte count (Meg), erythroblast PAS, neutrophil alkaline phosphatase (N-ALP), and serous levels of indirect bilirubin (IBIL), lactose dehydrogenase (LDH), folic acid (FA), VitB12 and ferritin. Chromosome abnormalities were found in 74 MDS patients (48.7%) but in none of CAA patients (P < 0.001). Furthermore, for differentiating MDS with less than 0.05 blasts from CAA, the sensitivity and specificity of combination of Meg, PAS, and IBIL level was 89.1% and 92.7%, the Youden index (gamma) was 0.818. Moreover, in the seven hypoplastic MDS cases, BPC, myeloblast percentage, Ratio G, Meg, erythroblast PAS and FA were statistically different from those of CAA; the sensitivity and specificity of combination of PAS and BPC was 85.7% and 100%, the gamma was 0.857; the sensitivity and specificity combination of Ratio G, Meg PAS was 85.7% and 98.8% respectively, the gamma was 0.845. CONCLUSION: The routine laboratory parameters, especially BPC, Meg, Ratio G, PAS, IBIL may be helpful for the diagnosis of MDS and differential diagnosis of hypoplastic MDS from CAA.

Biomechanical properties of ascending aorta and pulmonary trunk in pigs and humans.

BACKGROUND: This study aims to obtain the biomechanical properties of ascending aorta and pulmonary trunk between healthy humans and pigs of different months, so as to provide necessary biomechanical experimental basis for anastomosing blood vessel in pig-to-human heart xenotransplantation. METHODS: Ascending aorta and pulmonary trunks of the six deceased donors (male 4, female 2) and 42 Chinese Hubei white pigs aged 1-7 months were performed biomechanical test. The blood vessel was given periodic permanent loading and unloading, and repeated force-deformation data were obtained. The elastic properties of the blood vessels were obtained by curve from experimental data. RESULTS: The biomechanical material constant of ascending aorta and pulmonary trunk of pigs did not increase with the increase of age (F = 14.569, P = 0.126). The biomechanical material constant of humans was basically similar to that of pigs aged 1-7 months (F = 12.264, P = 0.225). The elastic modulus was the biggest in pigs aged 7 months in comparison with that in other ages (F = 27.425, P = 0.032). There was no significant difference of elastic modulus of corresponding blood vessel between humans and pigs of different months (F = 17.328, P = 0.215). CONCLUSIONS: Our present study suggests that there was no significant difference of elastic properties of ascending aorta and pulmonary trunks between humans and pigs. From biomechanical aspects, anastomosis of corresponding ascending aorta and pulmonary trunks in the process of pig-to-human heart xenotransplantation may be feasible.

[Chromosomal structural changes in patients with myelodysplastic syndrome].

OBJECTIVE: To study the clinical and laboratory features of myelodysplastic syndromes (MDS) with chromosomal structural changes. METHODS: Among 584 MDS cases with cytogenetic data, 50 patients with chromosomal structural changes, 34 males and 16 females, aged 50.5 (9 approximately 77), were reclassified according to the WHO criteria, and their clinical and laboratory features were analyzed retrospectively. RESULTS: The incidence of chromosomal structural changes in the MDS patients was 7.4%. i (17) (q10), t (1; 3) (p36; q21), der (1; 7) (q10; p10), and der (22) occurred frequently. The chromosomal structural changes in 13 cases were reported in the literatures for the first time. The patients with i (17) (q10) were characterized by moderate to severe anemia and a poor prognosis. Predominant dysgranulocytopoiesis and dysmegakaryocytopoiesis, including a nuclear shift to the left, pseudo-Pelger-Hüet anomaly, hypogranularity, and increased micromegakaryocytes. The patients with t (1; 3) (p36; q21) revealed macrocytic anemia, obvious dysmegakaryocytopoiesis, and dysgranulocytopoiesis, accompanied by defective differentiation and monocytosis. The bone marrow cells from the MDS patients with t (1; 3) (p36; q21) mainly or only expressed MEL1. The initial symptom of the patients with der (1; 7) (q10; p10) was infection. These patients showed macrocytic or normocytic anemia. Trilineage dysplasia was found in the bone marrow smears. The patients had short median survival. The patients with der (22) revealed anemia, and normal or elevated platelet counts. Hypogranularity and pseudo-Pelger-Hüet anomaly were present in all cases with der (22). The megakaryocytes were small and generally contained one or two nuclei. A translocation involvement of 22q11 was frequently found in the patients with der (22). CONCLUSION: MDS patients with i (17) (q10), t (1; 3) (p36; q21), and der (1; 7) (q10; p10) may be a new unique clinical-pathologic subsets. Whether the MDS patients with der (22) can be considered as a new unique subject remains to be confirmed by future studies.

[Karyotypic and IPSS grouping of primary myelodysplastic syndromes patients: a comparison between FAB- and WHO-classification].

OBJECTIVE: To compare the results of cytogenetic and IPSS grouping of primary myelodysplastic syndromes (pMDS) patients classified by FAB- or WHO classification. METHODS: Two hundred and thirty seven cases of pMDS who were previously classified according to FAB criteria were reclassified with WHO classification. A comparison was made between the results of the two classifications. RESULTS: For the detection rates of cytogenetic abnormality and its risks group, there was no difference among the FAB subgroups but the detection rate was different between the WHO refractory cytopenia with multilineage dysplasia (RCMD) and RA subgroups (74.4% and 42.5%, respectively) (P < 0.001). The percentage of good karyotype abnormalities in RA (65.0%) was higher than that in RCMD (24.4%) (P < 0.001), and the percentages of intermediate and poor karyotype abnormalities in RCMD (48.9% and 26.7%, respectively) were higher than that in RA (27.5% and 7.5%, respectively) (P < 0.05). There was a good correlation between the subgroups and IPSS risk groups for both the WHO classification and the FAB classification, but the WHO classification further reflected the differences between RCMD and RA and RAEB-I and RAEB-II subgroups. The percentage of low-risk group in RCMD (1.1%) was lower than that in RA (10.0%) (P < 0.05), and the percentage of high-risk group in RAEB-II (30.5%) was higher than that in RAEB-I(0) (P < 0.001). CONCLUSION: For the correlation between subgroups and cytogenetic abnormalities and IPSS risk groups, the WHO-classification is better than the FAB-classification.

[Morphologic and clinical study of 131 cases of plasma cell myeloma].

OBJECTIVE: To study the characteristics histologic and cytologic features and clinical usefulness of plasma cell myeloma (PCM) subtyping according to WHO PCM classification. METHODS: Bone marrow biopsy plastic-embedded sections were stained with H-G-E and Gomori's stains, and bone marrow aspirate smears were stained with Wright's stain. The clinicopathologic findings were then analyzed. RESULTS: Of the 131 cases with PCM, three types of growth patterns were noted: interstitial (21 cases, 16.0%), nodular (46 cases, 35.1%) and packed (64 cases, 48.9%). Besides, there were three cytologic subtypes: mature plasma cell type (43 cases, 32.8%), immature (81 cases, 61.8%) and pleomorphic (7 cases, 5.3%) types. The age of patients with mature plasma cell type was significantly higher than that of immature type (P = 0.005); and the number of tumour cells in bone marrow smears was significantly higher than that of immature type (P = 0.003). The numbers of WBC and platelets in peripheral blood were also significantly higher than that of pleomorphic type (P = 0.024, P = 0.002, respectively). On the other hand, the number of platelets in peripheral blood of immature type was significantly higher than that of pleomorphic type (P = 0.019). Marrow fibrosis was more frequently observed in immature type than in mature plasma cell type (P = 0.000). The incidence of marrow fibrosis and osteolytic lesions was higher in high risk group than in low risk group (P = 0.000, P = 0.023 respectively). Twenty-one cases (56.8%) of the 37 cases treated with MP or MP and M2 chemotherapeutic regimens showed good response. However, there was no significant difference in treatment response and survival between different subtypes. CONCLUSIONS: Each subtype of PCM carries different clinicopathologic features in some aspects. The classification carries important value in pathologic diagnosis and probably in predicting prognosis.