Network-Based Transcriptome Analysis Reveals FAM3C as a Novel Potential Biomarker for Glioblastoma.

Glioblastoma (GBM) is the most common form of malignant primary brain tumor with a high mortality rate. The aim of the present study was to investigate the clinical significance of Family with Sequence Similarity 3, Member C, FAM3C, in GBM using bioinformatic-integrated analysis. First, we performed the transcriptomic integration analysis to assess the expression profile of FAM3C in GBM using several data sets (RNA-sequencing and scRNA-sequencing), which were obtained from TCGA and GEO databases. By using the STRING platform, we investigated FAM3C-coregulated genes to construct the protein-protein interaction network. Next, Metascape, Enrichr, and CIBERSORT databases were used. We found FAM3C high expression in GBM with poor survival rates. Further, we observed, via FAM3C coexpression network analysis, that FAM3C plays key roles in several hallmarks of cancer. Surprisingly, we also highlighted five FAM3C­coregulated genes overexpressed in GBM. Specifically, we demonstrated the association between the high expression of FAM3C and the abundance of the different immune cells, which may markedly worsen GBM prognosis. For the first time, our findings suggest that FAM3C not only can be a new emerging biomarker with promising therapeutic values to GBM patients but also gave a new insight into a potential resource for future GBM studies.

Altering biomolecular condensates as a potential mechanism that mediates cannabidiol effect on glioblastoma.

Glioblastoma (GBM) is an extremely aggressive primary brain tumor with poor prognosis, short survival time post-diagnosis and high recurrence. Currently, no cure for GBM exists. The identification of an effective therapeutic modality for GBM remains a high priority amongst medical professionals and researches. In recent studies, inhalant cannabidiol (CBD) has demonstrated promise in effectively inhibiting GBM tumor growth. However, exactly how CBD treatment affects the physiology of these tumor cells remains unclear. Stress granules (SG) (a sub-class of biomolecular condensates (BMC)) are dynamic, membrane-less intracellular microstructures which contain proteins and nucleic acids. The formation and signaling of SGs and BMCs plays a significant role in regulating malignancies. This study investigates whether inhaled CBD may play an intervening role towards SGs in GBM tumor cells. Integrated bioinformatics approaches were preformed to gain further insights. This includes use of Immunohistochemistry and flow cytometry to measure SGs, as well as expression and phosphorylation of eukaryotic initiation factor-2α (eIF2α). The findings of this study reveal that CBD receptors (and co-regulated genes) have the potential to play an important biological role in the formation of BMCs within GBM. In this experiment, CBD treatment significantly increased the volume of TIAR-1. This increase directly correlated with elevation in both eIF2α expression and p-eIF2α in CBD treated tissues in comparison to the placebo group (p < 0.05). These results suggest that inhalant CBD significantly up-regulated SGs in GBM, and thus support a theory of targeting BMCs as a potential therapeutic substrate for treating GBM.

Inhalant cannabidiol impedes tumor growth through decreased tumor stemness and impaired angiogenic switch in NCI-H1437-induced human lung cancer model.

Lung cancer remains the most chronic form of cancer and the leading cause of cancer mortality in the world. Despite significant improvements in the treatment of lung cancer, the current therapeutic interventions are only partially effective, necessitating the continued search for better, novel alternative treatments. Angiogenesis and cancer stem cells play a central role in the initiation and propagation of cancers. Tumor angiogenesis is triggered by an angiogenic switch when pro-angiogenic factors exceed anti-angiogenic components. Although many anti-angiogenic agents are used in cancer treatment, there are therapeutic limitations with significant side effects. In recent years, cannabinoids have been investigated extensively for their potential anti-neoplastic effects. Our previous findings showed that cannabidiol (CBD) could impede tumor growth in mouse models of melanoma and glioblastoma. Importantly, CBD has been suggested to possess anti-angiogenic activity. In this study, we tested, for the first time, inhalant CBD in the treatment of heterotopic lung cancer and whether such potential effects could reduce cancer stem cell numbers and inhibit tumor angiogenesis. We implanted NCI H1437 human lung cancer cells in nude mice and treated the mice with inhalant CBD or placebo. The outcomes were measured by tumor size and imaging, as well as by immunohistochemistry and flow cytometric analysis for CD44, VEGF, and P-selectin. Our findings showed that CBD decreased tumor growth rate and suppressed expression of CD44 and the angiogenic factors VEGF and P-selectin. These results suggest, for the first time, that inhalant CBD can impede lung cancer growth by suppressing CD44 and angiogenesis.

[Effect of splenectomy on the risk of hepatocellular carcinoma development among patients with liver cirrhosis and portal hypertension: a multi-institutional cohort study].

Objective: To identify whether splenectomy for treatment of hypersplenism has any impact on development of hepatocellular carcinoma(HCC) among patients with liver cirrhosis and hepatitis. Methods: Patients who underwent splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension between January 2008 and December 2012 were included from seven hospitals in China, whereas patients receiving medication treatments for liver cirrhosis and portal hypertension (non-splenectomy) at the same time period among the seven hospitals were included as control groups. In the splenectomy group, all the patients received open or laparoscopic splenectomy with or without pericardial devascularization. In contrast, patients in the control group were treated conservatively for liver cirrhosis and portal hypertension with medicines (non-splenectomy) with no invasive treatments, such as transjugular intrahepatic portosystemic shunt, splenectomy or liver transplantation before HCC development. All the patients were routinely screened for HCC development with abdominal ultrasound, liver function and alpha-fetoprotein every 3 to 6 months. To minimize the selection bias, propensity score matching (PSM) was used to match the baseline data of patients among splenectomy versus non-splenectomy groups. The Kaplan-Meier method was used to calculate the overall survival and cumulative incidence of HCC development, and the Log-rank test was used to compare the survival or disease rates between the two groups. Univariate and Cox proportional hazard regression models were used to analyze the potential risk factors associated with development of HCC. Results: A total of 871 patients with liver cirrhosis and hypertension were included synchronously from 7 tertiary hospitals. Among them, 407 patients had a history of splenectomy for hypersplenism (splenectomy group), whereas 464 patients who received medical treatment but not splenectomy (non-splenectomy group). After PSM,233 pairs of patients were matched in adjusted cohorts. The cumulative incidence of HCC diagnosis at 1,3,5 and 7 years were 1%,6%,7% and 15% in the splenectomy group, which was significantly lower than 1%,6%,15% and 23% in the non-splenectomy group (HR=0.53,95%CI:0.31 to 0.91,P=0.028). On multivariable analysis, splenectomy was independently associated with decreased risk of HCC development (HR=0.55,95%CI:0.32 to 0.95,P=0.031). The cumulative survival rates of all the patients at 1,3,5,and 7 years were 100%,97%,91%,86% in the splenectomy group,which was similar with that of 100%,97%,92%,84% in the non-splenectomy group (P=0.899). In total,49 patients (12.0%) among splenectomy group and 75 patients (16.2%) in non-splenectomy group developed HCC during the study period, respectively. Compared to patients in non-splenectomy group, patients who developed HCC after splenectomy were unlikely to receive curative resection for HCC (12.2% vs. 33.3%,χ²=7.029, P=0.008). Conclusion: Splenectomy for treatment of hypersplenism may decrease the risk of HCC development among patients with liver cirrhosis and portal hypertension.

Cardiac Disease Associated Genetic Variants in Yi Nationality in Regions with High Incidence of Yunnan Sudden Unexplained Death.

ABSTRACT: Objective To explore the association of cardiac disease associated genetic variants and the high incidence of Yunnan sudden unexplained death （YNSUD） in Yi nationality. Methods The genomic DNA was extracted from peripheral blood samples collected from 205 Yi villagers from YNSUD aggregative villages （inpatient group） and 197 healthy Yi villagers from neighboring villages （control group）. Fifty-two single nucleotide variants （SNVs） of 25 cardiac disease associated genes were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF-MS）. The SPSS 17.0 was used to analyze data. The pathogenicities of variants with differences between the two groups that have statistical significance were predicted by protein function prediction software PolyPhen-2 and SIFT. All villagers from inpatient group were given electrocardiogram （ECG） examination using a 12-lead electrocardiograph. Results The allele frequency and the genotype frequency of missense mutation DSG2 （rs2278792, c.2318G>A, p.R773K） of pathogenic genes of arrhythmogenic right ventricular cardiomyopathy （ARVC） in inpatient group was higher than that in control group （P<0.05）. Abnormal ECG changes were detected in 71 individuals （34.6%） in the inpatient group, among which 54 individuals carried R773K mutation, including clockwise （counterclockwise） rotation, left （right） axis deviation, ST segment and T wave alteration and heart-blocking. Conclusion Definite pathogenic mutations have not been found in the 52 cardiac disease genes associated SNVs detected in Yi nationality in regions with high incidence of YNSUD. The cause of high incidence of YNSUD in Yi nationality needs further study.

[Effect of imatinib on the height of children with chronic myeloid leukemia in the chronic phase].

Objective: To evaluate the effect of imatinib on growth impairment in children with chronic myeloid leukemia (CML-CP) in the chronic phase. Methods: From July 2018 to July 2019, questionnaires were distributed to CML children aged <18 years at the time of diagnosis who were receiving imatinib for at least 3 months or to their parents in China. The height-for-age standard deviation score (HtSDS) and the difference of standard deviation integral (△HtSDS) were used to explore the change in height with imatinib therapy. Results: The data of 238 respondents were included; 138 (58.0% ) respondents were men. The median age at the first diagnosis of CML was 11.0 years (range, 1.4-17.9 years) , and 93 (39.0% ) respondents were at the prepuberty stage. At the time of completing the questionnaires, the median age was 15.0 years (range, 2.0-34.0 years) . The median duration of imatinib therapy was 28 months (range, 3-213 months) . Among all the respondents, the mean HtSDS when completing the questionnaires (-0.063±1.361) was significantly lower than that at the time of starting imatinib treatment (0.391±1.244) (P<0.001) . Total 71.0% respondents showed growth impairment that was more common in those starting imatinib therapy at prepubertal age than in those starting at pubertal age. Multivariate analysis showed that younger at the start of imatinib therapy (P<0.001) and longer duration of imatinib therapy (P<0.001) were significantly associated with severe growth impairment on imatinib therapy. Conclusions: Imatinib induced growth impairment in children with CML-CP. Younger the age of initiation and longer the duration of imatinib therapy, more obvious the effect of imatinib on growth impairment.

[The influence and clinical significance of proteasome inhibitor on serum bone metabolite markers in patients with myeloma bone disease].

Objective: To investigate the influence and clinical significance of proteasome inhibitor on serum bone metabolite markers including tartrate-resistant acid phosphatase 5b isoenzyme (TRACP-5b), type I collagen carboxy terminal peptide ß(ß-CTX), type I procollagen amino terminal prolongation peptide (PINP) and vitamin D3 in patients with myeloma bone disease (MBD). Methods: From April 2015 to June 2018, 68 patients with newly diagnosed MBD who admitted to our hospital were treated with proteasome inhibitor-based regimen. Serum concentration of TRACP-5b、ß-CTX、PINP and vitamin D3 were measured before treatment and after 4 and 8 cycles of chemotherapy, and imaging changes were observed. Results: After 4 and 8 cycles of chemotherapy, serum levels of TRACP-5b, ß-CTX and vitamin D3 were decreased significantly (P<0.05). The serum concentration of PINP was (78.1±44.9) ng/L before chemotherapy, while after 4 cycles, it turned to (94.5±56.1) ng/L without significant difference (t=-1.871, P=0.063). Moreover, it increased to (173.3±80.5) ng/L after 8 cycles of chemotherapy with significant difference (t=-8.272, P<0.001). The proportion of imaging classification ≥3 among all patients was 66.2%, and it decreased to 60.3% after 4 cycles of chemotherapy without significant difference (χ(2)=0.569, P=0.477). The proportion of imaging classification ≥3 after 8 cycles of chemotherapy decreased to 44.5%, which was significantly lower than that before treatment (χ(2)=6.260, P=0.012). After 8 cycles of chemotherapy, 63 patients were evaluable, of which 50 were effective and 13 were ineffective. Serum concentration of PINP in the effective group was higher than that in the ineffective group ((190.7±78.5) ng/L vs (106.5±47.3) ng/L,t=5.762, P<0.001), and the serum concentration of vitamin D3 in the effective group was lower than that in the ineffective group ((11.7±4.8) µg/L vs (15.6±5.5) µg/L, t=-2.478, P=0.016). The proportion of patients with more than grade 3 bone disease of the effective group was also significantly lower than that of the ineffective group (38.0% vs 69.2%, χ(2)=4.076, P=0.044). There was no significant difference in the serum concentration of TRACP-5b and ß-CTX between two groups. Conclusion: After treatment with the proteasome inhibitor -based regimen, the serum concentrations of TRACP-5b, ß-CTX and vitamin D3, which reflect osteoclast activity in MBD patients were decreased, the serum concentration of PINP indicating osteoblast activity was increased, and the grade of imaging of bone disease was decreased.

hsa_circ_0121582 inhibits leukemia growth by dampening Wnt/ß-catenin signaling.

PURPOSE: The prognosis of AML patients with chemotherapy is poor, especially those who are insensitive to and resistant to chemotherapy drugs. To clarify the underlying pathogenesis of AML and provide new therapeutic targets for clinical treatment, we explore the role of circRNA in leukemia. METHODS: High-throughput circRNA sequencing analysis was performed in patients with leukemia and healthy donors. RT-qPCR and western blot analysis were used to determine expression of GSK3ß. RNA pull-down assay was used to detect miRNAs pulled down by hsa_circ_0121582. RNA immunoprecipitation assay was performed to evaluate the binding capacity between TET1 and hsa_circ_0121582. RESULTS: A new and highly stable circRNA was found, which was derived from the reverse splicing of GSK3ß exon 1 to exon 7, and hsa_circ_0121582 was down-regulated in leukemia cells. In gain-of-function experiments, the up-regulated hsa_circ_0121582 inhibited the proliferation of leukemia cells in vitro and in vivo. In the cytoplasm, hsa_circ_0121582 could act as a sponge for miR-224, attenuate the inhibiting effect of miR-224 on GSK3ß, and thus up-regulate the expression level of GSK3ß. In addition, hsa_circ_0121582 could bind to GSK3ß promoter in the nucleus, and recruit DNA demethylase TET1 to ensuring the transcription of GSK3ß. The upregulated GSK3ß inhibited the Wnt/ß-catenin signaling pathway, and reduced the aggregation of ß-catenin in the nucleus, thus inhibited the proliferation of leukemia cells. CONCLUSIONS: This study found that hsa_circ_0121582 was involved in the inhibition of tumor proliferation, and the restoration of hsa_circ_0121582 could be an effective treatment strategy for patients with leukemia.

[Expression of CD45 in newly diagnosed multiple myeloma and the relationship with prognosis].

Objective: To explore the expression of CD45 in newly diagnosed multiple myeloma (MM) and its relationship with clinical efficacy and prognosis. Methods: This study retrospectively analyzed expression and distribution of CD45 in 130 cases of newly diagnosed MM, comparing clinical efficacy and prognosis in CD45(+)/CD45(-) groups. Results: ①The CD45(+) group was 33 cases (25.38%) , and CD45(-) group was 97 cases (74.62%) . ②The objective remission rate (ORR) of CD45(+) and CD45(-)group was 33.33% and 64.95%, respectively. The difference was statistically significant (P=0.002) . For patients in Bortezomib regimen, the ORR of CD45(+) and CD45(-) group was 35.71% and 66.25%, respectively. The difference was statistically significant (P=0.005) . ③The median progress free survival (PFS) of CD45(+) group and CD45(-) group was 29.8 (95%CI 10.0-59.0) months vs 34.5 (95%CI 6.0-69.0) months (χ(2)=14.59, P<0.001) and the median overall survival (OS) was 32.5 (95%CI 10.0-68.0) months vs 37.6 (95%CI 6.0-78.0) months (χ(2)=11.42, P=0.001) , respectively. Among the patients in bortezomib regimen, The median PFS and median OS of CD45 (+) group and CD45(-) group were 30.3 (95%CI 10.0-59.0) months vs 36.3 (95%CI 6.0-69.0) months (χ(2)=14.75, P=0.001) and 34.0 (95%CI 10.0-68.0) months vs 39.5 (95%CI 6.0-78.0) months (χ(2)=10.62, P=0.001) . ④Cox risk regression model analysis showed that serum creatinine≥176.8 µmol/L (HR=5.078, 95%CI 1.744-14.723, P=0.001) , CD45 positive (HR=14.504, 95%CI 0.168-0.42, P=0.001) , LDH≥220 IU/L (HR=1.308, 95%CI 1.16-2.417, P=0.015) were independent risk prognostic factors. Conclusion: CD45 expression is a risk prognostic factor of MM patients. Bortezomib did not improve the poor prognosis of CD45(+) MM patients.

[PDCD4 enhances the inhibitory effect of As(2)O(3) on the growth and NF-κB signaling pathway in neuroblastoma cells].

Objective: To investigate the inhibitory effect of programmed cell death factor 4 (PDCD4) on arsenic trioxide (As(2)O(3))-induced cell growth and nuclear factor kappa B (NF-κB) signaling pathway in neuroblastoma. Methods: The PDCD4 overexpression vector was transfected into neuroblastoma cells and detected by fluorescence quantitative PCR and Western blot. As(2)O(3) was used to treat PDCD4 overexpressing neuroblastoma cells. MTT assay was used to measure the proliferation. Colony formation assay was used to determine the cell clone forming ability. Apoptosis was measured by flow cytometry. Western blot was used to detect the expression of NF-κB p65 and cleaved caspase-3 protein in cells. Results: The transfection of PDCD4 overexpression vector significantly increased the expression level of PDCD4 in neuroblastoma cells. The cell survival rates of the control group, PDCD4 group, As(2)O(3) group and As(2)O(3)+ PDCD4 group were 100%, (72.14±5.20)%, (62.58±3.14)% and (40.87±2.47)%, respectively. The colony formation rates in these four groups were (91.25±8.36)%, (65.32±7.14)%, (57.23±5.28)% and (37.14±3.64)%, respectively. In addition, the cell apoptotic rates of these four groups were (3.57±0.24)%, (28.64±3.20)%, (36.41±4.58)% and (49.65±5.27)%, respectively. Therefore, overexpression of PDCD4 in the absence or presence of As(2)O(3) inhibited cell proliferation and clone formation ability, while promoted apoptosis. Furthermore, the expression levels of cleaved caspase-3 in the control group, PDCD4 group, As(2)O(3) group and As(2)O(3)+ PDCD4 group were 0.21±0.03, 0.30±0.02, 0.43±0.05 and 0.57±0.06, respectively. And the expression levels of NF-κB p65 protein were 0.68±0.04, 0.52±0.03, 0.43±0.04, and 0.32±0.02, respectively. Compared with the control group, the expression levels of NF-κB p65 protein in PDCD4 group, As(2)O(3) group and As(2)O(3)+ PDCD4 group were significantly decreased (P<0.05), whereas the expression level of cleaved Caspase-3 protein was significantly increased (P<0.05). The changes in As(2)O(3)+ PDCD4 group were more significant than those in PDCD4 group and As(2)O(3) groups (both P<0.05). Conclusion: PDCD4 enhances the inhibitory effect of As(2)O(3) on the growth and NF-κB signaling pathway in neuroblastoma cells.

[Effects of miR-144 on proliferation, apoptosis and cisplatin resistance by targeting MYCN in pediatric neuroblastoma].

Objective: To investigate the effects and mechanisms of miR-144 on proliferation, apoptosis and cisplatin (DDP) resistance of neuroblastoma cells. Methods: Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the mRNA expressions of miR-144 and MYCN in neuroblastoma cell lines, including SH-SY5Y and SK-N-SH, and human umbilical vein endothelial cells HUVEC. The miR-negative control, miR-144 mimics, si-negative control, si-MYCN, miR-144 mimics and pcDNA, miR-144 mimics and pcDNA-MYCN co-transfected SH-SY5Y cells were described as miR-NC, miR-144, si-NC, si-MYCN, miR-144+ pcDNA and miR-144+ pcDNA-MYCN group, respectively. The half maximal inhibitory concentration (IC(50)) and cell proliferation were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. The protein expressions of MYCN, p21, cyclin D1, Bax, Bcl-2 were analyzed by western blot. Cell apoptosis was detected by flow cytometry. The cell fluorescence activity was detected by double luciferase reporter gene assay. Results: Compared with HUVEC cells, the expressions of miR-144 in neuroblastoma cells SH-SY5Y and SK-N-SH significantly decreased, while the mRNA and protein expression of MYCN significantly increased. The IC(50) of DDP was 9.16 µg/ml in SH-SY5Y cells. The absorbance value in 490nm (A(490) value) of miR-144 group was 0.30±0.03, significantly lower than 0.46±0.03 of miR-NC group. The cell apoptotic rate of miR-144 group was 26.94%±2.01%, significantly higher than 9.68%±0.52% of miR-NC group. The IC(50) value of DDP in miR-144 group was 2.95±0.26, significantly lower than 9.23±0.61 of miR-NC group. The expressions of p21, cyclin D1, Bax, Bcl-2 in miR-NC and miR-144 group were 2.67±0.19, 0.41±0.04, 2.12±0.21, 0.18±0.01 and 1.01±0.07, 1.00±0.06, 1.00±0.05, 1.00±0.06, respectively, with statistical significance (all P<0.05). Knockdown of MYCN showed the similar effects with those of miR-144 overexpression in SH-SYSY cells. MiR-144 significantly inhibited the fluorescence activity of ectopic MYCN expressing cells and negatively regulated the expression of MYCN. Overexpression of MYCN can reverse the effects of miR-144 on proliferation inhibition, apoptosis promotion and sensitization of SH-SY5Y cells to DDP. Conclusion: MiR-144 inhibits proliferation, promotes apoptosis and enhances the sensitivity of neuroblastoma cells to DDP through targeting MYCN, which provides a potential treatment for neuroblastoma.

Forensic Pathology Analysis of 363 Sudden Death Cases in Yunnan Province.

OBJECTIVES: To study the epidemiological and pathological features of sudden death （SD） in Yunnan Province and to provide scientific evidence for prevention and forensic identification of sudden death. METHODS: Totally 363 SD cases were collected from the autopsies between 2009 and 2017 in the Forensic Centre of Kunming Medical University. The related factors such as etiology, age, inducing factor, time interval between the onset of disease and death, morbidity season and pathological change were retrospectively analysed. RESULTS: The incidence of SD in males was significantly higher than that of females. The peak age was ≥35-55 years. The mortality rate was relatively high within 6 h after the onset of disease. The season order with descending number of deaths was spring, summer, winter and autumn. The top ten causes of SD were coronary heart disease, sudden unexplained death （SUD）, cerebral hemorrhage, acute hemorrhagic necrotic pancreatitis, aortic dissection rupture, cardiomyopathy, pneumonia, pulmonary thromboembolism, amniotic fluid embolism and allergy. Exercise, infusion, surgery, medication and minor injury were the most common predisposing factors of sudden coronary death. Consciousness disorder or coma, chest pain or chest tightness, and abdominal pain were the most common premortem symptoms of sudden coronary death. CONCLUSIONS: The SD is more common in middle-aged males, which is the key population for the prevention of SD. For the forensic identification and prevention of SD, the attention on SUD should be paid.

[Clinical significance of the ratio of serum beta-CTX/PINP in multiple myeloma bone diseases and bone metastases].

Objective: To explore the clinical significance of serum bone metabolites ß C-termianl telopeptide of type Ⅰ collagen(ß-CTX), Procollagen type Ⅰ N-terminal peptide(PINP) concentration and ratio of beta -CTX/PINP in multiple myeloma bone disease (MMBD) and bone metastases. Methods: A total of 31 cases of MM, 46 cases of bone metastases and 12 healthy controls were enrolled in the department of hematology, oncology and physical examination center of Henan Provincial People's Hospital respectively from October 2016 to October 2017. According to the imaging findings, MMBD was divided into 0-4 grades, group A included the patitents with grade 0-2 of osteopathy (n=8), and group B included the grade 3-4 (n=23). After two courses of chemotherapy, the curative effect was evaluated. MM group were divided into effective group (above partial remission , n=22) and uneffective group (unreached partial remission, n=9). ELISA method was used to detect the concentration of serum beta -CTX and PINP, and the ratio of beta -CTX/PINP was calculated. Results: The serum beta -CTX concentration in newly diagnosed MM, bone metastases and healthy control were (3 563 ± 544)ng/L, (6 690±343)ng/L, (2 726±1 026)ng/L (χ2=22.207, P<0.001), PINP concentration were (72 ± 14) ng/L, (112 ± 62) ng/L, (171 ± 62) ng/L (χ2=7.418, P=0.024) , and beta -CTX/PINP ratio were 93±19, 141±21, 17±8 (χ2=20.192, P<0.001), the differences were statistically significant. The ratio of initial MM beta -CTX/PINP was higher than that of healthy control (P=0.001). The concentration of beta -CTX (P=0.003) and the ratio of beta -CTX/PINP(P<0.001) in bone metastases were higher than those in healthy controls. The serum concentration of beta-CTX in newly diagnosed MM was lower than that in bone metastases (P<0.001). Before chemotherapy, the serum levels of beta -CTX and PINP in A and B groups were not statistically significant, but the ratio of serum beta -CTX/PINP in A group was lower than that in group B, and the difference was statistically significant. After two courses chemotherapy, the concentration of serum beta -CTX (P=0.023) and the ratio of beta -CTX/PINP (P<0.001) were decreased in MM group. There were no significant difference of serum beta -CTX, PINP concentration, and beta-CTX/PINP ratio before and after treatment in Group A. Patients in the group B, there was no significant difference in the changes of serum PINP concentration, but both serum beta -CTX concentration and beta-CTX/PINP ratio decreased after two courses[(4 027 ± 648)ng/L vs (2 370± 460) ng/L, P=0.043; 111± 23 vs 30± 6, P=0.002]. The ratio of serum beta-CTX/PINP decreased in the effective group, and the difference was statistically significant. There was no significant difference in serum beta-CTX, PINP concentration and beta-CTX/PINP ratio before and after treatment in the uneffective group. Conclusions: There is a difference between newly diagnosed MMBD and bone metastases in serum beta-CTX, which might be helpful for differential diagnosis, and the ratio of beta-CTX/PINP is positively correlated with the severity of MMBD, which might be used to evaluate the severity of bone disease and have a certain monitoring significance for the treatment of MM.

[Analysis of clinical characteristics and prognostic factors in patients with non-Hodgkin lymphoma and HBV infection].

Objective: To explore the clinical characteristics and prognostic factors of the patients with non-Hodgkin's Lymphoma (NHL) complicated with HBV infection, so as to provide a basis for clinical accurate diagnosis and prognosis evaluation. Methods: The data of 313 newly diagnosed NHL patients from August 2012 to July 2016 were collected. The HBV serological markers were detected by ELISA, and HBV DNA was quantified by full automatic microparticle chemiluminescence immunoassay (≥1×10(5) copies/ml as high copy group, 1×10(3)-<1×10(5) copies/ml as low copy group). The relationship between HBV infection and prognosis was analyzed combined with the clinical features of the patients, and the HBV detection rate was compared with that of the common population (from the national HBV sero epidemiological data). Results: ①The positive rate of HBsAg in NHL patients was 12.5% (39/313), which was higher than 7.2% in the general population (χ(2)=14.596, P<0.001). HBV infection in the past (HBsAg negative but HBcAb positive) in 114 cases (36.4%), the incidence was slightly higher than that in the general population (34.1%). ②Compared HBsAg positive group with the negative group, the proportion of B cell type (87.2% vs 70.3%, P=0.027), Ann Arbor stage Ⅲ-Ⅳ(69.2% vs 34.6%, P<0.001), IPI score 3-5 (74.4% vs 50%, P=0.004), LDH level (79.5% vs 47.8%, P<0.001) and liver involvement (45.5% vs 31.7%, P=0.006) were all higher. The difference was statistically significant. ③Compared the HBV infected group (114 cases) with the non-infected group (160 cases), the difference had statistical significance in the proportion of Ann Arbor stage Ⅲ-Ⅳ (P=0.023) and IPI score 3-5 scores P=0.035). ④Compared HBV DNA positive group (30 cases) with negative group (71 cases), Ann Arbor stage Ⅲ-Ⅳ (P=0.011), IPI score 3-5 score (P=0.030), LDH level (P=0.025) and liver involvement (P<0.001) in the proportion of patients had statistical significance. The positive patients were divided into HBV DNA high and low copy groups with 1×10(5) copies of /ml as the boundary. The results showed that there was no statistical difference between the two groups (P>0.05). Conclusions: The HBV infection rate of NHL patients is significantly higher than that of the general population, and HBV infection is more closely related to B cell type NHL. Patients with HBV infection and HBV DNA positive had late Ann Arbor stage, high IPI score, high LDH level and liver involvement, and the prognosis is poor.

[Comparison of different styles of allogeneic hematopoietic stem cell transplantation as first-line treatment treated with severe aplastic anemia in children and adolescents].

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors as first-line treatment for children and adolescents with severe aplastic anemia (SAA) . Methods: The clinical data of 79 children and adolescents with SAA diagnosed from January 2013 to December 2016 in Henan Province were retrospectively analyzed. There were 50 males and 29 females, with a median age of 14(4-18) years. 40 cases received matched sibling transplantation (MSD-HSCT), 17 with unrelated donor transplantation (UD-HSCT), and 22 with haploidentical transplantation (haplo-HSCT). Results: The comparison of MSD-HSCT, UD-HSCT, haplo-HSCT groups was conducted and the median times of neutrophils engraftment were statistically significant [12(9-25) d, 14(10-22) d, 16(11-26) d, respectively (χ2=13.302, P=0.001)], but no difference in+30 d engraftment rate [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The median times of PLT engraftment were not statistically significant [14(6-34)d, 16(7-32)d, 19(10-34)d, respectively, χ2=5.892, P=0.053], and the +30 d engraftment rate had no difference [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The post-transplant infection rate showed no statistically significance [35.0% (14/40), 29.4% (5/17), 45.5% (10/22), χ2=1.158, P=0.560], as well as the incidences of aGVHD, grade III/IV aGVHD and cGVHD(χ2=0.230, P=0.891; χ2=2.628, P=0.269; χ2=3.187, P=0.203). The two-years OS rate was not statistically significant respectively [(77.1±6.7)%, (70.6±11.1)%, (77.3±8.9)%, χ2=0.330, P=0.845]. Severe post-transplant infection (RR=4.617, P=0.009), grade Ⅲ/Ⅳ aGVHD (RR=2.707, P=0.048) were independent risk factors for OS. Conclusion: The overall efficacy of MSD-HSCT, UD-HSCT and haplo-HSCT as first-line therapy for children and adolescents with SAA/VSAA is comparable.