[Clinical features and prognosis of core binding factor acute myeloid leukemia children in South China: a multicenter study].

Objective: To analyze the clinical features, efficacy and prognosis factors of core binding factor (CBF) acute myeloid leukemia (AML) children in South China. Methods: This was a retrospective cohort study. Clinical data of 584 AML patients from 9 hospitals between January 2015 to December 2020 was collected. According to fusion gene results, all patients were divided into two groups: CBF-AML group (189 cases) and non-CBF-AML group (395 cases). CBF-AML group were divided into AML1-ETO subgroup (154 cases) and CBFß-MYH11 subgroup (35 cases). Patients in CBF-AML group chosen different induction scheme were divided into group A (fludarabine, cytarabine, granulocyte colony stimulating factor and idarubicin (FLAG-IDA) scheme, 134 cases) and group B (daunorubicin, cytarabine and etoposide (DAE) scheme, 55 cases). Age, gender, response rate, recurrence rate, mortality, molecular genetic characteristics and other clinical data were compared between groups. Kaplan-Meier method was used for survival analysis and survival curve was drawn. Cox regression model was used to analyze prognostic factors. Results: A total of 584 AML children were diagnosed, including 346 males and 238 females. And a total of 189 children with CBF-AML were included, including 117 males and 72 females. The age of diagnosis was 7.3 (4.5,10.0)years, and the white blood cell count at initial diagnosis was 21.4 (9.7, 47.7)×109/L.The complete remission rate of the first course (CR1) of induction therapy, relapse rate, and mortality of children with CBF-AML were significantly different from those in the non-CBF-AML group (91.0% (172/189) vs. 78.0% (308/395); 10.1% (19/189) vs. 18.7% (74/395); 13.2% (25/189) vs. 25.6% (101/395), all P<0.05). In children with CBF-AML, the CBFß-MYH11 subgroup had higher initial white blood cells and lower proportion of extramedullary invasion than the AML1-ETO subgroup, with statistical significance (65.7% (23/35) vs. 14.9% (23/154), 2.9% (1/35) vs. 16.9% (26/154), both P<0.05). AML1-ETO subgroup had more additional chromosome abnormalities (75/154), especially sex chromosome loss (53/154). Compared with group B, group A had more additional chromosome abnormalities and a higher proportion of tumor reduction regimen, with statistical significance (50.0% (67/134) vs. 29.1% (16/55), 34.3% (46/134) vs. 18.2% (10/55), both P<0.05). Significant differences were found in 5-years event free survival (EFS) rate and 5-year overall survival (OS) rate between CBF-AML group and non-CBF-AML group ((77.0±6.4)%vs. (61.9±6.7)%,(83.7±9.0)%vs. (67.3±7.2)%, both P<0.05).EFS and OS rates of AML1-ETO subgroup and CBFß-MYH11 subgroup in children with CBF-AML were not significantly different (both P>0.05). Multivariate analysis showed in the AML1-ETO subgroup, CR1 rate and high white blood cell count (≥50×109/L) were independent risk factors for EFS (HR=0.24, 95%CI 0.07-0.85,HR=1.01, 95%CI 1.00-1.02, both P<0.05) and OS (HR=0.24, 95%CI 0.06-0.87; HR=1.01, 95%CI 1.00-1.02; both P<0.05). Conclusions: In CBF-AML, AML1-ETO is more common which has a higher extramedullary involvement and additional chromosome abnormalities, especially sex chromosome loss. The prognosis of AML1-ETO was similar to that of CBFß-MYH11. The selection of induction regimen group FLAG-IDA for high white blood cell count and additional chromosome abnormality can improve the prognosis.

[Clinicopathological and molecular genetic features of cyclin D1-negative mantle cell lymphoma].

Objective: To investigate the clinicopathological features and molecular genetics of cyclin D1-negative mantle cell lymphoma (MCL). Methods: The clinicopathological features and molecular genetics of CyclinD1-negative MCL diagnosed between January 2016 and July 2021 at the First Affiliated Hospital of Zhengzhou University were analyzed using immunohistochemistry and fluorescence in situ hybridization. Clinical information was collected and analyzed. Results: A total of five Cyclin D1-negative MCL cases from all 212 MCL patients (5/212, 2.4%)were included. There were three male and two female patients,age ranged from 59 to 70 years (median 64 years). All patients presented with nodal lesions. None of the patients had B symptoms but four had bone marrow involvement. Histopathologically, four cases were classic MCL and one case was pleomorphic variant type. All five cases were negative for Cyclin D1 but SOX-11 were positive in all cases. CD5 was positive in four cases and one case was weakly positive for CD23. CD10 and bcl-6 were negative in all cases. CCND1 translocation was identified in three cases and CCND2 translocation in one case by FISH analysis. However,CCND3 translocations were not found in the five cases. Conclusions: Cyclin D1-negative MCL are uncommon, its accurate diagnosis needs combined analysis with morphologic and immunophenotypic characteristics and genetic changes. It may be particularly difficult to distinguish from other small cell type B cell lymphomas. FISH analyses for CCND1/CCND2/CCND3 translocations and immunohistochemistry for SOX-11 are helpful to resolve such a difficult distinction.

[Clinicopathological characteristics of natural killer cell enteropathy: report of two cases and review of literature].

Objective: To study the clinicopathological and genetic features of natural killer (NK)-cell enteropathy for better understanding of this rare disease and prevention of its misdiagnosis. Methods: Two cases of NK-cell enteropathy were diagnosed in the First Affiliated Hospital of Zhengzhou University, China from October 2017 to February 2021. The clinical characteristics, morphology, immunohistochemistry, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization and T cell receptor gene rearrangement were analyzed. The patients were followed up by a telephone interview. Results: The patients were both male, aged 40 and 28 years, respectively. Both patients were admitted to the hospital for an annual checkup without obvious gastrointestinal symptoms. The endoscopy showed that the gastric body of case 1 had a mucosal bulge, small area of congestion and erosion, while the rectum of case 2 had congestion and erosion. Microscopically, the lesions of the 2 cases were relatively limited. Many lymphoid cells infiltrated within the lamina propria of the mucosa and into the muscularis mucosa in case 2. In case 1, the glands were reduced in the lesion, and the glandular cavity was slightly compressed and deformed. There was no infiltration or destruction of the glands in either case. Lymphoid cells were atypical, with medium-to-large cell sizes. Their cytoplasm was medium-to-slightly abundant and appeared eosinophilic or translucent. In case 2, characteristic eosinophilic granules were seen in the cytoplasm of a few cells. The nuclei in both cases were round, oval and irregular, with fine chromatin, inconspicuous nucleoli, and no mitotic figures were noted. Necrosis was seen in case 1 while both cases had no central growth or destruction of blood vessels. Immunophenotyping showed that CD56, granzyme B and TIA-1 were positive in both cases, part of the cells was CD3-positive, and some cells were weakly CD4-positive in case 2. The CD5, CD8, CD30, ALK and B-lineage markers (CD20, CD79α) were all negative. The Ki-67 proliferation index was about 60% and 30%, respectively. Both cases were EBER negative. TCR gene rearrangement was polyclonal. Follow-up showed that none of the 2 patients had any special treatments and stayed well. Conclusions: NK-cell enteropathy is rare, with biological behaviors similar to benign tumors, and occasional recurrence. Its histology and immunophenotype are easily confused with NK/T cell-derived lymphomas. Combination of its unique endoscopic features, EBER negativity, polyclonal TCR gene rearrangement and good prognosis can confirm the diagnosis and avoid misdiagnosis and overtreatment.

[Recommendations of diagnosis and treatment of juvenile idiopathic arthritis in China].

The common clinical subtypes of juvenile idiopathic arthritis (JIA) include systemic onset juvenile idiopathic arthritis (SOJIA), oligoarthritis/polyarthritis juvenile idiopathic arthritis and juvenile spondyloarthritis. Juvenile idiopathic arthritis has no specific diagnostic index, and needs to be differentiated from infectious diseases and malignant diseases. The onset of SOJIA is rapid, the disease progresses rapidly, and it is easy to be complicated with macrophage activation syndrome (MAS) which is life-threatening. The experience of pediatric rheumatologists in dealing with JIA is still insufficient, and the standardized diagnosis and treatment level of this disease needs to be further improved. Based on the experience and guidelines of diagnosis and treatment in China and abroad, we formulated this diagnosis and treatment standard, aiming at standardizing the diagnosis and treatment of the subtypes of JIA and MAS, so as to reduce the incidence of disability and serious complications and improve the prognosis.

[Research progress and clinical application value of exosomal circRNAs in hepatocellular carcinoma].

Primary liver cancer (hereinafter referred to as HCC) is the sixth most common type of cancer and the third leading cause of cancer-related mortality worldwide. Since patients in the early stage of HCC are typically asymptomatic and there are currently no specific detection methods for the early stage of HCC, the majority of patients are diagnosed in the late stage. Exosomes carry proteins, non-coding RNAs, such as cyclic RNAs (circRNAs), and other biological molecules. Patients with hepatocellular carcinoma have a higher concentration of serum exosomes than healthy individuals, and the circRNAs in the exosomes can reflect the source cells and real-time disease status, suggesting it has the potential to detect liver cancer early. This paper focuses on the latest progress of exosomal circRNAs and analyzes the potential value of exosomes in the early diagnosis, treatment, and progression of HCC.

[Screening core genes and cyclin B2 as a potential diagnosis, treatment and prognostic biomarker of hepatocellular carcinoma based on bioinformatics analysis].

Objective: To screen out and explore the core gene (Hub gene) involvement and the potential role of cyclin B2 (CCNB2) in the development and prognosis of hepatocellular carcinoma (HCC) through bioinformatics methods. Methods: Four HCC-related datasets were screened, and downloaded from the GEO database. GEO2R tool was used to analyze data and identify the differentially expressed genes (DEGs). Gene Ontology (GO) and KEGG signal pathway enrichment analysis were completed using DAVID database and Cytoscape (ClueGO) plug-in, respectively. Protein-protein interaction network (PPI) of DEGs was established using the STRING database. Cytoscape software was used to visualize PPI network, key modules (cluster) construction and core genes identification. UCSC and UALCAN database were used to analyze the differential expression and survival of TCGA hepatocellular carcinoma core genes. Firebrowse, Oncomine and UALCAN databases were used to analyze the expression of core genes in multiple tumors including HCC. Real-time quantitative reverse transcription PCR (RT-qPCR) was used to detect the expression levels of candidate genes in HCC tissues and liver cancer cell lines. Results: A total of 73 DEGs were identified from the four datasets, including 15 up-regulated genes and 58 down-regulated genes. KEGG pathway enrichment analysis signal showed that DEGs were mainly enriched in tumor-related pathways. PPI network based on DEGs had screened the key modules and 10 core genes. CCNB2 and NCAPG were highly expressed in liver cancer tissues in multiple databases. CCNB2 was positively correlated with NCAPG and was considered as a key gene related to prognosis (P < 0.01). RT-qPCR results showed that CCNB2 was highly expressed in human HCC tissues and cell lines (P < 0.01). Conclusion: Successfully screened DEGs and core genes related to HCC. Among them, CCNB2 is highly expressed in HCC and is related to the survival and prognosis of patients, so it is expected to become a biomarker for the diagnosis and prognosis of HCC.

[The prevalence and relationship between laryngopharyngeal reflux disease, anxiety and depression in otolaryngology outpatients].

Objective: To obtain the prevalence laryngopharyngeal reflux disease (LPRD), anxiety and depression in otorhinolaryngology outpatients and to explore the role of mental and psychological factors (anxiety and depression) in their pathogenesis. Methods: A questionnaire survey of reflux symptom index(RSI) scale and hospital anxiety and depression (HAD) scale were used to report 1 111 cases of outpatients in Department of Otorhinolaryngology Head and Neck Surgery, Peking University People's Hospital, from July 2017 to June 2018 (486 males, 625 females, age of 18-96 years old, median age of 38[30,53] years old) and to obtain the prevalence of LPRD, anxiety and depression. RSI-positive patients were selected in the case group, and RSI-negative patients were selected in the control group. The differences in HAD scores between the two groups were compared, and the risk factors of laryngopharyngeal reflux were analyzed. Statistical analysis was performed using SPSS 20.0 software. Results: There were 151 cases in the case group and 960 cases in the control group. The prevalence of LPRD was 13.59% (151/1 111).There was no significant difference in the prevalence of LPRD between different genders (P>0.05). The prevalence rate was the highest in the 18-40 age group, and the difference in the prevalence of all age groups (18~ 40 years old; 41-65 years old; >65 years old) was statistically significant (P<0.05). The prevalence of LPRD among smokers and non-drinkers was higher than that of non-smokers and non-drinkers and the prevalence of the two groups was statistically significant (P<0.05). The most common symptoms of the RSI scale were pharyngeal foreign body sensation (92.72%,140/151), persistent clearing throat (88.74%,124/151), excessive sputum or nasal reflux (82.12%, 124/151). There were significant statistical differences between the two groups (P<0.05). Ninty-one patients with anxiety, the prevalence was 8.19%(91/1 111); 76 patients with depression, the prevalence was 6.84%(76/1 111).Among the LPRD patients, the hospital anxiety scale scored 29.14% (44/151), and the hospital depression scale scored 17.22% (26/151). The scores of anxiety symptoms and depressive symptoms in the LPRD group were higher than those in the non-LPRD group. The above scores were statistically significant (P<0.05). Logistic regression analysis showed that smoking, anxiety and symptoms of gastroesophageal reflux disease were independent risk factors for laryngopharyngeal reflux. Conclusions: The prevalences of LPRD, anxiety and depression in the otorhinolaryngology clinic are 13.59%, 8.19% and 6.84%, respectively. Among patients with laryngopharyngeal reflux, the prevalence of anxiety is 29.14%, and the prevalence of depression is 17.22%. Age, smoking, drinking, alcohol consumption, education level, course of disease, symptoms of gastroesophageal reflux disease, pharyngeal foreign body sensation, etc. are related to LPRD. Mental factors (anxiety and depression) may play a role in LPRD. Smoking, anxiety symptoms and symptoms of gastroesophageal reflux disease are closely related to the incidence of LPRD.

[Investigation of laryngopharyngeal reflux prevalence and risk factors in otolaryngology].

Objective:To investigate the prevalence and related risk factors of laryngopharyngeal reflux in otolaryngology. Method:During January 2019 to March 2019, the inpatients in otolaryngology were investigated by the questionnaire of reflux symptom index scale and the laryngopharyngeal reflux related risk factors were analyzed. Result:Among the 227 patients, 33 patients with suspected LPR contained 19 patients（20.7%） of 92 patients in the laryngopharyngeal group, 10 patients（16.1%） of 62 patients in the nasal group, and 4 patients（5.5%） of 73 patients in the ear group. LPR prevalence in the laryngopharyngeal group was statistically different from that in the ear group（P<0.05）. Univariate logistic regression analysis showed that age, gender, smoking, drinking and BMI were risk factors of LPR（P<0.01）. Multivariate logistic regression analysis indicated that BMI was an independent risk factor of LPR（P<0.01）. Conclusion:LPR had a high prevalence rate in otolaryngology related diseases, and appropriate synergistic anti-LPR treatment could be carried out while treating otolaryngology related diseases.

[Establishment and research of a New Zealand rabbit model of laryngopharyngeal reflux].

Objective: To establish a New Zealand rabbit animal model of laryngopharyngeal reflux disease (LPRD) using esophageal balloon together with metal internal stent dilation and to investigate the changes of mucosa. Methods: 20 New Zealand rabbits were randomly divided into experimental group and control group, with 10 in each group. Balloon dilatation and metal internal stent dilation were carried out in experimental group to reproduce the animal model of LPRD.The middle of balloon was placed at the lower esophageal sphincter (LES) while the stent was placed at the upper esophageal sphincter (UES). The guide wire was placed in the control group, but the balloon was not expanded and the stent was not placed. The general condition, pH value of hypopharynx, laryngeal histopathology and changes of pepsin content of New Zealand rabbits were observed regularly. The difference between experimental group and control group was compared. Results: The 24-hour Dx-pH monitoring results showed that the number of reflux episodes(20.0[9.5, 35.0], 13.0[6.5, 22.0]), and the percent time below pH 5.5 (1.36%[0.60%, 4.57%], 1.36%[0.43%, 2.77%]) in the experimental group at the 2nd and 4th week were significantly different from those in the control group (0[0,3.0], 1.0[0.5, 3.8]; 0[0, 0.01%], 0[0, 0], respectively, all P<0.01), suggesting that the experimental group New Zealand rabbits developed LPRD. Compared with the control group under microscope, lymphocytes infiltration and submucosal gland hyperplasia increased in the mucosa of the throat of the experimental group. The results of pepsin immunohistochemical staining between the two groups were statistically significant (P=0.014). Conclusion: The use of balloon dilatation of the LES combined with metal stent dilatation of the UES can successfully establish a laryngopharyngeal reflux model, and lesions in the throat tissue can be observed.

[Effect and mechanism of adipocyte co-culture on aquaporin-9 expression in HepG2 cells].

Objective: To observe the effect of differentiated mature adipocytes on hepatic steatosis and aquaporin-9 (AQP9) expressions in HepG2 cells and further explore its possible mechanism of action. Methods: Human preadipocytes were cultured and differentiated to full maturity. HepG2 cells were co-cultured with non-differentiated adipocytes and differentiated mature adipocytes for 48 h, and then labeled as control group and experimental group. Oil red O staining and intracellular triglyceride content were performed on co-cultured HepG2 cells and simultaneous changes in phosphatidylinositol 3-kinase (PI3K) - serine/threonine kinase (Akt) signaling pathway, and AQP9 mRNA and protein levels were detected. The experimental group was co-cultured with recombinant human insulin-like growth factor-I (IGF-I), with the addition of 100ng/ml PI3K-Akt pathway agonist, labeled as experimental group + IGF-I group. The activation of PI3K-Akt pathway was verified by Western blotting (WB). The expression of AQP9 was detected by RT-q PCR and WB. The recombinant lentivirus LV-AQP9 or empty-loaded virus LV-PWPI was transfected with HepG2 cells by recombinant lentiviral transfection tecnique, and labeled as HepG2-AQP9 and HepG2-PWPI. The transfection efficiency was assessed by confocal laser scanning microscopy and RT-qPCR and WB detected the change of AQP9 expression level after virus transfection. Afterwards, the stable over-expressed HepG2-AQP9 cells and the empty-loaded HepG2-PWPI cells were co-cultured with differentiated mature adipocytes for 48h, and labeled as HepG2-AQP9 co-culture group, and then intracellular triglyceride content were detected with Oil red O staining. Finally, IGF-I was added to the HepG2-AQP9 co-culture group, which was recorded as HepG2-AQP9 co-culture + IGF-I group. Intracellular triglyceride content was detected with Oil red O staining, and WB verified PI3K-Akt signaling pathway activation and changes in AQP9 mRNA and protein levels. A t-test was used to compare the two independent samples. Results: The intracellular lipid droplets and triglyceride content (0.052 ± 0.005) in the experimental group was increased significantly than the control group (0.033 ± 0.003) (t= 5.225,P= 0.006), suggesting that adipocyte co-culture had induced steatosis in HepG2 cells. RT-qPCR and WB results indicated that the expression levels of AQP9 mRNA (3.615 ± 0.330) and protein levels (0.072 ± 0.005) in the experimental group were significantly higher than the control group (t= 13.708, 11.225,P= 0.005, < 0.001). WB results showed that the expression level of phosphorylated Akt (p-Akt) protein (0.116±0.003) in the experimental group was significantly lower than the control group (0.202 ± 0.003) (t= 27.136,P< 0.001). The total Akt protein was constant, and the p-Akt/total Akt (0.182 ± 0.017)was significantly lower than the control group (0.327 ± 0.019) (t= 2.431,P= 0.001), suggesting that adipocyte co-culture had inhibited PI3K- Akt signaling pathway in HepG2 cells and up-regulated the expression level of AQP9. WB results indicated that the expression level of p-Akt protein (0.194 ± 0.021) in the experimental group + IGF-I group was significantly higher than the experimental group (0.132 ± 0.003) (t= 5.082,P= 0.007). The total Akt protein was constant, and the p-Akt/total Akt (0.281 ± 0.009) was significantly higher than the control group (0.184 ± 0.132) (t= 10.311,P< 0.001). Simultaneously, RT-qPCR and WB results indicated that the expression levels of AQP9 mRNA (0.327 ± 0.347) and protein levels (0.042 ± 0.004) in the experimental group + IGF-I group were significantly lower than the experimental group (t= 33.573, 5.598,P< 0.001, 0.005), suggesting that adipocyte co-culture had possibility to regulate the expression level of AQP9 through the PI3K-Akt pathway. Confocal laser microscopy analysis showed that the transfection efficiency was more than 90%. RT-q PCR and WB results indicated that the expression levels of AQP9 mRNA and protein levels (0.373 ± 0.221) in HepG2-AQP9 group were significantly higher than HepG2-PWPI group (t=14.953, 28.931,P= 0.002 and 0.000), suggesting that the stable overexpression of AQP9 cell line was successfully constructed. The intracellular lipid droplets and triglyceride content in HepG2-AQP9 co-culture group was significantly increased (t= 5.478, 5.369,P= 0.005) than HepG2-PWPI co-culture group and HepG2-AQP9 co-culture+ IGF-I group, suggesting that the increased expression of AQP9 had promoted HepG2 steatosis in co-cultured adipocytes. WB results showed the expression levels of p-Akt protein (0.168 ± 0.006) and p-Akt/total Akt (0.265±0.009) in HepG2-AQP9 co-culture + IGF-1 group was significantly increased (t= 16.311, 8.769,P< 0.001) than HepG2-AQP9 co-culture group, while the expression levels of AQP9 mRNA (0.327 ± 0.034) and protein (0.375 ± 0.025) was significantly decreased (t= 33.573, 9.146,P< 0.001 and 0.001). Conclusion: Adipocytes co-culture can induce steatosis in HepG2 cells, and may participate in inhibiting PI3K-Akt signaling pathway to upregulate the expression of AQP9 in steatotic HepG2 cells.

[Analyses of pathogenic factors and clinicopathological characteristics of vocal leukoplakia].

Objective: To investigate the pathogenic factors of vocal leukoplakia and its clinical and pathological features. Methods: Eighty-one patients with vocal cord leukoplakia who underwent surgery between February 2010 and December 2016 and 160 volunteers without pharyngeal symptoms designed as controls were included in this case control study. The clinicopathological characteristics of 81 patients were summarized and analyzed synthetically. Results: There was statistical significance in reflux symptom index(RSI), reflux finding score(RFS), smoking index, and drinking index between case group and control group(Z=-5.35, -4.82, -4.76, -2.44, P<0.05). The voice-using duration per day in case group was significantly longer than that of control group.There was no statistical significance in hospital anxiety and depression scale for anxiety(HADA) scores、hospital anxiety and depression scale for depression(HADD) scores between case group and control group(P>0.05). In 42 patients who received 24-hour dual probe pH monitoring the prevalence of pathologic LPR was 42.8%. In 81 patients, 39(48%)patients were pathologically diagnosed as squamous cell hyperplasia, 18(22%)patients as mild dysplasia, 12(15%)sides as moderate dysplasia , 10(12%)patients as severe dysplasia and 2(2%)patients as carcinoma in-situ. The average age of high-risk pathological vocal leukoplakia was significantly higher than that of low-risk leukoplakia(t=-2.73, P<0.01). The propotion of speckled leukoplakia in high-risk leukoplakia was significantly higher than that of low-risk leukoplakia(χ(2)=23.81, P<0.01). There was no statistical significance between high-risk leukoplakia and low-risk leukoplakia in the prevalence of pathologic LPR(P>0.05). The bilateral lesions, speckled leukoplakia were more likely to relapse(χ(2)=4.27, 12.17, P<0.05). The more serious the pathology, the more likely it was to relapse (Z=-2.168, P=0.03). There was no statistical significance between recurrence group and non-recurrence group in the prevalence of pathologic LPR(P>0.05). Conclusions: LPR, smoke constitute the risk factors of vocal cord leukoplakia. Drinking, voice abuse are related to vocal cord leukoplakia. Senile, speckled leukoplakia are more likely to be malignancy. A speckled leukoplakia, bilateral leukoplakia, severe pathological degree are important factors to predict recurrence.

[Analysis on 10 year survival of HIV/AIDS patients receiving antiretroviral therapy during 2003-2005 in Henan province].

Objective: To understand the survival of HIV/AIDS patients after receiving antiretroviral therapy for 10 year in Henan province and related factors. Methods: The database of national integrated management system of HIV/AIDS was used to collect the basic information and follow-up information of HIV/AIDS patients who received antiretroviral therapy between 2003 and 2005 in Henan province. Software SPSS 23.0 was used to analyze the patients' survival and related factors based on the life-table method and Cox proportional hazards model. Results: Among the 2 448 HIV/AIDS patients who started antiretroviral therapy during 2003-2005, the men accounted for 53.5%, and women accounted for 46.5%. Up to 70.1% of the patients were aged 40-59 years and 95.5% of the patients had blood borne infections. The patients were observed for 10 years after antiviral treatment, and 719 cases died from AIDS related diseases, with a mortality rate of 3.78/100 per year (719/19 010 per year). The cumulative survival rates of patients within 1-year, 3 years, 5 years and 10 years were 0.94, 0.86, 0.78, 0.69 respectively. Compared with the patients aged <40 years, the HRs of the patients aged 40-, 50-, 60- and ≥70 years were 1.417 (95%CI: 0.903-2.222), 1.834 (95%CI: 1.174-2.866), 2.422 (95%CI: 1.539-3.810) and 3.424 (95%CI: 2.053-5.709) respectively. Compared with patients with baseline CD(4+)T lymphocyte >350 unit/ul, the HRs of the patients with CD(4+)T lymphocyte <50 unit/µl, 50-199 unit/ul and 200-350 unit/ul were 7.105 (95%CI: 5.449-9.264), 4.175 (95%CI: 3.249-5.366) and 2.214 (95%CI: 1.691-2.900) respectively. Compared with the women, the HR of the men was 1.480 (95%CI: 1.273-1.172). Compared with the patients who received second line ART therapy, the HR of patients receiving no second line therapy was 11.923 (95%CI: 9.410-15.104). Conclusions: The cumulative survival rate the HIV/AIDS patients after 10 years of antiretroviral therapy reached 0.69 in Henan. Male, old age, low basic CD(4+)T lymphocyte count and receiving no second line therapy were the risk factors for long-term survival of AIDS patients.

[Application of neuroendoscope combined with minimal-access for elderly patients with idiopathic trigeminal neuralgia in enhanced recovery after surgery of microvascular decompression].

Objective: To explore the value of neuroendoscope and minimal-access in enhanced recovery after surgery of microvascular decompression (MVD) for treatment elderly patients with idiopathic trigeminal neuralgia (ITN). Methods: The clinical data of 62 elderly patients with ITN who undergoing neuroendoscope-assisted minimal-access microvascular decompression were analyzed retrospectively, including operative data and follow-up results. Results: In 62 cases, the effective rate was 96.8%, with 88.7% complete cure and 8.1% little residual pain. Sixty successful cases were followed-up for an average of 61 months.Three cases recurred within 3 years after operation.Eight cases had complications after MVD. Conclusions: There was no serious complications that could be ascribed to old age and the operative result was satisfactory compared with younger age cases.Endoscope and minimal-access can help shorten operation time, raise the effectiveness of MVD, reduce postoperative recurrence rate, and enhanced recovery after surgery for elderly patients.

A review of hematopoietic cell transplantation in China: data and trends during 2008-2016.

Hematopoietic cell transplantation (HCT) activity in China was surveyed to assess its current status. A record number of HCTs (21 884: 16 631 allogeneic (76%) and 5253 autologous (24%)) were reported by 76 centers in China between 1 January 2008 and 30 June 2016. HCT trends included continued growth in transplant activity, a continued rapid increase in haploidentical donors (HID), and slower growth for unrelated donors, matched-related donors (MRD) and cord blood transplantation (CBT). The proportion of HID HCT among allogeneic HCTs increased from 29.6% (313/1062) in 2008 to 48.8% (1939/3975) in 2015, even 51.7% (1157/2237) in the first half of 2016. During this time frame, the proportion of MRD HCTs among allogeneic HCTs decreased from 48.1% (511/1062) to 33.0% (332/3975). The proportion of unrelated donor HCTs among allogeneic HCTs decreased from 20.4 (216/1062) to 13.6% (540/3975). The proportion of CBTs among allogeneic HCTs was increased from 2.1% (22/1062) to 4.2% (184/3975). HCTs have been increasing continuously for all indications except chronic myelogenous leukemia. Severe aplastic anemia is a common HCT indication among non-malignant diseases in China. The number of cases of allogeneic HCT for this disorder has increased annually, from 59 (5.6%) in 2008 to 569 (14.3%) in 2015, even 334 (14.9%) in the first half year in 2016. This survey clearly shows recent trends for HCTs in China.

Skp2 deficiency restricts the progression and stem cell features of castration-resistant prostate cancer by destabilizing Twist.

Castration-resistant prostate cancer (CRPC) remains a major clinical challenge because of the lack of effective targeted therapy for its treatment. The mechanism underlying how CRPC gains resistance toward hormone depletion and other forms of chemotherapy is poorly understood. Research on understanding the factors that drive these processes is desperately needed to generate new therapies to cure the disease. Here, we discovered a fundamental role of S-phase protein kinase 2 (Skp2) in the formation and progression of CRPC. In transgenic adenocarcinoma mouse prostate model, Skp2 depletion leads to a profound repression of prostate tumor growth and distal metastasis and substantially prolonged overall survival. We revealed that Skp2 regulates CRPC through Twist-mediated oncogenic functions including epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) acquisitions. Mechanistically, Skp2 interacted with Twist and promoted the non-degradative ubiquitination of Twist. Consequently, Skp2 stabilized Twist protein expression by preventing proteasomal degradation of Twist by ß-TrCP. We found that Twist overexpression augments CSC self-renewal and population and that Skp2 inhibition reverts Twist's effects on CSC regulation. Furthermore, genetically depleting or pharmacologically inactivating Skp2 synergistically re-sensitized CRPC cells toward chemotherapies such as paclitaxel or doxorubicin. Together, this study uncovering Skp2-mediated Twist stabilization and oncogenic functions in CRPC offers new knowledge on how CRPC progresses and acquires chemoresistance during tumor progression. It provides proof of principle that Skp2 targeting is a promising approach to combat metastatic CRPC by targeting Twist and CSCs.

Antimicrobial and antitumor activity and diversity of endophytic fungi from traditional Chinese medicinal plant Cephalotaxus hainanensis Li.

Endophytes from Cephalotaxus hainanensis Li, an important source of anti-leukemia drugs, have not been widely explored. In this study, 265 endophytic fungal isolates from C. hainanensis Li were screened for antimicrobial activities against tilapia, banana, rice, and rape and for antitumor activities against human leukemia cell lines (K562, NB4, and HL-60). Diversity was also analyzed. The results showed that 17.7% of the endophytic fungi had antimicrobial activities against at least three different test microbes, and activity against Fusarium oxysporum RKY102 was the highest at 15.8%. Cytotoxicity against at least one tumor cell line tested was observed in 18.5% of the endophytic fungi; with the highest value of 10.6% against K562. The endophytic fungal strains also showed relatively high activities against K562, NB4, and HL-60 while relatively fewer strains were cytotoxic against the human hepatic Hep-G2 and colon LoVo cancer cell lines. Thirty endophytic fungal strains showed both high antimicrobial and antitumor activities. Moreover, the analyses of the diversity of the 30 highly active strains showed they belonged to 20 species from 14 genera, and this is the first report of endophytic fungi Albonectria rigidiuscula, Colletotrichum magnisporum, and Nemania diffusa being isolated from Cephalotaxus plants. These findings suggest that natural antibacterial products for humans and tilapia; antifungal compounds for rice, rape, and banana; and antitumor compounds for leukemia therapy could be isolated from fungal strains derived from C. hainanensis Li.

Decreased miR-452 expression in human colorectal cancer and its tumor suppressive function.

MicroRNA-452 (miR-452) is dysregulated in some human malignancies, and is correlated with tumor progression. However, its expression and function in human colorectal cancer (CRC) remain unclear. The aim of our study was to explore the effects of miR-452 in CRC tumorigenesis and development. Using reverse transcription quantitative real-time polymerase chain reaction, we detected miR-452 expression in CRC cell lines and primary tumor tissues. We also examined the association between miR-452 expression and clinicopathological factors. We then investigated the effects of miR-452 on the biological behavior of CRC cells. miR-452 expression was significantly downregulated in CRC compared with the adjacent noncancerous tissues. A low level of miR-452 was associated with larger tumor size, deeper invasion depth, and advanced TNM stage. Multivariate Cox regression analysis identified decreased miR-452 expression as an independent factor predicting poor prognosis for CRC patients. In addition, in vitro functional analysis showed that overexpression of miR-452 in HCT116 cells reduced cell proliferation, promoted cell apoptosis, and inhibited cell invasion and migration. These findings indicate that miR-452acts as a tumor suppressor in CRC, and would serve as a novel molecular therapeutic agent for the treatment of the disease.

Effects of hemodialysis and hemoperfusion on inflammatory factors and nuclear transcription factors in peripheral blood cell of multiple organ dysfunction syndrome.

OBJECTIVE: To investigate the effects of hemodialysis (HD) and hemoperfusion (HP) on inflammatory factors and nuclear transcription factors in peripheral blood cell of multiple organ dysfunction syndrome (MODS) patients. PATIENTS AND METHODS: 92 cases of MODS patients undergoing maintained hemodialysis in our hospital were randomly divided into the control group and observation group. The control group was treated with conventional hemodialysis (HD), the observation group was treated with hemoperfusion combined therapy (HD+HP) based on the control group. The levels of serum creatinine (SCR), serum total cholesterol (TC), blood urea nitrogen (BUN) and serum albumin (Alb) were compared and analyzed between two groups before and after treatment. The levels of NK-κB p65 in the white cell of peripheral blood were compared between two groups before and after treatment by Western blot. The levels of inflammatory factors TNF-α and IL-6 in peripheral blood were detected between two groups before and after treatment using ELISA method. RESULTS: Compared with the control group, the levels of Scr, BUN and TC were significantly decreased, while the level of Alb was significantly increased (p < 0.05). The level of cytoplasm NK-κB p65 protein in peripheral blood was significantly increased in the observation group, while the level of nuclear NK-κB p65 in peripheral blood was significantly decreased (p < 0.05). CONCLUSIONS: Hemodialysis combined with hemoperfusion in treating MODS patients could significantly improve the biochemical indicators, effectively remove the inflammatory mediums, and significantly inhibit the activation of NK-κB.