[Minimal residual disease assessment and progress in multiple myeloma].

With the rapid iteration of multiple myeloma therapeutics over the last two decades, as well as increasing remission rates and depth of remission in patients, traditional methods for monitoring disease response are insufficient to meet the clinical needs of new drugs. Minimal residual disease (MRD) is a more sensitive test for determining the depth of response, and data from multiple clinical trials and meta-analyses show that a negative MRD correlates with a better prognosis than a traditional complete response. MM is at the forefront of MRD evaluation and treatment. MRD detection methods have been continuously updated. The current MRD assessment has three dimensions: bone marrow-based MRD testing, MRD testing based on images of residual metabolic of focal lesions, and peripheral blood-based MRD testing. The various MRD assessment methods complement one another. The goal of this article is to discuss the currently used MRD assays, the progress, and challenges of MRD in MM, and to provide a reference for clinicians to better use the techniques.

[Prognostic value of the Second Revision of the International Staging System in patients with newly diagnosed transplant-eligible multiple myeloma].

Objective: To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China. Methods: This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival. Results: The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS (HR=2.37, 95%CI 1.30-4.30; HR=4.50, 95%CI 2.35-9.01) and OS (HR=4.20, 95%CI 1.50-11.80; HR=9.53, 95%CI 3.21-28.29). Conclusions: The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

[Clinical features and related factors of invasive pulmonary aspergillosis in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To study the clinical features and related factors of invasive pulmonary aspergillosis (IPA) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: This retrospective study enrolled patients hospitalized for AECOPD in ten tertiary hospitals of China from September 2017 to July 2021. AECOPD patients with IPA were included as case group, AECOPD patients without IPA were randomly selected as control group from the same hospitals and same hospitalization period as the patients with IPA using the random function in the software of Microsoft Excel 2003, at a ratio of 2∶1. The clinical characteristics, treatment and outcome were compared between the two groups. Binary logistic regression model was used to analyze the factors associated with IPA in AECOPD patients. Results: A total of 14 007 inpatients with AECOPD were included in this study, and 300 patients were confirmed to have IPA, with an incidence rate of 2.14%. According to the above matching method, 600 AECOPD patients without aspergillus infection were enrolled as the control group. The age of the case group and the control group were (72.5±9.7) and (73.5±10.3) years old, with 78.0%(n=234) male and 76.8%(n=461) male, respectively. There were no significant differences in age and gender composition between the two groups (all P>0.05). The prognosis of case group was significantly worse than that of the control group, with longer hospital stay [M(Q1,Q3)], [14 (10-20) d vs 11 (8-15) d, P<0.001], higher ICU admission rate [16.3% (49 case) vs 10.0% (60 case), P=0.006], higher in-hospital mortality [4.0% (12 cases) vs 1.3% (8 cases), P=0.011], and higher hospitalization costs (28 000 ¥ vs 13 700 ¥, P<0.001). The smoking index of the case group and proportions of patients with diabetes mellitus, chronic pulmonary heart disease in the case group were significantly higher than those in control group (all P<0.05). In terms of clinical features, the proportions of patients with cough, expectoration, purulent sputum, hemoptysis and fever in the case group were higher than those in the control group, the serum albumin was significantly lower than that in the control group, and the proportions of patients with bronchiectasis and pulmonary bullae on imaging were significantly higher than those in the control group (all P<0.05). Diabetes (OR=1.559, 95%CI: 1.084-2.243), chronic pulmonary heart disease (OR=1.476, 95%CI: 1.075-2.028), bronchiectasis (OR=1.506, 95%CI: 1.092-2.078), pulmonary bullae (OR=1.988, 95%CI: 1.475-2.678) and serum albumin<35 g/L (OR=1.786, 95%CI: 1.325-2.406) were the related factors of IPA in patients with AECOPD. Conclusions: The incidence of IPA in AECOPD patients is relatively high and the prognosis of these patients is worse. Diabetes, chronic pulmonary heart disease, bronchiectasis, pulmonary bulla, hypoproteinemia are the related factors of IPA in patients with AECOPD.

[Study on related factors and characteristics of multimorbidity of overweight and obesity-related diseases in children in Hunan Province].

From January 2019 to December 2021, overweight and obese children who visited in health outpatient Center of Hunan Children's Hospital were studied to explore and analyze the rate, related factors and patterns of multimorbidity of overweight and obesity-related diseases in children in Hunan Province. Univariate and multivariate logistic regression models were used to analyze the multimorbidity-related factors of overweight and obesity-related diseases in children. Association rules (apriori algorithm) were used to explore the multimorbidity patterns of overweight and obesity-related diseases in children. A total of 725 overweight and obese children were included in this study. The multimorbidity rate of overweight and obesity-related diseases in children was 46.07% (334/725). Age, waist circumference, the frequency of food consumption such as hamburgers and fries and adding meals before bedtime were multimorbidity-related factors of overweight and obesity-related diseases in children. The multimorbidity associated with nonalcoholic fatty liver disease (NAFLD) was relatively common. The patterns with the top three support degrees were "NAFLD+dyslipidemia","NAFLD+hypertension" and "NAFLD+hyperuricemia". The patterns with the top three confidence and elevation degrees were "Hypertension+dyslipidemia => NAFLD","Hyperuricemia => NAFLD" and "NAFLD+hypertension => dyslipidemia".

[Clinical analysis of multiple myeloma with second primary malignancies and multiple myeloma secondary to malignancies].

Objective: To compare the clinical characteristics and survival outcomes of multiple myeloma (MM) with second primary malignancies (SPMs) and MM secondary to malignancies. Methods: The clinical data of MM patients diagnosed and treated in Beijing Chaoyang Hospital, Capital Medical University from January 2002 to January 2021 were included. The patients were divided into two groups: MM with SPMs group and MM secondary to malignancies group. The gender, age at first diagnosis, classification, stage, type of combined malignant tumor and the treatment were analyzed. The clinical characteristics and survival differences were compared between the two groups. Results: There were 20 patients in the MM with SPMs group, 9 males and 11 females, aged [M(Q1,Q3)] 61.5(56.8, 68.0)years, and the overall survival (OS) was 49.5(32, 58) months, while the time to death from secondary tumor was 12(4,21)months. There were 29 patients in the MM secondary to malignancies group, 13 males and 16 females, aged 64.0(57.0, 71.0)years, and the OS was 97(61, 171) months, while the time to death from secondary MM was 32(18, 47) months. The time from patients diagnosed with MM to SPMs was 37(18, 50) months, which was significantly earlier than that of MM secondary to malignancies [53(31,117) months](P=0.016). The type of tumor was also different between the two groups (P<0.001). In the group of MM with SPMs, the most common type of SPMs was hematopoietic malignancies (12/20, 60.0%), whereas in the group of MM secondary to malignancies, MM was most often secondary to genitourinary malignancies (13/29, 44.8%) (P<0.001). Conclusions: Both MM with SPMs and MM secondary to malignancies can affect the survival of patients. Secondary hematological malignancies account for a high proportion of the second tumors in MM patients, while genitourinary malignancies account for a high proportion of malignant tumors associated with MM.

[Analysis of the relationship between syncope and poor prognosis in patients with acute pulmonary embolism and related factors].

Objective: To explore the association between syncope and poor prognosis and related factors of syncope in patients with acute pulmonary embolism (APE). Methods: A total of 740 patients with first diagnosed APE treated in West China Hospital of Sichuan University from September 1, 2016 to December 30, 2019 were enrolled. The basic information and clinical information (including clinical manifestations, complications, auxiliary examination, treatment and prognosis, etc.) of the patients were obtained from inpatient medical records. The patients were divided into the syncope group and the non-syncope group according to whether they had syncope or not. The basic and clinical conditions of the two groups were compared, and the factors related to syncope in APE patients were analyzed by multiple logistic regression model. Results: The proportion of APE patients with syncope was 12.6% (93/740). Age was (59±16) years in the syncope group (93 cases) and (59±17) years in the non-syncope group (647 cases), with 57.0% (53/93) and 60.4% (391/647) males, respectively. The body mass index, in-hospital mortality, proportions with high risk APE and mechanical ventilation of the syncope group were higher than those of the non-syncope group [(24.5±4.0) kg/m2 vs (23.3±3.8) kg/m2, 16.1% vs 7.7%, 4.4% vs 1.3% and 9.7% vs 2.5%, respectively]. The length of hospital stay [M (Q1, Q3)] of the syncope group was longer than that of the non-syncope group [15 (10, 22) d vs 14 (9, 22) d], and the proportions with chest pain and hemoptysis were lower than those of the non-syncope group (19.4% vs 36.8% and 14.0% vs 27.2%, respectively) (all P values<0.05). Multivariate logistic regression analysis showed that enlargement of the right heart [OR (95%CI): 2.46 (1.07, 5.64)] was a factor associated with syncope in APE patients. Conclusion: The proportion of APE patients with syncope is relatively high and is associated with poor prognosis, while enlargement of the right heart is associated with syncope in APE patients.

[The prognostic relationship between CD56 expression and newly diagnosed multiple myeloma].

Objective: To evaluate the prognostic value of CD56 expression in newly diagnosed MM (NDMM). Methods: A total of 332 NDMM patients were enrolled in Beijing Chaoyang Hospital, Capital Medical University from January 1, 2011 to January 1, 2021, with a median age of 60 years and a male to female ratio of 1.2∶1. CD56 expression on myeloma cells was detected by flow cytometry before induction therapy. Overall survival (OS) and progression-free survival (PFS) data were collected. In order to reduce the confounding factors, the propensity score matching technique was used to match CD56 positive versus negative patients at a ratio of 1∶1. Results: Among 332 patients, CD56 positivity rate was 65.1% (216/332). Patients with CD56 expression had significantly longer median OS (58.4 vs. 43.1 months, P=0.024) and PFS (28.7 vs. 24.1 months, P=0.013) than those with negative CD56. Univariate Cox proportional hazards regression analyses showed that CD56 expression was positively correlated with OS (HR=0.644, 95%CI 0.438-0.947, P=0.025) and a favorable prognostic factor for PFS (HR=0.646, 95%CI 0.457-0.913,P=0.013). The favorable effect of CD56 expression on PFS was confirmed in multivariate analysis (HR=0.705, 95%CI 0.497-0.998, P=0.049), but OS was not affected (P>0.05).In the propensity score matching analysis, 194 patients with 97 in each group were identified. CD56 positivity consistently predicted longer PFS (34.2 vs.25.1 months, P=0.047), but not OS (63.4 vs.43.1 months, P=0.056). Conclusion: These results demonstrate that CD56 expression is a favorable prognostic factor for PFS of newly diagnosed MM patients.

[Risk factors associated with in-hospital mortality in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: a multicenter retrospective study].

Objective: To investigate the risk factors associated with in-hospital mortality in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: A total of 6 668 patients hospitalized for AECOPD in seven tertiary hospitals from September 2017 to January 2021 were consecutively included, and clinical data related to medical history, laboratory tests, treatment and prognosis were collected, and patients were divided into death group and survival group according to whether they died during hospitalization. After univariate analysis, multivariate logistic regression analysis was then performed to explore the independent risk factors related to in-hospital mortality. Results: Among 6 668 patients hospitalized for AECOPD, 128 patients experienced in-hospital death, with a mortality rate of 1.9%. The mean age of the death group was (81±9) years, which was significantly older than that of the survival group ((72±11) years P<0.001). The proportion of patients in the AECOPD in-hospital death group with a combination of prolonged bed rest, hypertension, myocardial infarction within 3 months, cardiac insufficiency, chronic pulmonary heart disease, pneumonia, type 2 diabetes, venous thromboembolism (VTE), and chronic renal insufficiency was also significantly higher than in the survival group (all P<0.05) The median length of stay in the in-hospital death group was 18 d, which was significantly longer than that in the survival group (9 d, P<0.001), and the proportion of patients admitted to the ICU, receiving invasive mechanical ventilation and non-invasive mechanical ventilation was also significantly higher than that in the survival group (all P<0.05). The white blood cell count, glutamic transaminase, blood creatinine, calcitoninogen, C-reactive protein, D-dimer, N-terminal B-type natriuretic and Pseudomonas aeruginosa infection rates were significantly higher than those in the survival group (all P<0.05). Multifactorial analysis showed that age>80 years (OR=3.82, 95%CI 2.36 to 6.18, P<0.001), prolonged bed rest (OR=2.95, 95%CI: 1.79 to 4.86, P<0.001), chronic pulmonary heart disease (OR=1.85, 95%CI: 1.14 to 3.00, P=0.012), and pneumonia (OR=2.75, 95%CI: 1.65 to 4.60, P<0.001), invasive mechanical ventilation (OR=7.33, 95%CI: 4.40 to 12.21, P<0.001), noninvasive mechanical ventilation (OR=3.73, 95%CI: 2.30 to 6.04, P<0.001), anemia (OR=2.03. 95%CI: 1.21 to 3.42, P=0.008), and calcitoninogen>0.5 ng/ml (OR=2.38, 95%CI: 1.41 to 4.02, P=0.001) were independent risk factors for in-hospital mortality in patients with AECOPD. Conclusion: Advanced age (>80 years), prolonged bed rest, chronic pulmonary heart disease, pneumonia, invasive mechanical ventilation, noninvasive mechanical ventilation, anemia, and calcitoninogen>0.5 ng/ml were independent risk factors for in-hospital mortality in patients hospitalized with AECOPD.

[Effect and mechanism of circular RNA BICD2 on the biological behavior of oral squamous cell carcinoma cells].

Objective: To investigate the effects of circular RNA (circRNA) BICD2 (circ-BICD2) on glutamine metabolism, cell proliferation, migration, invasion and apoptosis of oral squamous cell carcinoma (OSCC) cells and to further explore the possible mechanism. Methods: OSCC cells were purchased from Shanghai Institute of Cellular Cells, Chinese Academy of Sciences. Samples of OSCC tissues and corresponding adjacent tissues were collected from 35 OSCC patients who underwent surgical resection at the First Affiliated Hospital of Zhengzhou University from January 2016 to January 2018. Real-time quantitative PCR (RT-qPCR) and western blot were performed to detect the expression levels of circ-BICD2, miR-296-5p and transgelin2 (TAGLN2) in OSCC tissues and cells. Bioinformatics, dual luciferase report experiment and RNA immunoprecipitation (RIP) experiment were used to determine the targeting relationship between circ-BICD2 and miR-296-5p, miR-296-5p and TAGLN2. According to different transfection oligonucleotides or plasmids, CAL27 and SCC9 cells were divided into si-NC group (transfection si-NC), si-circ-BICD2 group (transfection si-circ-BICD2), si-circ-BICD2+anti-miR-NC group (transfected with si-circ-BICD2 and anti-miR-NC), si-circ-BICD2+anti-miR-296-5p group (transfected with si-circ-BICD2 and anti-miR-296-5p), miR-NC group (transfected with miR-NC), miR-296-5p group (transfected with miR-296-5p mimic), miR-296-5p+pcDNA (transfected with miR-296-5p mimic and pcDNA) and miR-296-5p+TAGLN2 group (transfected with miR-296-5p mimic and pcDNA-TAGLN2). Cell counting kit 8(CCK-8), colony formation experiment, flow cytometry, Scratch healing test and Transwell experiment were applied to detect OSCC cell viability, number of colonies, cycle distribution, apoptosis rate, migration rate and invasive cell numbers. Glutamine (gln) consumption, α-ketoglutaric acid (α-KG) production and adenosine triphosphate (ATP) concentration were also detected by the kit. The expression of cyclinD1 and Glutamine hydrolase (GLS1) proteins of CAL27 and SCC9 cells in each of the groups were detected by western blot. Twelve four-week-old clean BALB/c female nude mice were injected with a single-cell suspension of SCC9 cells into the axillary skin to establish a transplanted tumor model. Twelve transplanted tumor model mice were divided into sh-circ-BICD2 group and sh-NC group. Mice were sacrificed by cervical dislocation at 32 days after injection, the tumors were removed and the tumor weight was tested. Results: The expressions of circ-BICD2 (2.54±0.74) and TAGLN2 (1.86±0.15) were increased (P<0.05), while the expression of MiR-296-5p was decreased in OSCC tissues (P<0.05). Cell viability, clone formation numbers, migration rate, invasive cell numbers, S phase cell ratio, glu consumption, α-KG production, ATP concentration, expression of cyclinD1 and GLS1 proteins of OSCC cells were significantly reduced after interference with circ-BICD2 expression. The apoptosis rate, the proportion of cells in G0-G1 phase and the expression of miR-296-5p were significantly increased (P<0.05). Inhibiting the expression of miR-296-5p coulld reverse the effect of interfering with circ-BICD2 on OSCC cell proliferation, migration, invasion, apoptosis and glutamine metabolism (P<0.05). After overexpression of miR-296-5p, cell viability, clone formation red number, migration rate, number of invasive cells, S phase cell ratio, glu consumption, α-KG production, ATP concentration and expressions of cyclinD1, GLS1 and TAGLN2 proteins in OSCC cells were significant decrease. The rate of apoptosis and the proportion of cells in G0-G1 phase were significantly increased (P<0.05). Compared with overexpression of miR-296-5p, cell viability, clone formation red number, migration rate, number of invasive cells, S phase cell ratio, glu consumption, α-KG production, ATP concentration, cyclinD1, GLS1 and TAGLN2 proteins in OSCC cells after overexpression of miR-296-5p and TAGLN2 were significantly increased, and the apoptosis rate and the proportion of cells in the G0-G1 phase were significantly decreased (P<0.05). Compared with the sh-NC group, the tumor weights of mice in the sh-circ-BICD2 group were significantly reduced (P<0.05). Conclusions: Circ-BICD2 was highly expressed in OSCC cells. Interfering with circ-BICD2 could inhibit the proliferation, migration and invasion of OSCC cells, glutamine metabolism and tumor growth and promote cell apoptosis, which might be relate to the regulation of miR-296-5p/TAGLN2 molecular axis.

[Autologous stem cell transplantation improve the survival of newly diagnosed multiple myeloma patients].

Objective: To evaluate the effect of autologous stem cell transplantation (auto-HSCT) on treatment remission and survival of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 243 new diagnosed MM patients (age ≤65 years) who had received auto-HSCT were selected, and 176 MM patients (age ≤65 years) who had not received auto-HSCT were selected as the control group to evaluate the effect of auto-HSCT on the remission and survival. To balance the distribution of prognostic factors between auto-HSCT and non-auto-HSCT patients, the propensity score matching technique was used to reduce the bias between groups in a 1∶1 scale, 64 in each group, and correlation analysis was performed. Results: A total of 128 patients (64 cases in each group) were screened by propensity score matching analysis. 64 patients received auto-HSCT after induction therapy. After auto-HSCT, 24 patients (37.5%) obtained sCR, 16 patients (25.0%) obtained CR, 15 patients (23.4%) obtained VGPR, and 9 patients (14.1%) obtained PR. The efficacy of patients with auto-HSCT was significantly better than that of non-auto-HSCT patients (P=0.032) . Progression-free survival (PFS) and overall survival (OS) were significantly longer in auto-HSCT patients compared with non-auto-HSCT patients[PFS: 42.2 (95% CI 29.9-54.5) months vs 22.4 (95% CI 17.1-27.7) months, P=0.007; OS: 87.6 (95% CI 57.3-117.9) months vs 53.9 (95% CI 36.1-71.7) months, P=0.011]. Multivariate analysis confirmed that auto-HSCT had a favorable effect on OS (HR=0.448, 95%CI 0.260-0.771, P=0.004) and PFS (HR=0.446, 95%CI 0.280-0.778, P=0.003) . Conclusion: These results demonstrated that auto-HSCT was a favorable prognostic factor for newly diagnosed MM patients.

Diagnostic value of miRNA-122 in Kawasaki disease.

OBJECTIVE: To explore the expression pattern and diagnostic value of microRNA-122 (miRNA-122) in childhood Kawasaki disease (KD). PATIENTS AND METHODS: A total of 150 children with KD were included in the KD group. During the same period, 150 children with respiratory infection complicated with fever and without myocardial involvement were included in the control group.  Serum level of miRNA-122 in children with acute phase of KD and those in the control group was detected. The relationship between serum level of miRNA-122 and clinical features of KD was analyzed by Pearson correlation test. ROC curves were depicted to assess the diagnostic value of miRNA-122 in KD. RESULTS: Serum level of miRNA-122 was higher in the KD group than controls. In the acute phase of KD, the serum level of miRNA-122 was positively correlated to CRP and NT-proBNP, while negatively correlated to the sodium level. The specificity and sensitivity of miRNA-122 in diagnosing KD was 78.67% and 84.67%, respectively (AUC=0.8861, cut-off value=2.905). CONCLUSIONS: Serum level of miRNA-122 is significantly enhanced in the acute phase of KD, and highly expressed miRNA-122 is related to systematic inflammation. MiRNA-122 may be used as a diagnostic hallmark of KD.

[Effect of circular RNA hsa_circ_0008898 on oral squamous cell carcinoma and its mechanism].

Objective: To investigate the effect and molecular mechanism of hsa_circ_0008898 on the cell proliferation, migration, invasion and tumor formation of oral squamous cell carcinoma (OSCC). Methods: Quantitative real-time PCR (qPCR) and Western blotting were used to detect the expression of hsa_circ_0008898, miR-197-5p and ras homolog gene family member A (RHOA) in OSCC tissues, adjacent tissues, OSCC cells and human normal oral keratinocytes (NOK). CAL27 and SCC-25 cells were transfected with si-hsa_circ_0008898#1 (knockdown group 1), si-hsa_circ_0008898#2 (knockdown group 2), hsa_circ_0008898 (circ overexpression group) and blank plasmid (circ blank group), respectively. Then miR-197-5p inhibitor (inhibition group) and blank plasmid (inhibition control group) were transfected into hsa_circ_0008898 knockdown cells (knockdown group 1). CAL27 and SCC-25 cells were transfected with miR-197-5p mimics (miR overexpression group) and blank plasmid (miR blank group), and then transfected hsa_circ_0008898 vector (co-transfection group 1), RHOA vector (co-transfection group 2) and blank plasmid (co-transfection control group) in cells overexpressing miR-197-5p. Cell counting kit 8 (CCK-8), colony formation, Transwell and scratch test were used to detect cell proliferation, cloning ability, cell cycle distribution, cell invasion and migration ability. Ten nude mice were equally divided into two groups, with 5 mice in each group. SCC-25 cells transfected with blank plasmid (control group) and SCC-25 cells transfected with sh-hsa_circ_0008898 (knockout group) were subcutaneously injected into the armpit. The volume and mass of the tumor were measured. Results: The expressions of hsa_circ_0008898 (2.89±0.72) and RHOA (2.62±0.21) in OSCC tissues were significantly higher than those in para-carcinoma tissues (1.00±0.48, 1.00±0.11, respectively), while the expression of miR-197-5p in OSCC tissues （0.46±0.24） was significantly lower than that in para-carcinoma tissues (1.00±0.42) (P<0.05). Compared with NOK, the expression of hsa_circ_0008898 and RHOA in CAL27 and SCC-25 cells increased significantly, while the expression of miR-197-5p decreased (P<0.05). Compared with circ blank group, the cell viability, colony formation, scratch healing rate and invasive cell number of CAL27 and SCC-25 cells in knockdown group 1 and group 2 were significantly decreased, while the proportion of cells in G1 phase was significantly increased (P<0.05). Compared with inhibition control group, the cell viability, colony formation, scratch healing rate and invasive cell number of CAL27 and SCC-25 in inhibition group were significantly increased, while the proportion of cells in G1 phase was significantly decreased in inhibition group (P<0.05). Compared with miR blank group, the cell viability, colony formation, scratch healing rate and invasive cell number of CAL27 and SCC-25 in miR overexpression group were significantly decreased, while the proportion of cells in G1 phase was significantly increased in miR overexpression group (P<0.05). Compared with co-transfection control group, the cell viability, colony formation, migration area and invasive cell number of CAL27 and SCC-25 in co-transfection group2 were significantly increased, while the proportion of cells in G1 phase was significantly decreased in co-transfection group 2 (P<0.05). The volume and mass of transplanted tumor in knockout group ï¼»(660.4±67.8) mm(3 )and (0.60±0.06) g, respectivelyï¼½ were significantly lower than those in control group ï¼»(1 210.4±198.9) mm(3) and (1.00±0.12) g, respectivelyï¼½. Conclusions: Knockdown of hsa_circ_0008898 inhibited OSCC cells proliferation, cloning, migration and invasion and induced cell cycle arrest in vitro by regulating the miR-197-5p/RHOA. Additionally, Knockdown of hsa_circ_0008898 also inhibited tumor formation of OSCC cells in vivo.

[Risk factors associated with mortality in patient with non-high-risk pulmonary embolism and cancer and the prognostic value of Charlson comorbidity index].

Objective: To investigate the risk factors associated with mortality and the prognostic value of Charlson comorbidity index (CCI) for mortality in patients with non-high-risk pulmonary embolism complicated by caner. Methods: Patients diagnosed with non-high-risk pulmonary embolism and caner from the medical departments of West China Hospital of Sichuan University from May, 2015 to April, 2018 were included in this study. The patients were classified into death group and survival group according to whether they died during hospitalization. Clinical information was collected and univariate along with multivariate analysis were performed in order to identify the independent risk factor related to short-term mortality in these patients. Besides, all the patients were assessed the comorbidity burden using CCI score and thereby to evaluate the prognostic value of CCI for short-time mortality. Results: A total of 195 patients were included in this study, including 115 males and 80 females. In all, 32 patients died during hospitalization and the mortality rate was 16.4%. Univariate analysis showed that male (P=0.044), age ≥65y (P=0.008), staying in bed (P=0.001), chronic pulmonary diseases (P=0.030), central venous catheterization (P=0.015), stroke history within 1 month (P=0.015), pneumonia (P=0.017), respiratory failure (P=0.017), diabetes mellitus (P=0.005) and anemia (P=0.035) were related to short term mortality of these patients. As for laboratory examination results, levels of hemoglobin and sodium in death group were significantly lower than survival group (P<0.05). Multivariate logistic regression showed that age ≥65y (OR=3.01, 95%CI: 1.05-8.68, P=0.041), staying in bed (OR=4.15, 95%CI: 1.37-12.54, P=0.012), central venous catheterization (OR=16.10, 95%CI: 2.09-124.08, P=0.008), stroke history within 1 month (OR=6.56, 95%CI: 1.05-40.95, P=0.044) and hyponatremia (OR=2.75, 95%CI: 1.06-7.15, P=0.038) were independent risk factors of short term mortality in these patients. Besides, CCI score in death group was significantly higher than that in survival group (5.66±2.96 vs 4.13±2.74, P=0.005). Pulmonary embolism patients with CCI≥4 were associated with 4.25-fold increased risk of mortality compared with patients with CCI<4 (OR=4.25, 95%CI: 1.83-9.89, P=0.001), and the per additional 1-score increase of CCI after 4 was associated with 4.89-fold increased risk of mortality (OR=4.89, 95%CI: 2.07-11.55, P<0.001). Survival analysis showed that patients with CCI≥4 had lower survival rate than the patients with CCI<4 during hospitalization (P<0.001). Conclusions: Age ≥65y, staying in bed, central venous catheterization, stroke history within 1 month and hyponatremia are independent risk factor of short-term mortality in patients with non-high-risk pulmonary embolism and caner. CCI score has prognostic value of short term mortality in these patients, and the risk increases with the increase of comorbidities patients have.

[Review of upper urinary modified minimal invasive surgical technology].

Upper urinary surgery is an important area of urology surgery. Open surgery used to be the gold standard of upper urinary surgery. With the development of medical techniques, minimal invasive surgeries including laparoscopic and robot assisted-laparoscopic surgery have gradually replaced the open surgery. Because of the complexity and diversity of upper urinary diseases, surgeries sometimes are difficult, and minimal invasive surgeries require higher surgical abilities of urologists than open surgeries. In recent years, depending on our surgical experience and international reports, our team from three Chinese medical centers summarizes techniques of upper urinary minimal invasive surgeries. For malignant diseases, such as renal and ureteral carcinomas, it's important to totally remove the tumor first, and then to avoid the surgical injuries. We summarize surgical experience of retroperitoneal laparoscopic partial nephrectomy for moderately complex renal hilar tumors. Our team modified minimal invasive techniques for some complex tumors, including ring suture technique for renal hilar tumors, internal suspension technique for renal ventral tumors, and combination retroperitoneal laparoscopic surgery with mini-flank incision for complex renal tumors. While for begin diseases, urologists should focus on the resections and surgical injuries at the same time. We have reported the novel technique of laparoscopic aspiration for central renal angiomyolipoma, making the surgery simple and available. For reconstruction surgeries, operations should be based on several principals. We generalize it as "4TB principals", which include "tension-free", "water-tight", "thin suture", "no touch of the key area" and "protecting the blood supply". Depending on the localization, length, and etiology of the strictures, different techniques are required. Our team summarize the pyeloplasty, ureteral reimplantation and ileal ureter replacement based on our surgical experience. For infant upper urinary surgeries, our team has made invasive surgeries that can be used in complex diseases, such as duplex kidney. Based on years of surgical techniques, our modified surgeries achieve a better subjective cosmetic result than the traditional surgeries. In the future, the standardized, practical, simple and individual minimal invasive surgical technique will become the main direction in the future researches.

[Comparison of minimal residual disease in multiple myeloma patients detected by 8-color panels and next generation flow cytometry].

Objective: To compare the sensitivity of 8-color panels and next generation flow cytometry (NGF) for detecting minimal residual disease of multiple myeloma patients. Methods: 8-color-membrane antigens (8C-Mem) panel was built including CD45, CD38, CD138, CD19, CD56, CD81, CD27 and CD117 to identify the plasma cells, while 8-color-cytoplasmic antigens (8C-Cyto) panel was built including CD45, CD38, CD138, CD19, CD56, CD81, cKappa (cK) and cLambda (cλ) , and 8-color-two-tubes (8C-2tubes) panel were built including 8C-Mem and 8C-Cyto panels, the data of three groups was analyzed by Diva software. NGF uses Infinicyt software to fuse 8C-2tubes data to further analyze the expression of plasma antigens. Bone marrow aspiration obtained from 20 controls and 76 multiple myeloma patients who achieved complete remission were measured and analyzed. Results: Positive MRD samples were discriminated in 88.2% of the specimen evaluated through either abnormal plasma cells (aPCs) or clonal plasma cells (cPCs) by NGF antigens panel, Among of them, consistency was 94.7%. The median percentage of cPCs was 0.3530%, The lowest sensitivity of NGF was 0.0003%. In 8-color panels, the positive MRD rates of 8C-Mem, 8C-Cyto and 8C-2tubes panels were 84.2%, 85.5% and 86.8%, respectively, which lower than that of NGF (P<0.001) . The positive MRD rate of 8C-Mem and 8C-Cyto panels were lower than that of 8C-2tubes panel (P<0.001) , and the positive MRD rate of 8C-Mem panel was lower than that of 8C-Cyto panel (P<0.001) . Sensitivity and specificity of NGF was higher than that of 8-color panels. 8C-2tubes panel has the best sensitivity, accuracy, negative predicted value, positive predicted value and specificity than other 8-color panels. However, huge data and low efficiency for analysis is the disadvantage. 8C-Cyto panel was the second choice, and 8C-Mem panel was the last. Conclusions: Membrane and cytoplasmic light chain is a better method for multiple myeloma-MRD detection and NGF panel is an ideal approach. 8C-Cyto panel is recommended in 8-MFC groups.

[Comparison of risk factors and short-term and long-term prognosis of pulmonary embolism between the Tibetan and Han people].

Objective: To compare the differences of risk factors and prognosis of pulmonary embolism (PE) between the Tibetans and the Hans. Methods: Patients over 18 years old with confirmed PE and complete clinical data from West China Hospital of Sichuan University from January 2010 to January 2016 were prospectively enrolled and divided into Tibetan group and Han group. Clinical data were collected to compare risk factors and short-term prognosis between Han group and Tibetan group. In addition, a 2-year follow-up was conducted among patients after discharge to investigate the long-term prognosis. Results: A total of 90 patients in Tibetan group and 626 patients in Han group were finally included in this study. Patients in Tibetan group were younger than Han group [(52.2±15.8) vs (59.8±16.6) years old, P<0.001], and the proportion of elderly patients (age ≥70 years) in Tibetan group was significantly lower than that of Han group (15.6% vs 33.7%, P=0.001). The hemoglobin, hematocrit, platelet counts and fibrinogen in Tibetan group were higher than those in Han group [(134.0±32.0) vs (122.2±25.7) g/L, (41.2±9.2)% vs (37.6±7.3)% and (222.2±97.5)×10(9)/L vs (187.5±87.2)×10(9)/L, 3.71(2.51, 4.89) vs 3.31(2.44, 4.42) g/L; P<0.001, <0.001 and P=0.001, 0.048, respectively]. Malignancy and chronic obstructive pulmonary disease were more common in Han group (P=0.011, 0.001), while prior venous thromboembolism history, pregnancy or a history delivery within 1 month were more common in Tibetan group (P=0.041, 0.001). Both short-term and long-term mortality in Tibetan group were significantly lower than that in Han group (2.2% vs 11.5%, 13.6% vs 24.9%; P=0.005, 0.020). Conclusions: Hypercoagulable state plays an important role in the pathogenesis of PE in Tibetan patients. Both short-term and long-term prognosis of PE in Tibetan patients are better than that in Han patients.

Reemergence of high-Tc superconductivity in the (Li1-xFe x )OHFe1-ySe under high pressure.

In order to elucidate pressure-induced second superconducting phase (SC-II) in A x Fe2-ySe2 (A = K, Rb, Cs, and Tl) having an intrinsic phase separation, we perform a detailed high-pressure magnetotransport study on the isoelectronic, phase-pure (Li1-xFe x )OHFe1-ySe single crystals. Here we show that its ambient-pressure superconducting phase (SC-I) with a critical temperature Tc ≈ 40 K is suppressed gradually to below 2 K and an SC-II phase emerges above Pc ≈ 5 GPa with Tc increasing progressively to above 50 K up to 12.5 GPa. Our high-precision resistivity data uncover a sharp transition of the normal state from Fermi liquid for SC-I to non-Fermi liquid for SC-II phase. In addition, the reemergence of high-Tc SC-II is found to accompany with a concurrent enhancement of electron carrier density. Without structural transition below 10 GPa, the observed SC-II with enhanced carrier density should be ascribed to an electronic origin presumably associated with pressure-induced Fermi surface reconstruction.

[A retrospective analysis of prognosis in favorable-risk acute myeloid leukemia patients with different consolidation regimens].

Objective: To explore the impact on prognosis in favorable-risk acute myeloid leukemia (AML) patients with different consolidation regimens after first complete remission (CR(1)). Methods: A total of 107 cases of non-refractory adult AML from January 2010 to June 2015 in single center were enrolled in the study. HD-Ara-C group (38 cases) as the control group, we explore the prognosis in three consolidation regimens, including micro-transplantation (16 cases) , autologous transplantation (auto-PBSCT, 14 cases) , allogeneic transplantation (allo-HSCT, 39 cases). Results: Of 107 patients (59 males and 48 females) , with a median age of 33 (16-59) years old and a median follow-up of 36.5 (5.3-79.1) months, the overall relapse rate was 20.6% (22/107) , and overall mortality rate was 18.7% (20/107). The 5 years cumulative relapse rate (CIR) of HD-Ara-C, micro-transplantation, auto-PBSCT and allo-HSCT group were 39.7%, 6.2%, 14.3% and 5.6%, respectively (P<0.001). The CIR of the observed group was lower than the HD-Ara-C group. The 5 years progression-free survival (PFS) rate of HD-Ara-C, micro-transplantation, auto-PBSCT and allo-HSCT group were 44.7%, 93.8%, 85.7% and 78.1%, respectively (P=0.011). The PFS of observed groups were similar, but superior to that in HD-Ara-C group. The 5-year overall survival (OS) in four groups was 54.9%, 100%, 92.9% and 77.4%, respectively (P>0.05). Multiple factors analysis showed that compared to HD-Ara-C regimen, allo-HSCT could improve PFS (HR=0.376, P=0.031) , but not OS (P>0.05) ; micro-transplantation and auto-PBSCT could not improve the PFS or OS (P>0.05). Conclusion: As compared with HD-Ara-C regimen, allo-HSCT could obviously decrease CIR, improve PFS, but treatment-related mortality is high. These results show that auto-PBSCT and micro-transplantation have similar outcomes, compared to HD-Ara-C regimen, so both can be used as a option of consolidation treatment for favorable-risk AML.

Floral nectar of the obligate outcrossing Canavalia gladiata (Jacq.) DC. (Fabaceae) contains only one predominant protein, a class III acidic chitinase.

Floral nectar can affect the fitness of insect-pollinated plants, through both attraction and manipulation of pollinators. Self-incompatible insect-pollinated plants receive more insect visits than their self-compatible relatives, and the nectar of such species might face increased risk of infestation by pathogens carried by pollinators than self-compatible plants. Proteins in nectar (nectarins) play an important role in protecting the nectar, but little is known regarding nectarins in self-incompatible species. The nectarins from a self-incompatible and insect-pollinated leguminous crop, Canavalia gladiata, were separated using two-dimensional electrophoresis and analysed using mass spectrometry. The predominant nectarin gene was cloned and the gene expression pattern investigated using quantitative real-time PCR. Chitinolytic activity in the nectar was tested with different substrates. The C. gladiata nectar proteome only has one predominant nectarin, an acidic class III chitinase (CaChi3). The full-length CaChi3 gene was cloned, coding for a protein of 298 amino acids with a predicted signal peptide. CaChi3 is very similar to members of the class III chitinase family, whose evolution is dominated by purifying selection. CaChi3 was expressed in both nectary and leaves. CaChi3 has thermostable chitinolytic activity according to glycol-chitin zymography or a fluorogenic substratem but has no lysozyme activity. Chitinase might be a critical protein component in nectar. The extremely simple nectar proteome in C. gladiata disproves the hypothesis that self-incompatible species always have more complex nectar proteomes. Accessibility of nectar might be a significant determinant of the evolutionary pressure to develop nectar defence mechanisms.