Doxycycline Combined With Bortezomib-Cyclophosphamide-Dexamethasone Chemotherapy for Newly Diagnosed Cardiac Light-Chain Amyloidosis: A Multicenter Randomized Controlled Trial.

BACKGROUND: Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac light chain amyloidosis. METHODS: This was a multicenter, open-label, randomized controlled trial. Patients with Mayo 2004 stage II to III light chain amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression, or organ progression (heart, kidney or liver). Hematologic progression was defined on the basis of a substantial increase in free light chain. An increase in either NT-proBNP (N-terminal pro B-type natriuretic peptide) or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated with a Cox regression model. RESULTS: One hundred forty patients underwent randomization, with 70 in each group. The median age was 61 years (range, 33-78 years) with a male:female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32 of 70 (45.7%) patients in the doxycycline group and 30 of 70 (42.9%) patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio, 0.97 [95% CI, 0.59-1.60]; P=0.91). Cardiac progression occurred in 29 of 70 (41.4%) patients in the doxycycline group and 26 of 70 (37.1%) patients in the control group. The death rates for both groups by the end of follow-up was the same, 25 of 70 (35.7%). No significant differences were observed for either cardiac PFS (hazard ratio, 0.91 [95% CI, 0.54-1.55]; P=0.74) or overall survival (hazard ratio, 1.04 [95% CI, 0.60-1.81]; P=0.89). CONCLUSIONS: Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac light chain amyloidosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03401372.

Comprehensive geriatric assessment in newly diagnosed older myeloma patients: a multicentre, prospective, non-interventional study.

BACKGROUND: Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. OBJECTIVE: We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. RESULTS: We studied 349 older patients with newly diagnosed MM (age range, 65-86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA 'fit' group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1-38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). CONCLUSIONS: Our study justifies the need for a CGA in older patients with newly diagnosed MM.

Direct arterial puncture for hemodialysis, a neglected but simple and valuable vascular access.

INTRODUCTION: The purpose of this study is to present the prevalence and effects of direct arterial puncture (DAP) for hemodialysis patients, and to introduce optimal option for the vascular access (VA) in certain hemodialysis patients with poor condition of vascular or cardiac function in a compelling situation. METHODS: This was a cross-sectional study. Demographic characteristics and laboratory data were extracted from the health care system. Relevant DAP information was collected by a questionnaire. Case-control matching was performed to compare the hemodialysis adequacy between DAP and other VAs. RESULTS: A total of 526 patients were selected for analysis by convenience sampling, of which 38 patients relied https://www.baidu.com/link?url=eaDh8Hn-yZGJyDB0_h4zBenKd7qY1yX-KNxO-qU49gktQOGTJJg3slTjIbG095st4hRfprQIHRjfhfeGOZyH73y8tvSUCwMmvWbUhyix2ZK on DAP for hemodialysis. The main reasons using DAP for hemodialysis included the cost of arteriovenous access creation or maintenance in 19(50%) patients and the poor condition of vascular or cardiac function in 14 (39.5%) patients. Some complications of DAP occurred, such as aneurysm or pseudoaneurysm in 16(42.1%) patients, infiltration in 12 (31.6%) patients. Differences in hemodialysis adequacy were not statistically significant between DAP and other types of VA. CONCLUSION: In conclusion, DAP can meet the need of prescription hemodialysis, yet it has several limitations. Although the patients in our study were long-term dependent on DAP for hemodialysis with various reasons, we do not recommend DAP as a long-term vascular access if better options are available. However, DAP should not be overlooked to be a supplemental VA for hemodialysis with adequate blood flow and availability for individuals with poor condition of vascular or cardiac function in a compelling situation.

How to Reduce the Risk of Arteriovenous Fistula Dysfunction by Observing Prepump Arterial Pressure during Hemodialysis: A Multicenter Retrospective Study.

OBJECTIVE: Prepump arterial (Pa) pressure indicates the ease or difficulty with which the blood pump can draw blood from the vascular access (VA) during hemodialysis. Some studies have suggested that the absolute value of the Pa pressure to the extracorporeal blood pump flow (Qb) ratio set on the machine (|Pa/Qb|) can reflect the dysfunction of VA. This study was conducted to explore the impact of arteriovenous fistula (AVF) dysfunction and to explore the clinical reference value of |Pa/Qb|. METHODS: We retrospectively identified adults who underwent hemodialysis at 3 hospitals. Data were acquired from electronic health records. We evaluated the pattern of the association between |Pa/Qb| and AVF dysfunction during 1 year using a Cox proportional hazards regression model with restricted cubic splines. Then, the patients were grouped based on the results, and hazard ratios were compared for different intervals of |Pa/Qb|. RESULTS: A total of 490 patients were analyzed, with an average age of 55 (44, 66) years. There were a total of 85 cases of AVF dysfunction, of which 50 cases were stenosis and 35 cases were thrombosis. There was a U-shaped association between |Pa/Qb| and the risk of AVF dysfunction (p for nonlinearity <0.001). |Pa/Qb| values <0.30 and >0.52 increased the risk of AVF dysfunction. Compared with the group with a |Pa/Qb| value between 0.30 and 0.52, the groups with |Pa/Qb| <0.30 and |Pa/Qb| >0.52 had a 4.04-fold (p = 0.002) and 3.41-fold (p < 0.001) greater risk of AVF dysfunction, respectively. CONCLUSIONS: The appropriate range of |Pa/Qb| is between 0.30 and 0.52. When |Pa/Qb| is <0.30 or >0.52, the patient's AVF function or Qb setting should be reevaluated to prevent subsequent failure.

MH-STRALP: A scoring system for prognostication in patients with upper gastrointestinal bleeding.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common medical emergency and early assessment of its outcomes is vital for treatment decisions. AIM: To develop a new scoring system to predict its prognosis. METHODS: In this retrospective study, 692 patients with UGIB were enrolled from two centers and divided into a training (n = 591) and a validation cohort (n = 101). The clinical data were collected to develop new prognostic prediction models. The endpoint was compound outcome defined as (1) demand for emergency surgery or vascular intervention, (2) being transferred to the intensive care unit, or (3) death during hospitalization. The models' predictive ability was compared with previously established scores by receiver operating characteristic (ROC) curves. RESULTS: Totally 22.2% (131/591) patients in the training cohort and 22.8% (23/101) in the validation cohort presented poor outcomes. Based on the stepwise-forward Logistic regression analysis, eight predictors were integrated to determine a new post-endoscopic prognostic scoring system (MH-STRALP); a nomogram was determined to present the model. Compared with the previous scores (GBS, Rockall, ABC, AIMS65, and PNED score), MH-STRALP showed the best prognostic prediction ability with area under the ROC curves (AUROCs) of 0.899 and 0.826 in the training and validation cohorts, respectively. According to the calibration curve, decision curve analysis, and internal cross-validation, the nomogram showed good calibration ability and net clinical benefit in both cohorts. After removing the endoscopic indicators, the pre-endoscopic model (pre-MH-STRALP score) was conducted. Similarly, the pre-MH-STRALP score showed better predictive value (AUROCs of 0.868 and 0.767 in the training and validation cohorts, respectively) than the other pre-endoscopic scores. CONCLUSION: The MH-STRALP score and pre-MH-STRALP score are simple, convenient, and accurate tools for prognosis prediction of UGIB, and may be applied for early decision on its management strategies.

GM1 Ameliorates Neuronal Injury in Rats after Cerebral Ischemia and Reperfusion: Potential Contribution of Effects on SPTBN1-mediated Signaling.

Monosialoganglioside GM1 (GM1) has long been used as a therapeutic agent for neurological diseases in the clinical treatment of ischemic stroke. However, the mechanism underlying the neuroprotective function of GM1 is still obscure until now. In this study, we investigated the effects of GM1 in ischemia and reperfusion (I/R) brain injury models. Middle cerebral artery occlusion and reperfusion (MCAO/R) rats were treated with GM1 (60 mg·kg-1·d-1, tail vein injection) for 2 weeks. The results showed that GM1 substantially attenuated the MCAO/R-induced neurological dysfunction and inhibited the inflammatory responses and cell apoptosis in ischemic parietal cortex. We further revealed that GM1 inhibited the activation of NFκB/MAPK signaling pathway induced by MCAO/R injury. To explore its underlying mechanism of the neuroprotective effect, transcriptome sequencing was introduced to screen the differentially expressed genes (DEGs). By function enrichment and PPI network analyses, Sptbn1 was identified as a node gene in the network regulated by GM1 treatment. In the MCAO/R model of rats and oxygen-glucose deprivation and reperfusion (OGD/R) model of primary culture of rat cortical neurons, we first found that SPTBN1 was involved in the attenuation of I/R induced neuronal injury after GM1 administration. In SPTBN1-knockdown SH-SY5Y cells, the treatment with GM1 (20 µM) significantly increased SPTBN1 level. Moreover, OGD/R decreased SPTBN1 level in SPTBN1-overexpressed SH-SY5Y cells. These results indicated that GM1 might achieve its potent neuroprotective effects by regulating inflammatory response, cell apoptosis, and cytomembrane and cytoskeleton signals through SPTBN1. Therefore, SPTBN1 may be a potential target for the treatment of ischemic stroke.

Skeletal muscle alterations indicate poor prognosis in cirrhotic patients: a multicenter cohort study in China.

INTRODUCTION: We aimed to determine the diagnostic criteria of myosteatosis in a Chinese population and investigate the effect of skeletal muscle abnormalities on the outcomes of cirrhotic patients. METHODS: Totally 911 volunteers were recruited to determine the diagnostic criteria and impact factors of myosteatosis, and 480 cirrhotic patients were enrolled to verify the value of muscle alterations for prognosis prediction and establish new noninvasive prognostic strategies. RESULTS: Multivariate analysis showed age, sex, weight, waist circumference, and biceps circumference had a remarkable influence on the L3 skeletal muscle density (L3-SMD). Based on the cut-off of a mean - 1.28 × SD among adults aged < 60 years, the diagnostic criteria for myosteatosis was L3-SMD < 38.93 Hu in males and L3-SMD < 32.82 Hu in females. Myosteatosis rather than sarcopenia has a close correlation with portal hypertension. The concurrence of sarcopenia and myosteatosis not only is associated with poor liver function but also evidently reduced the overall and liver transplantation-free survival of cirrhotic patients (p < 0.001). According to the stepwise Cox regression hazard model analysis, we established nomograms including TBil, albumin, history of HE, ascites grade, sarcopenia, and myosteatosis for easily determining survival probabilities in cirrhotic patients. The AUC is 0.874 (95% CI 0.800-0.949) for 6-month survival, 0.831 (95% CI 0.764-0.898) for 1-year survival, and 0.813 (95% CI 0.756-0.871) for 2-year survival prediction, respectively. CONCLUSIONS: This study provides evidence of the significant correlation between skeletal muscle alterations and poor outcomes of cirrhosis, and establishes valid and convenient nomograms incorporating musculoskeletal disorders for the prognostic prediction of liver cirrhosis. Further large-scale prospective studies are necessary to verify the value of the nomograms.

miR-15a and miR-16 affect the angiogenesis of multiple myeloma by targeting VEGF.

Deregulated microRNAs (miRNAs) and their roles in cancer development have attracted much attention. Two miRNAs, miR-15a and miR-16, which act as putative tumor suppressor by targeting the oncogene BCL2, have been implicated in cell cycle, apoptosis and proliferation. In this study, we investigated the possible role of miR-15a/16 in the angiogenesis of multiple myeloma (MM). Using a stem-loop quantitative reverse transcription-PCR, we analyzed miR-15a/16 expressions in bone marrow samples from newly diagnosed MM patients and a panel of MM cell lines. miRNA transfection, western blotting analysis and assay of luciferase activity were used to examine whether vascular endothelial growth factor (VEGF) is the target of miR-15a/16. The functional roles of miR-15a/16 on tumorigenesis and angiogenesis were examined by in vitro angiogenesis models and in vivo tumor xenograft model. We showed that miR-15a and miR-16 were significantly underexpressed in primary MM cells as well as in MM cell lines. The aberrant expression of miR-15a/16 was detected especially in advanced stage MM. In human MM cell lines and normal plasma cells, expression of miR-15a/16 inversely correlated with the expression of VEGF-A. Western blotting combined with the luciferase reporter assay demonstrated that VEGF-A was a direct target of miR-15a/16. Ectopic overexpression of miR-15a/16 led to decreased pro-angiogenic activity of MM cells. Finally, infection of lentivirus-miR-15a or lentivirus-miR-16 resulted in significant inhibition of tumor growth and angiogenesis in nude mice. This study suggest that miR-15a/16 could play a role in the tumorigenesis of MM at least in part by modulation of angiogenesis through targeting VEGF-A.

Gene silencing of the BDNF/TrkB axis in multiple myeloma blocks bone destruction and tumor burden in vitro and in vivo.

Osteolytic bone diseases are a prominent feature of multiple myeloma (MM), resulting from aberrant osteoclastic bone resorption that is uncoupled from osteoblastic bone formation. Myeloma stimulates osteoclastogenesis, which is largely dependent on an increase in receptor activator of NF-κB ligand (RANKL) and a decrease in osteoprotegerin (OPG) within the bone marrow milieu. Recently, brain-derived neurotrophic factor (BDNF) was identified as a MM-derived factor that correlates with increased RANKL levels and contributes to osteolytic bone destruction in myeloma patients. Because tyrosine receptor kinase B (TrkB), the receptor of BDNF, is abundantly expressed in osteoblasts, we sought to evaluate the role of BDNF/TrkB in myeloma-osteoblast interactions and the effect of this pathway on the RANKL/OPG ratio and osteoclastogenesis. Coculture systems constructed with noncontact transwells revealed that, in vitro, MM-derived BDNF increased RANKL and decreased OPG production in osteoblasts in a time- and dose-dependent manner. These effects were completely abolished by a specific small interfering RNA for TrkB. BDNF regulates RANKL/OPG expression in osteoblasts through the TrkB/ERK pathway. To investigate the biological effects of BDNF on myeloma in vivo, a SCID-RPMI8226 mice model was constructed using lentiviral short hairpin RNA-transfected RPMI8226 cells. In this system, stable knockdown of BDNF in MM cells significantly restored the RANKL/OPG homostasis, inhibited osteolytic bone destruction and reduced angiogenesis and tumor burden. Our studies provide further support for the potential osteoclastogenic effects of BDNF, which mediates stroma-myeloma interactions to disrupt the balance of RANKL/OPG expression, ultimately increasing osteoclastogenesis in MM.

Role of brain-derived neurotrophic factor in bone marrow angiogenesis in multiple myeloma.

This study examined the expression of brain-derived neurotrophic factor (BDNF) in multiple myeloma (MM) and its role in bone marrow angiogenesis. The peripheral blood plasma was harvested from 71 MM patients and 63 patients without hematological malignancy. The BDNF level in the blood plasma was determined by ELISA. Human bone marrow endothelial cells (HBMECs) were cultured. The mRNA and protein expression levels of the BDNF receptor TrkB in HBMECs were detected by using RT-PCR and flow cytometry, respectively. The viability of HBMECs treated with recombinant human (rh) BDNF or not was measured by using MTT assay. The migration of HBMECs in the presence of rhBDNF or not was determined by modified Boyden chamber assay. In vitro tube formation assay was used to assess the effect of rhBDNF on HBMECs differentiation. The results of ELISA revealed that the BDNF level was significantly higher in peripheral blood plasma of MM patients than in that of control patients (4.39±0.67 vs. 1.96±0.39 ng/mL, P<0.05). The BDNF receptor TrkB was expressed in HBMECs at mRNA and protein level. MTT assay manifested that rhBDNF could significantly concentration-dependently promote the HBMECs proliferation. The number of HBMECs treated with 160 ng/mL rhBDNF for 48 h was 1.57±0.10 folds higher than that in control group (P<0.05). Moreover, rhBDNF could enhance HBMECs migration in a concentration-dependent manner and the maximal migration was reached in the presence of 100 ng/mL rhBDNF. The migration indexes were 1.40±0.11, 1.64±0.16, 2.06±0.25 and 2.18±0.21 in 25, 50, 100 ng/mL rhBDNF groups and 25 ng/mL rhVEGF group, respectively. In vitro tube formation assay demonstrated that the area of the formed tubular structure was increased with the rhBDNF concentration. In control group, there was no formation of intact tubular structure and the HBMECs on the matrigel were irregularly dispersed. HBMECs treated with 100 ng/mL rhBDNF could form intact tubular structure and the area and the diameter of tubes were significantly greater than those in control group (P<0.05). There was no significant difference in the formed tubular area between 25 ng/mL VEGF group and 100 ng/mL rhBDNF group. It was concluded that BDNF plays an important role in myeloma cell-induced angiogenesis, and it may become a new target of anti-angiogenesis treatment for MM.

[Clinical research on bilateral arcuate artery suture hemostasis of corpus uteri for postpartum hemorrhage due to uterine inertia during caesarean section].

OBJECTIVES: To investigate the effect of bilateral arcuate artery suture hemostasis of corpus uteri (haemostasia) for postpartum hemorrhage due to uterine inertia during caesarean section, and to explore the change of blood vessels and blood flow of the uterus after surgery. METHODS: From May 2009 to Dec. 2011, the 212 patients in No. 202 People's Liberation Army Hospital received bilateral arcuate artery suture hemostasis of corpus uteri for postpartum hemorrhage due to uterine inertia during caesarean section. Among them, 127 patients who failed to respond to conservative management and received haemostasia were defined as the 'haemostasia' group. 23 patients who received the suture after they failed to respond to conservative management and other conventional surgical hemostasis were defined as the 'other + haemostasia' group. 62 patients who received the suture simultaneously with conservative management were defined as the 'drug + haemostasia' group. The suture was done by the following steps: (1) The uterus should be exteriorised, and the fundus of uterus should be towards the head. (2) Transfix the anterior and posterior wall of corpus uteri with big blunt round needle and absorbable suture. The entry point was 2 cm above the uterine incision and 2 cm to lateral border of corpus uteri. The suture spanned the fundus of uterus, and was stretched tightly in front of the fundus, then tied knots were made. Bleeding volume, prompt hemostatic rate, effect rate, total effect rate and operation time were recorded. The resistance index (RI) of uterine artery, systolic/diastolic blood pressure (S/D), the visualization ratio of uterine artery and the mean value of artery diameter were obtained through color Doppler ultrasonography and enhancement CT 6 - 12 months after the surgery. RESULTS: (1) In the 'drug + haemostasia' group, the bleeding volume was (532 ± 28) ml. The operation time was (34 ± 3) min, and the prompt hemostatic rate was 97%. While the 'haemostasia' group had more bleeding volume, longer operation time and lower prompt hemostatic rate than the 'drug + haemostasia' group, with no statistically significant difference (P > 0.05). In 'other + haemostasia' group, the bleeding volume was (1379 ± 95) ml. The operation time was (79 ± 15) min, and the prompt hemostatic rate was 78%. The differences were significant when compared to the other groups (P < 0.01). There was no statistically significant difference on total effect rate among the three groups (P > 0.05). (2) There was no statistically significant difference on the RI and S/D of bilateral uterine artery among all the groups 6-12 months after the surgery. (3) The visualization ratio of left uterine artery of the 'other + haemostasia' group was lower (87%) than the 'haemostasia' group (97%) and the 'drug + haemostasia' group (95%, P < 0.05). There was no statistically significant difference between the 'haemostasia' group and the 'drug + haemostasia' group on the visualization ratio of bilateral uterine artery and the mean value of bilateral uterine artery diameter (P > 0.05). CONCLUSIONS: The bilateral arcuate artery suture hemostasis of corpus uteri is a simple, rapid, effective and safe method to control postpartum hemorrhage due to uterine inertia during caesarean section. The ovary and uterine blood flow are not affected after the surgery.

Social isolation does not alter the relationship between flexibility in metabolic rate and growth in grass carp (Ctenopharyngodon idella) under changing food availability.

Growth and energy metabolism are highly flexible in fish species in response to food availability, and these two traits depend to some extent on the social rearing environment (e.g., isolated vs. group rearing). Currently, how social rearing environments influence flexibility in metabolic rate of fish and their ecological consequences (e.g., somatic growth) remain largely unknown. Here, we investigated how social isolation (i.e., group-reared vs. isolation-reared) and food availability (i.e., high vs. low) affect metabolic rates, growth and their correlations in a group-living fish, grass carp (Ctenopharyngodon idella), which were subjected to a 4-week growth experiment. The metabolic rates (e.g., standard metabolic rate, SMR; maximum metabolic rate, MMR; aerobic scope, AS = MMR-SMR) and morphology (e.g., body mass and length) of the fish in four treatments were measured at the beginning and end of the growth experiment, and then the growth parameters (e.g., food intake, FI; feeding efficiency, FE; and specific growth rate, SGR) were also obtained. We found that social isolation did impair growth of fish with individuals showing a lower SGR compared to those group-reared fish irrespective of food availability. However, the growth advantage of group-reared fish under two food availabilities did not result from their FIs or FEs. Metabolic rates (i.e., SMR) seemed to decrease in response to social isolation, but increased greater when fish were reared at high food ration. These shifts in metabolic rates were positively linked with individual differences in somatic growth; individuals who increased metabolic rates more grew faster, while those who increased their metabolic rates less or even reduced had a lower growth, but these links were independent on both social isolation and food ration. These results suggested that social isolation can inhibit the growth of individual fish, but not the AS. Flexibility in metabolic rates could confer a growth advantage under changing food availability, but the links between variation in energy metabolism and growth were not altered by social deprivation. Our study demonstrates the importance of metabolic plasticity accounting for inter-individual difference in growth performance under the challenges of changing food resource.

[Retracted] siRNA­mediated inhibition of endogenous brain­derived neurotrophic factor gene modulates the biological behavior of HeLa cells.

Subsequently to the publication of the above article and a Corrigendum that was published to indicate corrections made to Fig. 7 (DOI: 10.3892/or.2021.7922; published online on January 5, 2021), a concerned reader drew the Editor's attention to the fact that, comparing between a pair of panels in the Figure, there was an overlapping section of data; moreover, this overlapping section contained apparent anomalies that could not be easily accounted for through a straightforward re­use of one of the data panels. The authors conceded that there was partial duplication between the images shown in Fig. 7B and F, although they were unable to access the related raw data as the experiments had been performed almost 10 years ago. Secondly, the authors informed the Editor that the corresponding author did not know he was on the author list at the time of submission. Although the authors' were granted permission to publish the Corrigendum, the Editor now considers that the paper should be retracted on account of the uncertainties in the presented revised data and the authors' admission concerning the corresponding author. Therefore, this paper has been retracted from the Journal. The authors are in agreement with the decision to retract the article. The Editor apologizes for any inconvenience caused. [Oncology Reports 37: 2751­2760, 2017; DOI: 10.3892/or.2017.5569].

Impact of pulmonary hypertension on arteriovenous fistula failure of hemodialysis patients: A 10 years follow-up cohort study.

BACKGROUND: Pulmonary hypertension (PH) is common in patients with end-stage renal disease (ESRD). Arteriovenous fistulas (AVF) creation may involve in the pathogenesis of PH. The aim of this study was to explore the impact of PH after AVF creation on the AVF failure rate in maintenance hemodialysis (MHD) patients. METHODS: From January 1, 2009, to January 1, 2019, we retrospectively collected data of 578 MHD patients in Guangdong Provincial People's Hospital Blood Purification Center, China. Patients were followed-up until AVF failure or death or May 25, 2020. According to the systolic pulmonary artery pressure (SPAP) within 1 year after the establishment of AVF, the MHD patients were divided into three groups: SPAP ⩽ 35 mmHg, 35 < SPAP < 45 mmHg, SPAP ⩾ 45 mmHg. The primary outcome was AVF failure defined as AVF cannot complete hemodialysis. The secondary outcomes were all-cause mortality. RESULTS: A total of 578 patients were analyzed. The average age was 60.66 ± 15.34 years (58.1% men). Of these, 26.1% of patients were reported PH. The SPAP exhibited a left-skewed nonparametric distribution and the overall SPAP after the creation of AVF was 39.00 (29.00-52.00) mmHg. The median follow-up was 5.8 (5.5-6.3) years. Overall, 12.8% (74/578) patients were reported AVF failure events. There was no significant difference in AVF failure rate among three groups (p = 0.070). A total of 111 (19.2%) died during the follow-up period. Compared with the SPAP ⩽35 mmHg group, only the all-cause death rate significantly increased in MHD patients with PH (p < 0.001). CONCLUSIONS: The secondary pulmonary hypertension after AVF creation did not increase the risk of AVF failure in MHD patients, but significantly increased the risk of mortality for this portion of the patients. Future larger sample sizes, multi-center, and prospective trials are needed to make sure which type of access will benefit on their survival for MHD patients with SPAP ⩾35 mmHg.

Prevalence and risk factors of covert hepatic encephalopathy in cirrhotic patients: A multicenter study in China.

OBJECTIVE: We aimed to investigate the prevalence of covert hepatic encephalopathy (CHE) in cirrhotic patients in China and its risk factors. METHODS: A multicenter prospective observational study was conducted from January 2021 to March 2022 at 16 medical centers across China to investigate the risk factors of CHE and establish a prediction model for CHE episodes. RESULTS: A total of 528 patients were enrolled in the study. Based on both the psychometric hepatic encephalopathy score and Stroop test results, the prevalence of CHE was 50.4% (266/528), and the consistency between these two tests was 68.9%. Multivariate analysis showed that age (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.022-1.063, P < 0.001), duration of education (OR 0.891, 95% CI 0.832-0.954, P = 0.001), comorbidities of cardiovascular diseases, hypertension, cerebral apoplexy or diabetes mellitus (OR 2.072, 95% CI 1.370-3.133, P < 0.001), Child-Pugh score (OR 1.142, 95% CI 1.029-1.465, P = 0.025), and blood urea nitrogen concentration (OR 1.126, 95% CI 1.038-1.221, P = 0.004) were associated with CHE episodes. According to the Chronic Liver Disease Questionnaire, CHE patients had lower scores for abdominal symptoms and systemic symptoms (P < 0.001), indicating a poor health-related quality of life. Based on a stepwise Cox regression hazard model, we established a nomogram for determining the probabilities of CHE episodes, and the area under the receiver operating characteristic curve was 0.733 (95% CI 0.679-0.788) and 0.713 (95% CI 0.628-0.797) in the training and validation cohorts. CONCLUSIONS: CHE is a common complication of cirrhosis in China. Large-scale studies with long-term follow-up are needed to determine the natural history of Chinese CHE patients.

A national, multicenter, retrospective study of Castleman disease in China implementing CDCN criteria.

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

Brain-derived neurotrophic factor is a potential osteoclast stimulating factor in multiple myeloma.

Multiple myeloma (MM) is characterized by accumulation of monoclonal plasma cells in the bone marrow and progression of lytic bone lesions. The mechanisms of enhanced bone resorption in patients with myeloma are not fully defined. We have previously identified the role of brain-derived neurotrophic factor (BDNF) in proliferation and migration of MM cells. In our study, we investigated whether BDNF was possibly involved in MM cell-induced osteolysis. We showed that BDNF was elevated in MM patients and the bone marrow plasma levels of BDNF positively correlated with extent of bone disease. In osteoclast formation assay, bone marrow plasma from patients with MM increased osteoclast formation and the effect was significantly blocked by neutralizing antibody to BDNF, suggesting a critical role for BDNF in osteoclast activation. Furthermore, the direct effects of recombinant BDNF on osteoclast formation and bone resorption support the potential role of BDNF in the MM bone disease. BDNF receptor TrkB was expressed by human osteoclast precursors and a Trk inhibitor K252a markedly inhibited osteoclast formation stimulated with BDNF, demonstrating that BDNF used TrkB for its effects on osteoclast. Finally, bone marrow plasma BDNF level positively correlated with macrophage inflammatory protein-1α and receptor activator of nuclear factor-κB ligand, two major osteoclast stimulatory factors in MM. These results support an important role for BDNF in the development of myeloma bone disease.

Long-term outcomes in health-related quality of life influence chronic disease management in patients with pulmonary hypertension.

Background: Significantly improved survival in patients with pulmonary hypertension (PH) has raised interest in maintaining a good quality of long-term survivorship. In this study, health-related quality of life (HRQOL) measurement was used to assess the long-term changes of physical and mental outcomes. Methods: A total of 559 consecutive inpatients with PH completed generic HRQOL (Short Form-36) who were diagnosed with PH by right heart catheterization. Assessments were carried out at short-term (1 year), midterm (3 years), and long-term (5 years) follow-ups. Results: Patients with PH suffered more severe impairments in both physical and emotional domains than the U.S. population normative values. Patients with PH due to chronic lung disease had the worst physical component summary (PCS) score, but there was no difference in mental component summary (MCS) score among different PH types. A reduced PCS score was correlated with WHO FC severity and pulmonary vascular resistance (PVR). The Z score showed that the changing trend of mental conditions continuously declined from baseline to midterm and long-term follow-ups, but the PCS score seemed to be stable or improved. Cox regression analysis indicated increased baseline PVR and WHO FC III and IV, and decreased physical subscale of role physical, mental subscale of social functioning, and the MCS score have increased risk of mortality in the long-term follow-up. Conclusion: Patients with PH have poor HRQOL. The long-term change of physical status seemed to be stable, but the mental state was continuously worse. These suggested identifying and intervening mental health progresses is a noteworthy issue in PH chronic management.

A sodalite-type porous metal-organic framework with polyoxometalate templates: adsorption and decomposition of dimethyl methylphosphonate.

A sodalite-type porous metal-organic framework with polyoxometalate templates, H(3)[(Cu(4)Cl)(3)(BTC)(8)](2)[PW(12)O(40)]·(C(4)H(12)N)(6)·3H(2)O (NENU-11; BTC = 1,3,5-benzenetricarboxylate), was obtained by a hydrothermal reaction. As a reasonable candidate for eliminating nerve gas, NENU-11 displays good adsorption behavior for dimethyl methylphosphonate (15.5 molecules per formula unit). In virtue of the catalytic activity of polyoxometalate guests, this nerve gas mimic could be facilely decomposed by a hydrolysis reaction.

[Characterization of vinflunine tartrate liposomes in vitro and in vivo].

Vinflunine tartrate-loaded liposomes (VT-L) with two drug-to-lipid ratios were prepared by pH gradient method. Vesicle size and zeta potential were determined by the Zetasizer Nano ZS. Entrapment efficiency was evaluated by cation exchange resin centrifugalization method. The toxicity and tumor inhibition to nude mouse administrated by VT-L with different drug-to-lipid ratios were investigated and compared with the vinflunine tartrate injection (VT-I). The results showed that the mean particle size, zeta potential and entrapment efficiency of the VT-L with drug-to-lipid ratios of 1 : 5 and 1 : 10 were 124.6 nm and 128.3 nm, -25.3 mV and -22.8 mV, 94.46% and 97.31%, respectively. The VT-L with two different drug-to-lipid ratios has significantly higher anti-tumor effect to nude mouse transplanted human non-small cell lung carcinoma A549 and lower toxicity than VT-I. While there were no significant differences in anti-tumor effect and toxicity between VT-L with two different drug-to-lipid ratios.