[Integrated Analysis on Source-exposure Risk of Heavy Metals in Farmland Soil Based on PMF Model: A Case Study in the E-waste Dismantling Area in Zhejiang Province].

In order to explore the characteristics and sources of heavy metals in farmland soil and their risks to human health and to provide an important scientific basis for farmland pollution control, 133 surface soils (0-20 cm) were collected from typical agricultural production areas in Zhejiang Province, and the contents of soil Cd, Pb, Cr, Cu, Zn, Ni, As, and Hg were determined. Various methods were applied to evaluate the degree of heavy metal pollution in farmland and its ecological risks in the study area. The method of combining Kriging interpolation and positive definite matrix factor analysis (PMF) was applied to analyze the pollution sources and quantify the contribution of each pollution source. Combined with the health risk assessment model, the risk to human health of each pollution source was evaluated from the perspective of source exposure. The results showed that the average ω(Cd), ω(Pb), ω(Cr), ω(Cu), ω(Zn), ω(Ni), ω(As), and ω(Hg) were 0.76, 65.22, 92.02, 103.92, 198.49, 36.65, 5.97, and 0.20 mg·kg-1, respectively. The average contents of Cd and Cu were higher than the risk screening values of soil contamination of agricultural land, and 85.71% and 96.24% of soil was contaminated by heavy metals. The average contents of Pb, Cr, Zn, and Ni exceeded the soil background values of the Wenhuang Plain in Zhejiang Province, and the As and Hg contents were within the limit values. The potential soil ecological risks were mainly light-moderate, accounting for 90.98%, and both high and higher risk accounted for 4.51%; Cd was the main potential ecological risk element. The main sources of heavy metal pollution in the study area were the sources of the electronic waste dismantling process (26.82%), the mixed sources of coal combustion and traffic emissions (34.50%), mixed sources of natural parent materials and agricultural inputs (25.59%), and e-waste pickling runoff and solid waste leaching sources (13.09%). The health risk of heavy metal exposure to children was significantly greater than that in adults. Mixed sources of natural parent materials and agricultural inputs contributed the most to human health risks, and Cr was the element with the greatest contribution to human health risks.

Efficacy and safety of pomalidomide and low-dose dexamethasone in Chinese patients with relapsed or refractory multiple myeloma: a multicenter, prospective, single-arm, phase 2 trial.

BACKGROUND: Pomalidomide in combination with dexamethasone has demonstrated positive results in patients with relapsed or refractory multiple myeloma (RRMM), but no data are available in China. We conducted a multicenter, single-arm trial to examine the efficacy and safety of bioequivalent generic pomalidomide plus low-dose dexamethasone in Chinese RRMM patients. METHODS: Adult (≥ 18 years of age) RRMM patients who progressed after at least two previous treatments, including bortezomib and lenalidomide, were eligible. Pomalidomide was given orally at 4 mg/day on days 1 to 21 of a 28-day cycle. Dexamethasone was given at 40 mg/day (either orally or intravenously; 20 mg/day at 75 years or older) on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression or intolerable adverse events (AEs). The primary end point was objective response rate (ORR). RESULTS: Seventy-four patients were enrolled between February 2017 and February 2019. All patients had progressed within 60 days of their last therapy. 74.3% of the patients were resistant to lenalidomide, 31.1% had renal insufficiency and 33.8% had high-risk cytogenetic RRMM. The median follow-up duration was 33.0 months (range 31.1-34.8 months). The ORR was 37.8% in the overall analysis, 32.7% in lenalidomide-refractory patients, 36.0% in patients with high-risk cytogenetics and 34.8% in RRMM patients with renal impairment. The median progression-free survival was 5.7 months (95% CI 3.7-8.8 months). The median overall survival was 24.3 months (95% CI 14.4-41.1 months). The most common grade 3 and 4 treatment-emergent adverse events (TEAEs) were neutropenia (63.5%), leukopenia (37.8%), thrombocytopenia (28.4%), and anemia (31.1%). Pulmonary infection (27.0%) was the most frequent grade 3 and 4 nonhematologic TEAE. No previously unreported AEs were observed. No venous thromboembolism was reported. CONCLUSIONS: Pomalidomide in combination with low-dose dexamethasone is effective and safe in Chinese RRMM patients. TRIAL REGISTRATION: The study is registered at Chinese Clinical Trial Registry (ChiCTR) ( ChiCTR-OIC-17013234 , first registered on 03/11/2017).

Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2).

BACKGROUND: LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years. METHODS: LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 × 106 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy. RESULTS: As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade ≥ 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer. CONCLUSIONS: The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285.

[Microbial Composition and Diversity in Soil of Torreya grandis cv. Merrillii Relative to Different Cultivation Years After Land Use Conversion].

In order to explore the impacts of the land use conversion from a Phyllostachy pubescens (moso bamboo) forest to a Torreya grandis cv. Merrillii plantation, as well as the cultivating years of the T. grandis cv. Merrillii plantation, on the soil microbial community, this research studied the soil microbial structure and diversity of a moso bamboo forest, T. grandis cv. Merrillii plantations (5, 10, and 30 a), and a T. grandis cv. Merrillii-mountain rice interplanting plantation (5 a) using the high-throughput sequencing technique, and the relationship between the microbial community and environmental factors was further explored. The results showed that after the land use change, the Shannon index and Chao1 index of the soil bacterial community increased significantly; the Simpson index increased significantly in the 30 a T. grandis cv. Merrillii plantation, whereas the Shannon index decreased significantly. Both the Simpson index and Chao index of the soil fungal community had no significant difference under different land use types. whereas the Shannon index was significantly decreased in the 30 a T. grandis cv. Merrillii plantation. PCoA analysis of the soil microbial community at the genus level showed that land use type played a vital role in driving the changes in soil bacterial and fungal communities. The compositions of the soil microbial communities between the two 5 a stands were most similar. The dominant phyla of soil bacteria mainly included Acidobacteria, Proteobacteria, Actinobacteria, and Chloroflexi. The results of cluster analysis showed that the soil bacterial community changed significantly at the genus level after the conversion of land use; the abundance of most dominant bacterial communities decreased with increasing cultivation. The fungal community was mainly composed of Ascomycota, Basidiomycota, and Zygomycota, whose changes in community characteristics were similar to those of bacteria. The results of RDA analysis showed that pH, organic matter, available phosphorus, available potassium, and water-soluble organic carbon and nitrogen were significantly correlated with soil microbial community. Therefore, these soil fertility properties might be the driving factors affecting the structure of bacterial communities. This study provided a theoretical basis for solving the problem of soil quality deterioration in T. grandis cv. Merrillii stand land management.

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.

[Spatial Distribution Characteristics and Risk Assessment of Cadmium Pollution in Soil-crops system of an E-waste Dismantling Area].

With the rapid development of electronic technology, soil heavy metal contamination caused by electronic waste dismantling activities has attracted the attention of many researchers. To investigate the contamination status and spatial distribution of Cd in soil-crop systems around an e-waste dismantling area, 171 pairs of soil and crop samples were collected for analysis. The concentrations of cadmium in root vegetable soil, leaf vegetable soil, solanaceous vegetable soil, and orchard soil were (1.292±0.647), (1.010±0.201), (0.921±0.125), and (0.861±0.135) mg·kg-1, respectively. The average values of cadmium in these four soil types were 10.0, 7.8, 7.1, and 6.3 times the background values of soil Cd in Zhejiang Province, respectively, and 4.31, 3.4, 3.07, and 2.72 times the risk screening values for soil contamination of agricultural land, clearly indicating cadmium accumulation in the soil. However, only a small percentage of crops contained cadmium levels that exceeded food safety limits. Moreover, different types of crops showed different capacities for cadmium enrichment and can be ranked accordingly: leaf vegetables > root vegetables > solanaceous vegetables > fruits. The single factor pollution index and the potential ecological risk assessment revealed severe Cd contamination in the study area, with a high potential ecological risk. Cadmium exposure posed a higher health risk for children than for adults. However, the single heavy metal cadmium pollution index does not indicate a threat to local residents at this time. Moran's I index and kriging interpolation results revealed that Cd has significant spatial autocorrelation, with high values mainly concentrating around the e-waste dismantling area, indicating a significant correlation with e-waste dismantling activities.

Comparison of outcomes after human leukocyte antigen-matched and haploidentical hematopoietic stem-cell transplantation for multiple myeloma.

BACKGROUND: Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs). METHODS: Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up. RESULTS: Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90-30.10%) and 24.2% (95% CI, 13.81-34.59%) for the MRD group and 16.80% (95% CI, 1.71-31.89%) and 28.70% (95% CI, 8.71-48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24-71.36%) and 45.4% (95% CI, 33.44-57.36%), and 65.6% (95% CI, 47.18-84.02%) and 26.8% (95% CI, 7.59-46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD. CONCLUSION: Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma.

Relapsed and refractory (R/R) multiple myeloma (MM) patients have very poor prognosis. Chimeric antigen receptor modified T (CAR T) cells is an emerging approach in treating hematopoietic malignancies. Here we conducted the clinical trial of a biepitope-targeting CAR T against B cell maturation antigen (BCMA) (LCAR-B38M) in 17 R/R MM cases. CAR T cells were i.v. infused after lymphodepleting chemotherapy. Two delivery methods, three infusions versus one infusion of the total CAR T dose, were tested in, respectively, 8 and 9 cases. No response differences were noted among the two delivery subgroups. Together, after CAR T cell infusion, 10 cases experienced a mild cytokine release syndrome (CRS), 6 had severe but manageable CRS, and 1 died of a very severe toxic reaction. The abundance of BCMA and cytogenetic marker del(17p) and the elevation of IL-6 were the key indicators for severe CRS. Among 17 cases, the overall response rate was 88.2%, with 13 achieving stringent complete response (sCR) and 2 reaching very good partial response (VGPR), while 1 was a nonresponder. With a median follow-up of 417 days, 8 patients remained in sCR or VGPR, whereas 6 relapsed after sCR and 1 had progressive disease (PD) after VGPR. CAR T cells were high in most cases with stable response but low in 6 out of 7 relapse/PD cases. Notably, positive anti-CAR antibody constituted a high-risk factor for relapse/PD, and patients who received prior autologous hematopoietic stem cell transplantation had more durable response. Thus, biepitopic CAR T against BCMA represents a promising therapy for R/R MM, while most adverse effects are clinically manageable.

[Spatial Variation of Soil Heavy Metals in Lin'an City and Its Potential Risk Evaluation].

Urban soil is an important part of the urban ecosystem, which is strongly correlated with human health and life quality. In this study, Lin'an city was chosen as a typical small city to study the spatial variation and distribution of heavy metals in urban soils and their pollution characteristics using multivariate analysis, geostatistics, and GIS techniques. A total of 62 soil samples were collected from the study areas. The results indicated that the average concentrations of soil Mn, Cu, Zn, Pb, Cr, and Cd were 439.42, 42.23, 196.80, 62.55, 63.65, and 0.22 mg·kg-1, respectively. Compared with the background values and the environmental quality standards, these heavy metals were accumulated in urban soils to some extent. Almost 80% of the study area was polluted by heavy metals. The single potential ecological risk index of heavy metals indicated that Pb had the highest ecological risk. The pH and most of the heavy metals had strong correlations, and there were strong correlations among the heavy metals. The principle component analysis (PCA) showed that Pb, Zn, and Cu had the same pollution source, which was related to vehicle exhausts; Mn and Cr were mainly from the parent material; and Cd was from the emissions of manufacturing plants. The spatial structure and distribution of heavy metals and their corresponding available fractions had strong spatial autocorrelation with all of the C0/(C0+C)<50%. Their spatial patterns were influenced by human activities.

[A case of circulatory collapse during laparoscopic hepatectomy].

OBJECTIVE: We report a case of intractable circulatory failure event in a hypertensive patient during laparoscopy hepatectomy and analyze the diagnosis and treatment by multidisciplinary physicians. This case suggests that both surgeons and anesthesiologists should give attention to oral angiotensin II receptor antagonist during the preoperative period to avoid refractory hypotension. In addition, the use of EV1000 hemodynamic monitoring system in intensive care provides more convenience for clinical liquid management.

In vivo and in vitro anti-sepsis effects of physcion 8-O-ß-glucopyranoside extracted from Rumex japonicus.

The present study was designed to investigate the anti-sepsis effects of physcion 8-O-ß-glucopyranoside (POG) isolated from Rumex japonicas and explore its possible pharmacological mechanisms. POG was extracted from R. japonicas by bioactivity-guided isolation with the anti-sepsis agents. Survival analysis in septic mouse induced by LPS and heat-killed Escherichia coli were used to evaluate the protective effect of POG (40 mg·kg-1, i.p.) on sepsis. Cytokines including TNF-α, IL-1ß and IL-6 in RAW 264.7 cells induced by LPS (100 ng·mL-1) were determined by ELISA. In addition, the proteins expressions of TLR2 and TLR4 were determined by Western blotting assay. Our results demonstrated that POG (40 mg·kg-1, i.p.) possessed significant protective activity on the endotoxemic mice. The POG treatment (20, 40, and 80 µg·mL-1) significantly decreased the TNF-α, IL-1ß and IL-6 induced by LPS (P < 0.01) in a concentration-dependent manner. Furthermore, the TLR4 and TLR2 proteins were also down-regulated by POG at 20 (P < 0.01), 40 (P < 0.01), and 80 µg·mL-1 (P < 0.01). The present study demonstrated that the POG extracted from R. japonicas possessed significant anti-sepsis effect on endotoxemic mice, and can be developed as a novel drug for treating sepsis in the future.

Novel perfusion-decellularized method to prepare decellularized ureters for ureteral tissue-engineered repair.

As the endoscopic technique is widely used in the diagnosis and treatment of diseases, the incidence of ureteral injuries increases annually. The classical surgical therapies are not always satisfactory. With the constant development of the tissue engineering technology in the field of urinary reconstruction, the ureteral reconstruction has become possible technology. In this study, a novel perfusion-decellularized protocol, which combined a perfusion system with the commonly used physical and chemical methods, was used to prepare the decellularized ureters for ureteral reconstruction and the urinary tract-derived cells (UDCs) were seeded on the surface of the perfusion-decellularized ureters (PDUs) in order to observe the cells survival, adhesion, proliferation and distribution. The data of H&E staining, DAPI staining, and the agarose gel electrophoresis demonstrated that the cellular components of PDUs were removed, and the decellularized time was shorter than previous study. In addition, compared with the native ureters, the DNA content of the PDUs was significantly decreased just two percent residue (P<0.05). Scanning electron microscopy, collagen and glycosaminoglycan content assay showed that the three-dimensional (3D) ultrastructure and the compositions of the extracellular matrix (ECM) of PDUs were well preserved. When the UDCs were seeded onto the PDUs, the UDCs formed multilayer structure on the surface of the PDUs, infiltrated into the deep layer of the decellularized ureters and then formed laminated structure. In conclusion, the decellularized ureters prepared by the novel perfusion-decellularized method may be the potential surrogate for ureteral tissue-engineered repair.

[A perfusion system for preparing canine ureteral acellular matrix].

OBJECTIVE: To explore the feasibility of preparing ureteral acellular matrix (UAM) using perfusion systems. METHODS: Using the luminal structure of the ureter, the UAM was prepared by perfusing canine ureter with SDS, TritonX-100, or both. The residual nuclei in the UAM were evaluated using HE staining, DAPI staining, DNA quantification, and agarose gel electrophoresis. The three-dimensional ultrastructure and the bioactive components were evaluated by Masson's trichrome staining, Alcian Blue staining, collagen quantification, GAG quantification, scanning electron microscopy (SEM), and toxicity detection. RESULTS: HE staining and DAPI staining showed the absence of obvious nuclear materials in the combined group, which was further confirmed by DNA quantification and agarose gel electrophoresis. Masson's trichrome staining, Alcian Blue staining, collagen quantification and GAG quantification all verified that the ultrastructure and the bioactive components were well preserved in the combined group. SEM showed a large amount of porous structure on the surface of the UAM prepared by combined perfusion, and toxicity assay confirmed that the prepared UAM was nontoxic. CONCLUSION: Perfusion of canine ureter with SDS and TritonX-100 is feasible to prepare UAM for ureteral reconstruction.

[Spatial Variation of Soil Heavy Metals in an E-waste Dismantling Area and Their Distribution Characteristics].

A total of 90 soil samples were collected from the study area. The spatial variation of soil heavy metals and their spatial distribution characteristics were studied. The results indicated that the mean soil concentrations of five heavy metals including Cd, Cu, Zn, Pb and Ni were 0.38, 35.13, 121.38, 35.40 and 28.13 mg·kg-1, respectively. Compared with the background values in Zhejiang, the heavy metals were enriched in paddy soils of the study area. Part of study area was seriously contaminated by heavy metals. For the soil Cd, it had obvious contamination characteristics with a high Pi Avevalue (>1). The Cd, and Pb concentrations in paddy soil had strong coefficients of variance (C.V.): 121.05% and 109.38%, respectively. Soil pH and organic matter (SOM) had significant correlations with most of the total heavy metals and their available fractions in soils. The total heavy metals and their available fractions also had strong correlations, such as total Cd and available Cd in soils. Geostatistics and the Local Moran's Ⅰ were used to identify the contaminated hotspots of these five metals. It was found out that the high soil Cd, Cu, Zn, Pb were located in Daxi and Zeguo towns, which could be attributed to E-waste dismantling and other anthropogenic activities. Soil Ni was mainly influenced by the parent material. The heavy metals in soils may pose a potential threat to local ecosystem and human health.

Study of clinical practical model of urinary system injury.

BACKGROUND: In order to improve the clinical treatment level of urinary system injury, it is necessary to build up an animal model of urinary system wound, which is not only analogous to real clinical practice, but also simple and practical. METHODS: We have developed the third generation of firearm fragment wound generator based on the first and the second producer. The best explosive charge of the blank cartridge was selected by gradient powder loading experiments. The firearm fragment injuries were made to the bulbous urethra of 10 New Zealand male rabbits. One week preoperatively and 2, 4 and 8 weeks postoperatively, all the animals underwent urethroscopy and urethrography. At 2, 4 and 8 weeks postoperatively, two animals were randomly selected and killed, and the urethra was cut off for pathological examination. RESULTS: The shooting distance of the third generation of firearm fragment wound generator is 2 cm. The best explosive charge of the blank cartridge is 1 g of nitrocotton. All rabbits survived the procedures and stayed alive until they were killed. Injuries were limited to bulbous urethra and distal urethra. Round damaged areas, 1-1.5 cm in length, on the ventral wall were observed. Ureteroscopy results showed that canal diameter gradually shrank by over 50% in 9 rabbits. The rate of success was 90%. Urethrography result noted that a 1-1.3 cm stricture was formed at the bulbous urethra. Histology results of injured stricture urethra showed that fibrous connective tissue hyperplasia and hyaline degeneration caused further stricture in the canal. CONCLUSIONS: The third generation of firearm fragment wound generator imitates the bullet firing process and is more accurate and repeatable. The corresponding rabbit model of traumatic complex urethral stricture simulates the real complex clinical conditions. This animal model provides a standardized platform for clinical researches on treating traumatic injuries to the urinary system.

Aerobic oxidation of alcohols and the synthesis of benzoxazoles catalyzed by a cuprocupric coordination polymer (Cu(+)-CP) assisted by TEMPO.

A Cu(+)-CP based on the tetranuclear unit {[(HSQPA)2Cu4(bipy)4]·2H2O}n·2nH2O has been constructed through Cu(2+) salt, 2-(sulfonylquinlium-8-yloxy)phthalic acid (H3SQPA), and 4,4'-bipyridine (bipy). This Cu(+)-CP combined with 2,2,6,6-tetramethylpiperidine-1-oxyl as the cocatalyst is an effective catalyst for aerobic oxidation of alcohols and the synthesis of benzoxazoles and can be recycled at least four times without losing its catalytic activity.

ß-catenin SUMOylation is involved in the dysregulated proliferation of myeloma cells.

Over-activation of SUMOylation is correlated with poor prognosis in multiple myeloma (MM), with the mechanism unclear. Wnt signaling is one of the aberrantly regulated pathways related to cancer tumorigenesis and progression. Whether SUMOylation is involved in regulating the activity of Wnt/ß-catenin pathway, however, has not been reported in MM. Here we found that the TOPflash reporter activity and the expression of Wnt/ß-catenin target genes can be down-regulated after interference with SUMOylation through SUMO-1 small interfering RNA (siRNA). SUMOylation inhibition down-regulated ß-catenin at protein level via promotion of ubiquitin-proteasomal mediated degradation. Furthermore, over-expression of ß-catenin rescued Wnt/ß-catenin pathway activity and partially prevented increased apoptosis and growth inhibition induced by SUMOylation inhibition, indicating that ß-catenin was responsible for the observed effect on Wnt/ß-catenin pathway. To gain a clearer view, we exploited the inter-protein interactions of ß-catenin and SUMO-1 in myeloma cell lines. Immunoprecipitation and immunofluorescence assay proved that ß-catenin is subjected to SUMOylation in vivo, which may, at least partially explain the impact of SUMOylation inhibition on ß-catenin. The association of SUMO-1 and ß-catenin was confirmed in myeloma patient samples. Taken together, our data proved that SUMOylation inhibition down-regulates Wnt/ß-catenin pathway by promoting the ubiquitin-proteasomal mediated degradation of ß-catenin. SUMOylation of ß-catenin is part of the mechanisms involved in the dysregulated proliferation of myeloma cells.

N-Heterocyclic carbene (NHC)-modulated Pd/Cu cocatalyzed three-component synthesis of 2,6-diarylquinolines.

Two new NHC adducts of cyclopalladated ferrocenylpyrazine complexes 1-2 have been prepared and characterized. An efficient NHC-modulated Pd/Cu cocatalyzed three-component coupling reaction for the synthesis of 2,6-diarylquinolines from aminobenzyl alcohols, aryl ketones, and arylboronic acids in air is described. The reaction involves oxidation, cyclization and Suzuki reactions. The luminescence of the resulting arylquinolines 3-30 was also investigated.

[The clinical characteristics and prognostic analysis of 147 cases of diffuse large B-cell lymphoma].

OBJECTIVE: To investigate the relationship between the clinical features, pathogenesis, immunophenotype, different classification models and prognosis in Chinese patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 147 patients with DLBCL who were treated with CHOP-like or R-CHOP were subjected to analysis. Standard two-step Envision method of immunohistochemical staining was used to assess the expression of CD10, Bcl-6, MUM1, FOXP1, GCET1, CD5, Bcl-2, Ki-67, then according to Hans algorithm, Choi algorithm and Molecular markers, we compared the differences of their prognoses. RESULTS: (1) Kaplan-Meier univariate analysis of the clinical data of 147 DLBCL patients found that the 3-year overall survival (OS) rates were better in early stage (P=0.032), low IPI score (P=0.001), less than one extranodal involvement (P=0.014), and complete remission (P<0.01). The prognoses had no significant difference in terms of gender, age, LDH, B symptoms and treatment options (P value> 0.05). (2 )For Hans model, GCB group had 42 cases, the ABC group 85 cases; GCB were 47 cases, ABC 80 cases (according to Choi model). Choi model suggested GCB subtype showed much better prognosis than ABC subtype (P=0.047), while Hans model shed no statistically significant difference (P=0.285). (3) Ki-67 of 75% was found to significantly discriminate patients with good or bad prognosis. In R-CHOP group at the same time, low Ki-67 (P=0.017) and CD5-negative groups (P=0.012) were better. Cox proportional hazards regression model showed that IPI score (P=0.002) and Ki-67 (P=0.019) were independent adverse prognostic factors. CONCLUSION: The Ann Arbor stage, IPI score, extranodal involvement status and Ki-67 were significantly associated with prognosis .Compared to Hans algorithm, Choi had an advantage to predict the different prognosis between subtypes, and ABC group had poor outcome. Finally, both Ki-67 and IPI score were independent adverse prognostic factors.

One-pot synthesis of ferrocenyl ketones containing biaryls and 6-aryl-2-ferrocenylquinolines via Ir/Pd-cocatalyzed α-alkylation/Suzuki reaction.

An efficient PPh3-cyclometalated iridium(III) benzo[h]quinoline hydride 1/Pd(OAc)2-cocatalyzed three-component α-alkylation/Suzuki reaction has been developed. The three-component reaction of 4-bromobenzyl alcohol, acetylferrocene, and arylboronic acids gives ferrocenyl ketones containing biaryls in moderate to good yields. This method was successfully applied to a one-pot synthesis of 6-aryl-2-ferrocenyl quinolines, using (2-amino-5-bromophenyl)methanol instead of 4-bromobenzyl alcohol.