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.

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).

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.

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.

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.

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.

[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.

Transdifferentiation of human adipose-derived stem cells into urothelial cells: potential for urinary tract tissue engineering.

Autologous urothelial cells (UCs) provide a cell source for urinary tissue engineering because they can be used safely due to their lack of immunogenicity. However, these cells cannot be harvested under the following circumstances: malignancy, infection and organ loss, etc. Human adipose-derived stem cells (HADSCs) possess the traits of high differentiation potential and ease of isolation, representing a promising resource for tissue engineering and regenerative medicine. Nevertheless, HADSCs have been poorly investigated in urology and the optimal approaches to induce HADSCs into urothelium are still under investigation. In this study, we hypothesized that the change of microenvironment by a conditioned medium was essential for the transdifferentiation of HADSCs into UCs. We then used a conditioned medium derived from urothelium to alternate the microenvironment of HADSCs. After 14 days of culture in a conditioned medium, about 25-50% HADSCs changed their morphology into polygonal epithelium-like shapes. In addition, these cells expressed up-regulating of urothelial lineage-specific markers (uroplakin 2and cytokeratin-18) and down-regulating of mesenchymal marker (vimentin) in RNA and protein level, respectively, which confirmed that HADSCs were induced into urothelial lineage cells. We also measured the growth factors in the conditioned medium in order to analyze the molecular mechanisms regulating transdifferentiation. We observed that the expression levels of PDGF-BB and VEGF were significantly higher than those of the control group after 14 days induction, suggesting they were abundantly secreted into the medium during the culturing period. In conclusion, HADSCs showed in vitro the upregulation of markers for differentiation towards urothelial cells by culturing in an urothelial-conditioned medium, which provides an alternative cell source for potential use in urinary tract tissue engineering.

Synthesis and characterization of triphenylphosphine adducts of ferrocene-based palladacycles and their performance in the Suzuki and Sonogashira reactions with bromo- and chloroarenes.

A new triphenylphosphine adduct of cyclopalladated ferrocenylpyridazine containing a chloride anion, 2a, has been synthesized from the reaction of the chloride-bridged palladacyclic dimer 1a with triphenylphosphine. The corresponding adducts 3a,b containing iodide anion have been readily prepared through anion exchange reactions of 2a,b with NaI in acetone. These complexes were characterized by elemental analysis, IR and 1H-NMR. Additionally, their crystal structures have been determined by X-ray diffraction and intermolecular C-H···X (Cl, Br, I) bonds were found in the crystals. The use of these palladacycles as catalysts for the Suzuki and Sonogashira reactions was examined. The complexes 2a,b exhibited higher catalytic activity than the corresponding 3a,b in the Suzuki reaction. However, the order of activity of adducts with varying halogen anions is 3a~3b > 2a~>2b in the Sonogashira reaction.

[Microscopic versus laparoscopic varicocelectomy in the treatment of varicocele: effects and complications].

OBJECTIVE: To compare the effects and postoperative complications of microscopic varicocelectomy (MV) and laparoscopic varicocelectomy (LV) in the treatment of varicocele. METHODS: We assigned 72 varicocele patients to two groups of equal number to be treated by MV and LV. We compared the two groups in the semen parameters before and 3 months after surgery, postoperative complications, and pregnancy rates of the patients'wives. RESULTS: The operative time was significantly longer in the MV than in the LV group (P<0.05). The postoperative hospital stay showed no significant difference between the MV and LV groups ([2.2 +/- 2.7] d vs [2.8 +/- 0.8] d). Sperm concentration, sperm motility and the percentage of grade a + b sperm were significantly increased in both groups after surgery (P<0.05), but with no significant differences between the two. The pregnancy rate was 65.2% in the former and 57.1% in the latter. Postoperative hydrocele occurred in 5 cases in the LV, but none in the MV group. There were no statistically significant differences in recurrence between the two groups (P>0.05). CONCLUSION: MV is superior to LV for its minimal invasiveness, economical anesthesia, faster recovery and lower rates of postoperative complications and recurrence.

[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.

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.

Introduction to biodegradable polylactic acid ureteral stent application for treatment of ureteral war injury.

OBJECTIVE: • To study the operability and effectiveness of a biodegradable ureteral stent for clinical treatment of ureteral war injury using a canine model. MATERIALS AND METHODS: • A device was designed and employed to generate firearm fragment wounds in unilateral ureters (on randomly chosen sides) of nine beagles (Group A). The wounded ureters were then debrided and sutured. • Intravenous pyelography (IVP) and radioactive renography were performed 40, 80 and 120 days postoperatively. In Group B, firearm fragment wounds were made to the bilateral ureters in nine beagles. A polylactic acid stent was placed unilaterally (on a randomly chosen side) whereas the ureter on the other side was debrided and sutured without stenting. • Both IVP and radioactive renography were performed 40, 80 and 120 days postoperatively. The operability and effectiveness of the biodegradable ureteral stent were studied thereafter. RESULTS: • In Group A, hydronephrosis and hydroureter occurred and worsened postoperatively on the wounded sides in all nine beagles. The ratio of the renal partial concentration indices (RPCI) between the kidneys (unwounded side : wounded side) increased. • The ratio of the kidney washout half-time between the kidneys (unwounded side : wounded side) decreased. In Group B, neither hydronephrosis nor hydroureter was found postoperatively in the stented ureters but both occurred in the unstented ureters in all nine beagles. • The ratio of RPCI between kidneys (stented side : unstented side) increased whereas the kidney washout half-time ratio between the stented and unstented sides decreased. Differences were significant. CONCLUSION: • In Group A, the new canine model for firearm fragment wounds was tested and proved to be operable and effective. In Group B, hydronephrosis and hydroureter were effectively prevented in ureters by biodegradable stent placement compared with the non-stented ureters where hydronephrosis and hydroureter occurred. The renal concentration capacity was effectively protected and the half-time of kidney washout was shortened.

[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.

Vaporesection for managing benign prostatic hyperplasia using a 2-microm continuous-wave laser: a prospective trial with 1-year follow-up.

OBJECTIVE: To explore the safety and clinical efficacy of continuous-wave laser vaporesection for the treatment of obstructive benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: We treated 72 consecutive patients with obstructive BPH using a 70 W 2-microm continuous-wave laser. The mean (range) age of the patients was 68.6 (52-86) years. Before laser treatment, the patients were examined. The mean (SD, range) prostatic volume was 65.8 (21.7, 36-108) mL. The operative outcomes assessed were: resection time, transfusion rate, catheter time, and haemoglobin and serum sodium levels. The following variables were assessed before and after vaporesection: maximum urinary flow rate (Qmax), postvoiding residual urine volume (PVR), International Prostate Symptom Score (IPSS), Quality of Life Index (QoL) and sexual function. RESULTS: All cases were successful using general (two cases), epidural (28) or sacral block regional anaesthesia (42). The mean (SD) vaporesection time was 56 (12.8) min. None of the patients required a transfusion. The mean (SD) catheter time was 1.7 (0.6) days. The mean Qmax increased from 5.7 (1.2) mL/s before to 20.8 (2.1) mL/s after vaporesection and the PVR decreased from 150 to 36 mL. The IPSS and QoL scores improved after vaporesection from 24.6 (4.5) to 6.8 (1.2) and 4.8 (0.2) to 1.4 (0.3), respectively (P < 0.05). Apart from transient dysuria (8%) and irritative symptoms (29%), all patients were satisfied with voiding outcome after vaporesection and none had incontinence. CONCLUSION: Vaporesection using the 2-microm continuous-wave laser for the treatment of obstructive BPH is a safe and effective ablative procedure with minimal morbidity and rare bleeding.

Biodegradable urethral stents seeded with autologous urethral epithelial cells in the treatment of post-traumatic urethral stricture: a feasibility study in a rabbit model.

OBJECTIVE: To evaluate the adhesion and growth of rabbit urethral epithelial cells (UECs) on a biodegradable unbraided mesh urethral stent, and to assess the feasibility and effect of the cell-seeded urethral stent for treating post-traumatic urethral stricture (PTUS) in a rabbit model. MATERIALS AND METHODS: Rabbit UECs were collected by biopsy from adult rabbit urethra and seeded onto the outer layer of a mesh biodegradable urethral stent. The growth of UECs in cell-scaffolds was assessed by scanning electron microscopy, immunohistochemical and fluorescence staining. In all, 32 male New Zealand rabbits were used, with either PTUS or uninjured, as a control group. Cell-seeded stents were implanted into the rabbits strictured urethra. The histological and immunohistochemical findings were assessed after death at 1, 2, 8, 12 and 24 weeks, respectively. The reconstruction and function were evaluated by urethroscopy and retrograde urethrography. RESULTS: The cultured UECs adhered to the stent and grew well. Immunohistochemistry showed that the cells were stained positively for cytokeratin. At 4 weeks, vs 2 weeks, the thickness of the papillary projections of the epithelium decreased and inflammatory cell infiltration diminished. At 24 weeks the injured urethra was completely covered by integrated regeneration of three to five layers of urothelium. There was no evidence of voiding difficulty, stricture recurrence or other complications. CONCLUSIONS: The unbraided mesh biodegradable urethral stent with autologous UECs seemed to be feasible for treating PTUS in the rabbit urethra, and provides a hopeful avenue for clinical application allowing reconstruction of PTUS.

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.

Photoselective laser vaporization prostatectomy for acute urinary retention in China.

PURPOSE: To assess the clinical efficacy and safety of photoselective laser vaporization of the prostate (PVP) in the treatment of patients with acute urinary retention (AUR) secondary to benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Forty-two patients (mean age 72 +/- 5 years, range 65-89) with AUR because of BPH were treated with a prospective trial of PVP with the potassium-titanyl-phosphate (KTP) laser. The treatment outcome was evaluated with subjective and objective tests at 1, 3, 6, and 12 months after PVP using the International Prostate Symptom Score (IPSS), disease-specific quality of life (QoL) score, postvoid residual (PVR) urine volume, and maximum urinary flow rate (Qmax). The International Index of Erectile Function questionnaire and a self-designed ejaculatory questionnaire were completed at different follow-up times to determine patient satisfaction and changes in sexual function. RESULTS: After preliminary urine drainage and adequate preoperative preparation, PVP was performed and bladder outlet obstruction was effectively relieved. The mean prostate volume was 62.5 +/- 11.7 cc, and the mean residual volume with retention was 650 mL (range 240-1200 mL). Mean operative time was 28.6 +/- 5.7 minutes. Mean catheterization duration was 5.6 days (range 3-14 d). There was significant subjective improvement of symptoms and objective improvement in urinary flow rates at 12 months. The mean IPSS and QoL score decreased significantly (P < 0.05). Mean PVR volume also decreased. The mean Qmax was 16.2 +/- 4.6 mL/sec after treatment. Only two patients had recurrent urinary retention during follow-up. There were no intraoperative or postoperative adverse events. CONCLUSIONS: The early clinical results suggest that the PVP is a promising safe, effective, and less-invasive treatment with minimal morbidity for patients with urine retention secondary to BPH.

[Bortezomib-based combination therapy for relapsed or refractory multiple myeloma].

OBJECTIVES: To investigate the efficacy and toxicity of bortezomib based combination therapy for Chinese patients with relapsed or refractory multiple myeloma (MM), and to determine the combination regimen, dosage and cycles in application of bortezomib for MM therapy. METHODS: Forty-six patients with refractory or relapsed myeloma were treated with bortezomib (1.3 mg/m2) as an intravenous bolus twice weekly for 2 weeks on day 1, 4, 8, and 11 in a 3-4 week cycle, in combination with dexamethasone, dexamethasone plus thalidomide, CD (C-cytoxan, D-dexamethasone), MD (M-mitoxsnteone), DCEP (E-etoposide, P-platinol), and DT-PACE regimens (T-thalidomide, A-adriamycin). Response to bortezomib was evaluated according to the criteria of the International Myeloma Working Group (IMWG) before initiation of each cycle. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Forty-nine matched patients with relapsed and refractory MM who received thalidomide based combination therapy were used as a historical control group. RESULTS: Among 43 of the 46 patients whom could be evaluated, the overall response rate was 72.1% (the control group was 51.0%, P < 0. 05), including complete response in 5 patients (11.6%), very good partial response in 12 patients (27.9%), and partial response in 14 patients (32.6%). The overall response rate after one and two cycles was 30.2% and 58.1% (P < 0.05), respectively. The frequent adverse events were thrombocytopenia (62.8%), fatigue (55.8%), nausea (51.2%) and peripheral neuropathy (30.2%); all of the events could be tolerated. The most common adverse event in the control group was constipation( 69.4%), followed by fatigue (59.2%) and dizziness (46.9%). CONCLUSIONS: Bortezomib based combination therapy is a new effective therapy in relapsed or refractory myeloma patients with a higher response rate and different toxicities as compared with thalidomide based combinations.

[DNA damage induces BRCA1 distribution alteration in prostate cancer cell lines].

OBJECTIVE: To investigate the role of the tumor suppressor gene BRCA1 in response to DNA damage and to confirm that the function of the BRCA1 protein is regulated by a variety of mechanisms including transcriptional control, phosphorylation and protein-protein interaction. METHODS: With the human breast cell line MCF7 as the positive control, we determined the subcellular distribution of BRCA1 in the prostate cancer cell lines LNCaP, DU145 and PC3 by immunohistochemical staining and Western blotting analyses. RESULTS: BRCA1 was present in the prostate cancer cell lines LNCaP, DU145 and PC3. Ionizing radiation induced BRCA1 nuclear export, increasing from 14% to 40% in the cytoplasma (P < 0.01) and decreasing from 46% to 21% in the nuclei (P < 0.01). This DNA damage-induced BRCA1 nuclear export occurred only in the p53 wild-type but not in the p53 mutant cell line. The apoptosis rate of LNCaP cells was as high as 40% after nuclear export, with an obvious increase of cleaved caspase-3, which was correlated with BRCA1 nuclear-cytoplasmic shuttling. CONCLUSION: Cytoplasmic relocalization of the BRCA1 protein may be a mechanism whereby the BRCA1 function is regulated in response to DNA damage. Its induction of a higher rate of cell apoptosis indicates BRCA1 to be another good biomarker for the treatment of prostate cancer.