[Efficacy and safety of first-line treatment with anti-CD38 monoclonal antibody-based regimen for primary plasma cell leukemia].

Objective: To analyze the efficacy and safety of first-line treatment with an anti-CD38 monoclonal antibody regimen for primary plasma cell leukemia (pPCL). Methods: Patients diagnosed with pPCL from December 1st, 2018 to July 26th, 2023, receiving first-line treatment of anti-CD38 monoclonal antibody-based regimens across multiple centers including Peking University People's Hospital, Fuxing Hospital of Capital Medical University, Qingdao Municipal Hospital, Shengjing Hospital of China Medical University, Handan Central Hospital, the First Affiliated Hospital of Harbin Medical University, the Fourth Hospital of Hebei Medical University and General Hospital of Ningxia Medical University were consecutively included. A total of 24 pPCL patients were included with thirteen being male and eleven being female. The median age [M(Q1, Q3)] was 60 (57, 70) years. Patients were grouped according to peripheral blood plasma cell (PBPC) percentage [5%-19% (n=14) vs ≥20% (n=10)]. Last follow-up date was September 26th, 2023. The median follow-up period was 9.1 (4.2, 15.5) months. Patients' data related with clinical baseline characteristics, efficacy, survival and safety were retrospectively collected. Cox proportional hazards regression model was used to analyze risk factors associated with survival. Results: Among 24 pPCL patients, 16 (66.7%) patients had anemia at diagnosis, 13(54.2%) patients had thrombocytopenia, 8 (33.3%) patients had a baseline estimated glomerular filtration rate (eGFR)<40 ml·min-1·(1.73m2)-1, 13 (54.2%) patients had elevated lactate dehydrogenase (LDH) levels. The median PBPC percentage was 16% (8%, 26%) . Fluorescence in situ hybridization testing indicated that patients harboring 17p deletion, t(4;14) or t(14;16) were 6 (25.0%), 4 (16.7%) and 4 (16.7%), respectively. The overall response rate was 83.3% (20/24). The median progression-free survival (PFS) was 20.5 (95%CI: 15.8-25.2) months, and the median overall survival (OS) was not reached. Estimated 1-year and 2-year PFS and OS rates were 75.0% and 89.1%, 37.5% and 53.4%, respectively. The median PFS and OS for patients with PBPC percentages 5%-19% and≥20% were not reached and 20.5 (95%CI:15.7-25.3) months, 17.8 months and not reached, respectively. There was no significant statistical difference of PFS and OS between two groups (all P>0.05). Multivariate Cox regression analysis showed that 1p32 deletion was the risk factor associated with PFS (HR=7.7, 95%CI: 1.1-54.9, P=0.043). Seventeen patients (70.8%) developed grade 3-4 hematologic toxicities. Twelve patients (50.0%) developed grade 3-4 thrombocytopenia. Sixteen patients (66.7%) developed infection. All hematologic toxicities and infections were improved after supportive treatment. Conclusion: First-line treatment with anti-CD38 monoclonal antibody-based therapy for pPCL is effective and safe.

Predictive effect of net water uptake on futile recanalisation in patients with acute large-vessel occlusion stroke.

AIM: To determine whether net water uptake (NWU) based on automated software evaluation could predict futile recanalisation in patients with acute anterior circulation large-vessel occlusion (LVO). MATERIALS AND METHODS: Patients with acute anterior circulation LVO undergoing mechanical thrombectomy in Jinling Hospital were evaluated retrospectively. NWU and other baseline data were evaluated by performing univariate and multivariate analyses. The primary endpoint was 90-day modified Rankin scale score ≥3. A nomogram to predict poor clinical outcomes was developed based on multivariate logistic regression analysis. RESULTS: Overall, 135 patients who underwent thrombectomy with a TICI grade ≥2b were enrolled. In multivariate logistic regression analysis, the following factors were identified as independent predictors of futile recanalisation: age (odds ratio [OR]: 1.055, 95 % confidence interval [CI]: 1.004-1.110, p=0.035), female (OR: 0.289, 95 % CI: 0.098-0.850, p=0.024), hypertension (OR: 3.182, 95 % CI: 1.160-8.728, p=0.025), high blood glucose level (OR: 1.36, 95 % CI: 1.087-1.701, p=0.007), admission National Institutes of Health Stroke Scale score (OR: 1.082, 95 % CI: 1.003-1.168, p=0.043), and NWU (OR: 1.312, 95 % CI: 1.038-1.659, p=0.023). CONCLUSIONS: NWU based on Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) could be used to predict the occurrence of futile recanalisation in patients with acute anterior circulation LVO ischaemic stroke.

[Predictive value of net water uptake with respect to early neurological improvement after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke].

Objective: To investigate the value of net water uptake (NWU) for predicting early neurological improvement (ENI) after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke. Methods: A case-control study. A total of 132 patients (80 men, 52 women, median age 68 years) with acute anterior circulation large vessel occlusive stroke receiving endovascular treatment were retrospectively analyzed at Jinling Hospital from October 2014 to September 2019. Patients were divided into two groups based on the occurrence of ENI, which was defined as either an improvement of NIHSS score of ≥4 points, or an NIHSS score of 0 or 1 at 24 hours after endovascular treatment. The rank sum test, Chi square test, and other methods were used to compare differences in baseline characteristics between the two groups. Logistic regression analysis was used to investigate independent predictors of postoperative ENI. Receiver operating characteristic curve analysis used to assess the capacity of NWU to predict ENI. Results: Of the 132 patients in the study, ENI occurred in 47 and did not occur in 85. In multivariate logistic regression analysis age [odds ratio (OR)=0.940, 95% confidence interval (CI) 0.903-0.979, P=0.003], time from stroke onset to puncture (OR=0.995, 95%CI 0.991-0.999, P=0.025), time from puncture to recanalization/end of operation (OR=0.985, 95%CI 0.974-0.996, P=0.007), NWU (OR=0.762, 95%CI 0.620-0.937, P=0.010), and mTICI (OR=1.644, 95%CI 1.043-2.590, P=0.032) were predictive factors for ENI. Receiver operating characteristic curve analysis indicated that NWU could effectively predict ENI (area under the curve=0.642, 95%CI 0.543-0.741, P=0.007), and prediction accuracy was improved when it was combined with other clinical parameters. Conclusion: NWU is an independent predictor of ENI in patients with acute anterior circulation large vessel occlusive stroke undergoing endovascular treatment.

[The influence of apolipoprotein A1 on the prognosis of multiple myeloma].

Objective: In this study, we aimed to determine the change and clinical significance of serum level Apo A1 in MM patients. Methods: In total, 412 multiple myeloma patients were examined. SPSS 22.0 was used for data analysis. Correlation analysis was performed using linear correlation or Spearman rank correlation coefficients. Measurement data were analyzed with the t-test, Mann-Whitney U-test, or oneway analysis of variance (ANOVA) . Used the ROC curve to calculate the cutoff value and compared the OS and PFS between high Apo A1 subgroup and low Apo A1 subgroup with Kaplan-Meier survival analysis. Results: Our study showed that value of Apo A1 in the patient group was lower than that in the control group (0.89 g/L vs 1.24 g/L, P<0.05) . We found that Apo A1 dynamically changed with different MM stages. As it was increased when the disease was in remission, and decreased after disease in progression. According the result of multivariate analysis Apo A1 reduction become the independent risk factors of MM. On the basis of Kaplan-Meier survival analysis between high Apo A1 subgroup and low Apo A1 subgroup, we found higher Apo A1 patienta had longer OS rate and PFS. Conclusions: Apo A1 is a useful biomarker of tumor burden and a prognostic factor of multiple myeloma.

Imatinib enhances the anti-tumour effect of doxorubicin in canine B-cell lymphoma cell line.

Canine lymphoma is one of the most common malignant tumours occurring in dogs and has a high incidence worldwide. Despite advances in cancer prevention, the treatment of neoplastic diseases still requires improvement. Some cancer cells may resist the effect of chemotherapeutic agents by up-regulating drug transporters leading to increased drug efflux, resulting in intrinsic or acquired drug resistance, which is a mechanism commonly seen in doxorubicin-resistant tumour cells. In this study, canine B-cell lymphoma cell line CLBL1-8.0, a doxorubicin-resistant B cell lymphoma cell line derived from CLBL-1 by increasing the doxorubicin concentration during culturing, exhibited high expression of P-glycoprotein (P-gp, ATP-binding cassette sub-family B member 1 [ABCB1]). These proteins are commonly involved in cancer cell resistance to doxorubicin. Imatinib, a tyrosine kinase inhibitor significantly potentiated the sensitivity of doxorubicin in P-gp-overexpressing doxorubicin-resistant cells. Moreover, a combination of these two drugs may increase the retention of doxorubicin by decreasing the efflux of doxorubicin without affecting P-gp protein overexpression. In conclusion, imatinib reversed doxorubicin resistance by decreasing drug efflux in P-gp-overexpressing doxorubicin-resistant canine lymphoma cells. These results suggest that combining doxorubicin, one of the most widely used chemotherapeutic drugs in the treatment of canine lymphoma, with imatinib might potentially overcome doxorubicin resistance in a clinical setting.

A nonmyeloablative chimeric mouse model accurately defines microglia and macrophage contribution in glioma.

AIMS: Resident and peripherally derived glioma associated microglia/macrophages (GAMM) play a key role in driving tumour progression, angiogenesis, invasion and attenuating host immune responses. Differentiating these cells' origins is challenging and current preclinical models such as irradiation-based adoptive transfer, parabiosis and transgenic mice have limitations. We aimed to develop a novel nonmyeloablative transplantation (NMT) mouse model that permits high levels of peripheral chimerism without blood-brain barrier (BBB) damage or brain infiltration prior to tumour implantation. METHODS: NMT dosing was determined in C57BL/6J or Pep3/CD45.1 mice conditioned with concentrations of busulfan ranging from 25 mg/kg to 125 mg/kg. Donor haematopoietic cells labelled with eGFP or CD45.2 were injected via tail vein. Donor chimerism was measured in peripheral blood, bone marrow and spleen using flow cytometry. BBB integrity was assessed with anti-IgG and anti-fibrinogen antibodies. Immunocompetent chimerised animals were orthotopically implanted with murine glioma GL-261 cells. Central and peripheral cell contributions were assessed using immunohistochemistry and flow cytometry. GAMM subpopulation analysis of peripheral cells was performed using Ly6C/MHCII/MerTK/CD64. RESULTS: NMT achieves >80% haematopoietic chimerism by 12 weeks without BBB damage and normal life span. Bone marrow derived cells (BMDC) and peripheral macrophages accounted for approximately 45% of the GAMM population in GL-261 implanted tumours. Existing markers such as CD45 high/low proved inaccurate to determine central and peripheral populations while Ly6C/MHCII/MerTK/CD64 reliably differentiated GAMM subpopulations in chimerised and unchimerised mice. CONCLUSION: NMT is a powerful method for dissecting tumour microglia and macrophage subpopulations and can guide further investigation of BMDC subsets in glioma and neuro-inflammatory diseases.

[Impact of KIT D816 mutation on salvage therapy in relapsed acute myeloid leukemia with t(8;21) translocation].

Objective: To evaluate the impact of KIT D816 mutation on the salvage therapy in relapsed acute myeloid leukemia (AML) with t(8;21) translocation. Method: The characteristics of the first relapsed AML with t(8;21) translocation from 10 hospitals were retrospectively collected, complete remission (CR(2)) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR(2) rate was analyzed. Results: 68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR(2). All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR(2) compared with non-KIT D816 group (23.1% vs 57.1%, χ(2)=7.559, P=0.006), and patients with longer CR(1) duration achieved significantly higher CR(2) than those with CR(1) duration less than 12 months (74.1% vs 31.9%, χ(2)=9.192, P=0.002). KIT D816 mutation was tightly related to shorter CR(1) duration. No significant difference of 2 years post relapse survival was observed between KIT D816 mutation and non-KIT D816 mutation group. Conclusion: KIT D816 mutation at diagnosis was an adverse factor on the salvage therapy in relapsed AML with t(8;21) translocation, significantly related to shorter CR1 duration, and can be used for prediction of salvage therapy response. KIT D816 mutation could guide the decision-making of salvage therapy in relapsed AML with t(8;21) translocation.

[A retrospective study of the BiRd regimen in the treatment of relapsed/ refractory multiple myeloma].

Objective: To evaluate efficacy of the BiRd regimen, a combination of clarithromycin, lenalidomide, and dexamethasone, in the treatment of patients with relapsed/refractory multiple myeloma (RRMM) . Methods: Patients with RRMM treated with BiRd between September 11, 2013 and August 1, 2016 at six centers were included to evaluate overall survival rate (ORR) , clinical benefit rate (CBR) , progression-free survival (PFS) , overall survival (OS) , as well as adverse events. Results: Of 30 patients with RRMM, 27 patients were evaluable, and ORR and CBR were 51.9% (14/27) and 66.7% (18/27) respectively, including 1 sCR (3.7%) , 3 CR (11.1%) , 3 VGPR (11.1%) , and 7 PR (25.6%) . In 13 patients with prior Rd, ORR and CBR were 38.5% (5/13) and 61.5% (8/13) respectively, of which 5 patients with ≥MR carried high-risk cytogenetic[ (e.g.17p- or t (4;14) ] together with at least one of other adverse-prognostic cytogenetic (e.g.13q- and/or 1q21+) . In 24 patients with prior bortezomib-based therapy, ORR and CBR were 45.8 and 62.5%, respectively. With a median follow-up time of 14.9 (range 1.0-33.8) months, the median PFS and OS were 12.0 (95%CI 11.6-12.4) and 27.6 (95%CI 15.1-40.1) months, respectively. The BiRd regimen was well tolerated. Conclusion: The BiRd regimen is an effective and safety protocol for RRMM, including those carrying high-risk cytogenetic markers.

[A prospective multi-center trial of non-interventional and observational study of lenalidomide in Chinese patients with multiple myeloma].

Objective: To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM). Methods: It was a prospective, multi-center, observational study. A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015. Relevant information was recorded, such as baseline clinical data, cytogenetic abnormalities, treatment regimens, and duration of treatment, safety, and survival. Results: (1)There were 126 relapsed and refractory MM (RRMM) patients, 25 newly diagnosed patients and 19 maintenance patients. The evaluable RRMM patients accounted for 120 cases, among which 74 cases(61.7%) reached the partial response (PR) or above, and a very good partial response (VGPR) in 16 patients (13.3%), a complete response (CR) in 14 cases (11.7%), a strictly complete response (sCR) in 4 cases (3.3%). Thus, a VGPR or above in 34 patients accounted for 28.3%. (2)The median follow-up was 13 months, the median time to progression 12 months. The median survival after receiving lenalidomide was 19 months, and the median overall survival (OS) was 62 months. (3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype, international staging system (ISS) Ⅰ-Ⅱ, t(4; 14) negative (detected by fluorescence in situ hybridization), non-bortezomib resistance and response to previous regimens. As to OS, non-bortezomib resistance, response to previous regimens and non-primary refractoriness were positive factors. Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival(PFS), non-bortezomib resistance and non-primary refractoriness for OS. (4) Grade 3 or 4 adverse events that occurred in more than 10% of all enrolled patients were neutropenia (12.7%), leukocytosis(11.5%) and thrombocytopenia (12.7%). Owing to intolerance of toxic side effects, 7 cases withdrew lenalidomide. Conclusions: No matter what combination, regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7%, a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable. In addition, the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS, non-bortezomib resistance and non-primary refractoriness for OS. Clinical trail registration: Clinicaltrials.gov, NCT01947309.

Combining ultrasound and lactobacilli treatment for high-fat-diet-induced obesity in mice.

Chronic systemic lipopolysaccharide-induced inflammation can cause obesity. In animal experiments, lactobacilli have been shown to inhibit obesity by modifying the gut microbiota, controlling inflammation and influencing the associated gene expression. A previous study found that high-fat-diet-induced (HFD) obesity was suppressed by lactobacilli ingestion in rats via the inhibition of parasympathetic nerve activity. This study explored the combined use of lactobacilli ingestion and ultrasound (US) to control body weight and body fat deposition in HFD mice over an 8-week experimental period. Male C57BL/6J mice received an HFD during treatment and were randomly divided into four groups: (i) control group (H), (ii) lactobacilli alone (HB), (iii) US alone (HU) and (iv) lactobacilli combined with US (HUB). The US was targeted at the inguinal portion of the epididymal fat pad on the right side. At the 8th week, body weight had decreased significantly in the HUB group (15.56 ± 1.18%, mean ± SD) group compared with the HU (26.63 ± 0.96%) and H (32.62 ± 5.03%) groups (p < 0.05). High-resolution microcomputed tomography (micro-CT) scans revealed that the reduction in total body fat volume was significantly greater in the HUB group (69%) than in the other two experimental groups (HB, 52%; HU, 37%; p < 0.05). The reductions in the thickness of the subcutaneous epididymal fat pads were significantly greater in the HUB group (final thickness: 340 ± 7 µm) than in the H (final thickness: 1150 ± 21 µm), HB (final thickness: 1060 ± 18 µm) and HU (final thickness: 370 ± 5 µm) groups (all p < 0.05). Combination therapy with lactobacilli and US appears to enhance the reduction in body weight, total and local body fat deposition, adipocyte size and plasma lipid levels over an 8-week period over that achieved with lactobacilli or US alone in HFD mice. These results indicate that US treatment alone can reduce hyperlipidemia in HFD mice.

Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (CC-RCC) is the most lethal of all genitourinary cancers. The functional loss of the von Hippel-Lindau (VHL) gene occurs in 90% of CC-RCC, driving cancer progression. The objective of this study was to identify chemical compounds that are synthetically lethal with VHL deficiency in CC-RCC. An annotated chemical library, the library of pharmacologically active compounds (LOPAC), was screened in parallel on VHL-deficient RCC4 cells and RCC4VHL cells with re-introduced VHL. The ROCK inhibitor, Y-27632, was identified and validated for selective targeting of VHL-deficient CC-RCC in multiple genetic backgrounds by clonogenic assays. Downregulation of ROCK1 by small interfering RNA (siRNA) selectively reduced the colony-forming ability of VHL-deficient CC-RCC, thus mimicking the effect of Y-27632 treatment, whereas downregulation of ROCK2 had no effect. In addition, two other ROCK inhibitors, RKI 1447 and GSK 429286, selectively targeted VHL-deficient CC-RCC. CC-RCC treatment with ROCK inhibitors is cytotoxic and cytostatic based on bromodeoxyuridine (BrdU) assay, propidium iodide (PI) staining and growth curves, and blocks cell migration based on transwell assay. On the one hand, knockdown of hypoxia-inducible factor (HIF) ß in the VHL-deficient CC-RCC had a protective effect against Y-27632 treatment, mimicking VHL reintroduction. On the other hand, CC-RCCVHL cells were sensitized to Y-27632 treatment in hypoxia (2% O2). These results suggest that synthetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC.

[Efficacy and safety of IA regimen containing different doses of idarubicin in de-novo acute myeloid leukemia for adult patients].

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m(2), 10 mg/m(2) or 12 mg/m(2) as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m(2)) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m(2) group, IDA 10 mg/m(2) group and IDA 12 mg/m(2) group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m(2) group and IDA 12 mg/m(2) group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m(2) group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m(2) was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m(2) when compared with the IDA 8 mg/m(2) was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10(9)/L in IDA 8 mg/m(2) group, IDA 10 mg/m(2) group and IDA 12 mg/m(2) group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10(9)/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions: For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m(2) is clinically superior to IDA 8 mg/m(2) and IDA 12 mg/m(2) in favorable intermediate AML subgroup. However, idarubicin 12 mg/m(2) is more suitable to adverse AML subgroup.

Short-term safety evaluation of the offspring conceived by 7272 artificial insemination cycles with donor spermatozoon.

This case-control study was designed to investigate the safety of the AID technology. The health status of the offspring conceived by 1620 couples who underwent 7272 AID cycles in our Center for Reproductive Medicine between June 2006 and December 2012 was retrospectively analysed. The control group included 1018 women who naturally conceived and delivered in the same period. Twin birth rate was significantly higher in the AID group (no triplet birth) than in the control group (2.01% versus 0.39%, P < 0.01). In the AID group, Caesarean delivery was used in 1299 cases (81.65%), spontaneous vaginal delivery (18.04%) and forceps-assisted vaginal delivery (0.31%).There was no significant difference in male/female ratio of the offspring between AID and control groups (113.55 : 100 versus 113.36 : 100, P > 0.05). Compared to natural pregnancy, a pregnancy through AID resulted in higher multiple birth rate, premature delivery rate and neonatal congenital malformation rate. Increased multiple birth rate was attributable to ovulation induction, and increased rate of low-birthweight infants was related to multiplets and premature delivery. Caesarean delivery was preferred in couples who received AID treatment. The male/female ratio of the AID offspring was similar between natural pregnancy and AID pregnancy.

Chemotherapy-induced neutropenia is associated with prolonged remission duration and survival time in canine lymphoma.

Myelosuppression is one of the most common side effects of chemotherapy. The aim of this study was to determine whether chemotherapy-induced neutropenia is a positive prognostic indicator for remission and survival time in dogs with lymphoma. Fifty dogs with multicentric lymphoma received CHOP-based (C-cyclophosphamide; H-hydroxydaunorubicin; O-vincristine; P-prednisolone) chemotherapy using conventional dosages. Complete blood counts were recorded to determine the presence or absence of neutropenia after treatment. Toxicity, remission, and survival times were recorded and analysed. Thirteen dogs had chemotherapy-induced neutropenia and 37 had no neutropenia during the study period. No statistical difference was found between the groups for signalment or the presence of historical negative prognostic factors, except for bodyweight (P = 0.02). The median first remission times in the neutropenia and no neutropenia groups were 812 and 219 days, respectively (P <0.01). The median survival times of dogs in the neutropenia and no neutropenia groups were 952 and 282 days, respectively (P <0.01). Dogs with lymphoma that had chemotherapy-induced neutropenia exhibited significantly increased remission and survival times compared with dogs without neutropenia. Chemotherapeutic dosages may be adjusted individually to induce neutropenia without severe adverse effects in order to achieve longer remission and survival times.

Effect of TIEG1 on apoptosis and expression of Bcl-2/Bax and Pten in leukemic cell lines.

We examined the effect of transforming growth factor-b inducible early gene-1 (TIEG1) on the apoptosis of leukemic cell lines and expression of B-cell lymphoma 2 (Bcl-2) and phosphatase and tensin homolog (Pten). Four leukemic cell lines (HL-60, U937, Raji, and K562) were treated with 0, 1, 5, 10, and 20 ng/mL TIEG1, respectively. The cell growth inhibitory ratio was assessed using the MTT assay. An inhibitory curve was drawn, and half-maximal inhibitory concentration was calculated. Additionally, 1640 culture medium containing 10 ng/mL TIEG1 was used to culture leukemic cell lines for 0, 6, 12, 24, and 48 h. The apoptosis of each cell line at different time points was detected by flow cytometry. Total RNA was extracted before reverse transcription-polymerase chain reaction. The products of this reaction were analyzed by electrophoresis, and the expression of Bcl-2/Bcl-2-associated X protein (Bax) and Pten were detected. After treatment with TIEG1, proliferation of the 4 leukemic cell lines was inhibited both time- and dose-dependently. During apoptosis induction, the expression of Bcl-2 was decreased and the expressions of Bax and Pten were increased in the 4 leukemic cell lines induced by TIEG1 (P < 0.05). TIEG1 can inhibit the proliferation of leukemic cells and induce their apoptosis in a time- and dose-dependent manner. A close relationship exists between Bcl-2/Bax and Pten expression and cell apoptosis induced by TIEG1.

Longitudinal reference range for umbilical cord cross-sectional area in twin pregnancies at 18-32 weeks of gestation.

OBJECTIVES: The objectives of this study were to establish gestational age-specific reference ranges for cross-sectional area of the umbilical cord, and its components, in twin pregnancies and to compare them with previously reported singleton reference ranges. METHODS: This was a prospective longitudinal study involving uncomplicated dichorionic twin pregnancies. Sonographic measurements of the cross-sectional area of the umbilical cord, umbilical vein and arteries and Wharton's jelly were obtained in a plane adjacent to the fetal abdomen, every 3 weeks, between 18 and 32 weeks of gestations. Multilevel regression analysis was used to determine gestational age-specific reference ranges for each parameter, and these were plotted against singleton pregnancy references. RESULTS: Three hundred and thirty four ultrasound scans were performed in 44 twin pregnancies, between 18 and 32.9 weeks (mean: 3.8 ± 0.7 scans/pregnancy and mean interval between scans: 3.3 ± 0.9 weeks). All umbilical cord cross-sectional areas (total, vein, artery and Wharton's jelly) showed a significant increase with gestational age. Compared with singleton pregnancy ranges, mean values were considerably lower in twin pregnancies and resemble the lower limits observed in singletons. CONCLUSION: In twin pregnancies, cross-sectional area of the umbilical cord, and its components, increases between 18 and 32 weeks, and mean values are substantially lower compared with singleton pregnancies.

Placental transfer of IgG antibodies specific to Klebsiella and Pseudomonas LPS and to group B Streptococcus in twin pregnancies.

Group B Streptococcus (GBS), Klebsiella spp. and Pseudomonas spp. are important aetiological agents of neonatal infections in Brazil. There is a lack of data in the literature regarding the specific transport of immunoglobulin G (IgG) against these pathogens in multiple pregnancies. Maternal (n = 55) and umbilical cord (n = 110) blood samples were prospectively collected at birth from 55 twin pregnancies. The factors associated with cord levels and transfer ratios of IgG against GBS, Klebsiella and Pseudomonas were examined. The IgG umbilical cord serum levels specific to GBS, Klebsiella LPS and Pseudomonas LPS were significantly associated with maternal-specific IgG concentrations and the presence of diabetes. The anti-Klebsiella IgG cord serum concentrations were also related to birthweight and the presence of hypertension. The transfer ratios against GBS and Pseudomonas LPS were associated with maternal-specific IgG concentrations. The transfer ratios for GBS and Pseudomonas LPS were associated with gestational age at delivery and the presence of diabetes, respectively. None of the examined parameters were related to Klebsiella LPS transfer ratios. We conclude that in twin pregnancies, specific maternal IgG serum concentrations and diabetes were the parameters associated with umbilical cord serum IgG concentrations reactive with the three pathogens investigated. All the other parameters investigated showed different associations with neonatal-specific IgG levels according to the antigen studied. There was no uniformity of the investigated parameters regarding association with placental IgG transfer ratios against the GBS, Pseudomonas LPS and Klebsiella LPS.

Efficacy of ultrasound mediated microbubbles in diclofenac gel to enhance transdermal permeation in rheumatoid arthritis induced rat.

In previous study in the literature, the effect of ultrasound on the transdermal permeation of the nonsteroidal anti-inflammatory drug, diclofenac has been investigated. Therapeutic ultrasound can increase circulation in the inflamed joint and decrease arthritic pain. Recently, transdermal drug delivery has been demonstrated by ultrasound (US) combining with microbubbles (MBs) contrast agent. In this study, the efficiency of US-MBs mediated diclofenac delivery for adjuvant-induced rheumatoid arthritis (RA) in rats was evaluated. RA was induced by injection of 100 µl Freund's complete adjuvant into the ankle joint in SD male rats (250-300g) and were randomly divided into five groups: (1) control group (C); (2) penetrating diclofenac alone (D); (3) US alone (U); (4) US combined with penetrating diclofenac (DU); (5) US combined with MBs and penetrating diclofenac (DUB). The evaluations of ankle width were performed for 10 days by high frequency (40MHz) US B-mode and color Doppler mode imaging before and after treatment. Longitudinal US images of arthritis induced show synovitis and neovascularity. After treatment, only a little neovascularity has been observed. The recovery rate at 10th day in the group DUB (97.7±2.7 %) was significantly higher than in the group C (1.0±2.7 %), group D (37.5±4.6 %), group U (75.5±4.2 %) and group DU (87.3±5.2 %) (p <; 0.05). Our results investigated that the treatments of US and MBs can increase skin permeability to enhance diclofenac sodium delivery and inhibit inflammation of the tissues surrounded the arthritic ankle. In color Doppler imaging, after the combination treatment, the synovial neoangiogenesis in the arthritic area was reduced quickly.